Familial Glucocorticoid Deficiency 

Updated: Feb 16, 2019
Author: Andrea Haqq, MD; Chief Editor: Sasigarn A Bowden, MD 

Overview

Practice Essentials

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive condition.[1, 2]  Pathologic evaluation of children affected with this disorder reveals that the zona glomerulosa of the adrenal glands is well preserved. The zona fasciculata and zona reticularis are markedly atrophic. These changes are accompanied by low plasma cortisol concentrations because the zona fasciculata is primarily responsible for glucocorticoid production. Low circulating serum cortisol results in a lack of feedback inhibition to the hypothalamus; markedly increased adrenocorticotropic hormone (ACTH) levels are often observed. Because the zona glomerulosa is generally well preserved, mineralocorticoid production is usually unaffected. Plasma renin and aldosterone concentrations are usually within the reference range in the baseline state and demonstrate normal variability on salt restriction.

Deep hyperpigmentation of the skin is the most common initial presenting sign and is almost always present at diagnosis. The hyperpigmentation is due to the action of ACTH on cutaneous melanocyte-stimulating hormone (MSH) receptors. This hyperpigmentation fades once proper treatment is initiated with glucocorticoids, which reduce ACTH concentrations.

Molecular defects of the ACTH receptor gene, consisting of point mutations, are described in approximately 25-40% of patients with FGD. Mutations in the MC2 receptor accessory protein (MRAP) are responsible for another estimated 15-20% of cases of FGD.[3, 4]  The remainder (approximately 50-60%) of patients with FGD have unknown mutations; these mutations may affect ACTH signal transduction, expression of the ACTH receptor, or differentiation of the adrenal cortex. The pathogenesis of Allgrove syndrome (AS), another distinct clinical entity, is due to a defect in a WD-repeat regulatory protein named for alacrima-achalasia-adrenal insufficiency neurologic (ALADIN) disorder.[5]

Mutations have also been identified in mini chromosome maintenance-deficient 4 homologue (MCM4), which is involved in DNA replication, and nicotinamide nucleotide transhydrogenase (NNT), which is involved in antioxidant defense.[2]

Clinically judge the adequacy of glucocorticoid treatment by documenting reduced hyperpigmentation, absence of hypoglycemia and weakness, and normal growth at frequent follow-up visits. Administer the lowest dosage of glucocorticoid sufficient to control symptoms of adrenal insufficiency to permit normal growth in these patients.

Patients with FGD have a lifelong loss of adrenal function. They remain at risk of adrenal insufficiency during periods of stress when the adrenal gland normally secretes more hormones. If patients receive adequate glucocorticoid replacement and are properly educated regarding readjustment of medication during times of illness and stress, they should have a normal lifespan and be able to have children of their own.

Epidemiology

Familial glucocorticoid deficiency (FGD) is a rare disease, and only isolated case reports are documented. The incidence of FGD may be underestimated because some patients may have episodes of recurring hypoglycemia or convulsions, but FGD may remain undiagnosed for many years.

The most frequent cause of FGD death is undiagnosed glucocorticoid insufficiency. Although this disease is easily treatable when recognized, if left untreated it may be fatal or lead to severe mental disability as a result of recurrent hypoglycemia secondary to glucocorticoid insufficiency. Of more than 50 cases, 18 patients died as a result of glucocorticoid insufficiency.

In early life, patients have feeding problems characterized by chronic spitting or vomiting and poor appetite. As a result, some patients may also experience poor weight gain. Hypoglycemic seizures secondary to glucocorticoid deficiency are a frequent complication of this disorder when inadequate treatment is provided. Finally, deep hyperpigmentation of the skin is the most common initial presenting sign and is almost always present at diagnosis. The hyperpigmentation is due to the action of ACTH on cutaneous melanocyte-stimulating hormone (MSH) receptors. This hyperpigmentation fades once proper treatment is initiated with glucocorticoids, which reduce ACTH concentrations.

Cases of the condition have been reported in white, black, East Indian, and Middle Eastern populations. FGD is a rare autosomal recessive condition with no racial predilection.

