A gram negative stain never rules out the presence of infection.

A 41-year-old man comes to the Emergency Department with three days of swelling and pain in the right knee, with functional impotence and fever Two weeks earlier he had had a self-limited diarrhea. On examination there is joint effusion, so we proceed to perform an arthrocentesis and obtain 50 cc of cloudy liquid, with decreased viscosity and the following analytical parameters: leukocytes 40. 000/microL (85% of neutrophils), glucose 40 mg/dL, absence of crystals, Gram stain: no microorganisms are observed. Which of the following statements about this patient is WRONG:

Treatment with cloxacillin and ceftriaxone should be initiated pending the result of the fluid culture.

It is advisable to perform daily arthrocentesis to relieve symptoms and prevent joint destruction.

If the culture is negative, it is likely to be reactive arthritis.

Negative Gram stain rules out septic arthritis.

Approach to septic arthritis.

Prompt diagnosis and treatment of infectious arthritis can help prevent significant morbidity and mortality. The acute onset of monoarticular joint pain, erythema, heat, and immobility should raise suspicion of sepsis. Constitutional symptoms such as fever, chills, and rigors are poorly sensitive for septic arthritis. In the absence of peripheral leukopenia or prosthetic joint replacement, synovial fluid white blood cell count in patients with septic arthritis is usually greater than 50,000 per mm3. Isolation of the causative agent through synovial fluid culture is not only definitive but also essential before selecting antibiotic therapy. Synovial fluid analysis is also useful to help distinguish crystal arthropathy from infectious arthritis, although the two occasionally coexist. Almost any microorganism can be pathogenic in septic arthritis; however, septic arthritis is caused by nongonococcal pathogens (most commonly Staphylococcus species) in more than 80 percent of patients. Gram stain results should guide initial antibiotic choice. Vancomycin can be used for gram-positive cocci, ceftriaxone for gram-negative cocci, and ceftazidime for gram-negative rods. If the Gram stain is negative, but there is strong clinical suspicion for bacterial arthritis, treatment with vancomycin plus ceftazidime or an aminoglycoside is appropriate. Evacuation of purulent material with arthrocentesis or surgical methods is necessary. Special consideration should be given to patients with prosthetic joint infection. In this population, the intraarticular cutoff values for infection may be as low as 1,100 white blood cells per mm3 with a neutrophil differential of greater than 64 percent.

Septic arthritis

Diagnosis Septic arthritis should be considered whenever a person has rapid onset pain in a swollen joint, regardless of fever. One or multiple joints can be affected at the same time. The diagnosis of septic arthritis is based on physical exam and prompt arthrocentesis which yields synovial fluid from within the affected joint. This fluid should be collected before the administration of antibiotics and should be sent for gram stain, culture, leukocyte count with differential, and crystal studies. This can include NAAT testing for N. gonorrhoeae if suspected in a sexually active person.

Septic arthritis

The Gram stain can rule in the diagnosis of septic arthritis, however, cannot exclude it. Synovial fluid cultures are positive in over 90% of nongonoccocal arthritis; however, it is possible for the culture to be negative if the person received antibiotics prior to the joint aspiration. Cultures are usually negative in gonoccocal arthritis or if fastidious organisms are involved. If the culture is negative or if a gonococcal cause is suspected, NAAT testing of the synovial fluid should be done. Positive crystal studies do not rule out septic arthritis. Crystal-induced arthritis such as gout can occur at the same time as septic arthritis. A lactate level in the synovial fluid of greater than 10 mmol/l makes the diagnosis very likely.

[Arthrocentesis in the Emergency Department].

Arthrocentesis in the Emergency Department <bAbstract.</b Acute joint swelling is a common presentation to the emergency department. Although routine investigations like clinical exam, labs and eventually x-ray are usually obtained, definitive diagnosis must be established since timely recognition of septic arthritis in particular is crucial. Definitive diagnosis is achieved by performing an arthrocentesis of the affected joint. While arthrocentesis of larger joints and large effusions (e. g. knee) are relatively easy to perform using the landmark-technique, smaller and less accessible joints (shoulder, elbow, hip) are more difficult to access and it is therefore recommended to use ultrasound guidance. Compared with the landmark-technique, ultrasound-guided arthrocentesis is more successful and less painful. Synovial fluid should be analyzed for cell count with differential, crystals as well as for microbiological analysis such as Gram-stain and culture. Once the diagnosis of septic arthritis has been established, irrigation of the joint should be performed by orthopedic surgery. Antibiotic therapy should be withheld until the sampling of synovial fluid has been completed. After exclusion of septic arthritis, acute arthritis due to crystal arthropathy (CPPD or gout) is treated with either glucocorticoid-infiltration of the joint or with nonsteroidal anti-inflammatory drugs. In this article, the different technical aspects of arthrocentesis are discussed, including asepsis, landmark- and ultrasound-guided access, preanalytics and interpretation of the laboratory results.

Does this adult patient have septic arthritis?

In patients who present with an acutely painful and swollen joint, prompt identification and treatment of septic arthritis can substantially reduce morbidity and mortality. To review the accuracy and precision of the clinical evaluation for the diagnosis of nongonococcal bacterial arthritis. Structured PubMed and EMBASE searches (1966 through January 2007), limited to human, English-language articles and using the following Medical Subject Headings terms: arthritis, infectious, physical examination, medical history taking, diagnostic tests, and sensitivity and specificity. Studies were included if they contained original data on the accuracy or precision of historical items, physical examination, serum, or synovial fluid laboratory data for diagnosing septic arthritis. Three authors independently abstracted data from the included studies. Fourteen studies involving 6242 patients, of whom 653 met the gold standard for the diagnosis of septic arthritis, satisfied all inclusion criteria. Two studies examined risk factors and found that age, diabetes mellitus, rheumatoid arthritis, joint surgery, hip or knee prosthesis, skin infection, and human immunodeficiency virus type 1 infection significantly increase the probability of septic arthritis. Joint pain (sensitivity, 85%; 95% confidence interval [CI], 78%-90%), a history of joint swelling (sensitivity, 78%; 95% CI, 71%-85%), and fever (sensitivity, 57%; 95% CI, 52%-62%) are the only findings that occur in more than 50% of patients. Sweats (sensitivity, 27%; 95% CI, 20%-34%) and rigors (sensitivity, 19%; 95% CI, 15%-24%) are less common findings in septic arthritis. Of all laboratory findings readily available to the clinician, the 2 most powerful were the synovial fluid white blood cell (WBC) count and percentage of polymorphonuclear cells from arthrocentesis. The summary likelihood ratio (LR) increased as the synovial fluid WBC count increased (for counts <25,000/microL: LR, 0.32; 95% CI, 0.23-0.43; for counts > or =25,000/microL: LR, 2.9; 95% CI, 2.5-3.4; for counts >50,000/microL: LR, 7.7; 95% CI, 5.7-11.0; and for counts >100,000/microL: LR, 28.0; 95% CI, 12.0-66.0). On the same synovial fluid sample, a polymorphonuclear cell count of at least 90% suggests septic arthritis with an LR of 3.4 (95% CI, 2.8-4.2), while a polymorphonuclear cell count of less than 90% lowers the likelihood (LR, 0.34; 95% CI, 0.25-0.47). Clinical findings identify patients with peripheral, monoarticular arthritis who might have septic arthritis. However, the synovial WBC and percentage of polymorphonuclear cells from arthrocentesis are required to assess the likelihood of septic arthritis before the Gram stain and culture test results are known.

Septic arthritis caused by Granulicatella adiacens: diagnosis by inoculation of synovial fluid into blood culture bottles.

Granulicatella species, formerly known as nutritionally variant streptococci, cause a variety of infections, primarily endocarditis. We report the first culture-proven case of a Granulicatella species causing septic arthritis. A 68-year-old female presented with knee pain and swelling. She was initially evaluated with arthrocentesis and arthroscopy, but no organism was identified. Her pain improved after a brief course of antibiotics but recurred 3 months later. She underwent repeat arthrocentesis, with direct inoculation of synovial fluid into blood culture bottles. Granulicatella adiacens was recovered from both bottles. She was treated with cefazolin for 4 weeks combined with gentamicin for the first 2 weeks. Her knee pain and swelling resolved without evidence of recurrence. Granulicatella should be considered in cases of septic arthritis with initially negative synovial fluid cultures. Inoculation of blood cultures bottles with synovial fluid may increase the diagnostic yield for these species.

[Diagnosis of septic arthritis and initial antibiotic treatment].

This study was designed to determine the similarities and differences in clinical, laboratory and radiographic presentation of septic arthritis in childhood and at adult ages, to find out its etiological profile, and to establish an antibiotic treatment protocol for the initial period and for patients in whom the causative agent could not be identified. Thirty-four patients (age range 15 months to 85 years) who underwent surgery with a diagnosis of septic arthritis were retrospectively studied in two groups, namely, children-adolescents (age = or < 15 years ; 16 patients) and adults (age >15 years; 18 patients). Clinical and laboratory findings of septic arthritis were compared with operation findings. The etiological profile and sensitivity patterns were investigated. Unflatering features in both groups were clinical findings of decreased range of motion and tenderness, laboratory findings of elevated erythrocyte sedimentation rate and C-reactive protein, and domination of polymorphonuclear leukocytes in the joint fluid. Gram staining of the joint fluid was highly informative in terms of probable bacteria. During the first two years of life, the most common bacteria were H. influenzae and S. pneumoniae, and after two years, staphylococci and streptococci. Ciprofloxacin and sulbactam-ampicillin were found effective against most of the Gram-positive microorganisms isolated in both groups. The most useful test for septic arthritis is arthrosynthesis and macroscopic and microscopic analyses of the material. Gram staining is of great help in the planning of initial antibiotic treatment. For patients older than two years of age, treatment with sulbactam-ampicillin is effective against staphylococci and streptococci, and amikacin against Gram-negative bacteria. Detection of Gram-negative bacteria in patients younger than two years should bring H. influenzae in mind, for which ampicillin must be the first choice.

