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Pituitary-Thyroid Feedback in a Patient with a Sporadic Activating Thyrotropin (TSH) Receptor Mutation: Implication That Thyroid-Secreted Factors Other Than Thyroid Hormones Contribute to Serum TSH Levels

Pediatric Endocrinology Department (G.G., N.d.R., J.C.C., J.L.), Centre de Référence Maladies Endocriniennes de la Croissance and Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 690; and Pediatric Biochemistry and Hormonology Unit (N.d.R., D.C.), Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Université Paris-Diderot Paris 7, 75019 Paris, France

Address all correspondence and requests for reprints to: Juliane Léger, M.D., Pediatric Endocrinology Unit and INSERM Unité 690, Robert Debré Hospital, 48 Bd Sérurier, 75019 Paris, France. E-mail: juliane.leger{at}rdb.aphp.fr.

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 ultrashort 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: The aim of the study was 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 yr are presented for the patient on drug treatment and after 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.