++
The adult adrenal cortex consists of three zones responsible for synthesis of different steroids from the precursor, cholesterol (see Figure 34–8):
++
Outermost zona glomerulosa—aldosterone.
Middle zona fasciculata—cortisol and small amounts of mineralocorticoids.
Innermost zona reticularis—androgens.
++
The predominant regulator of mineralocorticoid (primarily aldosterone) production and secretion is the volume- and sodium-sensitive renin-angiotensin-aldosterone system. Mineralocorticoids promote sodium retention and stimulate potassium excretion in the distal renal tubule.
++
Glucocorticoid production, primarily cortisol, is under the control of pituitary adrenocorticotropic hormone (ACTH; see Figure 34–1 and Table 34–1), which is in turn regulated by hypothalamic corticotropin-releasing hormone (CRH). ACTH concentration is greatest during the early morning hours with a smaller peak in the late afternoon and a nadir at night. The pattern of serum cortisol concentration follows this pattern with a lag of a few hours. In the absence of cortisol feedback, there is dramatic CRH and ACTH hypersecretion.
++
Glucocorticoids are critical for gene expression in a many cell types. Glucocorticoids also help maintain blood pressure by promoting peripheral vascular tone and sodium and water retention. In excess, glucocorticoids are both catabolic and antianabolic; they promote the release of amino acids from muscle and increase gluconeogenesis while decreasing incorporation of amino acids into muscle protein. They also antagonize insulin activity and facilitate lipolysis.
++
At the onset of puberty, production of androgens (dehydroepiandrosterone and androstenedione) increases and is an important contributor to pubertal development in both sexes. The adrenal gland is the major source of androgen in females.
+++
ADRENOCORTICAL INSUFFICIENCY
++
Adrenal insufficiency may be primary—due to disorders of the adrenal gland itself, or central/secondary—due to disorders of CRH and/or ACTH secretion. Primary adrenal insufficiency impairs the production of all adrenal steroids, whereas secondary adrenal insufficiency should not affect production of mineralocorticoids or androgens as these are not regulated by ACTH. The causes of primary and secondary adrenal insufficiency are listed in Table 34–10.
++
++
Secondary adrenal insufficiency may be isolated ACTH deficiency or combined with other pituitary hormone deficiencies.
+++
A. Symptoms and Signs
+++
1. Acute form (adrenal crisis)
++
Nausea, vomiting, abdominal pain; dehydration; fever (sometimes followed by hypothermia); weakness; hypoglycemia; hypotension and circulatory collapse; confusion and coma. Hyponatremia and hyperkalemia are seen in primary adrenal insufficiency. Acute illness, surgery, trauma, or hyperthermia may precipitate an adrenal crisis in patients with adrenal insufficiency.
++
Fatigue, hypotension, weakness, weight loss or failure to gain weight, vomiting and dehydration, recurrent hypoglycemia. In primary adrenal insufficiency, salt craving and hyponatremia and/or hyperkalemia can be seen. Diffuse tanning occurs with increased pigmentation over pressure points, scars, and mucous membranes in primary adrenal insufficiency due to melanocyte-stimulating activity of alternate products of hypersecreted pro-opiomelanocortin, the parent molecule of ACTH.
+++
B. Laboratory Findings
+++
1. Suggestive of adrenocortical insufficiency
++
Primary adrenal insufficiency
Decreased—serum sodium, serum bicarbonate, serum glucose, blood pH, and blood volume.
Increased—serum potassium, urea nitrogen levels.
Urinary sodium and the ratio of urinary sodium to potassium inappropriate for the degree of hyponatremia.
Central adrenal insufficiency—serum sodium levels may be mildly decreased as a result of impaired water excretion but true salt-wasting is not present (mineralocorticoid function should remain intact).
Eosinophilia and moderate lymphopenia occur in both forms of insufficiency.
+++
2. Confirmatory tests
+++
A. ACTH (COSYNTROPIN) STIMULATION TEST
++
Primary adrenal insufficiency—plasma cortisol less than 18 mcg/dL 30 and 60 minutes after 250 mcg of cosyntropin (high-dose stimulation test) given intravenously and failure of aldosterone to rise above baseline
Central adrenal insufficiency—plasma cortisol less than 18 mcg/dL 30 and 60 minutes after 1 mcg of cosyntropin given intravenously (low-dose stimulation)
+++
B. BASELINE SERUM ACTH CONCENTRATION
++
Elevated in primary adrenal failure and low/low-normal in central adrenal insufficiency
+++
C. URINARY FREE CORTISOL
++
++
After administration of ovine CRH, serum concentrations of ACTH and cortisol are measured. Localization of the site of impairment is possible based on careful interpretation of results. The CRH test has not been widely used in pediatrics.
