Frequency of major affective disorders in first-degree relatives of patients with type 2 diabetes mellitus.

BACKGROUND & OBJECTIVES: A genetic link between diabetes and depression has been proposed, but hardly explored. Data on family studies exploring relation between depression and diabetes are scanty. This study attempted to assess the prevalence of major affective disorders in first-degree relatives of patients with type 2 diabetes mellitus (T 2 DM). METHODS: Fifty probands with T 2 DM, in whom other psychiatric disorders had been excluded, were chosen. Morbid risks and prevalence figures for depression and mania were estimated in 481 first-degree relatives of these 50 probands using the family interview for genetic studies. RESULTS: Of the 481 first-degree relatives of probands, only six had affective disorders. The morbid risk for depression in first-degree relatives was 2.99 and 3.87 per cent, assuming age of risk at 15-60 and 15-50 yr respectively, while the morbid risk for mania was 0.59 and 0.77 per cent in these age groups. INTERPRETATION & CONCLUSION: The morbid risks/prevalence rates among first-degree relatives of probands with T2 DM were not higher than those of the general population rates derived from earlier Indian and western studies. This study did not demonstrate a family aggregation of affective disorders in patients with T 2 DM. Increased prevalence of affective disorders in diabetes could be due to non-genetic factors.

Plasma cortisol response to 1-24 adrenocorticotropin in patients with treated/untreated sellar & suprasellar mass lesions.

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.

Pulmonary mucormycosis presenting with recurrent laryngeal nerve palsy.

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.

Parathyroid carcinoma: difficult management options.

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.

Plasma cortisol response to 1 microgram adrenocorticotropin at 0800 h & 1600 h in healthy subjects.

BACKGROUND & OBJECTIVES: Cortisol response to 250 micrograms adrenocorticotropin (ACTH) exhibits no circadian variation. Information on the circadian variation, if any, in cortisol response to 1 microgram ACTH, which is considered as a physiological dose is not available. As the 1 microgram 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 cortisol response to 1 microgram ACTH in healthy 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 microgram ACTH, and 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/1 or more was defined as a normal response. RESULTS: 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). However, a stimulated cortisol response of 500 nmol/l or more was observed at both 0800 h and 1600 h in all subjects at 30 min but not at 60 min. The [symbol: see text] (peak-basal) response was higher at 1600 h than that at 0800 h (432.8 +/- 136.8 vs 351.5 +/- 177.3, P < 0.01). INTERPRETATION & CONCLUSION: The demonstration of normal cortisol response to 1 microgram ACTH both at 0800 h and 1600 h suggests that the test can be performed at any time of the day.

A preliminary report on basal & stimulated plasma cortisol in patients with acquired immunodeficiency syndrome.

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.

Hypothalamo-pituitary-adrenal axis function in asthmatics taking low dose inhaled beclomethasone dipropionate.

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.

Pituitary adenoma and parasagittal meningioma: an unusual association.

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.

Suprasellar arachnoid cyst presenting with precocious puberty : report of two cases.

Suprasellar arachnoid cysts (SSAC) are uncommon intracranial lesions. Two patients of SSAC presenting with precocious puberty are described. In both the cases partial excision of the cyst wall, through a pterional craniotomy, establishing communication with the basal subarachnoid spaces was carried out. The endocrinological symptoms regressed after surgery. The clinical presentations of SSAC and the treatment options available are reviewed.

Growth hormone therapy.

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.

Cortisol response to arginine-vasopressin does not compare with cortisol response to insulin-hypoglycemia in pituitary tumors.

