A Rare Case of Autoimmune Polyglandular Syndrome Type 2 in a Child With Persistent Fatigue

Smith, Ryan Kenneth; Gerrits, Peter M.

Adrenal insufficiency is decreased or deficient production of glucocorticoids and/or mineralocorticoids that has potential to be life-threatening. 1,2 First described by Thomas Addison in 1855, this disease can present insidiously with weakness, fatigue, weight loss, abdominal pain, nausea, vomiting, hypotension, salt cravings, depression, anxiety, as well as mucosal and epithelial hyperpigmentation. 1, 2 Adrenal insufficiency is related to dysfunction of the hypothalamic-pituitary-adrenal axis. 1, 2 Primary disease refers to pathology of the adrenal cortex; secondary refers to inadequate or deficient release of adrenocorticotropic hormone (ACTH) or inappropriate response to this hormone by the adrenal gland; and tertiary refers to disordered hypothalamic production of corticotropin releasing hormone. 1 Primary adrenal disease occurs more commonly in women, frequently presenting between 30 and 50 years of life. Tuberculosis was formerly the most common cause; however, autoimmune adrenal insufficiency is now responsible for close to 90% of cases of primary adrenal insufficiency. [1] [2] [3] Infectious diseases, neoplasia, adrenalectomy, and genetic causes account for other etiologies. 2 Among pediatric patients, most cases are related to genetic causes, while only a small fraction are related to autoimmune disease. 1,2 Secondary insufficiency is more common than primary in all age groups and often develops around 60 years of age. 1 Tertiary insufficiency is most often caused by suppression of the hypothalamicpituitary-adrenal axis by long-term steroid use. 1 Approximately 80% to 90% of cases of primary adrenal insufficiency have autoimmune etiology, with approximately 60% of those being related to an APS. 1, 4 APSs refer to various clusters or combinations of autoimmune disorders that are rare and consist of 2 or more concomitant autoimmune-mediated diseases. 5 To make a diagnosis of an APS, an autoimmune basis for each component of the syndrome must be confirmed. 3 845074G PHXXX10.1177/2333794X19845074Global Pediatric HealthSmith and Gerrits case-report2019 1 Beaumont Hospital, Troy, MI, USA 2 Beaumont Children's Hospital, Royal Oak, MI, USA APS type 1, or autoimmune polyglandular, candidiasis, ectodermal dystrophy (APECED), is an autosomal recessive disorder related to mutations in the autoimmune regulator (AIRE) gene. Often seen in groups of people indigenous to Finland and Sardinia, APS type 1 is notable by adrenocortical insufficiency, hypoparathyroidism, candidiasis, dental enamel hypoplasia, and nail dystrophy. 1, 6 Diabetes, pernicious anemia, hypothyroidism, and hypogonadism are examples of other autoimmune disorders that may be associated with APS type 1. 1,7 APS type 1 generally manifests in infancy, between ages 3 and 5 years, or in early adolescence; as such, APS type 1 is also known as juvenile autoimmune poly-endocrinopathy. 5 APS type 1 is considered very rare, with an incidence of less than 1:100 000/year. 5 APS type 2, also known as Schmidt's or Carpenter's syndrome, is a cluster of autoimmune diseases characterized by autoimmune adrenal insufficiency and thyroid disease with or without type 1 diabetes. 1, [5] [6] [7] Autoimmune diseases that may be associated include hypogonadism, hypopituitarism, immunoglobulin A deficiency, myasthenia gravis, celiac disease, and vitiligo. 1,5-7 APS type 2 is more prevalent than APS type 1, often associated with multiple autoimmune conditions, and is more common in women than men. 1,3