BACKGROUND Primary hyperparathyroidism (PHPT) has a variable clinical expression. Symptomatic PHPT is still the predominant form of the disease in many parts of the world, especially developing countries. Because the clinical profile of the disease has changed from that described in the past, we sought to improve our understanding of the disease in patients in north India. METHODS We summarized the clinical presentation, biochemical and radiological features, and operative findings from the case records from the last 13 years of 52 patients at a tertiary care centre in north India who had documented PHPT. RESULTS The male: female ratio was 1: 3.3 with ages ranging from 6 to 60 years (mean±SD, 36.38±12.73). Bone disease (46%), recurrent renal stones (21%) and body aches and pains (21%) were the most common modes of presentation. The lag time varied ranged from 1 month to 16 years. Common clinical manifestations included bone pain (67%), weakness/fatigue (56%), fracture of the long bones (48%), abdominal pain (39%), polyuria (37%) and psychiatric manifestations (23.1%). Hypertension was observed in 42% and a palpable nodule in the neck in 19%. Biochemical features included hypercalcemia (86.5%), hypophosphatemia (65.4%) and hyperphosphatasia (67.3%). Mean intact PTH (±SD) was 809.0±696.3 ng/L with levels significantly lower in patients who had only kidney stone disease as compared with those with bone disease (P=0.017). A single parathyroid adenoma was localized in 50 (98%) patients. Hungry bone disease was seen in 59% patients. CONCLUSION PHPT in India continues to be a symptomatic disorder with skeletal and renal manifestations at a much younger age.

AIM:To report presentation and outcome of rhino-orbital-cerebral mucormycosis (ROCM) exclusively in patients with diabetes mellitus.METHODS:Retrospective, non-comparative, interventional analysis of the medical records of 35 patients with ROCM among 22 316 patients with diabetes seen over the last 12 years.RESULTS:A cohort of 23 men and 12 women with a mean (SD) age of 47.3 (14.4) years (range 18-70 years) was studied. Five patients had type 1 diabetes mellitus, 29 had type 2 diabetes mellitus, and one had secondary diabetes. Nine patients had ROCM as the first clinical manifestation of diabetes. The mean (SD) blood glucose at presentation was 20.6 (8.3) mmol/l (range 10.0 to 53.3 mmol/l) and 17 patients had ketosis/ketoacidosis. Ophthalmic symptoms and signs were pronounced: external ophthalmoplegia (89%), proptosis (83%), visual loss (80%), chemosis (74%), and eye lid gangrene (14%). Non-ophthalmic manifestations included sinusitis (100%), nasal discharge/ulceration (74%), infranuclear VI nerve palsy (46%), palatal necrosis (29%), cerebral lobe involvement (20%), and hemiparesis (17%). Computed tomography/magnetic resonance imaging showed involvement of paranasal sinuses in all patients with ethmoid (86%) and maxillary (80%) sinuses being most frequently involved. Orbital involvement was observed in 80% of patients with cavernous sinus thrombosis in 11%, and internal carotid occlusion and hydrocephalus in 3% each. All were treated with amphotericin B (3-3.5 g) and 26 (74%) patients underwent appropriate surgery. Twenty one patients (68%) survived with a mean (SD) follow up of 39.6 (34.1) months (range 10 months to 11 years). Factors related to poor survival included delay in diagnosis and treatment (p<0.05), facial and/or eye lid gangrene (p<0.05), hemiplegia (p<0.05), cerebral invasion by mucorales (p<0.05), and treatment with amphotericin B alone (p<0.05).CONCLUSIONS:In patients with diabetes and ROCM, ROCM was the presenting manifestation in one fourth of the patients. Ophthalmic and extensive cerebral involvement predominated in the clinical picture. Delay in treatment due to late presentation and associated complications were major determinants of the survival outcome in these patients.

