Pituitary stalk interruption syndrome due to novel ROBO1 mutation presenting as combined pituitary hormone deficiency and central diabetes insipidus.

OBJECTIVES: The genetic causes of pituitary stalk interruption syndrome (PSIS) remain elusive in 95 % of cases. The roundabout receptor-1 gene (ROBO1) plays critical roles in axonal guidance and cell migration. Recently, mutations in the ROBO1 gene have been reported patients with PSIS. CASE PRESENTATION: We report a 2.9-year-old boy with PSIS who presented with combined pituitary hormone deficiency, central diabetes insipidus, and the classical triad of MRI findings. Through clinical exome sequencing using next-generation sequencing techniques, a previously unidentified novel heterozygous frame shift mutation in the ROBO1 gene was identified. This is the first report of ROBO1 mutation associated with posterior pituitary dysfunction. CONCLUSIONS: We conclude and emphasize that ROBO1 should be investigated in patients with PSIS. Our case is unique in the published literature in that we are first time reporting posterior pituitary dysfunction as manifestation of ROBO1 mutation. The full clinical spectrum of the mutations may not be fully known.

Sella Turcica Size in Women with Sheehan Syndrome-A Case-Control Study.

Introduction: Sheehan syndrome is a common cause of hypopituitarism in developing countries. Among risk factors, in addition to post-partum haemorrhage, a smaller sellar volume is also believed to predispose to pituitary necrosis. Some earlier studies have reported smaller sellar volume in these patients but involved a small number of patients and lacked matched controls. The main of the present study was to study the sellar volume in a large cohort of patients with Sheehan syndrome and compare it with age- and parity-matched controls. Methods: Fifty women with Sheehan syndrome and an equal number of age- and parity-matched controls were studied. Baseline investigations, relevant hormonal assay, and MRI of pituitary were studied in all. Results: Sellar volume was significantly lower in patients with Sheehan syndrome (334.50 ± 129.08 mm3 in patients as against 456.64 ± 169.25 mm3 in controls, P = 0.000). Far more women with Sheehan syndrome than controls had decreased sellar volume (40% vs. 12%). Conclusions: Patients with Sheehan syndrome have a smaller sellar volume that may be a non-modifiable risk factor for the development of post-partum pituitary necrosis.

Metabolic Abnormalities, Inflammatory Markers and Endothelial Dysfunction in Hyperprolactinemia due to Prolactinoma before and after Normalization of Serum Prolactin: A Prospective Case Control Study.

Background: Hyperprolactinemia is associated with obesity, dyslipidemia, insulin resistance, and low-grade inflammation which may promote endothelial dysfunction (EnD). Limited work has been done on EnD in prolactinomas and we, therefore, studied serum markers of inflammation and EnD in patients with prolactinomas before and after treatment with dopamine agonists. Methodology: Fifty-six treatment naïve patients with prolactinomas and fifty-three (apparently healthy age and sex-matched) controls were enrolled in the study and subjected to clinical assessment and laboratory investigations including blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, urea, creatinine, uric acid, erythrocyte sedimentation rate (ESR), highly sensitive C-reactive protein (hsCRP) and markers of EnD i.e., intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Patients were treated with a dopamine agonist (cabergoline) and parameters (like ESR, hsCRP, ICAM-1, and VCAM-1) were measured at 12 weeks. Results: The majority of the patients (84%) were female, more than half (52%) had metabolic syndrome and over a third (36%) were obese. Blood glucose fasting, HbA1c, lipid fractions, ESR, hsCRP, ICAM-1, and VCAM-1 were significantly higher in patients than in controls. Median ICAM-1 was 1331.95 ng/ml (IQR 803.43-1825.99) in patients vs 753.04 ng/ml (IQR 402.04-871.55) in controls, P < 0.001 and median VCAM-1in patients was 971.35 ng/ml (IQR 695.03-1285.23) as against 634.56 ng/ml (IQR 177.49-946.50) in controls, p0.001. Serum ICAM-1 and VCAM-1 correlated positively with hsCRP. On multivariate regression analysis, serum hsCRP was the only significant predictor of change in ICAM-1 and VCAM-1. Normalization of serum PRL with CAB resulted in a significant decrease in metabolic parameters, ESR, hsCRP, ICAM-1, and VCAM-1. Conclusion: Hyperprolactinemia because of prolactinoma is associated with EnD secondary to systemic inflammation and metabolic abnormalities which improve after treatment with DA.

