Case 1: A 17 year old single mom brings her first born one week old male infant to your office with a chief complaint of not feeding well. He is described as having one episode of vomiting yesterday and 2 episodes of spitting up with poor feeding today. There is no history of fever, diarrhea or coughing. His urine output is decreased. Perinatal history is positive only for an inconsistent prenatal care. He was born at term weight 3.2 kg. Family history is negative.
Exam: VS are all normal. Weight is 3.0 kg; length is at the 25th percentile. He is sleepy but arousable. When awake, he appears irritable, failing to be consoled by sucking on a pacifier. The anterior fontanel is somewhat sunken but the conjunctivae and the oral mucosa are both moist. Cardiac exam is positive only for a borderline tachycardia. There are no murmurs or extra heart sounds. His abdomen is soft and negative. Genitalia are prepubertal and adequately developed. Both testes are descended. His neurological exam is non-focal and physiologic except as described above. His skin is clear with good turgor and his capillary refill is 3 seconds.
Lab: Na 128, K 6.9, Cl 98, bicarb 18. Blood sugar 70. CBC is unremarkable except for evidence of hemoconcentration. Urinalysis is negative with a specific gravity of 1.025. Lumbar puncture reveals clear fluid with no cells or bacteria on gram stain. CSF glucose is 33, protein 45. A urine Na is ordered and this shows an inappropriately high urine Na of 50. A tentative diagnosis of salt wasting due to adrenal insufficiency and probable congenital adrenal hyperplasia is made. An EKG is normal except for slightly prominent T waves.
The infant is started on IV hydration with D5NS (without potassium). His clinical hydration status improves markedly after a total of 30 cc/kg is infused. After obtaining advice from an endocrinologist, additional blood studies are drawn and the infant is given IV hydrocortisone. A repeat chemistry panel 4 hours later shows a Na 134, K 5.2, Cl 98, bicarb 18, glucose 80.
Case 2: A nine year old female is brought to your office by her parents with a chief complaint of thickened nails. The thickened nails have been present for over six months and have not responded to topical ointments. Two visits to a podiatrist also failed to clear the problem although the nails did temporally improve after filing. She is now increasingly distressed because of an upcoming hula presentation (in her bare feet).
Her past medical history is negative. Review of systems is positive for a tanned complexion (even with only average sun exposure) and for intermittent complaints of lower leg cramps. The leg cramps are, at times, quite painful but resolve spontaneously after 1 to 2 minutes with rest and massage. They occur randomly without an association to increased exercise and were diagnosed by a local practitioner last year as growing pains. Family history shows that both parents are Swedish born, having migrated to the United States just shortly before the patient's birth. There is an older sister, aged 16 years, quite tall and post-menarchal. Her parents and sister have a fair skin complexion. There has been no recent travel.
Exam: VS T37, P80, R25, BP 90/70. Height and weight are both at the 50th percentile. HEENT, cardiac, pulmonary and abdominal exams are non-contributory. Breasts and genitalia are Tanner stage I. Neurological evaluation is physiologic and non-focal. Her complexion is well tanned even in areas that are not sun exposed. Her nails are thickened and brittle (8 of the 10 toenails and 4 of the 10 fingernails) consistent with a fungal process. The nails are not upturning.
Addison's disease is suspected on the basis of the tanned complexion and the onychomycosis. A serum cortisol level is low and an ACTH level is high. Treatment with oral hydrocortisone replacement is initiated.
The adrenal gland is basically composed of a cortex and medulla. The cortex produces glucocorticoids, mineralocorticoids (also known as mineralocorticoids), and small amounts of sex steroids (progestins, androgens). Excess glucocorticoids may result in hyperglycemia and symptoms and signs of Cushing's syndrome. mineralocorticoid excess results in excess sodium retention and potassium depletion. Deficiencies of glucocorticoids and mineralocorticoids result in the opposite conditions. The adrenal medulla produces catecholamines. Adrenal disorders result when the production of any of these hormones is insufficient or in excess.
