Original Research ARTICLE
Endocrine disorders are prominent clinical features in patients with primary antibody deficiencies
- 1Department of Internal Medicine, Erasmus Medical Center, Erasmus University Rotterdam, Netherlands
- 2Erasmus Medical Center, Netherlands
- 3Department of Internal Medicine, Erasmus Medical Center, Netherlands
- 4Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand
- 5Department of Clinical Genetics, Erasmus University Medical Center, Netherlands
- 6Department of Immunology, Erasmus Medical Center, Netherlands
- 7Department of Pathology, Erasmus University Medical Centre, Netherlands
Background: Primary antibody deficiencies (PADs) and anterior pituitary dysfunction are both rare conditions. However, recent studies have remarkably reported the occurrence of anterior pituitary dysfunction in PAD patients.
Methods: In this cross-sectional, single-centre study we evaluated the prevalence of endocrine disorders in adult PAD patients. Our study focused on common variable immunodeficiency (CVID), immunoglobulin G (IgG) subclass deficiency (IgGSD) and specific anti-polysaccharide antibody deficiency (SPAD). We assessed hormone levels, performed provocative tests and genetic testing in a subset of patients by direct sequencing of the nuclear factor kappa beta subunit 2 (NFKB2) gene and primary immunodeficiency (PID) gene panel testing by whole exome sequencing (WES).
Results: Our results demonstrated that one out of 24 IgGSD/SPAD patients had secondary hypothyroidism and three out of 9 men with IgGSD/SPAD had secondary hypogonadism. Premature ovarian failure was observed in four out of 9 women with CVID, possible polycystic ovary syndrome (PCOS) in one out of 5 women with IgGSD/SPAD and primary testicular failure in one out of 15 men with CVID. In two out of 26 CVID patients we found partial adrenal insufficiency (AI) and in one out of 18 patients with IgGSD/SPAD secondary AI was found. Moreover, in one out of 23 patients with CVID and in two out of 17 patients with IgGSD/SPAD severe growth hormone deficiency (GHD) was found, while one patient with IgGSD/SPAD showed mild GHD. Combined endocrine disorders were detected in two women with CVID (either partial secondary AI or autoimmune thyroiditis with primary hypogonadism) and in three men with IgGSD/SPAD (two with either mild GHD or secondary hypothyroidism combined with secondary hypogonadism, and one man with secondary AI and severe GHD). Genetic testing in a subset of patients did not reveal pathogenic variants in NFKB2 or other known PID-associated genes.
Conclusion: This is the first study to describe a high prevalence of both anterior pituitary and end-organ endocrine dysfunction in adult PAD patients. As these endocrine disorders may cause considerable health burden, assessment of endocrine axes should be considered in PAD patients.
Keywords: Common variable immunodeficiency (CVID), Endocrine disorders, Immunodeficiency - primary, Endocrine dysfunction, Hormones
Received: 13 May 2019;
Accepted: 16 Aug 2019.
Copyright: © 2019 Coopmans, Chunharojrith, Neggers, van der Ent, Swagemakers, Hollink, Barendregt, van der Spek, Van der Lely, van Hagen and Dalm. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: MD, PhD. Virgil A. Dalm, Erasmus Medical Center, Rotterdam, Netherlands, email@example.com