In many case reports in the literature, age of onset of symptoms ranges from birth to 9 years. Patients almost always present with symptoms by age 5 years. Patients usually present with onset of symptoms in the first year of life but may present in early childhood. In an analysis of the current medical literature, approximately 50% of cases occurred in the first year of life.

Patient Education

Educate patients regarding readjustment of glucocorticoid dosage during intercurrent illness or stress and during minor stress. Regarding fever or upper respiratory tract infections, double or triple the dosage of glucocorticoid until the illness is resolved.

Advise parents and/or caregivers to contact their pediatric endocrinologist if vomiting or diarrhea is present and the child cannot tolerate oral fluids and medication. They may be instructed to administer a prefilled Solu-Cortef syringe intramuscularly in a dose appropriate for the size of the patient. Alternatively, hospitalization may be required in this situation.

In cases of major stress, such as surgery or serious illness, advise parents to contact their pediatric endocrinologist. As a life-saving measure, parents may need to administer a prefilled Solu-Cortef syringe intramuscularly if medical assistance is not immediately available. Following this, advise parents to arrange transfer of their child to the hospital.

In serious illness, the daily requirement of parenteral hydrocortisone is 40-100 mg/m2 (approximately 4-10 times the maintenance dose) in 3 or 4 divided doses. Advise all patients with FGD to 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 should a visit to the emergency department be necessary. Counsel patients, families, and/or caregivers regarding the importance of compliance in taking this life-sustaining medication; this medication should never be stopped in any circumstance.

Counsel patients with FGD and their families regarding the autosomal recessive inheritance pattern of FGD.

Monitor siblings and close relatives for potential symptoms of FGD; obtain appropriate laboratory screening to rule out this condition, which is potentially fatal if left untreated.

 

Presentation

History

Focus the history on symptoms compatible with glucocorticoid deficiency such as hypoglycemia and shock. Children with hypoglycemia can present with pallor, sweating, palpitations, anxiety, shakiness, hunger, abdominal symptoms, vision changes, or changes in mental status such as confusion, mood changes, lethargy, seizures, and coma. In newborns, symptoms of hypoglycemia can be subtle; a high index of suspicion is needed. Newborns can present with irritability, jitteriness, respiratory distress, cyanosis, apnea, hypotonia, or seizures. A history of failure to thrive, poor feeding, absence of weight gain, lethargy, and recurrent or severe infections due to glucocorticoid deficiency suggest familial glucocorticoid deficiency (FGD). A positive family history of consanguinity or early unexplained infant deaths or other affected family members supports a diagnosis of FGD.

Patients with FGD generally present with signs and symptoms of adrenal insufficiency with the important distinction that mineralocorticoid production is always normal. The most common initial presenting sign is deep hyperpigmentation of the skin,[6] mucous membranes, or both as a result of the action of adrenocorticotropic hormone (ACTH) on cutaneous melanocyte-stimulating hormone (MSH) receptors. Many patients present with recurrent hypoglycemia or severe infections, although these are not the most common initial presenting signs. In the neonatal period, frequent presenting signs include feeding problems, failure to thrive, regurgitation, and hypoglycemia manifesting as seizures. The hypoglycemia-related seizures may be fatal. Finally, hypoglycemia, lethargy, seizures, shock, or sudden death may be the initial presentation in early childhood. Some children present with tall stature.

Physical

Distinguish FGD from other disorders that cause adrenal insufficiency.

Positive findings

Focus the physical examination of individuals with FGD on eliciting signs of ACTH excess and glucocorticoid deficiency. The most striking physical examination finding may be the presence of excess pigmentation of skin, areolae, genitalia, and mucous membranes. The deep pigmentation of the skin is the result of the action of ACTH on cutaneous MSH receptors.

Signs of isolated glucocorticoid deficiency may be present on physical examination. These include lethargy, decreased level of consciousness, and muscle weakness. Blood pressure and hemodynamic status may be preserved in these patients because of normal mineralocorticoid function.

