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

Abstract

Objective: Subclinical hypothyroidism occurs in a number of children with Down's syndrome (DS). The reason for the mildly elevated plasma thyrotropin (TSH) concentrations is not known. The present study investigated whether decreased TSH bioactivity plays a role in this phenomenon. Design: A retrospective study of plasma specimens from DS children with mildly elevated plasma TSH concentrations and thyroid hormone levels within the 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 (1/10 diluted in hypotonic incubation medium) of 10 DS children with subclinical hypothyroidism and nine euthyroid children with insulindependent diabetes mellitus as controls. cAMP released in the incubation medium was measured by RIA. Mock-transfected CHO cells were used to correct for non-specific CHO response. WHO Second International Reference Preparation of human TSH was dissolved and diluted in pooled normal human plasma and simultaneously bioassayed to match patient and control results. Results: Plasma TSH levels were slightly increased in DS (mean^s.d., 6X5^1X3 mUalY reference range 0.4±4.0 mU/l). Plasma TSH levels for controls 1X3^0X4 mUal were within the reference range. Plasma thyroid hormone levels in patients and controls were normal, plasma TSH binding inhibitory immunoglobulin and thyroid peroxidase antibodies were negative. cAMP levels (corrected for non-specific CHO response) in DS patients 18X4^3X9 pmolawell and in controls 14X31 X3 pmolawell did not significantly differ from cAMP levels generated by patient-TSH equivalent TSH standards 16X3^0X9 pmolawellX Conclusions: The present results demonstrate normal TSH bioactivity in plasma of DS children, indicating that subclinical hypothyroidism in these patients is of primary (thyroidal) origin.

TSH neurosecretory dysfunction (TSH-nd) in Down syndrome (DS): low risk of progression to Hashimoto's thyroiditis

“…However, Konings and cols. (18) showed normal TSH bioactivity in DS children who had subclinical hypothyroidism.…”

Avaliação etiológica da hipertirotropinemia em crianças com síndrome de Down

“…7,10 Selikowitz 10 pointed out the inappropriate release of TSH resulting from a central dysfunction, production of a less active type of TSH or some form of unresponsiveness of the thyroid gland to TSH as possible explanations for this transient elevation. However, the study carried out by Konings et al 19 showed normal bioactivity of TSH in the plasma of children with DS who had subclinical hypothyroidism. An increased response of TSH to TRH is observed in DS patients.…”

“…7,10 Controversy exists over whether such elevation is a risk factor for impaired intellectual outcome in these children 11 and the cause for such elevation has not been clarified yet. [16][17][18][19] Culter et al 2 suggest that the isolated elevation of TSH levels in children with DS, even in the absence of thyroid peroxidase autoantibody (anti-TPO), might be an early sign of primary autoimmune hypothyroidism. Cases with positive anti-TPO are expected to have a frequent progression to overt thyroid disease.…”

Neonatal Pituitary-Thyroid Axis Dysregulation with Combined Thyroid Hormone and Thyrotropin Resistance in Infant with Trisomy 21 and Maternal Subclinical Hypothyroidism

“…Some authors have challenged this hypothesis as proteins involved in mild TSH resistance were normal in patients with Trisomy 21 as well as bioactivity of TSH was normal in children with Trisomy 21 and mildly raised TSH [9]. It has been proposed that these thyroid abnormalities are likely to be thyroidal in origin [10].…”