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Treatment of adrenal insufficiency in children

Treatment of adrenal insufficiency in children
Literature review current through: Jan 2024.
This topic last updated: Sep 07, 2022.

INTRODUCTION — Adrenal insufficiency is a potentially life-threatening condition defined by glucocorticoid deficiency, with or without associated mineralocorticoid deficiency [1]. Classic congenital adrenal hyperplasia (CAH), which is caused by 21-hydroxylase deficiency, is responsible for approximately 75 percent of cases of primary adrenal insufficiency in childhood. The diagnosis and treatment of this form of adrenal insufficiency are discussed in separate topic reviews:

(See "Clinical manifestations and diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children".)

(See "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children".)

The treatment of adrenal insufficiency other than CAH will be discussed below. The causes, clinical manifestations (table 1), and diagnosis of adrenal insufficiency are discussed separately.

(See "Clinical manifestations and diagnosis of adrenal insufficiency in children".)

(See "Causes of primary adrenal insufficiency in children".)

(See "Causes of central adrenal insufficiency in children".)

OVERVIEW — Treatment of adrenal insufficiency depends on the underlying mechanism:

Primary adrenal insufficiency – Primary adrenal insufficiency is caused by disease intrinsic to the adrenal cortex that causes cortisol deficiency, with or without mineralocorticoid deficiency (table 2). The most common cause in children is classic congenital adrenal hyperplasia (CAH). (See "Causes of primary adrenal insufficiency in children".)

Treatment for patients with primary adrenal insufficiency includes physiologic replacement with glucocorticoid and, in most cases, mineralocorticoid. Glucocorticoid dosing must be increased during times of stress.

Central adrenal insufficiency – This is characterized by lack of adrenocorticotropic hormone (ACTH) stimulation of cortisol production. It can be caused by either pituitary disease that impairs production of ACTH (secondary adrenal insufficiency) or by interference with corticotropin-releasing hormone release from the hypothalamus (tertiary adrenal insufficiency) (table 3). The most common cause is chronic high-dose glucocorticoid therapy, which suppresses the hypothalamic-pituitary-adrenal axis. (See "Causes of central adrenal insufficiency in children".)

Treatment for central adrenal insufficiency generally requires only glucocorticoid replacement because these patients do not have mineralocorticoid deficiency. However, they may have other pituitary hormone deficiencies that require treatment, depending on the underlying central nervous system disease.

ADRENAL HORMONE REPLACEMENT THERAPY

Glucocorticoids — Most children with adrenal insufficiency require continuous glucocorticoid replacement, with increased doses during times of stress. For some children with preserved marginal adrenal function, the deficit becomes apparent only during times of stress.

Choice of glucocorticoid — Glucocorticoid preparations vary in their potency and duration of action (table 4):

PreferredHydrocortisone is the preferred formulation for glucocorticoid replacement for children while their epiphyses remain open. This is because hydrocortisone has a short duration of action and lower potency compared with other glucocorticoids, allowing for finer titration to the optimal dose. Hydrocortisone also has modest mineralocorticoid activity.

Second-line choicesPrednisolone or prednisone are synthetic intermediate-acting glucocorticoids. They are sometimes used instead of hydrocortisone, primarily because they require less frequent dosing (once or twice daily). However, they are also more likely to suppress growth. They are approximately four to five times more potent than hydrocortisone in terms of adrenocorticotropic hormone (ACTH) suppression [2] and 5 to 15 times more potent in terms of growth suppression [3]. The mineralocorticoid activity of these preparations is very low and generally clinically insignificant.

Not recommended – Long-acting potent synthetic glucocorticoid preparations, such as dexamethasone, are not generally used for replacement therapy in children, although they are sometimes used in adults [1]. The potency of dexamethasone is approximately 60 to 80 times that of hydrocortisone, as measured by its growth-suppressive effect [4,5]. This high potency makes it difficult to titrate the appropriate dose for children. However, with the availability of a commercial oral suspension, dexamethasone has been used successfully in some children without causing growth suppression [4,6,7]. Dexamethasone has no mineralocorticoid activity.