Thyroid Autoimmunity and Subclinical Hypothyroidism in Prolactinoma: A Case Control Study.

Background: This study was aimed at determining the frequency of thyroid autoimmunity and subclinical hypothyroidism in patients with hyperprolactinemia due to prolactinoma compared to well-matched healthy controls. Methods: This was a cross-sectional study wherein 78 treatment naïve prolactinoma patients and ninety-two healthy control subjects were recruited. Serum prolactin (PRL), thyroid-stimulating hormone (TSH), total thyroxine (T4), circulating anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-Tg) antibody levels were measured in all study subjects. Progression of the antibody-positive population to subclinical hypothyroidism was determined. Results: The median PRL level among patients was 166 ng/ml (IQR 85-467) compared to 11.4 ng/ml (IQR 8.5-15.9) in controls (P < 0.001). There was no significant difference in levels of T4 (P = 0.83) and TSH (P = 0.82) between the cases and controls. Overall, 25% of patients had the presence of anti-thyroid antibodies as compared to 20% of controls (P = 0.56). SCH was more common in antibody-positive hyperprolactinemia subjects compared with antibody-positive controls. Conclusion: We did not find an increased prevalence of thyroid autoimmunity among untreated prolactinoma patients compared to healthy controls. At the same time, subclinical hypothyroidism was more common in thyroid antibody-positive patients with hyperprolactinemia than positive controls.

High prevalence of coronary artery calcification and increased risk for coronary artery disease in patients with Sheehan syndrome-A case-control study.

OBJECTIVE: Patients with Sheehan syndrome (SS) are predisposed to coronary artery disease (CAD) due to risk factors like abdominal obesity, dyslipidemia and chronic inflammation. In addition to estimate CAD risk enhancers like high sensitive C reactive protein (hsCRP), apolipoprotein B (ApoB) and lipoprotein A [Lp(a)], this study applies Framingham risk score (FRS) and coronary artery calcium (CAC) score to compute a 10-year probability of cardiovascular (CV) events in SS patients. DESIGN: Case-control study Sixty-three SS patients, on a stable hormonal replacement treatment except for growth hormone and 65 age, body mass index and parity-matched controls. MEASUREMENTS: Measurement of serum hsCRP, ApoB and Lp(a) and estimation of CAC with 16-row multislice computed tomography scanner. RESULTS: The concentrations of hsCRP, ApoB and Lp(a) were significantly higher in SS patients than in controls (p < .01). After calculating FRS, 95.2% of SS patients were classified as low risk, 4.8% as intermediate risk and all controls were classified as low risk for probable CV events. CAC was detected in 50.7% SS patients and 7.6% controls (p = .006). According to the CAC score, 26.9% SS patients were classified as at risk (CAC > 10) for incident CV events as against 1.6% controls. The mean Multi-Ethnic Study of Atherosclerosis (MESA) score was significantly higher in patients with SS than controls. CAC corelated significantly with fasting blood glucose (r = .316), ApoB (r = .549), LP(a) (r = .310) and FRS (r = .294). CONCLUSION: Significant number of asymptomatic SS patients have high coronary artery calcium score and are classified at risk for CAD.

Primary Hyperaldosteronism and Renal Medullary Nephrocalcinosis: A Controversial Association.

Primary hyperaldosteronism (PA) is a common disease with a prevalence of 5-10% in unselected patients with hypertension. Medullary nephrocalcinosis is a radiological diagnosis and refers to diffuse calcification in the renal parenchyma. The three commonest causes of nephrocalcinosis are hyperparathyroidism, distal renal tubular acidosis, and medullary sponge kidney. PA is not a recognized cause of nephrocalcinosis. There are a few case reports linking PA with nephrocalcinosis published till date. In this case series, we report three cases where PA was possibly associated with medullary nephrocalcinosis. In all three cases, the common causes of nephrocalcinosis were excluded by careful clinical history, biochemical evaluation, and radiological findings. We conclude and emphasize that a diagnosis of PA as an etiology of medullary nephrocalcinosis should be sought after common causes have been excluded, at least in those with hypertension that is difficult to control.

