The nature of human chorionic gonadotrophin glycoforms in gestational thyrotoxicosis.
Talbot JA., Lambert A., Anobile CJ., McLoughlin JD., Price A., Weetman AP., Robertson WR.
OBJECTIVE: We examined the charge heterogeneity and carbohydrate complexity of hCG in healthy pregnant Asian subjects and Asian women with gestational thyrotoxicosis to assess whether particular glycoforms of hCG are associated with the thyrotoxicosis of pregnancy. DESIGN: Blood was taken at 8-16 weeks of gestation from five pregnant Asian women with clinical symptoms of gestational thyrotoxicosis and biochemical indicators of hyperthyroidism and from six age-matched healthy pregnant women. hCG charge heterogeneity and carbohydrate complexity were assessed by fast protein liquid chromatography chromatofocusing and concanavalin A affinity chromatography, respectively. The degree of terminal sialylation of the different glycoforms was measured by ricin affinity chromatography, which detects exposed galactose residues following desialylation. RESULTS: Free T3, free T4 and hCG levels were elevated and TSH suppressed in the thyrotoxic subjects compared to controls (P < 0.007). Overall, the glycoform distribution of the hCG in the blood from the control and thyrotoxic groups was similar, with a median pI of 4.34 (median and range: 3.78-4.68) and pI 4.23 (3.98-4.38). Free T4 (P < 0.028) and free T3 (P < 0.03) levels were positively correlated to both the absolute hCG concentration and the percentage of hCG forms between pI 3.36-4.0. The distribution of simple (73-88.6%), intermediate (9.7-26.4%) and complex (0.1-7.3%) branching oligosaccharide forms was similar in both groups, as was the percent hCG which bound to ricin (< 3.2%). CONCLUSION: We conclude that excessive thyroid stimulation in the thyrotoxic patients is associated both with the absolute concentration of hCG and the relative proportion of acidic glycoforms between pI 3.36 and 4.0.