Influence of age and sex in modulating TSH level in primary hypothyroidism

Previous studies addressing the interaction of age and sex with the function of the hypothalamic-pituitary-thyrotrophs axis yielded conflicting results, due in part to inability to control for the effect of variable free thyroid hormone levels. We studied the effect of age and sex on TSH levels in patients with severe primary hypothyroidism who have essentially undetectable plasma thyroid hormone levels. The TSH levels were measured in 116 thyroid cancer patients four weeks after the withdrawal of thyroxine therapy in preparation for radioidine scan/treatment. All patients has a TSH >/= 30 mU/L (normal = 0.2-5) and a free T4 < pmol/L (normal = 10-25). Thirty males and 86 females with a mean age (+/- SD) of 40 +/- 16 (range 6-89 years) were studied on up to four hypothyroid episodes, with a total of 191 episodes. The TSH level during the first hypothyroid episode correlated significantly with the TSH level during subsequent episodes (first episode versus second episode, r = 0.7, P = 0.0001; first versus third episode, r = 0.6, P = 0.03). There was a significant negative correlation between age and TSH level (r = -0.24, P = 0.0009) that persisted when only the first hypothyroid episode was considered (r = -0.23, P = 0.01), or when only males (r = -0.32, P = 0.02) or only females (r = -0.23, P = 0.005) were considered. Means of TSH levels in males and females were not significantly different (130 verus 114 mU/L, respectively; P = 0.28). We conclude that age but not sex may modulate the sensitivity/responsiveness of the hypothalamic-pituitary thyrotroph axis to primary hypothyroidism.