This is severe primary hypothyroidism. Treatment is with thyroxine. If there is no nodule, neither echo nor FNA is indicated.

A 24-year-old man reports progressive asthenia for at least 6 months, hoarse voice, slow speech, drowsiness and swelling of the hands, feet and face. Examination: pulse at 52 beats per minute, abotarada face and dry and pale skin. CBC: mild anemia, cholesterol 385 mg/dL (normal <220), creatinine 1.3 mg/dL (normal: 0.5-1.1), negative proteinuria, TSH 187μIU/mL (normal 0.35-5.5) and Free T4 0.2 ng/dL (normal 0.85-1.86). What strategy do you think is most appropriate?

Perform a thyroid ultrasound before starting treatment.

Determine free T3 and perform a pituitary MRI.

Treat with L-triiodothyronine and a statin.

Treat with L-Tyroxine and determine antithyroid antibodies.

Perform thyroid cytology prior to treatment.

[Hypothyreoidism with thyroglobulin antibodies during corticoid replacement in a 54-year-old man with isolated ACTH deficiency]

Hypothyroidism with thyroglobulin antibodies during corticoid replacement in a 54-year-old man with isolated ACTH deficiency. HISTORY AND ADMISSION FINDINGS: A 54-year-old previously healthy man was admitted because of fatigue, tiredness, diarrhoea and weight loss for the last 3 years. Physical examination revealed dry but normally pigmented skin and markedly reduced Achilles reflex bilaterally. INVESTIGATIONS: Erythrocyte sedimentation rate was slightly elevated at 32 mm/h, C-reactive protein was normal. Both haemoglobin (12.4 mg/dl) and the corpuscular indices were normal, as were serum electrolytes, and sodium bicarbonate. But basal levels of thyroid stimulating hormone (TSH, 8.5 mU/ml) was markedly elevated, while free peripheral triiodothyronine (3.2pg/ml) was normal and free thyroxine (fT4) at 0.7 ng/d was slightly reduced. Thyroid ultrasound was normal. Test for antinuclear antibodies was slightly positive, but double-strand DNA was not demonstrated. Antithyroglobulin antibodies were slightly raised to 1012 IU/ml (normal <350). The basic level of ACTH was repeatedly below detection, as were plasma cortisol and cortisol excretion in 24-hour urine. Nuclear magnetic imaging was normal. Failure to stimulate corticol synthesis in the short ACTH test and by CRH indicated an isolated ACTH deficiency at the level of the anterior pituitary, while other hypophyseal functions were unaffected. TREATMENT AND COURSE: The patient"s condition rapidly improved on replacement with hydrocortisone, 30 mg/d, and thyroxine, 100 mg/d. No thyroglobulin antibodies or antinuclear antibodies were demonstrable after 6 months. Thyroxine was discontinued after 15 months. Frequent monitoring of thyroid function over the next 2 years always indicated a euthyroid state. CONCLUSION: Subnormal concentration of peripheral thyroid hormone combined with elevated TSH levels can, in the presence of hypercorticolism, be due to reversible abnormal thyroid function.

[Rhabdomyolysis, hyponatremia and fever in a patient with Schmidt's syndrome].

A 38-year-old man had fever (40 degrees C) and a swollen right leg. Two weeks before admission he had received non-steroid anti-inflammatory drugs (paracetamol and ibuprofen) after a tooth extraction. Some weeks before he had noticed a rough voice and a dry skin. The patient had a sinus tachycardia of 145/min (blood pressure of 130/80 mm Hg). Laboratory data revealed a CK of 16,650 U/l (< 80 U/l), myoglobin of 2420 U/l (< 90 microg/l) and LDH of 1250 U/l (<240 U/l), leukocyte count of 12,000 / microl and C-reactive protein of 3.0 mg/dl (<0.5 mg/dl). Sodium was markedly decreased (110 mmol/l (135 - 145 mmol/l)). Determination of thyroid hormone showed primary hypothyroidism with an elevated TSH of 62.6 mU/l (0.3 - 4.0 mU/l); T4 of 38 nmol/l (58 - 154 nmol/l), T3 1.17 of nmol/l (1.23 - 3.08 nmol/l) and fT4 of 6 pmol/l (10 - 25 pmol/l). The thyroid autoantibodies were increased (thyroxine peroxidase antibodies of 684 U/l (<35 U/l) and thyroglobulin antibodies of 173 U/l (<40 U/l)). Ultrasound of the thyroid revealed an nonhomogeneous structure. Cortisol at 8.00 a. m. was reduced by 63 mmol/l (180 - 640 mmol/l) and did not increase after administration of ACTH (60 min. cortisol at 90 mmol/l (>550 mmol/l)). ACTH was increased (141 pg/ml; normal range 17 - 52 pg/ml). The initial therapy consisted of hydrocortisone (100 mg i.v as bolus and 100 mg during the next 24 hours) and levothyroxine replacement (200 micro g) was initiated. During the following 8 days clinical symptoms regressed. Values of sodium, myoglobin and LDH decreased. After therapy with cephalosporin (Ceftriaxon) and penicillin (Flucloxacillin) fever and inflammation parameters decreased. This is a rare case of a rhabdomyolysis and hyponatriaemia due to hypothyroidism and Addison's disease (Schmidt's syndrome).

Case report: Rhabdomyolysis and kidney injury in a statin-treated hypothyroid patient-kill two birds with one stone.

Statin treatment for hypercholesterolemia may cause reversible rhabdomyolysis and acute kidney injury in susceptible patients. However, persistent rhabdomyolysis and acute kidney injury following discontinuation of statins require careful evaluation of the underlying causes to avoid missing a curable disease. We describe a 50-year-old woman with hypercholesterolemia [total cholesterol 345 mg/dl, low-density lipoprotein cholesterol (LDL-C) 266 mg/dL] on atorvastatin therapy (40 mg daily) for 1 month that presented with myalgia and muscle weakness. Relevant laboratory studies revealed persistent higher hypercholesterolemia with total cholesterol (312 mg/dL), high creatine kinase (CK) (5,178 U/L), and high creatinine levels (1.5 mg/dL) without dysmorphic red blood cells and proteinuria. Despite the cessation of statin therapy, serum CK level increased to 9,594 U/L, and creatinine remained at 1.5 mg/dL. A thorough work-up to assess potential underlying causes indicated low T3 and free T4 and high thyroid-stimulating hormone (TSH) levels, consistent with hypothyroidism. With aggressive thyroxine replacement for 1 month, all of the clinical features, along with elevated serum CK and creatinine levels, were completely resolved. This case highlights the fact that hypothyroidism must be kept in mind as a potential cause of concomitant myopathy and kidney injury, especially in patients with statin-resistant hypercholesterolemia.

Klinefelter's syndrome presenting with leg ulcers.

