Endocrine Abstracts

Objective: Report of hypothyroidism due to primary hypotriiodothyronaemia caused by a deficiency in peripheral generation.

Design: Case report and computer modelling.

Main outcome: A 28-year-old woman presented with hypothyroid symptoms and delayed ankle reflex relaxation times. She was not on any medications. The average thyroid stimulating hormone (TSH) concentrations was 2.5 (N: 3.8–5.5 mU/l), free thyroxine (T4) 12.3 (N: 10.5–20 pmol/l) and free triiodothyronine (T3) 3.15 (N: 3.50–6.50 pmol/l). Pituitary and hypothalamic hypothyroidism and secondary causes of the low T3 syndrome were ruled out. The reverse triiodothyronine (rT3) was 180 (N: 120–540 pmol/l). Serum selenium and iodine levels were normal. The log/linear plot of the TSH versus T4 values and suppression of TSH to sub-physiologic levels at mid-normal T4 concentrations, suggested a hyper-sensitive TSH-negative feedback mechanism. Computer modelling of the initial thyroid hormone levels and their response to L-thyroxine replacement was most compatible with a 30% primary decrease in peripheral type 2 deiodinase activity, and a 2% compensatory decrease in T3 inactivation, occurring in the presence of an extra sensitive TSH-negative feedback mechanism.

Conclusion: The patient’s hypothyroidism was due to a deficiency in peripheral T3 generation caused by a primary deficiency in type 2 deiodinase activity, most likely as the result of a mutation in the gene coding for the enzyme.