Gram Stain is Not Clinically Relevant in Treatment of Pediatric Septic Arthritis.

The diagnosis of pediatric septic arthritis (SA) can be challenging due to wide variability in the presentation of musculoskeletal infection. Synovial fluid Gram stain is routinely obtained and often used as an initial indicator of the presence or absence of pediatric SA. The purpose of this study was to examine the clinical utility of the Gram stain results from a joint aspiration in the diagnosis and management of pediatric SA. All patients with suspected SA who underwent arthrocentesis and subsequent surgical irrigation and debridement at an urban tertiary care children's hospital between January 2007 and October 2016 were identified. Results of the synovial fluid Gram stain, as well as synovial cell count/differential and serum markers, were evaluated. A total of 302 patients that underwent incision and drainage for suspected SA were identified. In total, 102 patients (34%) had positive synovial fluid cultures and 47 patients (16%) had a microorganism detected on Gram stain. Gram stain sensitivity and specificity for the detection of SA were 0.40 and 0.97, respectively. This yielded a number needed to misdiagnose of 4.5 (ie, every fifth patient was misdiagnosed by Gram stain). For gram-negative organisms, the sensitivity dropped further to 0.13, with only 2/16 gram-negative organisms identified on Gram stain. Stepwise regression showed that age, serum white blood cell, and absolute neutrophil count were significant independent predictors for having a true positive Gram stain result. Elevated synovial white blood cell count was a significant predictor of having an accurate (culture matching the Gram stain) result. The Gram stain result is a poor screening tool for the detection of SA and is particularly ineffective for the detection of gram-negative organisms. The clinical relevance of the Gram stain and cost-effectiveness of this test performed on every joint aspiration sent for culture requires additional evaluation. Patients with gram-negative SA may be at high risk for inadequate coverage with empiric antibiotics due to poor detection of gram-negative organisms on initial Gram stain. Level III-case-control study.

[Two cases of pneumococcal septic arthritis complicating rheumatoid arthritis].

It is reported that most of the causative organisms of suppurative arthritis complicating rheumatoid arthritis (RA) is Staphylococcus aureus and that Streptococcus pneumoniae is rare, representing less than 5% of cases of suppurative arthritis complicating RA. We here report two cases of pneumococcal septic arthritis complicating RA. Both were female, and 68 and 64 years old, respectively. They had active, long-standing RA with destructed changes. Infected joints included both knees (case 1) and right knee (case 2). Pain and loss of motion in the septic joints were prominent. On admission, the physical examination showed severe redness, swelling and tenderness of the septic joints and the range of motion of those was markedly decreased. The radiograph of affected joints showed stage III. Laboratory data showed markedly elevated ESR of 127 mm/hr (case 1) and 142 mm/hr (case 2) and C-reactive protein of 49.91 mg/dl (case 1) and 30.36 mg/dl (case 2). Aspirate of the left knee of case 1 showed numerous neutrophils. Cultures of the joint fluid grew S. pneumoniae. Grossly purulent material was aspirated from the right knee of case 2 and cultures also grew S. pneumoniae. They were started on intravenous antibiotics with a good response and the function of involved joints returned to preseptic condition. The source of infection on case 1 was presumed to be otitis media because she had discharge from left ear concurrently with the exacerbation of joint symptoms. Case 2 had productive cough and cultures of sputum also disclosed S. pneumoniae when pain of right knee joint developed. The suggested source of infection was upper respiratory tract.(ABSTRACT TRUNCATED AT 250 WORDS)

How sensitive is the synovial fluid white blood cell count in diagnosing septic arthritis?

This study was conducted to determine the sensitivity of the current standard for synovial fluid leukocytosis analysis in diagnosing infectious arthritis or a septic joint. How accurate is the standard synovial fluid white blood cell (WBC) cutoff of 50,000 WBC/mm3 to rule out septic arthritis? We conducted a retrospective study at an urban tertiary care medical center with 50,000 adult emergency department visits per year. The study population consisted of patients with infectious arthritis confirmed by synovial fluid culture growth of a pathogenic organism. The study period lasted from January 1996 to December 2002. Extracted data included synovial fluid leukocyte count, Gram's stain, culture, past medical history, and discharge diagnosis. Fisher exact test was used to compare proportions. Sensitivity and means were calculated with 95% confidence intervals (CI). There were 49 culture-positive synovial fluid aspirates in the 6-year study period. Nineteen (39%) of 49 patients (95% CI, 25%-52%) had a synovial WBC of less than 50,000/mm3 and 30 (61%) of 49 patients (95% CI, 48%-75%) had a synovial WBC of more than 50,000/mm3. The sensitivity of the 50,000 synovial WBC/mm3 cutoff was 61% (95% CI, 48%-75%). Twenty-seven (55%) of 49 patients had a negative Gram's stain (95% CI, 41%-69%) and 15 (56%) of 27 patients (95% CI, 37%-74%) with negative Gram's stain had a synovial WBC of less than 50,000/mm3. A synovial fluid WBC cutoff of 50,000/mm3 lacks the sensitivity required to be clinically useful in ruling out infectious arthritis.

Septic Arthritis -- Treatment / Management

Treatment of septic arthritis comprises antimicrobial therapy and joint fluid drainage (arthrotomy, arthroscopy, or daily needle aspiration). Empiric intravenous antimicrobial therapy should be initiated promptly after joint aspiration is complete and cultures obtained. Empiric antibiotic coverage includes antistaphylococcal coverage (nafcillin, oxacillin, or vancomycin) for all age and risk categories. Empiric antibiotics for nongonococcal septic arthritis usually involves the use of intravenous vancomycin directed against gram-positive organisms especially if there is a suspicion of MRSA based on community and institutional data. If the patient is immunocompromised, abuses intravenous drugs or the gram stain is negative, then a third-generation cephalosporin like ceftriaxone, ceftazidime or cefotaxime should be added for the additional gram-negative coverage. [4] [6] Age, risk factors, and gram stain result should direct additional antibiotics (e.g., a third-generation cephalosporin for suspected Salmonella or N. gonorrhea ). Blood and synovial fluid cultures and sensitivities should direct prolonged antimicrobial treatment. Early involvement by an orthopedic surgeon is essential. The procedure used to drain joint fluid depends on multiple factors and is determined by the orthopedic surgeon.

Preliminary results of a new test for rapid diagnosis of septic arthritis with use of leukocyte esterase and glucose reagent strips.

Most currently used tools to diagnose septic arthritis are either not readily available or fail to provide real-time results. Reagent strip tests have identified infections in various body fluids. We hypothesized that combined leukocyte esterase and glucose strip tests can aid in diagnosing septic arthritis in native synovial fluid because (1) leukocyte esterase concentrations would be elevated at the infection site because of secretion by recruited neutrophils, and (2) glucose concentrations would be reduced because of bacterial metabolism. We prospectively investigated synovial fluid from consecutive patients with an atraumatic joint effusion who underwent arthrocentesis in our emergency department during a one-year period. Leukocyte esterase and glucose strip tests were performed on the synovial fluid. Synovial fluid leukocyte count, crystal analysis, Gram staining, culture, and glucose concentration results were also assessed. Nineteen fluids were classified as septic and 127 as aseptic. Considering septic arthritis to be present when the leukocyte esterase reading was positive (++ or +++) and the glucose reading was negative (-) yielded a sensitivity of 89.5% (95% confidence interval [CI], 66.9% to 98.7%), specificity of 99.2% (95% CI, 95.7% to 99.9%), positive predictive value of 94.4% (95% CI, 72.7% to 99.9%), negative predictive value of 98.4% (95% CI, 94.5% to 99.8%), positive likelihood ratio of 114, and negative likelihood ratio of 0.11. The synovial leukocyte counts and polymorphonuclear cell percentages were consistent with the semiquantitative readings on the leukocyte esterase strip tests, and the glucose concentrations were consistent with the glucose strip test results. Combined leukocyte esterase and glucose strip tests can be a useful additional tool to help confirm or rule out a diagnosis of septic arthritis.

Knee Effusion -- Evaluation -- Septic Arthritis

Joint fluid appears cloudy or purulent. A cell count with WBC greater than 50,000 is considered diagnostic for septic arthritis. However, lower counts may still indicate infection (not sensitive). [9] A prosthetic joint with WBC greater than 1100 is considered septic. Gram stains only identify infective organisms one-third of the time. Glucose will be less than 50% of the serum level.

Arthrocentesis

Arthrocentesis, or joint aspiration, is the clinical procedure performed to diagnose and, in some cases, treat musculoskeletal conditions. The procedure entails using a syringe to collect synovial fluid from or inject medication into the joint capsule. Laboratory analysis of synovial fluid can further help characterize the diseased joint and distinguish between gout, arthritis, and synovial infections such as septic arthritis. Uses In general, arthrocentesis should be strongly considered if there is suspected trauma, infection, or effusion of the joint. Diagnostic Arthrocentesis can be used to diagnose septic arthritis or crystal arthropathy. In the case of a septic joint, arthrocentesis should preferably be performed prior to starting treatment with antibiotics, in order to ensure a proper sample of synovial fluid is obtained.

Gram staining in the diagnosis of acute septic arthritis.

This study aimed at determining the sensitivity and specificity of Gram staining of synovial fluid as a diagnostic tool in acute septic arthritis. A retrospective study was made of 22 patients who had arthroscopic lavage following a provisional diagnosis of acute septic arthritis of the knee joint. Gram stains and cultures of the knee aspirates were compared with the clinical and laboratory parameters, to evaluate their usefulness in diagnosing acute arthritis. All patients who had septic arthritis had pain, swelling and limitation of movement. CRP was elevated in 90% of patients. The incidence of elevated white blood cell count was higher in the group of patients with a positive Gram stain study (60%) as compared to patients with a negative Gram stain study (33%). Gram staining sensitivity was 45%. Its specificity was however 100%. Gram staining is an unreliable tool in early decision making in patients requiring urgent surgical drainage and washout.

