Approach

Replacement therapy aims to mimic endogenous hormonal secretion. Oral glucocorticoid and mineralocorticoid replacement are the first-line therapies, and are given for life.[2]

All patients should be empowered by careful education, so that they know when to increase replacement doses appropriately (e.g., when febrile, or vomiting, or in preparation for elective surgical procedures).[42] This may include parenteral administration of glucocorticoids.

Adrenal crisis

Patients presenting with features of adrenal crisis (i.e., hypotension, circulatory failure, marked acute abdominal symptoms) require immediate treatment with intravenous hydrocortisone, even if an appropriate laboratory diagnosis has not yet been made.[2][26][38][41]

Saline should be administered to correct hypotension and dehydration.[26][38] This may be the most important component in the immediate resuscitation of a critically ill patient. It is usually necessary to administer 1 L rapidly, and a further 4 to 6 L over the first 24 hours, to correct hypotension.[26] Careful monitoring of blood pressure, fluid status, and serum sodium and potassium levels should be maintained.

Glucose should be administered when necessary to correct hypoglycemia, but care should be taken to avoid worsening hyponatremia.[38] The use of normal saline supplemented with dextrose 5% is helpful in this regard.

The underlying cause that precipitated the crisis should be sought and treated. Once the patient is stable, usually 2 to 3 days later, oral glucocorticoid should be commenced or resumed in the usual dose.

Long-term replacement therapy for primary adrenal insufficiency

All patients should receive an oral glucocorticoid and mineralocorticoid on diagnosis.[2] Patients with primary adrenal insufficiency also have androgen deficiency, but the benefits of androgen replacement are less clearly defined.[3]

Hydrocortisone is the preferred medication in most countries.[3] If hydrocortisone is not available, alternative glucocorticoids are cortisone and prednisone.[2][43] Dexamethasone is not recommended as it lacks mineralocorticoid activity and is associated with increased adverse metabolic consequences.[2][3] The adequacy of glucocorticoid replacement is guided by clinical symptoms. Persistent fatigue, weight loss, and nausea are symptomatic of insufficient dosage.[3] Excessive weight gain or facial plethora is symptomatic of over-replacement.[2]

Mineralocorticoid dosage is impacted by the mineralocorticoid potency of the glucocorticoid administered and is adjusted based on clinical symptoms (particularly salt craving and postural hypotension) and serum potassium.[2] Plasma renin activity may be useful when clinical features and other laboratory tests are conflicting.[44]

Women with complaints of decreased libido or sexual wellbeing may benefit from additional treatment with dehydroepiandrosterone (prasterone).[2]

Adrenal deficiency in children is not specifically covered in this topic, but should result in referral to a pediatric endocrinology specialist.

During stress, trauma, or infection

During times of injury, trauma, or infection, it is necessary to increase glucocorticoid doses to compensate for the physiologic increase in cortisol levels that occurs during significant stress. Increasing oral glucocorticoid dose may be sufficient, but in times of severe stress or trauma, it may be necessary to administer intravenous glucocorticoids.[2][45]

Minor stress

  • Patients experiencing minor intercurrent stress (e.g., febrile illness; minor procedure/surgery not requiring fasting such as tooth extraction or local anesthesia) should be instructed to double their chronic maintenance dose of glucocorticoid therapy on the day of the procedure or for the duration of illness, then return to the usual dose when the stress resolves.[2][26]

Severe stress

  • Patients who undergo severe stress situations (e.g., unable to take oral glucocorticoid, such as acute gastroenteritis or prolonged fasting for colonoscopy; surgery under general or regional anesthesia; critical illness requiring ventilation; major trauma; active phase of labor and delivery) require a stress dose of a parenteral glucocorticoid (usually hydrocortisone).[2][26][46] However, evidence for the timing and dosage of perioperative stress-dose glucocorticoids is limited and will benefit from studies comparing different strategies.[47][48][49]

  • If patients are out of the critical phase of illness in less than 1 week but remain ill, then the dose of the corticosteroid can be tapered, using an oral formulation, back to previous pre-illness doses.

During pregnancy

There may be a physiologic increase in glucocorticoid and mineralocorticoid requirement during pregnancy.[2][50] This should be monitored frequently (e.g., every 6 to 8 weeks), and dose adjustments made as appropriate.

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