THYROID FUNCTION IN CHORIOCARCINOMA: DEMONSTRATION OF A THYROID STIMULATING ACTIVITY IN SERUM USING FRTL‐5 and HUMAN THYROID CELLS

Hyperthyroidism is a well recognized complication of gestational trophoblastic tumours (GTT) and may be due to high circulating concentrations of human chorionic gonadotrophin (hCG) or its variants. We have studied 24 clinically euthyroid women with GTT. Eight were biochemically hyperthyroid with low or undetectable serum thyrotrophin (TSH) and had a mean serum hCG of 3612 |MX 103 IU/1 compared to 76.2 |MX 103 IU/1 in the other patients (P < 0.01). Purified hCG stimulated iodide uptake into FRTL‐5 cells with 25 |MX 103 IU/1 being equivalent in potency to 1 mU/1 of thyrotrophin (TSH). Sixteen out of the 24 sera (67%) stimulated iodide uptake when applied to the cells at a 1:10 dilution. Sera from all eight hyperthyroid patients contained thyroid stimulating activity. The mean hCG concentration in the 16 stimulatory sera was 238.2 |MX 103 IU/1 compared to 37.1 |MX 103 IU/1 in the other eight sera (P < 0.01). Six men with hCG‐secreting testicular tumours were biochemically euthyroid although three of their sera stimulated iodide uptake into FRTL‐5 cells. In human thyroid cells the mean cAMP production over 4 h with sera from five healthy controls was 54.2 |Mp 1.81 pmol/mg cell protein compared to 67.0 |Mp 3.8 pmol/mg protein with sera from five choriocarcinoma patients (P < 0.02). Serum from patients with gestational trophoblastic tumours contains a thyroid stimulating activity which may be hCG and whose presence correlates with hyperthyroidism.

[1]  H. Griffiths,et al.  Thyroid-stimulatory effects of human chorionic gonadotrophin in early pregnancy. In vivo and in vitro studies. , 1990, Hormone research.

[2]  H. Hatabu,et al.  STIMULATION OF CYCLIC AMP PRODUCTION IN FRTL‐5 THYROID CELLS BY CRUDE IMMUNOGLOBULIN FRACTIONS OF SERUM FROM PREGNANT WOMEN , 1989, Clinical endocrinology.

[3]  J. E. Midgley,et al.  Low-normal concentrations of free thyroxin in serum in late pregnancy: physiological fact, not technical artefact. , 1989, Clinical chemistry.

[4]  B. Morris,et al.  A longitudinal study of thyroid function in pregnancy. , 1989, Clinical chemistry.

[5]  R. Desai,et al.  SPECTRUM OF THYROID FUNCTION ABNORMALITIES IN GESTATIONAL TROPHOBLASTIC NEOPLASIA , 1988, Clinical endocrinology.

[6]  W. Robertson,et al.  Thyroid cell growth, differentiation and function in the FRTL-5 cell line: a survey. , 1988, The Journal of endocrinology.

[7]  R. Hoermann,et al.  Evidence that partially desialylated variants of human chorionic gonadotropin (hCG) are the factors in crude hCG that inhibit the response to thyrotropin in human thyroid membranes. , 1988, Endocrinology.

[8]  L. Chailurkit,et al.  Trophoblastic hyperthyroidism: clinical and biochemical features of five cases. , 1988, The American journal of medicine.

[9]  M. Sugawara,et al.  Human chorionic gonadotropin stimulates iodide uptake, adenylate cyclase, and deoxyribonucleic acid synthesis in cultured rat thyroid cells. , 1988, The Journal of clinical endocrinology and metabolism.

[10]  D. Hay Histological origins of discordant chorionic gonadotropin secretion in malignancy. , 1988, The Journal of clinical endocrinology and metabolism.

[11]  M. Sugawara,et al.  Human chorionic gonadotropin stimulates iodide uptake, adenylate cyclase, and deoxyribonucleic acid synthesis in cultured rat thyroid cells. , 1988, The Journal of clinical endocrinology and metabolism.