Primary Meningococcal Septic Arthritis Case Report and Literature Review of an Unusual Manifestation of Meningococcal Disease.

Primary meningococcal septic arthritis (PMSA) is an unusual manifestation of meningococcal disease. It is defined as the presence of acute septic arthritis without association with meningitis or the classic meningococcemia and isolation of Neisseria meningitidis in synovial fluid and blood culture. Diagnosis and early treatment, combining antibiotic and joint drainage, are fundamental. We present the case of a healthy 17-year-old male who presented with history of an acute onset, painful knee accompanied by fever. N. meningitidis was cultured from the synovial fluid. He was treated with arthroscopic lavage and intravenous ceftriaxone for 2 weeks. He was discharged 7 days after admission receiving outpatient intravenous ceftriaxione for 6 days and was ultimately transitioned to oral ciprofloxacin for 2 weeks thereafter. At the final follow-up visit, he had returned to sports activity with a normal knee joint. We have done an exhaustive literature review in PubMed. Forty-four articles were included, with a total of 46 patients, to which we added ours. We collected the available demographic data, analytical values, culture tests, treatment, and evolution. This case illustrates an unusual presentation of N. meningitidis infection. Diagnostic suspicion is essential. Joint washing and antibiotics are the mainstays of treatment. Early and proper treatment prevents complications and mortality. Our main objective was to evaluate the diagnostics tools and treatment in PMSA. As a secondary objective, we evaluated the cases with negative cultures in order to evaluate the criteria for the diagnostic suspicion of PMSA.

Septic arthritis

In the joint fluid, the typical white blood cell count in septic arthritis is over 50,000-100,000 cells per 10−6/l (50,000-100,000 cell/mm3); where more than 90% are neutrophils is suggestive of septic arthritis. For those with prosthetic joints, white cell count more than 1,100 per mm3 with neutrophil count greater than 64% is suggestive of septic arthritis. However, septic synovial fluid can have white blood cell counts as low as a few thousand in the early stages. Therefore, differentiation of septic arthritis from other causes is not always possible based on cell counts alone. Synovial fluid PCR analysis is useful in finding less common organisms such as Borrelia species. However, measuring protein and glucose levels in joint fluid is not useful for diagnosis. The Gram stain can rule in the diagnosis of septic arthritis, however, cannot exclude it.

Bilateral septic arthritis of the knee caused by group B streptococci: a case report.

Septic arthritis (SA) remains to be a critical diagnosis for a swollen knee at the emergency department. Here, we report a rare case of bilateral knee arthritis in a 59-year-old diabetic woman who had been immobilized 5 months prior to admission. Her right knee swelling exacerbated in 10 days leading to left knee involvement. In 5 days the clear synovial tap in the first hospital turned purulent in the second hospital and empirical antibiotics get started with high WBC count, dominant neutrophils, and Gram-positive cocci in smear. Knee arthrotomy was performed after 6 days in the third hospital with the same smear results but negative blood and synovial cultures of both knees. When followed in retrograde, two positive blood cultures were reported for <iStreptococcus agalactiae</i in the second hospital. Vancomycin was changed to ampicillin and symptoms were resolved in 4 weeks. Despite improvement, mobility was not retained. Uncommon etiologic agents of knee arthritis should be in mind specifically in debilitated patients. Timely initiation of proper antibiotics hinders permanent sequels, hence clinicians should be suspicious of such organisms.

Reactive arthritis

Reactive arthritis usually manifests about 1–3 weeks after a known infection. The mechanism of interaction between the infecting organism and the host is unknown. Synovial fluid cultures are negative, suggesting that reactive arthritis is caused either by an autoimmune response involving cross-reactivity of bacterial antigens with joint tissues or by bacterial antigens that have somehow become deposited in the joints. Diagnosis There are few clinical symptoms, but the clinical picture is dominated by arthritis in one or more joints, resulting in pain, swelling, redness, and heat sensation in the affected areas. The urethra, cervix and the throat may be swabbed in an attempt to culture the causative organisms. Cultures may also be carried out on urine and stool samples or on fluid obtained by arthrocentesis.

Pneumococcal septic arthritis of the shoulder. Case report and literature review.

Septic arthritis due to Streptococcus Pneumoniae appears to be relatively uncommon. Single- or clustered-case histories constitute the majority of reports on pneumococcal septic arthritis. A 70-year-old man presented with a 7-day history of pain, erythema and swelling of the left shoulder. Physical examination of the left shoulder revealed a warm, swollen, erythematous, and markedly tender to light palpation. The patient was unable to elevate his arm more than 30 degrees without pain. Arthrocentesis performed on admission produced 30 cc of grossly purulent fluid whose culture demonstrated S. Pneumoniae. The septic arthritis was treated with intravenous vancomycin and imipenem. The antibiotics were substituted when the sensitivities were known with oral ciprofloxacin and rifampycin to complete 8 weeks' total treatment. On follow-up examination 1 year later, the patient has remained afebrile and asymptomatic without evidence of increasing joint effusion or acute joint inflammation. Pneumococcal arthritis is classically described as a painful monoarticular arthritis complicating an active pneumococcal infection, generally a primary pulmonary infection. Pneumococcal arthritis appears to be predominantly a disease affecting the elderly. Clinical presentation ranges from septicemia to indolent infection with few systemic symptoms. With adequate antibiotic therapy and aspiration or drainage of the joint, the prognosis for return of normal joint function appears to be excellent. Although pneumococcal organisms are not likely causes, this bacteria should certainly be considered as a possible cause of arthritis or prosthetic infection.

Knee Effusion -- Evaluation -- Synovial Fluid Aspirate Analysis

Complete cell count with differential (white blood cell [WBC], polymorphonuclear leukocytes) Crystal examination of synovial fluid Bacterial Culture and Gram staining of synovial fluid Viscosity (RA: expect decreased viscosity and poor mucin clot formation) [8] Glucose A low level of synovial-fluid glucose is suggestive of an infected joint, but low glucose levels are present in only about 50% of patients with septic joints and can also occur in rheumatoid arthritis. Fasting glucose levels are usually reduced to less than half of the simultaneously obtained blood levels. The presence of crystals cannot exclude septic arthritis with certainty.[8] Septic arthritis occurs concurrently with gout or pseudogout in less than 5% of cases.

Septic Arthritis -- Evaluation -- Laboratory Studies

The most useful diagnostic laboratory test for identifying septic arthritis is an evaluation of the synovial fluid from the affected joint (culture, Gram stain, crystals analysis, white blood cell count with differential). Synovial fluid with a white blood cell (WBC) count greater than 50,000 and 90% neutrophil predominance suggests a bacterial source. [5] Identification of a bacterial organism in the synovial fluid confirms the diagnosis. Other useful laboratory tests include a complete blood count, an erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and blood cultures. The peripheral blood WBC count is typically elevated with a left shift. An elevated ESR and CRP support the diagnosis but are not definitive. A low synovial fluid WBC count may occur in peripheral leukopenia, early infection, disseminated gonococcal arthritis, and the presence of joint prosthesis. [3] [4] [5] [6]

Septic arthritis

Empiric antibiotics for suspected bacteria should be started. This should be based on Gram stain of the synovial fluid as well as other clinical findings. General guidelines are as follows: Gram positive cocci – vancomycin Gram negative cocci – Ceftriaxone Gram negative bacilli – Ceftriaxone, cefotaxime, or ceftazidime Gram stain negative and immunocompetent – vancomycin Gram stain negative and immunocompromised – vancomycin + third generation cephalosphorin IV drug use (possible pseudomonas aeruginosa) – ceftazidime +/- an aminoglycoside

InternalMed_Harrison

An algorithm for synovial fluid aspiration and analysis is shown in Fig. 393-6. Synovial fluid should be analyzed immediately for appearance, viscosity, and cell count. Monosodium urate crystals (observed in gout) are seen by polarized microscopy and arelong,needle-shaped,negativelybirefringent,andusuallyintracellular. In chondrocalcinosis and pseudogout, calcium pyrophosphate dihydrate crystals are usually short, rhomboid-shaped, and positively birefringent. Whenever infection is suspected, synovial fluid should be Gram stained and cultured appropriately. If gonococcal arthritis is suspected, nucleic acid amplification tests should be used to detect either Chlamydia trachomatis or N. gonorrhoeae infection. Synovial fluid from patients withchronicmonarthritisshouldalsobeculturedfor M. tuberculosis and fungi. Last, it should be noted that crystal-induced arthritis and septic arthritis occasionally occur together in the same joint.

In prosthetic joint infections, synovial fluid WBC count of 1100 with a neutrophil differential of 64% suggests septic arthritis. [6] Two sets of blood cultures should be obtained to rule out bacteremia. If Neisseria is suspected, one should obtain cultures from the cervix, rectum, and throat.

Arthrocentesis

Synovial Fluid Analysis Patients with a fever, suspected flare of existing arthritis, or unknown cause of joint effusion should undergo arthrocentesis with synovial fluid analysis. Samples of synovial fluid can be analyzed for gross appearance, presence of crystals, white blood cell count with differential, red blood cell count, and bacterial culture. Normal synovial fluid should not have any cells or crystals present and should appear colorless and clear.

