General Surgery (Board Review Series) 1st Edition

20

Adrenal Gland

1. James Renz III
2. Functional Anatomy
3. Adrenal glands
4. The adrenal glands are retroperitoneal organs located near the superior pole of each kidney (Figure 20-1).
5. Each gland is composed of two functionally distinct regions, the cortex and medulla.
6. The cortexarises from primitive mesoderm.
7. The medullaarises from ectodermal neural crest cells that migrate to the adrenal cortex.

• Extra-adrenal rests of neural crest tissuealong the aorta may persist in the retroperitoneum. The organ of Zuckerkandl is the most notable example, located at the aorta at the level of the inferior mesenteric artery.

1. Arterial supply and venous drainage
2. The arterial supply

• is derived from the inferior phrenic artery, aorta, and the renal artery, which form the superior, middle, and inferior suprarenal arteries, respectively.

2. The adrenal veins
3. The short right adrenal veindrains into the inferior vena cava.
4. The left adrenal veindrains into the left renal vein.
5. Lymphatic drainage and innervation
6. Lymphatics

• parallelthe vascular supply.
• draininto para-aortic, subdiaphragmatic, and renal lymph nodes.

2. There is no innervation to the cortex

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• although the medullareceives preganglionic sympathetic innervation via the splanchnic nerves.

Figure 20-1. Adrenal anatomy. (Adapted with permission from O'Leary JP: The Physiologic Basis of Surgery. Baltimore, Williams & Wilkins, 1996, p 332.)

1. Physiology of the Adrenal Cortex
2. Overview
3. The cortex is subdividedinto 3 zones that are characterized by distinct steroid secretory patterns.
4. Outer zona glomerulosa: aldosteronesecretion.
5. Middle zona fasciculata:predominantly cortisol secretion.
6. Inner zona reticularis:predominantly androgen secretion.
7. The various pathways involved in steroid synthesiswithin the adrenal cortex are outlined in Figure 20-2.
8. The adrenal steroidsexist in unbound and bound (active) forms.

• Binding is mainly by corticosteroid binding globulinand albumin.

1. Secretory products
2. Glucocorticoids
3. Cortisol

• is the principal glucocorticoid in humans.
• is released in episodic bursts with a diurnal peak around 4–6 AM.

1. Secretionis stimulated and regulated by the episodic secretion of adrenocorticotropic hormone (ACTH), sympathetic activation, and feedback inhibition of cortisol.
2. Aldosterone
3. Aldosterone

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• stimulates renal sodium reabsorptionand the secretion of potassium, hydrogen, and ammonia.

1. Secretionis stimulated by the activation of the renin-angiotensin system, hyperkalemia, and ACTH.
2. Sex steroids
3. Dehydroepiandrosterone(DHEA)

• is the major sex steroid produced by the adrenal cortex.

1. Secretionis stimulated and regulated by ACTH, not gonadotropins.
2. Actions of sex steroids
3. DHEA influences male external genitalia and ductal structures.

• Its absence prompts development of female genitalia in the fetus.

2. This steroid also promotes development of male secondary sexual characteristics.

Figure 20-2. Steroid biosynthetic pathway. (Adapted with permission from O'Leary JP: The Physiologic Basis of Surgery. Baltimore, Williams & Wilkins, 1996, p 333.)

III. Diseases of the Adrenal Cortex

1. Hyperadrenocorticism (i.e., Cushing's syndrome)

• is caused by chronically elevated levels of cortisol and corticosterone.

1. Causes of Cushing's syndrome

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1. The most common cause of Cushing's syndromeis chronic exogenous administration of corticosteroids.
2. Other endogenous causes of Cushing's syndrome are outlined in Table 20-1.
3. Clinical manifestationsinclude

• truncal obesity.
• moon facies.
• purple striae.
• hirsutism.
• hypertension.
• menstrual disorders.
• Buffalo hump.
• muscle wasting.
• easy bruising.
• diabetes mellitus.
• amenorrhea.
• impotence.
• edema.
• osteoporosis.
• emotional lability.

