Prevalence and Impact of Thyroid Disorders on Maternal Outcome in Asian-Indian Pregnant Women

Aims. To establish the prevalence and the effect of thyroid dysfunction on pregnancy outcomes in Asian-Indian population. Subjects and Methods. The study cohort comprised of 483 consecutive pregnant women in the first trimester attending the antenatal clinic of a tertiary center in Mumbai, India. Thyroid hormone levels and thyroid peroxidase antibody were estimated. Patients with thyroid dysfunction were assessed periodically or treated depending on the severity. Subjects were followed until delivery. Results. The prevalence of hypothyroidism, Graves' disease, gestational transient thyrotoxicosis, and thyroid autoimmunity (TAI) was 4.8% (n = 24), 0.6% (n = 3), 6.4 % (n = 31), and 12.4% (n = 60), respectively. Forty percent of the hypothyroid patients did not have any high-risk characteristics. Hypothyroidism and TAI were associated with miscarriage (P = 0.02 and P = 0.001, resp.). Conclusions. The prevalence of hypothyroidism (4.8%) and TAI (12.4%) is high. TAI and hypothyroidism were significantly associated with miscarriage

Virilising ovarian tumors: a single-center experience

Literature on virilising ovarian tumors (VOTs) is limited to case reports and series reporting single pathological type. We have analyzed the clinical, hormonal, radiological, histological, management and outcome data of VOT. This retrospective study was conducted at a tertiary health care center from Western India. Consecutive patients with VOT presenting to our endocrine center between 2002 and 2017 were included. Our study included 13 patients of VOT. Out of 13 patients, two were postmenopausal. All patients in the reproductive age group had secondary amenorrhea except one who presented with primary amenorrhea. Modified F and G score (mFG) at presentation was 24 ± 4.3 and all patients had severe hirsutism (mFG ≥15). Change in voice (n = 11) and clitoromegaly (n = 7) were the other most common virilising symptoms. Duration of symptoms varied from 4 to 48 months. Median serum total testosterone level at presentation was 5.6 ng/mL with severe hyperandrogenemia (serum testosterone ≥2 ng/mL) but unsuppressed gonadotropins in all patients. Transabdominal ultrasonography (TAS) detected VOT in all except one. Ten patients underwent unilateral salpingo-oophorectomy whereas three patients (peri- or postmenopausal) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Seven patients had Sertoli Leydig cell tumor, three had steroid cell tumor and two had Leydig cell tumor and one had miscellaneous sex cord stromal tumor. All patients had normalization of serum testosterone after tumor excision. In conclusion, VOTs present with severe hyperandrogenism and hyperandrogenemia. Sertoli Leydig cell tumor is the most common histological subtype. Surgery is the treatment of choice with good surgical outcome

Efficacy and safety of once-monthly pasireotide in Cushing's disease: A 12 month clinical trial

© 2017 Elsevier Ltd. Background: Cushing's disease is a rare debilitating endocrine disorder for which few prospective interventional studies have been done. We report results of the first phase 3 trial assessing long-acting intramuscular pasireotide in patients with Cushing's disease. Methods: In this phase 3 clinical trial we recruited patients aged 18 years or older with persistent, recurrent, or de-novo (non-surgical candidates) Cushing's disease who had a mean urinary free cortisol (mUFC) concentration (from three 24 h samples) of 1·5-5·0 times the upper limit of normal (ULN), a normal or greater than normal morning plasma adrenocorticotropic hormone concentration, and a pituitary source of Cushing's syndrome, from 57 sites across 19 countries. Exclusion criteria included previous pasireotide treatment, mitotane therapy within 6 months, and pituitary irradiation within 10 years. We randomly allocated patients 1:1 (block size of four) using an interactive-response-technology system to intramuscular pasireotide 10 mg or 30 mg every 4 weeks for 12 months (in the core phase). We stratified randomisation by screening mUFC concentration (1·5 to < 2·0 × ULN and 2·0-5·0 × ULN). The dose could be uptitrated (from 10 mg to 30 mg or from 30 mg to 40 mg) at month 4 if the mUFC concentration was greater than 1·5 × ULN, and at month 7, month 9, or month 12 if the mUFC concentration was greater than 1·0 × ULN. Investigators, patients, site personnel, and those assessing outcomes were masked to dose group allocation. The primary endpoint was the proportion of patients in each group with an mUFC concentration of less than or equal to the ULN at month 7. Efficacy analyses were based on intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01374906. Findings: Between Dec 28, 2011, and Dec 9, 2014, we randomly allocated 150 patients to receive pasireotide 10 mg (74 [49%] patients) or 30 mg (76 [51%] patients). The primary efficacy endpoint was met by 31 (41·9% [95% CI 30·5-53·9]) of 74 patients in the 10 mg group and 31 (40·8% [29·7-52·7] ) of 76 in the 30 mg group. The most common adverse events were hyperglycaemia (36 [49%] in the 10 mg group and 36 [47%] in the 30 mg group), diarrhoea (26 [35%] and 33 [43%] ), cholelithiasis (15 [20%] and 34 [45%] ), diabetes mellitus (14 [19%] and 18 [24%] ), and nausea (15 [20%] and 16 [21%] ). Serious adverse events suspected to be study drug related were reported in eight (11%) patients in the 10 mg group and four (5%) in the 30 mg group. Two (3%) patients in the 30 mg group died during the study (pulmonary artery thrombosis and cardiorespiratory failure); neither death was judged to be related to the study drug. Interpretation: Long-acting pasireotide normalised mUFC concentration in about 40% of patients with Cushing's disease at month 7 and had a similar safety profile to that of twice-daily subcutaneous pasireotide. Long-acting pasireotide is an efficacious treatment option for some patients with Cushing's disease who have persistent or recurrent disease after initial surgery or are not surgical candidates, and provides a convenient monthly administration schedule. Funding: Novartis Pharma AG

Promise and pitfalls of molecular markers of thyroid nodules

Thyroid nodules are common in the general population with a prevalence of 5-7% The initial evaluation of thyroid nodules commonly involves thyroid function tests, an ultrasound (USG) and fine needle aspiration biopsy (FNAB). The optimal management of patients with thyroid nodules with indeterminate cytology is plagued by the lack of highly sensitive and specific diagnostic modalities In this article we attempt to review the available literature on the molecular markers which are increasingly being studied for their diagnostic utility in assessing thyroid nodules. The various molecular markers consist of gene mutations, gene re arrangements, RNA based assays and immunohistochemical markers. The molecular markers definitely would help to optimise the management of such patients

Management issues with exogenous steroid therapy

Glucocorticoids (GCs) are extensively used for various inflammatory and autoimmune disorders, but long term use of these agents is not without complications. Almost every GC formulations (e.g. oral, topical, inhaled, etc.) can cause systemic side effects. It can range from minor side effects (e.g. weight gain) to life-threatening effects (e.g. adrenal suppression, sepsis, etc.), which may require immediate intervention. Therefore, the decision to institute steroid therapy always requires careful consideration of the relative risk and benefit in each patient. The objectives of this study are to discuss monitoring of patients on GCs and management of the complications of GCs