From what is described it is a macroprolactinoma as it is a pituitary tumor of more than one centimeter, which secretes prolactin and with an insufficiency of the rest of pituitary hormones. The first line treatment of choice is dopaminergic agonists, although when the visual field is affected, surgery may be chosen. In this case, the cavernous sinus is pressured by the mass, so the surgical risk increases. Therefore, in this particular case, the surgical option seems more risky. Taking this into account and the fact that it is a tumor that produces high levels of prolactin, which indicates that it probably responds to pharmacological blockade, the most appropriate option would be option 1, treatment with dopaminergic agonists.

From what is described it is a macroprolactinoma as it is a pituitary tumor of more than one centimeter, which secretes prolactin and with an insufficiency of the rest of pituitary hormones. The first line treatment of choice is dopaminergic agonists, although when the visual field is affected, surgery may be chosen. In this case, the cavernous sinus is pressured by the mass, so the surgical risk increases. Therefore, in this particular case, the surgical option seems more risky. Taking this into account and the fact that it is a tumor that produces high levels of prolactin, which indicates that it probably responds to pharmacological blockade, [HIDDEN].

We are referred from ophthalmology to a 31-year-old man who consulted for loss of vision and progressive headache. Physical examination showed temporal hemianopsia and pituitary MRI showed a 35 x 30 x 20 mm turnoration compressing chiasm and cavernous sinus. The results of the functional study are cortisol 14 microg/dL, TSH 1.4 microU/ml, T4L 1.2 ng/dL, prolactin 480 microg/L (vn < 15), testosterone 160 ng/dL (vn 300-1200), FSH 1.2 U/I., (vn 5-15) and LH 2 U/L (vn 3-15). What is the initial therapeutic approach?

Treatment of hypogonadotropic hypogonadism with testosterone.

Gonadotropin-secreting pituitary tumor associated with hypersecretion of testosterone and hypogonadism after hypophysectomy.

To review gonadotropin-secreting pituitary tumors and report the rare case of one of these tumors that caused high serum testosterone concentrations, followed by hypogonadism after hypophysectomy. A case report is presented of a 61-year-old man who had decreased vision in his left eye, found by computed tomography of the sella to be attributable to a soft tissue pituitary mass with upward extension that caused elevation and deviation of the optic chiasm. Endocrine and pathologic evaluations are presented, and the treatment and follow-up course are discussed. Endocrine evaluation revealed a serum follicle-stimulating hormone (FSH) of 72.48 mIU/mL, luteinizing hormone (LH) of 31.65 mIU/mL, prolactin of 26.42 ng/mL, and total testosterone of 15.24 ng/mL (all values higher than the normal ranges). A soft tissue mass (3.2 by 2.5 by 1.2 cm) with negative immunocytochemical staining for prolactin and growth hormone but positive staining for synaptophysin, FSH, and LH was removed. One month postoperatively, the patient's chief complaints were a decrease in penile size and erectile dysfunction. Endocrine evaluation revealed a decreased LH of <0.3 mIU/mL, total testosterone of <0.2 ng/mL, and FSH of 4.3 mIU/mL. Three months later with testosterone replacement therapy, testosterone levels normalized, LH was <0.3 mIU/mL, and FSH was 3.9 mIU/mL. Thyroid function and adrenal function were normal before and after surgical intervention. This rare case indicates that gonadotropin tumors can produce a functional LH that can increase serum testosterone levels.

Sparsely Granulated Corticotroph Pituitary Macroadenoma Presenting With Pituitary Apoplexy Resulting in Remission of Hypercortisolism.

Pituitary corticotroph macroadenomas, which account for 7% to 23% of corticotroph adenomas, rarely present with apoplexy. This report aimed to describe a patient with a sparsely granulated corticotroph tumor (SGCT) presenting with apoplexy and remission of hypercortisolism. A 33-year-old male patient presented via ambulance with sudden onset of severe headache and nausea/vomiting. Physical examination revealed bitemporal hemianopsia, diplopia from right-sided third cranial nerve palsy, abdominal striae, facial plethora, and dorsal and supraclavicular fat pads. Magnetic resonance imaging demonstrated a 3.2-cm mass arising from the sella turcica with hemorrhage compressing the optic chiasm, extension into the sphenoid sinus and cavernous sinus. Initial investigations revealed a plasma cortisol level of 64.08 (reference range [RR], 2.36-17.05) mcg/dL. He underwent emergent transsphenoidal surgery. Pathology was diagnostic of SGCT. Postoperatively, the following laboratory findings were found: (1) cortisol level, <1.8 ug/dL (RR, 2.4-17); (2) adrenocorticotropic hormone level, 36 pg/mL (RR, 0-81); (3) thyroid-stimulating hormone level, 0.07 uIU/mL (RR, 0.36-3.74); (4) free thyroxine level, 1 ng/dL (RR, 0.8-1.5); (5) luteinizing hormone level, <1 mIU/mL (RR, 1-12); (6) follicle-stimulating hormone level, 1 mIU/mL (RR, 1-12); and (7) testosterone level, 28.8 ng/dL (RR, 219.2-905.6), with ongoing requirement for hydrocortisone, levothyroxine, testosterone replacement, and continued follow-up. Corticotroph adenomas are divided into densely granulated, sparsely granulated, and Crooke cell tumors. Sparsely granulated pattern is associated with a larger tumor size and decreased remission rate after surgery. This report illustrates a rare case of hypercortisolism remission due to apoplexy of an SGCT with subsequent central adrenal insufficiency, hypothyroidism, and hypogonadism.

Medical therapy of macroprolactinomas in males: I. Prevalence of hypopituitarism at diagnosis. II. Proportion of cases exhibiting recovery of pituitary function.