Tall stature, advanced bone age, or both have been described in some children with FGD. Not all patients with the same ACTH receptor mutation manifest tall stature. To date, growth hormone levels and adrenal androgens have been within the reference range in these children. At this time, the mechanism for this increase in height and advanced bone age in FGD is unknown. Possible explanations for this phenomenon have included an effect of elevated ACTH levels on the MSH receptors in cartilaginous growth plates or an effect of excess ACTH stimulating estradiol synthesis or acting on bone growth factors such as aromatase. For example, a patient with FGD type 2 and an elevated estradiol level that was related to the increase in plasma ACTH has been described. Alternatively, the anabolic properties of growth hormone unopposed by cortisol may result in this increase in height.

Negative findings

Negative findings include the following:

  • Absence of ambiguous genitalia or congenital adrenal hyperplasia

  • Absence of cutaneous candidiasis or polyglandular autoimmune syndrome

  • Absence of alacrima and achalasia or Allgrove syndrome (AS)

  • Neurologic signs such as observed in AS, adrenoleukodystrophy, and Wolman disease

  • Absence of adrenarche is a feature typical of children with FGD

An important distinction should be made between FGD and AS (AAA syndrome), another rare autosomal recessive disease. Although both of these syndromes are characterized by glucocorticoid deficiency, AS has the additional features of alacrima (absence of tears), achalasia of the cardia, and a wide spectrum of neurologic abnormalities. AS is discussed in Allgrove (AAA) Syndrome.

Causes

Patients with FGD present with an isolated defect in glucocorticoid production. Because ACTH levels are in fact elevated, the apparent defect was hypothesized to be signaling either in the ACTH receptor or in post–ACTH receptor mechanisms. Alternatively, an isolated defect in the development of the adrenal zona fasciculata can also result in isolated deficiency of glucocorticoid production.

DNA analysis of all patients with FGD has demonstrated that only about 25-40% of these patients have mutations in the ACTH receptor gene. Dividing FGD into the following subcategories has been proposed: type 1 (with ACTH receptor mutations), type 2 (with mutations in the MC2 receptor accessory protein [MRAP] but a normal ACTH receptor), and type 3 and others.[7]

Mutations have also been identified in mini chromosome maintenance-deficient 4 homologue (MCM4), which is involved in DNA replication, and nicotinamide nucleotide transhydrogenase (NNT), which is involved in antioxidant defense.[2]

Allgrove syndrome is a completely separate entity. The presence of mineralocorticoid deficiency in some cases of AS, frequent association with progressive and variable neurologic impairment, and different underlying genetic etiology clearly distinguish AS from FG

Type 1 FGD is associated with ACTH receptor mutations (approximately 25-40% of FGD cases). Mountjoy et al reported the cloning of the human ACTH receptor in 1992.[8] Defects in the ACTH receptor, a small G protein–coupled receptor, have been described in families and individuals in whom a clinical diagnosis of FGD has been suspected. In 1993, Clark et al were the first to report a point mutation (S741) in the human ACTH receptor that resulted in a serine substitution for the normal amino acid at site 741 in a male proband of an FGD family.[9] A similar defect was found in an affected sister and a normal sequence in an unaffected brother. Both parents were heterozygous for this defect. This mutation segregated with the disease in an autosomal recessive fashion. Furthermore, this mutation was found to decrease the ability of ACTH to bind to the ACTH receptor in vivo.

Several other human ACTH receptor point mutations have been functionally characterized. Several classes of defects were observed. Most of these mutations caused a decrease in the ability of ACTH to bind to the ACTH receptor.

Other mutations were found to not only decrease the ability of ACTH to bind to the ACTH receptor (MC2R) but also to lead to defects in downstream signal transduction. For example, several MC2R mutations that cause loss of ligand binding (D103N, D107N, I118fs, T159K, I44M, C251F), structural disruption (S741, S120R, T159K, P273H, A126S), impairment of disulfide bonds (C251F, T254C), truncated receptor (1052delC, 1272delTA, R201X, 1347insA, L192fs, G217fs, F119fs), or loss of signal transduction (I44M, R128C, R146H, V142L, R137W, G116V) have been described. At least two compound heterozygous mutations in the ACTH receptor have now been reported (S74I and T159K; C21Y and R146H).