InternalMed_Harrison

Laboratory Findings Specimens of peripheral blood and synovial fluid should be obtained before antibiotics are administered. Blood cultures are positive in up to 50–70% of S. aureus infections but are less frequently positive in infections due to other organisms. The synovial fluid is turbid, serosanguineous, or frankly purulent. Gram-stained smears confirm the presence of large numbers of neutrophils. Levels of total protein and lactate dehydrogenase in synovial fluid are elevated, and the glucose level is depressed; however, these findings are not specific for infection, and measurement of these levels is not necessary for diagnosis. The synovial fluid should be examined for crystals, because gout and pseudogout can resemble septic arthritis clinically, and infection and crystal-induced disease occasionally occur together. Organisms are seen on synovial fluid smears in nearly three-quarters of infections with S. aureus and streptococci and in 30–50% of infections due to

InternalMed_Harrison

disease occasionally occur together. Organisms are seen on synovial fluid smears in nearly three-quarters of infections with S. aureus and streptococci and in 30–50% of infections due to gram-negative and other bacteria. Cultures of synovial fluid are positive in >90% of cases. Inoculation of synovial fluid into bottles containing liquid media for blood cultures increases the yield of a culture, especially if the pathogen is a fastidious organism or the patient is taking an antibiotic. NAA-based assays for bacterial DNA, when available, can be useful for the diagnosis of partially treated or culture-negative bacterial arthritis.

Sternoclavicular Joint Infection -- Evaluation

The gold standard for diagnosing sternoclavicular joint septic arthritis remains arthrocentesis. Aspirated joint fluid should undergo evaluation for crystals, cell count, percentage of neutrophils, and the presence of bacteria using gram stain and culture. A total nucleated cell count greater than 50000 with over 90% neutrophils with no crystals is concerning for infection. A positive gram stain or culture is virtually diagnostic regardless of the other synovial fluid analyses.

Arthrocentesis

Therapeutic Aspiration of synovial fluid in cases of joint effusion or hemarthrosis can help reduce pressure around the joints, thus providing pain relief. Corticosteroid medications may also be injected into the joint capsule to provide pain relief and anti-inflammatory effects, especially for rheumatoid arthritis and less commonly osteoarthritis. Care should be taken to ensure sepsis has been ruled out before injecting corticosteroids, as doing so may worsen the joint infection. Less commonly, recurrent joint aspirations may be performed for cases of septic arthritis. Procedure Ultrasound is often used in conjunction with arthrocentesis to help identify appropriate anatomic markers of the joint. Typically, a 22 gauge needle is used along with a 5 mL syringe, but the sizes can be modified depending on the size of the joint that the procedure is being performed on.

InternalMed_Harrison

Prompt administration of systemic antibiotics and drainage of the involved joint can prevent destruction of cartilage, postinfectious degenerative arthritis, joint instability, or deformity. Once samples of blood and synovial fluid have been obtained for culture, empirical antibiotics should be given that are directed against the bacteria visualized on smears or the pathogens that are likely in light of the patient’s age and risk factors. Initial therapy should consist of IV administration of bactericidal agents; direct instillation of antibiotics into the joint is not necessary to achieve adequate levels in synovial fluid and tissue. An IV third-generation cephalosporin such as cefotaxime (1 g every 8 h) or ceftriaxone (1–2 g every 24 h) provides adequate empirical coverage for most community-acquired infections in adults when smears show no organisms. IV vancomycin (1 g every 12 h) is used if there are gram-positive cocci on the smear. If methicillin-resistant S. aureus is an

Arthrocentesis -- Clinical Significance -- Fluid Analysis

Septic synovial fluid will have the following characteristics: Cloudy/opaque appearance, greater than 50,000 leukocytes per microL, greater than 90% neutrophils, and a positive gram stain between 30% to 80% of the time.


Young woman with secondary amenorrhea, with no history of interest. Prolactin values are normal (values above 20ngr/ml are considered hyperprolectinemia), thus ruling out hyperprolactinemia as the cause of amenorrhea. They tell us that the estrogen level is low. In this case we should suspect early ovarian failure. For its diagnosis we will ask for a basal FSH (in cases of premature ovarian failure it would be elevated).

Young woman with secondary amenorrhea, with no history of interest. Prolactin values are normal (values above 20ngr/ml are considered hyperprolectinemia), thus [HIDDEN] as the cause of amenorrhea. They tell us that the estrogen level is low. In this case we should suspect early ovarian failure. For its diagnosis we will ask for a basal FSH (in cases of premature ovarian failure it would be elevated).

A 27-year-old woman consults for secondary amenorrhea of one year of evolution. She has no iatrogenic history. Analytically, the estradiol concentration is below normal and the prolactin value is 12 ng/mL. Indicate which of the following examinations would you request as a first step to try to identify the origin of the disorder:

[Hypothalamo-hypophyseal amenorrhea. I. The clinical and laboratory manifestations].

This study included 15 women 18-36 years old with primary or secondary amenorrhea, low FSH and LH, a negative response to clormadinone and serum prolactin (Prl) levels less than 20.0 ng/ml. The following tests were performed on alternate days: LH and FSH determinations every 20 minutes (pulses) during 2-4 hours (n = 15); LH and FSH response to a single dose of GnRH 100 micrograms IV (n = 15) and after administration of 100 micrograms IM of GnRH daily during four consecutive days (n = 7); TRH test 200 micrograms IV (n = 9); oral metoclopramide-Prl induced response (10 mg) (n = 2); one to three basal determinations of cortisol, estradiol (E2), T3, T4, and TSH (n = 15). All patients had serum E2 levels less than 10.0 pg/ml and none showed a regular LH or FSH pulsatility. In seven patients (group A) serum LH had a 10-30 fold increase above basal levels in response to GnRH, while the other eight patients (group B) showed no response at all; serum FSH changes were most irregular in both group. In group A no other hormonal deficiencies were detected, while in group B only three patients had an isolated LH-FSH deficiency, and in the other five this deficiency was accompanied by Prl, TSH, and/or ACTH lack. The present results suggest that: 1) group A represents isolated GnRH deficiency and the amenorrhea has hypothalamic etiology; 2) group B had LH-FSH deficiency of pituitary origin, in most cases associated to other pituitary hormone deficiencies; 3) the lack of LH response to an initial single dose of GnRH is not an absolute indicator of hypophyseal amenorrhea.

Evolution of clinical symptoms in a young woman with a recurrent gonadotroph adenoma causing ovarian hyperstimulation.

To demonstrate the clinical course in a young female with gonadotroph adenoma causing ovarian stimulation. Our patient was a 23-year-old woman with a history of oligomenorrhea who had previously undergone bilateral ovarian wedge resection owing to the clinical appearance of polycystic ovaries. Two years later, she sought treatment for headache, galactorrhea, history of spotting and lower abdominal distension. FSH, LH, beta-LH, inhibin A and B, estradiol, prolactin (PRL), and beta-chorionic gonadotrophin (beta-CG) were measured, and the responses of FSH, LH and beta-LH to thyrotrophin-releasing hormone (TRH) were documented. Immunohistochemical analysis of the tumor tissue was performed after surgery. Five years after the trans-sphenoidal surgery, the patient again became oligomenorrheic. A large recurrent adenoma was diagnosed on CT one year later. Transvaginal ultrasound showed ovaries of normal size with multiple small cystic formations simulating a polycystic pattern, While the patient was awaiting surgery, a pituitary apoplexy occurred. Emergency decompressive surgery was performed and the patient fully recovered. Enlarged ovaries were found on ultrasound examination simulating a hyperstimulation-like pattern. At that time, elevated levels of FSH (13.4IU/l) and marginally elevated levels of beta-LH (1.43ng/ml) were found, whereas the level of LH (0.5IU/l) was subnormal. Plasma estradiol was markedly supranormal (6150pmol/l). Levels of inhibin A and B were elevated (326pg/ml and 588pg/ml respectively). The prolactin level (70ng/ml) was increased, whereas beta-chorionic gonadotrophin (beta-CG) was normal. Significantly increased FSH, LH, and beta-LH responses to TRH stimulation were documented. Pituitary macroadenoma was found on MRI scan and removed by trans-sphenoidal surgery. Immunohistochemical examination showed high positivity for beta-CG and LH, and slight positivity for FSH. Five years after the surgery, estradiol was elevated (1160pmol/l), whereas basal levels of LH (4.65IU/l) and FSH (3.98IU/l) were not suppressed. After the second operation, immunostaining of the adenoma tissue confirmed the previous findings. Measurement of gonadotrophins in our case did not prove to be a method for identifying a large recurrent gonadotroph pituitary adenoma. The sonographic ovarian imaging varied from a polycystic- to an ovarian hyperstimulation-like pattern during the evolution of the tumour.

[Androgen-producing steroid cell ovarian tumor. Report of a case].

Ovarian Tumors with Endocrine Repercussion make-up 5% of neoplasms in this gland, occupying the first place are the estrogen-producing tumors, in the second place are the androgen-producing tumors, progesterone, corticosteroids and renin are exceptional. In these tumors' nomenclature has existed a kind of synonyms that create confusion about their histogenesis and their difficult use in the literature. A 23 yr-old woman with opsomenorrhea of several years evolution, secondary amenorrhea, deep voice and progressive hirsutism. Weight: 98.500 kg. Height: 1.74 m. Body Mass Index (BMI): 32.61 (kg/m2). Vellus hair in the face (beard and moustache), android distribution in abdomen, forearms, thighs and legs (Ferriman score of 20), acne and bilateral breast involution. All paraclinic exams were negative. Human chorionic gonadotropin quantification in urine of 24 hours was negative. X-Ray: Right ovarian tumor was demonstrated with pelvic ultrasound and computerized axial tomography of abdomen. Cytogenetic study expressed 46 XX chromosomes. Presurgery endocrinologic studies were: total and free testosterone: 3.55 ng/mL and 14.30 pg/mL, respectively. Insulin: 43.3 microU/mL and C peptide: 5.7 ng/mL. The glucose tolerance test demonstrate intolerance to carbohydrates. During operation, the hormone levels in the right ovarian vein were: total and free testosterone of 2.70 ng/mL and 12.70 pg/mL respectively, which normalized after 12 hours of surgery. Other steroid hormones were normal. After six months of surgery the patient had Ferriman score of 10 and eumenorrhea. Weight: 98.100 kg, glucose tolerance test and basal hormone levels were normal. Electron Microscopy showed characteristic data of a steroid producing tumor without crystalloids of Reinke.