A 54-year-old man of Persian origin presented to our department with a 1-year history of ulcers on the right leg that had been unresponsive to numerous topical treatments, accompanied by lymphedema of the right leg. Medical history included hypergonadotropic hypogonadism, which had not been further investigated. He was treated for 20 years with testosterone IM once monthly, which he stopped a year before the current hospitalization for unclear reasons. The patient reported no congenital lymphedema. Physical examination revealed two deep skin ulcers (Figure 1) on the right leg measuring 10 cm in diameter with raised irregular inflammatory borders and a boggy, necrotic base discharging a purulent hemorrhagic exudate. Bilateral leg pitting edema and right lymphangitis with lymphadenitis were noted. He had low head hair implantment, sparse hair on the body and head, hyperpigmentation on both legs, onychodystrophia of the toenails (mainly the large toe and less prominent on the other toes), which was atrophic lichen-planus-like in appearance and needed no trimming (Figure 2), normal hand nails, oral thrush, and angular cheilitis. Other physical findings were gynecomastia, pectus excavatum, small and firm testicles, long extremities, asymmetrical goiter, systolic murmur 2/6 in left sternal border, and slow and inappropriate behavior. The patient's temperature on admission was 39 degrees C. Blood cultures were negative for bacterial growth. Results of laboratory investigations included hemoglobin (11.2 g/dL), hematocrit (26.8%), normal mean corpuscular volume and mean corpuscular hemoglobin volume, and red blood cell distribution width (16%). Blood smear showed spherocytes, slight hypochromia, anisocytosis, macrocytosis, and microcytosis. Blood chemistry values were taken for iron (4 micro g/dL [normal range 40-150 micro g/dL]), transferrin (193 mg/dL [normal range 220-400 mg/dL]), ferritin (1128 ng/mL [normal range 14-160 ng/mL]), transferrin saturation (1.5% [normal range 20%-55%]), serum folate (within normal limits), and vitamin B12 (within normal limits). Direct Coombs' test equaled positive 2 + IgG. All these values indicated anemia of chronic diseases combined with hemolytic anemia. Further blood work-up tested antinuclear antibody (positive <1:80 homogeneous pattern), rheumatoid factors (143 IU/mL [positive >8.5 IU/mL]), C-reactive protein (286 mg/L [normal range 0-5 mg/L]), anticardiolipin IgM antibody (9.0 monophosphoryl lipid U/mL [normal range 0-7.00 MPL U/mL]) and antithrombin III activity (135% [normal range 74%-114%]). Results of other blood tests were within normal limits or negative, including lupus anticoagulant, beta2 glycoprotein, anticardiolipin IgG Ab, anti-ss DNA Ab, C3, C4, anti-RO, anti-LA, anti-SC-70, anti-SM Ab, P-ANCA, C-ANCA, TSH, FT4, anti-T microsomal, antithyroglobulin, protein C activity, protein S free, cryoglobulins, serum immunoelectrophoresis, VDRL, hepatitis C antibodies, hepatitis B antigen, and human immunodeficiency virus. Endocrinological work-up examined luteinizing hormone (22.9 mIU/mL [normal range for adult men 0.8-6 mIU/mL]), follicle stimulating hormone (49.7 mIU/mL [normal range for adult men 1-11 mIU/mL]), testosterone (0.24 ng/mL [normal range for adult men 2.5-8.0 ng/mL]), bioavailable testosterone (0.02 ng/mL [normal range for adult men >0.6 ng/mL]), and percent bioavailable test (8.1% [normal value >20%]). These results indicate hypergonadotropic hypogonadism. Plasminogen activator inhibitor 1 was 6 U (normal value 5-20 U/mL). Karyotyping performed by G-banding technique revealed a 47 XXY karyotype, which is diagnostic of Klinefelter's syndrome. Doppler ultrasound of the leg ulcers disclosed partial thrombus in the distal right femoral vein. X-rays and bone scan displayed osteomyelitis along the right tibia. Histological examination of a 4-mm punch biopsy from the ulcer border revealed hyperkeratosis, acanthosis, hypergranulosis, and mixed inflammatory infiltrate containing eosinophils compatible with chronic ulcer. Multiple vessels were seen, compatible with a healing process. Direct immunofluorescence of the biopsy revealed granular IgM in the dermo-epidermal junction. Indirect immunofluorescence was negative. Thyroid function tests showed normal thyroid stimulating hormone and free throxine4. Multinodular goiter was seen on thyroid scan and ultrasound. Thyroid fine needle aspiration was compatible with multinodular goiter (normal follicular cells, free colloid, macrophages with pigment). IV treatment with amoxicillin-clavulanic acid 1 g t.i.d. was administered for 2 weeks, with a decrease in temperature and normalization of the leukocyte level. Oral antibiotic treatment with amoxicillin-clavulanic acid was continued for 10 more days, followed by 25 days of ciprofloxacin for the osteomyelitis. Local treatment included saline soakings followed by application of Promogran (Johnson & Johnson, New Brunswick, NJ) and Kaltostat (ConvaTec Ltd., a Bristol-Myers Squibb Company, New York, NY) with slight improvement. At the same time, the patient was treated with warfarin sodium due to deep vein thrombosis under international normalized ratio 2-3. The patient was treated with IM testosterone once monthly for 1 year, which resulted in a reduction in the diameter and depth of the leg ulcers (Figure 3). Blood tests were not performed for follow-up of the immune state.

Kidney failure in the elderly due to hypothyroidism: a case report.

Hypothyroidism is more prevalent in the elderly and its symptoms can be confused with other changes due to aging. Doctors caring for the elderly need to be attentive to this diagnostic possibility. This case report case is notable not only because it presents a rare complication of hypothyroidism (kidney failure), but also because patients with chronic kidney failure of any etiology may suffer increased renal dysfunction as a result. This was a 66-year-old male outpatient with a history of generalized edema over the preceding eight years, with periods of worsening, that was intractable to treatment with diuretics. Physical examination revealed bradycardia (heart rate: 52 bpm), pallor, dry and infiltrated skin, macroglossia, edema in the lower limbs and a palpable thyroid with hard consistency. Laboratory tests showed: creatinine 3.9 mg/dl; urea 95 mg/dl; potassium 6.0 mEq/l; thyroid-stimulating hormone > 100 mUI/ml; triiodothyronine 0.01 ng/dl; free thyroxin 0.01 ng/dl; antithyroglobulin 31 IU/ml (normal values: < 40 IU/ml); antithyroperoxidase 85 IU/ml (normal values: < 15 IU/ml); creatinine clearance 30 ml/min/1.73 m(2); and proteinuria 122 mg/24 h. After five months of treatment with thyroxin (100 mcg/day), the patient returned without any symptoms and presented the following test results: urea 48 mg/dl; creatinine 1.4 mg/dl; creatinine clearance 67 ml/min/1.73 m(2); potassium 4.2 mEq/l; thyroid-stimulating hormone: 20.85 mUI/ml; free thyroxin: 0.71 ng/dl. Hypothyroidism alone can cause renal impairment or worsen renal function in preexisting illnesses. Its treatment can stabilize the clinical condition, or possibly improve it.

Hyperthyroidism

In addition to testing the TSH levels, many doctors test for T3, Free T3, T4, and/or Free T4 for more detailed results. Free T4 is unbound to any protein in the blood. Adult limits for these hormones are: TSH (units): 0.45 – 4.50 uIU/mL; T4 Free/Direct (nanograms): 0.82 – 1.77 ng/dl; and T3 (nanograms): 71 – 180 ng/dl. Persons with hyperthyroidism can easily exhibit levels many times these upper limits for T4 and/or T3. See a complete table of normal range limits for thyroid function at the thyroid gland article. In hyperthyroidism CK-MB (Creatine kinase) is usually elevated. Subclinical

A case of simultaneous occurrence of Graves' disease and Hashimoto's thyroiditis.