Adrenocortical insufficiency in pediatric patients is principally the result of two distinct pathophysiologic processes. The first type, and by far the most common in infants, is the salt-losing form of congenital adrenal hyperplasia (CAH) (see first case above). Approximately 95% of CAH is secondary to an inherited, autosomal recessive deficiency of the 21-hydroxylase adrenal enzyme (21-OHase CAH). Less frequent etiologic enzyme defects include deficiencies of 11-OHase and 17-OHase, both associated with hypertension as a result of the abnormal accumulation of adrenal precursor hormones with weak mineralocorticoid activity. The second type of adrenal insufficiency in pediatrics is acquired, typically idiopathic and presents during childhood and adolescence (see second case above). Addison's disease classically refers to idiopathic acquired adrenal insufficiency, but autoimmune and other acquired conditions resulting in adrenal insufficiency are often also referred to as Addison's disease. Less common causes of primary adrenal insufficiency include congenital adrenal hypoplasia (as opposed to hyperplasia), fulminant sepsis, adrenal hemorrhage from various etiologies, inadequate replacement of adrenocortical hormones after surgical removal of adrenal neoplasms, and inappropriate tapering of corticosteroids in children who have received long-term, high dose adrenal glucocorticoid therapy. Additionally, rare forms of adrenal insufficiency result secondarily from a primary ACTH deficiency associated with various pathologic conditions of the hypothalamic-pituitary region.
Infants with 21-OHase CAH classically present with clinical virilization (obvious in females, much less obvious in males), hypotension and mild hypoglycemia from cortisol deficiency, and an associated aldosterone deficiency with a resultant sodium depletion and hyperkalemia. Although the exact pathophysiology for the lack of a normal aldosterone effect is still debatable, the resulting salt-wasting abnormalities can lead to severe life-threatening hyperkalemia, hyponatremia and acidosis. Approximately two-thirds of children with classical 21-hydroxylase deficiency will present clinically with the salt-losing form within the first 2 to 3 weeks of life. A rare condition that may mimic salt-losing congenital adrenal hyperplasia, and which must be considered in the differential diagnosis is pseudohypoaldosteronism. This "functional" aldosterone disorder is caused by a defect at the aldosterone receptor site. Although similarly hyponatremic and hyperkalemic, these latter patients, unlike 21-OHase CAH infants, are not virilized and display contrastingly elevated aldosterone levels and usually normal, or only mildly stress-increased adrenal androgen concentrations (e.g. 17-hydroxyprogesterone, androstenedione and DHEA-S).
Congenital, virilizing, 21-hydroxylase deficiency may be either salt wasting or non-salt-wasting. Infants with the salt-losing type are easier to diagnose and will present to medical attention sooner. Alternatively, infants, especially males, with the non-salt-losing type may be difficult to diagnose since they lack the typical electrolyte abnormalities of salt-losers and may remain unrecognized for years until clinical signs of excess early virilization become evident.
The basic biochemical pathway within the adrenal cortex converts cholesterol to aldosterone, cortisol and adrenal androgens. ACTH stimulates this pathway and the production of cortisol provides negative feedback to reduce ACTH stimulation. The 21-hydroxylase enzyme is required to convert precursors to both cortisol and aldosterone. In salt-wasting 21-hydroxylase CAH, cortisol production is deficient resulting in high ACTH levels. Similarly, the resultant aldosterone deficiency leads to elevated levels of plasma renin. In the non-salt-wasting variety of CAH, the aldosterone pathway remains intact, although renin levels may be inappropriately elevated, suggesting an inefficient mineralocorticoid production. In both CAH types, however, the elevated ACTH stimulates the adrenal cortex's biochemical pathway. This causes shunting of hormone production away from cortisol towards an excess accumulation of various androgenic precursors, such as 17-OH progesterone and androstenedione that lead to the evident virilization.
The usual infant with the salt-losing form of congenital adrenal hyperplasia will present with dehydration and signs of both acute and chronic hypovolemia, with or without peripheral vascular collapse, sometime between the third and 28th day of life. Such signs, however, may appear under uncommon circumstances as late as three to four months of age (e.g., premature infants receiving supportive salt-containing intravenous fluids). Male infants with salt-losing, virilizing CAH tend to have subjectively normal external genitalia at birth. In contrast, female babies with this condition will characteristically demonstrate virilized ambiguous external genitalia at delivery from a prolonged intrauterine exposure to excessive adrenal androgens; a dysfunctional response maintained by the absence of a negative pituitary ACTH feedback effect from the underlying primary cortisol deficiency. Although a disease with autosomal recessive inheritance, prior collected data has documented an unexpected majority (greater than 60%) of CAH female infants, suggesting that a substantial number of male infants with congenital adrenal hyperplasia remain undiagnosed. More recent studies based on newborn screening data, however, have revealed more predictable gender proportions, thus supporting the value-added benefits of such a prevention strategy of newborn screening for treatable metabolic defects.
