eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Familial Glucocorticoid Deficiency: Treatment & Medication

Author: Andrea Haqq, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, Duke University Medical Center
Coauthor(s): Bruce A Boston, MD, Director, Pediatric Endocrine Training Program, Associate Professor, Department of Pediatrics, Division of Pediatric Endocrinology, Oregon Health Sciences University and Doernbecher Children's Hospital
Contributor Information and Disclosures

Updated: Oct 7, 2008

Treatment

Medical Care

Treatment of familial glucocorticoid deficiency (FGD) includes the following:

  • Hypoglycemia
    • Immediate diagnosis and treatment of hypoglycemia is essential. Children with seizures or prolonged recurrent episodes of hypoglycemia are more likely to experience brain damage.
    • When the cause of hypoglycemia is unknown, start an intravenous line and collect 5-10 mL of blood in a heparinized tube.
    • When hypoglycemia is suspected, start treatment without waiting for the results of the blood or plasma glucose tests.
    • In neonates, administer intravenous (IV) 10% dextrose at 2.5 mL/kg as a rapid IV bolus followed by a continuous IV infusion of 3-5 mL/kg/h (5-8 mg glucose per kg/min).
    • In children, administer 50% dextrose diluted to 25% in water at an initial dose of 1 mL/kg IV followed by an IV infusion of 10% dextrose at 2-3 mL/kg/h (3-5 mg glucose per kg/min).
    • If any difficulty in establishing IV access occurs, intramuscularly administer glucagon at 0.03 mg/kg (not to exceed 1 mg). Glucagon therapy has a transient effect and must be followed by an intravenous dextrose infusion as above.
  • Glucocorticoid deficiency
    • Treatment for FGD includes the replacement of glucocorticoids in order to avoid not only adrenal crisis but to allow normal growth in these children. Glucocorticoid replacement is achieved with hydrocortisone (12-16 mg/m2/24h PO divided into 3 doses). An equivalent dose of prednisone or dexamethasone may be administered to adults and the occasional patient who has difficulty with compliance. However, the potential for growth suppression with either prednisone or dexamethasone is greater than hydrocortisone; and, therefore, these agents should be used with caution. Administer the lowest dosage necessary to prevent symptoms of adrenal failure in order to avoid suppression of growth.
    • The adequacy of a treatment regimen may be clinically judged by noting decreased hyperpigmentation, absence of weakness, and normalization of blood sugar values. Adequate glucocorticoid replacement should not cause any adverse effects. Suppression of adrenocorticotropic hormone (ACTH) levels in FGD can be very difficult and, therefore, should not be used as a goal for therapy.
    • Overtreatment may result in poor linear growth, hypertension, edema, euphoria, insomnia, headache, steroid-induced acne, hyperglycemia, Cushing syndrome, peptic ulcers, and cataract formation.
    • Intercurrent illness or stress necessitates a readjustment of glucocorticoid dosage. For minor stress, such as a fever or upper respiratory tract infection, double or triple the glucocorticoid dosage until the illness has resolved. If the patient is ill with vomiting or diarrhea and cannot tolerate oral fluids and medication, hospitalization may be necessary. In individuals with severe stress, such as surgery or serious illness, the daily requirement for parenteral hydrocortisone is 40-100 mg/m2/24h (approximately 3-10 times the maintenance dose) in 3-4 divided doses.
    • With a major decline in the clinical condition of the patient (eg, development of hypotension, fever, decreasing mental status, acute intercurrent illness), promptly initiate treatment for possible adrenal crisis even before the diagnosis is confirmed.
    • The treatment of an adrenal crisis includes fluid, dextrose, and glucocorticoid replacement in order to restore fluid volume and prevent hypoglycemia and death. Adequately treat any precipitating event such as an infection.
    • Fluids administered (eg, 0.9% NaCl with 5% dextrose) should be administered at 1.5-2 times the maintenance rate (2250-3000 mL/m2/d). If the patient presents in shock, administer 0.9% NaCl (10-20 mL/kg) during the first hour of treatment. In addition, cortisol as a soluble ester (21-hemisuccinate or 21-phosphate) must be administered as an immediate IV bolus and every 6 hours (25 mg for infants; 50 mg for small children; 100-150 mg for larger children or adolescents).
    • Once the clinical condition improves, gradually taper down the steroid dosage by one third every day until the patient is back to maintenance dose.
    • All patients with FGD on replacement glucocorticoid therapy must be instructed on appropriate sick day management to adjust steroid dosage and taught how to administer parenteral hydrocortisone at home in cases of severe stress or when oral intake is compromised, and they should be provided a 24-hour physician contact number in case of emergency.
    • All patients with FGD should wear a MedicAlert bracelet outlining their condition and medical treatment. Because of the rarity of this condition, provide families with a physician letter outlining FGD and its potential complications and treatments to present to an emergency care facility if a visit to the emergency department becomes necessary.
  • Achalasia and alacrima
    • In those cases of FGD associated with achalasia and alacrima, these conditions should be carefully monitored and managed.
    • See Allgrove (AAA) Syndrome for full details.

Surgical Care

FGD associated with achalasia and Allgrove syndrome (AS) requires surgical intervention (see Allgrove (AAA) Syndrome).

