A 38 year old man with history of obstructive sleep apnea and polycythaemia presented with hypercapnic respiratory failure that required intubation. He developed fever with infiltrates on chest radiography that required empiric antifungal therapy with fluconazole along with broad spectrum antibiotics. He developed acute adrenal insufficiency that recovered after fluconazole was stopped. It is believed that this complication of adrenal suppression attributable to fluconazole is underrecognised and it may be prudent to monitor all critically ill patients who are given fluconazole for this complication.A zole antifungal therapy has been in use for nearly a quarter of century when ketoconazole was first introduced. They are generally safe, efficacious, and easy to give orally in treatment of various systemic mycoses. 1Ketoconazole is reported in daily dose exceeding 400 mg to reversibly inhibit synthesis of testosterone and cortisol leading to various endocrine disturbances including adrenal insufficiency.2 Even though fluconazole does not generally inhibit steroidogenesis, there are rare reports 3-5 of adrenal suppression, raising the possibility that this problem is currently underrecognised. We report a patient who developed reversible adrenal suppression on fluconazole. CASE REPORTA 38 year old obese man with medical history significant for obstructive sleep apnea and secondary polycythaemia presented to emergency room with complaints of cough for three days before admission with greenish expectoration. His drug treatment included hydrochlorothiazide, lopressor, and aspirin. He denied taking corticosteroids recently. He was found to be in hypercapnic respiratory failure that required intubation. Chest radiography was normal.He was given ampicillin and sulbactam and azithromycin intravenously for pneumonia. Pulmonary embolus and acute coronary syndrome were ruled out. He developed fever on second day of admission. As fever persisted after 48 hours with new infiltrates on chest radiography, antibiotics were changed to vancomycin and imipenam. Trimethoprin-sulfamethoxazole was added to cover for Pneumocystis carini. A cosyntropin test done on day 4 of admission as a part of an ongoing study showed a peak cortisol concentration of 663 nmol/l. This was consistent with normally functioning adrenals.Later, fluconazole 400 mg intravenous once a day was started empirically as he remained febrile. Two days after starting fluconazole sodium decreased to 113 and potassium increased to 5.6. Cosyntropin test was repeated. Basal cortisol was 45 nmol/l with a peak of 375 nmol/l, at 60 minutes consistent with adrenal insufficiency. 6 Hydrocortisone 100 mg intravenously every eight hours was started.Computed tomography of adrenals was negative for haemorrhage. He became afebrile and fluconazole was stopped after nine days together with other antibiotics. All cultures remained negative. He was extubated and had an uneventful recovery. Repeat cosyntropin test done 10 days after stopping fluconazole showed a basal cortisol of 38 nmo...

The case of a 39-year-old woman who was referred for weight gain and amenorrhoea is reported. Laboratory evaluation showed high levels of thyroid-stimulating hormone (TSH). The patient was started on increasing doses of levothyroxine for subclinical hypothyroidism. TSH remained persistently raised and the patient became thyrotoxic. Evaluation at another laboratory showed normal levels of TSH, raising the possibility of interfering substances. TSH levels were normalised with the addition of mouse serum to the patient's sample, confirming the presence of human anti-mouse antibodies as the interfering substance in the TSH assay. S ubclinical hypothyroidism refers to mildly increased serum thyroid-stimulating hormone levels in the presence of normal free thyroxine (T4) and triiodothyronine (T3).1 In the US National Health and Examination Survey, 2 4.3% of 16 533 people had subclinical hypothyroidism. Progression to overt hypothyroidism is reported to vary from 3% to 20%, the risks being greater in those patients with goitre or thyroid antibodies.3 Although subclinical hypothyroidism is often asymptomatic, potential risks include progression to overt hypothyroidism, cardiovascular effects, hyperlipidaemia and neuropsychiatric effects. Treatment of subclinical hypothyroidism remains controversial. It is suggested that treatment of subclinical hypothyroidism will reduce cardiovascular risk factors, improve lipid profile and minimise neurobehavioural abnormalities. 4 It is recommended that patients with TSH .10 or TSH level between 5 and 10 in conjunction with goitre or positive anti-thyroid peroxidase should be treated. 1 We present a patient treated for hypothyroidism, it was later found that human anti-mouse monoclonal antibody (HAMA) had interfered with the TSH assay.A 39-year-old Hispanic woman was referred to the Division of Endocrinology, Metropolitan Hospital Center, New York, for evaluation of weight gain, increased appetite and amenorrhoea for 5 months. She denied any blurring of vision, headache, hoarseness of voice or intolerance to cold. Medical history showed hypertension, depression and schizophrenia treated for several years, and excision of an ovarian cyst. Her drugs included fosinopril, imipramine, olanzapine, haloperidol, benzatropine, fluphenazine, paroxetine and hydroxyzine. Family history was notable for breast cancer in her mother. Examination was unremarkable except for a weight of 196 pounds (89 kg). Initial laboratory evaluation showed a TSH concentration of 13.86 (range 0.35-5.50) mU/ l, a total T4 concentration of 8.4 (range 3-13) mg/dl and a T3 concentration of 1.03 (range 0.6-1.18) ng/ml. Anti-microsomal antibody titre was normal (,2 U/ml). On the basis of these results, a diagnosis of subclinical hypothyroidism was made and the patient was started on levothyroxine. She was followed up every 4-6 weeks and the thyroid function was monitored. During this period, she was given increasing doses of levothyroxine without adequate suppression of TSH. Prolactin level was raised at 135 ng/ml (range ...

Apathetic hyperthyroidism was first described in the medical literature by Lahey in 1931. It is a form of hyperthyroidism found principally in the elderly population. In this disorder the usual hyperkinetic presentation of thyrotoxicosis is replaced by apathy and inactivity, often leading to an erroneous psychiatric diagnosis. Although there is a paucity of literature on apathetic hyperthyroidism, it has been described in the elderly and as an extremely rare complication of hyperthyroid disorder in children. It was described only rarely in middle age. The following case highlights the diagnostic and therapeutic dilemmas encountered in a middle-aged patient who presented with dementia and apathetic hyperthyroidism.

The acquired immunodeficiency syndrome (AIDS) has been associated with abnormalities of adrenocortical function, and hypoaldosteronism due to hyporeninaemic hypoaldosteronism (HHA). We here report the case of a woman with AIDS associated with orthostatic hypotension, persistent hyponatraemia and hyperkalaemia, in whom basal serum cortisol levels were normal and serum renin activity was low. Subsequent post-mortem examination revealed almost complete adrenocortical destruction. A possible explanation of this apparently contradictory combination of findings is discussed, together with the therapeutic implications for similar cases.