Timed cortisol responses to insulin-hypoglycemia (IH) and arginine-vasopressin (AVP) were compared in 16 patients with pituitary tumors and six healthy controls. Serum cortisol was estimated by a specific and sensitive radioimmunoassay as per the WHO protocol. The basal cortisol (AM) was normal (> 290 nmol/l) in 9 patients and low in seven. With IH peak cortisol response was normal (> 550 nmol/l) in 10 patients, 8 of whom had normal and 2 had low basal (AM) cortisol. In contrast AVP evoked normal cortisol responses in only 5 of these patients, all of whom had normal basal (AM) cortisol and none had low basal (AM) cortisol. The data indicate lower sensitivity for AVP stimulation test (50%) and favour IH as the standard cortisol stimulation test in patients with pituitary tumors awaiting surgery.

Alterations in circulating thyroid hormones in Indian smokers (bidi and cigarette).

T4, T3 and TSH were estimated in 56 bidi and 50 cigarette smokers and their mean estimates were compared with the corresponding values in 25 healthy non-smokers. T4, T3 and their ratios were significantly lower in both bidi and cigarette smokers (p < 0.001). Circulating TSH in both groups of smokers was similar to that in nonsmokers. T4 and T4/T3 were lower in bidi smokers compared to those in cigarette smokers (p < 0.05 and < 0.01, respectively). Severity of smoking affected T4/T3, and TSH in bidi smokers and T4 in cigarette smokers. Normal TSH excluded any significant decrease in thyroid function in smokers. The alterations in circulating T4 and T3 might have been influenced by thyroid hormone production, protein binding as well as peripheral metabolism of T4 by adverse constituents of bidi/cigarette smoke.

Drug induced endocrine problems.

Drug induced effects on the various endocrine and metabolic processes constitute a very common differential diagnostic possibility in investigating endocrine disorders. Knowledge of drug-effect is of paramount importance to avoid unnecessary and expensive investigations and treatment. Since most of the effects are type A effects and hence predictable, reduction of dose or modification of therapy is sufficient to reverse the adverse effects.

Hormone profile & polycystic ovaries in acne vulgaris.

Thirty women with acne vulgaris, 20 of whom had moderate/severe acne and ten mild acne, and ten controls matched for age were studied. Grade of hirsutism and menstrual irregularities, if any, were recorded. Hormonal measurements included gonadotropins, LH/FSH, prolactin, testosterone and androstenedione in the early follicular phase and progesterone in the luteal phase to assess ovulation. Pelvic ultrasound examination for polycystic ovaries (PCO) was done in all subjects. Sixteen patients with moderate/severe acne and one with mild acne had polycystic ovaries on ultrasound. Patients with moderate/severe acne with polycystic ovaries had high luteinizing hormone, prolactin, testosterone and androstenedione and LH/FSH ratio of more than three. Patients with polycystic ovaries were detected to have at least one hormonal abnormality.

Plasma and urine osmolality in untreated thyroprivic hypothyroidism: effect of eltroxin therapy.

Plasma and urine osmolality were determined in 56 thyroprivic hypothyroid patients before and at 2 and 6 months of eltroxin treatment. Normal range of plasma osmolality (Posm) was defined at 95% confidence limits of values obtained from 25 euthyroid healthy controls. Thirty patients (53%) had lower Posm. The mean Posm in 56 hypothyroid patients increased from 283.4 +/- 2.06 SEM pretreatment, to 295.3 +/- 1.5 at 2 months (p < 0.001) and 296.5 +/- 1.07 at 6 months. The improvements in Posm from those with lower values (30 patients) were more appreciable: 272.3 +/- 1.03 pretreatment, 290.3 +/- 1.9 at 2 months (p < 0.001) and, 296.16 +/- 1.1 at 6 months (p < 0.001). Urine osmolality also increased from a low normal mean of 477.04 +/- 29.64 to 582.48 +/- 28.67 at 2 months (P < 0.05) and 651.46 +/- 28.35 at 6 months (P < 0.001) of eltroxin treatment. Plasma and urine osmolality correlated positively with the clinical severity of hypothyroid state (plasma T3,T4,&TSH) (P < 0.001). These observations suggested a positive influence of thyroid hormones on plasma and urine osmolality and that plasma and urine osmolality increased with achievement of euthyroid state.