Consultations

  • Geneticist
    • Counsel patients with FGD and their families regarding the inheritance pattern of FGD, which is autosomal recessive.
    • Observe siblings and other close relatives for potential symptoms of FGD.
    • Screen family members with a Cortrosyn stimulation test to exclude this condition, which is potentially fatal if unrecognized and untreated.
    • Some cases of FGD have been associated with mutations in the MC2R gene. Confirming this diagnosis by DNA analysis may be possible in some cases.
  • Other consultations: In individuals with FGD associated with alacrima, achalasia, or AS, other consultations are warranted, including an ophthalmologist to assess alacrima and a neurologist to assess development and to address the neurologic manifestations of AS (see Allgrove (AAA) Syndrome).

Diet

In individuals with FGD, the renin-aldosterone axis is normal and no dietary manipulation, such as salt replacement, is needed.

Activity

No restriction of physical activity is necessary in adequately treated cases of FGD. In a small subset of patients with AS and autonomic disturbance, some activities may need to be limited because of problems, including recurring postural hypotension and decreased heart rate variability.

Medication

Glucocorticoids

These are used for physiologic replacement of glucocorticoid deficiency. They elicit anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.


Hydrocortisone (Hydrocortone, Cortef)

DOC because of mineralocorticoid activity and glucocorticoid effects.

Adult

15-20 mg PO every am and 5-10 mg PO every pm

Pediatric

Physiologic replacement: 12-16 mg/m2/d PO divided tid
Mild illness (fever, URI): Triple the above dose
Severe illness (surgery, serious illness): 40-100 mg/m2/d IV divided tid (4-10 times the physiologic replacement dose)

None when used as physiologic replacement; in higher doses, may decrease effect of live virus vaccines (eg, MMR); CYP450 2D6 and 3A3/4 substrate; corticosteroid clearance may increase with phenytoin, barbiturates, or rifampin treatment or decrease with estrogens; cholestyramine may decrease AUC

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with hypertension, osteoporosis, thromboembolic tendencies, peptic ulcer, and diabetes; avoid overtreatment, which could lead to poor growth and iatrogenic Cushing syndrome


Prednisone (Deltasone, Orasone, Sterapred, Pediapred)

Not first-line drug in children because of concerns of growth suppression. Can be used in cases of severe noncompliance. Replace physiologic dose of hydrocortisone with an equipotent dose of prednisone. Prednisone is 4 times more potent than hydrocortisone.

Adult

2.5-7.5 mg PO qhs

Pediatric

3-4 mg/m2/d PO typical physiologic replacement dose; when replacing hydrocortisone, use equipotent prednisone dose (ie, 1 mg prednisone equipotent to 4 mg hydrocortisone)

None when used as physiologic replacement; may decrease effect of live virus vaccines (eg, MMR); CYP450 2D6 and 3A3/4 substrate; corticosteroid clearance may increase with phenytoin, barbiturates, or rifampin treatment or decrease with estrogens; cholestyramine may decrease AUC

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with hypertension, osteoporosis, thromboembolic tendencies, peptic ulcer, and diabetes; avoid overtreatment, which can lead to poor growth and iatrogenic Cushing syndrome

More on Familial Glucocorticoid Deficiency

Overview: Familial Glucocorticoid Deficiency
Differential Diagnoses & Workup: Familial Glucocorticoid Deficiency
Treatment & Medication: Familial Glucocorticoid Deficiency
Follow-up: Familial Glucocorticoid Deficiency
References
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References

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Further Reading

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Keywords

familial glucocorticoid deficiency, FGD, adrenocorticotropic hormone, ACTH, unresponsiveness, Allgrove syndrome, AS, hypoglycemia, hyperpigmentation, pallor, sweating, palpitations, anxiety, shakiness, hunger, abdominal symptoms, vision changes, jitteriness, respiratory distress, cyanosis, apnea, hypotonia, seizures, ambiguous genitalia, congenital adrenal hyperplasia, cutaneous candidiasis, polyglandular autoimmune syndrome, adrenoleukodystrophy, Wolman disease, distal motor neuropathy, distal sensory neuropathy, dysarthria, ataxia, Parkinsonian disease features, mild dementia, developmental delay, optic atrophy

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Contributor Information and Disclosures

Author

Andrea Haqq, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, Duke University Medical Center
Andrea Haqq, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Coauthor(s)

Bruce A Boston, MD, Director, Pediatric Endocrine Training Program, Associate Professor, Department of Pediatrics, Division of Pediatric Endocrinology, Oregon Health Sciences University and Doernbecher Children's Hospital
Bruce A Boston, MD is a member of the following medical societies: Alpha Omega Alpha, American Diabetes Association, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

Thomas A Wilson, MD, Professor of Clinical Pediatrics, Department of Pediatrics; Director of Pediatric Endocrinology, Division of Pediatric Endocrinology, Department of Pediatrics, State University of New York at Stony Brook
Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

George P Chrousos, MD, FAAP, MACP, MACE, Professor and Chair, Department of Pediatrics, Athens University Medical School
George P Chrousos, MD, FAAP, MACP, MACE is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfiser, Inc. Honoraria Consulting

 
 
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