Hyperprolactinaemia frequently causes secondary hypogonadism through central suppression of gonadotropin secretion. Macroprolactinomas (> 1 cm diameter) are more common in males and may additionally cause more generalised hypopituitarism. Recovery of the thyrotropic and/or corticotropic axes is well described following selective adenomectomy, but remains poorly defined in relation to medical (dopamine-agonist) therapy of macroprolactinomas. We therefore performed a retrospective examination of case records of male patients who had received medical therapy alone for macroprolactinoma between 1980-2001 (n = 35) and in whom tumor shrinkage was documented by interval pituitary imaging (reported throughout by a single neuroradiologist). Mean prolactin level at baseline was 59,932 mU/L (median 31,400; range 3,215-332,000); mean period of follow up was 4.2 years (median 2.6; range: 1.0-15). Defects of the following axes were evident at diagnosis: LH/FSH-testosterone (n = 27; 77%), TSH-T4 (n = 14; 41%-not including one case with pre-existing 1 degress hypothyroidism), ACTH-cortisol (n = 8; 23%). Overall, 14 men (40%) were deficient in 1 axis, seven (20%) in 2 axes and seven (20%) in 3 axes. Growth hormone secretory status was not systematically evaluated. In all but 6 patients, prolactin levels fell to normal or near-normal levels (mean 764 mU/L; median 260; range: < 10-4,833). Of the patients in whom adequate reassessment had been performed, thyrotroph function recovered in 4/9, corticotroph function in 4/6 and gonadotroph function in 16/26 cases. In four cases (11%) previously described, development of visual impairment as a result of the chiasmal traction syndrome necessitated a dose reduction in medical therapy to allow a degree of controlled tumor re-expansion. The prevalence at diagnosis of TSH and ACTH deficiency in men with macroprolactinomas was 41% and 23%, respectively. Among eight patients with insufficiency of TSH and/or ACTH secretion who underwent complete interval reassessment over several years of treatment, recovery of at least one axis occurred in six cases (75%). This study highlights the importance of screening ACTH- and/or TSH-deficient men during dopamine agonist therapy in order to identify cases where hypopituitarism has resolved.

[Prolactin microadenoma in men. Study of 14 cases].

Macroprolactinomas have been well documented in men over the past several years. By contrast, to the best of our knowledge, there have been no reports of microprolactinomas in men. We describe here 14 cases of microprolactinomas occurring in male patients (14 to 53 years old) and discovered on the basis of endocrine symptoms. Nine patients complained of impotence and/or decreased libido, 8 had gynecomastia with or without galactorrhea, 1 had undergone incomplete puberty. All patients had hyperprolactinemia (225 +/- 65 micrograms/l, mean +/- SEM, N less than 13 micrograms/l); plasma testosterone levels were low in 9 (162 +/- 33 ng/dl, mean +/- SEM; N = 308 - 876 ng/dl), while plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels and their responses to LH-releasing hormone (LHRH) were normal in all cases. Among the 14 patients, 12 had no hypopituitarism and 2 had only partial corticotrope insufficiency; none had visual disturbances and only one complained of headaches. The sella turcica was normal in size and shape in 2 cases but a double floor and/or a thinner part of the floor was observed in 12. CT scan of MRI demonstrated in all cases an intrasellar microadenoma with a mean size of 7 mm (range, 3 to 10 mm) and no preferential localization. One patient was treated with bromocriptine, while the others underwent surgery via the transsphenoidal route. Immunocytochemistry demonstrated immunoreactive-prolactin (IR-PRL) cells in all the adenomas. Surgery resulted in normalization of plasma PRL in 11 of the 13 patients and in lowering PRL levels in the others 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypogonadism -- Introduction

Nintey-five percent of the total testosterone in males is synthesized in the Leydig cells of the testis. Defects, whether acquired or congenital, that interefere with interactions in the hypothalamic-pituitary-testicular axis can cause male hypogonadism It is essential to distinguish between primary hypogonadism (which originates in the testes) and secondary hypogonadism (which originates in the hypothalamus or pituitary). Symptoms highly suggestive of hypogonadism include decreased spontaneous erections, decreased nocturnal penile tumescence, decreased libido, and reduced testicular volume. The normal range for early morning testosterone in a male is between 300 ng/dL to 1000 ng/dL [1] . Hypogonadism is diagnosed when the morning serum testosterone level is less than 300 ng/dL. However, clinical judgment can be exercised in the diagnosis of hypogonadism for patients with persistent symptoms of testosterone deficiency despite having testosterone levels are in the normal range [2] . Of note, total testosterone less than 405.9 ng/dL is below the fifth percentile [3] . Elderly males should aim for testosterone levels between 500 and 800 ng/dL while young adults should aim for testosterone levels between 600 and 900 ng/dL.

Hypogonadism

Normal total testosterone levels depend on the man's age but generally range from 240 to 950 ng/dL (nanograms per deciliter) or 8.3-32.9 nmol/L (nanomoles per liter). According to American Urological Association, the diagnosis of low testosterone can be supported when the total testosterone level is below 300 ng/dl. Some men with normal total testosterone have low free or bioavailable testosterone levels which could still account for their symptoms. Men with low serum testosterone levels should have other hormones checked, particularly luteinizing hormone to help determine why their testosterone levels are low and help choose the most appropriate treatment (most notably, testosterone is usually not appropriate for secondary or tertiary forms of male hypogonadism, in which the LH levels are usually reduced).

Pituitary Cancer -- Evaluation -- Laboratory Tests

Hyposecretory adenomas are tumors that cause the hyposecretion of hormones from the pituitary gland and can involve one or more hormones. Hyposecreting tumors require measuring levels of multiple hormones such as thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), free T4, total testosterone (in men), and cortisol. Hypogonadotropic hypogonadism requires magnetic resonance imaging (MRI) of the brain at the time of diagnosis to rule out a pituitary tumor as the underlying etiology. Confirmatory testing with stimulatory testing follows basic laboratory testing, and these tests are specific to the hormone of interest. [27] [28] [29]

Male Infertility -- Pathophysiology -- Prolactinoma

Prolactin levels in men are normally quite low. When elevated, they suggest a possible prolactin-secreting pituitary tumor.  Such tumors may cause infertility, hypogonadism (low testosterone), gynecomastia, galactorrhea, and possibly a reduction of the peripheral visual fields due to compression of the optic chiasm. Prolactin levels above 150 mcg/L are suggestive of this condition, while a level above 300 mcg/L is pretty much diagnostic. An MRI or CT scan of the sella should be done for confirmation. Dopamine agonists, such as cabergoline and bromocriptine, are generally used as medical therapy to suppress prolactin secretion, and many men will then normalize their testosterone levels and sperm counts. Surgical therapy with a trans-sphenoidal resection of the prolactinoma is successful in 80% to 90% of cases, but the tumors often recur.  Surgery is usually reserved for patients with visual field loss and in those where medical therapy is unsuccessful or not well tolerated. [34]

Gonadotropin-releasing hormone insensitivity

Diagnosis When suspected on the basis of the clinical presentation or physical findings, the diagnosis of GnRH insensitivity should be confirmed biochemically. The diagnosis requires the following findings: The demonstration of prepubertal serum concentrations of sex steroid hormones (serum testosterone less than 100 ng/dL [3.5 nmol/L] in males or serum estradiol less than 20 pg/mL [73 pmol/L] in females). Inappropriately low or normal serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations (usually less than 4 to 5 international units/L) rather than the high concentrations expected with primary gonadal failure. Otherwise normal anterior pituitary function.

