Knowing it for Detecting it: Addison Disease with Type 2 Autoimmune Polyendocrine Syndrome

Here we describe a patient who developed autoimmune hypoadrenalism many years after developing Graves’ disease. This combination depicts an autoimmune polyendocrine syndrome type-2 (APS-2).

APS-2 is an autoimmune syndrome involving endocrine (adrenal glands + thyroid, and/or type 1 diabetes mellitus) and non-endocrine autoimmune disorders. APS-2 has a genetic background showing an association with the class II major histocompatibility complex. APS-2 is an uncommon disease (1:8,000 inhabitants) with higher prevalence in females and mean onset age of 35 years.

Despite the fact that hypoadrenalism is characterized by specific symptoms and signs (asthenia, fatigue, orthostatic hypotension, weight loss, nausea, arthralgia, anorexia, skin hyperpigmentation) it is not easy to diagnose at early stages. In late referral patients clinical symptoms can worsen, due to stress events, until a possibly fatal addisonian crisis.

Hyponatremia, hyperkalemia, increased levels of ACTH, renin, and low levels of Cortisol, hepatic failure as well as clinical signs and symptoms of dehydration are late laboratory findings.

The natural history of the disease develops in different, progressive phases: (i) presence of adrenal cortex autoantibodies many years before the first clinical manifestations, (ii) initial increased levels of plasmatic renin and low levels of aldosterone, (iii) followed by a reduced response of Cortisol to the intravenous ACTH stimulation, (iv) and finally increased levels of plasmatic ACTH and low levels of Cortisol and clinical manifestations of adrenal insufficiency. The therapy of APS-2 is mainly focused on hormone therapy of the affected glands.