Multiple Uterine Leiomyomas in Multiple Endocrine Neoplasia Type 1 with a Novel MEN1 Gene Mutation.

To report the clinical, hormonal, and genetic features of a female with multiple endocrine neoplasia type 1 (MEN1) with multiple uterine leiomyomas. The study was conducted at a tertiary care endocrinology unit. A 27-year-old female was diagnosed with prolactinoma, primary hyperparathyroidism (PHPT), and multiple uterine leiomyomas. In view of prolactinoma and PHPT, a clinical diagnosis of MEN1 syndrome was made. She also had multiple uterine leiomyomas for which myomectomy was done. Genetic analysis revealed a novel mutation c.1763C>T, p.S588L of MEN1 gene. The association of uterine leiomyomas with MEN1 is exceptionally rare. This is the first report of multiple uterine leiomyomas in a patient with MEN1 from our country and the first report of this mutation in the MEN1 gene in the world. We conclude that in the presence of multiple uterine leiomyomas and endocrine tumor, clinical examination and laboratory evaluation may uncover the diagnosis of MEN1 syndrome in these patients.

Disorders of Sex Development: A 10 Years Experience with 73 Cases from the Kashmir Valley.

PURPOSE: To present the clinical data, investigative profile, and management of patients with disorders of sex development (DSD) from the endocrine unit of a tertiary care university hospital. MATERIALS AND METHODS: This retrospective study included 73 cases of DSD, evaluated and managed at Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, over a period of 10 years from September 2008 to August 2018. RESULTS: Twenty-nine patients (39.7%) had 46 XY DSD and twenty-nine patients (39.7%) had 46 XX. Sex chromosome DSD was diagnosed in 15 (20.5%) patients. Of 29 patients with 46 XY DSD, 17 (58.6%) had 5α-reductase type-2 deficiency (5α-RD) and 6 (20.7%) had complete androgen insensitivity syndrome. In our patients with 5α-RD, the history of consanguinity was documented in nine (52.9%) patients. Two patients had testosterone biosynthetic defect and one patient had partial androgen insensitivity syndrome. Of 29 patients with 46 XX DSD, 16 (55.1%) had congenital adrenal hyperplasia (CAH). Of 15 patients with sex chromosome DSD, 7 patients had Turner's syndrome, 7 had Klinefelter's syndrome, and 1 patient had mixed gonadal dysgenesis. CONCLUSION: In our study, equal number of patients had 46 XY DSD and 46 XX DSD. We are for the first time reporting from India that the most common cause of 46 XY DSD is 5α-RD, whereas CAH is the most common cause of 46 XX DSD as reported previously.

The Clinical Spectrum of Fibrocalculous Pancreatic Diabetes in Kashmir Valley and Comparative Study of the Clinical Profile of Fibrocalculous Pancreatic Diabetes and Type 2 Diabetes Mellitus.

BACKGROUND: Fibrocalculous pancreatic diabetes (FCPD) is a secondary form of diabetes, described from several tropical countries, including India. We described the existence of this entity in the subtropical region-the Kashmir valley of the Indian subcontinent and compared the clinical characteristics of these patients with type 2 diabetes mellitus (T2DM) patients. AIM: The present study aimed to compare the clinical characteristics of patients with FCPD and those with T2DM to identify the characteristics distinctive of FCPD. MATERIALS AND METHODS: A total of 124 patients with FCPD were compared with 124 patients with T2DM matched for age and duration of diabetes. Biochemical parameters and microvascular and macrovascular complications were assessed in all patients. Multivariate regression analyses were performed to study the determinants of microvascular complications in both groups. RESULTS: FCPD patients had significantly lower serum cholesterol, serum triglyceride, and serum calcium levels but higher glycosylated hemoglobin levels compared to T2DM patients. FCPD participants were significantly leaner. The prevalence of retinopathy, neuropathy, and nephropathy was similar between the two. Five T2DM patients had documented cardiovascular disease compared to one in FCPD patients (P < 0.05). Multiple logistic regression analysis revealed glycosylated hemoglobin and duration of diabetes to be significantly associated with retinopathy and nephropathy in T2DM. Among FCPD patients, glycosylated hemoglobin showed a strong association with retinopathy as well as nephropathy. BMI showed a significant negative association with nephropathy in FCPD patients. Age and age at onset showed a strong association with neuropathy in FCPD patients while the duration of diabetes showed the association with neuropathy (P = 0.015) in T2DM. CONCLUSION: There are several differences in the phenotype, biochemical parameters, and prevalence of diabetic complications between patients with FCPD and T2DM.

