Sheehan's Syndrome in a Patient With Factor XI Deficiency.

Sheehan's syndrome (SS) is a condition characterized by panhypopituitarism that generally occurs after an episode of postpartum bleeding. There are certain hypotheses regarding the development of SS in the postpartum period. Coagulation factor abnormalities have been reported to be associated with SS. Associated hypothyroidism and hypocortisolism have been found to cause coagulation abnormalities. After the correction of the hypothyroidism and hypocortisolism, there is a gradual correction of the coagulation abnormality. In our case, a middle-aged woman presented with recurrent episodes of hospital admission because of generalized weakness and fever. She was found to have a biochemistry profile suggestive of hypopituitarism with preserved gonadal function. Her hemogram was normal, but the coagulogram showed a prolongation of activated partial thromboplastin time with a near-normal prothrombin time. She was evaluated and found to have factor XI deficiency. In the background of excessive vaginal bleeding and hypopituitarism, a diagnosis of SS was made. The presence of factor XI deficiency may have led to excessive bleeding and the development of SS. To the best of our knowledge, there is no reported association of factor XI deficiency with SS in the literature, and this is the first reported case.

Corrigendum to "Amiodarone Induced Hyponatremia Masquerading as Syndrome of Inappropriate Antidiuretic Hormone Secretion by Anaplastic Carcinoma of Prostate".

[This corrects the article DOI: 10.1155/2014/136984.].

Effect of Linagliptin and Voglibose on metabolic profile in patients with Type 2 Diabetes: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control by promoting GLP1-mediated glucose-dependent insulin secretion and suppression of glucagon. Sitagliptin and vildagliptin have been shown to improve insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, these patients had uncontrolled blood glucose at inclusion; therefore, the improvement in insulin sensitivity observed in these studies could be attributed to the drug per se and/or reduction in glucotoxicity. This study examines the effect of linagliptin on insulin sensitivity and ß-cell function in patients with well-controlled T2DM. METHODS: Thirty patients with T2DM of duration ≤5 years, and having HbA1c < 7.5% were randomized to receive linagliptin, voglibose or placebo (n = 10 each), and were followed up for 6 months. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and insulin secretory response was measured by basal (M0) and postprandial (M1) ß-cell function, and area under curve (AUC) for C-peptide during mixed meal tolerance test. RESULTS: The median HbA1c of the study subjects at inclusion was 6.9% and there was no significant difference among the groups in terms of age, duration of diabetes, body mass index (BMI), HbA1c, insulin sensitivity, AUC of C-peptide and M0 and M1 at baseline. At the end of the study, there was a modest reduction in HbA1c (- 0.2%) in the linagliptin group, and a significant decrease (- 0.8%) in the voglibose group, as compared to placebo (p = 0.038). However, there were no significant differences in insulin sensitivity, M0 and M1 and AUC of C-peptide, within, or among the groups. CONCLUSION: Linagliptin modestly improves glycemic profile in patients with well controlled T2DM; however, it may not have an effect on insulin sensitivity in these patients. TRIAL REGISTRATION: Retrospectively Registered in Clinicaltrials.gov (ID number, NCT02097342 ). Registered: March 27, 2014.

HbA1c: A Useful Screening Test for Gestational Diabetes Mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse maternal and fetal outcomes, and the oral glucose tolerance test (OGTT) is the recommended test for its diagnosis. We evaluated the role of glycated hemoglobin (HbA1c) in screening and diagnosis of GDM and its correlation with adverse pregnancy outcomes. SUBJECTS AND METHODS: In this prospective observational study, OGTT and HbA1c were performed in 500 antenatal women between 24 and 28 weeks of gestation; the pregnant women were followed up thereafter. Repeat OGTT and HbA1c were done in women with GDM at 6 weeks postpartum. RESULTS: Among the 500 women, 45 were diagnosed with GDM, for an incidence of 9%. The mean HbA1c level in women with GDM was 6.2 ± 0.6%, whereas it was 5.4 ± 0.5% in those with normoglycemia. Women with GDM had a higher incidence of pregnancy-related complications compared with normoglycemic women. An HbA1c cutoff of 5.3% had a sensitivity of 95.6% and a specificity of 51.6% for the diagnosis of GDM and would have avoided OGTT in approximately half of antenatal women, while missing 5% of the women. However, those with an abnormal HbA1c will require a confirmatory OGTT, as 50% of normoglycemic women would be misclassified as having GDM by this approach. On repeat testing postpartum, two of 45 women (4.4%) had overt diabetes mellitus, whereas five (11.1%) had impaired glucose tolerance. CONCLUSIONS: Although HbA1c cannot replace OGTT in the diagnosis of GDM, it can be used as a screening test, avoiding OGTT in approximately 50% of women, if a cutoff of 5.3% is used.

Prostatic hyperplasia in acromegaly, a myth or reality: a case-control study.

