Episode 141: Adrenal Insufficiency Basics - a podcast by Rio Bravo Family Medicine Residency Program

Episode 141: Adrenal Insufficiency Basics

Future doctor Wilson explains how to recognize an acute adrenal insufficiency and explains how to treat it. Also, chronic adrenal insufficiency is explained. Dr. Arreaza adds comments about congenital adrenal hyperplasia.

Written by Candace Wilson, MSIV, American University of the Caribbean. Comments by Hector Arreaza, MD.

June 2, 2023.

You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.

Introduction: 

After having seen patients with adrenal insufficiency when I did a rotation in ICU, I saw how important it is to be able to recognize it quickly to ensure that patients receive appropriate treatment as quickly as possible. 

Arreaza: AI is adrenal insufficiency but also AI stands for Artificial intelligence, so we had the idea to ask Chat GPT what are the adrenal glands and this is what we got: “The adrenal glands are small endocrine glands located on top of each kidney. They are small in size, but they play a vital role in producing and secreting essential hormones.” (end of quote)

Glucocorticoids play an important role in the mobilization of energy reserves by increasing gluconeogenesis, glycogen synthesis, protein catabolism, lipolysis, appetite, and insulin resistance. 

Each adrenal gland is composed of two main parts: the outer region called the adrenal cortex and the inner region called the adrenal medulla. These two regions have distinct structures and functions.” The adrenal cortex has three zones, Zona glomerulosa (mineralocorticoids, mainly aldosterone), Zona fasciculata (cortisol), and Zona reticularis (androgens). 

Mineralocorticoids are a class of steroid hormones produced by the Zona glomerulosa of the adrenal gland that influence electrolyte and water balance through modifying renal absorption of sodium and potassium.

Definition of AI: AI is “inadequate functioning of the adrenal glands”. Adrenal gland hormones: glucocorticoids, mineralocorticoids, and sex hormones.

Primary vs. secondary adrenal insufficiency.

Candace: Primary adrenal insufficiency is caused either by the abrupt destruction of the adrenal gland or by progressive destruction/atrophy, whereas secondary adrenal insufficiency is due to conditions that impair the hypothalamic-pituitary-adrenal axis leading to decreased ACTH production. 

Causes of 

primary

 adrenal insufficiency includes autoimmune adrenalitis (which is the most common cause in the US); infectious adrenalitis (tuberculosis being the most common cause worldwide); adrenal hemorrhage; infiltration of the adrenal gland by tumors, amyloidosis, or hemochromatosis; adrenalectomy; cortisol synthesis inhibitors (such as rifampin, fluconazole, phenytoin, ketoconazole); 21B-hydroxylase deficiency; and vitamin B5 deficiency. 

Fluconazole is commonly used to treat pulmonary cocci (Valley Fever in our community). What about secondary causes?

Causes of secondary adrenal insufficiency include sudden discontinuation of chronic glucocorticoid therapy; stress (such as infection, trauma, or surgery) during prolonged glucocorticoid therapy; and hypopituitarism. 

Clinical presentation of adrenal crisis.

Adrenal insufficiency can present acutely or chronically with more insidious symptoms. We will first discuss the acutemanifestation of adrenal insufficiency, also known as adrenal crisis. In any patient who demonstrates vasodilatory shock, unexplained severe hypoglycemia, or unexplained hyponatremia whether or not the patient is known to have adrenal insufficiency, adrenal crisis should be considered a possibility. Adrenal crisis is a life-threatening emergency that requires immediate medical treatment and can occur in either primary or secondary adrenal insufficiency, though it is most common in patients with primary adrenal insufficiency. The main feature of adrenal crisis is shock, but patients may also have vague symptoms such as anorexia, nausea, vomiting, abdominal pain, weakness, fatigue, lethargy, fever, confusion, or coma. In patients with adrenal crisis from primary adrenal insufficiency, volume depletion and hypotension are the major clinical features, resulting from mineralocorticoid deficiency. In contrast, the patients with adrenal crisis from secondary adrenal insufficiency (which is an isolated glucocorticoid deficiency) will have hypotension secondary to decreased vascular tone without volume depletion.

Treatment of adrenal crisis.

Signs of an adrenal crisis should be recognized quickly, and management should be started as quickly as possible. When adrenal crisis is suspected, do not wait for laboratory results before initiating treatment as this is a life-threatening medical emergency. After all necessary laboratory tests have been collected (including serum electrolytes, glucose, routine measurement of plasma cortisol and ACTH) and IV access has been established, infuse 2-3L of isotonic saline or 5% dextrose in isotonic saline as quickly as possible and give bolus of hydrocortisone 100mg IV followed by 50mg IV every 6 hours or 200mg/24 hours as a continuous IV infusion for the first 24hrs. 

The answer to many endocrine emergencies is IV fluids, in this case, you also add hydrocortisone and mineralocorticoids.

Alternative glucocorticoids if hydrocortisone is unavailable include methylprednisolone and dexamethasone. While patient is hemodynamically unstable, it is important to frequently monitor vital signs and serum electrolytes to avoid iatrogenic fluid overload. When the patient has stabilized, continue IV isotonic saline at a slower rate for 24-48 hours, and for patients with primary adrenal insufficiency, begin mineralocorticoid replacement with fludrocortisone 0.1mg orally daily when saline infusion is stopped. If there is concern for infectious precipitating cause of the adrenal crisis, perform an extensive infectious workup. 

Addison’s disease.