Analysis of now available genetic information indicates that the genetic mutations leading to congenital adrenal hyperplasia have been mapped to the class III region of the HLA complex (specifically HLA-B and HLA-DR) located on chromosome six. Subsequent work by the pediatric endocrinology group at Cornell has successfully defined the precise 21-OHase gene structure. These investigations have shown that CAH patients with classic 21-hydroxylase deficiency, with and without clinical salt loss, have a similar genetic abnormality. Alternatively, although located at the same genetic locus, patients with the other non-classical, virilizing forms of 21-OHase CAH, carry a different and distinct allelic abnormality, a genetic pattern analogous to that seen with hemoglobin S and C diseases.
The diagnosis of CAH is established by laboratory findings of a low cortisol in the presence of elevated levels of ACTH and adrenal androgens, the latter either obtained randomly or after stimulation with ACTH. Patients with the salt-wasting form will additionally demonstrate laboratory evidence of hyponatremia and hyperkalemia in association with a suppressed aldosterone concentration and an elevated plasma renin activity. A simple test to demonstrate inappropriate salt wasting from aldosterone deficiency is to obtain a urine sodium measurement when the patient is hyponatremic. In contrast to the expected findings of appropriately low urine sodium in the setting of hyponatremia, the urine sodium in salt wasting states such as mineralocorticoid deficiency or resistance will be inappropriately high.
In the not too distant past, infection-associated causes of acquired adrenal insufficiency predominated and included, most commonly, tuberculosis and fulminant bacterial sepsis. Today, however, acquired, idiopathic adrenal insufficiency occurs principally as a result of an autoimmune destruction of the adrenal gland. Autoimmune Addison's disease may occur either as an isolated phenomenon or, more commonly, as part of a more generalized, autosomal dominant polyglandular autoimmune failure syndrome. Given the often subtle clinical symptoms of acquired primary adrenal insufficiency, most patients with the polyglandular failure syndrome, if Type I, present characteristically with complaints of recurrent oral thrush and chronic ungual candidiasis from the underlying T-cell immune dysfunction. Both finger and toe nails can be affected with findings of opaque, thickened, friable and brittle nails. The polyglandular failure syndrome itself occurs in two types and typically consists of the following constellations of endocrinopathies:
Type I: Hypoparathyroidism (90 %), Addison's disease (60%), Hypogonadism (45%), Mucocutaneous candidiasis (75%), Autoimmune thyroid disease (10%)
Type II: Addison's disease (100 %), Autoimmune thyroid disease (70 %), Insulin-dependent diabetes (50 %), Hypogonadism (10 %), Vitiligo (5 %)
Acquired adrenal insufficiency can also commonly occur from an iatrogenic suppression of the hypothalamic-pituitary-adrenal axis. Given the widespread use of corticosteroids as therapeutic anti-inflammatory agents in the treatment of such conditions as asthma, arthritis or as adjunctive chemotherapy, iatrogenic adrenal insufficiency is at present, probably the number one etiology of adrenal cortisol deficiency. Supraphysiologic dosages of exogenous corticosteroids for periods as short as 4 weeks have been associated with the prolonged (up to one year!) inhibition of ACTH-mediated cortisol production.
Even when temporally associated with an acute event (e.g., adrenal hemorrhage from sepsis-associated disseminated intravascular coagulation), the clinical presentation of acquired adrenal insufficiency is typically insidious as well as nonspecific in its symptomatology. Unless the health care provider carries a high index of suspicion, suggestive clinical symptoms of lethargy and easy fatigability and physical signs of postural hypotension and fasting hypoglycemia in at-risk patients will surely be missed. In patients with primary cortisol deficiency, and thus with elevated ACTH levels, the presence of a generalized bronzing ("tanning") of the skin from an excess ACTH effect can be diagnostically helpful in supporting the laboratory evaluation for a suspected adrenal insufficiency. With in-vitro findings of ACTH receptors in melanocytes, it is believed that the increased tanning of the skin results from excess melanin deposition in the dermis.