CONTEXT: Disorders of the prostate gland are more prevalent in patients with acromegaly. GH-insulin-like growth factor 1 (IGF1) axis plays an additive role in prostatic growth and development. OBJECTIVE: To correlate the structural and histopathological changes of the prostate and prostatic symptoms with GH/IGF1 in patients with acromegaly. DESIGN: Case-control study, from January 2012 to November 2013. SETTING: Tertiary referral centre university hospital in Northern India. PATIENTS: Fifty-three men with acromegaly and 50 healthy men matched for age and BMI. MAIN OUTCOME MEASURES: International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, dimensions of the prostate on trans-rectal ultrasonography, parameters on uroflowmetry, and immunopositivity with anti-IGF1 antibody in prostatic tissue biopsies. RESULTS: Despite low serum testosterone levels (8.9 nmol/l vs 14.3 nmol/l, acromegaly vs control), patients with acromegaly had marginally higher IPSS, PSA levels, and grades of enlarged prostate and obstructive features on uroflowmetry compared with controls. Dimensions of the prostate on ultrasonography were also significantly higher in patients. These changes were present irrespective of age, current gonadal status, and disease activity. Evidence of prostatic hyperplasia on biopsy was seen in six of 14 patients (42.8%) who underwent prostatic biopsy while it was absent in the controls. Immunohistochemistry with anti-IGF1 antibody showed moderate positivity in all the 14 patients who underwent biopsy with benign prostatic hyperplasia, compared with mild positivity in 21% of controls. Similarly, 14 control patients with prostatic malignancies showed variable positivity, four patients had strong, two each had mild and moderate positivity, while six were negative. CONCLUSIONS: In patients with acromegaly, there is a higher frequency of structural changes in the prostate, along with greater prostatic volume and obstructive features, compared with healthy controls, irrespective of age, gonadal status, and disease activity.

Short-term efficacy of recombinant human GH therapy in cured acromegaly patients with GH deficiency: a single-center experience.

The effectiveness and short-term safety of recombinant human GH (r-hGH) in acromegaly patients with GH deficiency (GHD) after treatment are not well established. The study includes ten subjects with acromegaly who had GHD treated with r-hGH for 6 months. Control groups consisted of ten age-, gender-, and BMI-matched healthy subjects and ten active acromegaly patients who were treatment naïve. Body composition, quality of life (QoL), muscle strength, lipid profile, and cardiovascular risk factors were assessed in all subjects at baseline, and the same parameters were reassessed after 6 months of therapy with r-hGH in acromegaly with GHD. Repeat magnetic resonance imaging of the sella was performed in treated subjects. Optical colonoscopy was done and biopsies were taken from multiple sites for proliferation indices (Ki67). The median duration of GHD was 17.8 months and dose of r-hGH administered was 5.7±1.5 µg/kg per day. There was improvement in bone mineral content (P=0.01), bone mineral density (P=0.04), muscle strength (P<0.001), total cholesterol (P=0.003), high-density cholesterol (P<0.001), and QoL - score (P=0.005), and reduction in low-density cholesterol (P=0.003) and triglyceride (P=0.004) after treatment. There was no change in lean body mass, total body fat, hsCRP, lipoprotein (a), and fibrinogen levels. There was a modest increase in plasminogen activator inhibitor 1 (P=0.002), but it was lower compared with healthy controls and treatment naïve acromegalics (P=0.007). Six month-r-hGH therapy improves body composition, atherogenic lipid profile, QoL, and muscle strength in GHD patients who had acromegaly. Long-term prospective studies are needed to evaluate the effect of r-hGH therapy in these patients.

True mycotic aneurysm in a patient with gonadotropinoma after trans-sphenoidal surgery.

BACKGROUND: Immunosuppressive therapy, prolonged antibiotic use, and intrathecal injections are known risk factors for the development of invasive aspergillosis. Central nervous system (CNS) aspergillosis can manifest in many forms, including mycotic aneurysm formation. The majority of the mycotic aneurysms presents with subarachnoid hemorrhage after rupture and are associated with high mortality. Only 3 cases of true mycotic aneurysms have been reported following trans-sphenoidal surgery. CASE DESCRIPTION: A 38-year-old man was admitted with nonfunctioning pituitary adenoma for which he underwent trans-sphenoidal surgery. Three weeks later, he presented with cerebrospinal fluid (CSF) rhinorrhea and meningitis. He was treated with intrathecal and intravenous antibiotics, stress dose of glucocorticoids, and lumbar drain. The defect in the sphenoid bone was closed endoscopically. After 3 weeks of therapy, he suddenly became unresponsive, and computed tomography of the head showed subarachnoid hemorrhage. He succumbed to illness on the next day, and a limited autopsy of the brain was performed. The autopsy revealed extensive subarachnoid hemorrhage and aneurysmal dilatation, thrombosis of the basilar artery (BA), multiple hemorrhagic infarcts in the midbrain, and pons. Histopathology of the BA revealed the loss of internal elastic lamina and septate hyphae with an acute angle branching on Grocott's methenamine silver stain, conforming to the morphology of Aspergillus. CONCLUSION: The possibility of intracranial fungal infection should be strongly considered in any patient receiving intrathecal antibiotics who fails to improve in 1-2 weeks, and frequent CSF culture for fungi should be performed to confirm the diagnosis. Since CSF culture has poor sensitivity in the diagnosis of fungal infections of CNS; empirical institution of antifungal therapy may be considered in this scenario.

Amiodarone induced hyponatremia masquerading as syndrome of inappropriate antidiuretic hormone secretion by anaplastic carcinoma of prostate.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the most common causes of hyponatremia. The usual causes are malignancies, central nervous system, pulmonary disorders, and drugs. Amiodarone is a broad spectrum antiarrhythmic agent widely used in the management of arrhythmias. The different side effects include thyroid dysfunction, visual disturbances, pulmonary infiltrates, ataxia, cardiac conduction abnormalities, drug interactions, corneal microdeposits, skin rashes, and gastrointestinal disturbances. SIADH is a rare but lethal side effect of amiodarone. We describe a 62-year-old male who was suffering from advanced prostatic malignancy, taking amiodarone for underlying heart disease. He developed SIADH which was initially thought to be paraneoplastic in etiology, but later histopathology refuted that. This case emphasizes the importance of detailed drug history and the role of immunohistochemistry in establishing the diagnosis and management of hyponatremia due to SIADH.