A rare RET mutation in an Indian pedigree with familial medullary thyroid carcinoma.

Familial medullary thyroid carcinoma (FMTC) is a variant of multiple endocrine neoplasia type 2 (MEN2) associated with the RET gene mutation. We report a rare RET mutation of c.2671T>G; p.Ser891Ala in Exon 15 of the RET gene in an Indian pedigree where seven family members out of 14 screened were found to be positive for the same. RET genetic analysis should be considered as an early approach in the diagnosis of medullary thyroid carcinoma (MTC) since it improves the prognosis and permits surveillance of other family members.

Clinicopathological features and outcome of thyroglobulin elevation and negative iodine scintigraphy (TENIS) patients with negative neck ultrasound: Experience from a thyroid carcinoma clinic in India.

Management of differentiated thyroid carcinoma (DTC) patients with thyroglobulin (Tg) elevation and negative iodine scintigraphy (TENIS) and negative neck ultrasound scan causes considerable diagnostic and therapeutic dilemma, especially in resource-poor settings. The aim of this study was to evaluate clinicopathological features and outcome of TENIS patients with negative neck US attending a thyroid cancer clinic in India. From a DTC database of 722 containing 193 TENIS patients, subjects with negative neck US and negative Tg antibody (TgAb) were selected retrospectively and analyzed using appropriate statistical methods. The study group included 64 patients (male - 17, female - 47, mean age - 44.7 ± 12.8 years) with 54 papillary and 10 follicular thyroid carcinomas, American Thyroid Association (ATA) recurrence risk categorization (2009) - low - 16, intermediate - 28, and high - 2 0. Most of the patients became TENIS within 1 year of diagnosis with median Tg level of 6.5 ng/mL (1.2-996 ng/mL) and mean follow-up of 7.8 years. On follow-up, Tg dropped spontaneously in 27 patients, more among the low and intermediate-risk categories. For those with high or increasing Tg level, further imaging (fluorodeoxyglucose positron emission tomography/computed tomography) was done and 14 out of 18 were positive. Treatment included empiric radioactive iodine therapy-16, external beam radiation therapy (EBRT)-7, and lymph node dissection (LND)-10. A favorable outcome was seen in 36 patients and unfavorable in 28. Distant metastases were associated with unfavorable outcome and poor survival. Progression-free survival was significantly better in the Tg group of <10 at the time of TENIS (111 months) compared to the Tg group >10 (72 months). Tg level dropped spontaneously in nearly half the patients, especially if levels were <10 and more so among the low-risk category. Distant metastasis was predictive of unfavorable outcomes. Along with Tg level, the ATA risk category might help to predict clinical course and reduce unnecessary expensive imaging in resource-poor settings.

Metabolic profile, cardiovascular risk factors and health-related quality of life in children, adolescents and young adults with congenital adrenal hyperplasia.

Background The present study was designed to evaluate the metabolic profile, cardiovascular risk factors and quality of life in children with congenital adrenal hyperplasia (CAH) and compare it with age- and sex-matched controls. Methods Fifty-two patients aged 3-21 years with classic CAH due to 21-hydroxylase deficiency were included in the study. Metabolic profiling was done for 36 cases and compared with 28 healthy age- and sex-matched controls. Quality of life was assessed in all 52 children and their parents using a validated Pediatric Quality of Life Inventory (PedsQL) questionnaire and was compared with normative data from the same population. Results The median age was 12 years with 14 (27%) males and 38 (73%) females. Out of the total 52 patients, 35 (67%) had salt wasting and 17 (33%) had simple virilising CAH. The median height standard deviation score (SDS) of cases was similar to that of controls (-0.72 vs. -0.64, p = 0.57) and 81% of females had normal pubertal status indicating a good control of the disease. Weight SDS, body mass index (BMI) SDS, mean diastolic blood pressure and insulin resistance were significantly higher in cases when compared to controls (0.31 vs. -0.3; 0.96 vs. 0.17; 67.8 ± 10.49 vs. 61 ± 8.49 and 2.1 vs. 0.95, respectively). The quality of life was significantly reduced in all domains as per parents' perspective, whereas the children reported reduced quality of social and school functioning. There was no significant correlation between quality of life and metabolic parameters. Conclusions Children with CAH despite a reasonably good control of the disease have a higher cardiovascular risk and reduced quality of life when compared to healthy controls.