Impact of Severity of Illness on the Function of the Hypothalamo-pituitary-gonadal Axis in Postmenopausal Women with Acute Severe Illness: Implications for Predicting Disease Outcome.

BACKGROUND: While elevated levels of estradiol were predictive of mortality in critically ill surgical and trauma patients, their ability to predict outcome in nonsurgical patients has not been studied. We aimed to study the determinants of gonadotropin levels in acutely ill postmenopausal women with nonsurgical disease and the impact of changes in the gonadal axis on the outcome of these patients. METHODS: Thirty-five postmenopausal women admitted to medical intensive care with acute severe illness and having a Simplified Acute Physiology Score (SAPS II score) ≥30 (in-hospital mortality rate ≥ 10%) were recruited. On the 5th day of hospitalization, fasting samples were collected at 8.00 am and tested for luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, free triiodothyronine, free thyroxine, thyrotropin, cortisol, prolactin, dehydroepiandrosterone, androstenedione, and sex hormone-binding globulin. Multiple linear regression analysis was performed to identify independent determinants if any of LH and FSH. Receiver operating characteristic (ROC) curves were drawn for different cutoffs of LH, FSH, and estradiol to diagnose mortality and prolonged hospitalization. RESULTS: There was an independent negative association between the FSH and the SAPS II score (beta = -0.435; P = 0.014), but not with any of the other tested parameters (estradiol, prolactin, or cortisol). Among components of the SAPS II score, the total leukocyte count (TLC) was negatively associated with serum FSH (beta coefficient = -0.635, P = 0.013). None of these parameters were determinants of LH. On ROC analysis, neither estradiol nor gonadotropins were diagnostic for in-hospital mortality. However, among survivors, low estradiol was diagnostic for prolonged hospital stay (area under the curve = 0.785; P = 0.015). CONCLUSION: FSH, but not LH, is negatively associated with the severity of illness, particularly to its inflammatory component (TLC). Low estradiol in survivors was a predictor of prolonged hospital stay.

Ischemic stroke as a presenting feature of VIPoma due to MEN 1 syndrome.

INTRODUCTION: Presentation of the ischemic stroke due to vasoactive intestinal peptide producing tumor (VIPoma) or Verner Morrison syndrome is rare. This is first of its kind case which we are reporting here which was later turned out to be multiple endocrine neoplasia type 1 (MEN 1) syndrome with diagnosis of primary hyperparathyroidism in the same patient in follow-up. DESCRIPTION OF THE CASE: A 13-year-old girl presented to our emergency department with features of disorientation, weakness of left sided extremities. She had watery high volume diarrhea and related dehydration with renal failure. Blood chemistry was suggestive of hypokalemia with metabolic acidosis. Patient had flushing on her face during this episode of illness. Magnetic resonance imaging (MRI) of brain suggested venous infarct. Computed tomography (CT) scan of abdomen done with high index of suspicion was suggestive of mass in tail of pancreas mostly a VIPoma. Patient was operated for the tumor after which there was no recurrence of diarrhea. Biopsy of tumor was consistent with VIPoma with chomogranin A positivity. Patient improved of her stroke episode with time. On follow-up she is diagnosed to have primary hyperparathyroidism with hypercalcemia due to left inferior parathyroid adenoma which improved with intravenous (IV) zolindronic acid therapy and now she is planned to undergo parathyroidectomy. CONCLUSION: VIPoma is a rare tumor but is well-described with MEN 1. Stroke as a presenting feature of VIPoma is first reported with this case.

Visual disturbances as a presenting feature of pseudohypoparathyroidism.

INTRODUCTION: Visual disturbance as a presenting feature of pseudohypoparathyroidism (PHP) is uncommon. Although papilledema is commonly reported with hypoparathyroidism primary or secondary, but not reported commonly with PHP. DESCRIPTION OF THE CASE: A 10-year-old male child presented to our outpatient service with the complaints of blurring of vision, diplopia, and associated headache. There was no history of seizure episode. Patient had rounded face with a short, stocky built. Shortening of the fourth metacarpal and fifth metatarsal was present. Pitted nails and bilateral cataract. Patient also had clinical signs and biochemical parameters of hypocalcemia, along with normal parathyroid hormone (PTH) levels. Consistent with pseudohypopathyroidism. CONCLUSION: In cases of chronic papilledema, the assessment of the calcium serum level is a safe and simple method to exclude hypoparathyroidism or PHP.

