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Hypothyroidism associated with anti-human chorionic gonadotropin antibodies secondarily produced by gonadotropin therapy in a case of idiopathic hypothalamic hypogonadism

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Abstract

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 μU/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 γ-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.

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Authors and Affiliations

  1. Health and Medical Center, Okayama University, Japan

    T. Ogura & K. Tobe

  2. Faculty of Education, Okayama University, Japan

    Y. Mimura

  3. Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, 700-8558, Japan

    Fumio Otsuka MD, PhD, M. Kishida, K. Yokota, J. Suzuki & H. Makino

  4. Department of Urology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan

    A. Nagai

  5. Hirakawa Clinic, Souja, Japan

    S. Hirakawa

Authors
  1. T. Ogura
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  2. Y. Mimura
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  3. Fumio Otsuka MD, PhD
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  4. M. Kishida
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  5. K. Yokota
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  6. J. Suzuki
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  7. A. Nagai
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  8. S. Hirakawa
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  9. H. Makino
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  10. K. Tobe
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Corresponding author

Correspondence to Fumio Otsuka MD, PhD.

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Ogura, T., Mimura, Y., Otsuka, F. et al. Hypothyroidism associated with anti-human chorionic gonadotropin antibodies secondarily produced by gonadotropin therapy in a case of idiopathic hypothalamic hypogonadism. J Endocrinol Invest 26, 1128–1135 (2003). https://doi.org/10.1007/BF03345263

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  • DOI: https://doi.org/10.1007/BF03345263

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