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.
Ogura
T
T
Health and Medical Center, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Mimura
Y
Y
Otsuka
F
F
Kishida
M
M
Yokota
K
K
Suzuki
J
J
Nagai
A
A
Hirakawa
S
S
Makino
H
H
Tobe
K
K
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