Effect of lifestyle modification and metformin therapy on emerging cardiovascular risk factors in overweight Indian women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovarian syndrome (PCOS) is common among women of reproductive age. Although traditional cardiac risk factors are known to be altered and improved with short-term metformin therapy, not much is known about novel cardiac risk factors. OBJECTIVE: The aim of this study was to evaluate the effects of lifestyle modification and short-term metformin therapy on the fasting serum lipids, homeostasis model assessment of insulin resistance (HOMA-IR), serum high-sensitivity C-reactive protein (hsCRP), and serum homocysteine. METHODS: Native overweight [body mass index (BMI) >23 kg/m(2)] Indian women diagnosed with PCOS were evaluated and subjected to an oral glucose tolerance test and determination of insulin, homocysteine, hsCRP, and fasting lipids levels. They were started on maximally tolerated doses of metformin along with lifestyle modification. Following 3 months of therapy, they were resampled. RESULTS: Out of 36 consecutive patients included, 25 women completed 3 months of metformin treatment and were eligible for repeat evaluation. The age of study group was 22.2 ± 5 years. Twenty-two (61%) women were obese (BMI >25 kg/m(2)). Improvement was seen in body weight, BMI, serum total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), hsCRP, and serum testosterone on metformin therapy. However, no improvement was seen in serum fasting insulin, HOMA-IR, or homocysteine. CONCLUSION: Serum hsCRP improved with lifestyle modification and metformin therapy for 3 months in overweight subjects from India with PCOS, along with serum total cholesterol, triglycerides, and HDL-C. However, markers of insulin resistance and serum homocysteine did not improve.

Efficacy of low dose atorvastatin in diabetic dyslipidaemia.

Coronary heart disease (CHD), the commonest cause of morbidity and mortality in patients with type 2 diabetes, requires multipronged approach for management, including especially treating dyslipidaemia with statins. We conducted this study to demonstrate that low dose (10 mg) atorvastatin is effective in reducing LDL cholesterol (LDL-C) to the target levels in patients from Indian subcontinent. Eighty-one subjects with type 2 diabetes mellitus and dyslipidaemia (LDL-C >100 mg/dl in those without coronary artery disease, n=77; LDL-C >70 mg/dl in those with coronary artery disease, n=4) were included. All patients were initiated on 10 mg atorvastatin daily. Serum lipid profile was repeated after 3 months. The mean body mass index among men and women were 25.0 +/- 4 and 26.7 +/- 3.6 kg/m2 respectively. Pretreatment mean HbA(1c) was 7.9 +/- 1.8 % and total cholesterol, triglycerides and HDL cholestrol (HDL-C) and LDL-C was 214 +/- 27 mg/dl, 164 +/- 63 mg/dl, 46 +/- 6 mg/dl and 135 +/- 24 mg/dl respectively. After three months of treatment the mean decrease was 62 +/- 31 mg/dl in total cholesterol (p < 0.001), 31 +/- 57 mg/dl in triglycerides (p < 0.001), 51 +/- 27 mg/dl in LDL-C (p < 0.001) and 4 +/- 8 mg/dl in HDL-C (p < 0.001). The LDL-C level was reduced by 37.6% in these patients, from 135 +/- 24 mg/dl to 84 = 27 mg/dl (p < 0.001) with 10 mg of atorvastatin daily. It was possible to achieve target LDL-C of less than 100 mg/dl in 75.5% (n=58) in subjects without CHD (n=77) and less than 70 mg/dl in 75% (n=3) of those patients with CHD (n=4). The present study showed that in patients with type 2 diabetes mellitus, 10 mg of atorvastatin daily was safe, well tolerated, and effective in reducing LDL-C to target levels.