Trimester-specific thyroid hormone reference data in Sri Lankan women.

Introduction: Regional differences in thyroid hormones are noted, especially during pregnancy. Objectives: Establish reference values for thyroid function tests for Sri Lankan pregnant women and to determine their comparability with regional data; and determine the prevalence of 2. Thyroid Peroxidase (TPO) antibody positivity and 3. Iodine deficiency among pregnant women with uncomplicated clinical history. Methods: A cross-sectional study conducted in antenatal clinics of a tertiary care maternity center recruited a minimum of 56 women in each trimester in a multistep approach to derive an "ideal-reference population"; Participants with clinically manifested thyroid disease, followed by subjects with sonographically abnormal thyroids and finally those at high risk for thyroid disease as shown by positive TPO levels and urine iodine deficiency were excluded in sequence. Thyroid hormones were measured by chemiluminescence in the ideal reference population. Reference ranges were derived using median and 5th and 95th centiles. Results: Final sample included 369 women. TSH reference ranges of the first (n=64), second (n=188) and third (n=117) trimesters were 0.014-2.77mIU/L, 0.31-3.2 mIU/L and 0.34-3.4 mIU/L, respectively. TPO antibody level showed a weak but significant correlation with TSH (r=0.10,p 0.021) in the final sample. No significant association was found between urine iodine and thyroid function tests. Conclusions: TSH reference ranges observed in this study are concordant with the Caucasian reference values more than the regional values. Discrepancies in study methodology, defining and selection of reference population and methods employed in measuring thyroid hormones in different studies may have accounted for these differences.

Giant Prolactinoma of Young Onset: A Clue to Diagnosis of MEN-1 Syndrome.

Multiple endocrine neoplasia (MEN) type 1 syndrome is an autosomal dominant disorder caused by germline mutations in MEN1 gene, characterized by tumours in endocrine and nonendocrine organs. Giant prolactinoma is defined as tumours larger than 40mm with very high prolactin secretion. We report two unrelated Sri Lankan patients (8-year-old boy and a 20-year-old female) who presented with giant prolactinomas with mass effects of the tumours. The female patient showed complete response to medical therapy, while the boy developed recurrent resistant prolactinoma needing surgery and radiotherapy. During follow-up, both developed pancreatic neuroendocrine tumours. Genetic analysis revealed that one was heterozygous for a nonsense mutation and other for missense mutation in MEN1 gene. Screening confirmed familial MEN-1 syndrome in their families. High clinical suspicion upon unusual clinical presentation prompted genetic evaluation in these patients and detection of MEN1 gene mutation. Pituitary adenomas in children with MEN-1 syndrome are larger tumours with higher rates of treatment resistance. This report emphasizes importance of screening young patients with giant prolactinoma for MEN-1 syndrome and arranging long-term follow-up for them expecting variable treatment outcomes. Sri Lanka requires further studies to describe the genotypic-phenotypic variability of MEN-1 syndrome in this population.