Patients with acute adrenal insufficiency may present with both hypothermia and shock from peripheral vascular collapse. Vital signs including systemic arterial blood pressure, heart rate, respiratory rate and temperature must be monitored hourly until stable. In addition, the ECG must also be monitored continuously since hyperkalemia can cause severe ventricular dysrhythmias. Patients who do not respond to the initial fluid challenges with an increase in systemic arterial blood pressure, peripheral perfusion and urinary output require a central venous catheter for appropriate monitoring of central venous blood pressure.
Serum electrolytes (Na, K, C1, and HCO3) must be obtained immediately upon admission and followed at 4 hour intervals for the first 24 hours of management. Prior to the start of therapy in infants, blood must also be obtained for ACTH, androstenedione, 17-hydroxyprogesterone (17-OHP) and plasma renin studies. The 17-OHP serum assay has been shown to be a dependable and reliable diagnostic technique in infants with congenital adrenal hyperplasia, even when acutely ill. Collection of 24 hour urine for determination of 17-hydroxycorticosteroids (17OHCS), reflecting blood levels of glucocorticoids, or 17-ketosteroids, the standard diagnostic test for evaluating adrenal androgen excretion in the past, is not presently considered practical in young children and much less so in those with vascular instability. In older children who present with primary adrenal insufficiency, a blood sample for determination of serum cortisol and ACTH levels must be similarly obtained prior to the initiation of steroid therapy. In patients with primary adrenal insufficiency, the cortisol level will be low, whereas the ACTH level will be substantially elevated as a result of an absent, negative pituitary feedback mechanism. Although optimal, dynamic studies such as ACTH stimulation tests should be avoided if they, in any way, compromise the patient's clinical status.
The aim of endocrine treatment is to replace the deficient adrenal steroids. Acute fluid therapy must be continued until hormonal replacement is, by itself sufficient to sustain the patient's clinical stability.
For glucocorticoid replacement, an initial bolus of glucocorticoids, such as hydrocortisone sodium succinate, or its therapeutic equivalent (See table 1), must be administered intravenously at a bolus dose of 60 to 80 mg per square meter (body surface area). Initial dosages less than 25 mg in an infant or greater than 100 mg in an older child should be avoided. The initial bolus of glucocorticoids should be repeated if there is an inadequate clinical response to treatment as judged by systemic arterial blood pressure, peripheral perfusion, and urine output. Intramuscular cortisone acetate (60 mg per square meter of body surface area) may be administered as a repository dose of glucocorticoid at the same time as the initial bolus treatment. The half-life of cortisone acetate is approximately 24 hours and its duration of action may last up to 2 to 3 days.
As soon as a pattern of clinical improvement has been established, one-third to one-half of the initial dose of intravenous hydrocortisone sodium succinate must be continued every 4 hours for the subsequent 24 hours, by which time effective glucocorticoid replacement should be complete. The half-life of hydrocortisone sodium succinate is approximately 60 to 90 minutes and its duration of action is about 4 hours. Upon effective completion of glucocorticoid replacement, and provided the patient's clinical status permits, the patient may then be switched to oral maintenance therapy with hydrocortisone at 15 mg per square meter per day divided into three equal doses, a dosage intended to approximate the physiologic daily secretory rate of cortisol, 12 mg per square meter of body surface area.
If adrenal insufficiency is severe at presentation, a regimen of intramuscular cortisone acetate 30 mg per square meter given every 12 hours should be continued for an additional 24 to 48 hours before changing to oral hydrocortisone maintenance.
Table 1 - Glucocorticoid Potency Equivalency
Cortisone: 25 mg (least potent)
Hydrocortisone: 20 mg
Prednisone: 5 mg
Prednisolone: 5 mg
Methylprednisolone: 4 mg
Dexamethasone: 0.75 mg (most potent)
For mineralocorticoid replacement, parenteral mineralocorticoid therapy as intramuscular aqueous deoxycorticosterone acetate (DOCA) has been unavailable for close to 10 years. Current recommendations for salt-wasting CAH patients presenting with hyponatremia and/or hyperkalemia consist of oral fludrocortisone acetate (Florinef), 0.05 to 0.2 mg/day given b.i.d. or as a single daily dose, started as soon as the patient is able to retain oral fluids. Unfortunately, although Florinef is an effective medication for long-term maintenance therapy, the acute biochemical mineralocorticoid effects of oral fludrocortisone acetate may be delayed by 48 to 72 hours. Until then, the continued infusion of salt containing intravenous solutions will be needed to correct the hyponatremia and hyperkalemia seen with salt-losing adrenal insufficiency.
