Intern Core Content: Disorders of the Adrenal Glands
/The adrenal system allows our bodies to respond to physiologic stressors and to regulate multiple metabolic processes within the body. Disorders of the adrenal axis can be chronic in onset, causing subacute or subclinical presentations, or acute, leading to frank clinical presentations that need to be managed more emergently by ER physicians. Recognition and diagnosis of these disorders can be difficult as the presenting symptoms are often subtle and nonspecific, making it all the more important for emergency practitioners to be able to recognize them in order to initiate timely management.
Anatomy and Physiology
Let’s take a quick trip back to medical school and review how the adrenal glands are structured and their several functions in their normal state.
The adrenal glands lie just superior to the kidneys bilaterally. The adrenal gland consists of the cortex, which is divided into three zones with each zone responsible for production of a certain steroid hormone, and the adrenal medulla, which produces the catecholamines epinephrine and norepinephrine. Within the cortex, the three zones are the zona glomerulosa (produces mineralocorticoids or aldosterone), the zona fasciculata (produces glucocorticoids or cortisol and its derivatives), and the zona reticulata (produces androgen precursors) (11,12).
Adrenal Cortex
Glucocorticoids, mainly cortisol, allow the body to respond to stress by acting on a variety of cellular processes. Metabolically, it causes increased gluconeogenesis and fat deposition and it plays a pivotal role in blood pressure maintenance as well by promoting vascular smooth muscle constriction. Long term exposure however can lead to muscle atrophy, bone reportion, skin thinning, and immune suppression (11,12).
Original image created by dr Rachel haupt
HPA Feedback Axis
To understand fully the adrenal glands and their function, one must also understand the hypothalamic-pituitary-adrenal axis (HPA axis) and its role in regulating responses to various stressors on the body.
Stressors cause the release of corticotropin releasing hormone (CRH) from the hypothalamus, which stimulates the anterior pituitary to release adrenocorticotropin releasing hormone (ACTH). ACTH then stimulates the adrenal cortex to increase cortisol production / release, and also increases androgen synthesis. This increase in glucocorticoid production facilitates the physiologic response to the stressor which activated HPA axis. Importantly, cortisol and other glucocorticoids establish negative feedback on both the anterior pituitary and the hypothalamus, preventing overstimulation of the HPA axis (1,11,12).
Renin-Angiotensin-Aldosterone System (RAAS)
ACTH from the hypothalamus and pituitary is NOT the primary regulator of mineralocorticoids. Instead, mineralocorticoid production is regulated in response to the renin-angiotensin-aldosterone system and serum potassium levels. Specifically, the kidneys are triggered to release renin in response to decreased renal perfusion. Renin is converted to angiotensinogen —> angiotensin I —> angiotensin II which ultimately stimulates aldosterone synthesis and release from the adrenal glands. This leads to an increase in water absorption in the kidneys and subsequent increase in blood pressure / renal perfusion (1).
Adrenal Medulla
The adrenal medulla functions independently from the cortex. Similar to the adrenal cortex, the medulla is through the hypothalamus by neural pathways which are activated when the body is under stress. The medulla subsequently releases epinephrine and norepinephrine to activate various alpha- and beta-adrenergic receptors throughout the body. These effects are most readily appreciated within the cardiovascular system, causing increased cardiac function and vascular contractility (1,11,12).
original table created by dr rachel haupt from information in reference #1,11,12 below in references
Disorders involving adrenal excess
Though there are a variety of causes of adrenal excess, the ultimate result is an overactive adrenal axis which can have devastating effects on the body. Syndromes of excess can result from primary adrenal problems (i.e. tumors, hyperplasia of the gland) vs secondary adrenal activation by another cause (i.e. exogenous medications, pituitary and hypothalamus dysregulation). The most common adrenal excess disorders are described below.
1) Cushing Syndrome
Cushing Syndrome is one of the most commonly known patterns of adrenal excess, and is caused by a prolonged exposure to excess cortisol. Cushing Syndrome can be broadly divided into two categories: ACTH-dependent and ACTH-independent (2,4).