Presentation, Morbidity and Treatment Outcome of Acromegaly Patients at a Single Centre.

INTRODUCTION: The management of acromegaly, a rare and potentially curable disease, has undergone a paradigm shift in the past few decades. Many of the treatment modalities recommended for acromegaly are either too expensive or not available in many parts of India. There is a dearth of treatment and outcome data in Indian patients. AIM: Our aim was to study the clinical presentation, hormonal profile, radiology, management, and outcome of the disease at our center. MATERIALS AND METHODS: Fifty one patients with acromegaly who attended the Department of Endocrinology, SKIMS, Srinagar, between October 2015 and April 2017, were included in the study. Clinical and hormonal profiles, comorbidities, treatment modalities, and outcome were evaluated. RESULTS: The gender distribution was equal with the mean age of 42.3 ± 10.9 years at diagnosis. The majority (41) of the patients had macroadenoma. The most common presenting manifestations were acral enlargement and headache. Hypertension was present in 23, musculoskeletal manifestations in 19, and diabetes mellitus in 11 patients. Surgery was the most common method of treatment. Preoperatively only one patient with micro-adenoma had hypocortisolism, which was persistent in postoperative period, while no patient had preoperative or postoperative hypothyroidism or hypogonadism. As per the present consensus criteria, 23.7% patients achieved disease control (40% with microadenoma and only 19.5% with macroadenoma). The surgical complications occurred in 5 patients-CSF leak in 3 meningitis in 2 patients all except one having macroadenoma. CONCLUSIONS: The presentation of disease was generally comparable to that reported in literature. Cure rates were significantly lower than those reported from many large centers.

A Comparison between Silent and Symptomatic Renal Stones in Primary Hyperparathyroidism.

BACKGROUND: Nephrolithiasis is a common complication of primary hyperparathyroidism (PHPT), and in a subgroup of patients stones are clinically silent. Patients with silent and symptomatic stones may differ biochemically. There is a scarcity of data available comparing patients with silent and symptomatic renal stones in PHPT. AIMS: To characterize patients with PHPT with nephrolithiais and to compare patients with silent and symptomatic stones. MATERIALS AND METHODS: We reviewed clinical data of 186 patients with PHPT managed at our center from January 1996 to December 2017. Silent renal stones were defined as ultrasonography finding of renal stones without symptoms. Symptomatic renal stones were defined as those with symptoms or a history of graveluria or any procedure for nephrolithiasis. A 5-mm diameter was set as the cut-off between micro- and macrolithiasis. We compared those with (n = 95) and without (n = 91) stones, and, among stone formers, those with symptoms (n = 66) and silent (n = 29) were compared. RESULTS: There was no significant difference between stone formers and nonstone formers with respect to biochemical parameters. Patients with silent renal stones had significantly lower serum calcium and higher phosphate, than those with symptomatic stones. Most (75%) patients with silent renal stones had microlithiais, while only a fifth (22%) with symptomatic renal stones had microlithiasis. CONCLUSION: Nephrolithiasis is a common complication of PHPT. Most patients with silent renal stones had microlithiasis and biochemical features of less severe disease. Patients with silent renal stones may represent early mild stage of PHPT.

FSH ß-subunit mutations in two sisters: the first report from the Indian sub-continent and review of previous cases.

