Plasma thyrotropin bioactivity in Down's syndrome children with subclinical hypothyroidism

Objective: Subclinical hypothyroidism occurs in a number of children with D own's syndrome (DS). The reason for the mildly elevated plasma thyrotropin (TSH) concentrations is not known. The present study investigated whether d ecreased TSH bioactivity plays a role in this phenomenon. Design: A retrospective study of plasma specimens from DS children with mil dly elevated plasma TSH concentrations and thyroid hormone levels within th e reference range, using a TSH receptor-adenylate cyclase mediated bioassay . Methods: Strain JP26 Chinese hamster ovary (CHO) cells, stable transfected with the human TSH receptor, were incubated with unfractionated plasma (1/1 0 diluted in hypotonic incubation medium) of 10 DS children with subclinica l hypothyroidism and nine euthyroid children with insulin-dependent diabete s mellitus as controls, cAMP released in the incubation medium was measured by RIA. Mock-transfected CHO cells were used to correct for non-specific C HO response. WHO Second international Reference Preparation of human TSH wa s dissolved and diluted in pooled normal human plasma and simultaneously bi oassayed to match patient and control results. Results: Plasma TSH levels were slightly increased in DS (mean +/- S.D., 6. 5 +/- 1.3 mU/l, reference range 0.4-4.0 mU/l). Plasma TSH levels for contro ls (1.3 +/- 0.4 mU/l) were within the reference range. Plasma thyroid hormo ne levels in patients and controls were normal, plasma TSH binding inhibito ry immunoglobulin and thyroid peroxidase antibodies were negative. cAMP IP levels (corrected for non-specific CHO response) in DS patients (18.4 +/- 3 .9 pmol/well) and in controls (14.3 +/- 1.3 pmol/well) did not significantl y differ from cAMP levels generated by patient-TSH equivalent TSH standards (16.3 +/- 0.9 pmol/well). Conclusions: The present results demonstrate normal TSH bioactivity in plas ma of DS children, indicating that subclinical hypothyroidism in these pati ents is of primary (thyroidal) origin.