A Randomized controlled trial on safety and efficacy of single intramuscular versus staggered oral dose of 600 000IU Vitamin D in treatment of nutritional rickets.

OBJECTIVE: Comparison of efficacy and safety of two different regimens of vitamin D-600 000 IU as a single intramuscular dose, and 60 000IU orally once a week for 10 weeks-in treatment of nutritional rickets. METHODS: Children with nutritional rickets (age: 0.5-5 years, n = 61) were randomized to receive either 60 000IU vitamin D orally once a week for 10 weeks or 600 000IU single intramuscular injection. Serum calcium, phosphate, alkaline phosphatase, urinary calcium/creatinine ratio, serum 25 hydroxy vitamin D and radiological score were compared at 12-week follow-up. RESULTS: No difference was found in efficacy of the two regimens on comparing biochemical and radiological parameters. Serum 25 hydroxy vitamin D >100 ng/ml was found in two children in the oral group and one child in the intramuscular group. No child developed hypercalcemia or hypercalciuria after starting treatment. CONCLUSION: Staggered oral and one-time intramuscular administrations of 600 000IU vitamin D are equally effective and safe in treatment of nutritional rickets.

Avascular osteonecrosis of femoral head in a postoperative patient of pituitary Cushing's disease.

We describe a rare association of Cushing's disease causing avascular osteonecrosis of the femoral head in a patient with operated pituitary macroadenoma. Avascular necrosis of the femoral head (AVN) is not a common cause of musculoskeletal disability. Though AVN of the hip is a well-recognized complication of steroid treatment, it is rare in cases of endogenous hypercortisolism. To our knowledge, only 16 patients with AVN, associated with endogenous Cushing's syndrome (CS), have been documented in the medical literature. AVN associated with glucocorticoid use is more likely to manifest as bilateral disease than either idiopathic AVN or ethanol-associated AVN. We describe a 26-year-old woman who was diagnosed with Cushing's disease in 2007 and operated in the same year for an ACTH secreting pituitary adenoma, who was consequently given replacement dose steroid therapy for post operative panhypopituitarism. During follow up, she complained of bilateral hip pain and difficulty in ambulation. Magnetic resonance imaging showed multiple bony infarcts in the proximal femur and distal femur with femoral head collapse fractures bilaterally, consistent with AVN. She further underwent decompression surgery on bilateral hip joints. This case illustrates that AVN, an orthopaedic emergency, can be an alarming manifestation of Cushing's disease.

Switching to a fixed-ratio combination of insulin degludec/liraglutide (IDegLira) is associated with improved glycaemic control in a real-world population with type 2 diabetes mellitus in the United Arab Emirates: Results from the multicentre, prospective INTENSIFY study.

AIM: Investigate the effectiveness of IDegLira, a fixed-ratio combination of insulin degludec/liraglutide, in a real-world setting in patients with type 2 diabetes mellitus in the United Arab Emirates. METHODS: This non-interventional study enrolled adults switching to IDegLira from basal insulin (BI) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with/without concomitant oral antidiabetic drugs (OADs). Primary endpoint was change in HbA1c from baseline, assessed using a mixed model for repeated measurements. RESULTS: Among 263 patients (BI ± OADs, n = 206; GLP-1 RA ± OADs, n = 57), mean baseline HbA1c was 9.29 % (78 mmol/mol). After 26 weeks, HbA1c was significantly reduced (BI ± OADs, -0.83 % [-9.0 mmol/mol] and GLP-1 RA ± OADs, -1.24 % [-13.5 mmol/mol]; both p < 0.0001). Fasting plasma glucose (FPG) was significantly reduced (-39.48 mg/dL [BI ± OADs] and -82.49 mg/dL [GLP-1 RA ± OADs]; both p < 0.0001). Before treatment initiation, 3/263 patients experienced ≥ 1 severe hypoglycaemic episode and 7/263 patients experienced ≥ 1 non-severe hypoglycaemic episode compared with 1/263 patients who had ≥ 1 severe and 1/263 who had ≥ 1 non-severe episode at end of study. Body weight decreased significantly among patients switching from BI ± OADs (-1.05 kg [p < 0.0001]). Treatment was well tolerated. CONCLUSIONS: IDegLira significantly reduced HbA1c and FPG in this real-world setting, along with less frequent episodes of hypoglycaemia. Switching to IDegLira offers effective treatment intensification for type 2 diabetes patients with inadequate glycaemic control.