To correct the initial hypovolemia and hyponatremia, patients with acute adrenal insufficiency must be treated with volume replacement as appropriate. Using hourly bedside monitoring, blood sugar levels below 60 mg/dl should be avoided and treated with intravenous dextrose as indicated. Subsequent fluid therapy should be continued as directed by the patient's clinical status and ongoing fluid losses. Evaluation of the patient's continuing fluid needs must be performed at 4 hour intervals to determine if the scheduled replacement is adequate to compensate for persistent volume and salt requirements.
Replacement intravenous fluids should be potassium free for the first 24 hours unless the serum potassium level drops below 3.5 mEq/L. When signs of hyperkalemic electrocardiographic toxicity exist, the patient must be treated aggressively to avoid clinical toxicity. If the patient develops a non-perfusing dysrhythmia due to extreme hyperkalemia (this frequently may resemble ventricular tachycardia on the EKG), IV calcium should be given immediately. Although parenteral calcium is potentially effective in converting the dysrhythmia to a perfusing sinus rhythm, hyperkalemic dysrhythmias will recur unless the serum potassium level can be reduced. A fast, simple way to reduce the serum potassium although only temporarily, is by administering sodium bicarbonate 1 mEq/kg IV. Sodium bicarbonate is readily available and requires no special preparation to administer. Sodium bicarbonate works by raising the serum pH and shifting potassium intracellularly, thus lowering the serum potassium. Other rapid measures for treating severe hyperkalemia by similarly shifting potassium intracellularly include: 1) albuterol aerosol and 2) insulin (0.1 unit per kg) IV. It is important to administer insulin with a concurrent dextrose containing IV solution to avoid hypoglycemia. These latter potassium-lowering methods are only temporary since they merely shift potassium intracellularly. Excess potassium must be removed from the body by administering sodium polystyrene sulfonate (Kayexalate) resin. Kayexalate exchanges sodium for potassium thereby increasing the patient's serum sodium while removing potassium. Kayexalate may be given PO or as a retention enema. Furosemide IV may also be used to remove excess potassium through its effect in increasing renal sodium and potassium excretion.
Acute episodes of adrenal insufficiency usually resolve by the second day of appropriate therapy. Intravenous fluids containing a sodium chloride solution with dextrose should be continued until the institution and tolerance of oral feedings allows for adequate sodium intake. Patients with salt-losing adrenal insufficiency, especially infants, may require prolonged oral sodium replacement, which may be given in conjunction with feedings. Likewise, in the older child with adrenal insufficiency secondary to an acute episode of Addison's Disease, supplementary sodium may be similarly needed in some patients and may be added to their meals as tolerated.
In the chronic long-term management of CAH, insufficient glucocorticoids result in excess ACTH stimulation of adrenal androgen production, which leads to virilization and premature puberty with eventual short stature. Alternatively, excess glucocorticoids result in clinical findings of hypercortisolism such as central weight gain, striae, hypertension, and growth suppression. Adrenal androgen levels, 17OHP and androstenedione, can be monitored to assess the adequacy of glucocorticoid replacement. Elevated levels indicate inadequate glucocorticoid treatment with incomplete suppression of excess ACTH release. Low adrenal androgen levels may indicate that glucocorticoid dosing is excessive especially if associated with age-inappropriate growth rates or other clinical evidence of an excess glucocorticoid effect. The adequacy of mineralocorticoid dosing may be monitored through serial determinations of plasma renin and electrolyte levels. Elevated renin levels indicate an insufficient mineralocorticoid replacement regimen even in the absence of associated hyponatremia or hyperkalemia. Suppressed plasma renin may alternatively suggest an excess mineralocorticoid effect especially in the presence of an elevated blood pressure.
