Understanding Adrenal Insufficiency in Adults: Types, Clinical Features, Diagnosis, and Treatment

Adrenal insufficiency is a condition characterized by inadequate production of hormones by the adrenal glands, leading to a variety of systemic effects. It is a rare but potentially life-threatening disorder that requires prompt recognition and treatment. This article explores the types of adrenal insufficiency in adults, their clinical manifestations, diagnostic approaches, treatment strategies, and prevalence.

Types of Adrenal Insufficiency

Adrenal insufficiency is classified into three main types:

Primary Adrenal Insufficiency (Addison's Disease): This occurs due to direct dysfunction or destruction of the adrenal glands, leading to reduced production of cortisol, aldosterone, and adrenal androgens. Common causes include autoimmune adrenalitis (most frequent in developed countries), infections like tuberculosis (prevalent in developing nations), adrenal hemorrhage, metastases, and genetic conditions such as adrenoleukodystrophy.

Secondary Adrenal Insufficiency: Secondary insufficiency arises from insufficient adrenocorticotropic hormone (ACTH) secretion by the pituitary gland. This reduces cortisol production but typically spares aldosterone synthesis, as aldosterone is regulated by the renin-angiotensin system. Causes include pituitary tumors, trauma, surgical removal of the pituitary, and long-term use of glucocorticoids leading to suppression of the hypothalamic-pituitary-adrenal (HPA) axis.

Tertiary Adrenal Insufficiency: This type is due to hypothalamic dysfunction or suppression, resulting in decreased corticotropin-releasing hormone (CRH) secretion and subsequent reduced ACTH stimulation of the adrenal glands. It is most commonly caused by prolonged exogenous glucocorticoid use, with subsequent abrupt withdrawal.

Clinical Features

The presentation of adrenal insufficiency can vary, but common signs and symptoms of primary adrenal insufficiency include: fatigue, muscle weakness, weight loss, hyperpigmentation of skin and mucous membranes, salt craving and dehydration, and nausea and vomiting. Signs and symptoms of secondary and tertiary adrenal insufficiency include the symptoms of primary except there is a lack of hyperpigmentation and salt craving because aldosterone production is preserved. In addition, hypoglycemia is more pronounced due to the lack of cortisol’s gluconeogenic effects. Adrenal crises, a severe manifestation of the condition, are life-threatening and characterized by profound hypotension, shock, hypoglycemia, hyponatremia, and hyperkalemia.

Diagnosis

Diagnosis involves a combination of clinical suspicion, biochemical testing, and imaging studies. These include initial hormonal evaluation, ACTH stimulation test, and renin, aldosterone and electrolyte level testing. Initial hormonal evaluation measures morning serum cortisol and ACTH levels. Low cortisol with elevated ACTH indicates primary insufficiency, whereas low cortisol with low ACTH suggests secondary or tertiary insufficiency. ACTH stimulation test is a test in which synthetic ACTH (cosyntropin) is administered, and cortisol levels are measured at baseline and 30-60 minutes post-administration. An inadequate rise in cortisol confirms adrenal insufficiency. Other tests include imaging studies such as CT or MRI may be necessary to evaluate adrenal glands or pituitary-hypothalamic structures for underlying pathology.

Treatment

Management of adrenal insufficiency involves hormone replacement therapy and addressing the underlying cause. These include hormone replacement such as glucocorticoid replacement (e.g., hydrocortisone or prednisone) and mineralocorticoid replacement (e.g., fludrocortisone) are required to mimic physiological hormone levels. For secondary and tertiary insufficiency only glucocorticoid replacement is typically necessary. Adrenal crises require immediate intravenous administration of hydrocortisone, fluid resuscitation with saline and dextrose, and correction of electrolyte imbalances. Patients should carry medical alert identification and an emergency injection kit with hydrocortisone. They should be educated on dose adjustments during stress or illness to prevent crises.

Prevalence

Adrenal insufficiency is rare but has an estimated prevalence of 93-144 cases per million for primary adrenal insufficiency in developed countries. Secondary adrenal insufficiency is more common, with a prevalence ranging from 150 to 280 per million, often due to the widespread use of exogenous glucocorticoids. Tertiary insufficiency’s exact prevalence is unclear but likely mirrors patterns of glucocorticoid usage.

Conclusion

Adrenal insufficiency in adults is a rare but serious endocrine disorder requiring timely recognition and management. Understanding the distinct types, clinical features, and diagnostic strategies is crucial for effective treatment. With appropriate hormone replacement therapy and patient education, individuals with adrenal insufficiency can lead healthy, productive lives.

UpToDate. (n.d.). Clinical manifestations of adrenal insufficiency in adults. Retrieved January 6, 2025, from  https://www.uptodate.com/contents/clinical-manifestations-of-adrenal-insufficiency-in-adults?search=addison%20disease&source=search_result&selectedTitle=2%7E150&usage_type=default&display_rank=2