First_Aid_Step2

Anatomic: Generally requires surgical intervention. Defned as the absence of menses for six consecutive months in women who have passed menarche. First step: Get a pregnancy test. Second step: β-hCG: Measure TSH and prolactin. ■↑ TSH: Indicates hypothyroidism. ■↑ prolactin (inhibits the release of LH and FSH): Points to a thy roid pathology. Order an MRI of the pituitary to rule out tumor. ■↑↑ prolactin: Suggests a prolactin-secreting pituitary adenoma. Normal β-hCG: Initiate a progestin challenge (10 days of progestin). progestin challenge (withdrawal bleed): Indicates anovulation that is likely due to noncyclic gonadotropin secretion, pointing to PCOS or idiopathic anovulation. Check LH levels, and if LH is moderately high, the etiology is likely PCOS. Marked elevation of LH can indicate premature menopause. progestin challenge (no bleed): Indicates uterine abnormality or estrogen defciency. Check FSH levels. ■↑ FSH: Indicates hypergonadotropic hypogonadism/ovarian fail ure.

First_Aid_Step2

F IGU R E 2.1 2-3. Causes of primary and secondary amenorrhea. Ultrasound may be needed to evaluate the ovaries. Normal breast development and no uterus: Obtain a karyotype to evalu- The f rst step in the workup of 1° or 2° amenorrhea is a pregnancy test! ate for androgen insensitivity syndrome. Stigmata of Turner’s syndrome: Obtain a karyotype. Normal breast development and uterus: Measure prolactin and obtain a cranial MRI. Constitutional growth delay: No treatment is needed. Hypogonadism: Begin HRT with estrogen alone at the lowest dose. Twelve to eighteen months later, begin cyclic estrogen/progesterone therapy (if the uterus is present). Anatomic: Generally requires surgical intervention. Defned as the absence of menses for six consecutive months in women who have passed menarche. First step: Get a pregnancy test.

Growth hormone deficiency as the only identifiable cause for primary amenorrhea

Background: There is much evidence that growth hormone plays an important role in the development and function of the reproductive system of both males and females. Growth hormone exerts its effects on the ovarian follicular cycle directly or by local production of insulin-like growth factor 1 (IGF-1). It is known that growth hormone deficiency during childhood may delay pubertal development, but there is limited data about primary amenorrhea in GH-deficient girls with sufficient stimulated gonadotropin levels.Methods: Case series.Results: In the evaluation of primary amenorrhea and delayed puberty, 3 cases of adolescent females aged 17-19 years were identified as isolated GH-deficiency. Among the 3 patients, 2 had history of intracranial surgery due to hydrocephalus (shunt operation) or prolactin-secreting pituitary macro-adenoma (transphenoidal surgery, one year before). 17-year-old patient with shunted hydrocephalus and 19-year-old patient with primary amenorrhea showed short statue (< 5%) and delayed bone maturation. The patient undertaken transphenoidal surgery for prolactinoma showed normal height and bone maturation. There was no familial history of delayed puberty. On physical examination, 3 patients showed variable degree of breast development from Tanner stage II to IV without sex-steroid replacement. In sella MRI, small pituitary gland were identified in 2 patients with short statue and delayed bone maturation. All of the 3 patients underwent combined pituitary function test. After insulin-induced hypoglycemia, peak growth hormone levels of the 3 patients were 0.08, 1.4 and 1.4 ng/ml and were compatible with growth hormone deficiency. Peak LH after intravenous gonadrelin (FACTREL) were 19.0 to 56.1 mIU/ml and LH % responses were 217 to 1100% and were hence defined as not being gonadotropin deficiency. Other anterior pituitary functions were normal in all of the 3 patients.Conclusions: We found isolated growth hormone deficiency as the only identifiable cause for primary amenorrhea in three patients with sufficient gonadotropins secretion. These findings suggest a complementary role of GH to gonadotropins in the occurrence of menarche.

Functional hypothalamic amenorrhea

normal in FHA patients. No single E2 value can confirm FHA as each reflects only a certain time point, but in individuals whose E2 is <20 pg/mL persistently, an acute gonadotropin response to GnRH stimulation may distinguish FHA from hypogonadotropic hypogonadism. Testosterone and prolactin are expected to be in low normal ranges, and gonadotropins will be in a range lower than that which is characteristic of PCOS. In cases of stress-induced FHA, cortisol secretion, both basal and pulsatile, may be altered—increased concentrations are greatest in the early morning hours and overnight. However, these values may still be in the normal range. If clinical hyperandrogenism is evident, total testosterone and DHEA-S levels may also be obtained. 17α-hydroxyprogesteone levels should be evaluated if late onset congenital adrenal hyperplasia is suspected.

Gynecology_Novak

2. Prolactin is most accurately obtained in a patient who is fasting and who has not had any recent breast stimulation to avoid concluding that a patient is hyperprolactinemic on the basis of a transient prolactin elevation. If a patient still has some menstrual cycles, it is advisable to obtain the prolactin level in the follicular phase. Assessment of serum FSH levels is required to determine whether the patient has hypergonadotropic, hypogonadotropic, or eugonadotropic amenorrhea. A circulating FSH level of greater than 25 to 40 mIU/mL indicated on at least two blood samples is indicative of hypergonadotropic amenorrhea. Hypergonadotropism implies that the cause of amenorrhea is ovarian insufficiency. The history should establish whether the cause of ovarian insufficiency is chemotherapy or radiation therapy.

Functional hypothalamic amenorrhea

In all cases of amenorrhea, pregnancy should be excluded. This can be done by obtaining serum B-hCG levels. In cases of suspected FHA, screening laboratory tests include a complete blood count (CBC), electrolytes, glucose, bicarbonate, blood urea nitrogen (BUN), creatinine, liver panel, and when appropriate, sedimentation rate and/or C-reactive protein levels. Liver function tests may be abnormal in females with extreme energy restriction. The initial endocrine evaluation includes testing for levels of TSH and free T4, prolactin, LH, FSH, estradiol (E2), and anti-Müllerian hormone (AMH). FHA patients may display a combination of the following: FSH concentrations that are normal but lower than LH levels, low or low normal LH, E2 <50 pg/mL, and progesterone <1 ng/mL. LH and FSH are often normal in FHA patients. No single E2 value can confirm FHA as each reflects only a certain time point, but in individuals whose E2 is <20 pg/mL persistently, an acute gonadotropin response to GnRH

Gynecology_Novak

The anatomic causes of amenorrhea are relatively few, and the majority may be diagnosed by history and physical examination. The most important elements in the diagnosis of amenorrhea include physical examination for secondary sexual characteristics and anatomic abnormalities, measurement of human chorionic gonadotropin (hCG) to rule out pregnancy, serum prolactin and thyroid stimulating hormone (TSH) levels, and assessment of follicle-stimulating hormone (FSH) levels to differentiate between hypergonadotropic and hypogonadotropic forms of hypogonadism.

Multiple ovarian cysts and oligomenorrhea as the initial manifestations of a gonadotropin-secreting pituitary macroadenoma.

To report a case of a follicle-stimulating hormone (FSH)-secreting pituitary adenoma, which manifested with oligomenorrhea, dysmenorrhea, and multiple bilateral ovarian cysts. We present a case report of a 29-year-old woman, including detailed laboratory, radiologic, and pathologic findings, who was diagnosed as having an FSH-secreting pituitary tumor. The pertinent literature is also reviewed. A 29-year-old woman, after experiencing oligomenorrhea and increasing abdominal girth for >1 year, presented with an acute abdomen. Ultrasonography revealed multicystic ovaries >15 cm in maximal diameter, causing bilateral adnexal torsion. After bilateral ovarian cystectomies, ultrasound study showed recurrence of the cysts. Relevant laboratory data were as follows: serum FSH 6.8 mIU/mL, luteinizing hormone 0.1 mIU/mL, prolactin 67 ng/mL, human chorionic gonadotropin <2 mIU/mL, progesterone 3.5 ng/dL, estradiol 237 pg/mL, thyrotropin 1.8 microIU/mL, testosterone <4 ng/dL, insulin 8.0 microIU/mL, and fasting plasma glucose 87 mg/dL. Magnetic resonance imaging (MRI) of the brain revealed a 2.5-cm pituitary mass, although the patient had no symptoms of pituitary dysfunction. Transsphenoidal removal of the mass was performed, and pathology studies were positive for FSH-secreting adenoma. Repeated MRI at 3 months showed an 0.8-cm residual tumor. The patient refused adjuvant radiotherapy. Regular menses resumed within 2 months postoperatively, and she later successfully became pregnant. Almost 3 years after treatment, the patient remained asymptomatic, results of pituitary function tests were normal, and follow-up MRI showed no signs of tumor regrowth. Although very uncommon, gonadotropin-secreting pituitary adenomas should be considered in the differential diagnosis of new-onset oligomenorrhea and dysmenorrhea, especially if associated with multicystic ovaries on ultrasound study, even in the absence of elevated levels of serum gonadotropins. Furthermore, we propose that it may be acceptable to withhold adjuvant radiotherapy in patients who are asymptomatic after transsphenoidal surgical excision of these tumors.

[Evolution of plasma levels of SHBG (sex-hormone binding globulin) during ovulation induction using gonadotrophins].

The plasma levels of proteins bound to steroids come under the influence of the levels of estrogens. This is why we have studied the changes in plasma SHBG in sterile women who were being treated by gonadotropins (HMG-HCG). The plasma level of SHBG was worked out using Laurell's electroimmunoassay technique with an autoradiographic display using estradiol labeled with I.125. It only takes 48 hours contact with radio films. Out of 12 patients 9 responded to the treatment as demonstrated by the plasma levels of estradiol (E2) and progesterone (P). We have found that in these women there was a rise in plasma SHBG which was significant from the 7th day of the treatment onwards (3.7 +/- 1.7 mg/l as against 5.9 +/- 2.6 mg/l, p less than 0.01) and this reached nearly twice the base level when E2 reached its maximum level (6.4 +/- 2.7 mg/l). When treatment was stopped the plasma level of SHBG dropped to that of the follicular phase, but it was out of step with the plasma E2 levels. The index of free E2 as compared with E2/TEBG showed a close superimposition when compared with the levels of E2 obtained using a radioimmunological method. This fact reinforces the value of plasma E2 as the way of monitoring the effect of induction of ovulation. Our overall conclusion is that a marked and rapid change in the level of plasma E2 directly influences the level of plasma SHBG. The consequences for treatment are that it is important to respect as far as possible the physiological conditions that are present when induction of ovulation is undertaken.