Table 20-1. Causes of Endogenous Cushing's Syndrome*

Etiology Pathogenesis Laboratory Findings Cushing's disease (70%) Ecotopic ACTH syndrome (e.g., lung cancer) ACTH-dependent Suppression of cortisol with low-dose and high-dose dexamethasone, high ACTH, and increased skin pigmentation Adrenal adenoma Adrenal carcinoma Adrenal hyperplasia ACTH-independent No suppression of cortisol with low-dose or high-dose dexamethasone, and low ACTH Major depression Alcoholism PseudoCushing's syndrome Suppression of cortisol with low-dose dexamethasone *Exogenous administration of corticosteroids remains the leading cause of Cushing's syndrome. ACTH = adrenocorticotropic hormone.

3. Evaluation of Cushing's syndrome

• includes appropriate laboratory and radiologic assessment (Figure 20-3).

1. Screening tests

• document hyperadrenocorticism.
• include 24-hour urinary free cortisoland the low-dose dexamethasone suppression test.

1. Diagnostic tests
2. These tests differentiate causes of Cushing's syndrome.

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2. Tests include

• serum ACTH levels.
• high-dose dexamethasone suppression test.
• metyrapone stimulation test.
• inferior petrosal sinus sampling.

Figure 20-3. Algorithm for evaluation of Cushing's syndrome. (Adapted with permission from Sabiston DC: Scientific Principles of Surgery. Saunders, 1997, p 681.) ACTH = adrenocorticotropic hormone; CT = computed tomography; MRI = magnetic resonance imaging; CRH = corticotropin releasing hormone.

1. Radiologic assessment
2. A magnetic resonance imaging (MRI)scan should be performed if a pituitary lesion is suspected.
3. An abdominal computed tomography (CT)scan is performed if an adrenal source is suspected.
4. A chest and abdominal CTmay identify an ectopic source.
5. An NP-59 radionuclide imagingstudy may differentiate

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adrenal adenoma or hyperplasia (positive uptake) from an adrenal carcinoma (negative uptake).

4. Treatment

. Cushing's disease

• is treated with transsphenoidal resectionof the pituitary lesion in adults.
• is treated with irradiation in children.

1. An adrenal adenoma

• is treated with unilateral adrenalectomy.

1. Nodular hyperplasia

• is treated with bilateral adrenalectomywith or without reimplantation.

1. Adrenal carcinoma(see III E)
2. Ectopic ACTH syndrome
3. Treatment

• involves either resection of the primary lesionor debulking of unresectable lesions and metastases.

1. Pharmacological adrenalectomy

• with agents that block adrenal steroid production(e.g., metyrapone, aminoglutethimide, ketoconazole, or mitotane) may be performed for inoperable lesions.

2. Bilateral adrenalectomy

• may be performed if one is unable to localize the source or if uncontrollable hypercortisolism is present.

1. Hyperaldosteronism (i.e., Conn's syndrome)
2. Overview

• This syndrome is caused by hypersecretion of aldosterone, which is more common in females(2:1).
• It usually presents in the third to fourth decade.

2. Etiologies
3. Primary causes(decreased plasma renin) include

• aldosterone-producing adenoma (65%–85%).
• bilateral adrenal hyperplasia (25%).
• unilateral adrenal hyperplasia.

1. Secondary causes(increased plasma renin) include

• renal artery stenosis.
• congestive heart failure.
• cirrhosis.
• pregnancy.
• diuretic therapy.
• Bartter's syndrome (renin-secreting tumor).

3. Clinical manifestationsinclude

• hypertension secondary to sodium retention without edema.

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• weakness and fatigue.
• polyuria and polydipsia.
• tetany secondary to hypokalemia.
• menorrhagia.

4. Evaluation of Conn's syndrome

. Initial laboratory studies include

• serum potassium.
• 24-hour urine aldosterone.
• plasma renin activity.

1. The saline infusion test

• can be used to confirm the diagnosis because saline infusioncauses a decrease in plasma aldosterone levels in normal patients, but is unaffected in hyperaldosteronism.

1. Studies differentiating hyperplasia from an adenoma

• include postural studies and 18-hydroxycorticosterone levels.

1. Postural studies

• Because of persistent renin suppression associated with adenomas, morning plasma aldosterone levels remain unchanged or decreasedin the upright position versus initial supine measurements.
• In hyperplasia, the postural renin response is not suppressed, thus the aldosterone level increasesin the upright position.

1. 18-hydroxycorticosteronelevels

• are greater than 100 ng/dL with adenomas.
• are less than 100 ng/dL with hyperplasia.