Simultaneous occurrence of Hashimoto's thyroiditis (HT), and Graves' disease (GD) is rare. We report a case of simultaneous occurrence of GD and HD, at presentation. A 60-year-old lady presented with tremulousness of hands, palpitation, and excessive sweating. She had a history of weight loss and neck-swelling. Her weight was 46 kg, BMI 17, afebrile, regular pulse rate of 110/min with fine tremor in hands. Thyroid gland was symmetrically enlarged, firm, without any bruit, but mildly tender with lobular surface. There were no occular manifestations. Initial thyroid function tests (TFT) revealed: T3: 3.80 ng/ml (0.80-2.10), T4: 12.40 ug/dl (5.10-12), thyroid stimulating hormone (TSH): 0.20 μU/L (0.70-5). Her anti thyroperoxidase (TPO) antibody: 374 IU/ml (normal [nl.] <35) and TSH receptor antibody: 15 U/L (nl. <1) were both strongly positive. Ultrasonogram of thyroid revealed a hypoechoic enlarged gland. 99mTc pertechnetate scan showed an enlarged gland with increased uptake of radiocontrast: 17% (nl. 0.4-4%) with some patchy defects in both lower poles. Thyroid fine needle aspiration cytology (FNAC) showed sheets of Hurthle cells with abdunce of lymphocytes indicating HT. She was observed on beta blockers. Repeat TFT, 3 months later showed: T3: 4.20 ng/ml, T4: 14.40 ug/dl, TSH: 0.001 μU/L, with increased uptake on repeat scan. HT rarely occurs following GD. Our case of an elderly lady with no eye signs, lobular, firm tender goiter with patchy uptake in both lower poles on Tc99m scan were odd points in diagnosing isolated GD. FNAC confirmed simultaneous HD with GD.

InternalMed_Harrison

Adult patients under 60 years old without evidence of heart disease may be started on 50–100 μg levothyroxine (T4) daily. The dose is adjusted on the basis of TSH levels, with the goal of treatment being a normal TSH, ideally in the lower half of the reference range. TSH responses are gradual and should be measured about 2 months after instituting treatment or after any subsequent change in levothyroxine dosage. The clinical effects of levothyroxine replacement are slow to appear. Patients may not experience full relief from symptoms until 3–6 months after normal TSH levels are FIGURE 405-7 Evaluation of hypothyroidism. TPOAb+, thyroid peroxidase antibodies present; restored. Adjustment of levothyroxine TPOAb−, thyroid peroxidase antibodies not present; TSH, thyroid-stimulating hormone. dosage is made in 12.5or 25-μg increments if the TSH is high; decrements of the same magnitude should be made if the TSH is suppressed. Patients with a suppressed TSH of any

Hypothyroidism

Blood free thyroxine and TSH levels are monitored to help determine whether the dose is adequate. This is done 4–8 weeks after the start of treatment or a change in levothyroxine dose. Once the adequate replacement dose has been established, the tests can be repeated after 6 and then 12 months, unless there is a change in symptoms. Normalization of TSH does not mean that other abnormalities associated with hypothyroidism improve entirely, such as elevated cholesterol levels. In people with central/secondary hypothyroidism, TSH is not a reliable marker of hormone replacement and decisions are based mainly on the free T4 level. Levothyroxine is best taken 30–60 minutes before breakfast, or four hours after food, as certain substances such as food and calcium can inhibit the absorption of levothyroxine. There is no direct way of increasing thyroid hormone secretion by the thyroid gland.

Hashimoto Thyroiditis -- Evaluation

Hashimoto thyroiditis is an autoimmune disorder of inadequate thyroid hormone production. The biochemical picture indicates raised thyroid-stimulating hormone (TSH) in response to low free T4. A low total T4 or free T4 level in the presence of an elevated TSH level confirms the diagnosis of primary hypothyroidism. Integrative and functional medicine practitioners may also assess free T3 and reverse T3 levels; however, Western medicine does not use this approach. The presence of anti-thyroid peroxidase and anti-thyroglobulin antibodies suggests Hashimoto thyroiditis. However, 10%  of patients may be antibody negative. Anemia is present in 30 to 40%. There can be decreased glomerular filtration rate (GFR), renal plasma flow, and renal free water clearance with resultant hyponatremia. Creatine kinase is frequently elevated. Prolactin levels may be elevated. Elevated total cholesterol, LDL, and triglyceride levels can occur.

[A case of iodide myxedema observed for 3 years under a low iodide diet--especially on the restoration of the mechanism of escape from the Wolff-Chaikoff effect].

A 47-year-old housewife was admitted to our hospital because of general fatigue and constipation suggesting hypothyroidism. For 3 years before admission, general fatigue, arrhythmia, dry skin, drowsiness, cold intolerance and hypermenorrhea occurred insidiously. She had habitually taken considerable amounts of seaweed every day, e.g. more than 50 g of " Kombu " for more than 5 years and at least 1 g of " Wakame " for 6 months. On admission, serum thyroxine (T4) was 1.3 micrograms/dl, serum triiodothyronine (T3) was 47 ng/dl, TSH was 132 microunits/ml, and 123I thyroidal uptake was 60% at 3 hr. and 75% at 24 hr. Anti-thyroglobulin hemagglutination antibodies and anti-thyroid microsomal hemagglutination antibodies were both negative. When seaweed was omitted from her diet, T4 rose to 6.3 micrograms/dl and T3 rose to 113 ng/dl, whereas TSH lowered to 11 microunits/ml in 2 weeks. The seaweed-free diet was continued and 4 months later, when she had become euthyroid, an open biopsy of the thyroid gland was carried out. Histological examination of the specimen revealed a marked colloid deposition without characteristic features of Hashimoto's disease. Five months after admission, with the daily administration of 100 mg potassium iodide (KI), the effects of inorganic iodide on thyroid function had begun to be seen. On the 16th day of the KI regimen, palpitation and tachycardia (pulse rate 160/min.) with multifocal ventricular premature beat appeared, and T4 on the 11th day was 5.9 micrograms/dl, which was clearly lower than the pretreatment level of 8.4 micrograms/dl. KI was discontinued on the 16th day, and one week after the withdrawal, T4, T3 and TSH all returned to the pretreatment level. For more than 3 years on a seaweed-free diet, she remained euthyroid without any thyroid regimen. To see the effects of inorganic iodide on thyroid function after this long period on a seaweed-free diet, KI was again administered. One hundred mg/day KI for 14 days followed by 200 mg/day for 21 days had virtually no effect on T4, T3 and free T4 and she remained well. None of the perchlorate discharge tests performed on 3 occasions during the 6 month period after the initiation of the seaweed-free diet showed a discharge.(ABSTRACT TRUNCATED AT 400 WORDS)

[Agranulocytosis and acute coronary syndrome in apathetic hyperthyroidism].