[Clinical evolution of LH-RH reactivity in gynecology (author's transl)].

Impaired LH response to LH-RH has been found in 2/4 cases of primary amenorrhoea, in 2/8 cases of psychogenic secondary amenorrhoea, in 2/4 cases of secondary  amenorrhoea associated to a pituitary tumour and in 1/5 cases of iatrogenic secondary amenorrhoea post hormonal contraception. Therefore, this test appears not to differentiate these pathologic conditions.

Diagnostic role of inhibin B in resistant ovary syndrome associated with secondary amenorrhea.

To report two rare cases of gonadotropin-resistant ovary syndrome associated with secondary amenorrhea and normal levels of inhibin B. Case report. Two university teaching hospitals. Two women presenting with secondary amenorrhea and infertility. The control group for the inhibin B levels consisted of 30 cycling women of reproductive age. Medical history, physical examination, laboratory data, histologic findings, and IVF results. Diagnosis and treatment of resistant ovary syndrome. Case 1 was a 25-year-old woman with secondary amenorrhea and primary infertility. She had high serum levels of FSH and LH, low E(2) levels, and normal inhibin B levels (62 pg/mL). Karyotype was 46,XX, and ovarian biopsy showed primordial follicles with oocytes. Administration of GnRH analogue with hMG for 15 days did not affect E(2) levels. She had a successful pregnancy with IVF using donor oocytes. Case 2 was a 24-year-old woman with secondary amenorrhea. She had elevated serum levels of FSH and LH, low E(2) levels, and normal inhibin B levels (57 pg/mL). Karyotype was 46,XX and ovarian biopsy showed primordial follicles. Administration of GnRH analogue with hMG for 12 days did not affect E(2) levels. Both women were given estrogen-progestin replacement therapy. Inhibin B has a diagnostic role in women with gonadotropin-resistant ovary syndrome associated with secondary amenorrhea. A review of the literature confirms the uniqueness of the diagnostic role of inhibin B in these cases.

[Menometrorrhagia: to whom, why, on which criteria to propose a hormonal exploration?].

The hormonal exploration of menometrorrhagia concerns only the patients throughout their reproductive life, it is not indicated outside this period. In first intention at the woman in age to procreate, will be realized a determination of hCG, an inescapable determination to eliminate a pregnancy and a measure of serum TSH in the case of personal or family history for the screening of subclinical hypothyroidism. Further investigations can be carried out in second-based signs of appeal under the differential diagnosis of polycystic ovary syndrome (PCOS), as a measure serum prolactin, 17-hydroxyprogesterone and total testosterone and not bound to its binding protein the SHBG.

Poor ovarian reserve

Pretreatment with 50 mcg ethinylestradiol three times a day for two weeks, followed by recombinant FSH 200 IU/day subcutaneously. Ethinylestradiol treatment was maintained during FSH stimulation. When at least one follicle reached 18mm in diameter and serum estradiol was greater or equal to 150 pg/ML ovulation was induced with an intramuscular injection of 10,000 IU of hCG (human chorionic gonadotropin hormone). For luteal phase support 5,000 IU of hCG was administered every 72 hours. Out of 25 patients 8 ovulated and 4 became pregnant. In the control group there were no ovulations. The patients ranged in age between 24 and 39 years with an average age of 32.7. All women had amenorrhea for at least 6 months (average 16.75 months) and FSH levels greater or equal than 40 mIU/mL (average FSH 68 mIU/ML). The researchers believe this protocol would work for women in early post menopause as well.

The effect of gonadotropin-releasing hormone on ovarian estradiol secretion.

The present study was undertaken to determine if more than one dose of GnRh is necessary to induce luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion that is sufficient to cause a significant increase in circulating estradiol (E2) levels. Thirty-four women were studied. Of these, eight control women were studied in the early follicular phase (baseline E2, 48 +/- 4.5 pg/ml); eight patients had secondary amenorrhea caused by hypothalamic dysfunction (baseline E2, 52.0 +/- pg/ml), seven had secondary amenorrhea caused by hypothalamic pituitary failure (baseline E2, 21 +/- 2.5 pg/ml), and 11 women had amenorrhea, galactorrhea, and hyperprolactinemia (baseline E2, 16.5 +/- 3 pg/ml and baseline prolactin, 443 +/- 98 ng/ml). An initial intravenous bolus of 150 microgram  of gonadotropin-releasing hormone was followed 2 hours later by a smaller dose of 50 microgram. Thirty minutes following the first and second doses of GnRH, plasma LH and FSH increased significantly in all subjects. The initial increase of LH and FSH did not result in an increase in the plasmma E2 levels in any of the subjects. However, following the second gonadotropin peak, a significant increase in plasma E2 values was observed at 4 hours in all subjects (P less than 0.01). It can be concluded that (1) GnRH can be used to induce ovarian stimulation in normal women as well as in amenorrheic patients with low or normal baseline E2 levels as long as a sequential increase in LH and FSH can be elicited and (2) hyperprolactinemia does not interfere with ovarian E2 synthesis.

[Rational hormonal diagnosis of secondary amenorrhea].

The usefulness of the guideline recommended in 1976 by the World Health Organization (WHO) for the differential diagnosis of ovarian sterility needs critical reevaluation, since it does not take into account new aspects such as the pulsatility of GnRH secretion, androgen excess, or thyroid disorders and other phenomena related to ovarian dysfunction. In order to demonstrate the relative frequency of such phenomena, the authors examined 183 women with secondary amenorrhea of more than three months' duration (mean +/- SD = 12.7 +/- 18.4 months). The endocrine status of these women was examined under standardized conditions in two clinical endocrinology units in the cities of Hamburg and Berlin. The percentages of abnormal hormonal data (greater than mean +/- SD + gray zone) were as follows: testosterone (T) 39.9%; DHEA sulfate (DS) 29.5%; prolactin (PRL) 18.0%; TSH 11.5%; FSH or LH 26.8%; estradiol (E2) 30.1%. Among 96 patients with increased T and/or DS (52.5% of all patients), 53 patients (55.2%) did not show any clinical signs of androgenization (hirsutism, acne). Retrospective evaluation of all data revealed that a stepwise diagnostic procedure would have resulted in the following cumulative percentages of hormonal abnormalities: (1) T = 39.9%; (2) +DS = 52.5%; (3) +PRL = 60.2%; (4) +LH/FSH = 82.0%; (5) +E2 = 91.2%; (6) +TSH = 92.3%. Only in 7.7% of all patients were all hormonal parameters within normal ranges. Individual case analysis showed that 52.5% of all patients had hyperandrogenemia, while 18% had hypothalamic amenorrhea without any other pathologic condition; 17.5% had hyperprolactinemia and 3.3% primary ovarian insufficiency. Another 4.9% had hypothyroidism only, while 1.1% had exclusively hyperthyroidism. Combined hormonal deviations were found in 24% of all patients. Considering the differential diagnosis of secondary amenorrhea from an economic point of view, one comes to the conclusion that direct and indirect expenditures are similar in magnitude, no matter whether one prefers a conventional stepwise procedure or a one-step hormonal analysis encompassing all potentially relevant hormones (DM 859.00 + 10 weeks waiting time vs. DM 827.50 + 1 week waiting time). Androgen excess is much more frequent than was believed; hirsutism and/or acne by no means necessarily occur in cases of androgen excess. Hyperprolactinemia is less frequent than hyperandrogenemia. Thyroid status should be evaluated in all women with functional amenorrhea. The stepwise diagnostic procedure as recommended by the WHO is time-consuming, complicated, and sometimes incomplete in the diagnostic work-up, with obvious potential disadvantages for therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Turner syndrome and pituitary adenomas: a case report and review of literature.

Turner syndrome (TS) is the most common sex chromosome abnormality in females, typically associated with primary amenorrhea and premature ovarian failure due to gonadal dysgenesis. The association of TS with hypopituitarism is an uncommon finding. The objective of the study was to describe an adolescent with TS with hypergonadotropic hypogonadism and subsequent hypogonadotropic hypogonadism. A 16-year-old female with primary amenorrhea was diagnosed with TS based on karyotype 45,XO. Other laboratory values included FSH 45.52 IU/L, LH 17.4 IU/L, undetectable estradiol, and prolactin 1.08 nmol/L. Two months later and before treatment, she presented with severe headache and a new left cranial nerve VI palsy. Brain MRI showed a 2.7-cm hemorrhagic pituitary macroadenoma expanding the sella. Laboratory evaluation showed FSH 5.9 IU/L, LH 0.9 IU/L, prolactin 0.09 nmol/L, and GH 1.03 ng/mL. She underwent transphenoidal hypophysectomy, and pathology revealed pituitary adenoma with immunohistochemical staining positive for growth hormone and prolactin. She subsequently developed multiple pituitary hormone deficiencies. Review of the literature identified eight case reports of women with TS who developed pituitary adenomas. This case illustrates an uncommon co-occurrence of TS and pituitary macroadenoma. Sequential gonadotropin measurements demonstrate the evolution of hypergonadotropic hypogonadism into hypogonadotropic hypogonadism due to hemorrhagic pituitary macroadenoma.

[Rational hormone diagnosis in normocyclic functional sterility].