BACKGROUND & OBJECTIVES:One microgram short synacthene test is widely recommended as a screening test for evaluation of hypothalamo-pituitary-adrenocortical axis in patients with secondary adrenal insufficiency. Information on adequacy of cortisol response to this dose at different periods of the day in patients with hypothalamic-pituitary disorders is not available. Hence, this study was designed to assess the adequacy of cortisol response to 1 microg 1-24 adrenocorticotropin (ACTH) at 0800 h and 1600 h in patients with sellar and suprasellar mass lesions. METHODS:Thirty five consecutive patients with sellar and suprasellar mass lesions with mean age of 43.0+/-14.4 yr and 36 healthy controls with mean age of 32.3+/-9.0 yr were studied after obtaining informed consent. Maintenance doses of glucocorticoids in these patients were discontinued appropriately. On day 1, prestimulated and stimulated plasma cortisol samples at 0800 h and at 30 and 60 min following i.v. bolus of 1 microg 1-24 ACTH were collected. While on day 3, plasma cortisol samples were similarly collected at 1600 h. Cortisol estimation was done by a sensitive and specific radioimmunoassay. Stimulated plasma cortisol of 500 nmol/l or higher was defined as a normal response. RESULTS:In healthy controls, the prestimulated and peak cortisol levels at 0800 h (377.5+/-93.3 and 729.1+/-183.2 nmol/l) were higher (P<0.001 and P<0.01) than those at 1600 h (230.1+/-75.7 and 665.8+/-138.6 nmol/l). All subjects had a cortisol response of 500 nmol/l or higher in response to 1 microg 1-24 ACTH both at 0800 and 1600 h. In the patients' group, the prestimulated plasma cortisol at 0800 h (250.3+/-169.7 nmol/l) was higher (P<0.001) than that at 1600 h (166.3+/-128.9 nmol/l), while the peak cortisol response was comparable (P>0.05) in the morning as well as in the evening (490.9+/-309.4 vs 464.8+/-318.4). In 27 patients (77%) the morning and evening stimulated cortisol response to 1 microg 1-24 ACTH was consistent (normal in 13 and subnormal in 14) but was discrepant in the remaining 8 (23%). In 7 of these 8 patients, cortisol response was normal at 0800 h but not at 1600 h, while in only one, normal response was seen at 1600 h but not at 0800 h. INTERPRETATION & CONCLUSION:The demonstration of normal peak cortisol response to 1 microg 1-24 ACTH at 0800 h but not at 1600 h in substantial number of patients with sellar and suprasellar mass lesions suggests preference to morning for performing this test.

Radiation-induced brain disorders (RIBD) are uncommon and they are grave sequelae of conventional radiotherapy. In the present report, we describe the clinical spectrum of RIBD in 11 patients who received post-surgery conventional megavoltage irradiation for residual pituitary tumours. Of these 11 patients (nine men, two women), seven had been treated for non-functioning pituitary tumours and four for somatotropinomas. At the time of irradiation the age of these patients ranged from 30 to 59 years (mean, 39.4 +/- 8.3; median, 36) with a follow-up period of 6-96 months (mean, 18.3 +/- 26.4; median, 11). The dose of radiation ranged from 45 to 90 Gy (mean, 51.3 +/- 13.4; median, 45), which was given in 15-30 fractions (mean, 18.6 +/- 5.0; median, 15) with 2.8 +/- 0.3 Gy (median, 3) per fraction. The biological effective dose calculated for late complications in these patients ranged from 78.7 to 180 Gy (mean, 99.1 +/- 27.5; median, 90). The lag time between tumour irradiation and the onset of symptoms ranged from 6 to 168 months (mean, 46.3 +/- 57.0; median, 57). The clinical spectrum of RIBD included new-onset visual abnormalities in five, cerebral radionecrosis in the form of altered sensorium in four, generalized seizures in four, cognitive dysfunction in five, dementia in three and motor deficits in two patients. Magnetic resonance imaging (MRI)/CT of the brain was suggestive of radionecrosis in eight, cerebral oedema in three, cerebral atrophy in two and second neoplasia in one patient. Associated hormone deficiencies at presentation were hypogonadism in eight, hypoadrenalism in six, hypothyroidism in four and diabetes insipidus in one patient. Autopsy in two patients showed primitive neuroectodermal tumour (PNET) and brainstem radionecrosis in one, and a cystic lesion in the left frontal lobe following radionecrosis in the other. We conclude that RIBD have distinctive but varying clinical and radiological presentations. Diabetes insipidus and PNET as a second neoplastic disorder in adults following pituitary irradiation have not been reported previously.

