Autoimmune polyglandular syndrome 2
Autoimmune polyglandular syndrome type 2 (APS-2, or Schmidt syndrome) is the co-occurrence of autoimmune primary adrenal insufficiency with autoimmune thyroid disease and/or type 1 diabetes, plus often primary ovarian insufficiency, pernicious anemia, celiac disease, or vitiligo, over a patient's lifetime. Management is component-specific hormone replacement, with adrenal insufficiency treated first because untreated hypothyroidism can mask it and starting levothyroxine before glucocorticoid replacement can precipitate adrenal crisis.
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What this article covers
- Overview
Autoimmune polyglandular syndrome type 2 (APS-2), also called Schmidt syndrome, is the combination of autoimmune primary adrenal insufficiency with autoimmune thyroid disease and/or type 1 diabetes…
- Epidemiology
Approximately 50% of patients with autoimmune primary adrenal insufficiency (Addison disease) will develop another autoimmune endocrine disorder during their lifetime, most commonly primary…
- Risk factors
A personal history of one autoimmune endocrinopathy (autoimmune adrenal insufficiency, Hashimoto thyroiditis, Graves disease, type 1 diabetes, or primary ovarian insufficiency) is the dominant risk…
- Pathophysiology
Each component of APS-2 results from organ-specific autoimmune destruction, mediated by autoreactive T cells and autoantibodies, the same mechanism as when each condition occurs in isolation, but in…
- Clinical features
The clinical picture reflects whichever components are active at a given time and can evolve over years, so a patient may present initially with features of only one gland's failure.
- Differential diagnosis
Autoimmune polyglandular syndrome type 1 (APECED): shares autoimmune adrenal insufficiency, but is distinguished by the AIRE-driven triad of candidiasis and hypoparathyroidism together with adrenal…
- Diagnosis
The diagnosis is made when autoimmune adrenal insufficiency and autoimmune thyroid disease and/or type 1 diabetes are both confirmed in the same patient, with each component diagnosed by its own established biochemical criteria.
- Management
First, if adrenal insufficiency is confirmed or strongly suspected, start glucocorticoid replacement before addressing any coexisting thyroid disease: hydrocortisone 15-25 mg/day PO divided into 2-3…
- Complications
Adrenal crisis, including crisis precipitated by starting or increasing levothyroxine before adequate glucocorticoid replacement, is the most acutely dangerous complication of this syndrome.
- Prognosis
With correctly sequenced, component-specific hormone replacement, individual manifestations of APS-2 are generally well controlled, but the condition requires lifelong adherence and monitoring rather than a curative intervention.
- Prevention
There is no primary prevention for the underlying autoimmune process; prevention efforts focus on early recognition and avoiding iatrogenic precipitation of adrenal crisis.
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Related articles
- Primary adrenal insufficiency
Primary adrenal insufficiency (Addison disease) is destruction or dysfunction of the adrenal cortex, most often autoimmune, causing combined cortisol and aldosterone deficiency with hyperpigmentation, hyponatremia, and hyperkalemia. Lifelong glucocorticoid replacement with hydrocortisone plus mineralocorticoid replacement with fludrocortisone is required, with sick-day dose increases to prevent adrenal crisis.
- Hashimoto thyroiditis
Hashimoto thyroiditis is a chronic autoimmune process in which lymphocytic infiltration destroys the thyroid, and is the most common cause of hypothyroidism in iodine-sufficient regions such as the United States. Diagnosis rests on an elevated thyroid-stimulating hormone with a low or normal free thyroxine, and first-line treatment is lifelong levothyroxine replacement dosed to normalize thyroid-stimulating hormone.
- Type 1 diabetes mellitus
Type 1 diabetes mellitus is an insulin-deficient state from autoimmune (type 1A) or idiopathic (type 1B) destruction of pancreatic beta cells, presenting with hyperglycemia that can range from mild to life-threatening diabetic ketoacidosis. Diagnosis combines standard glycemic criteria with autoantibody testing (GAD65, IA-2), and lifelong insulin therapy, generally as a basal-bolus regimen, is required from diagnosis, with self-monitoring or continuous glucose monitoring to guide dosing.
- Autoimmune polyglandular syndrome 1
Autoimmune polyglandular syndrome type 1 (APS-1, also called APECED) is caused by mutation of the AIRE gene, which normally drives thymic negative selection against self-reactive T cells; loss of AIRE produces the classic triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. Management is component-specific and lifelong: fluconazole for candidiasis, calcium and calcitriol for hypoparathyroidism, and glucocorticoid plus mineralocorticoid replacement for adrenal insufficiency, with structured lifelong screening for additional autoimmune endocrinopathies as they emerge.