The Thyrotropin in Hydatidiform Moles is Human Chorionic Gonadotropin1

Abstract

Thyrotropic activity (TSH), measured by the McKenzie mouse bioassay, has been correlated with human chorionic gonadotropin (hCG) activity, measured by radioimmunoassay, in serum and tissue samples from 11 patients with hydatidiform mole and in partially and highly purified preparations of urinary hCG. Serum samples, taken at various times before and after removal of the moles, gave a ratio of 0.42 plus or minus 0.24 muU TSH/U hCG (mean plus or minus SD) (N)=43). In all cases where hCG activity fell below 150-175 U/ml (n=49), thyroid stimulating activity was undetectable (smaller than 40 muU/ml). We extracted lyophylized molar tissue by a modification of the Bates alcohol-saline method and purified the resultant extract by a combination of gel chromatography, affinity chromatography using Concanavalin A coupled to Sepharose, and isoelectrofocusing. Following extraction, an approximately 20-fold purification was achieved without significant alteration of the ratio of the two activities. Using results from all phases of purification the ratio of muU TSH/U hCG was 0.51 plus or minus 0.35(n = 23). Both activities were in the same position on disc gel electrophoresis. Activity ratios were less constant when partially purified preparations of urinary hCG were assayed for both thyrotropic and hCG activities. The presence of an hCG immunoreactive species, presumably hCG-beta subunit, which contains no thyrotropic activity but has an approximately 10-fold greater activity on a weight basis than intact hCG, may be a partial explanation for this observation. Isoelectrofocusing of a urinary hCG preparation showed that all hCG immunoreactive species with pl's between 3. 5 and 5.0 contained thyrotropic activity in proportion to their hCG content. Seven highly purified hCG preparations had thyrotropic activity with a ratio of 0.48 plus or minus 0.18 muU TSH/U hCG. These results indicate that hCG has intrinsic thyrotropic activity. On a molecular basis it is calculated that hCG contains approximately 1/4000 the thyrotropic activity of human pituitary TSH. In conditions of grossly elevated serum hCG levels, such as hydatidiform mole, this thyrotropic activity can be sufficient to produce hyperthyroidism.

Maternal thyroid function in multifetal pregnancies before and after fetal reduction

“…These data would explain why overt hyperthyroidism is seen only in some women and then only in the first trimester, when hCG concentrations are greatest, and the occurrence of clinical and biochemical hyperthyroidism in women with hCG-producing tumours such as hydatidiform mole and choriocarcinoma (Miyai et al 1976). Indeed, the spectrum of increasing thyroid activity correlates with the severity of disease and the concentration of hCG, suggesting a causal relationship (Kenimer et al 1975). At the cellular level, hCG is believed to increase intracellular release of cAMP in the thyroid, which leads to a degranulation response, and the secretion of thyroxine.…”

Should human chorionic gonadotropine treatment increase thyroid volume?

“…The thyroid-stimulating activity of a commercial preparation of hCG was first demonstrated by Burger in a mouse bioassay (7). Subsequently, thyrotrophic activity has been found in several hCG preparations (4,5). These studies showed that hCG is the molar TSH and that 1 Unite hCG has intrinsic thyrotrophic activity equivalent to approximately 0.5 µU TSH in the Mouse bioassay (4).…”

“…The beta subunit of hCG is unique to hCG but alpha-subunit is identical to that luteinizing hormone (LH), follicle stimulating hormone (FSH) and TSH (3). Human chorionic gonadotropin has thyroid-stimulating activity in bioassays in mice, rats, chicks and men (4)(5)(6). The thyroid-stimulating activity of a commercial preparation of hCG was first demonstrated by Burger in a mouse bioassay (7).…”

Uncommon Causes of Thyrotoxicosis

“…hCG is synthesized primarily by syncytiotrophoblastic tissue, maintaining the corpus luteum and progesterone production in pregnancy (36,37). Receptors for the structurally similar glycoprotein hormones share significant homology in their extracellular binding domains, and hCG has confirmed thyroid-stimulating activity when present at high concentrations in serum because of a direct interaction of hCG with the TSH receptor (37)(38)(39)(40)(41)(42).…”