Abstract
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-center 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 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.
Highlights
Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a B lymphocyte differentiation defect and an impaired production of antigen-specific antibodies resulting in increased risk of infections [1]
Monogenetic defects responsible for common variable immunodeficiency (CVID) have been described in 2–10% of patients, while the genetic defects for IgGSD/specific anti-polysaccharide antibody deficiency (SPAD) remain unknown to date [3, 4]
A total of 67 patients were included in our study and are categorized according to the type of PAD; 43 patients with CVID, 16 patients with IgGSD and 8 patients with SPAD
Summary
Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a B lymphocyte differentiation defect and an impaired production of antigen-specific antibodies resulting in increased risk of infections [1]. PADs represent a heterogeneous spectrum of conditions, including common variable immunodeficiency (CVID), immunoglobulin G (IgG) subclass deficiency (IgGSD) and specific anti-polysaccharide antibody deficiency (SPAD). IgGSD is defined by a reduction in one or more IgG subclasses [1,2,3,4], that may result in infectious diseases as well because of poor antibody responses [2, 3]. Primary antibody deficiencies (PADs) and anterior pituitary dysfunction are both rare conditions. Recent studies have remarkably reported the occurrence of anterior pituitary dysfunction in PAD patients
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