ESPE Abstracts

We report a 12-year-old boy who has grown up with central hypothyroidism diagnosed since newborn. The boy was born at 41 weeks of gestation with birth weight of 3520 gram. Newborn screening detected abnormal thyroid function – Cord blood TSH 0.86 mIU/L and free T4 6.76 pmol/L, day 6 TSH 0.63 mIU/L and free T4 9.65 pmol/L. History revealed no history of maternal thyroid disease nor family history of thyroid disease, no drugs or herbs intake during pregnancy, and no symptoms suggestive of diabetes insipidus. He remained clinically euthyroid and thrived along 25th centile. He had no midline defect, micropenis nor undescended testes. Electrolytes and glucose remained stable. Thyroid autoantibodies were negative in both mother and baby. Serial monitoring showed TSH ranged 1.9-2.9 mIU/L (1.4-8.8 mIU/L) and free T4 10.9-13.9 pmol/L (13.9-26.1 pmol/L). Short synacthen test showed good cortisol response. Cranial ultrasound was unremarkable. He was put on thyroxine 25 microgram daily since then. MRI pituitary at 3 months demonstrated normal hypothalamus, pituitary stalk, anterior pituitary and preserved high T1W signal of posterior pituitary. The boy grew along 90th centile with normal development. He had no symptoms suggestive of other pituitary dysfunction. Thyroxine dosage was up titrated to 25/50 microgram alternate day according to free T4 level. MRI pituitary repeated at 6 years demonstrated normal size of pituitary gland and preserved high T1W signal at posterior pituitary. At 8 years, he experienced easy fatigue during intercurrent illness. Morning cortisol was low at 102 nmol/L (166-507 nmol/L) with inappropriately normal ACTH at 5.8 pmol/L (<10.2 pmol/L). Low dose short synacthen test showed suboptimal cortisol response. He was advised to take a stress dose steroid cover during intercurrent illness. At 9 years, re-evaluation of hypothalamus-pituitary-adrenal axis remained at suboptimal cortisol response. In view of multiple pituitary hormones deficiency, molecular diagnosis was arranged. Whole exome sequencing revealed a pathogenic hemizygous c.2563C>T (p.Arg855*) variant in IGSF1 gene inherited from mother. At 11 years, his height dropped to 50th-75th centile. Pubertal examination revealed pre-pubertal testes measured 3ml in volume bilaterally. IGF-1 was low at 120 μg/L (123-497 μg/L). Bone age was 10.37 years (by Greulich and Pyle) at chronological age 11.61 years. Glucagon stimulation test showed suboptimal growth hormone response with peak growth hormone at 11 mIU/L. A second growth hormone provocation test was planned before further discussion for somatropin therapy.