Adrenal Hypoplasia Medication

Acute therapy

For a patient with suspected but unproved adrenal insufficiency, dexamethasone is best used to correct the glucocorticoid deficiency. This allows immediate procession to a cosyntropin stimulation test for confirming diagnosis. If a cosyntropin stimulation test is not planned, give stress doses of hydrocortisone (50-75 mg/m² or 1-2 mg/kg) intravenously as an initial dose and followed by 50-75 mg/m²/d intravenously in 4 divided doses. Hydrocortisone may be given intramuscularly if no intravenous access is available but works less quickly. Comparable stress doses of methylprednisolone are 10-15 mg/m² and of dexamethasone 1-1.5 mg/m² intravenously or intramuscularly.

Methylprednisolone and dexamethasone have negligible mineralocorticoid effects. Therefore, if the patient is hypovolemic, hyponatremic, or hyperkalemic, large doses of hydrocortisone (even double or triple the stress doses mentioned above) are preferred. At the present time, no parenteral form of mineralocorticoid is available in the United States. If the patient has good GI function, fludrocortisone (0.1-0.2 mg orally) may be given to replace aldosterone deficiency.

In hypotensive patients, normal saline (ie, 0.9% NaCl) must be administered by rapid intravenous infusion over the first hour followed by a continuous infusion. A reasonable amount to restore intravascular volume is 450 mL/m² or 20 mL/kg of normal saline intravenously over the first hour, followed by 3200 mL/m²/d or 200 mL/kg/100 kcal of estimated resting energy expenditure as normal saline or 0.45% NaCl in subsequent hours. Dextrose must also be provided. If the patient is hypoglycemic, 2-4 mL/kg of D10W corrects it. D5W must be provided to prevent further hypoglycemia or to prevent hypoglycemia from occurring if the patient is not hypoglycemic. Potassium is generally not needed in the acute situation, especially because patients with adrenal hypoplasia are often hyperkalemic.

Chronic medical therapy

In growing children with adrenal insufficiency, chronic glucocorticoid replacement must be balanced to prevent symptoms of adrenal insufficiency, while still allowing the child to grow at a normal rate and prevent symptoms of glucocorticoid excess. The dose must be tailored to each patient but generally runs in the range of 7-20 mg/m²/d of hydrocortisone orally in 2-3 divided doses. Hydrocortisone is available as tablets of 5 mg, 10 mg, and 20 mg. Hydrocortisone is recommended in the pediatric population because of its lower potency, which permits easier titration of appropriate doses. In large patients, prednisone or even dexamethasone may be substituted. The estimated equivalency is 1 mg prednisone = 4 mg hydrocortisone and 1 mg dexamethasone = 50 mg hydrocortisone, but this varies from patient to patient.

Patients with congenital adrenal hypoplasia also have mineralocorticoid deficiency and, therefore, must be provided with fludrocortisone (0.1-0.2 mg/d). Provide infants with NaCl (2-5 g/d PO) to counteract salt wasting. The dose of glucocorticoid is adjusted clinically (absence of symptoms of glucocorticoid deficiency or excess and normal growth).

In the author's experience, plasma adrenocorticotropic hormone (ACTH) concentrations are of little help in adjusting doses of glucocorticoid in patients with primary adrenal insufficiency. Symptoms of salt craving, blood pressure, plasma renin activity, and electrolytes are helpful in adjusting the dose of fludrocortisone. Salt craving and an elevated plasma renin activity suggest the need for a larger dose of fludrocortisone, whereas elevated blood pressure or suppressed plasma renin activity suggests the need for a lower dose of fludrocortisone.

Stress and illness

One of the important physiological responses to stress is an increase in cortisol production mediated by ACTH. Patients with adrenal insufficiency, of whatever etiology, are unable to mount this response and must be provided with stress doses of glucocorticoids. In patients with minor illness (fever < 38°C) administer at least double the dose of hydrocortisone. In patients with more severe illness (fever >38°C), administer triple the dose of glucocorticoids. If the patient is vomiting or listless, give parenteral glucocorticoids (hydrocortisone 50-75 mg/m² intramuscularly or intravenously or equivalent of methylprednisolone or dexamethasone).

Because hydrocortisone succinate has a short duration of action, the dose must be repeated every 6-8 hours until the patient is well. Cortisone acetate and hydrocortisone acetate both have a longer duration of action (up to 24 h) but are often difficult to obtain in the United States. All patients with adrenal insufficiency must have injectable glucocorticoid available, and the caretaker must be instructed in its use and importance.

Hydrocortisone suppositories may be tried in patients or families who cannot administer injectable glucocorticoids. However, absorption is less predictable.

No contraindications to glucocorticoid or mineralocorticoid replacement are recognized when it is needed, and few adverse drug-to-drug interactions occur.

Patients on physiologic replacement doses of glucocorticoids may receive live virus immunizations.

Class Summary

This agent is responsible for the replacement of aldosterone deficiency. It is essential in maintaining electrolyte equilibrium and intravascular volume. Mineralocorticoid deficiency results in hyponatremia, hyperkalemia, and hypotension.

Fludrocortisone acetate (Florinef)

The only available mineralocorticoid. It is only available PO in 0.1 mg tablets. If unable to tolerate PO medication, mineralocorticoid activity can be achieved with high-dose intravenous hydrocortisone.

Class Summary

These agents are used to replace insufficient cortisol production resulting from adrenal hypoplasia. This is necessary in unstressed children to maintain appetite and weight. It is especially important in individuals who are stressed or ill because cortisol secretion is an important stress response. In this setting, glucocorticoids are important in maintaining cardiovascular stability.

Hydrocortisone (A-Hydrocort, Cortef, Solu-Cortef)

This is preferable to other glucocorticoids (ie, prednisone, dexamethasone) for long-term glucocorticoid replacement in children because its lower potency and shorter half-life make growth inhibition less likely as a complication, provided the dose is correct. Hydrocortisone is available in tablets of 5 mg, 10 mg, and 20 mg.