A poor correlation between severity of gene defect and clinical phenotype has been observed.

Even with identical mutations of the human MC2R, considerable variation in clinical phenotype is observed. In general, correlation was poor between the estimated severity of the receptor defect in vitro and the age at clinical presentation and disease severity, as judged by basal and stimulated plasma cortisol levels.

When the clinical characteristics of FGD associated with an ACTH receptor mutation were compared with FGD associated with no known mutation, no significant differences were observed in either the age of presentation of the patients or in the symptoms present at diagnosis. In addition, cortisol values were comparable between these two subtypes. The only significant difference found between the two subtypes was a difference in the stature of these patients. All the patients presenting with above-average height standard deviation scores originated from the FGD ACTH receptor mutation–positive group. All measurements of growth hormone and insulin-like growth factor 1 (IGF-1) in these patients have been within the reference range to date.

Type 2 FGD is due to mutations in MRAP (approximately 15-20% of FGD cases). As a result of studying many families with FGD, mutations within the coding region of the ACTH receptor are recognized to account for the underlying defect in only some cases. That raised the possibility that defects may be located in the regulatory region of the ACTH receptor or that defects occur in other genes, such as cofactors of the ACTH receptor.

Metherall and colleagues conducted a whole-genome scan by microarray analysis of single nucleotide polymorphisms (SNPs) using genomic DNA from parents, affected children, and unaffected siblings who manifest FGD type 2.[10, 11] A single candidate region emerged at chromosome 21q22.1, with a maximum load score of 2.64. Further analysis identified a gene localized to this interval and expressed in the adrenal cortex. This gene has now been renamed MRAP. The MRAP gene consists of 6 exons and alternative splicing of exon 5 or 6 gives rise to two protein isoforms of 19 kDa and 14.1 kDa, respectively.

Mutations in MRAP have now been identified in families with FGD type 2 (approximately 15-20% of FGD cases). At least 8 different mutations in MRAP have been documented in these patients.

In vitro analysis further shows that MRAP and MC2R interact physically and are both colocalized in the endoplasmic reticulum and plasma membrane. Furthermore, MRAP is required for MC2R expression in certain cell types, suggesting that MRAP plays a role in processing, trafficking, or function of the MC2R.

Type 3 and type 4 FGD are due to additional genes.

Other possible candidate genes might include the following:

  • Genes involving ACTH signal transduction. Because many of these genes are fundamental mediators of signal transduction in multiple tissues, a mutation that would cause a disorder restricted to only the adrenal gland seems unlikely.

  • Gene-specific transcription factors or translational regulators affecting ACTH receptor expression. The further characterization of the ACTH receptor promoter will eventually shed light on this possibility.

  • Genes coding for differentiation factors of the adrenal cortex.

  • Linkage of genes on chromosome 8q to FGD has been described, implicating another gene in this disorder.

AS or AAA syndrome is associated with alacrima and achalasia. First described in 1978 by Allgrove et al,[12] AAA syndrome is characterized by glucocorticoid deficiency, alacrima, achalasia of the cardia, and a wide spectrum of neurologic abnormalities. Alacrima is often manifest at birth, and patients may present with conjunctival injection and irritation. If alacrima is unrecognized, it may lead to severe keratopathy and corneal melting (dehydration-induced ulceration). Achalasia is a neuromuscular disorder of the esophagus resulting in elevated lower esophageal sphincter (LES) pressure, incomplete relaxation of the LES, and aperistalsis of the body of the esophagus. In childhood, achalasia may result in complications of severe lung disease, growth retardation, and respiratory death. However, not all children with achalasia have AS.

In one study, 1 out of the 35 children with achalasia had AS.[13] Other neurologic abnormalities have been associated with AS, including distal motor and sensory neuropathy, dysarthria, ataxia, Parkinsonian disease features, mild dementia, developmental delay, and optic atrophy.