The Testosterone Effect on Metabolic and Urologic Outcomes in Patients with Nonfunctioning Pituitary Macroadenomas and Hypogonadotropic Hypogonadism.

To evaluate cardiovascular risk, metabolic profile, low urinary tract symptoms (LUTS), and sexual function in patients with nonfunctional pituitary macroadenoma (NFPMA) and hypogonadotropic hypogonadism with testosterone therapy (TTh). A retrospective clinical study at a tertiary care center was performed in 101 men with NFPMA, HH, and TTh; metabolic profile, cardiovascular risk, International Prostate Symptoms Score (IPSS), and International Index of Erectile Function 5 (IIEF-5) scores were evaluated before initiation of TTh and at the last checkup with TTh. Age was 49.3 ± 8.8 years; <iT</i before TTh was 195 ng/mL (101-259) vs. 574 (423-774) at the last checkup. The time of TTh administration was 34 months (12-72). An increase in triglyceride levels (200 (153-294) vs. 174 (134-233) mg/dL; <ip</i=0.03), dyslipidemia (40% vs. 52%; <ip</i=0.03), and MetS (25% vs. 34%; <ip</i=0.05) was corroborated. A statistical difference in the Globorisk score and cardiovascular (CV) risk stratification was not found. IIEF-5 score was 15.5 ± 6.5 vs. 17.8 ± 5.3 (<ip</i=0.11). An improvement in penetration quality (2.0 ± 1.5 vs. 2.6 ± 1.3; <ip</i=0.05), erection after penetration (1.8 ± 1.2 vs. 2.5 ± 1.6; <ip</i=0.02), completion of intercourse (1.8 ± 1.2 vs. 2.4 ± 1.3; <ip</i=0.03), and satisfaction of sexual intercourse (1.8 ± 1.3 vs. 2.5 ± 1.5; <ip</i=0.01) was evidenced. IPSS score was 6 (IQR 2-10) vs. 7 (IQR 4-12); <ip</i=0.30. A lower rate of intermittency (14% vs. 3%; <ip</i=0.02), urgency (39% vs. 16%; <ip</i=0.01), and episodes of nocturia (18% vs. 4%; <ip</i=0.02) was found. An increase of hematocrit (44.1 ± 4.4 vs. 47.3 ± 4.4%; <ip</i=0.001), hemoglobin (14.9 ± 1.4 vs. 15.9 ± 1.4 g/dL; <ip</i=0.001), and prostatic specific antigen (0.59 (0.43-1.19) vs. 0.82 (0.45-1.4) ng/mL; <ip</i=0.02) was evidenced during TTh. TTh in young men with NFPMA improves LUTS, sexual function, and some metabolic parameters, and it is relatively safe in the prostatic context.

[Brain tumor (germinoma) diagnosed after assessment for male late-onset hypogonadism syndrome: a case report].

A 44-year-old man suffered from sleep disturbance, headache, lack of energy and appetite loss. His local doctor recommended he consult our clinic for further examination of late-onset hypogonadism. His aging males' symptoms (AMS) and international index of erectile function (IIEF-5) scores were 62 and 1, respectively. His biochemistry revealed 0.29 mIU/ml luteinizing hormone (LH), 1.36 mIU/ml follicular stimulating hormone (FSH), 0.16 ng/ml total testosterone (TT) and＜0.6 pg/ml free testosterone (FT). Male hypogonadotropic hypogonadism was suspected from these results, He was then referred to a neurosurgeon for discrimination of intracranial disease where magnetic resonance imaging (MRI) revealed multiple intracranial tumors. An open brain biopsy was performed, and germinoma was diagnosed. After 4 courses of anti-cancer chemotherapy, complete remission was achieved. He was followed up endocrinologically by administration of testosterone injections along with other endocrinology replacement treatments. However, MRI 3 months later revealed tumor recurrence in the left lateral ventricle, and he has been receiving radiation therapy.

InternalMed_Harrison

Laboratory Investigation The presenting clinical features of functional pituitary adenomas (e.g., acromegaly, prolactinomas, or Cushing’s syndrome) should guide the laboratory studies (Table 403-2). However, for a sellar mass with no obvious clinical features of hormone excess, laboratory studies are geared toward determining the nature of the tumor and assessing the possible presence of hypopituitarism. When a pituitary adenoma is suspected based on MRI, initial hormonal evaluation usually includes (1) basal prolactin (PRL); (2) insulin-like growth factor (IGF) I; (3) 24-h urinary free cortisol (UFC) and/or overnight oral dexamethasone (1 mg) suppression test; (4) α subunit, follicle-stimulating hormone (FSH), and luteinizing hormone (LH); and (5) thyroid function tests. Additional hormonal evaluation may be indicated based on the results of these tests. Pending more detailed assessment of hypopituitarism, a menstrual history, measurement of testosterone and 8 A.M. cortisol levels,

Sarcoidosis within a pituitary adenoma.

A 54 year old man presented with frontal headaches for one year. A CT scan of the head revealed a pituitary mass. He denied a change in vision or galactorrhea, but did have decreased frequency of erections and a recent episode of renal stones. On physical exam, the cranial nerves were normal. Visual field exam revealed mild bilateral temporal defects. The genitalia were normal and the testes were soft. Laboratory evaluation revealed: Na, 134 mM/l; K, 6.7 mM/l; Cl, 104 mM/l; HCO3, 22 mM/l; BUN, 47 mg/dl; Cr, 8.3 mg/dl; Ca, 12.5 mg/dl; Phos, 5.5 mg/dl; prolactin, 32.0 ng/ml; T4, 4.46 microg/dl; TSH, 2.07 microU/ml; LH, 18.1 mIU/ml; FSH 3.2 mIU/ml; alpha subunit 1.6 ng/ml; testosterone 255 ng/dl; cortisol, 20.3 microg/dl; cortisol after 250 microg cortrosyn, 38.5 microg/dl (time 60 minutes); growth hormone, 1.4 ng/ml; IGF-1, 47 ng/ml; PTH, <1 pg/ml; 25-hydroxyvitamin D, 14 ng/ml; 1,25-dihydroxyvitamin D, 69 pg/ml. These results were felt to be consistent with a non-PTH-mediated hypercalcemia, such as humoral hypercalcemia of malignancy, or a vitamin D-mediated hypercalcemia, such as lymphoma, sarcoidosis or tuberculosis. Head MRI demonstrated a 3.5 x 3.5 x 2.5 cm heterogeneous mass enlarging the sella, deforming the clivus and compressing the cavernous sinus, basilar artery and left side of the optic chiasm. There was a small focus of high signal in the superior part of the mass on the T1-weighted image from either a proteinaceous cyst with early calcium deposition or sub-acute blood. These radiographic findings were felt to be consistent with a pituitary adenoma. The patient was treated with intravenous hydration and thyroxine 50 microg daily and underwent a transsphenoidal resection of the pituitary lesion. Pathologic examination revealed a pituitary adenoma with multiple granulomas and crystalline material; this was consistent with sarcoid within the adenoma. Post-operatively, the serum LH fell to 5.5 mIU/ml. A subsequent transbronchial biopsy revealed multiple non-caseating granulomas. A serum ACE level was elevated at 132.6 U/l. He received oral prednisone 60 mg daily with resolution of the hypercalcemia. Neurosarcoidosis occurs in 5 to 15% of patients with sarcoidosis and can involve the hypothalamus and pituitary gland. This is the first reported case of sarcoidosis occurring within a pituitary adenoma.

