Heterogenous biochemical expression of hormone activity in subclinical/overt hyperthyroidism and exogenous...

Subclinical hyperthyroidism/thyrotoxicosis originates from different causes and clinical conditions, sharing the laboratory constellation of a suppressed TSH in the presence of thyroid hormone concentrations within the reference range.

Presentation of hyperthyroidism can manifest itself in several ways. We questioned whether there is either a consistent biochemical equivalence of thyroid hormone response to these diagnostic categories, or a high degree of heterogeneity may exist both within and between the different clinical manifestations.

This secondary analysis of a former prospective cross-sectional trial involved 461 patients with untreated thyroid autonomy, Graves' disease or on levothyroxine (LT4) after thyroidectomy for thyroid carcinoma. TSH response and biochemical equilibria between TSH and thyroid hormones were contrasted between endogenous hyperthyroidism and thyrotoxicosis (LT4 overdose).

Concentrations of FT4, FT3, TSH, deiodinase activity and BMI differed by diagnostic category. Over various TSH strata, FT4 concentrations were significantly higher in LT4-treated thyroid carcinoma patients, compared to the untreated diseases, though FT3 levels remained comparable. They were concentrated in the upper FT4- but low deiodinase range, distinguishing them from patients with thyroid autonomy and Graves' disease. In exogenous thyrotoxicosis, TSH and FT3 were less responsive to FT4 concentrations approaching its upper normal/hyperthyroid range.

The presence or lack of TSH feedforward activity determines the system response in the thyroid-active (hyperthyroidism) and no-thyroid response to treatment (thyrotoxicosis). This rules out a consistent thread of thyroid hormone response running through the different diagnostic categories. TSH measurements should therefore be interpreted conditionally and differently in subclinical hyperthyroidism and thyrotoxicosis.