Children with isolated hypospadias have different hormonal profile compared to those with associated anomalies.

AIM: The objective of this study is to compare the hormonal profile of children with isolated hypospadias to controls and hypospadiacs with associated anomalies. STUDY DESIGN: Prospective observation at a tertiary referral hospital. STUDY SUBJECTS: One hundred consecutive children (0-12 years) with isolated hypospadias (H), 23 with hypospadias and associated anomalies (HO). CONTROLS: One hundred children (0-12 years) without any genitourinary/endocrine abnormalities (C). PROCEDURE: Prehuman chorionic gonadotropin (HCG) and post-HCG fasting blood samples were drawn for estimation of serum gonadotropins, dehydroepiandrosterone sulfate (DHEA-S), estrogen (E), progesterone (P), and testosterone (T) and dihydrotestosterone (DHT). STATISTICAL ANALYSIS: Differences in hormonal levels between controls and subjects were computed with p < or = 0.05 as significant. RESULTS: Compared with controls, "H" had significantly higher follicular stimulating hormone (FSH) (1.37 vs. 1.29 mIU/mL p=0.01), lower estrogen (8.08 vs. 13.78 pg/mL, p=0.00), and lower DHEA-S (27.34 vs. 40.24 microg/dL, p=0.03) levels; HO had higher FSH, lower basal T (0.13 vs. 0.46 ng/mL, p=0.01), and lower peak testosterone (1.53 vs. 2.32 ng/mL, p=0.01). "HO" had lower androgens (basal T, 0.13 vs. 0.29 ng/mL, p=0.03; peak T, 1.53 vs. 2.36 ng/mL, p=0.01), and higher estrogen (12.56 vs. 8.08 pg/mL, p=0.001) and progesterone (0.46 vs. 0.31 ng/mL, p=0.04) levels in comparison with H. CONCLUSION: Consistently lower output of androgens among HO explains the association of other anomalies (generally undescended testes) in them. High FSH among hypospadiacs hints at the possibility of Sertoli cell dysfunction and may have long-lasting sequelae for reproductive functions during adulthood. However, Leydig cell functions are affected more among HO.

Lack of secondary hyperparathyroidism in sub-group of vitamin D deficient postmenopausal women: Is VDR gene polymorphism behind this mystery?

BACKGROUND AND AIMS: We aimed to determine the cause of non-secondary hyperparathyroidism (Non-SHPT) in Indian postmenopausal women. MATERIALS & METHODS: 334 apparently healthy postmenopausal women were assessed for bone mineral homeostaisis including Vitamin D, PTH and VDR polymorphism. RESULTS: 83% of the subjects had vitamin D deficiency further associated with VDR gene polymorphism (P 0.000). A sizable number of subjects (N = 83) did evoke SHPT despite low vitamin D levels. We observe that VDR gene polymorphism was strongly associated in the sub-group of non-SHPT. CONCLUSION: lack of SHPT warrants researchers to study the pathophysiology of non-SHPT in detail to substantiate our findings.

Brain and optic chiasmal herniations into sella after cabergoline therapy of giant prolactinoma.

Optic chiasmal herniation following dopamine agonist therapy is a rare complication in patients with giant prolactinomas. But there are a few case reports of brain and chiasmal herniation following medical therapy in such cases. We report a young man who developed secondary visual loss and seizures after 6 months of medical treatment with cabergoline for giant prolactinoma. Magnetic resonance imaging of hypothalamic pituitary region revealed optic chiasmal and frontal lobe herniation into sella. There was marginal improvement in his vision after cabergoline dose reduction. The present case report highlights frontal lobe herniation in conjunction with optic chiasmal herniation as a very rare complication of medical therapy of giant prolactinoma. Different treatment options of this condition are being discussed.

Bone mineral density trends in Indian patients with hyperthyroidism--effect of antithyroid therapy.