Other adrenal conditions in pediatrics are less common. Cushing's syndrome is a symptom complex that reflects an excessive, peripheral adrenal glucocorticoid effect. This hypercortisolism may be iatrogenic or endogenous, the latter either primary from autonomous adrenal hyperactivity (ACTH-independent) or secondary to an excess ACTH stimulation (ACTH-dependent). When caused by excessive pituitary ACTH production, the condition is called Cushing's Disease. As suggested above, Cushing's syndrome may also be iatrogenic and result from exogenously administered corticosteroids used as therapy for various medical conditions. Symptoms of hypercortisolism from any cause are typically subtle, often nonspecific and slow to develop. Common findings consist of an increased subcutaneous fat deposition, especially in the temporal areas of the face ("moon facies"), the posterior neck ("buffalo hump") and the abdomen. These findings, however, are also seen with simple obesity. Other symptoms of hypercortisolism include facial plethora, easy bruising, cutaneous atrophy, striae, elevated blood pressure and, in children and adolescents, growth failure. This latter characteristic, especially when associated with increasing weight, is the most common presentation of Cushing's syndrome in pediatrics. Although not limited to Cushing's syndrome, decreasing height percentiles is a helpful diagnostic sign in differentiating hypercortisolism from exogenous obesity given that dietary overweight does not lead to poor growth and may in fact cause growth acceleration. In children less than 8 years, Cushing's syndrome is more commonly ACTH-independent and caused by either adrenal adenomas or carcinomas. Of interest, children with Cushing's syndrome from a virilizing adrenal carcinoma may actually present with growth acceleration from an associated, increased adrenal androgen production rather than with the growth failure commonly seen with hypercortisolism. Alternatively, in older children, ACTH-dependent Cushing's from pituitary corticotroph adenomas (Cushing's disease) accounts for about 50 percent of the cases.
The diagnosis of Cushing's syndrome is confirmed by findings of elevated, non-suppressible levels of glucocorticoids, determined either as serum cortisol concentrations or as 24-hour urinary excretion rates of 17OHCS or free cortisol. Differentiation of ACTH-dependent and independent types, as well as localization of the source of the hypercortisolism, may be achieved through a variety of suppression and stimulation studies. Their discussion, however, is beyond the scope of this book. Treatment of Cushing's syndrome is usually surgical, with subsequent adrenal hormone replacement, and is directed at correction of the primary cause. Medical therapy is often of last resort and only poorly effective.
Adrenal disorders localized to the adrenal medulla are even more rare, especially in pediatrics. Pheochromocytomas are catecholamine-producing tumors of neural crest origin. The vast majority are benign and localized to the adrenal gland although extra-adrenal pheochromocytomas are not uncommon in children. The presenting clinical symptoms are directly related to the excess catecholamines released by these tumors. Relevant among these are cold clammy skin, tachycardia, anxiety, agitation and potentially life-threatening hypertension from systemic vasoconstriction. Because release of catecholamines by these tumors is typically episodic, so may the patients' symptoms be also intermittent. The diagnosis may thus be difficult to establish and may require multiple investigations. The diagnosis however, may be confirmed by findings of significantly elevated blood and/or urine levels of catecholamines and their metabolites especially at the time of clinical symptoms. Pheochromocytomas may occur as unilateral or bilateral adrenal tumors (bilateral is more common in children) and either as an isolated or a familial phenomenon, the latter being often part of the Multiple Endocrine Neoplasia syndromes. Treatment is directed at surgical removal of the primary tumor with pre-operative, medical stabilization of the associated hypertension.
Neuroblastomas, ganglioneuromas and ganglioneuroblastomas are additional tumors of the adrenal medulla. Although these tumors may excrete catecholamines, characteristically dopamine and its metabolite, homovanillic acid (HVA), most are nonfunctional and detected through findings, often incidental, of an abdominal mass. Treatment is surgical with subsequent chemotherapy as indicated by the pathology findings.
1. Urinary excretion rates of 17-hydroxycorticosteroids (17-OHCS) reflect the blood levels of:
. . . . . a. mineralocorticoids
. . . . . b. Glucocorticoids
. . . . . c. Sex steroids
. . . . . d. Adrenal androgens
2. The daily secretory rate for plasma cortisol is approximately:
. . . . . a. 5 mg / square meter / day
. . . . . b. 12 mg / square meter / day
. . . . . c. 25 mg / square meter / day
. . . . . d. 50 mg / square meter / day
3. Congenital adrenal hyperplasia due to 21-alpha-hydroxylase deficiency is inherited as a(n):
. . . . . a. Autosomal recessive trait.
. . . . . b. Autosomal dominant trait.
