Sunday, May 24, 2009

Pituitary-thyroid feedback in a patient with a sporadic activating TSH-R mutation


Title:    Pituitary-thyroid feedback in a patient with a sporadic activating TSH-R mutation: implication that thyroid-secreted factors other than thyroid hormones contribute to serum TSH levels.

Author(s)    Gelwane G, de Roux N, Chevenne D, Carel JC, Léger J
Institution    Pediatric Endocrinology Department, Centre de Référence Maladies Endocriniennes de la Croissance and Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 690, Pediatric Biochemistry and Hormonology Unit, Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Université Paris-Diderot Paris 7, Paris, France.

Source:    J Clin Endocrinol Metab 2009 May 19.

Abstract:    Context: Constitutive mutations of the TSH receptor gene are a rare cause of severe congenital hyperthyroidism. Persistent TSH suppression has been described in euthyroid Graves' disease patients treated with antithyroid drugs. An ultra-short negative feedback loop affecting TSH secretion by activating the pituitary TSH receptor with TSH receptor autoantibodies has been suggested as a possible mechanism of TSH suppression in these patients.

Objective and Design:  To determine whether TSH suppression also occurs in euthyroid treated patients with non-autoimmune hyperthyroidism. We investigated the outcome of pituitary-thyroid feedback in a patient carrying an activating mutation of the TSH-R gene, in an observational prospective study. Repeated clinical investigations from birth until the age of 14 years are presented for the patient on drug treatment and following radical treatment.

Results: TSH was consistently undetectable or present at very low concentrations in the serum for several years, although FT4 and FT3 concentrations remained mostly in the normal range. Moreover, serum TSH concentrations increased only slightly when serum FT4 concentrations fell below normal levels. During drug treatment, serum TSH concentrations expressed as a function of serum FT4 and FT3 concentrations were significantly lower than those for control or congenital hypothyroid populations. By contrast, after radical treatment, serum TSH levels increased, reaching the normal range, and low serum FT4 and FT3 concentrations were associated with appropriate increases in serum TSH concentrations.

Conclusion: These data provide insight into the regulation of serum TSH concentrations and suggest an alternative mechanism, in addition to serum thyroid hormone levels, for adjusting TSH secretion.

Language    ENG
PubMed ID    19454581