What causes a prolactinoma to be aggressive or to become a pituitary carcinoma?

Malignant prolactinoma is an exceedingly rare endocrine tumor and cannot be diagnosed on histological grounds alone. Similarly to other neuroendocrine tumors such as pheochromocytoma, the mitoses index, Ki-67, p53, and others are utilized in helping understand whether a tumor is benign or malignant or to better predict tumor behavior. We here present the unusual case of an unfortunate young man with an aggressive prolactinoma, the complications of which led to his premature death. A 25-year-old white man developed severe headaches, low energy, and decreased libido. A brain magnetic resonance imaging (MRI) showed a 4 x 3 x 2 cm pituitary tumor invading the left cavernous sinus. Laboratory findings revealed elevated prolactin (470 ng/mL) and adrenocorticotropic hormone (ACTH, 82 pg/ml) and decreased total testosterone (176 ng/dl). Visual fields showed superior quadrantanopia in the left eye. Transsphenoidal pituitary resection was undertaken. Pathology revealed a prolactinoma with atypical cells, diffuse p53 nuclear labeling, and a Ki-67 index of 23% (high). Postoperatively, prolactin remained elevated (725-891 ng/ml) and cabergoline was increased to 1 mg three times weekly, with serum prolactin further increasing to 3507 ng/ml five months postoperatively. Repeat MRI revealed extension of the tumor with optic chiasm compression and left orbit invasion. Because of acute left vision loss with ophthalmoplegia, an urgent left frontotemporal craniotomy and tumor resection were conducted. The Ki-67 index of the tumor was 24.8%, the mitotic figure immunostain phosphohistone-H3 positive. Sixty percent (60%) of tumor cells were positive for p53. Cabergoline was increased to 1 mg daily but prolactin remained elevated (770 ng/ml). The patient then underwent proton beam radiation to the area of concern involving the sella. Prolactin thereafter improved to 44 ng/ml. He then developed acute vision loss of the right eye with an MRI showing tumor in the right cavernous sinus. A 15 mm dural-based right temporal mass believed to be a metastasis was also noted. Following this scan, he was considered too high risk for debulking surgery and instead underwent gamma knife irradiation to the sella area. This shrank the right cavernous sinus tumor mass, while the right temporal mass increased in size. The patient developed blindness and left-sided weakness and required enteral feeding and tracheostomy after prolonged intubation. A trial of chemotherapy with temozolomide (350 mg daily for 5 days) near the end of his life was unsuccessful. He died on home hospice 31 months after his first surgery. Headaches, vision changes, and symptoms of androgen deficiency syndrome can be manifestations of an aggressive prolactinoma that might require surgery and additional medical therapy including cabergoline and temozolomide with an unpredictable time of survival.

[Anterior pituitary regulation of testicular function in the elderly (author's transl)].

Pituitary gonadotrophin regulation was examined with the LH-RH test in 15 men (aged between 55 and 90 years), five of them aged between 71 and 90 years. Compared to normal mature males, the plasma testosterone in these subjects was reduced or was in the lower range of normal, while basal LH levels were increased in half the cases. However, basal FSH values were increased in three only. In most of these subjects with increased basal values of LH, the LH-RH stimulation caused a paradoxical temporary reduction in LH release which did not occur with FSH. This paradoxical response also did not occur when basal LH values were normal.

Symptomatic Pituitary Metastasis as Initial Manifestation of Renal Cell Carcinoma: Case Report and Review of Literature.

Metastasis to the pituitary gland is extremely rare (∼2% of sellar masses). Clinical, biochemical, and radiologic characteristics of pituitary metastasis are poorly defined and can be difficult to diagnose before surgery. We present an unusual case with pituitary metastasis as the first manifestation of renal cell carcinoma (RCC). A 70-year-old male presented with acute onset of weakness, dizziness, diplopia, and progressively worsening headache. The initial CT head revealed a heterogeneous sellar mass measuring 2.8 × 1.9 × 1.7 cm. A follow-up MRI showed the sellar mass invading the right cavernous sinus. The presumptive diagnosis was a pituitary macroadenoma. Physical examination revealed bilateral 6th cranial nerve palsy and episodes of intermittent binocular horizontal diplopia. Hormonal testing noted possible secondary adrenal insufficiency (AM serum cortisol: 3.3 mcg/dL, ACTH: 8 pg/mL), secondary hypothyroidism (TSH: <0.01 mIU/L, FT4: 0.7 ng/dL), secondary hypogonadism (testosterone: 47 ng/dL, LH: 1.3 mIU/mL, and FSH: 2.3 mIU/mL), and elevated serum prolactin (prolactin: 56.8 ng/ml, normal: 4.0-15.2 ng/ml). IGF-1 level was normal at 110 ng/mL (47-192 ng/mL). The patient was discharged on levothyroxine and hydrocortisone therapy with plans for close surveillance. However, his condition worsened over the next three months, and he was subsequently readmitted with nausea, vomiting, and hypernatremia secondary to diabetes insipidus. Repeat MRI pituitary showed an interval increase in the size of the sellar mass with suprasellar extension and a new mass effect on the optic chiasm. The sellar mass was urgently resected via a trans-sphenoidal approach. The tumor was negative for neuroendocrine markers and pituitary hormone panel, ruling out the diagnosis of pituitary adenoma and triggered workup for metastatic renal cell carcinoma, clear cell type. The diagnosis of renal cell carcinoma was confirmed by the diffuse and strong staining for renal cell carcinoma markers (Pax-8, RCC-1, and CD10). A follow-up CT scan noted large right renal mass measuring 11 × 10 × 11 cm. The patient underwent a cytoreductive robotic right radical nephrectomy for WHO/ISUP histologic grade II clear cell RCC, stage pT2b pNX pM1. He subsequently received fractionated stereotactic radiotherapy to the pituitary gland. He is presently stable with no radiological evidence of progression or new intracranial disease on subsequent imaging. Pituitary metastasis most commonly occurs from breast, lung, or gastrointestinal tumors but also rarely from renal cell carcinoma. Biochemical findings such as panhypopituitarism, acute clinical signs such as headache, visual symptoms, and diabetes insipidus and interval increase in sellar mass in a short time interval should raise suspicion for sellar metastasis.

