Molecular Mechanisms in the Etiology of Polycystic Ovary Syndrome (PCOS): A Multifaceted Hypothesis Towards the Disease with Potential Therapeutics.

Among the premenopausal women, Polycystic Ovary Syndrome (PCOS) is the most prevalent endocrinopathy affecting the reproductive system and metabolic rhythms leading to disrupted menstrual cycle. Being heterogeneous in nature it is characterized by complex symptomology of oligomennorhoea, excess of androgens triggering masculine phenotypic appearance and/or multiple follicular ovaries. The etiology of this complex disorder remains somewhat doubtful and the researchers hypothesize multisystem links in the pathogenesis of this disease. In this review, we attempt to present several hypotheses that tend to contribute to the etiology of PCOS. Metabolic inflexibility, aberrant pattern of gonadotropin signaling along with the evolutionary, genetic and environmental factors have been discussed. Considered a lifelong endocrinological implication, no universal treatment is available for PCOS so far however; multiple drug therapy is often advised along with simple life style intervention is mainly advised to manage its cardinal symptoms. Here we aimed to present a summarized view of pathophysiological links of PCOS with potential therapeutic strategies.

Prevalence of coronary calcium deposits in Sheehan's syndrome patients on long term replacement treatment.

PURPOSE: Sheehan's Syndrome (SS) is one of the most important causes of hypopituitarism in developing countries with patients having varying degrees and severity of anterior pituitary hormone deficiency including growth hormone deficiency (GHD). SS is characterized by increased clustering of metabolic and proinflammatory risk factors predisposing them to increased cardiovascular morbidity and mortality. Coronary calcium deposits (CCD), a marker for significant coronary atherosclerosis, is used for evaluation in asymptomatic individuals of global cardiac risk to develop events related to coronary heart disease (CHD). This study therefore aimed to evaluate the prevalence of coronary artery disease in patients with SS appropriately replaced for pituitary hormone deficiencies but untreated for GHD. METHODS: Thirty patients previously diagnosed with SS and stable on a conventional replacement treatment for at least 6 months before the study and thirty age and Body Mass Index (BMI) matched controls were enrolled in this observational study. The subjects underwent detailed clinical, biochemical, and hormone analysis. Coronary multidetector computed tomography was performed in 19 SS patients and 19 healthy participants by a 16-row multislice scanner. Non contrast acquisitions were performed to detect coronary calcifications. Calcium was quantified by the Agatston score (AS) in all subjects. AS > 10 indicates increased CHD risk. RESULTS: The mean (± SD) age was 38.30 ± 10.73 years and the diagnostic delay was 11.35 ± 4.74 years. Patients with SS had significantly higher mean triglyceride, total cholesterol, and low density lipoprotein (LDL) cholesterol and lower HDL cholesterol concentrations on conventional replacement therapy. The prevalence of CCD was significantly higher in patients of SS compared to controls (42.1% vs. 5.3%; P = 0.023). The presence of CCD and AS > 10 were detected in 42.1% and 31.6% of patients respectively. The presence of significant calcification (Agatston score > 10) was documented in 75% of patients (6/8) of the SS patients with CCD compared to none in the control group (P = 0.019). (Left anteriordescending, 1; left circumflex, 2; right coronary artery, 2 and posterior descending, 1) CONCLUSION: Since coronary artery calcium is an independent predictor of CHD events, the presence of significant prevalence of CCD in patients with SS compared to healthy matched controls, undermines the importance of early risk stratification of SS individuals with plethora of conventional cardiovascular risk factors that are at relatively high risk to avoid the adverse vascular consequences.

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.

Autoimmune polyglandular syndrome type 1 with reversible dilated cardiomyopathy: complete recovery after correction of hypocalcemia and hypocortisolemia.

Autoimmune polyglandular syndrome type 1 (APS1) - characterized by the triad of mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency - is an uncommon entity. In this case report we describe the case of a young girl who presented with classic features of APS1 and dilated cardiomyopathy, which were missed during her presentation to the children's hospital. Her condition improved only when appropriate replacement therapy in the form of calcium, calcitriol and hydrocortisone was instituted. Hypocalcemia and hypocortisol state are curable causes of myocardial dysfunction and subsequent congestive cardiac failure, and should always be considered in the differential diagnosis of resistant congestive cardiac failure, especially in children. To the best of our knowledge, cardiomyopathy in the setting of APS1 has never been described previously and can remain unrecognized for a long time and present with life threatening complications.

Hematological response of pancytopenia to glucocorticoids in patients with Sheehan's syndrome.