Children with primary adrenal insufficiency also usually require mineralocorticoid replacement, given as fludrocortisone. Because these glucocorticoid preparations vary in their mineralocorticoid activity, the fludrocortisone dose will generally be lower for children on hydrocortisone (which has some mineralocorticoid activity) compared with dexamethasone (which has no significant mineralocorticoid activity). (See "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children" and 'Mineralocorticoids' below.)

Dosing — The glucocorticoid dosing requirement varies with the type of adrenal insufficiency:

Classic congenital adrenal hyperplasia (CAH) – For newly diagnosed infants with classic CAH due to 21-hydroxylase deficiency, glucocorticoid dosing is substantially higher than for other causes of adrenal insufficiency because higher doses are often needed to suppress the ACTH-stimulated excessive adrenal androgens in CAH. (See "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children", section on 'Medications and dosing'.)

Other causes of primary adrenal insufficiency – For children with primary adrenal insufficiency that is not due to classic CAH, the starting oral dose of hydrocortisone is in the range of 8 to 10 mg/m2/day, based on a cortisol production rate of approximately 5 to 8 mg/m2/day [1,8]. The body surface area is calculated from the child's height and weight using a nomogram or calculator (calculator 1) [1].

The total daily oral hydrocortisone dose is usually divided into three doses and administered approximately every eight hours. The regimen should be tailored to the individual patient, based on their specific condition, symptomology, and ability to adhere to the dosing schedule. The diurnal production of cortisol can be mimicked by administering a larger portion of the daily dose in the morning, with progressively smaller doses at midday and evening.

Hydrocortisone is the preferred glucocorticoid for children while the epiphyses remain open because of its short duration of action and lower potency than other glucocorticoids (see 'Choice of glucocorticoid' above). It is typically dosed three times daily, a compromise between duration of action for immediate-release hydrocortisone (ie, six hours), quality of life, and avoidance of symptoms, which can develop with less frequent dosing. In the future, novel modified-release hydrocortisone preparations could help to mimic circadian cortisol dosing profiles [9,10].

The dose is subsequently adjusted based on the individual's biochemical and physiologic response to treatment including growth rate, as outlined below. (See 'Monitoring and dose adjustment' below.)

Central adrenal insufficiency – Central (secondary or tertiary) adrenal insufficiency, characterized by ACTH deficiency, is treated with glucocorticoid at physiologic replacement doses, ie, hydrocortisone 8 to 10 mg/m2/day. The dose must be titrated carefully to prevent overtreatment, which seems to occur at lower doses in children with central adrenal insufficiency than in those with primary adrenal insufficiency. Growth rates (weight and height) and general clinical well-being are useful parameters to follow for dose adjustments. If the frequency is reduced to twice daily, the child should be monitored carefully for symptoms of adrenal insufficiency.

The therapeutic doses suggested above are somewhat higher than normal daily cortisol secretion rates because of the short half-life of hydrocortisone given orally and its partial destruction by gastric acidity.

Mineralocorticoids

Indications — Patients with primary adrenal insufficiency usually require mineralocorticoid replacement with fludrocortisone. An exception is primary adrenal insufficiency due to adrenoleukodystrophy, which usually is not associated with mineralocorticoid deficiency in childhood. However, individuals with adrenoleukodystrophy occasionally develop mineralocorticoid deficiency over time, so they should be monitored and treated if suggestive signs and symptoms develop (salt craving, hyponatremia with hyperkalemia and elevated plasma renin activity [PRA]) [11,12]. (See "Clinical features, evaluation, and diagnosis of X-linked adrenoleukodystrophy".)

Patients with central adrenal insufficiency do not require mineralocorticoid replacement, because they have a normal renin-angiotensin-aldosterone axis and therefore have normal mineralocorticoid secretion. However, these patients may have deficiencies of other pituitary hormones that may require replacement. (See "Clinical manifestations and diagnosis of adrenal insufficiency in children", section on 'Evaluate for cause'.)

Dosing — The typical daily dose of fludrocortisone is 0.1 mg when given in conjunction with hydrocortisone, which has some of its own mineralocorticoid activity. The mineralocorticoid dose is then adjusted based on PRA. It is not adjusted by age or body surface area, because the aldosterone secretion rate is nearly constant throughout the lifespan. Higher doses are occasionally needed in early infancy (eg, <4 months of age) due to a physiologic aldosterone resistance of the immature newborn renal tubule [13].