+++
Differential Diagnosis
++
Acute adrenal insufficiency must be differentiated from sepsis, diabetic coma, CNS disturbances, dehydration and acute poisoning. In the neonatal period, adrenal insufficiency may be clinically indistinguishable from respiratory distress, intracranial hemorrhage, or sepsis. Chronic adrenocortical insufficiency must be differentiated from anorexia nervosa, depression, certain muscular disorders (myasthenia gravis), salt-losing nephropathy, and chronic debilitating infections.
+++
A. Acute Insufficiency (Adrenal Crisis)
++
Hydrocortisone sodium succinate (50 mg/m2 intravenously over 2–5 minutes or intramuscularly) is given initially followed by 12.5 mg/m2, every 4–6 hours until stabilization is achieved and oral therapy can be tolerated. Cortisol replacement is critical because pressor agents may be ineffective with cortisol insufficiency.
+++
2. Fluids and electrolytes
++
In primary adrenal insufficiency, 5%–10% glucose in normal saline, 10–20 mL/kg intravenously, is given over the first hour and repeated if necessary to reestablish vascular volume. Normal saline is continued thereafter at 1.5–2 times maintenance fluid requirements until volume and electrolytes have normalized. In central adrenal insufficiency, routine fluid management is generally adequate after initial restoration of vascular volume and institution of cortisol replacement.
++
Treatment with fludrocortisone, a mineralocorticoid agonist, is not required acutely, as hydrocortisone in stress doses has adequate mineralocorticoid action. When oral intake is tolerated, fludrocortisone, is started, 0.05–0.15 mg daily, and continued every 12–24 hours for primary adrenal insufficiency.
+++
B. Maintenance Therapy
++
A maintenance dosage of 6–10 mg/m2/day of hydrocortisone (or equivalent) is given orally in two or three divided doses. To prevent acute adrenal crises, the dosage of all glucocorticoids is increased to 30–50 mg/m2/day during intercurrent illnesses or other times of stress (fever > 101.5°F, trauma, surgery, or systemic illness) and should also be increased during significant diarrhea due to reduced absorption. Families should be encouraged to give stress doses of hydrocortisone if they have concerns, as brief exposure to stress doses of hydrocortisone will not have adverse effects. Rarely, families become overly anxious and give stress doses frequently. This should be avoided as it can contribute to obesity, growth retardation, and other cushingoid features.
+++
2. Mineralocorticoids
++
In primary adrenal insufficiency, fludrocortisone is given, 0.05–0.15 mg orally daily as a single dose or in two divided doses. Periodic monitoring of blood pressure is recommended to avoid overdosing.
++
Children should be given ready access to table salt. In the infant, supplementation of breast milk or formula with 3–5 mEq Na+/kg/day is generally required until table foods are introduced.
++
If treated appropriately, the prognosis of adrenal insufficiency is good however spontaneous recovery is unlikely unless the etiology was transient (exogenous glucocorticoid exposure, eg). If adrenal crisis is not recognized and promptly treated with pharmacologic glucocorticoids, the course of acute adrenal insufficiency is rapid and death may occur within a few hours, particularly in infants. Regular care with an endocrinologist is required to evaluate management and adjust dosing to ensure adequate replacement while avoiding overdosing that could lead to impaired growth, hypertension, and Cushingoid features.
+
Park
J, Didi
M, Blair
J: The diagnosis and treatment of adrenal insufficiency during childhood and adolescence. Arch Dis Child 2016 Sep;101(9):860–865
[PubMed: 27083756]
.
+
Tucci
V, Sokari
T: The clinical manifestations, diagnosis, and treatment of adrenal emergencies. Emerg Med Clin North Am 2014 May;32(2):367–378
[PubMed: 24766938]
.
+++
CONGENITAL ADRENAL HYPERPLASIAS
++
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Genital virilization in females, with labial fusion, urogenital sinus, enlargement of the clitoris, or other evidence of androgen action in the most common form.
Increased linear growth and advanced skeletal maturation.