Sheehan's syndrome presents with panhypopituitarism after childbirth, usually preceded by post partum hemorrhage. Hematological abnormalities like pancytopenia with hypocellular marrow in these patients are reported rarely. Though multiple hormone deficiencies may contribute to Pancytopenia in Sheehan's syndrome, complete recovery is observed after achieving eucortisolemic and euthyroid state. The predominant role of thyroxine or glucocorticoids in reversing pancytopenia in these patients has not been studied. We present the clinical, hormonal, hematological course and response to glucocorticoids in a patient of Sheehan's syndrome presenting with pancytopenia. Complete recovery of pancytopenia was observed after achieving eucortisolemic state thus concluding that gulcocorticoid replacement is sufficient to reverse pancytopenia in these patients.

Prevalence of hematological abnormalities in patients with Sheehan's syndrome: response to replacement of glucocorticoids and thyroxine.

Anemia and other hematological abnormalities are common in patients with Sheehan's syndrome. The response of these abnormalities to replacement of thyroxine and glucocorticoids is not clear. The aim of the present study was to document the profile of hematological abnormalities and response to treatment in patients with Sheehan's syndrome. Forty patients of Sheehan's syndrome and an equal number of age and parity matched healthy controls were studied for prevalence of hematological abnormalities. Hemoglobin concentration, hematocrit, red cell, white cell and platelet count were significantly decreased in patients with Sheehan's syndrome compared to controls. Frequency of anemia, leucopenia, thrombocytopenia and pancytopenia was significantly higher in these patients compared to controls. After achieving euthyroid and eucortisol state, there was a complete recovery of these hematological abnormalities. We conclude that anemia and other cytopenias are common in patients with Sheehan's syndrome and replacement with thyroxine and glucocorticoids results in complete recovery of these abnormalities.

Endocrine disrupting chemical Bisphenol A and its potential effects on female health.

BACKGROUND AND AIM: A large number of chemical compounds with endocrine-disrupting activity have been documented. These chemicals are ubiquitous and widely used in many products of our daily lives. Bisphenol A (BPA) is among the most common Endocrine Disrupting Chemical (EDC) that has been used for many years in the manufacture of polycarbonate plastics and epoxy resins. There is growing evidence that exposure to these EDCs poses a possible health risk. This review focuses on the effect of EDCs, in particular, BPA on female reproduction and Polycystic Ovary Syndrome (PCOS), which is the most prevalent endocrine disorder of reproductively aged women. METHODS: A relevant literature survey was conducted with Google scholar and Pubmed using several appropriate keywords to select the most relevant studies evaluating the role of endocrine disrupting-chemicals in female reproduction. RESULTS: The female menstrual cycle and fertility are very sensitive to hormonal imbalance and alteration in endocrine function during critical times and different stages of lifecycle owing to EDC exposure results in many abnormalities like menstrual irregularities, impaired fertility, PCOS, and Endometriosis among others. BPA is the most extensively studied EDC worldwide and has been strongly associated with female reproductive health. CONCLUSION: EDCs lead to deleterious effects on human health including reproductive health which are of global concern. Exposure to EDCs in early life can elicit disease in adult life and maybe even transgenerational. There is an immediate need to minimize the ill effect of EDCs which can be tackled through the collection of more data to clarify the clinical implications of EDCs.

Sheehan's syndrome with pancytopenia--complete recovery after hormone replacement (case series with review).

Reports of pancytopenia in patients with Sheehan's syndrome are rare, because the disorder is not commonly seen in western countries. A case series of pancytopenia in three patients of Sheehan's syndrome is presented. Three women aged 22, 30, and 34 years developed Sheehan's syndrome preceded by post partum hemorrhage. During investigations, they were found to have pancytopenia with hypocellular marrow. Treatment with thyroxine and glucocorticoids resulted in complete recovery after attaining euthyroid and eucortisolemic state. Review of literature revealed the rarity of the disorder, with only four cases reported so far. Multiple anterior pituitary hormone deficiencies in Sheehan's syndrome are responsible for pancytopenia; replacement of thyroid and cortisol hormones results in complete recovery.

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.

Medical therapy alone can be sufficient for bilateral emphysematous pyelonephritis: report of a new case and review of previous experiences.

Bilateral emphysematous pyelonephritis (EPN) is an extremely uncommon, life-threatening gas-forming infection of renal parenchyma and its surrounding areas. Surgical treatment, including percutaneous catheter drainage and nephrectomy, has been advocated as the treatment of choice in most of the patients. However, nephrectomy is itself a hazardous intervention in an unstable septic patient. Whenever bilateral disease is present, the need for long-term renal replacement therapy is unavoidable. We present the clinical course of a lady who presented with bilateral EPN and was successfully managed by medical therapy alone. We also reviewed almost all published cases of bilateral EPN that had been managed medically.