Pulmonary mucormycosis is an uncommon infection and its endobronchial form is rare. Fever, cough, dyspnoea and hemoptysis are the usual presenting symptoms. Hoarseness of voice, a rare manifestation of endobronchial mucormycosis, has been reported earlier but its exact anatomical basis was unclear. We report an instance of polypoid endobronchial mucormycosis and vocal cord paralysis in a patient with type I diabetes and diabetic ketoacidosis.

A 17 year-old girl with polyostotic fibrous dysplasia and hypophosphatemia had inappropriately low tubular reabsorption of phosphate. She had radiological evidence of rickets and osteomalacia. The patient showed clinical improvement after treatment with phosphate supplementation, active vitamin D (calcitriol) and alendronate. It is postulated that either a phosphaturic substance elaborated from the dysplastic bone or target-organ (kidney) unresponsiveness may interfere with phosphate reabsorption in the renal tubule.

The McCune-Albright syndrome (MAS) is characterized by a triad of poly/monostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies including growth hormone (GH) excess. Polyostotic bone lesions and café-au-lait macules are common while monostotic bone lesions are rare. Similarly, acromegaly as a manifestation of endocrine hyperfunction with MAS is uncommon and in most of the instances somatotropinoma has not been documented. We report 3 patients, two of them had monostotic lesion, none had café-au-lait macules and all had GH secreting pituitary macroadenoma. All of them underwent transfrontal pituitary adenomectomy and had histopathological confirmation of GH secreting pituitary adenoma. A brief review of literature is also presented.

ix patients with adrenal myelolipoma (AML) are reported. They included 3 men and 3 women with mean age (+ SD) of 42.3 + 10.9 yrs ranging from 26 to 60 yrs. Four patients were symptomatic, while the other 2 had no symptoms. Detection of AML was ‘incidental’ in 4 patients while being investigated for non-adrenal symptoms (pain abdomen in 2 and work-up for renal disease in 2), while the remaining 2 patients, one (#5) with congenital adrenal hyperplasia due to 21 alpha-hydroxylase deficiency had myelolipomatous alterations in the adrenal gland and the other (#6) had detection of AML during work-up for hypertension. All patients were obese (BMI > 27), four were hypertensive and one had type 2 diabetes. Imaging was suggestive of AML in five of them. However, in one case radiological diagnosis of angiomyolipoma of the kidney was considered. Interestingly, the right adrenal was involved in five of them. Four patients underwent adrenalectomy in view of symptoms and size of the mass, while the other 2 are under follow-up. Cyto/histopathology was consistent with AML in all these patients. However, in one case myelolipomatous alterations were noted in the background of adreno-cortical tumor. No recurrence or alterations in tumor size was noted during the follow-up period ranging from 6 months to 4 years. A brief review of literature is also presented.

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism and these tumours are usually hyperfunctional as opposed to other malignant endocrine tumors. Surgery is the only effective treatment while nonsurgical modalities yield poor results. We report a patient, who presented with palpable mass in the neck and severe hypercalcemia. He underwent debulking surgery and received allendronate, calcitonin, dacarbazine followed by in- situ alcohol instillation with some success.