Isolated FSH deficiency due to mutations in the gene for ß-subunit of FSH is an extremely rare autosomal recessive disease of which only eleven cases have been reported so far. The clinical features include absent breast development and primary amenorrhea in females and azoospermia with normal testosterone levels in males. In this study we report two Kashmiri sisters born to native Kashmiri consanguineous parents with failure of onset of puberty. Hormonal evaluation revealed undetectable serum FSH and estradiol and high LH. Genetic analysis of FSH ß-gene identified one nonsense mutation (c.343C > T:p. Arg115Stop) in exon 3. The two sisters were homozygous for this nonsense mutation while the parents were heterozygous. Incorporation of a stop codon at 115 codon position is predicted to result in the formation of truncated FSH ß protein, lacking 14 amino acid from the carboxy-terminus (p.Arg115Stop). Very recently, this same mutation was reported for the first time in a Chinese male. Ours is the first ever report of any FSH ß-subunit mutation from the Indian sub-continent and this particular mutation in any female from anywhere in the world. We conclude and emphasize that this diagnosis should be considered in girls with delayed puberty and selective deficiency of FSH.

Evaluation of Proinflammatory Cytokines in Obese vs Non-obese Patients with Metabolic Syndrome.

BACKGROUND: Obesity is one of the most common yet neglected public health problems in both the developed and developing countries. Metabolic syndrome (MS) is a multiplex of risk factor for the development of type 2 diabetes (T2D) and cardiovascular disease (CVD) and it reflects the clustering of multiple risk factors resulting from obesity and insulin resistance. Despite its predominance in obese individuals, MS does occur in non-obese individuals. Many individuals characterised as normal weight as per their body mass index (BMI), have increased visceral adiposity thereby leading to an unfavourable inflammatory cytokine profile. There are limited studies from India with respect to inflammatory cytokines in obesity and MS in general and non-obese patients with MS in particular. MATERIALS AND METHODS: An observational cross-sectional study was carried out in patients with MS with or without obesity. Anthropometric parameters such as height, weight and waist girth were measured and BMI was calculated. Serum levels of TNF-α, IL-6 and adiponectin were measured by using the enzyme-linked immunosorbent assay. RESULTS: A significant proportion of individuals categorised as normal weight had an increased waist circumference which correlated with BMI, acanthosis nigricans (AN) and fatty liver. There was no statistically significant difference in the cytokine levels in obese and non-obese patients with MS; similarly among non-obese patients with MS, cytokine levels were comparable in patients with or without abdominal obesity. However, triglycerides inversely correlated with adiponectin levels and there was no significant correlation between the cytokines and other parameters of MS. CONCLUSION: There was no significant difference in various metabolic and inflammatory parameters between obese and non-obese patients with MS. Even in non-obese group, there were no differences in metabolic and inflammatory markers between individuals with or without abdominal obesity. This finding indicates that apart from adipose tissue, other factors are also responsible for the development of MS and its associated proinflammatory profile. There could be a significant contribution of genetic and epigenetic factors which needs to be further explored.

Clinical and laboratory profile of primary hyperparathyroidism in Kashmir Valley: A single-center experience.

BACKGROUND: Although primary hyperparathyroidism (PHPT) has become an asymptomatic disease in the West, in India, PHPT is still an uncommonly diagnosed, overtly symptomatic disease with skeletal, muscular, and renal manifestations. AIMS: To describe the profile and surgical outcome of 78 consecutive PHPT patients over a period of two decades at a single center. MATERIALS AND METHODS: All patients who underwent evaluation and surgery for PHPT from January 1996 to December 2015 were included. Evaluation included measurement of serum total calcium, inorganic phosphorus, alkaline phosphatase, intact parathyroid hormone, 25-hydroxy Vitamin D, 24 hour urinary calcium and radiological survey. Ultrasonography neck and technetium-99m sestamibi scan were used for preoperative localization. RESULTS: A total of 78 patients were identified during the two decades of whom 29 patients were studied retrospectively and 49 patients prospectively. Mean age of patients was 44.72 ± 12.46, and male:female ratio was 1:6. The most common presenting features were nephrolithiasis and/or nephrocalcinosis (64.10%), bone pain (44.1%), abdominal pain (39%), constipation (26%), and myopathy (14.10%). Fractures were present only in 10.25%, and brown tumors in 6.41% patients. The cure rate in our series was 96.15%. The mean parathyroid gland weight was 2.05 ± 3.03 g. None of the 41 patients in whom long-term follow-up was available, had recurrence of PHPT. CONCLUSIONS: The profile of PHPT is changing with older age at presentation, and emergence of renal stone disease and decline in overt skeletal disease as common presentation. The parathyroid weight in our study resembles that reported from developed countries.