Early symptoms of chronic adrenal insufficiency can be vague and nonspecific (such as fatigue, weight loss, and GI complaints), making the clinical diagnosis more difficult than acute adrenal insufficiency. Diagnosis must be confirmed with a thorough endocrine evaluation to determine the type and cause of the adrenal insufficiency, but treatment should be started before the diagnosis is established in acutely ill patients. Primary and secondary adrenal insufficiency shares some common clinical manifestations, such as fatigue, weight loss, anorexia, nausea, vomiting, abdominal pain, amenorrhea, diffuse myalgia, arthralgia, confusion, delirium, stupor, depression, psychosis, mania, anxiety, disorientation, and hallucinations.

Clinical manifestations of indicative of primary adrenal insufficiency include orthostatic hypotension, salt craving, hyperpigmentation especially of areas not typically exposed to sunlight (such as palmar creases, mucous membrane of the mouth), vitiligo (though hyperpigmentation is more common), hypotension, and auricular calcifications. 

Lab findings.

Laboratory results will show electrolyte disturbances (such as hyponatremia, hyperkalemia, and hypercalcemia), azotemia, normocytic anemia, eosinophilia, increased renin, normal anion gap metabolic acidosis, hypoglycemia, increased ACTH, low cortisol, low aldosterone, increased cortisol releasing hormone, and decreased DHEA-S.

Clinical manifestations of secondary adrenal insufficiency is similar to those in primary adrenal insufficiency with the notable exceptions of: hypotension (which is less prominent than in primary AI), absence of dehydration, pale skin as opposed to hyperpigmentation. Laboratory results in secondary adrenal insufficiency will show normal aldosterone, sodium, potassium, and renin; decreased ACTH and cortisol; and increased cortisol-releasing hormone.

Treatment of chronic adrenal insufficiency. 

Treatment of primary adrenal insufficiency focuses on replacing hypocortisolism with glucocorticoids and hypoaldosteronism with mineralocorticoids. In contrast, the treatment of secondary adrenal insufficiency focuses on the replacement of hypocortisolism with glucocorticoids without the need to supplement aldosterone. 

Short-acting glucocorticoids (such as hydrocortisone) are the preferred medication for treatment since they roughly mimic the normal diurnal rhythm. Intermediate-acting (such as prednisone or prednisolone) and long-acting glucocorticoids (such as dexamethasone) are acceptable alternatives, especially in patients who are non-compliant with multiple-day dose schedules or those with severe late-evening or early-morning symptoms, but due to variable inter-individual metabolism of dexamethasone, be cautious of over-treating patients. 

Whether the patient is receiving short-acting, intermediate-acting, or long-acting, ensure that patients receive the lowest glucocorticoid dose that relieves symptoms while avoiding signs and symptoms of glucocorticoid excess (such as weight gain, facial plethora, truncal obesity, osteoporosis, etc.).

Summary: Primary = Glucocorticoids and mineralocorticoids. Secondary = Glucocorticoids. Glucocorticoids can be short, intermediate, and long-acting. What about mineralocorticoids?

Fludrocortisone 0.1mg/day is the preferred agent for mineralocorticoid replacement in patients with primary adrenal insufficiency, though patients who are receiving hydrocortisone therapy in conjunction may require a lower dose of 0.05mg/day. Mineralocorticoid therapy may need to be increased during the summer due to salt loss in perspiration. 

As a reminder, aldosterone works by controlling the reabsorption of sodium and excretion of potassium. It influences water reabsorption. It is part of the renin-angiotensin-aldosterone system (RAAS) to maintain blood pressure. 

In addition, it is important that patients receive adequate education about their medical condition and causes, whether it is primary or secondary adrenal insufficiency, especially the maintenance of medication, adjustment during minor illnesses, and when to consult a clinician.

Bottom line: Adrenal insufficiency can be acute or chronic, primary or secondary. In primary adrenal insufficiency, laboratory results will show electrolyte abnormalities, such as hyponatremia and hyperkalemia, with increased ACTH. Whereas in secondary adrenal insufficiency, electrolytes will be normal, and ACTH will be decreased. Both primary and secondary adrenal insufficiency require treatment with glucocorticoid, but a mineralocorticoid should be added in the setting of primary adrenal insufficiency. 

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Conclusion: Now we conclude episode number 141, “Adrenal Insufficiency Basics.” We encourage you to recognize acute adrenal insufficiency promptly and start IV fluids and glucocorticoid stat. Candace reminded us that chronic adrenal insufficiency presents with vague and insidious symptoms, including hypotension, fatigue, weight loss, anorexia, hyperpigmentation of the skin, and even vitiligo. Make sure to include our colleagues from endocrinology if you have concerns.   

This week we thank Hector Arreaza and Candace Wilson. Audio editing by Adrianne Silva.

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! 

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References:

1. Nieman, L. K. (n.d.). Diagnosis of adrenal insufficiency in adults. UpToDate. https://www.uptodate.com/contents/diagnosis-of-adrenal-insufficiency-in-adults. Accessed June 2, 2023.
2. Nieman, L. K. (2022, October 25). Clinical manifestations of adrenal insufficiency in adults. UpToDate. https://www.uptodate.com/contents/clinical-manifestations-of-adrenal-insufficiency-in-adults . Accessed June 2, 2023.
3. Nieman, L. K. (2022a, October 19). Treatment of adrenal insufficiency in adults. UpToDate. Treatment of adrenal insufficiency in adults - UpToDate. Accessed June 2, 2023.
4. Royalty-free music used for this episode: "Latina Havana Boulevard." Downloaded on October 13, 2022, from https://www.videvo.net/ 

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