Elevation of plasma 17-hydroxyprogesterone concentrations in the most common form; may be associated with hyponatremia, hyperkalemia, and metabolic acidosis if mineralocorticoid deficiency included.
+++
General Considerations
++
Autosomal recessive mutations in the enzymes of adrenal steroidogenesis cause impaired cortisol biosynthesis with increased ACTH secretion. ACTH excess subsequently results in adrenal hyperplasia with increased production of adrenal hormone precursors that are metabolized through the unblocked androgen pathway. Increased pigmentation, especially of the scrotum, labia majora, and nipples, is common due to excessive ACTH secretion. CAH is most commonly (> 90% of patients) the result of homozygous or compound heterozygous mutations in the cytochrome P-450 C21 (CYP21A2) gene causing 21-hydroxylase deficiency (see Figure 34–8). The defective gene is present in 1:250–1:100 people and the worldwide incidence of the disorder is 1:15,000, with increased incidence in certain ethnic groups. In its severe form, excess adrenal androgen production starting in the first trimester of fetal development causes virilization of the female fetus and life-threatening hypovolemic, hyponatremic shock (adrenal crisis) in the newborn, if untreated. There are also other enzyme defects that less commonly result in CAH. The clinical syndromes associated with these defects are shown in Figure 34–8 and Table 34–11.
++
++
Prenatal diagnosis is now possible and newborn screening by measurement of serum 17-hydroxyprogesterone has been established in all 50 US states and many other countries worldwide.
++
In nonclassic presentations of 21-hydroxylase deficiency, affected individuals have a normal phenotype at birth but develop virilization during later childhood, adolescence, or early adulthood. Hormonal studies are characteristic of 21-hydroxylase deficiency, with cosyntropin stimulated 17-OHP levels intermediate between those of nonaffected individuals and those with the classic form of the disease. Individuals with the nonclassic form of the disease may be asymptomatic or only mildly symptomatic, but they can carry a severe CYP21A2 mutation resulting in offspring with the classic form.
+++
Clinical Findings in 21-Hydroxylase Deficiency
+++
A. Symptoms and Signs
++
Abnormality of the external genitalia varies from mild enlargement of the clitoris to complete fusion of the labioscrotal folds, forming an empty scrotum, a penile urethra, a penile shaft, and clitoral enlargement sufficient to form a normal-sized glans (see Figure 34–7). Signs of adrenal insufficiency (salt loss) typically appear 5–14 days after birth. With milder enzyme defects, clinically apparent salt loss may not occur and virilization predominates with accelerated growth and skeletal maturation. Pubic hair appears early, acne may be excessive, and the voice may deepen. Excessive pigmentation may develop. Isosexual central precocious puberty may occur if treatment is not initiated before the bone age is significantly advanced. Final adult height is often compromised.
++
The male infant usually appears normal at birth but may present with salt-losing crisis in the first weeks of life if treatment is not initiated. In milder forms, salt-losing crises may not occur and virilization predominates, with enlargement of the penis and increased pigmentation, as well as other symptoms and signs similar to those of affected females. The testes are not enlarged unless there are rare adrenal rests in the testes producing asymmetrical enlargement. In some rare enzyme defects, ambiguous genitalia may be present due to impaired androgen production (see Table 34–11).
+++
B. Laboratory Findings
++
Hormonal studies are essential for accurate diagnosis. Findings characteristic of the enzyme deficiencies are shown in Table 34–11.
++
Rapid assessment of genetic sex should be obtained in any newborn with ambiguous genitalia since 21-hydroxylase deficiency is the most common cause of ambiguity in females.
++
Imaging is generally not required to make the diagnosis of CAH. Ultrasonography, CT scanning, and MRI may be useful in defining pelvic anatomy or to exclude an adrenal tumor.
++
Treatment goals in CAH are to provide the smallest dose of glucocorticoid that will adequately suppress excess androgen precursors and produce normalization of growth velocity and skeletal maturation; excessive glucocorticoids cause the undesirable side effects of Cushing syndrome. Mineralocorticoid replacement sustains normal electrolyte homeostasis, but excessive mineralocorticoids cause hypertension and hypokalemia.
++
Supraphysiologic doses of hydrocortisone are often needed to suppress androgen excess in CAH. Initially, parenteral or oral hydrocortisone (30–50 mg/m2/day) is provided until suppression of abnormal adrenal steroidogenesis has been accomplished, as evidenced by normalization of serum 17-hydroxyprogesterone. Subsequently, patients are placed on maintenance doses of 10–15 mg/m2/day in three divided doses. Dosage is adjusted to maintain normal growth rate and skeletal maturation. Serum 17-hydroxyprogesterone and androstenedione are usually used to monitor therapy; however, no one test is universally accepted.