Emphysematous pyelonephritis: A 10-year experience with 26 cases.

BACKGROUND: Emphysematous pyelonephritis (EPN) is a necrotizing infection which results in gas within the renal parenchyma, collecting system, or perinephric tissue. A majority of cases occur in patients with diabetes mellitus (DM). In EPN, early aggressive medical treatment may avoid nephrectomy. AIMS: The aim of this study was to analyze the characteristics of patients with EPN with respect to patient demographics, clinical presentation, diagnostic investigations, microbiological findings, treatment modality and outcome, and the influence of prognostic factors on the outcome. MATERIALS AND METHODS: We reviewed the hospital records of 26 patients with EPN for clinical, laboratory, radiological, and microbiological findings, treatments given, and outcome. The severity of EPN was graded as per the Huang classification. We applied the reported prognostic factors to our patients to find out whether these factors correlated with failure of conservative treatment. RESULTS: All the study subjects had DM and all but two of them were females. The majority of our patients (61.5%) had extensive EPN (class 3 or 4) and majority (76.9%) had two or more bad prognostic factors. Escherichia coli was the most common causative organism involved in 50% of our cases. Twenty-three (88.5%) of our patients responded to conservative treatment, two required nephrectomy, and one expired on conservative treatment. CONCLUSIONS: In this series of patients with EPN, all had DM, nearly all were women, and E. coli was the most frequently isolated pathogen. Nearly a third of our patients had bilateral disease. Despite the presence of two or more bad prognostic factors and extensive EPN (class 3 or 4) in a majority of our patients, conservative treatment afforded a striking success rate of 88.5%. We recommend early aggressive medical treatment and suggest that nephrectomy should be considered only if patients deteriorate or do not improve on conservative treatment.

CARDIAC STRUCTURAL AND FUNCTIONAL ABNORMALITIES IN FEMALES WITH UNTREATED HYPOPITUITARISM DUE TO SHEEHAN SYNDROME: RESPONSE TO HORMONE REPLACEMENT THERAPY.

OBJECTIVE: Data on cardiac abnormalities in females with untreated hypopituitarism are limited. We investigated echocardiographic abnormalities in females with untreated hypopituitarism and their response to treatment. METHODS: Twenty-three females with treatment-naïve hypopituitarism and 30 matched healthy controls were evaluated for cardiac structure and function. Echocardiographic evaluation was done at presentation and after achieving a euthyroid and eucortisol state. RESULTS: Fourteen (61%) patients had mitral regurgitation, and 11 (48%) had pericardial effusion as against none among controls. Indices of left ventricular (LV) size like LV end diastolic dimension (LVEDD; 44.5 ± 3.5 mm in cases vs. 47.6 ± 3.8 mm in controls, P = .004), and LV diastolic volume (LVEDV; 91.8 ± 18.0 mL versus 106.5 ± 20.4 mL, P = .009) were significantly lower in the SS group compared with controls. LV mass (LVM) was 70.8 ± 19.2 g in cases and 108.0 ± 33.2 g in controls (P = .02). Similarly, indices of LV systolic function like stroke volume (SV; 59.1 ± 12.0 mL in cases and 74.4 ± 15.8 mL in controls; P = .000), ejection fraction (EF; 64.3 ± 6.2 % in cases against 69.9 ± 9.2 % in controls; P = .03), and fractional shortening (FS; 34.9 ± 4.7% versus 40.1 ± 4.4%, P = .000) were significantly decreased in patients compared with controls. Cardiac abnormalities normalized with restoration of a euthyroid and eucortisol state. CONCLUSION: Pericardial effusion, mitral regurgitation, and diminished LVM are common in females with untreated hypopituitarism. ABBREVIATIONS: ACTH = adrenocorticotrophic hormone BMI = body mass index DT = deceleration time EDV = end-diastolic volume EF = ejection fraction FS = fractional shortening GH = growth hormone IGF-1 = insulin growth factor-1 ITT = insulin tolerance test IVSd = interventricular septal diameter LH = luteinizing hormone LV = left ventricular LVEDD = LV end diastolic dimension LVEDV = LV end diastolic volume LVM = LV mass MRI = magnetic resonance imaging MVP = mitral value prolapse PPH = postpartum hemorrhage PWd = posterior wall diameter SS = Sheehan syndrome SV = stroke volume T3 = triiodothyronine T4 = thyroxine TSH = thyroid-stimulating hormone.

