Supplementation with Three Different Daily Doses of Vitamin D3 in Healthy Pre-pubertal School Girls: A Cluster Randomized Trial

Objective: To compare the adequacy and efficacy of differentdoses of vitamin D3 in pre-pubertal girls.Design: Cluster Randomized controlled trial.Setting: Public school in Delhi, India, between August 2015 andFebruary 2016.Participants: 216 healthy pre-pubertal girls, aged 6.1-11.8 years.Intervention: Daily supplementation with 600 IU (n=74), 1000 IU(n=67) or 2000 IU (n=75) of vitamin D3 under supervision for 6months.Outcome measures: Primary: Rise in serum 25 hydroxy VitaminD (25(OH)D); Secondary: Change in bone formation andresorption markers.Results: Following 6 months of supplementation, the mean (SD)rise in serum 25(OH)D was maximum with 2000 IU (24.09 (8.28)ng/mL), followed by with 1000 IU (17.96 (6.55) ng/mL) and 600 IU(15.48 (7.00) ng/mL). Serum 25(OH)D levels of ?20 ng/mL wereseen in 91% in 600 IU group , 97% in 1000 IU group and 100% in2000 IU group. The overall mean (SD) rise in urinary calciumcreatinine ratio (0.05 (0.28) to 0.13 (0.12) mg/mg), and serumprocollagen type I N-terminal propeptide (538.9 (199.78) to 655.5(218.24) ng/mL), and reduction in serum carboxy-terminaltelopeptide (0.745 (0.23) to 0.382 (0.23) ng/mL) was significant(P<0.01). The change in the above parameters was comparableamong the three groups after adjustment for age.Conclusion: Daily vitamin D supplementation with 600 IU to 2000IU for 6 months results in Vitamin D sufficiency in >90% of pre-pubertal girls

Osteoporosis in Indians.

Osteoporosis is characterized by low bone mass with micro architectural deterioration of bone tissue leading to enhance bone fragility, thus increasing the susceptibility to fracture. Although exact numbers are not available, based on available data and clinical experience, on estimated 25 million Indians may be affected. Osteoporotic fractures in India occur commonly in both sexes, and may occur at a younger age than in the West. Recently published data have clearly demonstrated widespread vitamin D deficiency across India, at all ages and in both sexes, particularly in the urban areas. Poor sunlight exposure, skin pigmentation and a vitamin D-deficient diet are some obvious causes for this finding. Indians have low BMD as compared to the western Caucasians. This could be attributed to differences in skeletal size; however, the high prevalence of vitamin D deficiency is a major factor in the low BMD and poor bone health of Indians. Healthy lifestyle (diet, exercise and sunlight exposure) can have a major positive impact on the bone metabolism and bone health of Indians. These public health measures are recommended for the population at large as they are efficacious, safe and cost-effective. The peak bone mass of the population can be increased significantly by appropriate and timely intervention in children. Pharmacological interventions are expensive and should therefore be targeted to only those at high risk of fractures.

Does Paget's disease exist in India?: A series of 21 patients.

OBJECTIVE: Paget's disease of bone has been described as a few case reports from India. The aim of the present study is to document the existence of Paget's disease (PD) in India. MATERIAL AND METHODS: We describe demography, clinical manifestations, biochemical and radiological profile and the treatment outcome of 21 patients of PD. RESULTS: Mean (+/-SD) age of these patients at presentation was 49.2 +/- 17.6 years and the male to female ratio was 2.5:1. Common clinical manifestations included backache, headache and bone pains. Others were fracture, joint pain, deafness, gait ataxia, visual impairment and difficulty in biting. Two patients presented with hydrocephalus and one had recurrent paraparesis. Fifteen (71.4%) patients had polyostotic and six (28.6%) had monoostotic Paget's disease. More commonly involved bones were skull and spine (61.9%) followed by pelvis (38.1%), femur (33.3%), tibia (9%) and ulna (9%). Mean (+/-SD) serum alkaline phosphatase at diagnosis was 1514 +/- 1168 IU/L and nine months after treatment with bisphosphonates decreased to 454 +/- 406 IU/ L(P<0.03). CONCLUSION: This illustrates that Paget's disease does exist in India and a high index of suspicion is required to clinch the diagnosis.

Parathyroid carcinoma.

