Endocrine Abstracts

Introduction: Patients with resistance to thyroid hormone (RTH) have variable tissue hyporesponsiveness to thyroid hormone (TH) due to a defect in the TH receptor (TR) β gene. So far, 124 different mutations have been identified among 343 unrelated families. Despite the TH resistance, some patients have symptoms and signs of hyperthyroidism and may have goiter. RTH is characterised by high TH and normal or high TSH concentrations. Differential diagnosis includes a TSH-producing pituitary adenoma, TH cell membrane transport and metabolism defects and euthyroid hyperthyroxinemia. RTH is associated with autoimmune thyroid disease but not with other endocrinopathies.

Case report: A 47-year-old male with antecedents of atrial flutter, ischemic ictus and hypercholesterolemia was sent to rule out hyperthyroidism. He complains of flushing, sexual dysfunction and infertility. On examination there was no goiter, heart rate: 72 beats/min, weight: 78 kg, height: 173 cm, BMI: 29 kg/m², normal genitalia and secondary sexual characters. His IQ was slightly low. He had high T₄ and RT₃, normal T₃ and high-normal TSH levels: TT₄:17.5 ng/ml (5.0–12.0), FT₄: 2.96–4.32 ng/ml (0.70–1.85), FT₃: 2.8–5.1 pg/ml (2.0–6.8), RT3: 0.38 ng/ml (0.10–0.35) and TSH: 2.11– 4.03 μU/l (0.40–4.00). A TSH producing pituitary adenoma was excluded (normal pituitary MRI, SHBG: 22.6 nmol/l (10–50), α-subunit, TSH and α-subunit responses to IV TRH (0, 15, 30, 60 min: TSH: 1.70, 11.10, 14.80, 8.33 μU/l;α-subunit (0.02–0.8): 0.23, 0.49;0.42, 0.29 UI/l). Ultrasound scan showed mixed nodules with citology of nodular hyperplasia. Antithyroid antibodies were negative. Thyroglobulin: 48 ng/ml (1.5–56) and binding proteins were normal: TBG 18 mcg/ml (10–40), albumin 4.6 g/dl (3.7–5.4), prealbumin 30 mg/dl (10–40). Gonadal function tests showed total testosterone 2.41–2.60 ng/ml (2.70–10.69), FSH 7.09–11.10 mUl/ml (1.5–15), LH 0, 89–1.68 mUl/ml (1.4–7.7), PRL basal 4.79–6.56 ng/ml (2.50–17.00) and ferritin 316 ng/ml (20–300). The other pituitary hormones were normal as well as TH in his relatives (parents and a daughter). A TR β gene mutation was detected: switch G>T in heterozygosis in the c.959 position that produces a switch of the aminoacids p.Arg320Leu (R320L). This mutation have been described before.

Conclusions: We present a case of RTH clinically euthyroid due to a de novo mutation in the TR combined with idiopathic hypogonadotropic hypogonadism. This association have not been reported previously.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.