Tissue expose to excessive levels of circulating thyroid hormones results in thyrotoxicosis. In most cases, thyrotoxicosis is due to hyperactivity of the thyroid gland. Cardiovascular and myopathic manifestations are predominant clinical features in most hyperthyroid patients, aged 60 years and older. Some of patients have apathetic hyperthyroidism which presents with weight loss, small goiter, severe depression and without clinical features of increased sympathetic activity [3, 6]. About 50% of patients with cardiovascular manifestations have no evidence of underlying heart disease. Cardiac problems resolve when euthyroid state is established [3]. Three treatment modalities are available in hyperthyroidism, namely medicament therapy, surgery and radioactive iodine. Antithyroid drug therapy complications, can be mild such as rash, which is managed without cessation of therapy by antihistamines administration. On the other hand, very serious complications such as agranulocytosis, necessitate immediate discontinuation of the medication and appropriate treatment. Although extremely rear, it is life-threatening with highly variable recovery time. A 62-year-old woman with recurrent hyperthyroidism was admitted after treatment of agranulocytosis due to antithyroid drugs in another institution with G-CSF. The patient presented with clinical features of apathetic hyperthyroidism with extremely elevated thyroid hormone levels (total and free T4) and suppressed TSH. Radioactive iodine (5 mCi) was administered after increased thyroid uptake was confirmed. Echocardiography on admission was normal. ECG revealed moderately inverted T waves in standard and V1, V2 precordial leads. Laboratory analysis revealed mild normocytic anemia with normal white blood cell count, hypokaliemia and normal concentration of creatine phosphokinase, lactic dehydrogenase and mildly elevated aspartate transminase in sera. Chest X-ray was consistent with pulmonary emphysema. Because the worsening of ECG changes she was transferred to Coronary unit. The diagnosis of non-Q myocardial infarction was confirmed and treatment with nitrates and beta-adrenergic antagonists was instituted. Four weeks later she became euthyroid and coronarography was performed. Subepicardial coronary arteries were normal (Figure 1). She was dismissed, and still euthyroid three months later. Agranulocytosis is very rare but very serious complication of antithyroid drug therapy. It can be detected in about 0.1-1% patients during the first three months of treatment. Sudden appearance, heralded by sore throat and fever, prompt physicians to seek white blood cell and differential count [1-3]. Confirmation of diagnosis urges cessation of drug therapy and appropriate antibiotic treatment. Recently, it was reported that recombinant human granulocyte colony-stimulating factor (rhG-CSF) is to be effective in shortening the recovery time in the neutropenic patients undergoing chemotherapy and also in patients with other types of neutropenia [5]. Tamai at al. [7] confirmed positive outcome in 34 patients treated with rhG-CSF compared to corticosteroid treatment. Hematologic laboratory abnormalities disappear 7-10 days after session of therapy. Patients completely recover two to three weeks later. Fatal outcome was also described [1-5]. Thyroid hormones have profound effects on cardiovascular physiology, especially on heart rate, cardiac output and systemic vascular resistance. In patients with hyperthyroidism, cardiac output is much higher than in normal persons. This is the result of direct effect of thyroid hormones on cardiac muscle contractility, heart rate and decrease in systemic vascular resistance. Excessive thyroid hormone secretion increases cardiac Na-K-activated plasma membrane ATP-ase and sarcoplasmic reticulum Ca-activated ATP-ase with resultant in increase myocardial contractility [6, 9]. Sinus tachycardia is the most common rhythm disorder in hyperthyroidism, but paroxysmal tachycardia and atrial fibrillation are not rare. This can be explained by increased heart rate, cardiac output, blood volume, coronary artery flow and peripheral oxygen consumption in thyrotoxicosis [9]. Patients with coronary arteriosclerosis can develop angina pectoris during thyrotoxic stage, which can be explained by imbalance between cardiac demand and supply. Myocardial damage is often in thyrotoxic patients with chronic hart failure, together with myocardial infarction in patients without coronary disease [2,6]. Congestive heart failure and atrial fibrillation are relatively resistant to digitalis treatment because of high metabolic turn over of medication and excessive myocardial irritability in hyperthyroidism [6]. Cardiovascular and myopathic manifestations predominate in older hyperthyroid patients (over 60 years) and some of them can have only few symptoms of hyperthyroidism [1-3]. Thyrotoxic state characterized by fatigue, apathy, extreme weakness, low-grade fever and sometimes congestive heart failure are designated as apathetic hyperthyroidism. Such patients have small goiters, mild tachycardia and often cool and dry skin with few eye signs [6]. Patients with subclinical hyperthyroidism are at increased risk for atrial fibrillation [9]. Unstable angina and non-Q myocardial infarction (non ST elevation) are acute manifestation of coronary artery disease. The acute coronary syndrome of unstable angina, non-Q myocardial infarction and Q-wave myocardial infarction have atherosclerotic lesions of the coronary arteries as a common pathogenic substrate. Erosions or ruptures of unstable atherosclerotic plaque triggered pathophysiologic processes, resulted in thrombus formation at the site of arterial injury. This leads to abrupt reduction or cessation through the affected vessel. Clinical manifestations of unstable angina and non-Q myocardial infarction are similar and diagnosis of non-Q myocardial infarction is made on the basis of elevated serum markers indicative of cardiac necrosis, detected in peripheral circulation. Acute coronary syndrome ranging from unstable angina to myocardial infarction an non-Q myocardial infarction represents increasingly severe manifestations of the same pathophysiologic processes [10,11]. In conclusion, these 62-year-old woman presented with apathetic form of recurrent hyperthyroidism associated with two serious complications, life-threatening agranulocytosis and acute coronary syndrome.

Short-term hyperthyroidism followed by transient pituitary hypothyroidism in a very low birth weight infant born to a mother with uncontrolled Graves' disease.

Transient hypothyroxinemia in infants born to mothers with poorly controlled Graves' disease was first reported in 1988. We report that short-term hyperthyroidism followed by hypothyroidism with low basal thyroid-stimulating hormone (TSH) levels developed in a very low birth weight infant born at 27 weeks of gestation to a noncompliant mother with thyrotoxicosis attributable to Graves' disease. We performed serial thyrotropin-releasing hormone (TRH) tests in this infant and demonstrated that TSH unresponsiveness to TRH disappeared at 6.5 months of age. The maternal thyroid function was free triiodothyronine (FT(3)), 21.1 pg/mL; free thyroxine (FT(4)), 8.1 ng/dL; TSH, <0.03 microU/mL; thyroid-stimulating hormone receptor antibody, 52% (normal: <15%); thyroid-stimulating antibody, 294% (normal: <180%); and thyroid-stimulation blocking antibody, 9% (normal: <25%) on the day of delivery. A nonstress test revealed fetal tachycardia >200 beats per minute, and a male infant weighing 1152 g was born by emergency cesarean section. Thyroid-stimulating hormone receptor antibody was 16% and thyroid-stimulating antibody was 370% in the cord blood. We administered 10 mg/kg per day of oral propylthiouracil from day 1. Tachycardia along with elevated FT(4) and FT(3) levels in the infant decreased from 200/minute to 170/minute, 4.7 ng/dL to 2.9 ng/dL, 7.0 pg/mL to 4.8 pg/mL, respectively, in the first 33 hours. At 5 days, FT(4) and FT(3) were 1.1 ng/dL and 2.9 pg/mL, respectively, and we stopped propylthiouracil administration. Although FT(4) decreased to 0.4 ng/dL, TSH was quite low and did not respond to intravenous TRH by 14 days of age. We began daily levothyroxine 5-micro/kg supplementation. The responsiveness of TSH to TRH did not become significant until 4 months old and normalized at 6.5 months old. At this time, levothyroxine was stopped. We conclude that placental transfer of thyroid hormones may cause hyperthyroidism in the fetal and early neonatal periods and lead to transient pituitary hypothyroidism in an infant born to a mother with uncontrolled Graves' disease.

Newly diagnosed primary hypothyroidism applicant with massive pericardial effusion and acute renal failure.