PURPOSE:To report on a case of type 2 diabetes, with eyelid gangrene and endophthalmitis as a presenting manifestation of rhino-orbito-cerebral mucormycosis.RESULTS:CECT head showed proptosis, mucosal thickening in the ethmoid sinus and hypodense lesions in the frontal and occipital lobes. Vitreous tap showed right angle branched aseptate hyphae consistent with mucormycosis.CONCLUSIONS:A diabetic patient presenting with sudden loss of vision, eyelid gangrene and endophthalmitis, involvement by an angio-invasive fungus-like mucormycosis is an important consideration.

Background &, objectives: Cortisol response to 250mug adrenocorticotropin (ACTH) exhibits no circadian variation. Information on the circadian variation, if any, in cortisol response to 1 mug ACTH, which is considered as a physiological dose is not available. As the 1 mug ACTH stimulation test is projected as an outpatients procedure with no time constraint, this information is very important. Hence, this study was designed to assess whether any circadian variability exists in cortisal response to 1 mug ACTH in health), subjects.Methods: Thirty six healthy volunteers (23 male and 13 female) with mean age of 32.2 +/- 9.0 yr were consecutively studied after obtaining informed consent. On day 1, prestimulated and stimulated plasma cortisol samples were collected at 0800 h and, at 30 and 60 min following an intravenous bolus of 1 mug ACTH, and on day 3, plasma cortisol samples were similarly collected at 1600h. Cortisol estimation was done by a sensitive and specific radioimmunoassay. Stimulated plasma cortisol of 500 nmol/l or more was defined as a normal response.Results: The prestimulated and peak cortisol levels at 0800h (377.5 +/- 93.3 and 729.1 +/- 183.2 nmol/l) were higher (P < 0.001 and P <0.01) than those at 1600 h (230.1 +/- 75.7 and 665.8 +/- 138.6 nmol/l). However, a stimulated cortisol response of 500 nmol/l or more was observed at both 0800h and 1600h in all subjects at 30 min but not at 60 min. The A (peak-basal) response was higher at 1600h than that at 080011 (432.8 +/- 136.8 vs 351.5 +/- 177.3, P <0.01).Interpretation & conclusion: The demonstration of normal cortisol response to 1 mug ACTH both at 0800h and 1600h suggests that the test can be performed at any time of the day.

BACKGROUND & OBJECTIVES:Structural and/or functional alterations in adrenal glands have been reported in human immunodeficiency virus (HIV) infection. However, no information has been reported from India. Hence a study was undertaken to assess the basal and circadian variations in plasma cortisol, and cortisol response to bolus ACTH in patients with AIDS. METHODS:Basal and stimulated plasma cortisol levels at 0800 h and 1600 h and, at 30 and 60 min following an intravenous bolus of 250 micrograms ACTH (short synacthen test, SST) were estimated in 15 patients with AIDS (CD4 < or = 200/microliter) and 12 healthy controls. The nature of the opportunistic infections and/or associated disease in each patient was also studied. RESULTS:The patients had higher median basal plasma cortisol levels as compared to the controls at 0800 h (540 nmol/l vs 415 nmol/l, P < 0.005) and at 1600 h (420 nmol/l vs 285 nmol/l, P < 0.003). Five patients (33%) exhibited abnormal circadian cortisol rhythms. All subjects in the control group and all but one (6.6%) in the patients group had normal peak plasma cortisol response (> or = 550 nmol/l) to SST. The lone patient with subnormal cortisol response had no feature of adrenal insufficiency. On the contrary, 3 patients clinically suspected to have adrenal insufficiency, had normal plasma cortisol response. INTERPRETATION & CONCLUSIONS:These findings suggest that most patients with AIDS have elevated basal plasma cortisol levels with abnormal circadian rhythm in some and normal adrenocortical reserve irrespective of the symptoms/signs of adrenal insufficiency.

