June 14th, 2021

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Truncated Human Chorionic Gonadotropin Variant in Hyperemesis Gravidarum: Possible Links to Hyperthyroidism and Emesis as a Thyroid-Stimulating Hormone Analogue
Authors:  Stephen A. Butler, Ph.D., Jameel Luttoo, Ph.D., Thomas K. Abban, M.D., Ph.D., Zeenath B. Musthan-Timol, B.Sc., Paola T. A. Borrelli, M.D., Laurence A. Cole, Ph.D., and Ray K. Iles, Ph.D.
  OBJECTIVE: Hyperemesis gravidarum is a condition of extreme and persistent vomiting experienced by women during pregnancy; the condition has been associated with levels of hCG, but no absolute correlation has ever been established. Structural variation in hCG is well described, and peptide or oligo-saccharide structural variation may be one explanation for hyperemesis.

STUDY DESIGN: Neat and purified urine samples from early pregnancy were subjected to matrix-assisted laser desorption ionisation mass spectrometry in order to determine structural change. The spectra generated from hyperemesis samples were compared with samples from normal pregnancies and controls.

RESULTS: The hyperemesis samples produced mass spectral peaks for hCG with lower mass/charge values than those of normal pregnancy. Following tryptic digest and further mass spectral analysis, it was observed that the beta subunit of hCG from the hyperemesis samples had a portion of the carboxy-terminal peptide and associated oligosaccharides missing—a truncated human chorionic gonadotropin.

CONCLUSION: Truncated carboxyl-terminal peptide hCG from hyperemesis pregnancies is structurally homologous to thyroid-stimulating hormone. This homology may result in emetic symptoms due to aberrant thyroid signalling, as proposed by others. This particular variant of hCG can be easily and discriminately detected using mass spectrometry from a spot urine for clinical assessment.
Keywords:  gestational trophoblastic disease, hCG, hyperemesis gravidarum, morning sickness, nausea, nausea/vomiting prenatal/antenatal testing, pernicious vomiting of pregnancy, thyroid-stimulating hormone, TSH (thyroid stimulating hormone), vomiting
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