Higher fludrocortisone doses may be needed when using prednisone or prednisolone (which have low mineralocorticoid activity) or dexamethasone (which has essentially no mineralocorticoid activity) (table 4) [1].

Sodium chloride supplements — Infants younger than one year with mineralocorticoid deficiency should also be supplemented with sodium chloride in addition to mineralocorticoid replacement. The dose is approximately 1 gram (17 mEq) daily. Infants require this sodium supplement because of their relatively low dietary sodium intake in formula and breast milk and a relative renal resistance to mineralocorticoids in this age group.

Monitoring and dose adjustment

Frequency of monitoring – In infants, the response to therapy should be evaluated monthly in the first three months after starting treatment, every three months in older infants, and every six months thereafter while the child is still growing. More frequent monitoring is sometimes clinically indicated. After completion of growth, annual monitoring may be adequate.

Measures – Adjustments in glucocorticoid and mineralocorticoid doses are based on the following serial measures:

Growth – Serial measures of height and weight (every visit).

Skeletal maturation – As measured by bone age, a marker for skeletal growth. For children with adrenal insufficiency not due to CAH, we perform a baseline bone age determination at approximately age two years and repeat in patients with abnormal growth rates. For children with CAH, annual or semiannual bone age determination is recommended (due to potential effects of androgen excess) [14].

Symptoms – Inquire about gastrointestinal complaints and salt craving.

Signs – Check for skin hyperpigmentation (suggests increased ACTH due to a primary glucocorticoid deficiency), facial plethora or Cushingoid features (suggests glucocorticoid excess), hypotension and dehydration (suggests mineralocorticoid deficiency), and hypertension (suggests mineralocorticoid excess).

Electrolytes and PRA – For patients with primary adrenal insufficiency on fludrocortisone treatment, to monitor for mineralocorticoid deficiency, which causes hyponatremia, hyperkalemia, and elevated PRA.

We do not monitor plasma ACTH concentrations, because levels are highly variable and typically remain above the normal range even when glucocorticoid replacement doses are adequate based on clinical parameters. Moreover, accurate measurement of ACTH requires careful specimen collection and storage to avoid degradation of the sample [15].

Interpretation – Close follow-up of somatic growth (height and weight velocities and rate of bone age change) provides the most important guidelines for dose adjustment.

Insufficient glucocorticoid dose – Inadequate weight gain, headache, and gastrointestinal symptoms including nausea could suggest inadequate glucocorticoid dosing (or nonadherence). These same symptoms also reflect inadequate mineralocorticoid replacement, so they must be interpreted in the context of other symptoms and laboratory markers of mineralocorticoid status (table 1). Increasing hyperpigmentation suggests chronic insufficient glucocorticoid replacement in patients with primary adrenal insufficiency.

Decreased height velocity may be seen in cases of severe glucocorticoid underdosing (ie, cortisol deficiency). However, in patients with CAH, height velocity is not a useful indicator of sufficient glucocorticoid dosing, because of the accelerating effects of excess androgens on height velocity.

Excessive glucocorticoid dose – Cushingoid features do not develop with the physiologic replacement doses of glucocorticoids that are used to treat adrenal insufficiency.

Insufficient mineralocorticoid dose – In patients with primary adrenal insufficiency, signs and symptoms of inadequate mineralocorticoid replacement include salt craving, dehydration, headache, dizziness, and poor weight gain.

Laboratory testing can reveal an elevated PRA, sometimes with hyponatremia and hyperkalemia (in severe mineralocorticoid insufficiency) (table 1) [1]. Elevated PRA with normal electrolytes may also be caused by dehydration alone and may normalize with consumption of additional water. If PRA does not normalize with rehydration, this suggests ongoing salt loss. The next step is to increase the fludrocortisone and exogenous salt replacement doses (eg, in infants) to normalize the elevated PRA.

Excessive mineralocorticoid dose – An excessive mineralocorticoid dose is often associated with elevated blood pressure and suppressed PRA. However, suppressed PRA is also a common finding in patients on glucocorticoids that have significant mineralocorticoid activity (eg, hydrocortisone) and does not necessarily require mineralocorticoid dose adjustment.