Effect of cranial irradiation on hypothalamus and pituitary functions.

Hypopituitarism can occur after cranial irradiation for tumors distant from the pituitary gland. Recent studies have suggested that this is hypothalamic in origin. Hypothalamic and pituitary functions were studied in 11 patients, 4 men and 7 women, 4.5 years or more after radiotherapy for nasopharyngeal carcinomas. The estimated average total dose was 5000 cGys for the hypothalamus and pituitary gland. Except for 2 women with amenorrhea and 4 men with impotency, the patients did not have evident endocrine deficiency. Baseline hormone profiles revealed normal T4, T3 and cortisol levels, 6 with elevated prolactin, 3 with reduced testosterone and 3 with slightly elevated basal TSH. The four menopausal women had impaired gonadotropin response to LHRH (100 micrograms, i.v.). Four (1 menstruating, 1 amenorrheic, 2 menopausal) women did not reach peak FSH response 4 hours after LHRH injection. The other amenorrheic woman had minimal FSH and LH response to LHRH which persisted even after 8 days of pulsatile infusion of LHRH (1 microgram/90min). TSH response to TRH (400 micrograms, i.v.) was delayed in 7 patients. GH response to human GRH (1 microgram/kg, i.v.) was impaired in 6 patients (maximal GH less than 5 mU/l). ACTH response to ovine CRH (1 microgram/kg, i.v.) was impaired in 3 patients (less than 50% elevation from baseline). Three patients who had normal GRH tests had impaired GH response to insulin hypoglycemia. Six patients had an empty sella on CT scan. From this study the following conclusions are drawn: (1) Among the four axes, GH is the most vulnerable. (2) The insulin tolerance test is still the best single test for evaluation of hypothalamic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Incomplete deficiency of hypothalamic hormones in hypothalamic hypopituitarism associated with an old traumatic brain injury.

A 62 year-old man was admitted to determine the pathogenesis of his hypoglycemia. He was unconscious and his plasma glucose level was 26 mg/dL. When he was 31 years old, he had a traffic accident and was unconscious for several days. Physical findings on admittance showed that the patient's BMI was 17.8 and blood pressure, 114/70 mmHg. He was alert. He had a hypogonadal face with a lack of beard, and he had an atrophic testis with a volume of 1 to 2 ml. Laboratory findings showed that his fasting plasma glucose was 73 mg/dL; serum sodium, 133 mmol/l; potassium, 4.1 mmol/l; serum insulin, less than 1.0 muU/ml.; plasma ACTH, 45.8 pg/ml; serum cortisol, 5.2 microg/dL; and free cortisol urinary excretion, less than 4.5 microg/day; serum LH, 0.8 mIU/ml; serum testosterone, less than 0.05 ng/ml; serum TSH, 2.0 uIU/ml; free T(4), 0.7 ng/dL; free T(3), 1.5 pg/ml; and serum prolactin, 29.0 ng/ml. The levels of all the pituitary hormones were elevated in response to a mixture of exogenous corticotrophin-releasing hormone (CRH), luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone (TRH), and growth hormone-releasing hormone (GRH). However, there was no increased secretion of adrenocorticotropic hormone (ACTH) in response to hypoglycemia (induced by the administration of insulin) and there was no increased secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) in response to the administration of clomiphene. Magnetic resonance imaging revealed an atrophied pituitary gland with an empty sella, but there were no abnormal findings of the hypothalamus. Hydrocortisone replacement at a dosage of 20 mg/day increased the patient's plasma glucose from 73 to 100 mg/dL and his serum sodium from 133 to 138 mmol/l. These findings therefore indicate a partial impairment in hypothalamic hormone release, resulting from a traumatic brain injury that the patient had received 31 years ago.

Is it possible to avoid hypopituitarism after irradiation of pituitary adenomas by the Leksell gamma knife?

Radiation therapy is one of the treatment options for pituitary adenomas. The most common side effect associated with Leksell gamma knife (LGK) irradiation is the development of hypopituitarism. The aim of this study was to verify that hypopituitarism does not develop if the maximum mean dose to pituitary is kept under 15 Gy and to evaluate the influence of maximum distal infundibulum dose on the development of hypopituitarism. We followed the incidence of hypopituitarism in 85 patients irradiated with LGK in 1993-2003. The patients were divided in two subgroups: the first subgroup followed prospectively (45 patients), irradiated with a mean dose to pituitary <15 Gy; the second subgroup followed retrospectively 1993-2001 and prospectively 2001-2009 (40 patients), irradiated with a mean dose to pituitary >15 Gy. Serum TSH, free thyroxine, testosterone or 17β-oestradiol, IGF1, prolactin and cortisol levels were evaluated before and every 6 months after LGK irradiation. Hypopituitarism after LGK irradiation developed only in 1 out of 45 (2.2%) patients irradiated with a mean dose to pituitary <15 Gy, in contrast to 72.5% patients irradiated with a mean dose to pituitary >15 Gy. The radiation dose to the distal infundibulum was found as an independent factor of hypopituitarism with calculated maximum safe dose of 17 Gy. Keeping the mean radiation dose to pituitary under 15 Gy and the dose to the distal infundibulum under 17 Gy prevents the development of hypopituitarism following LGK irradiation.

[Secondary male hypogonadism induced by sellar space-occupying lesion: Clinical analysis of 22 cases].