BACKGROUND: Hyperthyroidism is associated with bone loss, which is reversible after treatment. The extent of reversibility of loss of bone mass density (BMD) in hyperthyroid patients after treatment especially at forearm is not clear. Therefore, the present study was conducted to assess degree of reversibility in bone mineral density following one-year medical treatment in Indian patients with hyperthyroidism. METHODS: A total of 30 consecutive patients with hyperthyroidism were included in this one year study at All India Institute of Medical Sciences, New Delhi, India. All the patients were assessed for parameters of bone mineral homeostasis such as calcium, phosphorous, alkaline phosphatase, 25-hydroxy vitamin D [25 (OH) D], parathyroid hormone (PTH) at the time of diagnosis and after one year medical treatment. Bone mineral density was measured using Hologic DXA scan at hip, spine and forearm. All the patients received medical therapy with carbimazole. The parameters of bone homeostasis and bone mineral density at base line and after one year medical treatment was compared. RESULTS: All patients attained euthyroid status after eight weeks of carbimazole therapy. Parameters of bone homeostasis such as calcium, phosphorous, 25 (OH) D and PTH did not show any significant change from base line. Bone mineral density expressed as bone mineral content in gm/cm2 at left hip neck, trochanteric and intertrochanteric region was significantly higher after carbimazole therapy (745.2 +/- 127.6 gm/cm2 vs. 688.2 +/- 123.5 gm/cm2; p = 0.02, 573.4 +/- 109.9 gm/cm2 vs. 641.0 +/- 138.0 gm/cm2, p = 0.005 and 1008.6 +/- 185.5 gm/cm2 vs. 938.0 +/- 145.3 gm/cm2 p = 0.0131 respectively). Bone mineral density at lumbar spine expressed as either T and Z score was significantly higher after treatment (10 months of euthyroid state) (-0.6 +/- 1.3 vs. -1.7 +/- 1.2, p = 0.013 and -0.4 +/- 1.2 vs. -1.4 +/- 1.2, p = 0.012 respectively). However Bone mineral measures as T and Z score at left forearm decreased significantly after one year of medical therapy. CONCLUSION: In Indian patients with hyperthyroidism, the pattern of recovery of bone loss after one year of antithyroid therapy suggests early recovery at hip and lumbar spine and deterioration at forearm.

COVID-19 and Clinical Trials: Current Challenges and Future Directions.

BACKGROUND: The outbreak of coronavirus disease (COVID-19) has posed a major threat to people's lives across the globe. It has drastically changed the way we perceive this world. A paradigm shift was observed globally as the world's emphasis shifted to testing, diagnosis, treatment, and developing a coronavirus cure. Clinical trials were also not untouched by this. The coronavirus pandemic has abhorrently affected the day-to-day clinical trial activities at sites. METHODS: The status of various ongoing clinical trials was assessed through a literature search, which also includes clinical trial portals. Our evaluations were based on these observations. RESULTS: Multiple challenges were present in clinical trials as recruitment, retention, the safety of trial subjects, protocol compliance, and this made the world to re-think to incorporate newer strategies and to cope with this untoward situation. CONCLUSION: Digitalization of clinical trials as virtual management of adverse events, remote monitoring visits, and web-based consulting with trial subjects are potential directions that can be applied to better manage clinical trials worldwide.

COVID-19 infection, inception and immunity: Observations and recommendations in the light of vitamin D?

Responsive immunity plays an important role fighting against infections. Worldwide, Vitamin D deficiency is a major concern not only for musculoskeletal health but also affecting the immunity status in population. Amidst COVID-19 pandemic, it is imperative to establish the role of vitamin D in destruction of pathogens. Vitamin D awareness program at school level might be an effective health governance policy to educate populations for the importance of vitamin D in overall health.

Hypothalamic pituitary abnormalities in tubercular meningitis at the time of diagnosis.