Deep vein thrombosis in a patient of Sheehan's syndrome: Autoimmunity or hypercoagulabilty.

INTRODUCTION: Literature is inconsistent whether patients with hypopituitarism have increased risk of thrombosis. Recent data has shown problems with the coagulation system in Sheehan's syndrome (SS). Here, we describe a case of SS which presented with deep vein thrombosis. OBJECTIVE: To describe a case of SS presenting as deep vein thrombosis. CASE REPORT: A 30-year-old female was admitted to the general medicine ward with 1 month history of gradual onset swelling and pain in the left leg. The left calf diameter was 5 cm greater than the right. Doppler of the lower limbs revealed thrombosis in the left popliteal vein. Patient's coagulation profile revealed a normal prothrombin time of 12 sec, activated partial thromboplastin time of 30 sec, positive D-dimer, negative protein C and protein S and normal titres of antinuclear antibodies. Echocardiography showed an ejection fraction of 52 percent. Endocrinology consultation was sought in view of clinical suspicion of hypothyroidism. Endocrinology review revealed a significant past history of primary postpartum hemorrhage, lactation failure and secondary amenorrhea since the delivery of the last child 6 years back. She had clinical features of growth hormone, thyroid hormone and adrenocorticotropic hormone deficiency. Hormonal analysis showed features of central hypothyroidism, secondary adrenal insufficiency and growth hormone deficiency which was subsequently confirmed by insulin tolerance test. CONCLUSION: SS patients may have increased risk of thrombosis.

Lithium toxicity and myxedema crisis in an elderly patient.

UNLABELLED: While thyroid dysfunction is a frequent complication of lithium treatment, myxedema crisis is a rare occurrence with a handful of cases described. Here, we describe a patient receiving lithium for about a decade for bipolar disorder, who presented with myxedema crisis and lithium toxicity. In this patient, myxedema crisis was likely precipitated by lithium toxicity and community acquired pneumonia. The effects of lithium on thyroid are briefly reviewed. OBJECTIVE: To describe an elderly male who was diagnosed with myxedema crisis and lithium toxicity. CASE REPORT: A 70-year-old male was admitted in our hospital with history of gradual onset progressive decrease in level of consciousness and altered behavior for last 1 month. Patient also had history of respiratory tract symptoms for 1 week. Patient was a known case of diabetes and bipolar affective disorder for which he had been receiving insulin and lithium for 10 years. One year earlier, patient was admitted in our ward for glycemic control and evaluation of complications and was found to be clinically and biochemically euthyroid; he never returned for follow up until the present admission. On examination patient had incoherent speech, hypothermia, and bradycardia. Thyroid function showed thyroid-stimulating hormone >150 IU/ml, Tetraiodothyronine (T4) <1 µg/dl, anti-thyroid peroxidase titer of 60 IU/ml. The serum lithium level was 2.9 nmol/L (therapeutic level 0.2-1.2 nmol/L). He was managed with levothyroxine, starting with a loading oral dose of 500 µg through ryles tube followed by 100 µg daily, IV antibiotics and fluids; lithium was stopped after consultation with a psychiatrist. From day 5, patient started showing progressive improvement and by day 10, he had a Glasgow Coma Scale of 15/15, normal electrolyte, serum creatinine of 1.8 mg/dl and serum lithium level of 0.5 nmol/L. CONCLUSION: Lithium-induced hypothyroidism may be life-threatening, thyroid function should be monitored before and during lithium therapy and drug should be discontinued and appropriate therapy instituted if hypothyroidism develops.

Dissociated hypopituitarism after spontaneous pituitary apoplexy in acromegaly.

INTRODUCTION: Pituitary apoplexy is an uncommon event and usually occurs in non-functioning pituitary tumors. Among the functioning tumors, prolactinomas are the ones most likely to apoplexy. Apoplexy in growth hormone (GH) producing adenomas is a very rare event with less than thirty cases reported worldwide. OBJECTIVE: To describe a case of spontaneous pituitary apoplexy in acromegaly. CASE REPORT: A 55 year old smoker male presented to the our outpatient clinic in 2004 with complaints of gradual onset increase in the size of hands and feet, bilateral knee pain, increased sweating and blurring of vision. Investigations uncovered diabetes mellitus by a casual blood glucose of 243 mg/dl and HbA1c of 8.5%. Growth hormone suppression test using 75 gram oral glucose showed a 60 minute growth hormone of 105 ng/ml. Magnetic resonance imaging of the sellar region showed a 12.0 mm × 10.0 mm pituitary adenoma. The patient was planned for transsphenoidal tumor decompression. However, the patient was lost to follow up. Eight-years later, he presented in the emergency department of our institute with sudden onset headache, vomiting and decreased level of consciousness of one day duration. CT scan of the head with focus on the sella was suggestive of apoplexy which was later confirmed by the MRI of the sellar region. CONCLUSION: Although acromegaly can remit following apoplexy of the responsible pituitary adenoma, long term follow up is needed for early detection of the development of deficiency of pituitary hormones which may occur over years following the event as well as to detect tumor regrowth which again may occur several years later.