+++
2. Mineralocorticoids
++
Fludrocortisone, 0.05–0.15 mg/day, is given orally once a day or in two divided doses. Periodic monitoring of blood pressure and plasma renin activity are recommended to avoid overdosing.
+++
B. Surgical Treatment
++
For affected females, consultation with a urologist or gynecologist experienced in female genital reconstruction should be arranged as soon as possible during infancy.
++
When initiated in early infancy, treatment with glucocorticoids permits normal growth, development, and sexual maturation. If not adequately controlled, CAH results in sexual precocity and masculinization throughout childhood. Affected individuals will be tall as children but short as adults because of rapid skeletal maturation and premature closure of the epiphyses. If treatment is delayed or inadequate, true central precocious puberty may occur in males and females.
++
Patient education stressing lifelong therapy is important to ensure compliance in adolescence and later life. Virilization and multiple surgical genital reconstructions may be associated with risk of psychosexual disturbances in female patients and ongoing psychological evaluation and support is a critical component of care.
+
Merke
DP and, Poppas
DP: Management of adolescents with congenital adrenal hyperplasia. Lancet Diabetes Endocrinol 2013 Dec;1(4):341–52.
[PubMed: 24622419]
.
+
Speiser
PW
et al: Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Sep;95(9):4133–60.
[PubMed: 20823466]
.
+
Speiser
PW
et al: Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2018; 103(11):4043
[PubMed: 30272171]
.
+++
ADRENOCORTICAL HYPERFUNCTION
++
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Truncal adiposity, thin extremities, moon facies, muscle wasting, weakness, plethora, easy bruising, purple striae, decreased growth rate, and delayed skeletal maturation.
Hypertension, osteoporosis, and glycosuria.
Elevated 24-hour urinary free cortisol, elevated midnight salivary cortisol, failed low-dose dexamethasone suppression test.
+++
General Considerations
++
Cushing syndrome may result from excessive autonomous secretion of adrenal steroids (adrenal adenoma or carcinoma), excess pituitary ACTH secretion (Cushing disease), ectopic ACTH or CRH secretion, or chronic exposure to exogenous glucocorticoids. In children younger than 12 years, Cushing syndrome is usually iatrogenic. It is less commonly due to adrenal tumor, adrenal hyperplasia, pituitary adenoma, or extrapituitary ACTH-producing tumor.
+++
A. Symptoms and Signs
+++
1. Excess glucocorticoid
++
Adiposity, most marked on the face, neck, and trunk—a fat pad (buffalo hump) in the interscapular area is characteristic but not diagnostic; fatigue; plethoric facies; purplish striae; easy bruising; osteoporosis and back pain; hypertension and glucose intolerance; proximal muscle wasting and weakness; retardation of growth and skeletal maturation.
+++
2. Excess mineralocorticoid
++
Hypokalemia and mild hypernatremia, increased blood volume, edema, hypertension.
++
Hirsutism, acne, virilization, and menstrual irregularities.
+++
B. Diagnosis of Cushing Syndrome
++
elevated salivary cortisol obtained at midnight is a noninvasive and highly specific and sensitive test for hypercortisolism.
+++
2. 24-Hour urinary-free cortisol excretion
++
elevated 24-hour urinary free cortisol/creatinine suggests Cushing Syndrome.
+++
3. Low-dose (15 mcg/kg) dexamethasone suppression test
++
dexamethasone (15mcg/kg, max 1mg) is given at midnight followed by measurement of fasting plasma cortisol and ACTH at 8 AM the following morning. Failure to suppress cortisol < 1.8 ug/dL suggests Cushing Syndrome.
+++
C. Establishing the Cause of Cushing Syndrome
+++
1. ACTH concentration
++
decreased ACTH values (< 5pg/mL) suggest an adrenal cause. Intermediate ACTH values (5–29 pg/mL) are indeterminant and warrant further investigation. Elevated ACTH values (> 29 pg/mL) suggest an ACTH-dependent (pituitary or ectopic) cause. ACTH.
+++
2. High-dose (8 mg) dexamethasone testing
++
high-dose dexamethasone testing may help to determine ACTH-dependent Cushing syndrome from ACTH-independent Cushing syndrome.