[12]  R. Ekins,et al.  Thyrotropic activity of crude hCG in FRTL-5 rat thyroid cells. , 1987, Acta endocrinologica.

[13]  T. Li,et al.  Thyroid function in trophoblastic disease , 1987, British journal of obstetrics and gynaecology.

[14]  T. Chard,et al.  Relationship Between Blood and Urine Concentrations of Intact Human Chorionic Gonadotropin and its Free Subunits in Early Pregnancy , 1987, Obstetrics and gynecology.

[15]  T. Davies,et al.  hCG-induced TSH receptor activation and growth acceleration in FRTL-5 thyroid cells. , 1986, Endocrinology.

[16]  R. Hoermann,et al.  Thyrotropic activity of acidic isoelectric variants of human chorionic gonadotropin from trophoblastic tumors. , 1986, Endocrinology.

[17]  T. Chard,et al.  DOUBTS ABOUT HUMAN CHORIONIC GONADOTROPIN AS A THYROID STIMULATOR , 1985, The Lancet.

[18]  R. Osathanondh,et al.  Divergent responses by human and mouse thyroids to human chorionic gonadotropin in vitro , 1985, Molecular and Cellular Endocrinology.

[19]  R. Osathanondh,et al.  Human chorionic gonadotropin and thyroid function in patients with hydatidiform mole. , 1985, American journal of obstetrics and gynecology.

[20]  K. Ashwell,et al.  SERUM FREE THYROXINE CONCENTRATION AND FREE THYROID HORMONE INDICES IN NORMAL PREGNANCY , 1983, Clinical endocrinology.

[21]  W. P. Soutter,et al.  HYPERTHYROIDISM IN GESTATIONAL TROPHOBLASTIC NEOPLASIA , 1981, Clinical endocrinology.

[22]  R. Norman,et al.  THE MANAGEMENT OF CHORIOCARCINOMA CAUSING SEVERE THYROTOXICOSIS , 1981, British journal of obstetrics and gynaecology.

[23]  矢崎 克己 Isoelectric heterogeneity of human chorionic gonadotropin : presence of choriocarcinoma specific components , 1981 .

[24]  K. Wakabayashi,et al.  Isoelectric heterogenity of human chorionic gonadotropin: Presence of choriocarcinoma specific components. , 1980, American journal of obstetrics and gynecology.

[25]  B. Nisula,et al.  Thyroid function in gestational trophoblastic neoplasia: evidence that the thyrotropic activity of chorionic gonadotropin mediates the thyrotoxicosis of choriocarcinoma. , 1980, American journal of obstetrics and gynecology.

[26]  J. Hershman,et al.  The thyrotoxicosis of hydatidiform mole. , 1975, Annals of internal medicine.

[27]  M. Mochizuki,et al.  Human chorionic TSH (hCTSH, hCT) during normal or molar pregnancy. , 1973, Endocrinologia japonica.

[28]  J. Hershman,et al.  Thyrotoxicosis from molar thyrotropin. , 1973, Archives of internal medicine.

[29]  J. Hershman,et al.  ALTERATIONS IN THYROID HORMONE ECONOMY IN PATIENTS WITH HYDATIDIFORM MOLE , 1971, Journal of Clinical Investigation.

[30]  J. Hershman,et al.  Hydatidiform mole--a cause of clinical hyperthyroidism. Report of two cases with evidence that the molar tissue secreted a thyroid stimulator. , 1971, The New England journal of medicine.

[31]  J. Cohen,et al.  Metastatic choriocarcinoma associated with hyperthyroidism. , 1970, The Journal of clinical endocrinology and metabolism.

[32]  P. Carbone,et al.  METASTATIC EMBRYONAL CARCINOMA OF THE TESTIS ASSOCIATED WITH ELEVATED PLASMA TSH-LIKE ACTIVITY AND HYPERTHYROIDISM. , 1964, The New England journal of medicine.

[33]  R. Rivlin,et al.  Increased thyroid function without clinical hyperthyroidism in patients with choriocarcinoma. , 1963, The Journal of clinical endocrinology and metabolism.