While non-symptomatic pericardial effusion is seen in primary hypothyroidism, massive pericardial effusion is a very rare finding. In the literature, newly diagnosed primary hypothyroidism cases presenting with massive pericardial effusion or acute renal failure are present, but we did not encounter any case first presenting with combination of two signs. In this case report, primary hypothyroidism case that presenting with massive pericardial effusion and acute renal failure will be discussed. Subject and Results. Forty-eight years old male patient was hospitalized with shortness of breath, chest pain, swelling of the eyelids and bilateral limbs complaints. On chest radiograph heart shadow was deleted, pleural effusion was present until the middle zone of the left lung. Biochemical parameters (urea, creatinine, alanine aminotransferase aspartate aminotransferase, lactate dehydrogenase, sodium, potassium, creatine kinase, Troponin I, CK-MB, erythrocyte sedimentation rate, c-reactive protein) and thyroid stimulating hormone (TSH, 52.6 μg/ml), free triiodothyronine (T3, 0.61pg/ml), free thyroxine (T4, 0.12 ng/dl), anti thyroperoxydase (343 IU/ml), anti thyroglobulin (1604 IU/ml), were analyzed. The patient underwent pericardiocentesis. Levothyroxine treatment started with a dose of 0.05 mg per day and increased gradually until the optimum dose provided. At the end of the third month, the values of TSH, free T4, and free T3 were measured (2.3 μg/ml, 1.1 ng/dl, 2.54 pg/ml, respectively). The patient recovered completely and pericardial effusion was not detected in echocardiography. Massive PE and acute renal failure due to primary hypothyroidism is a rare clinical condition. Primary hypothyroidism should be kept in mind in patients with symptoms like shortness of breath, chest pain, and generalized edema; moreover, when acute renal failure and PE were detected. It should be considered that patient's biochemical parameters can improve starting from the two weeks after levothyroxine treatment started with pericardiocentesis in severe symptomatic patients.

Graves' disease following allogenic hematopoietic stem cell transplantation for severe aplastic anemia: case report and literature review.

Similar autoimmune processes (defective T-cell function) take place during the pathogenesis of aplastic anemia (AA) and Graves' disease (GD). Antithyroid drugs used for the management of GD may induce AA and GD may occur following treatment of severe aplastic anemia (SAA). Clinical and laboratory investigations were performed for an 11-year-and-2-month-old girl who was referred for bilateral exophthalmus and abnormal thyroid function tests. She had been diagnosed as having severe acquired AA at the age of 8 years and had been treated with allogenic hematopoietic stem cell transplantation from her healthy human leukocyte antigen-matched sibling donor. Clinical examination revealed a weight of 32.6 kg (-0.88 standard deviation [SD] score); height, 145.7 cm (-0.14 SD score); body mass index 15.5 kg/m2 (-1.01 SD score); heart rate, 110/min; blood pressure, 128/74 mmHg; bilateral exophthalmos and an enlarged thyroid gland. The laboratory workup showed hemoglobin of 11.1 g/dL; white blood cells, 7500/mL; platelets, 172,000/mL; free thyroxine (FT4), 4.80 ng/dL (normal, 0.5-1.51); free triiodothyronine (FT3), 17.7 pg/mL (normal, 2.5-3.9); thyrotropin (TSH), 0.015 mIU/mL (normal, 0.38-5.3); antithyroglobulin peroxidase (TPO) antibody, 61.7 IU/mL (normal, 0-9); antithyroglobulin (TG) antibody, <0.9 IU/mL (normal, 0-4) and thyrotropin (TSH) receptor antibodies 14 U/L (normal, 0-1). Doppler ultrasonography showed diffuse enlargement of the thyroid gland and increased vascularity. She was treated with methimazole (0.6 mg/kg/day). L-thyroxine treatment was also needed (50 μg/day). Thrombocytopenia developed during follow-up. A thyroidectomy was performed for definitive treatment at the 14th month of treatment. The association of hyperthyroidism and AA in the pediatric age group is rare. The long-term use of antithyroid drugs and radioactive iodine should be avoided due to their hematologic toxic side effects.

Surgery_Schwartz

50 to 200 μg per day, depending on the patient’s size and condition. Starting doses of 100 μg of T4 daily are well tolerated; however, elderly patients and those with coexisting heart disease and profound hypothyroidism should be started on a considerably lower dose such as 25 to 50 μg daily because of associated hypercholesterolemia and atherosclerosis. The dose can be slowly increased over weeks to months to attain a euthyroid state. A baseline electrocardiogram should always be obtained in patients with severe hypothyroidism before treat-ment. T4 dosage is titrated against clinical response and TSH levels, which should return to normal. The management of patients with subclinical hypothyroidism (normal T4, slightly raised TSH) is controversial. Some evidence suggests that patients with subclinical hypothyroidism and increased antithy-roid antibody levels should be treated because they will sub-sequently develop hypothyroidism. Patients who present with myxedema coma may require

InternalMed_Harrison

Once clinical or subclinical hypothyroidism is confirmed, the etiology is usually easily established by demonstrating the presence of TPO antibodies, which are present in >90% of patients with autoimmune hypothyroidism. TBII can be found in 10–20% of patients, but measurement is not needed routinely. If there is any doubt about the cause of a goiter associated with hypothyroidism, FNA biopsy can be used to confirm the presence of autoimmune thyroiditis. Other abnormal laboratory findings in hypothyroidism may include increased creatine phosphokinase, elevated cholesterol and triglycerides, and anemia (usually normocytic or macrocytic). Except when accompanied by iron deficiency, the anemia and other abnormalities gradually resolve with thyroxine replacement.

InternalMed_Harrison

Thyroid function tests and clinical manifestations are reviewed 4–6 weeks after starting treatment, and the dose is titrated based on unbound T4 levels. Most patients do not achieve euthyroidism until 6–8 weeks after treatment is initiated. TSH levels often remain suppressed for several months and therefore do not provide a sensitive index of treatment response. The usual daily maintenance doses of antithyroid drugs in the titration regimen are 2.5–10 mg of carbimazole or methimazole and 50–100 mg of propylthiouracil. In the block-replace regimen, the initial dose of antithyroid drug is held constant, and the dose of levothyroxine is adjusted to maintain normal unbound T4 levels. When TSH suppression is alleviated, TSH levels can also be used to monitor therapy.

Vitiligo and alopecia areata associated with subclinical/clinical hypothyroidism.

The parents of an 18-year-old woman had noticed white hair while combing their daughter's hair 12 years ago. They found tiny white spots on her scalp, but she was asymptomatic. The spots have since progressed. Examination of the affected skin on the scalp was marked by the presence of a chalky/ivory white macule, 8 to 10 cm in diameter, conforming to that of segmental (zosteriformis) vitiligo (Figure 1). The lesions were located on the temporoparietal region of the scalp. The hair over the macules was white (leukotrichia) and dry, coarse, and brittle. The patient's nails were thin and dull. Her thyroid profile revealed the following: triiodothyronine, 1.12 nmol/L (0.95-2.5 nmol/L); thyroxine, 69.21 nmol/L (60.0-120.0 nmol/L); and thyroid-stimulating hormone, 6.26 microIU/mL (0.25-5.00 microIU/mL), indicative of primary hypothyroidism. Liver and renal function tests were within normal limits. A lipid profile revealed the following: total lipids, 503.8 mg% (400-700 mg %); triglycerides, 123.0 mg % (160 mg %); cholesterol, 212.0 mg % (150-250 mg %); high-density lipoprotein, 43.1 mg % (30-63 mg %); and low-density lipoprotein, 144.3 mg % (50 mg %). Electrocardiographic findings were normal. History of tiredness, constipation, depression, sensitivity to cold, weight gain, muscle weakness, cramps, and increased menstrual flow supported the diagnosis. The patient was administered 100 microg of thyroxine once a day along with methoxsalen, the dose of which was calculated at 0.6 mg/kg to 0.7 mg/kg body weight per day given on alternate days, followed 2 hours later by exposure to UV-A (1 J/cm2) irradiation (psoralen-UV-A [PUVA]), supplemented by 1 mg of beta-methasone, 150 mg of levamisole on 2 consecutive days per week, and an antioxidant. During the course of 7 weeks, the macules (13 exposures) had become erythematous, with an appearance of perifollicular/ marginal pigmentation. Repeat examination showed a thyroid profile of total triiodothyronine (T3), 127.3 microg/dL (86-186); total thyroxine (T4), 6.54 microg/dL (4.5-12.5 microg/dL); and thyroid-stimulating hormone (TSH), 0.32 microIU/mL (0.3-5.6 microIU/mL), supplemented by antithyroid microsomal peroxidase antibodies (thyroid microsomal antibody and thyroid peroxidase), 21.9 IU/mL (1-40 IU/mL), and antithyroglobulin antibodies, 78.1 U/mL (1-100 U/mL). During the patient's treatment period, 4 other patients with clinical symptoms and signs of long-standing hypothyroidism developed vitiligo, the duration of which was variable in each patient (Table I). All of the patients were taking thyroxin. Thyroid and lipid profiles were performed periodically to evaluate the progress (Table I). These patients were also treated with PUVA therapy and thyroxin. During the course of treatment, 2 of the patients noticed asymptomatic, progressive, localized, and well-circumscribed hair loss at the temporal region of the scalp that extended to involve the vertex, conforming to findings of alopecia areata (Figure 2A and Figure 2B).