ACTH-dependent Cushing Syndrome
An increase in ACTH secretion in the body resulting subsequently in increased serum cortisol
Often from a tumor (such as a pituitary adenoma or an ectopic ACTH secretion from a neuroendocrine tumor)
ACTH-independent Cushing Syndrome
An increase in cortisol primarily unrelated to ACTH levels
Typically due to a cortisol secreting adenoma (unilateral or bilateral) or adrenal hyperplasia
Can also be caused by exogenous steroid use for other medical comorbidities (i.e. frequent steroid bursts for COPD)
cushing syndrome presenting symptoms. Accessed may 18, 2025. file File:Cushing syndrome svg hariadhi.svg. from https://commons.wikimedia.org/wiki/File:Cushing_syndrome_svg_hariadhi.svg. from creative commons attribution share alike 4.9 international
Regardless of the type of Cushing Syndrome, the presentation from patient to patient can vary significantly. Common signs and symptoms include irritability, obesity, weight gain, round face, hirsutism, refractory hypertension, ecchymoses and striae, proximal muscle weakness, hyperglycemia, osteopenia, and recurrent infections (2,4).
Diagnostic Testing for Cushing Syndrome (2,4,13)
Usually based on a dexamethasone suppression test, urinary free cortisol measurements, or by a measurement of salivary cortisol
Severe cushings will show a 24h urinary cortisol > 4x the upper limit of normal and/or severe hypokalemia
Treatment for Cushing Syndrome (2,4)
Generally in the emergency department, treatment should focus on the signs and symptoms which caused the patient to present – often hypertension and hyperglycemia
In severe Cushings, patients are often triggered by other disease etiologies such as sepsis, thromboembolism, DKA / HHNS, refractory hypertension, heart failure – underlying causes should be treated per normal protocol before starting treatment specific to Cushing Syndrome
For Cushing Syndrome specifically, especially when it has been diagnosed on an outpatient basis already, providers can consider treatment with oral metyrapone or ketoconazole to reduce serum cortisol
Consider preventative anti-coagulation as Cushing’s patients have pro-thrombotic tendencies
Definitive management involves surgical resection of the offending tumor or emergent bilateral adrenalectomy in severe cases
2) Hyperaldosteronism
Hyperaldosteronism is another common disorder involving excess adrenal gland dysfunction. Primary hyperaldosteronism is due to independent secretion of aldosterone by an adrenal adenoma or adrenal hyperplasia, whereas secondary hyperaldosteronism results from increased activity of the RAAS system (5). Regardless of whether primary or secondary in nature, hyperaldosteronism frequently leads to secondary hypertension due to its significant ability to regulate sodium absorption and increase water absorption. In fact, over 20% of patients with resistant hypertension are thought to have undiagnosed hyperaldosteronism. If left untreated long term, hyperaldosteronism can lead significant co-morbidities such as cardiovascular disease and stroke (5).
Diagnostic Testing for Hyperaldosteronism (HA) (14,16)
Primary HA is diagnosed by an outpatient morning aldosterone-to-renin ratio (aldosterone will be high and renin low)
Secondary HA is diagnosed by outpatient aldosterone levels > 20 ng/dL
A salt loading test is a confirmatory test that can be performed as an outpatient – in HA patients, aldosterone levels will NOT decrease with salt loading as expected
In the emergency department, most patients will have refractory hypertension, significant hypokalemia due to the effects of aldosterone on potassium excretion, and a mild metabolic alkalosis
Treatment for Hyperaldosteronism (14,16)
In the emergency department, treatment involves stabilization of acute cardiovascular events, refractory hypertension, or severe electrolyte derangements
If discharging a patient from the ER and they have elevated blood pressure and known HA, starting a mineralocorticoid receptor antagonist such as spironolactone is the primary treatment of choice
For patients with primary HA, referral for surgical treatment is the most definitive management
3) Pheochromocytoma
Pheochromocytomas are rare tumors that grow within the adrenal medulla, causing catecholamine excess. Specifically, the chromafin cells within the tumor produce excess catecholemines and metabolize them into metanephrines. These tumors tend to periodically release their stored up metanephrines into the bloodstream, causing paroxysmal attacks of severely elevated blood pressure, severe headaches, diaphoresis, and abdominal pain (14,17). In some cases, catecholaminergic excess can lead to hypertensive crisis, cardiac arrythmias, pulmonary edema, strokes, and even multi-system organ failure (6,14).
Diagnostic Testing for Pheochromocytoma (17)
Serum or urine measurement of metanephrines, with serum metanephrines being more specific for pheo than urine
False positive metanephrine testing is more common than true positives, and all positive lab testing should be followed with imaging to confirm an adrenal lesion
Treatment for Pheochromocytoma (3,14)
Primary treatment in the emergency department is centered around treating hypertensive crises
When a pheo is suspected, alpha adrenergic blockade, such as phentolamine or phenoxybenzamine, is first line treatment
Nicardipine can be added to phentolamine if needed for resultant tachycardia or refractory hypertension
Beta blockade should only be undertaken after alpha blockade, as unopposed beta blockade could lead to worsening of the hypertensive crisis
All patients should be referred to surgery once a lesion is identified for definitive management
disorders involving Adrenal Insufficiency
Adrenal insufficiency is defined as the failure of adrenocortical function to secrete steroid hormones either in a basal state or during times of stress. Adrenal insufficiency (AI) requires prompt recognition and treatment as it can be fatal if it goes undiagnosed.