INTRODUCTION: Parathyroid carcinoma is a rare tumor with an incidence of 0.5 to 4%. Preoperative differentiation from benign adenoma is very difficult. Several features, though nonspecific, have been used in differentiating parathyroid carcinoma from the adenoma. MATERIAL AND METHOD: A retrospective analysis during the period of nine years, four cases of parathyroid carcinoma were diagnosed on the basis of per-operative local invasion and on histological evidence of capsular invasion and vascular invasion. RESULT: We have different observations to make. Diagnosis of parathyroid carcinoma which was done on the basis of intra operative suspicion only. One patient died on 6th post operative day due to development of pancreatitis. At the follow-up of two years there was no local recurrence or distant metastasis. CONCLUSION: It is preferable to have a high index of suspicion for parathyroid carcinoma when these features are present than to miss the opportunity for surgical cure by failing to consider it in the differential diagnosis.

Calcitropic hormonal status in north Indian patients with end-stage renal disease.

BACKGROUND: Bone disease in chronic renal failure has a wide spectrum that includes both high and low turnover conditions. Specific preventive and therapeutic measures require knowledge of the nature of bone involvement. Bone biopsy with static and dynamic histomorphometry is the gold standard for characterization of renal bone disease. However, non-invasive biochemical tests, especially serum intact parathyroid hormone (PTH), have a good correlation with histomorphometry. We studied the clinical and biochemical profile of bone disease in a sample of north Indian patients with chronic renal failure. METHODS: Twenty-nine patients of chronic renal failure were evaluated clinically, radiologically (subperiosteal erosions on hand X-rays) and biochemically (serum calcium, phosphorus, total alkaline phosphatase, intact PTH, osteocalcin, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D). Bone histomorphometry could be done in 4 patients. RESULTS: Serum intact PTH within or below the non-uraemic normal range, an index of low bone turnover, was seen in 17 (58.6%) patients. Serum osteocalcin, a bone formation marker, was within or below the non-uraemic normal range in 65.5% patients. Serum intact PTH and osteocalcin had a significant positive correlation (r = 0.6). Patient groups with clinical or radiological evidence of bone disease had serum intact PTH and osteocalcin levels comparable to those lacking such features. Serum intact PTH and total alkaline phosphatase were lower in haemodialysed (n = 25) patients than in those who had not received haemodialysis (n = 4). Low (< 10 ng/ml) serum 25-hydroxyvitamin D levels were seen in 7 (24%) patients while 1,25-dihydroxyvitamin D was low (< 15.9 pg/ml) in 20 (69%) patients. The biochemical parameters accurately reflected the bone histology (n = 4). CONCLUSIONS: Our data show that the majority of north Indian patients with chronic renal failure have biochemical evidence of low bone turnover. Empirical use of calcium salts and active vitamin D analogues without documentation of parathyroid status carry the risk of further suppression of bone turnover.

Ectopic ACTH syndrome due to bronchial carcinoid tumour--a case report.

A patient is reported who had Cushing's syndrome and carcinoid tumour of the bronchus. The case illustrates the difficulty in preoperative localization of the ectopic ACTH source and the surgical management of such patients.

Growth hormone-producing pituitary tumours: clinical profile and results of surgery.

BACKGROUND: Growth hormone-producing pituitary tumours present with a wide variety of manifestations. The optimum diagnostic work up, management and follow up of such patients is complex and involves a multidisciplinary approach. There is paucity of data from India with regard to the clinical presentation and results of surgery for growth hormone-producing tumours. METHODS: We studied the first 50 patients presenting during 1989-94 with growth hormone-producing pituitary tumours to our centre. The work up included detailed endocrine and radiological assessment. The surgical outcome was analysed for 35 patients who were operated (trans-sphenoidal 29, transcranial 6) at our centre. RESULTS: All the patients had macroadenomas [mean (SD) diameter 3.12 (0.87) cm]. Seventy-five per cent of the patients had supra- and/or parasellar extension and 57% had visual field defects. Tumour size correlated with the preoperative basal (r = 0.57) and glucose-suppressed (r = 0.54) growth hormone levels. Thirty-three of the 35 patients operated at our centre (trans-sphenoidal 28, transcranial 5) were available for follow up (median duration 34 months). After trans-sphenoidal surgery alone, 12 of the 28 (43%) patients had normalization of growth hormone levels (post-glucose growth hormone < 5 ng/ml), and 9 of 11 (82%) showed improvement in visual fields. CONCLUSION: In India, growth hormone-producing pituitary tumours are usually large in size. The growth hormone levels correlate with the size of the tumour. These tumours can be effectively treated by trans-sphenoidal or transcranial surgery.