Tubercular meningitis (TBM) is the most dreaded form of extra pulmonary tuberculosis associated with high morbidity and mortality. Various hypothalamic pituitary hormonal abnormalities have been reported to occur years after recovery from disease but there are no systematic studies in the literature to evaluate the pituitary hypothalamic dysfunction in patients with TBM at the time of presentation. Therefore, the present study was designed to evaluate hypothalamic pituitary abnormalities in newly diagnosed patients with TBM. Patient case series. This prospective study included 75 untreated adult patients with TBM diagnosed as "definite", "highly probable" and "probable" TBM by Ahuja's criteria and in clinical stage 1, 2 or 3 at the time of presentation to hospital. Basal hormonal profile was measured by electrochemilumniscence technique for serum cortisol, luetinizing hormone (LH), follicular stimulating hormone (FSH), prolactin (PRL), thyrotropin (TSH), free tri-iodothyronine (fT3), and free thyroxine (fT4). All patients were subjected to MRI to image brain and hypothalamic pituitary axis and CT for adrenal glands. Thirty-two (42.7%) cases showed relative or absolute cortisol insufficiency. Twenty-three (30.7%) cases showed central hypothyroidism and 37 (49.3%) cases had hyperprolactinemia. No patient had evidence of diabetes insipidus. Multiple hormone deficiency was seen in 22 (29.3%) cases. MRI of hypothalamic pituitary axis using dynamic scanning and thin cuts revealed abnormalities in 10 (13.3%) of the cases. CT adrenal gland was normal in all the patients. Tubercular meningitis is associated with both hormonal and structural abnormalities in the hypothalamic pituitary axis at the time of diagnosis.

Hypovitaminosis D and bone mineral metabolism and bone density in hyperthyroidism.

Little is known about the impact of concomitant vitamin D deficiency on bone mineral density in hyperthyroidism. Therefore, we evaluated bone mineral measures in vitamin D-deficient and sufficient patients with hyperthyroidism. Thirty newly diagnosed consecutive patients with hyperthyroidism were included. Blood samples were used for measurement of calcium, phosphate, alkaline phosphatase, 25-hydroxy vitamin D [25(OH) D], and parathyroid hormone (PTH). Bone mineral density (BMD) was measured at the hip, spine, and forearm. The patients were divided into vitamin D-deficient (< 25 nmol/L) and vitamin D-sufficient groups (≥ 25 nmol/L). Eight (26.6%) patients had 25(OH) D levels less than 25 nmol/L, with mean ± standard deviation (SD) level of 16.5 ± 3.2 (vitamin D-deficient group 1), and the remainder had a mean ± SD of 46.0 ± 13.5 nmol/L (vitamin D-sufficient group 2). Serum-intact PTH levels were significantly higher in group 1 compared with those in group 2 (31.2 ± 16.3 vs 18.0 ± 13.1 pg/mL; p=0.041). In the vitamin D-deficient group, the mean BMD T-scores were in the osteoporotic range at hip and forearm (-2.65 ± 1.13 and -3.04 ± 1.3) and in the osteopenia range at lumbar spine (-1.83 ± 1.71). However, in vitamin D-sufficient group, the mean BMD T-scores were in the osteopenia range (-1.64 ± 1.0, -1.27 ± 1.6, and -1.60 ± 0.7) at hip, forearm, and lumbar spine, respectively. The mean BMD Z-scores were also significantly lower in vitamin D-deficient group compared with those in vitamin D-sufficient group. Finally, BMD values (gm/cm(2)) at the hip and forearm were significantly lower in the vitamin D-deficient group compared with those in the vitamin D-sufficient group. In conclusion, hyperthyroid patients with concomitant vitamin D deficiency had lower BMD compared with vitamin D-sufficient patients.

Effect of high dose vitamin d supplementation on vitamin d nutrition status of pre-pubertal children on anti-epileptic drugs - A randomized controlled trial.