Cleidocranial dysplasia: a rare cause of disproportionate severe short stature.

Skeletal dysplasia is an uncommon cause of short stature in children. An 11-year-old girl was evaluated for severe short stature in a tertiary care hospital. Clinical examination revealed severe disproportionate short stature and classical triad of multiple supernumerary teeth, and complete absence of clavicles and open sagittal sutures and fontanelles. Skeletal survey confirmed these findings, in addition to other features associated with the syndrome.

High prevalence of vitamin D deficiency among newly diagnosed youth-onset diabetes mellitus in north India.

OBJECTIVES: Vitamin D deficiency is common at all ages, and low levels of vitamin D have been associated with high incidence of type 1 diabetes. Similar results are not consistent for type 2 diabetes. The aim of the present study was to estimate vitamin D status in newly detected youth-onset diabetes in north India. SUBJECTS AND METHODS: This was a prospective case control study at a tertiary care hospital in north India. Seventy two newly detected youth-onset diabetes subjects (age < 25 years), and 41 age- and gender-matched healthy controls were studied. In addition to basic information and management regarding their diabetes, metabolic parameters and serum 25(OH)D were measured in both the groups. RESULTS: Vitamin D deficiency was seen in 91.1% of the subjects with diabetes, and 58.5% of the healthy controls. Mean ±SD 25(OH)D was significantly low, 7.88 ± 1.20 ng/mL in subjects with diabetes against 16.64 ± 7.83 ng/mL in controls. Sixty percent of cases had severe Vitamin D deficiency compared with 8.3% in controls. Levels of vitamin D did not correlate with clinical parameters, such as gender, body mass index; or with biochemical parameters, such as serum calcium, phosphorus, alkaline phosphatase, fasting plasma glucose, and HbA1C. CONCLUSION: Vitamin D deficiency is common in people with youth-onset diabetes.

Conservative management of emphysematous pyelonephritis.

Emphysematous pyelonephritis, though uncommon, is a severe necrotizing kidney infection common in patients with diabetes. Surgical treatment has been advocated as the treatment of choice in most of the patients. We present the clinical course of an elderly lady who presented with emphysematous pyelonephritis and was successfully managed with medical treatment despite the presence of adverse prognostic factors like acute renal failure and thrombocytopenia.

Sheehan's syndrome with central diabetes insipidus.

Sheehan's syndrome refers to the occurrence of hypopituitarism after delivery, usually preceded by postpartum hemorrhage. The condition still continues to be a common cause of hypopituitarism in developing countries like India. The disorder usually presents with anterior pituitary failure with preservation of posterior pituitary functions. Posterior pituitary dysfunction in the form of central diabetes insipidus is rare in patients with Sheehan's syndrome. We describe the clinical course of a young lady who after her sixth childbirth developed severe postpartum hemorrhage followed by development of panhypopituitarism which was confirmed by hormonal investigation and demonstration of empty sella on imaging. In addition, she developed Polyuria. The water deprivation test and response to vasopressin test results indicated central diabetes insipidus. She needed oral desmopressin on a continuous basis to control polyuria.

Selective preservation of anterior pituitary functions in patients with Sheehan's syndrome.

BACKGROUND: Sheehan's syndrome manifests as hypopituitarism following a child birth usually preceded by postpartum hemorrhage. The symptoms range from vague feelings of ill health to symptoms of a full blown panhypopituitarism. A large series of such patients is not described in the literature. MATERIALS AND METHODS: We present the details of ten women with partial Sheehan's syndrome. They presented with post-partum hemorrhage and lactation failure. RESULTS: After delivery, seven out of ten patients had regular menstrual cycles indicating preservation of gonadotroph function. Lactotroph, thyrotroph, and somatotroph failure were present in all and corticotrophs preservation was documented in four out of ten patients. The hypophysial magnetic resonance imaging (MRI) confirmed empty sella in all. CONCLUSION: lactotroph, somatotroph and thyrotroph failure are common in patients with Sheehan's syndrome. In addition to known preservation of gonadotroph axis, corticotroph axis may be preserved in some of these patients arguing against the universal treatment of these patients with glucocorticoids.