Functional infertility in women with a normal menstrual cycle is the first symptom of a pathophysiological sequence of multiple different endocrinopathies. It usually progresses and leads to secondary amenorrhoea which is the most severe symptom of ovarian insufficiency. The percentage of abnormal hormonal parameters will increase with the duration and extent of the endocrinological aberration. The aim of this study is to examine the frequency of the different potential changes in hormone levels of an unselected group of female patients in a fertility clinic. 307 patients suffering from functional sterility (menstrual cycle 25-34 days) were investigated via basal hormone laboratory tests (including TRH test) under standardised conditions. 73 patients had pathological changes of the Fallopian tubes and in 116 patients their husbands had severe andrological problems. Excluded from this study were patients with bilateral occlusion of the Fallopian tubes and patients whose partners had a sperm count of less than 1 million/ml. The percentage of abnormal hormone levels (greater than mean + standard deviation + grey area) was 32.2% for prolactin (PRL), 7.8% for TSH, 20.9% for Delta-TSH, 18.4% for DHEA-sulfate (DS), 9.8% for testosterone (T), 18.9% for LH, and 11.5% for FSH (LH and FSH were specifically calculated only in 87 patients). In 65.5% of the patients the midluteal oestradiol (E2) and progesterone (P) levels were below normal, as sign of a corpus luteum insufficiency (CLI). A step- by-step diagnostic procedure would have yielded the following cumulative abnormal hormone levels retrospectively: (1) PRL (n = 99) = 32.2% (2) +TSH/delta TSH (n = 85) = 48.9% (3) +DS (n = 56) = 58.0% (4) +T (n = 30) = 59.3% (5) +LH/FSH (n = 28) = 62.2% [(6) +E2/P (n = 201) = 82.7%.] Only in 37.8% (116 patients) all hormone levels were within normal limits during the early follicular phase (FP); if the patients with signs of CLI are added, the percentage would be only 17.8% (n = 53). Case analysis demonstrated that functional sterility was accompanied by hyperprolactaemia in 32.4% of all patients, by abnormalities of the thyroid function (hypothyroidism 16.0%, hyperthyroidism 7.8%) in 23.8%, by hypothalamic and/or pituitary dysfunction in 28.7%, and by hyperandrogenaemia in 22.5%. Primary ovarian insufficiency was diagnosed in 4.6%. 31.3% of all patients (n = 307) had a combination of different hormonal abnormalities. The average duration of infertility among this group of patients was 6.3 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Gender Incongruity in a Person with 46,XY and Complete Androgen Insensitivity Syndrome Raised as a Female.

We present the case of a patient with female sex assignment at birth whose parents consulted with a pediatrician when the child was 12 years old, indicating that despite female sex assignment, she felt that she (henceforth "he") had a male gender identity and was gynephilic. Medical examination revealed a 46XY karyotype, a primary amenorrhea and an appropriate testosterone increase after HCG stimulation test. The patient was diagnosed then with a 46,XY disorder of sex development with androgen insensitivity syndrome, but then he missed subsequent appointments. At the age of 24, he resumed medical follow-up to reaffirm his male gender identity through sex reassignment surgery. His physical examination showed a Tanner stage III-IV breast development, vulva, clitoris, normal-sized vagina, absence of uterus and ovaries on transvaginal ultrasound, bilateral cryptorchidism on abdominal-pelvic MRI and osteoporosis on bone densitometry. The results of the blood tests were LH 24.5 mIU/mL [normal range, 1.7-8.6 mIU/mL for men] and testosterone 8.8 nmol/L [8.7-33 nmol/L]; conversely, FSH, estradiol, progesterone, and prolactin levels were normal. The molecular genetic analysis revealed an androgen receptor gene mutation associated with complete androgen insensitivity syndrome. At present, the patient has undergone bilateral orchiectomy and has initiated treatment with topical testosterone and bisphosphonates. We have yet to evaluate the effects and decide the best therapy taking into account that he has a male gender identity but complete androgen insensitivity syndrome.

Anti-goat antibodies as a rare cause of high gonadotropin levels during menopausal transition.

<bObjective:</b To understand the origin of extremely high gonadotropin levels in a perimenopausal woman.<bMethods:</b A 52-year-old woman with a 2 months of amenorrhea followed spontaneous menstrual cycles recovery was referred to our outpatient clinic with elevated follicle-stimulating hormone (FSH, 483 mUI/ml), luteinizing hormone (LH, 475 mUI/ml) and prolactin (PRL, 173 ng/ml). She was known to take levosulpiride. The gonadotropin levels did not fit with the clinical features.<bResults:</b A gonadotroph tumor was ruled out. Further analysis confirmed constantly high FSH, LH and PRL levels. The measurements were repeated using different analytical platforms with different results. After serial dilutions, nonlinearity was present suggesting an immunoassay interference. After post-polyethylene glycol recovery, hormone levels appeared in the normal range. Anti-goat antibodies were recognized in the serum of the patient.<bConclusions:</b This case report shows a case of falsely abnormal high gonadotropin and PRL levels in a woman during menopause transition. In the clinical practice the evaluation of gonadotropin profile is not recommended at this age, but the abnormal levels stimulated further evaluation. An interference in the assay due to anti-goat antibodies resulted in abnormally high level of FSH and LH. A strict collaboration between clinicians and the laboratory is needed, when laboratory findings do not correspond to clinical findings.

[Treatment with LH-RH in female sterility].

The discovery that LH/RH was secreted in a pulsatile manner has made it possible to use the substance therapeutically in certain endocrine conditions of female sterility. 29 patients had sterility because of ovarian dysfunction. 3 of these were polycystic ovaries, 13 unexplained malfunction of ovulation and 30 hypothalamic in cause. They were treated with LH/RH intravenously. The dose used with each pulse was 6-18 micrograms. The patients were treated for between 18 and 30 days. In the 9 pregnancies that occurred (30%) one was in a patient with polycystic ovaries, 8 (70%) were in patients with hypothalamic ovarian failure. In each case the dose of LH/RH had been administered either at a level of less than 10 micrograms/pulse throughout the follicular phase with an injection of 5000 IU of HCG after ovulation or throughout the whole cycle. 77% of the pregnancies were obtained during the two first cycles of treatment. This work shows that hypothalamic female sterility is the proper indication for treatment using LH/RH. The protocol of dosage should be as economical as possible by administering 5-10 micrograms pulses intravenously up to the time that ovulation has been achieved. This takes note of the difficulties of obtaining supplies of the substance.

A rare case report of 46XY mixed gonadal dysgenesis.

A 16-year-old person, reared as female presented with complaints of genital ambiguity and primary amenorrhoea along with lack of secondary sexual characters, but without short stature and Turner's stigmata. She was taking steroids after being misdiagnosed as congenital adrenal hyperplasia (CAH). Karyotype analysis revealed 46XY karyotype. There was no evidence of hypocortisolemia (cortisol 9.08 μg/dl, adrenocorticotropic hormone [ACTH] 82.5 pg/ml) or elevated level of 17-OH-progesterone (0.16 ng/ml). Pooled luteinizing hormone (LH) was 11.79 mIU/ml and follicle-stimulating hormone (FSH) was 66.37 mIU/ml. Serum estradiol level was 25 pg/ml (21-251). Basal and 72 h post beta-human chorionic gonadotropin (hCG) levels of androstenedione and testosterone levels were done (basal testosterone of 652 ng/dl and basal androstenedione of 1.17 ng/ml; 72 h post hCG testosterone of 896 ng/dl and androstenedione of 1.34 ng/ml). Magnetic resonance imaging (MRI) pelvis (with ultrasonogrphy [USG] correlation) revealed uterus didelphys with obstructed right moiety and bilateral ovarian-like structures. Right sided gonads and adjacent tubal structures were visualized laparoscopically and removed. Left sided gonads were not visualized and Mullerian remnants were adhered to sigmoid colon. Histopathological examination revealed presence of testicular tissue showing atrophic seminiferous tubules with hyperplasia of Leydig cells. No ovarian tissue was seen. Based on these results a diagnosis of 46XY mixed gonadal dysgenesis (MGD) was made, which is rare and is difficult to distinguish from 46XY ovotesticular disorder of sexual differentiation (OT-DSD). The patient was managed with a multidisciplinary approach and fertility issues discussed with the patient's caregivers.

[Clinical use of Gonadorelin as a diagnostic agent in one- and two-step tests].

Synthetic LH/RH Gonadorelin, produced by VEB Berlin-Chemie, was given to 11 women with a normal menstrual cycle during the middle of the follicle phase. It was proved as a very effective drug, which provoked a typical gonadotropin release. Also 10 patients with a secondary amenorrhea responded already to the first intravenous injection of 80 micrograms Gonadorelin with a peak level of gonadotropins, in particular with LH levels, after 30 to 60 minutes (delta 1 = 1 st peak level--0' level). The relative ascent of gonadotropins (delta 2 = 2nd peak level--120' level) after the second step i.v. administration of 80 micrograms Gonadorelin at a 120 minutes interval was not significantly higher than delta 1. The reaction of pituitary on LH/RH does not immediately depend on the basal level of gonadotropin values. It reflects the severity of the hypothalamic-pituitary functional disturbance. The "Gonadorelin-test" ist a good complement to the progesterone- and clomiphene-test.

Hypopituitarism

Basal tests Levels of LH/FSH may be suppressed by a raised prolactin level, and are therefore not interpretable unless prolactin is low or normal. In men, the combination of low LH and FSH in combination with a low testosterone confirms LH/FSH deficiency; a high testosterone would indicate a source elsewhere in the body (such as a testosterone-secreting tumor). In women, the diagnosis of LH/FSH deficiency depends on whether the woman has been through the menopause. Before the menopause, abnormal menstrual periods together with low estradiol and LH/FSH levels confirm a pituitary problem; after the menopause (when LH/FSH levels are normally elevated and the ovaries produce less estradiol), inappropriately low LH/FSH alone is sufficient. Stimulation tests with GnRH are possible, but their use is not encouraged.

The natural history of idiopathic hyperprolactinemia.