Efficacy and safety of Vitamin D supplementation during pregnancy: A randomized trial of two different levels of dosing on maternal and neonatal Vitamin D outcome.

INTRODUCTION: Pregnant women represent a typical group susceptible to dietary and mineral deficiencies. This study was sought to assess the efficacy and safety of various doses of 25-hydroxyvitamin D (25[OH]D) supplementation during pregnancy and ratify the inadequacy of the recommended daily allowance for Vitamin D in vulnerable groups. MATERIALS AND METHODS: A total of 100 pregnant women were included in this open-label, parallel group, prospective, randomized, and controlled trial. Study subjects were assigned to four treatment groups: Group 1 (n = 26), 1000 IU of Vitamin D daily; Group 2 (n = 21), 30,000 IU of Vitamin D monthly; Group 3 (n = 27), 2000 IU of Vitamin D daily; and Group 4 (n = 26), 60,000 IU Vitamin D monthly. Group 1 and 2 were further analyzed together as Group 1K (1000 IU daily and 30,000 IU monthly), and Group 3 and 4 as Group 2K (2000 IU daily and 60,000 IU monthly). The analysis was done on an intention to treat basis. RESULTS: A total of 87 patients completed the study; 21 in Group 1, 25 in Group 2, 18 in Group 3, and 23 in Group 4. The levels of 25(OH)D at baseline ranged from 1.3 to 58.0 with a mean of 24.2 ± 15.1 ng/ml. Postsupplementation, 25(OH)D levels ranged from 11.5 to 70.3 with a mean of 40.2 ± 12.2 ng/ml. The postsupplementation levels of 25(OH)D were higher in Group 2K (42.86 ± 12.83) than in Group 1K (36.96 ± 10.56) with P value of 0.023. CONCLUSION: We concluded that Vitamin D supplementation with 2000 IU/day or 60,000 IU/month is very effective and safe in achieving Vitamin D sufficiency in pregnant women.

Calcitriol-mediated Reversible Hypercalcemia in a Patient with Primary Adrenal Lymphoma.

Primary adrenal lymphomas (PAL) are rare occurrences with only less than 150 cases reported in the literature. Two-thirds of these cases were reported in the last decade due to the advancements in imaging techniques and immunohistochemistry. The non-specific signs and symptoms have resulted in a delayed onset of symptoms and diagnosis of these tumors. Reports of the results of chemotherapy are not gratifying, and most patients die within one year of the diagnosis. We report a 65-year-old male with adrenal non-Hodgkin's lymphoma (NHL), who presented with hypercalcemia and renal failure. We reviewed all adrenal NHL cases presented with hypercalcemia and attempted to comprehend its etiology and overall survival effect.

Allgrove (Triple A) Syndrome: A Case Report from the Kashmir Valley.

Allgrove (Triple A) syndrome is a rare autosomal recessive disorder characterized by cardinal features of adrenal insufficiency due to adrenocorticotropic hormone (ACTH) resistance, achalasia, and alacrimia. It is frequently associated with neurological manifestations like polyneuropathy. Since its first description by Allgrove in 1978, approximately 100 cases have been reported in the literature. Here we report an 18-year-old boy diagnosed as having Allgrove syndrome, with ACTH resistant adrenal insufficiency, achalasia, alacrimia, and severe motor polyneuropathy. Alacrimia was the earliest feature evident at the age of 8 years. He presented with achalasia and adrenal insufficiency at 12 and 18 years respectively and developed neurological symptoms in the form of severe muscle wasting at the age of 15 years. Patients with Allgrove syndrome usually manifest adrenal insufficiency and achalasia during first decade of life. Our patient manifested adrenal insufficiency and achalasia in the second decade and manifested neurological dysfunction before adrenal dysfunction.