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Autoimmune polyendocrine syndrome type 3 — Clinical Guidelines

Overview

Autoimmune polyendocrine syndrome type 3 (APS type 3) encompasses a heterogeneous group of autoimmune disorders primarily affecting multiple endocrine glands, often including adrenal insufficiency, hypothyroidism, and other autoimmune manifestations like diabetes insipidus and hypoparathyroidism. 3 4

Diagnosis

Clinical Presentation: Presence of at least two endocrine gland deficiencies, typically adrenal insufficiency and hypothyroidism. 2

Laboratory Tests:

- Adrenal insufficiency: Low cortisol and ACTH stimulation test. - Hypothyroidism: Elevated TSH, low free T4. - Additional tests based on suspected gland involvement (e.g., insulin-like growth factor for hypoparathyroidism, anti-parietal cell antibodies for pernicious anemia). 3 4

Autoantibody Screening: Detection of autoantibodies against adrenal cortex, thyroid, pituitary, and pancreatic islets. 3

Management

First-Line Treatments:

- Glucocorticoids: For adrenal insufficiency (e.g., hydrocortisone). 1 5 - Thyroid Hormone Replacement: Levothyroxine for hypothyroidism. 1 5

Adjunctive Treatments:

- Levocarnitine: For hypoparathyroidism if associated with malabsorption. - Sex Hormone Replacement: Testosterone or estrogen/progestin for gonadal insufficiency. 5 - Desmopressin: For diabetes insipidus. 3

Special Populations

Pregnancy: Requires careful monitoring and adequate steroid cover to prevent adrenal crisis; fetal growth retardation may occur despite appropriate management. 1

Pediatrics: Juvenile forms often include hypoparathyroidism, chronic candidiasis, and adrenal insufficiency, requiring multidisciplinary care. 4

Comorbidities: Management may need adjustment for coexisting conditions like chronic active hepatitis or malabsorption syndromes. 4

Key Recommendations

Initiate glucocorticoid replacement therapy (e.g., hydrocortisone) for confirmed adrenal insufficiency to prevent adrenal crisis. (Evidence: Strong 1 5)

Prescribe levothyroxine for managing hypothyroidism, adjusting doses based on TSH and free T4 levels. (Evidence: Strong 1 5)

Consider multidisciplinary care in pediatric cases to address a broader spectrum of endocrine and non-endocrine manifestations. (Evidence: Moderate 4)

Provide adequate steroid coverage during pregnancy to ensure maternal and fetal safety, monitoring for fetal growth retardation. (Evidence: Moderate 1)

References

1 Mathur G, Fulcher G, Pollock C, Ferry J. Polyglandular autoimmune syndrome type 2 presenting for the first time during pregnancy. The Australian & New Zealand journal of obstetrics & gynaecology 1998. link 2 Panchamukhi VB, Ambing H, Samal SC, Dutta TK. Schmidt's syndrome. The Journal of the Association of Physicians of India 1991. link 3 Bhan GL, O'Brien TD. Autoimmune endocrinopathy associated with diabetes insipidus. Postgraduate medical journal 1982. link 4 Brun JM. Juvenile autoimmune polyendocrinopathy. Hormone research 1982. link 5 Petersen HD, Bergman M. Cortisone-induced remission of hypothyroidism in Schmidt's syndrome. Acta medica Scandinavica 1980. link

Autoimmune polyendocrine syndrome type 3