A CASE OF FAMILIAL NONAUTOIMMUNE HYPERTHYROIDISM DURING PREGNANCY.

Familial nonautoimmune hyperthyroidism (FNAH) is a rare disease. To date there are few, if any, reports of pregnancies in women with FNAH. Our objective here is to present such a case. Free thyroxine (free T4), free triiodothyronine (free T3), thyroid-stimulating hormone (TSH), and antibodies related to the thyroid were measured. Fetal thyroid function indicators including thyroid volume and ossification were checked using ultrasound. Thyroid-stimulating hormone receptor (TSHR) gene analyses were performed. The patient was a 30-year-old woman with no past medical history. She was introduced to our hospital in the fifth gestational week for pregnancy care because her family history revealed that her mother had nonautoimmune hyperthyroidism with a TSHR-activating germ-line mutation (Asn406Ser). The serum free T4 was 1.88 ng/dL (normal, 0.62 to 1.19 ng/dL), free T3 was 3.27 pg/mL (normal, 2.55 to 3.88 pg/mL), TSH was 0.02 μIU/mL (normal, 0.007 to 3.619 μIU/mL), and TSHR was negative which were considered to be consistent with mild primary hyperthyroidism. Serum free T4, free T3, and TSH concentrations were monitored every 4 to 6 weeks with a peak free T4 of 2.23 ng/dL noted at gestational week 9. The patient had no signs related to hyperthyroidism throughout pregnancy. The patient delivered a 3,518 g girl at 40 weeks of gestation. Genetic analysis of her <iTSHR</i gene showed heterozygous Asn406Ser mutation. The offspring did not show any signs of prenatal hyperthyroidism, and thyroid function at day 6 after delivery revealed a free T4 of 2.41 ng/dL (normal, 1.83 to 2.91 ng/dL) and a TSH of 3.55 μIU/mL (normal, 0.51 to 4.57 μIU/mL). Women with FNAH and mild thyrotoxicosis prior to pregnancy may have continuous hyperthyroidism with additional change due to the series of human chorionic gonadotropin secretion during pregnancy.

Some aspects of hypothyroidism in elderly.

The frequency of hypothyroidism does not diminish with age but there is a considerable change in its clinical pattern. The data of 169 patients treated with primary hypothyroidism were processed by means of computer analysis. They were put, in accordance with their basic diseases, into 5 groups: idiopathic (50.3%); chronic thyroiditis (26.6%); as a result of the ablative treatment of Graves' disease (17.2%); nodular goitre (4.7%) and thyroid malignancy (1.2%). According to age, the patients fell into 4 groups. III patients were between 50 and 90 years of age. In most cases the identification of the disease was belated. The usual symptoms that might lead to the consideration of hypothyroidism are edema not reacting to diuretics, anemia, and high blood lipid values. In 18 patients with a previous case history of immunothyroiditis, the cultured monocyte monolayers were examined for the activity of the specific and the scavenger LDL receptors and for the intracellular breakdown of LDL.

Thyroid function tests of iodine deficiency goiter can mimic thyroid hormone resistance alpha.

Iodine deficiency goiter can develop in children on a restrictive diet and most have normal thyroid function. We report a 6-year-old girl with iodine deficiency goiter with thyroid function studies mimicking thyroid hormone resistance alpha. Thyroid hormones mediate its effects through thyroid hormone receptors alpha and beta. Biochemical picture of low/low-normal T4 and high/high-normal T3 levels, variably reduced reverse T3 and normal TSH is characteristic of thyroid hormone resistance alpha. A 6-year-old girl, born out of non-consanguineous marriage presented with goiter of 1.5 years duration. She was without symptoms of thyroid dysfunction. The patient was evaluated at one year of age for macrocephaly with cranial ultrasound which was normal. She had normal growth and development. Patient was vegan and was not on any medications or supplements. Laboratory work up showed TSH 5.03 uIU/mL (0.34-5.5), FT4 0.3 ng/dL (0.58-1.2), FT3 5.3 pg/mL (2.5-3.9), total T3 258 ng/dL (94-241), reverse T3 <5.0 ng/dL (8.3-22.9) and negative thyroglobulin antibody and thyroid peroxidase antibody. Thyroglobulin level was 1,098.8 ng/mL (<13 ug/L), and urine iodine 15.8 ug/L (<100 ug/L) confirming a diagnosis of iodine deficiency goiter. Patient was started on iodine supplements, 150 ug daily and repeat work up 3 months later were TSH: 2.717 uIU/mL, T3, total 182 ng/dL, T4, total 9.3 ug/dL, FT 4 2.1 ng/dL. Iodine deficiency goiter may present with low FT 4, elevated T3 and normal TSH mimicking thyroid hormone resistance alpha and should be considered in children on restrictive diet.

[Economic evaluation od the value of early diagnosis and management of hypothyroidism in hypercholesterolemia].

The aim of the study was to assess the economic consequences of the early screening and management for overt hypothyrodism in elderly women suffering from hypercholesterolaemia. A cost analysis was performed using screening decision tree followed by a Markov model, targeted on an hypothetical cohort of elderly women (i.e. > or = 55 years of age) suffering from hypercholesterolaemia. Two arms were compared, "no diagnosis", patients being treated by lipid lowering drugs in the long run, "diagnosis", patients being screened for thyroid disturbance and proposed adequate correction by hormone treatment. Relevant clinical data introduced into the model were obtained from published data and from experts. At the end of the initial diagnostic, patients could enter three different health states: euthyroidism, subclinical hypothyroidism or overt hypothyroidism. During 30 years, patients were assumed to be seen each year by a general practitioner for clinical examination and cholesterol dosage, plus, according to the health state evolution, TSH and T4 screening. In the baseline analysis, euthyroidian patients who had a inexplicable degradation of hypercholesterolaemia control were tested for TSH and, if abnormal, T4 serum; for subclinical hypothyroidian patients, TSH and T4 were measured every year. The direct costs taken into account were concerning medical supervision, drug treatment and biologic exams. Costs were analysed from the societal perspective and were expressed in 1998 French Francs (FF) with an accounting rate of 5% by year. A sensitivity analysis was also performed. The total cost at 30-year was equal to 25,006 F for "diagnosis" strategy, to 24,390 F for "no diagnosis" strategy. The incremental cost of the first strategy decreased according to the time horizon. It was 6.8% at 5-year and 2.5% at 30-year. Results were sensitive to variation in response rate of hypercholesterolaemic patients to hormone treatment of hypothyroidism (0.25 in base-case). The investment cost in screening and treatment of hypercholesterolemic female patient aged 55 and more can be considered offset in the long run (30 years). Considering the other important outcomes in favour of hormonal drug treatment of hypothyroidism, such as enhancement of well-being, functional capacities and quality of life, the "diagnosis" strategy can be recommended in the ambulatory medical practice.