BACKGROUND AND AIMS: Patients on long term anti-epileptic drug therapy are prone for Vitamin D deficiency for a myriad of reasons. The aim of this research was to study the effect of high dose vitamin D supplementation on vitamin D nutrition status of children newly started on anti-epileptic drug therapy. MATERIALS: This randomized controlled trial was conducted in a tertiary care Children's Hospital at New Delhi from November 2011 to March 2013. Eighty three children in the age group 5-10 years newly started on anti-epileptic drugs (AED) were randomized into two groups; group A - the intervention group, to whom 60,000 IU vitamin D3 was given orally/month under direct supervision along with AED for a period of 6 months, and group B- the control group, to whom AED without vitamin D3 was given. Serum 25(OH)D, ionized calcium (iCa), total calcium (tCa), inorganic phosphate (iP), alkaline phosphatase (ALP) and parathyroid hormone (PTH) levels were assayed at baseline and at the end of 6 months and were compared within and between the two groups. RESULTS: The mean 25(OH)D in Group A was maintained at 6 months follow up [ 26 ng/ml, 95% CI 20-34 ng/ml] compared to baseline [25 ng/ml, 95% CI -19 to 33 ng/ml] [ p = 0.83]. In group B, there was a significant decrease in 25(OH)D levels at 6 months [13 ng/ml (95% CI 9 ng/ml-17 ng/ml)] compared to baseline [18 ng/ml (95% CI 13-24 ng/ml)] [p = 0.01]. At 6 months, mean serum 25(OH)D was significantly higher in group A as compared to group B (p = 0.005). CONCLUSION: To conclude, oral administration of 60,000 IU vitamin D3/month is sufficient to maintain serum 25(OH)D level and prevent development of vitamin D deficiency in children newly started on AED over a period of 6 months. Non supplementation leads to the lowering of serum 25(OH)D in these children. TRIAL REGISTRATION NUMBER: CTRI/2017/08/009234.

All 25-hydroxyvitamin D-deficient Indian postmenopausal women do not have secondary hyperparathyroidism.

This study shows a high 25-hydroxyvitamin D deficiency among postmenopausal women accompanying secondary hyperparathyroidism. However, a sizable number of subjects did not have secondary hyperparathyroidism despite having low 25-hydroxyvitamin D levels. This condition arises a research question in clinical practice needed to be addressed in the future. PURPOSE: The present study was attempted to determine the prevalence of secondary hyperparathyroidism and also to analyze the mean value (cutoff) of 25-hydroxyvitamin D from where the PTH begins to rise in Indian postmenopausal women. METHODS: A cross-sectional study including 334 postmenopausal women attending the outpatient department (MOPD) of Lok Nayak Hospital, New Delhi, between July 2008 and June 2010. Institutional ethical approval was obtained for this study. The apparently healthy postmenopausal women and attendees of the patients were included in the study. Post-thyroidectomy, thyroid illness, pregnant women, subjects taking drugs that can affect bone mineral metabolism, such as glucocorticoids, antitubercular therapy, antiepileptic, and 25-hydroxyvitamin D supplement were excluded from the study. BMD parameters such as PTH and 25(OH)D were measured by using commercial kits from DiaSorin, USA, and blood chemistry was evaluated by standard methods from the central facility of the center. Dietary calcium was analyzed by applying a food frequency questionnaire by a trained dietician. RESULTS: Mean (SD) age of the subjects was 56.4 ± 7.7 years. The mean BMI was 24.7 ± 5.5 kg/m2. The baseline biochemical investigations such as total bilirubin, liver function test (LFT), kidney function test (KFT), calcium, phosphorous, total protein, and serum albumin were in reference range except alkaline phosphatase (ALP). The mean values of 25(OH)D and PTH were 12.95 ± 8.08 ng/ml and 91.60 ± 75.56 pg/ml respectively. The 24-h dietary calcium intake was 487.06 ± 239.36 mg/24 h. 25-hydroxyvitamin D deficiency was found in 277 subjects (82.93%) and was inversely related to PTH. Forty-three subjects had 25-hydroxyvitamin D levels between 20 and 29 ng/ml (12.87%), and only 14 subjects (4.19%) had optimum 25-hydroxyvitamin D levels. Secondary hyperparathyroidism was found in 235 (70.35%) subjects; however, it was not found in 30%. CONCLUSIONS: Majority of postmenopausal women of India had 25-hydroxyvitamin D deficiency with raised PTH levels. The cutoff point of 25-hydroxyvitamin D at which PTH began to rise was found at 25 ng/ml which seems similar to that of the Caucasians.

Risk factors and epidemiological profile of hip fractures in Indian population: A case-control study.