STRESS CONDITIONS — All patients with adrenal insufficiency require additional doses of glucocorticoids when subjected to physiologic stress [16]. The primary goal of treatment is to avoid the serious consequences of adrenal crisis. The treatment regimens described below provide ample glucocorticoid coverage for acute stress. If the stress is prolonged, patients require ongoing monitoring and additional glucocorticoid treatment.

Every patient should wear medical identification (eg, bracelet, necklace, or shoe tag) and carry specific supplemental emergency information on a card or smart phone (eg, the "Medical ID" feature in a Health App or emergency lock screen). The medical identification should indicate the diagnosis "adrenal insufficiency" and "needs hydrocortisone."

Acute illness

Oral — Glucocorticoid dosing depends on the severity of illness [1]:

Minor infection and/or low-grade fever (sore throat, rhinorrhea, fever up to 38°C) – Stress doses are generally not needed (ie, patients continue their usual glucocorticoid replacement dose).

Moderate acute illness (eg, severe upper respiratory infections) – Give double the patient's usual glucocorticoid replacement dose.

Major acute illness (eg, temperature above 38°C and/or occasional vomiting) – Give three times the patient's usual glucocorticoid replacement dose. Patients with repetitive vomiting require parenteral treatment. (See 'Parenteral' below.)

In general, oral hydrocortisone should be used for stress dosing to provide the advantages of rapid increases in serum cortisol levels as well as for its mineralocorticoid effect [17]. For patients receiving glucocorticoid therapy with dexamethasone or prednisone, increasing the dose of these medications during acute illness may not achieve the rapid increase in glucocorticoid blood levels that are needed to combat the stress. Conversions among these glucocorticoids to achieve equivalent cortisol effect are listed in the table (table 4).

Parenteral — Under stress conditions, infants and children frequently are unable to tolerate oral therapy. In such cases, the parent or caregiver should administer an intramuscular injection of approximately 50 mg/m2 of hydrocortisone sodium succinate (Solu-Cortef). The treating clinician can calculate the appropriate dose by using the body surface area calculated from the child's height and weight via a nomogram or calculator (calculator 1).

Alternatively, a simpler age-based dose regimen can be used [1]:

0 to 3 years old – Hydrocortisone 25 mg intramuscularly

>3 to 12 years old – Hydrocortisone 50 mg intramuscularly

>12 years and older – Hydrocortisone 100 mg intramuscularly

This treatment will provide up to six hours of coverage and allow the family time to get medical attention. For all patients with adrenal insufficiency, the treating endocrinologist should provide a letter outlining these steps and additional ones for management in the field and/or emergency department.

Surgical procedures — General anesthesia (with or without surgery) substantially increases the glucocorticoid requirement for patients with adrenal insufficiency. This is based on the fact that general anesthesia increases the cortisol secretion rate in normal subjects [18].

Minor to moderate surgical stress — We recommend administration of intravenous hydrocortisone as a single dose of 50 mg/m2, consistent with pediatric guidelines from the Endocrine Society [1].

Alternatively, the age-based parenteral doses listed above can be employed, given intravenously. (See 'Parenteral' above.)

If the patient is hospitalized after the procedure, the initial bolus is followed by the same dose at a constant intravenous rate over a 24-hour period or in four divided intravenous doses over 24 hours. The stress doses of hydrocortisone are tapered rapidly according to the pace of clinical improvement, generally by reducing the dose back to oral physiologic replacement within one to two days.

Major surgery — For surgeries requiring general anesthesia and/or associated with trauma, childbirth, or associated/underlying disease that requires intensive care, we suggest using a protocol that includes ongoing doses of glucocorticoid, as follows [1]:

Just prior to anesthesia induction, give hydrocortisone at a dose of 50 mg/m2 by rapid intravenous injection (maximum dose 100 mg). This is followed by hydrocortisone 50 to 100 mg/m2/day (adult dose 200 mg/day) as a continuous infusion or divided every six hours.

The following day, give hydrocortisone at three to four times the patient's usual replacement therapy dose. This can be given orally if the patient is clinically stable, or as a constant intravenous infusion or divided into four intravenous boluses given every six hours if clinically unstable. If the patient experiences significant hypotension or electrolyte abnormalities, additional hydrocortisone may be needed.

Stress dosing is generally continued until the patient can tolerate oral intake, is afebrile, and is hemodynamically stable. The timing depends on the nature of the surgery and expected recovery time.