To analyze the clinical characteristics of secondary male hypogonadism induced by sellar space-occupying lesion, explore its pathogenesis, and improve its diagnosis and treatment. We retrospectively analyzed the clinical data about 22 cases of secondary male hypogonadism induced by sellar space-occupying lesion, reviewed related literature, and investigated the clinical manifestation, etiological factors, and treatment methods of the disease. Hypogonadism developed in 10 of the patients before surgery and radiotherapy (group A) and in the other 12 after it (group B). The patients received endocrine therapy with Andriol (n=7) or hCG (n=15). The average diameter of the sellar space-occupying lesions was significantly longer in group A than in B (［2.35±0.71］ vs ［1.83±0.36］ cm, P<0.05) and the incidence rate of prolactinomas was markedly higher in the former than in the latter group (60% vs 0, P<0.01). The levels of lutein hormone (LH), follicle stimulating hormone (FSH) and testosterone (T) were remarkably decreased in group B after surgery and radiotherapy (P<0.01). Compared with the parameters obtained before endocrine therapy, all the patients showed significant increases after intervention with Andriol or hCG in the T level (［0.78±0.40］ vs ［2.71±0.70］ ng/ml with Andriol; ［0.93±0.44］ vs ［3.07±0.67］ ng/ml with hCG) and IIEF-5 score (5.00±2.61 vs 14.50±3.62 with Andriol; 5.36±1.82 vs 15.07±3.27 with hCG) (all P<0.01). The testis volume increased and pubic hair began to grow in those with hypoevolutism. The patients treated with hCG showed a significantly increased testis volume (P<0.01) and sperm was detected in 7 of them, whose baseline testis volume was markedly larger than those that failed to produce sperm (［11.5±2.3］ vs ［7.5±2.3］ ml, P<0.01). Those treated with Andriol exhibited no significant difference in the testis volume before and after intervention and produced no sperm, either. Hypothyroidism might be attributed to surgery- or radiotherapy-induced damage to the pituitary tissue, space-occupying effect of sellar lesion, and hyperprolactinemia. Both Andriol and hCG can improve the T level and erectile function, but the former does not help spermatogenesis.

An adolescent boy with thalassemia major presenting with bone pain, numbness, tetanic contractions and growth and pubertal delay: panhypopituitarism and combined vitamin D and parathyroid defects.

A 16-year-old boy with transfusion-dependent thalassemia major presented with tetany, numbness, bone pain, short stature and pubertal delay. His height SDS score=-2.6, BMI=22.4, spleen was palpable 5 cm and liver 7 cm below the costal margins. The cardio-vascular examination was normal. Laboratory investigations showed a hemoglobin level (8 g/dL), hypocalcemia, hyperphosphatemia and elevated alkaline phosphatase (ALP) with serum 25-OH D below 3 ng/ml and a normal magnesium level. Serum parathyroid hormone (PTH) level was lower (21 pg/mL; normal 16-70 pg/mL) than expected for the degree of hypocalcemia. Serum ferritin concentration was 4442 ug/L, insulin-like growth factor I (IGF-I) was 31 microg/L (normal 122- 286 microg/L), free T4 was 13.1 microg/dL, TSH 1.2 mIU/ml. These results revealed a combined vitamin D-parathyroid defect. Peak growth hormone (GH) responses to clonidine and glucagon tests were 7.6 ng/ml and 6.2 ng/ml, respectively. Serum LH and FSH concentrations were below 0.5 U/L and testosterone was below 10 ng/dl. Radiographs revealed osteopenia of the phalanges and long bones and DXA scanning revealed low BMD Z-score of the femoral neck and 4th and 5th lumbar spines. MRI showed evidence of hemosiderin deposition in the pituitary. The patient was started on oral daily calcium carbonate (1500 mg elemental calcium) and vitamin D2 (calciferol) 25,000 IU/day and intensive iron chelation therapy. A low dose of IM testosterone enanthate (1 mg/kg/month) was injected for 6 months. Follow-up after 4, 8 and 12 months revealed normal Ca, PO4, ALP, and 25-OH D concentrations and disappearance of spasms and numbness and increased growth velocity. In conclusion, investigating calcium homeostasis at regular intervals and early management of any abnormality can preclude the occurrence of complications.

The value of pituitary magnetic resonance imaging in men with hypogonadism.

We assessed the usefulness of magnetic resonance imaging (MRI) of the brain in the evaluation of hypogonadal men with a variety of endocrine patterns. A total of 51 men with low levels of total testosterone (TT) or free testosterone (FT) underwent MRI. Erectile dysfunction and/or decreased libido were present in 43 (84.3%) of cases and infertility in 8 (15.7%). Serum prolactin (PRL) was obtained in all cases. Low levels of TT and FT were defined as less than 300 and 1.5 ng/dl, respectively. Markedly low levels of TT were defined as less than 200 ng/dl. In 38 of 51 (74.5%) men the MRI was normal. A small pituitary gland (the partially empty sella syndrome) was noted in 9 (17.6%) cases and microadenoma was noted in 4 (7.8%). Prolactin levels were greater than twice the upper limit of normal in 3 of 4 (75%) cases of adenoma, and low FT was noted in all 4 cases. An additional case of adenoma was identified in a man with markedly decreased TT and normal PRL. All men with adenoma presented with the combination of erectile dysfunction and decreased libido. Among men without adenomas the highest PRL value was always less than twice the upper limit of normal. Overall, only 1 of 17 men with markedly decreased TT (less than 200 ng/dl) demonstrated adenoma. None of the 17 men with low luteinizing hormone with low TT or FT had an adenoma or pituitary/hypothalamic mass. The likelihood of identifying pituitary adenoma by MRI is high if PRL levels are more than twice the upper limit of normal. Medically significant abnormalities are identified in only a small percentage of hypogonadal men with low luteinizing hormone or if TT levels are markedly decreased. The decision to obtain MRI in these latter cases should be based on individual circumstances.

Physiology, Anterior Pituitary -- Pathophysiology

Both hypofunction and hyperfunction can result. Measurement of pituitary hormones and target hormones can help define the defects. In Cushing disease, there is an increase in both ACTH and Cortisol. In Prolactinomas, there are very high PRL levels, generally greater than 200 ng/mL. In Acromegaly IGF-1 levels are increased, and  GH fails to suppress during an oral GTT. In hypopituitarism, there is decreased GH, IGF-1, LH FSH, testosterone in males, ACTH, cortisol T4 and TSH levels and PRL in Sheehan Syndrome. [9] [10]

[Primary hypothyroidism mimicking pituitary macroadenoma].

A 21-year-old woman complaining of 8-month amenorrhea associated to weight gain, galactorrhea and frequent headaches, presented for clinical evaluation; her laboratory tests were: TSH: 1192 mUI/ml (0.27-4.2); TT4: 1.0 microg/dl (4.4-11.4 l); TT3: 0.41 ng/ml (0.7-2.1); prolactin: 69.2 ng/ml (3-20) and a diagnosis of myxedema associated to galactorrhea was made. A hypothalamic-pituitary magnetic resonance imaging (MRI) showed a suprasellar and intrasellar mass lesion of 1.9 x 1.4 x 1.9 cm, determining compression and deviation of the optic chiasm. Due to the possibility of hyperplasia of the TSH-producing cells, treatment of hypothyroidism was initiated with levothyroxine. Two months later, upon normalization of thyroid hormones and TSH levels, a second MRI showed an anatomically normal pituitary gland. Regression of the pituitary mass after treatment with levothyroxine confirmed the hypothesis of pituitary hyperplasia secondary to primary hypothyroidism. Our findings support the importance of determining thyroid function tests during the investigation of pituitary masses and thus avoiding an unnecessary surgery.

