Hypothyroidism associated with anti-human chorionic gonadotropin antibodies secondarily produced by gonadotropin therapy in a case of idiopathic hypothalamic hypogonadism.
We report a 22-yr-old male patient with idiopathic hypothalamic hypogonadism who showed secondary resistance to gonadotropin (Gn) therapy over 3 yr after successful treatment with hCG combined with human menopausal Gn. The patient simultaneously developed subclinical hypothyroidism. Endocrine examination revealed low levels of testosterone (0.3 ng/ml), free T4 (0.91 ng/dl), and increased levels of TSH (31.1 microU/ml) in the serum. Serum autoantibodies to thyroid gland were all negative. Interestingly, thyroid function was improved after discontinuation of Gn therapy. In vitro assays by immunoprecipitation using 125I-hCG or 125I-TSH elucidated the presence of anti-hCG antibody in the serum 13 months after commencement of Gn therapy but anti-TSH antibody was not detected in the serum. Furthermore, the anti-hCG antibody specifically bound to hCG but not to other glycoproteins including TSH and FSH based on a competitive displacement assay. Bioassays using porcine thyroid cells revealed that the serum gamma-globulin fraction enables the suppression of cyclic AMP (cAMP) synthesis stimulated by TSH. Our findings suggest that anti-hCG and/or anti-idiotypic hCG antibodies induced by hCG therapy impaired TSH-dependent cAMP production through interfering with binding of TSH to its receptor, and this resulted in subclinical hypothyroidism in this patient.
Health and Medical Center, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
T
T
Ogura
Y
Y
Mimura
F
F
Otsuka
M
M
Kishida
K
K
Yokota
J
J
Suzuki
A
A
Nagai
S
S
Hirakawa
H
H
Makino
K
K
Tobe
D000328:Adult; D000906:Antibodies / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D006063:Chorionic Gonadotropin / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D007006:Hypogonadism / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D007037:Hypothyroidism / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D008297:Male; D011233:Precipitin Tests; D011388:Prolactin; D013972:Thyrotropin / Q000097:blood
D000906:Antibodies; D001323:Autoantibodies; D006063:Chorionic Gonadotropin; D011388:Prolactin; D013972:Thyrotropin; D000242:Cyclic AMP