Primary Adrenal Insufficiency
Primary Adrenal Insufficiency: Excerpt from The 5-Minute Pediatric Consult
J. Nina Ham, MD
Lorraine E. Levitt Katz, MD
Primary Adrenal Insufficiency - BASICS
Primary Adrenal Insufficiency - description
Deficiency in the secretion of cortisol by the adrenal glands
Primary Adrenal Insufficiency - epidemiology
- Age:
- Addison disease is uncommon in children and usually presents between the ages of 20 and 50 years. In the pediatric population, it is most often seen in late childhood and adolescence.
- Adrenoleukodystrophy typically presents late in the 1st decade of life with neurologic symptoms. Signs and symptoms of adrenal insufficiency may present at any age.
- Adrenocorticotropic hormone (ACTH) unresponsiveness presents in late infancy or the toddler period.
- Adrenal hypoplasia congenita presents in infancy or early childhood.
- Adrenal insufficiency associated with congenital adrenal hyperplasia (CAH) presents in the newborn period.
- Sex:
- Addison disease is more common in girls.
- Adrenoleukodystrophy, an X-linked disorder, predominantly affects boys.
- ACTH unresponsiveness affects both sexes equally.
- Adrenal hypoplasia congenita, an X-linked disorder, predominantly affects boys.
Primary Adrenal Insufficiency - risk factors
Primary Adrenal Insufficiency - genetics
- Addison disease:
- Autoimmune adrenal insufficiency may be isolated or part of autoimmune polyglandular syndromes (APS) type 1 and 2. Familial and sporadic cases have been reported. Mutations in the AIRE1 gene have been identified as the cause of APS type 1. An association exists between idiopathic Addison disease and human leukocyte antigen (HLA)-138 and -Dw3.
- Adrenoleukodystrophy:
- X-linked recessive disorder of very long chain fatty acid metabolism
- An autosomal-recessive form of the disease exists, with presentation during infancy.
- ACTH unresponsiveness: Autosomal recessive ACTH receptor defect
- Adrenal hypoplasia congenita: X-linked mutation in DAX1 gene
- CAH: Autosomal recessive inheritance
Primary Adrenal Insufficiency - pathophysiology
- Addison disease:
- Primary hypoadrenalism owing to bilateral destruction of the adrenal cortices; this can be due to autoimmune destruction (isolated or as part of polyendocrine autoimmune syndromes), tuberculosis, hemorrhage, fungal infection, neoplastic infiltration, or AIDS.
- Adrenoleukodystrophy:
- Inherited disorders of impaired peroxisomal degradation of very long chain fatty acids, resulting in adrenal insufficiency and progressive neurologic deterioration
- ACTH unresponsiveness:
- Inherited defect in the ACTH receptor, resulting in isolated glucocorticoid deficiency with hypoglycemia in infancy and hyperpigmentation
- Adrenal hypoplasia congenita: A defect in adrenal organogenesis
- CAH: A group of enzymatic disorders of steroid metabolism, of which 21-hydroxylase deficiency is the most common
- Waterhouse–Friderichsen syndrome: Bilateral adrenal gland hemorrhage classically associated with fulminant meningococcemia, but also reported with Staphylococcus aureus and Streptococcus pneumoniae.
Primary Adrenal Insufficiency - associated conditions
- Deficiencies of other hormones, including aldosterone and adrenal androgens
- Adrenal hypoplasia congenita (DAX1 mutation) is associated with hypogonadotropic hypogonadism.
- APS are associated with other autoimmune disorders:
- APS type 1: Mucocutaneous candidiasis hypoparathyroidism
- APS type 2: Autoimmune thyroid disease, type 1 diabetes
- Both types can also present in conjunction with multiple other autoimmune disorders, e.g., pernicious anemia, vitiligo
Primary Adrenal Insufficiency - DIAGNOSIS
Primary Adrenal Insufficiency - signs & symptoms
The symptoms of primary adrenal insufficiency are nonspecific and similar to those found in many disease processes. The electrolyte picture of adrenal insufficiency can be seen in renal disorders, obstructive uropathy, and isolated aldosterone deficiency.
