Familial hyperthyroidism without evidence of autoimmunity

Abstract

Abstract. Thirty-four members of a single family were studied and 9 of them were found to be suffering from hyperthyroidism associated wiht diffuse goitre. Exophthalmos was absent and transmission seemed to be independent of HLA type. Four of the 9 were studied prior to treatment but in all cases serum immunoglobulin levels were normal, antithyroglobulin and antimicrosomal antibodies absent, thyroid stimulating antibodies negative and the lymphocyte transformation responses to mitogens not different from those of controls. The results of testing the euthyroid family members were similarly negative, except in the case of a woman with type I diabetes mellitus who showed a low titre of antimicrosomal antibody. Seven of the patients underwent subtotal thyroidectomy. Lymphocytic infiltration of the excised portion was rarely present. Four of the glands were subjected to immunofluorescent and electron microscopy but neither immunosecreting cells nor immune complex deposits were found. These results point to the existence of a non-autoimmune form of goitrous hyperthyroidism, different from Graves' disease.

TSH receptor mutation V509A causes familial hyperthyroidism by release of interhelical constraints between transmembrane helices TMH3 and TMH5

“…In contrast, in our kindred basal cAMP accumulation in the V509A TSH-R was only increased by 2·8-fold, similar to earlier studies using different in vitro cell systems (Duprez et al 1994, Kosugi et al 2000, Fuhrer et al 2003. Likewise, thyroid nodules and goitre develop earlier in patients carrying TSH-R variants with high constitutive receptor activation (Kopp et al 1995, de Roux et al 1996a, Fuhrer et al 1997, Holzapfel et al 1997, Tonacchera et al 2000 compared with V509A TSH-R, as described in this and previous reports (Thomas et al 1982, Leclere et al 1997.…”

“…This mutation was the first activating genomic TSH-R variant ever described (Thomas et al 1982, Duprez et al 1994. In comparison with the initial French family, thyrotoxicosis in our index patient developed much earlier and represents the youngest symptomatic patient carrying the V509A TSH-R variant reported so far.…”

“…Activating somatic mutations of the TSH-R have been found in thyroid neoplasia (Spambalg et al 1996, Russo et al 1997, 1999, Mircescu et al 2000 but until now thyroid carcinoma has not been reported in individuals carrying a genomic activating TSH-R mutation. The low prevalence for thyroid cancer in affected individuals with activating germline TSH-R mutations may be partially explained by early thyroidectomy due to thyrotoxicosis (Thomas et al 1982, Leclere et al 1997. In addition, malignant transformation may require additional (i.e.…”

Identification and functional characterization of a novel thyrotropin receptor mutation (V87L) in a Chinese woman with subclinical hypothyroidism

“…FNAH is also termed hereditary toxic thyroid hyperplasia or autosomal dominant autoimmune hyperthyroidism. It is hereditary through a dominant activating mutation of the TSHR affecting all thyroid cells (18). SCNAH is a result of germline neomutations affecting all thyroid cells (19).…”

Activating mutations of the thyrotropin receptor: a short review with emphasis on some pediatric aspects

“…Familial congenital non-autoimmune hyperthyroidism with thyroid hyperplasia (autosomal dominant toxic thyroid hyperplasia (ADTTH)) due to germline mutations of the TSH receptor gene have been reported (4,(21)(22)(23)(24). The characteristics of the cases of ADTTH described up to 1997 have been reviewed by Leclère (24).…”