Intraoperative hypertension during thyroidectomy for Graves' disease.

Hyperthyroidism is well known to be associated with cardiovascular manifestations. The authors have noted that patients of well controlled Graves' Disease often pose problems due to intrapoperative cardiovascular instability. Retrospective analysis of 137 case records of patients with Graves' disease (n = 35), toxic nodular goitre (n = 42) and those with euthyroid benign goitre (n = 60) were studied. In Graves' disease cardiovascular instability was found in the form of hypertension (n = 9) associated with tachyarrhythmia (n = 8) and bradycardia (n = 3). The incidence of first 2 of the above mentioned 3 problems was significantly higher in Graves disease (n = 9/35 patients) in contrast to a comparable group of patients with toxic nodular in (3/42 patients; P value 0.05) and euthyroid goiter (2/60 patients; P value < 0.001). Certain parameters such as high T3, T4 at the time of presentation were associated with higher incidence of these complications, in spite of very well controlled thyrotoxicosis. Whether heightened receptor sensitivity to catecholamines and higher renin-angiotensin activation explain these findings in Graves' disease, remains to be ascertained.

Extraovarian endocrine abnormalities in north Indian women with premature ovarian failure.

BACKGROUND. Premature ovarian failure is a rare syndrome characterized by cessation of menstruation before 35 years of age associated with an elevated gonadotropin level (serum follicle stimulating hormone > 40 IU/L) and oestrogen deficiency. Premature ovarian failure is often the result of an autoimmune process and involvement of other endocrine glands has been reported but available studies are hampered by a lack of uniformity in diagnostic criteria. METHODS. The endocrine profile of 37 north Indian women with premature ovarian failure was studied. The investigations included measurement of serum follicle stimulating hormone, luteinizing hormone, oestradiol, prolactin, total thyroxine, total triiodothyronine and thyroid stimulating hormone. To assess adrenocortical reserve, adrenocorticotropic hormone stimulated plasma cortisol levels were estimated. RESULTS. Eighteen (49%) patients had extraovarian endocrine abnormalities. Eight (22%) had abnormal thyroid function tests and 12 of 29 (41%) patients tested for adrenocortical reserve showed impaired response of plasma cortisol to adrenocorticotropic hormone stimulation. CONCLUSION. Extraovarian endocrine (especially adrenocortical) involvement is frequent in patients with premature ovarian failure. Because none of the patients had overt clinical evidence of thyroid or adrenocortical disease, we suggest that tests for thyroid and adrenal function be performed routinely in females presenting with premature ovarian failure.

The management of Graves' disease by Indian thyroidologists.

BACKGROUND. Although effective modes for treating Graves' disease are available, there is controversy over their choice. We conducted a nation-wide survey to determine trends in the diagnosis and management of Graves' disease in India. METHODS. A proforma was mailed to 45 practising thyroidologists who were members of the Endocrine Society of India or the Thyroid Association of India. One index case and 5 variations were provided, and the members were asked to indicate the investigations of choice, therapeutic modality and details about its implementation. RESULTS. The overall response rate was 71% (32). For diagnosis, serum T3, T4, TSH, sensitive TSH, free T3, and free T4 were asked for by 24, 25, 6, 13, 5, and 10 responders respectively. Radioactive iodine uptake with or without a scan was obtained by 19 of the responders. Antithyroid drugs were the choice of the majority in most situations (index case: 40-year-old female with first episode of typical Graves' disease--23; 40-year-old male--20; 16-year-old male--32; 40-year-old female without goitre--25), except for the patient with relapse and the 65-year-old female where radioiodine was the choice of the majority (20 and 23 respectively). CONCLUSION. Antithyroid drugs are the mainstay of treatment of Graves' disease in India. The predominant use of these drugs was similar to European data, but different from the practice in the USA, where radioiodine is used much more liberally.

Hyperkalemic periodic paralysis associated with thyrotoxicosis.

A 32 year old male presented with episodic pure motor weakness for 1 1/2 months. On evaluation he was found to be thyrotoxic. Hyperkalemic challenge test provoked similar weakness with raised serum potassium (6 meq/L). He responded to treatment with neomercazole. Till he became euthyroid, he responded to the addition of acetazolamide to his medication. He is symptom free on antithyroid drug alone over 8 months of follow up.

