Abstract
Graves’ disease (GD) is an autoimmune thyroid disease in which stimulation by thyrotropin-receptor antibodies (TRAb) causes thyroid enlargement and hyperfunction. GD is an uncommon condition during gestation, as it occurs in about 0.2% of pregnant women. The typical GD course during gestation is characterized by a progressive reduction of TRAb levels, with associated clinical improvement, but subsequent recurrence after delivery. Instead, gestational GD requires close monitoring, because if inadequately controlled with maternal TRAb levels remaining elevated, it is associated with adverse maternal, fetal, and neonatal outcomes. We describe the case of a 39-year-old woman, who was diagnosed with stress-triggered GD at 1st trimester of her pregnancy. At diagnosis, TRAb levels were very high (30.4 U/L, normal values < 1.5). Five weeks after antithyroid drug (ATD) was started, hyperthyroidism returned, coinciding with an increase of TRAb levels (> 40 U/L). Three additional exacerbations of hyperthyroidism occurred at weeks 28 (TRAb > 40 U/L), 32 (TRAb 36.4 U/L), and 36 (TRAb 26.2 U/L), despite close biochemical monitoring and adjustments of ATD. An uncomplicated spontaneous delivery of a healthy boy occurred at week 37. The neonate had normal weight, length, Apgar score, and was euthyroid (TSH 1.9 mIU/mL). He remained healthy and euthyroid at the last evaluation (9 months of age). This case is unusual because of several exacerbations of GD hyperthyroidism while on ATD during gestation, due to persistently high TRAb levels. Nevertheless, thanks to close maternal and fetal monitoring, neither maternal nor fetal complication occurred.
Similar content being viewed by others
References
Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev. 2010;31:702–55.
Nguyen CT, Sasso EB, Barton L, Mestman JH. Graves’ hyperthyroidism in pregnancy: a clinical review. Clin Diabetes Endocrinol. 2018;4:4.
Cooper DS, Laurberg P. Hyperthyroidism in pregnancy. Lancet Diabetes Endocrinol. 2013;1:238–49.
Falgarone G, Heshmati HM, Cohen R, Reach G. Mechanisms in endocrinology. Role of emotional stress in the pathophysiology of Graves’ disease. Eur J Endocrinol. 2012;168:R13–8.
Vita R, Lapa D, Vita G, Trimarchi F, Benvenga S. A patient with stress-related onset and exacerbations of Graves disease. Nat Clin Pract Endocrinol Metab. 2009;5:55–61.
Vita R, Lapa D, Trimarchi F, Benvenga S. Stress triggers the onset and the recurrences of hyperthyroidism in patients with Graves’ disease. Endocrine. 2015;48:254–63.
Vita R, Lapa D, Trimarchi F, Vita G, Fallahi P, Antonelli A, et al. Certain HLA alleles are associated with stress-triggered Graves’ disease and influence its course. Endocrine. 2017;55:93–100.
Weetman AP. Immunity, thyroid function and pregnancy: molecular mechanisms. Nat Rev Endocrinol. 2010;6:311–8.
Patil-Sisodia K, Mestman JH. Graves hyperthyroidism and pregnancy: a clinical update. Endocr Pract. 2010;16:118–29.
Delitala AP, Capobianco G, Cherchi PL, Dessole S, Delitala G. Thyroid function and thyroid disorders during pregnancy: a review and care pathway. Arch Gynecol Obstet. 2019;299:327–38.
Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. 2017 guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017;27:315–89.
Vita R, Mazzi V, Antonelli A, Benvenga S. Antithyroid medications and psychosis. Expert Opin Drug Saf. 2013;12:865–72.
Andersen SL, Olsen J, Carle A, Laurberg P. Hyperthyroidism incidence fluctuates widely in and around pregnancy and is at variance with some other autoimmune diseases: a Danish population-based study. J Clin Endocrinol Metab. 2015;100:1164–71.
Moleti M, Di Mauro M, Sturniolo G, Russo M, Vermiglio F. Hyperthyroidism in the pregnant woman: maternal and fetal aspects. J Clin Transl Endocrinol. 2019;16:100190.
Croce L, Di Dalmazi G, Orsolini F, Virili C, Brigante G, Gianetti E, et al. Graves’ disease and the post-partum period: an intriguing relationship. Front Endocrinol (Lausanne). 2019;10:853.
Rotondi M, Capelli V, Coperchini F, Pinto S, Croce L, Tonacchera M, et al. Post-partum and non-post-partum relapsing Graves’ hyperthyroidism display different response to anti-thyroid drugs. Eur J Endocrinol. 2018;178:589–94.
Fukao A, Takamatsu J, Murakami Y, Sakane S, Miyauchi A, Kuma K, et al. The relationship of psychological factors to the prognosis of hyperthyroidism in antithyroid drug-treated patients with Graves’ disease. Clin Endocrinol. 2003;58:550–5.
Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26(10):1343–421.
Huel C, Guibourdenche J, Vuillard E, Ouahba J, Piketty M, Oury JF, et al. Use of ultrasound to distinguish between fetal hyperthyroidism and hypothyroidism on discovery of a goiter. Ultrasound Obstet Gynecol. 2009;33:412–20.
Laurberg P, Nygaard B, Glinoer D, Grussendorf M, Orgiazzi J. Guidelines for TSH-receptor antibody measurements in pregnancy: results of an evidence-based symposium organized by the European Thyroid Association. Eur J Endocrinol. 1998;139:584–6.
Bucci I, Giuliani C, Napolitano G. Thyroid-stimulating hormone receptor antibodies in pregnancy: clinical relevance. Front Endocrinol (Lausanne). 2017;8:137.
McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid. 2013;23:14–24.
Zakarija M, McKenzie JM, Munro DS. Immunoglobulin G inhibitor of thyroid-stimulating antibody is a cause of delay in the onset of neonatal Graves’ disease. J Clin Invest. 1983;72:1352–6.
Vita R, Di Bari F, Perelli S, Capodicasa G, Benvenga S. Thyroid vascularization is an important ultrasonographic parameter in untreated Graves’ disease patients. J Clin Translational Endocrinol. 2019;15:65–9.
Pearce EN. Management of thyrotoxicosis: preconception, pregnancy, and the postpartum period. Endocr Pract. 2019;25:62–8.
Oltmann SC, Brekke AV, Schneider DF, Schaefer SC, Chen H, Sippel RS. Preventing postoperative hypocalcemia in patients with Graves disease: a prospective study. Ann Surg Oncol. 2015;22:952–8.
Laurberg P, Wallin G, Tallstedt L, Abraham-Nordling M, Lundell G, Torring O. TSH-receptor autoimmunity in Graves’ disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. Eur J Endocrinol. 2008;158:69–75.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Ethical Approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed Consent
Written informed consent was obtained from the patient for publication of this case report.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Medicine
Rights and permissions
About this article
Cite this article
Di Bari, F., Perelli, S., Scilipoti, A. et al. Stress-Triggered Graves’ Disease with Multiple Exacerbations in a Pregnant Woman with High Levels of Thyrotropin Receptor Antibodies and No Complicated Delivery: a Case Report. SN Compr. Clin. Med. 2, 355–360 (2020). https://doi.org/10.1007/s42399-020-00247-7
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s42399-020-00247-7