[Selective venous sampling of pituitary hormones under provocative tests after retrograde cavernous sinus sinography (author's transl)].

In 22 subjects, selective venous sampling from the inferior petrosal sinus was performed under provocative tests along with simultaneous sampling of pituitary blood from the antecubital vein, after retrograde cavernous sinography. The difference of hormonal levels between sinus blood (Bs) and peripheral blood (Bv) was measured by two antibody radioimmunoassay. Most extreme difference of hormonal levels was observed in acromegalic subjects, where Bs/Bv ratio of GH was 6.0 in the basal value and 4.9 in the peak value, and that of PRL 3.5 and 4.6, respectively. In subjects who reacted to provocative tests, the average ratio of Bs/Bv ranged from 6.9 to 1.1 in the order of GH, PRL, LH, TSH and FSH. Non-reactive subjects showed no significant difference in the hormonal levels between Bs and Bv. From the results obtained above, we assume a possible relationship between Bs/Bv ratio and metabolic clearance rate and between difference of Bs-Bv and basal production. The integral of Bs-Bv difference measured from time zero to the time returned to the basal value under provocative tests represents the sum of basal production and pituitary reserve according to compartment analysis.

Sixteen years post radiotherapy of nasopharyngeal carcinoma elicited multi-dysfunction along PTX and chronic kidney disease with microcytic anemia.

The hypothalamic-pituitary (h-p) unit is a particularly radiosensitive region in the central nervous system. As a consequence, radiation-induced irreversible, progressively chronic onset hypopituitarism (RIH) commonly develops after radiation treatments and can result in variably impaired pituitary function, which is frequently associated with increased morbidity and mortality. A 38-year-old male subject, previously having received radiotherapy for treatment of nasopharygeal carcinoma (NPCA) 16 years ago, appeared at OPD complaining about his failure in penile erection, loss of pubic hair, atrophy of external genitalia: testicles reduced to 2×1.5 cm; penile size shrunk to only 4 cm long. Characteristically, he showed extremely lowered human growth hormone, (HGH, 0.115 ng/mL), testosterone (<0.1 ng/mL), total thyroxine (tT4: 4.740 g/mL), free T4 (fT4, 0.410 ng/mL), cortisol (2.34 g/dL); lowered LH (1.37 mIU/mL) and estradiol (22 pg/mL); highly elevated TSH (7.12 IU/mL). As contrast, he had low end normal ACTH, FSH, total T3, free T3, and estriol; high end normal prolactin (11.71 ng/mL), distinctly implicating hypopituitarism-induced hypothyroidism and hypogonadism. serologically, he showed severely lowered Hb (10.6 g/dL), HCT (32.7%), MCV (77.6 fL), MCH (25.3 pg), MCHC (32.6 g/dL), and platelet count (139×103/L) with extraordinarily elevated RDW (18.2%), together with severely lowered ferritin (23.6 ng/mL) and serum iron levels; highly elevated total iron binding capacity (TIBC, 509 g/dL) and transferrin (363.4 mg/dL), suggesting microcytic anemia. Severely reduced estimated glomerular filtration rate (e-GFR) (89 mL/mim/1.73 m2) pointed to CKD2. Hypocortisolemia with hyponatremia indicated secondary adrenal insufficiency. Replacement therapy using androgen, cortisol, and Ringer's solution has shown beneficial in improving life quality. To our believe, we are the first group who report such complicate PTX dysfunction with adrenal cortisol insufficiency concomitantly occurring in a single patient.

Gonadotroph cell adenomas of the pituitary.

Although the frequency of gonadotroph cell adenomas among all unselected pituitary adenomas is not yet known, it is probably much higher than previously suspected. The true incidence is probably somewhere between the 3-4% found in surgical and autopsy series, which is probably an underestimate because of its reliance on tissue content, and the 17% (24% when alpha-secreting adenomas are included) of 139 patients from this institution, which may be an overestimate of the incidence among all adenomas, because it is heavily weighted to very large adenomas in men only. Most patients who have been reported to have gonadotroph cell adenomas have similar clinical characteristics. Most are middle-aged men who have a history of normal pubertal development and a normal fertility history, and by examination are normally virilized and have testes of normal size. They are brought to medical attention because of visual impairment, which is the result of the enormous size of the adenoma. The most common hormonal characteristic of gonadotroph cell adenomas in vivo is hypersecretion of FSH, which is often accompanied by hypersecretion of FSH beta and alpha-subunit and less often by hypersecretion of LH beta or intact LH. Another common characteristic is secretion of FSH and/or LH in response to TRH. A few patients with gonadotroph cell adenomas hypersecrete intact LH and, therefore, have supranormal serum testosterone concentrations. A larger number have secondary hypogonadism because the adenomas are not secreting intact LH, but are compressing the normal gonadotroph cells and impairing LH secretion. These patients have concentrations of intact LH that are not elevated in spite of subnormal testosterone concentrations. Testosterone levels increase markedly in response to hCG. The hormonal characteristics of gonadotroph adenomas in dispersed cell culture are similar to their characteristics in vivo, including hypersecretion of FSH and LH subunits and responsiveness to TRH. Both the clinical and hormonal characteristics of gonadotroph cell adenomas usually make them readily distinguishable from pituitary enlargement due to long-standing primary hypogonadism. Pituitary adenomas that hypersecrete only alpha-subunit in vivo may also be adenomas of gonadotroph cells, because some of them secrete large amounts of FSH as well as alpha-subunit in culture. Most gonadotroph cell adenomas are now treated first by transsphenoidal surgery, to attempt to restore vision as quickly as possible, and then by supervoltage radiation to prevent regrowth of the remaining adenomatous tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Unusual MRI finding of multiple adenomas in the pituitary gland: a case report and review of the literature.