These high doses will provide the needed extra glucocorticoid as well as mineralocorticoid coverage. Hydrocortisone 20 mg has approximately the same mineralocorticoid effect as 0.1 mg of fludrocortisone. Parenteral preparations with purely mineralocorticoid effects are not available.

ADRENAL CRISIS — Rapid recognition and prompt therapy of a salt-losing adrenal crisis are critical to survival. Electrolyte and fluid therapy must be instituted as soon as possible [19]. A rapid overview guiding the recognition and treatment of an adrenal crisis is shown in the table (table 5).

Clinical presentation and risk factors – In patients with adrenal insufficiency, an adrenal crisis is precipitated by absolute or relative glucocorticoid deficiency. Thus, an adrenal crisis can occur in patients who are receiving physiologic or even supraphysiologic doses of glucocorticoid if their requirements increase because of physiologic stress (eg, acute illness). Patients with primary adrenal insufficiency can also have associated mineralocorticoid deficiency, causing salt wasting, which presents with hyponatremia and hyperkalemia, as well as signs and symptoms of dehydration [20]. If the salt-wasting crisis is severe, patients can develop hypotension or shock.

Patients with central adrenal insufficiency are also at risk for adrenal crisis, precipitated by glucocorticoid deficiency. Clinical manifestations of an adrenal crisis in such patients include hypotension and shock. Because they have preserved mineralocorticoid function, they do not exhibit the electrolyte disturbances and severe dehydration that are seen when patients with primary adrenal insufficiency have an adrenal crisis.

Emergency management – In newborns presenting with an adrenal crisis, the most common cause is classic congenital adrenal hyperplasia (CAH). However, with the availability of newborn screening, most of these infants are diagnosed before an adrenal crisis occurs. The evaluation and management of CAH are discussed separately. (See "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children".)

For infants and children with an adrenal crisis not caused by CAH, we suggest the following measures be instituted as soon as the condition is suspected (table 5):

Baseline samples – Obtain blood samples for urgent testing of electrolytes and glucose to confirm the presence of an adrenal crisis and guide further management.

In patients without a known diagnosis of adrenal insufficiency, obtain additional diagnostic blood samples for serum cortisol and plasma adrenocorticotropic hormone (ACTH); these are only useful if they are drawn prior to the administration of glucocorticoid therapy.

Fluids and electrolytes – Give a bolus of D5 normal saline (5% dextrose with 0.9% saline, without potassium), 10 mL/kg intravenously in children, with a repeat bolus if needed (table 5). This will improve/correct the hyponatremic dehydration, as well as hypoglycemia if present. Patients with hypoglycemia may need additional dextrose infusions, as outlined in the table. After the bolus is given, the potassium concentration usually remains elevated and the acidosis may persist. If the hyperkalemia is associated with electrocardiographic changes, it may be necessary to use insulin and glucose for rapid reduction of serum potassium levels, sometimes in conjunction with an enteral sodium-potassium exchange resin (eg, Kayexalate). (See "Management of hyperkalemia in children".)

Glucocorticoids and mineralocorticoids – Initiate treatment with a glucocorticoid as soon as possible by giving an intravenous bolus over several minutes. We use hydrocortisone sodium succinate (Solu-Cortef) at a dose of 50 mg/m2 for children (maximum dose 100 mg) [1]. Alternatively, age-based dosing may be used emergently (table 5). (See 'Parenteral' above.)

The initial glucocorticoid bolus is followed by the same dose divided over the next 24 hours, either as a constant intravenous infusion or as four divided bolus doses.

Throughout the treatment, electrolytes and water balance must be monitored very carefully to prevent water retention and its complications. After the initial crisis is treated, a maintenance dose of glucocorticoid can be calculated and initiated. Mineralocorticoid replacement (fludrocortisone) may be continued concurrently with stress glucocorticoid dosing, although it is not strictly necessary while the patient is on high doses of hydrocortisone, because of the mineralocorticoid activity of the hydrocortisone. If the fludrocortisone is held, it should be resumed promptly as the hydrocortisone stress dosing decreases.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Classic and nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Society guideline links: Adrenal insufficiency".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Congenital adrenal hyperplasia (The Basics)")

SUMMARY AND RECOMMENDATIONS

Overview – Primary adrenal insufficiency results from pathology intrinsic to the adrenal cortex (table 2). Affected patients have glucocorticoid deficiency, with or without deficiencies of mineralocorticoids and adrenal androgens. Central adrenal insufficiency is caused by impaired production of adrenocorticotropic hormone (ACTH) in the pituitary gland (table 3). Patients with central adrenal insufficiency have glucocorticoid deficiency without mineralocorticoid deficiency. (See 'Overview' above.)

Glucocorticoid replacement – Almost all patients with adrenal insufficiency require maintenance glucocorticoid replacement (rare patients may only require stress dosing).

Initial dosing – The optimal dose depends on the type of adrenal insufficiency. (See 'Glucocorticoids' above.)

-For patients with primary adrenal insufficiency other than that due to classic congenital adrenal hyperplasia (CAH), initial replacement doses of hydrocortisone are approximately 8 to 10 mg/m2/day when given orally. The total daily oral hydrocortisone dose is divided into three doses and administered approximately every eight hours. (See 'Dosing' above.)

-Infants with classic CAH typically require substantially higher initial replacement doses of hydrocortisone. (See "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children", section on 'Medications and dosing'.)

Choice of glucocorticoid – For infants and children, we suggest treatment with hydrocortisone rather than prednisone or prednisolone (Grade 2C). The relatively low potency and short duration of action of hydrocortisone allow for fine titration of the dose (table 4). Longer-acting synthetic glucocorticoids such as prednisone and dexamethasone may be considered in older adolescents who have completed growth and in adults; these preparations have little or no mineralocorticoid effect. (See 'Choice of glucocorticoid' above.)

Subsequent dose adjustment – The dose should then be titrated to the individual patient's needs depending on the clinical response and height and weight trajectories. (See 'Monitoring and dose adjustment' above.)

Mineralocorticoid replacement – Patients with primary adrenal insufficiency usually require mineralocorticoid replacement. The dose of mineralocorticoid depends on the type of glucocorticoid given concurrently and is further adjusted based on the clinical response. Doses of mineralocorticoid may need to be adjusted to optimize growth, prevent salt craving, and maintain normal electrolytes and plasma renin activity (PRA), especially in infants. In general, the fludrocortisone dose is close to 0.1 mg/day (not weight based) and may be higher for infants. The dose does not typically need frequent adjustment over the lifespan. (See 'Mineralocorticoids' above.)

Stress conditions – Patients with adrenal insufficiency require increased glucocorticoid doses during physiologic stress:

Acute illness – For acute illness, the oral stress dose of glucocorticoid is two to three times the replacement dose, depending on the stressor. It may be preferable to use oral hydrocortisone for stress dosing to provide the advantages of rapid increases in serum cortisol levels as well as mineralocorticoid effect. (See 'Oral' above.)

Children who are unable to tolerate oral therapy should be given an intramuscular injection of hydrocortisone sodium succinate (Solu-Cortef) to meet their urgent need for glucocorticoid replacement and should then seek medical attention. (See 'Parenteral' above.)

Surgical procedures – General anesthesia sharply increases glucocorticoid requirements, in addition to the stress of surgery itself. Typical regimens for glucocorticoid replacement during surgery include an intravenous bolus at the time of anesthesia induction before beginning surgery, followed by variable regimens postoperatively, depending on the length of the surgery, degree of surgical stress, and any postoperative complications. (See 'Surgical procedures' above.)

Adrenal crisis – In patients with primary adrenal insufficiency, an adrenal crisis can be precipitated by mineralocorticoid deficiency; this is referred to as a salt-wasting adrenal crisis. Patients will present with hyponatremia and hyperkalemia, as well as signs and symptoms of dehydration. If severe, they can also present with hypotension or shock.

Patients with central adrenal insufficiency may present in an adrenal crisis due to cortisol deficiency, with hyponatremia, hypoglycemia (in younger children), and/or hypotension and shock if severe. (See 'Adrenal crisis' above.)

All patients with suspected adrenal crisis should be urgently treated with parenteral fluid boluses and glucocorticoid therapy, as described in the rapid overview (table 5).

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Patricia A Donohoue, MD, who contributed to earlier versions of this topic review.

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