Selective pituitary resistance to thyroid hormone masquerading as refractory primary hypothyroidism in a young female

Introduction

Resistance to thyroid hormone beta (RTH-β) is a rare autosomal dominant/recessive disorder characterized by reduced tissue sensitivity to thyroid hormone, with elevated free T3/T4 and non-suppressed TSH. It is frequently misdiagnosed as primary hypothyroidism due to inappropriately high TSH, leading to unnecessary and escalating levothyroxine (LT4) dosing. Case Details: A 19-year-old female presented with irregular menstrual cycles since March 2024, diagnosed with hypothyroidism and started on LT4 12.5 mcg. Despite good compliance and progressive dose escalation, TSH remained persistently elevated with normal-to-high free T3/T4. She developed amenorrhea (since January 2026), grade I goitre, and tachycardia (PR 100 bpm), without visual disturbance or hirsutism. Family history revealed hypothyroidism in maternal uncle & aunt. Investigations: Table 1 JOURNAL/trap/04.03/01235582-202610001-00030/table1/v/2026-10-07T061616Z/r/image-tiff Anti-TPO: Positive. MRI Sella: Normal pituitary, no adenoma, flat upper contour. Genetic Report: Whole exome sequencing revealed a heterozygous pathogenic variant in the ligand-binding domain of a nuclear thyroid hormone receptor, Thrb (-) / Exon 10 / c.1012C>T (p. Arg338Trp) / Thyroid hormone resistance – Selective pituitary (OMIM#145650)