- Weakness and fatigue
- Anorexia, weight loss
- Headache
- Nausea, vomiting, diarrhea, abdominal pain
- Orthostatic symptoms
- Muscle or joint pains
- Emotional lability
- Salt craving
- Hyperpigmentation
- Decreased axillary or pubic hair in females owing to lack of adrenal androgens
- Amenorrhea in females
Primary Adrenal Insufficiency - physical exam
- Hyperpigmentation, especially on lip borders, buccal mucosa, nipples, and over skin creases
- Weight loss
- Hypotension
- Evaluate for other signs of autoimmune disease (e.g., thyromegaly, vitiligo).
- Pubertal staging
- Signs of virilization in females
Primary Adrenal Insufficiency - tests
Specific:
- Cosyntropin (Cortrosyn) stimulation test: Administer cosyntropin (synthetic ACTH) 250 mcg IV and measure cortisol at 30 and 60 minutes. A normal response is a final cortisol >18 mcg/dL. An insufficient cortisol response is diagnostic of adrenal insufficiency:
- A baseline ACTH >200 pg/mL with inadequate cortisol is seen in primary adrenal insufficiency.
- Serum adrenal antibodies may be positive in autoimmune Addison disease.
- Very long chain fatty acids are elevated in adrenoleukodystrophy.
- Low gonadotropin and sex steroid levels suggesting hypogonadotropic hypogonadism may be seen with adrenal hypoplasia congenita.
- Adrenal steroid precursors will be elevated in CAH.
Primary Adrenal Insufficiency - lab
Nonspecific:
- Electrolytes:
- Hyponatremia: Result of the mineralocorticoid defect and glucocorticoid deficiency; combination sodium loss from kidneys, and the inability to excrete a water load
- Hyperkalemia and acidosis: Chronic mineralocorticoid deficiency with the inability to excrete potassium and acid
- Hypercalcemia: Most likely a result of increased calcium absorption owning to the lack of glucocorticoid effect on the gut
- Hypoglycemia: Glucocorticoids have permissive effects on gluconeogenesis.
- Renin levels are elevated when a mineralocorticoid deficiency is present.
Primary Adrenal Insufficiency - differencial diagnosis
- Autoimmune adrenal cortical destruction
- Infectious adrenal cortical destruction:
- Adrenal hemorrhage
- Neoplastic adrenal infiltration
- Adrenoleukodystrophy
- ACTH unresponsiveness
- Adrenal hypoplasia congenita
- CAH
Primary Adrenal Insufficiency - TREATMENT
Primary Adrenal Insufficiency - initial stabilization
- Acute adrenal crisis:
- An intercurrent illness or surgical procedure may provoke an episode of hypotension, tachycardia, and shock. Electrolytes reveal decreased serum sodium, elevated potassium, metabolic acidosis, and a decreased or normal glucose. Serum should be drawn and saved to aid in diagnosis, but treatment should not be delayed for a diagnostic Cortrosyn stimulation test.
- Treatment:
- 5% dextrose in normal saline solution (D5NS) for volume repletion and treatment of salt wasting
- Hydrocortisone
- Mineralocorticoid replacement
Primary Adrenal Insufficiency - general measures
Chronic adrenal insufficiency:
- Hydrocortisone for stress of fever, illness, vomiting
- Fludrocortisone acetate (Florinef): Mineral corticoid agent
- Patient education
Primary Adrenal Insufficiency - special therapy
Primary Adrenal Insufficiency - iv fluids
D5NS for volume repletion and treatment of salt wasting
Primary Adrenal Insufficiency - medication
- Acute adrenal crisis:
- Hydrocortisone: Stress dosage of hydrocortisone: 100 mg/m2 followed by 100 mg/m2/24 hours of hydrocortisone divided q4h. Taper steroids over the next 1–2 days to a physiologic replacement dosage.
- Mineralocorticoid replacement: Florinef 0.1 mg daily when able to take PO
- Chronic adrenal insufficiency:
- Hydrocortisone 10–12 mg/m2/d PO divided as t.i.d. Triple the dose for stress of fever, illness, or vomiting. For major stress (surgery, significant illness), give hydrocortisone 50–100 mg/m2 followed by 50–100 mg/m2/24 hours IV divided q4h. Intramuscular (IM) hydrocortisone is recommended for emergency home use.