OBJECTIVES: This analytic retrospective case-control study was designed to analyze risk factors and the epidemiological profile of hip fractures among the Indian population with special importance to the mechanism of injuries. METHODS: Patients of hip fractures (n = 41) and age- and sex-matched healthy volunteers (n = 41) were interviewed by a questionnaire regarding the occurrence of the fracture, past history of diseases and long-term medication usage, past and physical activity, supplements, smoking, and alcohol intake. The data were tabulated using descriptive statistics and logistic regression was used to determine significant risk factors. RESULTS: Age group 60-69 was found to be most affected by hip fractures, though an early onset of fractures was noted in males. Falls due to slipping indoors from standing position was found very commonly. However, an increasing trend of falls was noted from lying down position in the older age groups which was more common during the morning and night hours. Logistic regression analysis for the detection of risk factors was applied to the various variables in the questionnaire. Active status in the past was inversely related (odds ratio [OR], 0.33; P < 0.05) to fracture risk while alternative medication usage in the past 1 year (OR, 4.086; P < 0.05) and significant alcohol consumption were directly associated with fracture risk (OR, 5.484; P < 0.05). A potential inverse relation of use of calcium supplements in the past 3 months and fracture risk (OR, 0.872) was seen, although this was not significant. A potential positive relation of smoking with hip fractures was also seen, but not found significant (OR, 2.204). CONCLUSIONS: Hip fractures in the elderly population are on a rising trend especially in the Indian subcontinent due to a number of factors both hereditary and acquired. Simple measures like routine usage of bedside railing, wall-side railings at an appropriate height, high friction tiles inside rooms and washrooms, and adequate lighting indoors can play a significant role in reducing falls and hip fractures among the elderly.

Prevalence of hypothyroidism in pregnancy: An epidemiological study from 11 cities in 9 states of India.

BACKGROUND: A previous hospital based study from Delhi revealed a high prevalence of hypothyroidism in pregnant women. Several other studies with small sample size also indicate a rising trend of prevalence of hypothyroidism during pregnancy in India. OBJECTIVE: To assess prevalence of hypothyroidism in pregnant women from various states/cities across India. MATERIALS AND METHODS: This was a cross-sectional multicenter study conducted at Allahabad (Uttar Pradesh), Bengaluru (Karnataka), Chennai (Tamil Nadu), Kolkata (West Bengal), Hyderabad (Telangana), Nasik (Maharashtra), Rohtak (Haryana), Pune (Maharashtra), New Delhi (Delhi), Srinagar (Kashmir), and Vizag (Andhra Pradesh) enrolling 2599 pregnant women. Estimation of thyroid stimulating hormone (TSH), free T4, and antithyroid peroxidase (TPO) antibodies was carried out using Roche modular kit using ECLIA technology in a central laboratory. RESULTS: We found in our study population that 13.13% of pregnant women have hypothyroidism (n = 388), using a cutoff TSH level of 4.5 µIU/ml. This prevalence was much higher using the American Thyroid Association criteria. Anti-TPO antibodies were positive in 20.74% of all pregnant women (n = 613), whereas 40% (n = 155) of hypothyroid pregnant women were positive for anti-TPO antibodies. CONCLUSION: This study concludes that there is a high prevalence of hypothyroidism (13.13%), majority being subclinical in pregnant women during the first trimester from India and universal screening of hypothyroidism may be desirable in our country.

A rare case of autoimmune hypophysitis presenting as temperature dysregulation.

Autoimmune hypophysitis is a rare cause of pan-hypopituitarism. Hypothalamic involvement in autoimmune hypophysitis is rare and usually manifests as central diabetes insipidus due to antibodies against arginine vasopressin. Temperature dysregulation is occasionally seen with suprasellar tumours but has never been reported with hypophysitis. We report a case of a middle aged man who presented to us with the complaints of documented body temperature fluctuations since two months followed gradually by hoarseness of voice, sexual dysfunction and syncope. Examination was remarkable for postural hypotension, dry coarse skin and delayed ankle reflexes. Patient's hormone profile revealed pan-hypopituitarism and elevated titre of anti-TPO antibodies. Patient's work up for secondary causes of hypopituitarism was negative. MRI brain revealed typical findings of hypophysitis. Patient was suspected as a case of autoimmune hypophysitis and was immediately treated with prednisolone along with hormone replacement. Rapid response within 30 days was observed in the form of subsidence of temperature fluctuations, improvement in general well being, sexual function and repeat MRI done after one month which revealed a partial empty sella. Autoimmune hypophysitis as a potentially treatable cause of temperature dysregulation has been highlighted in this case.