OBJECTIVES:Anti-inflammatory drugs, particularly inhaled corticosteroids remain the mainstay of treatment of bronchial asthma. However, these drugs have potential side effects. This study was undertaken to evaluate the effects of inhaled beclomethasone dipropionate (400 and 800 micrograms) over a period of six months on the hypothalamo-pituitary-adrenal axis (HPA) suppression.METHODS:Assessment of the hypothalamo-pituitary-adrenal axis function was carried out by tetracosactrin test at time zero, (before start of treatment), three months, and six months. The baseline values served as the controls for each patient. Serum cortisol was estimated by radioimmuno assay. The response to short tetracosactrin test was classified as normal if serum cortisol levels rose at least 200 nmol/L to a minimum of 500 nmol/L.RESULTS:There were seven patients who were inhaling beclomethasone dipropionate in a dose of 400 micrograms/day and another seven patients were taking the same drug in a dose of 800 micrograms/day. There was no side effect of the drug in any patient except in one patient who had dysphonia. The mean basal cortisol levels were normal in all the subjects at 0, 3 and 6 months of therapy. Tetracosactrin stimulation test was also normal in all patients at all the times who were receiving the dose of 400 micrograms/day. However, one patient (14%) receiving 800 micrograms/day had HPA axis suppression at six months. Two patients in this group also had low basal cortisol levels. There was no clinical evidence of such suppression/deficiency.CONCLUSION:Beclomethasone dipropionate in a dose of 800 micrograms/day may suppress the hypothalamo-pituitary-adrenal axis if used for long periods (six months). However, this may not have any clinical significance.

A 7-year-old girl presented with bilateral symmetrical enlargement of breasts of one year duration and one episode of vaginal bleed in August 1996. She did not have history of seizure disorder, meningitic or encephalitic illness, head injury or administration of oestrogen-containing preparations. She was an active child and had good scholastic performance.

Simultaneous detection of an intracranial meningioma with a pituitary tumour prior to radiotherapy is an extremely uncommon occurrence. Authors have managed an elderly acromegalic lady with an acidophilic pituitary adenoma, who also harboured an asymptomatic anterior third parasagittal meningioma, There were no features of neurofibromatosis. Both tumours were concurrently excised.

We describe a patient with primary hypothyroidism due to autoimmune thyroiditis, presenting with acute myoedema and spontaneous rhabdomyolysis. During his hospital stay, he developed altered sensorium due to hypo-osmolal hyponatraemia and later developed bilateral foot drop that responded to appropriate treatment.

A 41-year-old woman presented in December 1997 with dry cough with streaky haemoptysis of 15 days duration. She had had a goitre for the last 25 years and had been diagnosed as having thyrotoxicosis on clinical and biochemical grounds (triiodothyronine (T3) 2.8 ng/ml and thyroxine (T4) 220 ng/ml) in September 1995. She had received carbimazole for 6 months and remained asymptomatic thereafter. On examination, her body mass index (BMI) was 24.1 kg/m2. She had no pallor, lymphadenopathy, clubbing, oedema or hyperkeratosis. Her pulse was 96 beats/min regular, blood pressure 110/70 mmHg. She denied a history of fever, weight loss, loss of appetite, or recent increase in goitre size, but had been dysphagic to solids for 2–3 days. She was a non-smoker and never consumed alcohol. She had a firm, grade III (WHO) non-tender multinodular goitre with retrosternal extension. Systemic examinations were normal except for diffuse bilateral rhonchi. Her haemogram and serum biochemistry, including thyroid hormone profile (T …

Growth hormone therapy with rhGH (recombinant human growth hormone) has been recommended for treatment of GH deficient short stature in children, repeated hypoglycemias in infancy and early childhood due to GH deficiency, short stature accompanying chronic renal failure prior to renal transplantation and Turner's syndrome. It is now increasingly recommended to adults with GH deficiency following pituitary tumour surgery or irradiation or idiopathic hypopituitarism. There are other indications for its use where evidence for protein catabolism is very strong such as burns injury. The end points of GH therapy in children include achievement of desirable adult height or a growth rate velocity of < 2.5 cm/year. In adults GH deficiency, GH therapy is intended for improvement of general well being, body composition and metabolic markers of GH function.