- Florinef 0.1 mg PO daily
Primary Adrenal Insufficiency - FOLLOW UP
An acute adrenal crisis usually improves rapidly with the administration of fluids and glucocorticoids. Steroids can usually be tapered in 12 days.
Primary Adrenal Insufficiency - prognosis
- Long-term prognosis of isolated adrenal insufficiency is good, provided adequate hydrocortisone is administered, particularly in times of illness.
- Adrenoleukodystrophy carries a poor prognosis.
Primary Adrenal Insufficiency - complications
- If not diagnosed and/or treated properly, a significant physical stress such as surgery or illness may result in a life-threatening adrenal crisis.
- Adrenoleukodystrophy results in severe neurologic impairment and death.
- Unrecognized ACTH unresponsiveness is associated with recurrent hypoglycemia, seizures, mental retardation, and death.
- Pubertal delay or hypogonadotropic hypogonadism is seen with adrenal hypoplasia congenita owing to DAX1 mutations.
- CAH can cause virilization/ambiguous genitalia in female infants with the disease and can cause salt-wasting crises in infants of both sexes.
Primary Adrenal Insufficiency - patient monitoring
- Clinical status
- Reduction in hyperpigmentation
- Electrolytes, ACTH, and renin levels
- Screen for polyautoimmune disorders.
- Growth
- Very long chain fatty acid levels and neurologic function in adrenoleukodystrophy
- Pubertal development
Primary Adrenal Insufficiency - bibliography
- Achermann JC, Meeks JJ, Jameson JL. Phenotypic spectrum of mutations in DAX-1 and SF-1. Mol Cell Endocrinol. 2001;62(2):202–206.
- Adem PV, Montgomery CD, Husain AN, et al. Staphylococcus aureus sepsis and the Waterhouse-Friderichsen syndrome in children. N Engl J Med. 2005;353:1245–1251.
- Anderson MS, Venanzi ES, Klein J, et al. Projection of an immunological self shadow within the thymus by the aire protein. Science. 2002;298:1395–1401.
- Dorin RI, Qualls CR, Crapo LM. Diagnosis of adrenal insufficiency. Ann Intern Med. 2003;139:194–204.
- Perheentupa J. APS-I/APECED: The clinical disease and therapy. Endocrinol Metab Clin North Am. 2002;31(2):295–320.
- Peter M, Viemann M, Partsch CJ, et al. Congenital adrenal hypoplasia: Clinical spectrum, experience with hormonal diagnosis, and report on new point mutations of the DAX-1 gene. J Clin Endocrinol Metab. 1998;83:2666–2674.
- Selva KA, LaFranchi SH, Boston B. A novel presentation of familial glucocorticoid deficiency (FGD) and current literature review. J. Pediatr Endocrinol Metab. 2004;17(1):85–92.
- Speiser PW, White PC. Congenital adrenal hyperplasia. N Engl J Med. 2003;349:776–788.
- Vaidya B, Pearce S, Kendall-Taylor P. Recent advances in the molecular genetics of congenital and acquired primary adrenocortical failure. Clin Endocrinol. 2000;53:403–418.
Primary Adrenal Insufficiency - CODES
Primary Adrenal Insufficiency - icd9
255.4 Primary adrenal insufficiency
Primary Adrenal Insufficiency - PATIENT TEACHING-MED
- Stress dosing
- Importance of seeking medical attention for significant illness, persistent vomiting, or the inability to take fluids by mouth
- MedicAlert bracelet
Primary Adrenal Insufficiency - FAQ
- Q: What are the indications for stress dosing and how rapidly can the stress hydrocortisone dose be tapered?
- A: Patients will require stress dosing of hydrocortisone for surgical procedures, fever (>37.7°C [100°F]), vomiting, diarrhea, and particularly vigorous exercise. The stress dose is typically given for 24 hours, after which the usual dose is resumed. Should it be necessary to administer the stress dosage for a more prolonged period, the dosage can usually be tapered to a physiologic dosage over 12 days, after the patient’s clinical condition has improved.
Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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