AS is inherited as an autosomal recessive trait. Using genetic linkage analysis, a causative locus was identified on chromosome 12q13. The AAA gene identified at this locus is called ALADIN and belongs to the WD-repeat family of regulatory proteins. The expression of this gene in neuroendocrine and neuronal structures suggests its role in normal development of the peripheral nervous system and the CNS.

For further details, see Allgrove (AAA) Syndrome.

 

DDx

 

Workup

Laboratory Studies

Patients should receive a baseline 9 am serum cortisol and adrenocorticotropic hormone (ACTH) stimulation test.

Familial glucocorticoid deficiency (FGD) is characterized in laboratory testing by a low or low-normal first morning serum cortisol and markedly elevated ACTH levels in contrast to a normal renin-aldosterone axis. Cortisol levels are typically in the range of less than 10-75 ng/mL (reference range is 50-150 ng/mL), whereas ACTH values are typically in the range of greater than 300-7000 ng/L (reference range is 10-80 ng/L).

The cortisol levels are unresponsive to exogenous ACTH stimulation (Cortrosyn stimulation test).

Plasma results reveal normal very long chain fatty acid (VLCFA) levels, thus ruling out adrenoleukodystrophy.

Serum tests include the following:

  • Test sodium, potassium, aldosterone, and renin levels.

  • Supine and standing renin and aldosterone concentrations are within the reference range in FGD, revealing normal variability in response to salt restriction. Note that although renin and aldosterone levels are typically normal in FGD, rare cases of minor impairment in the renin-aldosterone axis have been reported .

  • The electrolyte abnormalities, including hyponatremia and hyperkalemia, are not usually present. These abnormalities typically characterize other adrenal diseases.

  • FGD is often characterized by low levels of serum dihydroxyepiandrosterone sulphate (DHEAS).

  • Consider a diagnosis of congenital adrenal hyperplasia in any infant with signs of glucocorticoid deficiency. The most common form, 21-hydroxylase deficiency, can be ruled out by reference range 17-hydroxyprogesterone levels. Virilized genitalia may be present in some female infants with congenital adrenal hyperplasia, although this does not occur in FGD.

Patients with adrenoleukodystrophy also present with multiple adrenal hormone deficiencies. VLCFA levels are elevated in adrenoleukodystrophy.

Antiadrenal antibodies can usually be detected in patients with Addison disease (AD), an autoimmune form of adrenal insufficiency, and may be useful in ruling out AD as a diagnostic possibility.

Ophthalmologic examination is indicated when the diagnosis of Allgrove syndrome (AS) is under consideration. AS is characterized by glucocorticoid deficiency, alacrima (absence of tears), achalasia of the cardia, and a wide spectrum of neurologic abnormalities.

Alacrima is determined by a Schirmer test that provides a semiquantitative measure of tearing. In this test, a standardized test strip is placed in the conjunctival sac and wetting of the strip over a 5-minutes interval is determined. Alacrima is defined as less than 10 mm of wetting.

Slit lamp examination and fluorescein staining may be helpful in illustrating corneal pathology secondary to decreased tear production. Should these tests indicate a diagnostic possibility of AS, other investigations are warranted and include barium esophagraphy, esophageal manometry, endoscopy, neurologic evaluation, brainstem auditory evoked response (BAER), and autonomic testing.

For hypoglycemia testing, obtain a CBC count, serum glucose level, and a comprehensive metabolic panel with and without cerebrospinal fluid (CSF) studies for protein, glucose, cell count, and culture. In any patient presenting with seizures, ruling out hypoglycemia as the inciting cause is imperative. In some cases, a lumbar puncture may also be indicated. These investigations are not specific in making a diagnosis of FGD, but they can provide important clues to the etiology of the seizure.

Hypopituitarism can also lead to adrenal insufficiency. If ACTH levels are low in the setting of adrenal insufficiency, clinically evaluate other pituitary hormones with specific laboratory testing.

 

Treatment

Medical Care

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.[14]

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.

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

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.

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).

 

Medication

Medication Summary

For hypoglycemia 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.

For familial glucocorticoid deficiency, treatment 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.

Glucocorticoids

Class Summary

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.

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.