Pituitary enlargement in post-surgical hypothyroidism misdiagnosed as thyrotroph neoplasia. Report of a case.

Primary hypothyroidism may be associated with enlargement of the sella turcica, due to thyrotroph hyperplasia, in its turn due to the lack of feedback control by thyroid hormones. It may develop independently of the severity or of the duration of thyroid failure. A 42-year-old woman was referred to us. She presented us with a CT scan compatible with a pituitary microadenoma, in the left part of the sella. The patient showed obvious signs of myxedema, due to subtotal thyroidectomy which had been performed 14 months before, because of the presence of multinodular goiter. After operation, the patient has been discontinuously and inappropriately treated with desiccated thyroid. She complained of headache, nausea, galactorrhea without amenorrhea. Serum T4 (0.8 micrograms/dl), serum T3 (47 ng/dl) and TSH (174.5 +/- 60.1 mU/l: M +/- SD of 4 assays) were compatible with primary hypothyroidism as confirmed by TSH hyper-response to i.v. TRH (200 micrograms) and i.v. domperidone (10 mg), and by the normal TSH decrease after orally administered 2.5 mg bromocriptine or 90 min continuously infused 800 micrograms GHIRH. Moreover, an abnormal GH response to TRH was observed, whereas basal and appropriately stimulated PRL levels were normal. Serum alpha-subunit was marginally high (5.92 ng/ml), but alpha-subunit/TSH molar ratio fell within the normal range (0.1 molar ratio). Complete suppression of basal and TRH stimulated TSH values was achieved after a 14-day L-T3 (120 micrograms per day) and 4-month L-T4 (200 micrograms per day) administration. L-T4 treatment, first administered at suppressive doses (200 micrograms per day for 4 months) and subsequently at substitutive doses (150 micrograms per day for 2 months), induced complete remission of symptoms along with normalization of the CT scan picture.

[Clinical and subclinical hyperthyroidism: two faces of the coin?].

We have made a prospective study of 23 patients diagnosed of subclinical hypothyroidism and 45 of overt hypothyroidism, aged 68.3-70.3 years and with a mean illness of 4.5 and 6.5 years respectively. It has been proved a higher prevalence of females in both groups. The most frequent clinical symptoms, similar in both groups, were fatigue, constipation and dyspnea. The most repeated initial diagnosis at the entry were prymary hypothyroidism, heart failure, hypertensive urgencies and stroke. We have found differences of statistical significance between the Free Thyroxine (fT4), triiodothyronine (T3), total serum cholesterol (CT), triglycerides (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and thyrotropin (TSH) initial and ending serum levels in patients with overt hypothyroidism (p < 0.05). We only have found significant differences in TSH serum levels in patients with subclinical hypothyroidism. The antithyroglobulin and antimicrobial antibodies, have been both positive in two and one patient respectively. Both are more useful as a predictor than their diagnostic value. The levothyroxine (L-T4) daily dose needed to normalize the TSH serum concentration, was lesser in subclinical hypothyroidism (71.8 micrograms opposite 107 micrograms-p < 0.001). We didn't find significant differences between the different groups in the time necessary for normalizing TSH. It seems that the L-T4 therapy should be started in all patients with subclinical hypothyroidism and TSH > or = 10 microU/ml or with TSH > 5 and goiter or with thyroid antibodies. The aim to reach is to normalize the TSH serum levels. The mean daily necessary L-T4 dose is 50-100 micrograms.

[Two cases of TSH-secreting pituitary adenoma; endocrinological, diagnostic and therapeutic approach to the disease].

Two cases of TSH-secreting pituitary adenoma were reported. Endocrinological and immunohistochemical features of these cases were described and problems in diagnosis and treatment of the rare disease are discussed. [case 1] A 28 year-old woman suffered from hyperthyroidism with a relatively high value of serum TSH (T3; 350 ng/dl, T4; 10.0 micrograms/dl, TSH; 24.5 microU/ml). She was treated with antithyroid drug and then underwent subtotal thyroidectomy. Although the levels of serum T3 and T4 were lowered to within normal range, the level of serum TSH still remained high. One month later, she developed frontal headache, amenorrhea and bitemporal hemianopsia. A CT scan showed an enhanced mass in the sellar and suprasellar region. Preoperative endocrinological studies showed elevated values of TSH (47 microU/ml) and its alpha-subunit (9.0 ng/ml). The levels of both T3 (190 ng/dl) and T4 (10.0 micrograms/dl) were near the upper normal limit. Serum TSH was suppressed by administration of exogenous T3, but did not respond to exogenous TRH, l-Dopa nor bromocriptine. Under the diagnosis of TSH-secreting pituitary adenoma, the patient was operated on by craniotomy and received local radiation therapy (50 Gy). In 1990, 12 years after the treatment, she is well and endocrinologically normal. Immunohistochemical study revealed that most tumor cells were positive for TSH. [case 2] A 28 year-old woman visited our hospital for examination of hyperthyroidism. Serum level of TSH was detectable (4.5 microU/ml). A CT scan performed at that time disclosed no pituitary tumor. Thyroid function was normalized by antithyroid drug, but the level of TSH was still high and progressively increased.(ABSTRACT TRUNCATED AT 250 WORDS)

[Three-year follow-up of infraclinical hypothyroidism: course in a cohort of 97 women aged 45 to 70 years attending healthcare screening centers].

Infraclinical hypothyroidism is a recognized entity defined in terms of laboratory results which occurs more readily in women. The appropriateness of thyroid hormone multicentric prospective study initiated in 1997 has established that infraclinical hypothyroidism occurred in about 3% of women over 45 years of age undergoing routine check-ups at eleven health screening centers. Associated clinical signs and laboratory findings were reported. The purpose of the present study was to describe findings in a 3-year follow-up of these women with infraclinical hypothyroidism in order to assess natural history and appropriate care. Ninety-seven women of the 151 women with a TSH level between 4 and 12 mU/l in the 1997 survey were reviewed during the last three months of 2000. Forty-three of them had taken thyroid hormone replacement drugs since 1997. About 44% of the women examined still had infraclinical hypothyroidism or developing hypothyroidism. There was not significant difference between treated (33%) and non-treated (55%) patients. Clinical and biological signs associated with infraclinical hypothyroidism at the initial examination (elevated serum cholesterol, abnormal ECG, eyelid edema, recent weight gain) were unchanged at the second examination, both in treated and not treated women. A logistic model including all these factors demonstrated that the probability of prescription of thyroid hormone replacement therapy increased 5.4-fold when the starting TSH level was above 6 mU/l and 3.2-fold if ECG abnormalities were present. Using a statistical model with anti TPO antibodies, a level above 64 U/l increased the probability of treatment 7-fold, with ECG findings being related to probability of treatment. Age, cholesterol level, use to lipid lowering drugs, presence of eyelid edema or weight gain were not associated with replacement therapy in this model. No consistent conclusion concerning the appropriateness of screening for infraclinical hypothyroidism can be drawn from these three-year follow-up findings. Another examination scheduled for 2003 should provide further precision concerning the natural history of infraclinical hypothyroidism as well as long-term medical practices and therapeutic impact.