++
Pituitary imaging may demonstrate a pituitary adenoma. Adrenal imaging by CT scan may demonstrate adenoma or bilateral hyperplasia. MRI and nuclear medicine studies of the adrenals may be useful in complex cases. Skeletal maturation is usually delayed.
+++
Differential Diagnosis
++
Children with exogenous obesity accompanied by striae and hypertension are often suspected of having Cushing syndrome. However, children with Cushing syndrome have a poor growth velocity, relatively short stature, and delayed skeletal maturation, while those with exogenous obesity usually have a normal or slightly increased growth velocity, normal to tall stature, and advanced skeletal maturation. The color of the striae (purplish in Cushing syndrome, pink in obesity) and the distribution of the obesity may assist in differentiation. The urinary-free cortisol excretion (in milligrams per gram of creatinine) may be mildly elevated in obesity, but midnight salivary cortisol is normal and cortisol secretion is suppressed by low-dose dexamethasone suppression test.
++
In all cases of primary adrenal hyperfunction due to tumor, surgical removal is indicated if possible. Glucocorticoids should be administered parenterally in pharmacologic doses during and after surgery until the patient is stable. Supplemental oral glucocorticoids, potassium, salt, and mineralocorticoids may be necessary until the suppressed contralateral adrenal gland recovers, sometimes over a period of several months. Similarly, pituitary adenomas and ectopic sources of ACTH or CRH are generally treated surgically. Recurrent adenomas may respond to irradiation.
+
Stratakis
CA: Diagnosis and clinical genetics of Cushing syndrome in pediatrics. Endocrinol Metab Clin North Am 2016 Jun;45(2):311–328
[PubMed: 27241967]
.
+++
PRIMARY HYPERALDOSTERONISM
++
Primary hyperaldosteronism may be caused by an adrenal adenoma or adrenal hyperplasia. It is characterized by paresthesias, tetany, weakness, periodic paralysis; nocturnal enuresis; hypokalemia, hypernatremia, metabolic alkalosis; hypertension; glucose intolerance; elevated plasma and urinary aldosterone; and suppressed plasma renin activity.
++
Primary hyperaldosteronism is rare in pediatrics. However, there are three recognized genetic causes (types I–III). Type I (glucocorticoid remediable hyperaldosteronism) is due to a hybrid of the genes encoding 11β-hydroxylase and aldosterone synthase. Type III results from mutations in the KCNJ5 gene encoding a K+ channel. Somatic mutations of this gene are also seen in later onset hyperaldosteronism. The cause for type II is unknown.
++
Treatment is with glucocorticoids (type I), spironolactone (type II), or subtotal or total adrenalectomy for hyperplasia or tumor.
+
Funder
JW
et al: The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016 May;101(5):1889–1916
[PubMed: 26934393]
.
+++
USES OF GLUCOCORTICOIDS & ADRENOCORTICOTROPIC HORMONE IN TREATMENT OF NONENDOCRINE DISEASES
++
Glucocorticoids are used for their anti-inflammatory and immunosuppressive properties in a variety of conditions in childhood. Pharmacologic doses are necessary to achieve these effects, and side effects are common. Numerous synthetic preparations possessing variable ratios of glucocorticoid to mineralocorticoid activity are available (Table 34–12).
++
++
When prolonged use of pharmacologic doses of glucocorticoids is necessary, clinical manifestations of Cushing syndrome are common. Side effects may occur with the use of synthetic exogenous agents by any route, including inhalation and topical administration, or with the use of ACTH. Alternate-day therapy lessens the incidence and severity of some of the side effects (Table 34–13).
++
+++
Tapering of Pharmacologic Doses of Steroids
++
Prolonged use of pharmacologic doses of glucocorticoids causes suppression of ACTH secretion and consequent adrenal atrophy; the abrupt discontinuation of glucocorticoids may result in adrenal insufficiency. ACTH secretion generally does not restart until the administered steroid has been given in subphysiologic doses (< 6 mg/m2/day orally) for several weeks.
++
If pharmacologic glucocorticoid therapy has been given for less than 10–14 days, the drug can be discontinued abruptly because adrenal suppression will be short-lived. However, it is advisable to educate the patient and family about the signs and symptoms of adrenal insufficiency in case problems arise.