Idiopathic hyperprolactinemia (IH) can be defined as the presence of elevated serum PRL levels in a patient in the absence of demonstrable pituitary or central nervous system disease and of any other recognized cause of increased PRL secretion. This study examined the long term clinical outcome of 41 patients (mean age, 26 yr) with IH followed for up to 11 yr (mean, 5.5 yr). Initial and final PRL levels were determined by RIA in the same laboratory. A correction factor was used to obviate periodic changes in the potency of the NIH standards used in the PRL assay, so that all results are expressed in terms of the original VLS no. 1 standard. The initial serum PRL levels ranged from 27.2-243 ng/ml, with a mean of 57 ng/ml. Only three patients had initial serum PRL levels greater than 100 ng/ml. All had a normal skull x-ray and/or brain computed tomographic scan during their initial visit. All 41 patients had galactorrhea and/or amenorrhea. Serum PRL levels remained the same, decreased, or returned to normal in 34 of 41 patients. The mean PRL level at the time of reevaluation was 35 ng/ml. Thirty-four percent of the patients had a normal serum PRL level. Only 17% of the patients had serum PRL levels that were significantly higher (greater than 50% of their original value). Six of 9 patients with an initial serum PRL level less than 40 ng/ml had normal levels. One patient developed a pituitary tumor (initial PRL, 150 ng/ml). All patients reevaluated with brain computed tomographic scans had normal pituitary size. No patient reported a worsening of signs or symptoms, and in many, improvement (n = 16) or complete resolution (n = 8) of the amenorrhea and/or galactorrhea occurred. Twenty-seven spontaneous or bromocriptine-induced normal pregnancies and deliveries occurred without development of a pituitary tumor. Therefore, our data clearly challenge the use of ablative pituitary therapy for IH and raises questions of the benefit of chronic medical therapy for this condition.

Menstrual abnormalities in a woman with ACTH-dependent pituitary macroadenoma mimicking polycystic ovary syndrome.

Here, we present a case of ACTH-dependent pituitary macroadenoma (Cushing's disease) resulting in secondary amenorrhea mimicking polycystic ovary syndrome (PCOS). A 20-year-old nulligravid woman had been suffering from oligomenorrhea, amenorrhea, and moderate hirsutism since the age of 18 years. She visited a gynecologic clinic where PCOS was impressed according to the clinical manifestation and ultrasound finding. The patient responded to medication in the 1st year, but gradually failed to induce menses. She was advised to visit the endocrinology department for secondary amenorrhea and endocrine survey. Physical examination revealed central obesity, supraclavicle fatpad, abdominal striae, and myopathy of four limbs. Endocrine studies revealed: serum prolactin 21 ng/mL (3.0-20 ng/mL), FSH 5.69 mIU/mL (3.4-10.0 mIU/mL), LH 1.01 mIU/mL (1.1-11.6 mIU/mL), E2 < 20 pg/mL (follicular phase 53-258 pg/mL), ACTH 110 pg/mL (0-46.0 pg/mL), cortisol 26.7 microg/dL at 8 a.m. (5.0-25 microg/dL), cortisol 21.3 microg/dL at 11 p.m. (half of normal morning value). Right pituitary macroadenoma was diagnosed through a series of dexamethasone tests and MRI. The patient received staging surgery including transsphenoidal adenomectomy and right frontotemporal craniotomy. As a result, the patient's physical condition gradually improved, and her menstrual cycle became regular with medication after the operation in the outpatient follow-up. PCOS is a common disease resulting in secondary amenorrhea. However, Cushing's syndrome resulting from pituitary macroadenoma should also be considered. Therefore, a careful history, observation, physical examination, and endocrine studies can differentiate between patients with PCOS and Cushing's disease.

Etiological diagnosis of hyperprolactinemia.

There are numerous etiologies of hyperprolactinemia, a common reason for consultation. Diagnostic measures must be capable of identifying the tumors, the most frequent of which are prolactin adenomas. Hypothalamic-pituitary MRI is the reference morphological examination. In clinical practice, it is usually performed very early, following the discovery of increased plasma concentrations of PRL. This approach is warranted for marked increase in PRL in the absence of drugs with hyperprolactinemic effects (>10 x upper limit of normal) since a diagnosis of PRL adenoma is extremely likely under such circumstances. When hyperprolactinemia is moderate, which is the most common finding in practice, all etiologies are possible in theory and it is important to follow a rational diagnostic plan (history-taking to identify use of any drugs with hyperprolactinemic effects paying attention to renal and hepatic history, investigation for endocrine diseases occasionally associated with hyperprolactinemia such as hypothyroidism or polycystic ovary syndrome (PCOS), confirmation of hyperprolactinemia by a second assay when the initial level is less than five times the upper normal limit, pregnancy testing for women of childbearing age) in order to rule out all non-tumoral causes of hyperprolactinemia before proceeding with imaging. Absence of any consequences of hyperprolactinemia on gonadic function or the existence of a concomitant disease that could account for the clinical signs, demonstration of wide variations in PRL from one assay to another in a single patient could prompt screening for macroprolactinemia before MRI is ordered. Macroprolactinoma could also occur in the case of normal or doubtful MRI or discrepancy in response to medical or surgical treatment. T1- and T2-weighted coronal sections (with or without T1 after gadolinium injection) are generally sufficient for diagnosis of microprolactinoma. Dynamic tests may be useful if MRI is normal or unclear. Gadolinium injection with sagittal and axial sections is essential for examination of large lesions. In this case, when the increase of PRL is moderate (<150 mg/ml), a non-lactotropic lesion may be suspected without misdiagnosing a hook effect. Careful analysis of the images allows differentiation between tumoral lesions and pituitary hyperplasia.

Hypoestrogenism

Functional hypothalamic amenorrhea Functional hypothalamic amenorrhea (FHA) is diagnosed based on findings of amenorrhea lasting three months or more, low serum hormone of gonadotropins and estradiol. Since common causes of FHA include exercising too much, eating too little, or being under too much stress, diagnosis of FHA includes assessing for any changes in exercise, weight, and stress. In addition, evaluation of amenorrhea includes a history and physical examination, biochemical testing, imaging, and measuring estrogen level. Examination of menstrual problems and clinical tests to measure hormones such as serum prolactin, thyroid-stimulating hormone, and follicle-stimulating hormone (FSH) can help rule out other potential causes of amenorrhea. These potential conditions include hyperprolactinemia, POI, and polycystic ovary syndrome.

[Restricted importance of LRH test in clinical routine diagnosis (author's transl)].

The pituitary responsiveness to luteinising hormone releasing hormone (LRH) was studied in 68 women aged between 15 and 30 years. The patients suffered from primary and secondary amenorrhoea or anovulatory cycles in combination with hirsutism, primary sterility, oligo-amenorrhoea, adrenogenital syndrome, and nervous anorexia. Eleven women without any discernible endocrinological disorders were used as controls. Double stimulation was performed by two intravenous injections of 25 microgram LRH each, spaced by one two-hour interval. Blood samples were taken repeatedly prior to, between, and after the injections at intervals set beforehand. Luteinising hormone (LH) plasma concentrations were determined by radio-immuno-assay. The mean difference between the two basic values measured ten and five minutes before LRH application was as low as 20.1 per cent. In most cases, the maximum values occurred 30 minutes after both injections. A positive correlation (r = 0.91, p < 0.001) was found to exist between the level recordable 30 minutes after the first injection and the integral of all values included. Dependence of response to LRH application on the height of the basic values was more strongly pronounced than that on the underlying category of disease. The LRH test, perhaps, may be indicated in cases of low basic LH values (< 2 ng/ml) to verify suspicion of a hypogonadotrophic situation. Simplification of the test procedure to only one withdrawal of blood each immediately before and 30 minutes after LRH injection seems to be justified.

Juvenile granulosa cell tumour of the ovary presenting with hyperprolactinaemic amenorrhoea and galactorrhoea.

Secondary amenorrhoea and galactorrhoea represent a common endocrine presentation. We report a case of an oestrogen-producing juvenile granulosa cell tumour (JGCT) of the ovary in a 16-year-old post-pubertal woman with hyperprolactinaemia amenorrhoea and galactorrhoea which resolved following surgical resection of the tumour. This patient presented with a 9-month history of secondary amenorrhoea and a 2-month history of galactorrhoea. Elevated serum prolactin at 7081 mIU/l and suppressed gonadotropins (LH <0.1 U/l; FSH <0.1 U/l) were detected. Serum oestradiol was significantly elevated at 7442 pmol/l with undetectable β-human chorionic gonadotropin. MRI showed a bulky pituitary with no visible adenoma. MRI of the abdomen showed a 4.8 cm mass arising from the right ovary with no evidence of metastatic disease. Serum inhibin B was elevated at 2735 ng/l. A right salpingo-oophorectomy was performed, and histology confirmed the diagnosis of a JGCT, stage International Federation of Gynaecology and Obstetrics 1A. Immunohistochemical staining for prolactin was negative. Post-operatively, oestrogen and prolactin levels were normalised, and she subsequently had a successful pregnancy. In summary, we present a case of an oestrogen-secreting JGCT with hyperprolactinaemia manifesting clinically with galactorrhoea and secondary amenorrhoea. We postulate that observed hyperprolactinaemia was caused by oestrogenic stimulation of pituitary lactotroph cells, a biochemical state analogous to pregnancy. To the best of our knowledge, this is the first report of hyperprolactinaemia as a result of excessive oestrogen production in the context of a JGCT. Hyperprolactinaemia with bilateral galactorrhoea and secondary amenorrhoea has a wide differential diagnosis and is not always caused by a prolactin secreting pituitary adenoma.Significantly elevated serum oestradiol levels in the range seen in this case, in the absence of pregnancy, are indicative of an oestrogen-secreting tumour.JGCTs are rare hormonally active ovarian neoplasms mostly secreting steroid hormones.Serum inhibin can be used as a granulosa cell-specific tumour marker.JGCTs have an excellent prognosis in the early stages of the disease.