Single daily dose of carbimazole in the treatment of hyperthyroidism.

BACKGROUND. The antithyroid drugs, methimazole and carbimazole, are conventionally used in divided daily doses. However, these drugs have a longer intrathyroidal than a plasma half-life. We undertook this prospective, controlled study, in an area of mild iodine deficiency, to compare the efficacy of a single daily dose of carbimazole with divided doses in the treatment of hyperthyroidism. METHODS. Nineteen patients with hyperthyroidism received 30 mg of carbimazole daily at bed time (group A) while 14 received 10 mg of carbimazole every 8 hours (group B). These patients were assessed clinically and biochemically by estimation of serum total thyroxine, total triiodothyronine and thyrotropin before and 1, 2, 3, 4 and 6 weeks after treatment. RESULTS. There was no significant difference between mean baseline concentrations of thyroxine and triiodothyronine. After 1, 2, 3, 4 and 6 weeks there was a decline in their concentrations which was similar in both groups (p > 0.05). Euthyroidism was achieved in 4.6 +/- 1.4 weeks (range 2-6 weeks) in group A and in 3.8 +/- 1.2 weeks (range 3-6 weeks) in group B (p > 0.05). CONCLUSIONS. We conclude that carbimazole in a single daily dose is an effective method for treating hyperthyroidism in an area of mild iodine deficiency and its efficacy is comparable to divided dose therapy. This practical and acceptable method of treatment can be specially useful in patients who find it difficult to remember to take divided doses.

Iopanoic acid as an adjunct to carbimazole in the management of hyperthyroidism.

BACKGROUND. The thiourea drugs take a few weeks to control the symptoms of hyperthyroidism whilst iodine containing radiographic contrast agents (iopanoic acid and sodium ipodate) have a more rapid effect. There is no report on the use of iopanoic acid administered in conjunction with carbimazole, so we evaluated the efficacy of this combination in the early medical management of patients with hyperthyroidism. METHODS. Thirty hyperthyroid patients diagnosed by clinical and biochemical criteria were randomized into two treatment groups. Group A (n = 16) received iopanoic acid (500 mg orally twice a day for the first 3 weeks) and carbimazole (30 mg orally in three divided doses) while group B (n = 14) received carbimazole alone. Clinical examination and estimation of serum total T3, total T4 and TSH were done by radioimmunoassay at the start of therapy, weekly for 4 weeks and then at 6, 8 and 12 weeks. RESULTS. In the initial 3 weeks, iopanoic acid induced a significantly greater fall in mean serum total T3 levels (Z = 2.298, p < 0.02) and a slower fall in mean serum total T4 (Z = 2.396, p < 0.05) in group A patients compared to those in group B. This was accompanied by earlier clinical improvement in group A patients. The mean serum total T3 and T4 values rose to higher levels in group A at 4 weeks, one week after discontinuation of iopanoic acid. At the end of 12 weeks, however, there was no significant difference in the mean serum total T3 and T4 levels between the two groups (p > 0.05). Biochemical euthyroidism (i.e. total T3 < 3 nmol/L and total T4 < 170 nmol/L) was achieved later in group A patients than in group B (10.4 +/- 5.0 weeks v. 3.6 +/- 1.2 weeks, p < 0.0001). CONCLUSIONS. Iopanoic acid given together with carbimazole induces rapid clinical improvement in hyperthyroid patients than carbimazole alone. However, the delayed achievement of euthyroidism may preclude its routine use in the management of patients with hyperthyroidism except in those with thyrotoxic emergencies.

Malignant insulinoma presenting with recurrent episodic loss of consciousness.

A 57 year old male presented with episodic behavioural abnormalities and loss of consciousness for 2 years. His fasting blood glucose was 20 mg/dl and corresponding insulin level 119 uU/ml. His EEG showed intermittent rhythmic delta activity. Abdominal CT scan revealed an enhancing mass in the tail of the pancreas and secondaries in the liver. After distal pancreatectomy, resection of the left lobe of the liver and chemotherapy, the hypoglycaemic spells subsided. Histopathology revealed an islet cell tumour with metastases in the liver. Episodic neurobehavioural dysfunction should alert towards the possibility of hypoglycaemia.