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.
BACKGROUND
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
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 FT(4) and FT(3) concentrations remained mostly in the normal range. Moreover, serum TSH concentrations increased only slightly when serum FT(4) concentrations fell below normal levels. During drug treatment, serum TSH concentrations expressed as a function of serum FT(4) and FT(3) 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 FT(4) and FT(3) concentrations were associated with appropriate increases in serum TSH concentrations.


CONCLUSIONS
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.
Gelwane
Georges
G
Pediatric Endocrinology Unit, Centre de Référence Maladies Endocriniennes de la Croissance, and INSERM Unité 690, Robert Debré Hospital, Université Paris-Diderot Paris 7, 48 Boulevard Sérurier, Paris, France.
de Roux
Nicolas
N
Chevenne
Didier
D
Carel
Jean Claude
JC
Léger
Juliane
J
D025461:Feedback, Physiological; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010902:Pituitary Gland / Q000503:physiopathology*; D011989:Receptors, Thyrotropin / Q000235:genetics*; D013961:Thyroid Gland / Q000503:physiopathology*; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D011989:Receptors, Thyrotropin; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine