Pediatric Adrenal Insufficiency (Addison Disease) Treatment & Management

Glucocorticoid replacement is required in all forms of adrenal insufficiency (Addison disease). Mineralocorticoid replacement is required only in primary adrenal insufficiency, because aldosterone secretion is reduced in primary adrenal insufficiency but not in secondary (central) adrenal insufficiency. Consult an endocrinologist if adrenal insufficiency (Addison disease) is suspected.

Treat an acute adrenal crisis (eg, hypotension, hypoglycemia) with pharmacologic doses of glucocorticoids, which can be in the form of hydrocortisone, methylprednisolone, or dexamethasone.

After results for the patient's electrolyte, blood sugar, cortisol, and adrenocorticotropic hormone (ACTH) concentrations are obtained, administer glucocorticoids if adrenal insufficiency (Addison disease) is suspected. If a cosyntropin stimulation test is chosen, a single dose of dexamethasone may be administered without interfering with the measurement of the cortisol response to cosyntropin.

No surgical management is needed in most cases.

Supplementation of patients with primary adrenal insufficiency (Addison disease) with dehydroepiandrosterone has not proven to be beneficial.^{[43, 44]}

Do not forget that chronic infections, such as tuberculosis (TB) and human immunodeficiency virus (HIV) infection, can impair adrenal function. The possibility of central adrenal insufficiency (Addison disease) must be investigated, identified, and treated in all patients who have undergone pituitary surgery, irradiation, or prolonged treatment with glucocorticoids.

Patients with adrenal insufficiency (Addison disease) are generally hypovolemic and may be hypoglycemic, hyponatremic, or hyperkalemic. Initial therapy consists of intravenously administered saline and dextrose. Potassium is generally not needed in acute situations, especially in patients with primary adrenal insufficiency (Addison disease), who are often hyperkalemic.

Fluid resuscitation

In a hypotensive patient, rapidly administer isotonic sodium chloride solution (eg, 450 mL/m² or 20 mL/kg bolus) over the first hour. If patients are hypotensive, A second 20-mL/kg bolus of isotonic sodium chloride solution may be repeated if the patient's blood pressure remains low. Follow this with the typical continuous infusion of 3200 mL/m²/d or 200 mL per 100 calories of estimated energy expenditure at rest to restore intravascular volume.

Correction of hypoglycemia

Dextrose must be provided. If the patient is hypoglycemic, 2 mL/kg of 25% dextrose in water (D25W) or 4 mL/kg 10% dextrose in water (D10W) should correct hypoglycemia. Provide 5% dextrose in water (D5W) to prevent initial or further hypoglycemia.

Glucocorticoid administration

After intravenous fluids are provided, administer stress doses of glucocorticoid. The recommended stress dosage of hydrocortisone is an initial dose of 50-75 mg/m² given intravenously, followed by 50-75 mg/m²/d divided in 4 intravenous doses. Hydrocortisone may be given intramuscularly if intravenous access is unavailable. However, intramuscular administration works slowly. Comparable stress doses of methylprednisolone are 10-15 mg/m² and dexamethasone 1-1.5 mg/m².

Dexamethasone is preferable for patients with suspected but unproved adrenal insufficiency (Addison disease), because the physician can simultaneously treat the patient while performing a diagnostic cosyntropin stimulation test. Methylprednisolone and dexamethasone have negligible mineralocorticoid effects. Large doses of hydrocortisone (ie, even double or triple the stress doses previously mentioned) are preferred if the patient is hypovolemic, hyponatremic, or hyperkalemic, due to the mineralocorticoid effects of hydrocortisone (lacking in prednisone or dexamethasone).

No parenteral form of a mineralocorticoid is currently available in the United States. However, if the patient has good gastrointestinal function, fludrocortisone 0.1-0.2 mg may be orally administered.

Iatrogenic adrenal insufficiency (Addison disease) due to glucocorticoid therapy can be prevented by giving the patient dosages below his or her physiologic requirements. Treatment with alternate-day oral prednisone, or with topical or inhaled glucocorticoids, can reduce the risk of iatrogenic adrenal insufficiency (Addison disease).

If a patient with adrenal insufficiency (Addison disease) requires surgery, treat him or her with stress doses of glucocorticoids (eg, hydrocortisone 50-75 mg/m² given intramuscularly or intravenously when the patient is being transported to the operating room or in advance of the planned surgery). Fludrocortisone may be withheld on the day of surgery and while the patient is receiving stress doses of hydrocortisone.

Intraoperative period

During surgery, administer additional doses by giving either a hydrocortisone infusion at a dosage of 2-4 mg/m²/h or additional intravenous boluses of 10-25 mg/m² every 6 hours throughout the procedure. Note that these dosage recommendations are empiric, not evidence based.

Postoperative period

After surgery, continue the administration of hydrocortisone in the immediate postoperative period.

On the second and third postoperative days, the dosage of hydrocortisone can be decreased by 50% each day to a minimum of the patient's usual daily requirement if the patient is recovering well and has no complications.

By the fourth postoperative day, the usual daily dosage of steroids may be resumed if the patient is recovering satisfactorily. If complications occur, stress doses of glucocorticoids must be continued.

If the patient is unable to take oral fludrocortisone in the postoperative period, stress doses of hydrocortisone may be continued for a prolonged period to provide adequate mineralocorticoid activity.

An important physiologic response to stress is an increase in adrenocorticotropic hormone (ACTH)-mediated cortisol production. Patients with adrenal insufficiency (AI) (Addison disease) are unable to mount this response, regardless of the reason, and they must be given stress doses of glucocorticoid.

When a febrile illness occurs or when a patient requires a surgical or stressful procedure, triple the glucocorticoid dosage. If a patient is vomiting or listless, administer parenteral glucocorticoid (hydrocortisone 50-75 mg/m² given intramuscularly or intravenously or equivalent methylprednisolone 10-15 mg/m² or dexamethasone 1-1.5 mg/m²). Repeat the dose every 6-8 hours until patient recovers, because hydrocortisone succinate has a short duration of action.

Injectable glucocorticoid must be provided to all patients with adrenal insufficiency (Addison disease). The patient and caretaker must be instructed in its administration, the indications for its use and the lifesaving importance of its administration.

Mineralocorticoid therapy does not need to be tripled during periods of illness or physical stress.

Glucocorticoid or mineralocorticoid replacement is not contraindicated when needed. This therapy is involved in few drug-drug interactions.

Pregnant women

Preferred glucocorticoids during pregnancy are hydrocortisone or prednisone, because the placenta inactivates them and thereby prevents exposing the fetus to excess glucocorticoids. Therefore, dosage requirements may increase during pregnancy.

In contrast, dexamethasone and betamethasone readily cross the placenta and can suppress fetal adrenal function.

Because cortisol from the adrenal cortex stimulates phenylethanolamine N -methyltransferase, the last step in epinephrine synthesis, in the adrenal medulla, patients with cortisol deficiency have deficient epinephrine responses to stress, a condition not amenable to replacement therapy.^{[45, 46]}

In a child with adrenal insufficiency (Addison disease), long-term glucocorticoid replacement must be balanced between the need to prevent symptoms of adrenal insufficiency (Addison disease) and the need to allow the child to grow at a normal rate, because excess replacement with glucocorticoid diminishes growth velocity.

Hydrocortisone is available in 5-mg, 10-mg, and 20-mg tablets. This agent is recommended for long-term therapy because of its relatively low potency, which eases the titration of appropriate doses.

In a large patient, prednisone or dexamethasone may be substituted; however, individual sensitivity to these drugs widely varies. Estimated equivalencies are as follows^[47] :

• 1 mg of prednisone = typically given as 4-6 mg of hydrocortisone, but may be up to 15 mg
• 1 mg of dexamethasone = 40-100 mg of hydrocortisone

Patients with primary adrenal insufficiency (Addison disease) who also have mineralocorticoid deficiency require fludrocortisone at 0.1-0.2 mg/d. Young patients must be given adequate access to sodium chloride (typically 2-4 g/d) to counteract salt wasting.

If the patient's adrenal insufficiency (Addison disease) has an autoimmune etiology, monitor patients for the development of associated autoimmune phenomena, such as hypoparathyroidism, hypogonadism, vitiligo, pernicious anemia, thyroid dysfunction, and diabetes mellitus.

Glucocorticoid dosing

Individualize the dosage for each patient. The range for hydrocortisone is 7-20 mg/m²/d given orally in 2 or 3 divided doses.

Monitor the adequacy of dosing in patients with adrenal insufficiency (Addison disease) who receive long-term glucocorticoid therapy, and adjust the dose of glucocorticoid for each patient on the basis of clinical criteria (eg, absence of symptoms of glucocorticoid deficiency, excessive weight gain and normal growth). Too little glucocorticoid causes symptoms of adrenal insufficiency (Addison disease). Too much glucocorticoid causes excessive weight gain, cushingoid features, hypertension, hyperglycemia, cataracts, and growth failure. In children, growth failure is a sensitive indicator of exposure to excessive glucocorticoids.

In the authors' experience, plasma adrenocorticotropic hormone (ACTH) concentrations provide little guidance for adjusting doses of glucocorticoids. Growth pattern and symptoms of salt craving, blood pressure, plasma renin activity, and electrolytes help in adjusting doses of fludrocortisone.

Caloric and activity monitoring

The patient's caloric intake may need to be monitored. Restrict the patient's caloric intake if excess weight gain occurs and reevaluate the glucocorticoid dose, because excess glucocorticoid administration stimulates appetite.

Although no activity restrictions are necessary after adequate replacement therapy is started, provide patients who exercise in warm climates with sufficient sodium chloride to prevent hyponatremia. Stress doses of glucocorticoids are generally not needed for exercise.