Recombinant human thyrotropin is a potent stimulator of thyroid function in normal subjects.

Recombinant human TSH (rhTSH) is known to stimulate 131I uptake and thyroglobulin (Tg) release from the postoperative remnant and metastases in thyroid cancer patients, but its effects on serum thyroid hormone and Tg concentrations in normal subjects have not been reported. Before using rhTSH in the management of thyroid disorders other than cancer, the thyroid response to rhTSH in normal subjects must be assessed. Six subjects, two men and four women, without evidence of thyroid disease, including normal serum free T4 index and TSH concentrations and negative tests for antithyroid peroxidase and Tg, were studied. Each received 0.1 mg rhTSH, im, 11% of the lowest dose that has been administered to thyroid cancer patients. Blood was obtained before; 2, 4, and 8 h after; and 1, 2, 3, 4, 7, and about 3 weeks after rhTSH administration. Serum TSH significantly increased at 2 h (mean +/- SE, 2.4 +/- 0.9 to 40.7 +/- 7.4 mU/mL), peaked at 4 h (50.9 +/- 9.3), remained significantly elevated for 1 day, and was significantly below baseline (0.8 +/- 0.5) 7 days after rhTSH administration. Serum T3 increased significantly at 4 h (115 +/- 4 to 190 +/- 14 ng/dL), peaked at 24 h (217 +/- 23 ng/dL), and remained significantly elevated for 3 days (151 +/- 12 ng/dL). Serum T4 increased significantly at 8 h (7.3 +/- 0.2 to 9.8 +/- 0.4 micrograms/dL), peaked at 24 h (11.2 +/- 0.5 micrograms/dL), and remained significantly elevated for 4 days (9.4 +/- 0.5 micrograms/dL). Serum Tg did not change for the first 8 h, increased significantly at 1 day (15.9 +/- 3.9 to 34.7 +/- 6.0 ng/mL), peaked at 2 days (44.2 +/- 7.0 ng/mL), and remained significantly elevated for 4 days (37.7 +/- 13.7 ng/mL). All values returned to baseline at 3 weeks. TSH antibodies were not detected at 3 weeks. A single dose of 0.1 mg rhTSH is a potent stimulator of thyroid function in normal subjects. rhTSH may be a useful agent to test thyroid reserve and for use in clinical settings that require direct thyroid stimulation.

[Primary hypothyroidism in the adult older than 60 years. Characteristics and follow-up after initiation of replacement treatment in hospital].

Primary hypothyroidism is common in the elderly. Yet its care remains unclear. Clinical, biological characteristics and outcome of 45 patients aged over 60 years admitted for in-hospital initiation of treatment for primary hypothyroidism were recorded. Causes and tolerance of treatment (clinical and ECG monitoring in hospital) were seek for. Initial symptoms, predominantly fatigue (84.4%), were moderate, contrasting with severe biological hormonal deficiency. The most common routine biological change was hypercholesterolemia (57.6%). Female predominance was obvious (77.8%) and the most usual aetiology autoimmune chronic thyroiditis. Despite variability of symptoms, long term follow-up demonstrates a positive response to treatment, including an improvement in fatigue, eye-lid swelling, bradycardia and overweight. This clinical improvement was achieved on an average dose of 1.22 +/- 0.47 mg/kg/day L-T4 in order to maintain normal TSH (3.76 +/- 2.93 mUI/l). Cardiovascular incidents while starting treatment require experienced care and low dose initial treatment. Primary hypothyroidism is still lately discovered in the elderly. Yet, since treatment is efficacious and simple, the disease should be searched for and cared after whenever a related symptom occurs.

Tubulointerstitial nephritis and uveitis syndrome with transient hyperthyroidism in an elderly patient.

A 69-year-old Japanese woman without any specific medical or family history was admitted to our hospital for renal insufficiency with proteinuria. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 34.9 mg/dL and creatinine level was 1.78 mg/dL) and elevated urinary levels of N-acetyl-β-D-glucosaminidase (23.4 U/L) and β2-microgloblin (20200 μg/L) were observed. We performed a renal biopsy. The biopsied specimen showed severe diffuse infiltration of mononuclear cells into the interstitium, with normal glomeruli, and these findings were compatible with acute tubulointerstitial nephritis (ATIN). At that time, ATIN seemed to be idiopathic. We performed gallium scintigraphy, and the results revealed uptake by the bilateral kidneys, thyroid gland, and right parotid gland. Serum thyroid stimulating hormone (TSH) was undetectable, free triiodothyronine was normal (3.11 pg/mL), and free thyroxine was elevated to 2.4 ng/dL. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Two months later, burning pain and conjunctival congestion developed in both eyes. She had uveitis, as diagnosed by slit-lamp examination. Topical corticosteroid was used for the uveitis with success. We could not detect any cause of the uveitis, so a diagnosis of tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) with associated hyperthyroidism was made. Treatment was started with 15 mg/day of prednisolone. Now her renal function is slowly recovering. There are few reports of TINU syndrome with transient hyperthyroidism. This case suggests the possibility of thyroid dysfunction in patients with TINU syndrome. A laboratory evaluation of thyroid function should be considered in the diagnostic evaluation of TINU syndrome.

Multiple myeloma

Signs and symptoms Because many organs can be affected by myeloma, the symptoms and signs vary greatly. Fatigue and bone pain are the most common symptoms at presentation. The CRAB criteria encompass the most common signs of multiple myeloma: Calcium: serum calcium >0.25 mmol/l (>1 mg/dl) higher than the upper limit of normal or >2.75 mmol/l (>11 mg/dl) Renal insufficiency: creatinine clearance <40 ml per minute or serum creatinine >1.77 mol/l (>2 mg/dl) Anemia: hemoglobin value of >2g/dl below the lowest limit of normal, or a hemoglobin value <10g/dl Bone lesions: osteolytic lesions on skeletal radiography, CT, or PET/CT Bone pain

[Treatment of thyroid dysfunction].

The treatment of hypothyroidism and hyperthyroidism is briefly reviewed. L-T4, which is the treatment of choice of hypothyroidism, should be administered once daily after an overnight fast at the dosage of 10-12 mg/kg/day in newborns and of 100 mg/m2 in older children. FT4 and TSH serum levels will normalize within few weeks from the beginning of treatment and should be maintained in the normal range thereafter by appropriate increases of the dosage during growth. The first choice treatment in children with hyperthyroidism due to Basedow disease is the administration of antithyroid drugs, i.e. methimazole at the initial dosage of 0.4-0.6 mg/kg/day b.i.d. or t.i.d.; after remission, the dosage of this drug can either be reduced or L-T4 added in order to avoid hypothyroidism. Treatment should be continued for at least 24 months and the patient followed thereafter to detect possible relapses. Side effects are rare, the most frequent are skin rashes and the most severe is agranulocytosis, so complete blood count should be evaluated frequently especially in the first months of treatment. Surgery (total or near-total thyroidectomy) should be considered in case of failure of medical therapy, even if radioiodine administration, used until now mainly in adults, is gaining favour also for children especially in the United States.