Clinical manifestations vary widely depending on the degree of dysfunction and where along the HPA axis the dysregulation lies (7). Common signs and symptoms include fatigue, anorexia, generalized weakness, abdominal pain, nausea and vomiting, confusion, depression, hypoglycemia, weight loss, skin manifestations, and other manifestations of autoimmune disease (8).
Laboratory evaluation can reveal hyponatremia, hyperkalemia, metabolic acidosis, elevated ESR, and elevated TSH.
Similar to adrenal excess, adrenal insufficiency can be characterized as either primary or secondary. Primary AI refers to dysfunction originating in the adrenal gland itself, most commonly due to autoimmune conditions such as Addison’s disease, with other causes including infection or inborn errors of glucocorticoid production. In primary AI due to the lack of negative feedback to the pituitary and hypothalamus from the adrenal gland, labs will reveal an increased in ACTH. This is the body’s way of attempting to stimulate adrenal production of hormones. However, the increase in ACTH will also stimulate production of melanocyte-stimulating hormone, causing hyperpigmentation which is the classical differentiator of primary AI from other causes of AI (7,8,9,15)
Secondary AI refers to pituitary dysfunction resulting in insufficient synthesis or secretion of ACTH. This is most commonly due to pituitary disease, tumors, or disruption via surgery or radiotherapy (7,8,15).
There is also a tertiary AI, which refers to decreased hypothalamic stimulation of the pituitary to secrete ACTH. This is most frequently from chronic exogenous glucocorticoid treatment. Long term this leads to atrophy of the adrenal cortex and tertiary adrenal insufficiency (7,8,15).
If a patient presents to the ED and there is a concern for new adrenal insufficiency with no obvious traumatic / infectious cause, testing for occult infection such as HIV, TB, and fungal infections is recommended (7,8,15).
original table created by dr rachel haupt from content in reference #7,8,15 below in references
Diagnostic Testing for Adrenal Insufficiency (9)
Outpatient cortisol measurement from an ACTH stimulation test. If cortisol levels low after ACTH stimulation, this diagnoses AI
Testing in the emergency department may show hyponatremia and hyperkalemia from mineralocorticoid deficiency (as a reminder, in normal states, aldosterone stimulates the kidneys to retain sodium and excrete potassium, therefore in a deficiency the opposite will be seen on labs)
Treatment for Adrenal Insufficiency (3,9,10,15)
Outpatient management for patients not in adrenal crisis:
Glucocorticoid exogenous supplementation: hydrocortisone preferred over prednisone or dexamethasone
Mineralocorticoid exogenous supplementation: fludrocortisone
Emergency department management for adrenal crisis
Can be triggered by secondary insult such as trauma or severe infection
Patients often present in shock, refractory hypotension, obtundation
Treatment includes administration of “stress dose steroids” in the form of hydrocortisone 100mg IV or IM, followed by administration of hydrocortisone 200mg over the next 24h divided q6h.
Volume repletion with IVF, close monitoring of serum electrolytes and glucose levels
Patients can receive pressors for refractory hypotension but usually is not helpful without also giving stress dose steroids as above
Conclusion
What should the emergency physician take away from all of this information? Adrenal disorders are very rarely diagnosed in the emergency department. They are more often diagnosed in the outpatient setting. However, complications of adrenal excess and insufficiency can present to the emergency department and require emergent care, especially if they have precipitated other disease processes such as cardiac dysfunction, blood pressure issue, or electrolyte abnormality. Emergency department physicians should feel comfortable managing these rare but important presentations.
POST BY Rachel Haupt, MD
Dr. Haupt is a PGY-1 in Emergency Medicine at the University of Cincinnati
EDITING BY Raveena Chhabria, MD and Anita Goel, MD
Dr Chhabria is a PGY-4 in Emergency Medicine at the University of Cincinnati
Dr. Goel is an Associate Professor in Emergency Medicine at the University of Cincinnati and assistant editor of TamingtheSRU.com
Cite As: Haupt, R., Chhabria, R., Goel, A. Intern Core Content: Disorders of the Adrenal Glands. TamingtheSRU. www.tamingthesru.com/blog/intern-core-content-adrenal-gland-disorders. 5/18/2025.
References
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