eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Adrenal Hypoplasia: Treatment & Medication
Updated: Feb 18, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- Patients with adrenal hypoplasia are generally hypovolemic and may be hypoglycemic; therefore, initial therapy should consist of intravenous normal saline and dextrose.
- If hypotensive, a bolus dose of 20 mL/kg of isotonic intravenous fluid over the first hour may be necessary to restore blood pressure. This can be repeated if the blood pressure remains low.
- Once samples for serum electrolytes, blood sugar, cortisol, 17-hydroxyprogesterone, and adrenocorticotropic hormone (ACTH) concentrations are obtained, treat the patient with glucocorticoids. This therapy is based on suspicion of adrenal insufficiency because it may be life preserving.
- A cosyntropin stimulation test confirms the diagnosis of adrenocortical insufficiency.
- Dexamethasone may be given prior to the cosyntropin without interfering with the results of the test because acute administration of dexamethasone does not interfere with the cortisol response or with the cortisol assay. Otherwise, hydrocortisone is preferable because of its mineralocorticoid activity.
Surgical Care
- Surgery is not necessary in the management of congenital adrenal hypoplasia; however, a patient requiring surgery must be covered with stress doses of glucocorticoids during the perioperative period.
- The following recommendations are empiric rather than evidence-based:
- Administer 50-75 mg/m2 hydrocortisone intramuscularly or intravenously on call prior to surgery.
- During the procedure, treat the patient with additional hydrocortisone. This may be accomplished with either a hydrocortisone drip of 2-4 mg/m2/h, or as an additional bolus of 10-25 mg/m2 intravenously every 6 hours throughout the procedure.
- Continue hydrocortisone in the immediate postoperative period.
- On the second and third postoperative day, the dose of hydrocortisone can be decreased by 50% each day, to a minimum of the patient's usual daily requirement, provided no complications exist and the patient is recovering well.
- By the fourth postoperative day, the usual daily dose of steroids may be resumed if the patient is recovering well. If complications occur, stress doses of glucocorticoids must be continued.
- Fludrocortisone may be held on the day of surgery and while the patient is receiving stress doses of hydrocortisone because this high dose should provide ample mineralocorticoid effect.
- If the patient is unable to take fludrocortisone by mouth in the postoperative period, stress doses of hydrocortisone may be continued for a longer period to provide adequate mineralocorticoid activity.
Consultations
- Endocrinologist when adrenal insufficiency is suspected
- Geneticist for genetic diagnosis and counseling
Diet
- Patients should not be on a sodium-restricted or fluid-restricted diet.
- Patients should have ample access to salt since patients are deficient in aldosterone secretion and, therefore, are generally salt wasters.
- Monitor and restrict caloric intake if excess weight gain occurs on therapy because glucocorticoids stimulate appetite and weight gain.
Activity
- After appropriate glucocorticoid and mineralocorticoid therapy is instituted, no restrictions on activity are necessary.
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.
Mineralocorticoid
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.
Adult
0.1-0.2 mg PO daily
Pediatric
Pediatric doses are similar to adult doses because the aldosterone secretory rate is similar in infants, children, and adults
Usual dose: 0.05-0.2 mg/d PO
Infants may require supplementation with NaCl (2-4 grams/day PO) because infant formulas are low in sodium
Barbiturates, phenytoin, and rifampin can increase hepatic metabolism of fludrocortisone, diminishing its effect; fludrocortisone-induced hypokalemia can enhance digoxin toxicity
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May elevate blood pressure and must be used with caution and good justification in patients with hypertension; adverse effects include hypertension, edema, congestive heart failure, and hypokalemic alkalosis; carefully titrate dose to level of patient tolerance and effectiveness; monitor for dizziness, severe or continuing headaches, swelling of feet or lower legs, or unusual weight gain; administer with food to minimize GI adverse effects
Glucocorticoids
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.
Adult
Daily dose must be administered in divided PO doses bid/tid or divided q6-8h when given IV
Healthy nonstressed individual: Average cortisol secretory rate is 6-10 mg/m2/d
PO therapy generally must be higher because some metabolism of ingested glucocorticoids occurs as they pass through the liver
Daily replacement: Generally about 10-30 mg/d
Equivalent doses of prednisone 2.5-7.5 mg/d
Adjust dose according to the patient's sense of well-being; recurring abdominal pain, anorexia, nausea, and lack of energy indicate the need for a dose increase
Pediatric
Replacement dose: 6-15 mg/m2/d PO divided bid/tid or divided q6-8h when given IV
Excessive doses result in growth suppression; inadequate doses result in fatigue, GI complaints, or asthenia
Live virus immunizations may be provided to patients on physiologic replacement doses of glucocorticoids, higher doses may interfere with live virus vaccine response
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Administer with meals to decrease GI upset; early-onset adverse effects include glucose intolerance, hypertension, agitation, and indigestion; late-onset adverse effects include hypertension, urinary calcium loss and osteopenia, gastric irritation and bleeding
More on Adrenal Hypoplasia |
| Overview: Adrenal Hypoplasia |
| Differential Diagnoses & Workup: Adrenal Hypoplasia |
 Treatment & Medication: Adrenal Hypoplasia |
| Follow-up: Adrenal Hypoplasia |
| References |
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References
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Further Reading
Keywords
adrenal hypoplasia congenita, adrenal insufficiency, congenital adrenal hypoadrenalism, hypoplasia, primary adrenal hypoplasia, hypogonadotropic hypogonadism, Duchenne muscular dystrophy, glycerol kinase deficiency, intrauterine growth retardation, metaphysial dysplasia, hyperglycerolemia, sensorineural deafness, dehydration, hyponatremia, hyperkalemia, hypotension, hypoglycemia, micropenis, hypospadias, cryptorchidism, hearing loss