The simultaneous occurrence of multiple adenomas in the pituitary gland is a rare event. We report the coexistence of three non functioning pituitary microadenomas in a 37-year-old woman, referred to us for oligomenorrhea and headache. Biochemical evaluation revealed prolactin (131 U/liters), follicle-stimulating hormone (4.1 U/liters), luteinizing hormone (3.9 U/liters), 17beta-estradiol (74 pg/mL), free (2.0 pg/mL) and total testosterone (0.5 ng/mL), dehydroepiandrosterone-sulfate (3.5 microg/mL), 17OH-progesterone (0.8 ng/mL), cortisol (13.1 microg/dL), free triiodothyronine (4.8 pmol/L), free thyroxine (18.5 pmol/liters), thyrotropin (1.6 mU/L), and growth hormone (0.2 ng/mL) levels in the normal range, as for as the response to dynamic endocrine tests. MRI showed an enlarged sella turcica, occupied by three distinct hypointense areas that measured less than 5 mm in diameter in the left, medium and right side of the pituitary, respectively. This finding was confirmed 6 months later by a second MRI that revealed also a light increase in microadenomas dimensions. The patient, therefore, underwent neurosurgery by transfenoidal approach. Histologic examination showed no morphologic differences between the specimens obtained from the different microadenomas. Immunohistochemistry evaluation revealed a positive staining for the common alpha-subunit of glycoproteic hormones and negative for the other pituitary hormones tested, while electron microscopy showed cells with a poor secretory apparatus and a variable grade of cell differentiation. In conclusion, we report the fifth case described with multiple pituitary adenomas diagnosed in vivo and the first with three coexisting tumors revealed by MRI before neurosurgery. The occurrence of multiple pituitary tumors emphasizes the role of pituitary and extrahypophiseal factors in the clonal expansion of genetically altered cells.

[Gonadotropi adenoma linking labeled somatostatin analogs. Lack of relationship with therapeutic effect].

Somatotropin- and thyrotropin-secreting adenomas are well known for positive uptake of radio-labeled octreotide in vivo, this fact is not so well assessed for gonadotropin-secreting adenomas (GSA). We report one case of positive somatostatin receptor scintigraphy in a woman suffering from histologically proven GSA. This 63 year old patient has been suffering for two years of akinetic syndrome when the outcome of diplopia led to the discovery of a large hypophyseal tumor spreading till V3 floor and in left cavernous sinus by resonance magnetic imaging (RMI). Clinical examination showed anterior hypopituitarism and bitemporal hemianopsia. Biologically, blood gonadotropins were decreased more on LH (0.6 UI/l, N > 15) than on FSH (10 UI/l; N > 20). A lack of response of gonadotropins to LHRH with low blood estradiol concentration (< 10 pg/ml) was noticed. Basal blood measurement of alpha subunit was at 0.17 microgram/l (N = 0.10-1.6) and increased at 0.39 microgram/l after stimulation by LHRH. Although in low range of normal values, other hypophyseal hormones were normal except prolactinemia (45 mg/L; N < 20), however stimulated by TRH and related to dopaminergic deconnection; Indium 111 labeled octreotide scintigraphy showed an over uptake of the tumor. Three month treatment by octreotide (100 micrograms x 3/day subcutaneously) did not allow to decrease significantly FSH concentration or to reduce the tumoral mass. Incomplete removal of the tumor was performed by transphenoidal route. Immunohistochemical analysis revealed positive immunostaining for alpha subunit and FSH beta on numerous cells while the labeling was slightly less strong for LH beta. These data evoked a GSA. This case record depicts the possibility of detection of GSA by somatostatin receptor imaging. However a positive result does not preclude of somatostatin analog therapeutic efficiency.

Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment.

Persistence of hypogonadism is common in male patients with prolactinomas under dopamine agonist (DA) treatment. Conventional therapy with testosterone causes undesirable fluctuations in serum testosterone levels and inhibition of spermatogenesis. To evaluate the use of clomiphene as a treatment for persistent hypogonadism in males with prolactinomas. Open label, single-arm, prospective trial. Fourteen adult hypogonadal males (testosterone <300 ng/dl and low/normal LH) with prolactinomas on DA, including seven with high prolactin (range: 29-1255 microg/l; median: 101 microg/l) despite maximal doses of DA. Clomiphene (50 mg/day orally) for 12 weeks. Testosterone, estradiol, LH, FSH, and prolactin were measured before and 10 days, 4, 8, and 12 weeks after clomiphene. Erectile function, sperm analysis, body composition, and metabolic profiles were evaluated before and after clomiphene. Ten patients (71%), five hyperprolactinemic and two normoprolactinemic, responded to clomiphene (testosterone >300 ng/dl). Testosterone levels increased from 201+/-22 to 457+/-37 ng/dl, 436+/-52, and 440+/-47 ng/dl at 4, 8, and 12 weeks respectively (0.001<P<0.01). Estradiol increased significantly and peaked at 12 weeks. LH increased from 1.7+/-0.4 to 6.2+/-2.0 IU/l, 4.5+/-0.7, and 4.6+/-0.7 IU/l at 4, 8, and 12 weeks respectively (0.001<P<0.05). FSH levels increased in a similar fashion. Prolactin levels remained unchanged. Erectile function improved (P<0.05) and sperm motility increased (P<0.05) in all six patients with asthenospermia before clomiphene. Clomiphene restores normal testosterone levels and improves sperm motility in most male patients with prolactinomas and persistent hypogonadism under DA therapy. Recovery of gonadal function by clomiphene is independent of prolactin levels.

[Initial experience of an endocrinologist with the treatment of hypophyseal adenomas with the Leksell gamma knife].

Surgery of pituitary adenomas is not quite satisfactory so far and in some patients it is associated with a high risk. Conventional radiotherapy is only partly successful. Only few hospitals have experience with treatment of pituitary adenomas with Leksell's gamma knife. The objective of the presented paper is to give an account of the authors' own results of treatment of pituitary adenomas by irradiation with Leksell's gamma knife. The treated group comprised 13 patients (6 women, 7 men, 25-72 years old, median 44 years) with a pituitary adenoma. Hormonally active acromegaly was recorded in 9 patients, a prolactinoma in one female patient, afunctional adenoma in 3 patients. Twelve patients had been operated already previously, 3 of them twice. For visualization of the pituitary magnetic resonance (NMR) was used on a Magnetom apparatus 1.5 Tesla, Siemens Co. before surgery and one year after surgery. As hormonal indicators the following were examined: growth hormone (GH) profile in the course of the day and during the thyroliberin test (TRH), insulin-like growth factor I (IGF I), the prolactin level, the thyrotropin level (TSH) during the thyrotropin releasing hormone test (TRH) test the thyroxine level (T4) and the triiodothyronine level (T3), the plasma concentration of adrenocorticotropin (ACTH), the cortisol level, plasma testosterone level and 17-beta estradiol level. Complete recovery was achieved only in one female patient with acromegaly 18 months after irradiation, and in one patient with a prolactinoma a partial decline of hormone levels was recorded without detectable changes in the size of the adenoma. Only one female patient developed hypopituitarism. No other complications were recorded. Stereotactic irradiation with Leksell's gamma knife is valuable for treatment of pituitary adenomas and it is well tolerated therapy. Its effect is manifested only after several months. Complications in the sense of hypopituitarism may occur.

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.