++
If tapering is not required for the underlying disease, the dosage can be safely decreased to the physiologic range. Although a rapid decrease in dose to the physiologic range will not lead to frank adrenal insufficiency (because adequate exogenous cortisol is being provided), some patients may experience a steroid withdrawal syndrome, characterized by malaise, insomnia, fatigue, and loss of appetite. These symptoms may necessitate a two- or three-step decrease in dose to the physiologic range.
++
Once a physiologic equivalent dose (8–10 mg/m2/day hydrocortisone or equivalent) is achieved and the patient’s underlying disease is stable, the dose can continue to be tapered. There is no clinical evidence to support any particular regimen of glucocorticoid tapering. Patient age, frailty, concomitant illness, and duration of glucocorticoid should all be taken into account when creating a taper regimen. If patients become symptomatic during the taper, the dose should be increased back to the last asymptomatic dose and maintain that dose for two to four weeks. Then the taper can continue.
++
It is advisable to continue giving stress doses of glucocorticoids when appropriate until recovery of the response to stress has been documented. After basal physiologic adrenal function returns, the adrenal reserve or capacity to respond to stress and infection can be estimated by the low-dose ACTH stimulation test, in which 1 mcg of synthetic ACTH (cosyntropin) is administered intravenously. Plasma cortisol is measured 30 and 60 minutes after the infusion. A plasma cortisol concentration greater than 18 mg/dL indicates a satisfactory adrenal reserve. Even if the results of testing are normal, careful monitoring and the use of stress doses of glucocorticoids should be considered during severe illnesses and surgery.
+
Wildi-Runge
S
et al: A search for variables predicting cortisol response to low-dose
corticotropin stimulation following supraphysiological doses of glucocorticoids. J Pediatr 2013 Aug;163(2):484–488
[PubMed: 23414662]
.
+++
ADRENAL MEDULLA PHEOCHROMOCYTOMA
++
Pheochromocytoma is an uncommon tumor, but up to 10% of reported cases occur in pediatric patients. The tumor can be located wherever chromaffin tissue (adrenal medulla, sympathetic ganglia, or carotid body) is present. It may be multiple, recurrent, and sometimes malignant. Familial forms include pheochromocytomas associated with the dominantly inherited neurofibromatosis type 1, MEN type 2, and von Hippel-Lindau syndromes, as well as mutations of the succinate dehydrogenase genes. Neuroblastomas, ganglioneuromas, and other neural crest tumors, as well as carcinoid tumors, may secrete pressor amines and mimic pheochromocytoma.
++
The symptoms of pheochromocytoma are caused by excessive secretion of epinephrine or norepinephrine: headache; sweating; tachycardia, hypertension, vasomotor instability (flushing and postural hypotension); anxiety; dizziness, weakness; nausea, vomiting, diarrhea; dilated pupils, blurred vision; abdominal and precordial pain.
++
Laboratory diagnosis is possible in more than 90% of cases. Serum and urine catecholamines are elevated, but abnormalities may be limited to periods of symptomatology or paroxysm. Plasma-free metanephrine is the most sensitive and specific test, though phenoxybenzamine, tricyclic antidepressants, and β-adrenoreceptor blockers can cause false-positive results. A level three times the normal range is diagnostic. Intermediate values may require additional testing with serum and urine catecholamines. After demonstrating a tumor biochemically, imaging methods including CT or MRI are used to localize the tumor and nuclear medicine using functional ligands such as (123)I-MIBG, [18F]DA positron emission tomography scanning, and somatostatin receptor scintigraphy (with either [123I]Tyr3-octreotide or [111In] DTPA-octreotide) are useful in further diagnostic evaluation.
++
Laparoscopic tumor removal is the treatment of choice; however, the procedure must be undertaken with great caution and with the patient properly stabilized. Oral phenoxybenzamine or intravenous phentolamine is used preoperatively. Profound hypotension may occur as the tumor is removed but may be controlled with an infusion of norepinephrine, which may have to be continued for 1–2 days.
++
Unless irreversible secondary vascular changes have occurred, complete relief of symptoms is to be expected after recovery from removal of a benign tumor. However, prognosis is poor in patients with metastases, which occur more commonly with large, extra-adrenal pheochromocytomas.
+
Waguespack
SG
et al: A current review of the etiology, diagnosis, and treatment of pediatric pheochromocytoma and paraganglioma. J Clin Endocrinol Metab 2010;95(5):2023–2037
[PubMed: 20215394]
.