Thyroid function in gestational trophoblastic neoplasia: Evidence that the thyrotropic activity of chorionic gonadotropin mediates the thyrotoxicosis of choriocarcinoma

Nisula, Bruce C.; Taliadouros, George S.

doi:10.1016/0002-9378(80)90014-9

Cited by 67 publications

(14 citation statements)

References 15 publications

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“…In patients with trophoblastic tumours, where there are very high levels of circulating hCG, thyrotoxicosis is well recognized to occur [1,2]. Even in the absence of frank hyperthyroid ism, changes in thyroid function tests have been noted in these patients [3,4], The thyroid-stimulatory activity released from these tumours is identical to that of hCG [5].…”

Section: Introductionmentioning

confidence: 60%

Thyroid-Stimulatory Effects of Human Chorionic Gonadotrophin in Early Pregnancy

Kennedy

Darne²,

Griffiths³

et al. 1990

Horm Res

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Human chorionic gonadotrophin (hCG) shares structural similarity with pituitary thyrotrophin (TSH) and may act as a thyroid stimulator. We have studied serum hCG levels, thyroid function tests and the ability of serum to stimulate cultured thyroid cells in 40 subjects between 6 and 12 weeks of pregnancy. Serum free tri-iodothyronine was increased and serum TSH reduced in pregnancy samples (both p < 0.05). hCG was detectable in all pregnancy sera with a mean level of 105.6 × 10³ U/l. Serum from 24 of the 40 (60%) patients stimulated iodide uptake into cultured FRTL-5 thyroid cells. The potency of sera in stimulating cells correlated with the hCG level (r = 0.710, p < 0.01). The stimulatory activity in some, but not all, sera could be specifically neutralized with antiserum to hCG. Partially purified hCG stimulated iodide uptake and growth of thyroid cells at concentrations of 50 × 10³ U/l and above. In these experiments, 25 × 10³ U/l of hCG produced equivalent stimulation to 1 mU/1 of TSH. In 8 patients tested before and after termination of pregnancy, the thyroid-cell-stimulatory activity of serum declined rapidly in parallel with serum hCG. hCG may stimulate the thyroid gland at concentrations which prevail in normal pregnancy. Its potential as a physiological regulator of the thyroid gland is not widely appreciated and requires further study.

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Section: Introductionmentioning

confidence: 60%

Thyroid-Stimulatory Effects of Human Chorionic Gonadotrophin in Early Pregnancy

Kennedy

Darne²,

Griffiths³

et al. 1990

Horm Res

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“…This 'hyperthyroidism with suppressed TSH' is known with patients suffering Graves' disease, hyperemesis gravidarum, and trophoblastic diseases. The pathogenic agents causing these diseases have been identified: thyroid-stimulating antibodies in Graves' disease, excess levels of human chorionic gonadotropin (hCG) and in hyperemesis gravidarum (Lao et al 1988, Rodien et al 1998 and in trophoblastic diseases (Nisula & -Ketelslegers 1974, Nisula & Taliadouros 1980, Hoermann et al 1994. Recently, two cases of goitrous euthyroid patients presenting low TSH have been reported (Ikekubo et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Differential expression of the thyrostimulin subunits, glycoprotein 2 and 5 in the rat pituitary

Nagasaki

Wang

Jackson

et al. 2006

Journal of Molecular Endocrinology

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Two glycoprotein hormone subunits, (glycoprotein hormone a2-subunit GPA2) and (glycoprotein hormone b5-subunit GPB5) have been recently discovered which, when expressed in vitro, heterodimerize to form a new hormone called thyrostimulin. Thyrostimulin activates the thyroid-stimulating hormone receptor (TSHR) and has thyrotropic activity. Immunological studies have indicated that both subunits co-localize in pituitary cells. To explore the function of thyrostimulin in the rat, we have cloned rat GPA2 and GPB5, reconstituted the heterodimers in vitro, and confirmed that rat thyrostimulin activates TSHR with an affinity similar to that of TSH. In situ hybridization of the pituitary showed that while GPA2 is expressed in the anterior lobe, GPB5 is not detected in any of the lobes. A quantitative analysis showed that the co-localization of GPA2 and GPB5 is restricted in the rat to the eye and the testis. We found that GPB5 can be detected in the pituitary by quantitative-PCR, but at extremely low levels, 2000-fold lower than TSH b-subunit (GPBtsh). Furthermore, the levels of GPB5 remain constant during the estrus cycle, while those of GPA2 vary. Finally, we found that none of the thyrostimulin subunits was induced by TRH in pituitary cell culture. These data point at the thyrostimulin system as being functionally different to the TSH system.

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“…Human chorionic gonadotropin may result in hyperthyroidism through crossreaction with the TSH receptor (7,12). This form of hyperthyroidism may be associated with trophoblast neoplasms such as hydatiform moles, choriocarcinomas, embryonal cell carcinomas, teratocarcinomas and testicular carcinomas (7,9,10,(13)(14)(15)(16).…”

Section: Discussionmentioning

confidence: 99%

Hyperthyroidism due to secretion of human chorionic gonadotropin in a patient with metastatic choriocarcinoma

Meister

Hauck

Graf

et al. 2005

Arq Bras Endocrinol Metab

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A 26-year-old pregnant woman presenting with repeated episodes of vaginal bleeding, weight loss, and shortness of breath was diagnosed with choriocarcinoma with metastases to both lungs. Chorionic gonadotropin levels (hCG) were >2.5 x 10 6 mU/mL. Consistent with hCGinduced subclinical hyperthyroidism, she had a suppressed TSH of 0.037mU/L (0.49 -4.67), a T4 of 18.1µg/dL (4.9 -10.7), and T3 of 136ng/dL (45 -137). Chemotherapy with a combined regimen with etoposide, methotrexate, and dactinomycine was started. The initial course was complicated by urosepsis with respiratory distress requiring endotracheal intubation for 3 days. She then improved rapidly, and her thyroid function tests were within normal limits by day 12. Six months later, after ten cycles of chemotherapy, the patient was in remission without signs of residual tumor or hCG-induced paraneoplastic activity.

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Thyroid function in gestational trophoblastic neoplasia: Evidence that the thyrotropic activity of chorionic gonadotropin mediates the thyrotoxicosis of choriocarcinoma

Cited by 67 publications

References 15 publications

Thyroid-Stimulatory Effects of Human Chorionic Gonadotrophin in Early Pregnancy

Thyroid-Stimulatory Effects of Human Chorionic Gonadotrophin in Early Pregnancy

Differential expression of the thyrostimulin subunits, glycoprotein 2 and 5 in the rat pituitary

Hyperthyroidism due to secretion of human chorionic gonadotropin in a patient with metastatic choriocarcinoma

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