. . . . . c. X-linked recessive trait.
. . . . . d. Sporadic disorder from a spontaneous gene mutation.
4. Acquired adrenal insufficiency in school age children and adolescents may present with:
. . . . . a. Hypertension and a "Buffalo Hump".
. . . . . b. Hypernatremia and hypokalemia.
. . . . . c. Hypoglycemia and postural hypotension.
. . . . . d. Biochemical findings of suppressed ACTH levels.
5. Chronic, primary adrenal insufficiency (Addison's disease) in children is most commonly due to:
. . . . . a. Tuberculosis
. . . . . b. Adrenal hemorrhage
. . . . . c. Autoimmunity
. . . . . d. Tumor
6. True/False: If patients have received large doses (i.e., greater than physiologic replacement) of glucocorticoids for a short period of time (i.e., less than one month) or small doses (i.e. less than physiologic replacement) for any period of time, adrenal function will likely resume shortly after cessation of therapy.
7. Which of the following is a hypertensive form of congenital adrenal hyperplasia?
. . . . . a. Simple virilizing 21-hydroxylase deficiency
. . . . . b. Salt-losing 21-hydroxylase deficiency
. . . . . c. 11-hydroxylase deficiency
. . . . . d. 3-beta dehydrogenase deficiency
8. Which of the following laboratory tests are most appropriate for monitoring the effectiveness of steroid replacement therapy in acquired, primary adrenal insufficiency ?
. . . . . a. 17-OH progesterone, androstenedione and ACTH levels.
. . . . . b. fractionated catecholamines and homovanillic acid (HVA) levels.
. . . . . c. post-dexamethasone urinary free cortisol and 17OH corticosteroids levels.
. . . . . d. ACTH, plasma renin and serum electrolyte levels.
9. A 2 week old infant presents with projectile vomiting and dehydration. The infant's electrolytes are as follows: Na 126, K 6.5, Cl 92, Bicarb 15, glucose 60. These electrolyte results are most compatible with which of the following diagnosis ?
. . . . . a. pyloric stenosis with bicarbonate loss from repeated vomiting.
. . . . . b. congenital Cushing's syndrome from excess mineralocorticoid effect.
. . . . . c. pheochromocytoma from excess catecholamine effect.
. . . . . d. salt-wasting CAH from mineralocorticoid deficiency.
10. Cushing's syndrome is characterized by the presence of:
. . . . . a. hyponatremia and hyperkalemia.
. . . . . b. an elevated urinary free cortisol excretion.
. . . . . c. genital virilization from excess adrenal androgens.
. . . . . d. low serum cortisol and increased ACTH levels.
1. Bongiovani AM. Congenital Adrenal Hyperplasia and Related Conditions. In: Stanbury JB, Wyngaarden JB, Fredrickson, DS (eds). The Metabolic Basis of Inherited Disease, 4th edition. 1978, New York: McGraw-Hill, pp. 868-893.
2. New MI, et al. The Adrenal Cortex. In: Kaplan SA (ed). Clinical Pediatric Endocrinology, second edition. 1990, Philadelphia: W.B. Saunders, pp. 181-234.
3. White PC, Gonzalez JL, Marks JF. Acute Adrenal Insufficiency. In: Levin DL, Morriss FC. Essentials of Pediatric Intensive Care, second edition. 1997, New York: Churchill Livingstone, pp. 571-576.
4. Loriaux DL, McDonald WJ. Adrenal Insufficiency. In: DeGroot LJ & Jameson JL (eds). Endocrinology, 4th edition. 2001, Philadelphia: W.B. Saunders, pp. 1683-1690.
5. Coursin DB, Wood KE. Corticosteroid Supplementation for Adrenal Insufficiency. JAMA 2002;287(2):236-240.
6. Nieman LK. Cushing's Syndrome. In: DeGroot LJ, Jameson JL (eds). Endocrinology, 4th edition. 2001, Philadelphia: W.B. Saunders, pp. 1691-1715.
7. Keiser HR. Pheochromocytoma and Related Tumors. In: DeGroot LJ, Jameson JL (eds). Endocrinology, 4th edition. 2001, Philadelphia: W.B. Saunders, pp. 1862-1884.
Answers to questions
1.b, 2.b, 3.a, 4.c, 5.c, 6.True, 7.c, 8.d, 9.d, 10.b