1. Radiographic assessment

• is often used to localize and differentiate lesions.

1. CT and MRIlocalize lesions in approximately 90% of cases.
2. Adrenal venous sampling and NP-59 scintigraphyhelp differentiate adenomas from hyperplasia.
3. Treatment

• is surgicalfor adrenal adenomas.
• is medicalfor adrenal hyperplasia.

1. Both adenomas and hyperplasia

• are treated with potassium supplementation, calcium channel blockers, and diuresis.

1. Adrenalectomy

• Unilateral adrenalectomyis performed for adenomas.
• Subtotal adrenalectomymay be performed for hyperplasia associated with symptomatic hypokalemia refractory to medical therapy.

1. Adrenogenital syndromes

• are caused bycongenital adrenal hyperplasia (90%) or adrenal neoplasms (10%).

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1. Congenital adrenal hyperplasia (CAH)

• represents inherited defects of enzymes necessary for cortisol synthesis, which shunts cortisol precursors into androgen pathways (Table 20-2).

1. 21-Hydroxylase deficiency

• is the most common enzymatic defect that causes CAH (90%).
• occursin 1 in 10,000 live births.
• causesdeficits of aldosterone and cortisol and increased production of testosterone.

4. Clinical manifestationsinclude

• diarrhea.
• hypovolemia.
• hyponatremia.
• hyperkalemia.
• hyperpigmentation.
• virilization.

5. Diagnosis

• Increased 17-hydroxyprogesterone and testosteronelevels are often diagnostic.

6. Treatment

• is with glucocorticoid and mineralocorticoid replacement, and in females with ambiguous genitalia, surgical correction as well.

1. 11-B-hydroxylase deficiency

• is the second most common enzymatic defect causing CAH (5%).

Table 20-2. Syndromes of Congenital Adrenogenital Hyperplasia

Deficiency Characteristics Salt Metabolism 21-Hydroxylase Genotypic females present with ambiguous external genitalia and postnatal virilization Salt wasting 11-B-hydroxylase Genotypic females present with ambiguous external genitalia and postnatal virilization Hypertension 17-Hydroxylase Genotypic males present with ambiguous external genitalia Hypertension 3β-Dehydroxylase Genotypic males and females may present with ambiguous external genitalia and postnatal virilization in females With or without salt wasting

2. Adrenal neoplasms

• that cause adrenogenital syndromes are usually adrenal carcinomas or adenomas.

1. Virilizing adrenal tumorsare more common in women.

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1. Clinical manifestationsinclude

• premature hirsutism.
• macrogenitosomia praecox.
• small testes and infertility in boys.
• clitoral enlargement and premature pubic hair in girls.

1. Symptoms

• Menare often asymptomatic.
• Womendisplay hirsutism and masculinization.

2. Diagnosis
3. Elevated levels of plasma DHEA, testosterone, and urine 17-ketosteroids are frequently present.
4. CT scanningmay be useful for localization of lesions.
5. The ACTH stimulation testmay also help to confirm such tumors.
6. Treatment

• involves surgical resection and the administration of mitotanefor recurrent disease.

1. Feminizing adrenal tumors
2. Clinical manifestationsinclude

• impotence.
• amenorrhea.
• gynecomastia.
• testicular atrophy in men.
• precocious puberty.
• breast enlargement.
• early menses.

1. Diagnosis

• Elevated urinary 17-ketosteroidsand estrogens are often diagnostic.

2. Treatment

• is again surgical, while mitotane may be administered for recurrent disease.

1. Adrenal insufficiency (i.e., Addison's disease)
2. Overview

• This disease occurs in 1 in 5000 hospitalized patients, usually during the third to fifth decades.

2. Etiologies
3. Primary causes(adrenal source) include

• autoimmune disorders (65%–85%).
• infectious sources (30%).
• adrenal hemorrhage.

1. Secondary causesinclude

• withdrawal of exogenous steroids.
• pituitary disease.

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• surgical resection or injury to the glands.
• adrenal metastases.

3. Clinical manifestations

. These result from glucocorticoid and mineralocorticoid deficiencies.

1. Signs and symptomsinclude

• fever.
• nausea and vomiting.
• lethargy and fatigue.
• abdominal pain.
• weight loss.
• hypotension.
• anorexia.
• diarrhea.
• hyperpigmentation.

4. Diagnosis

. An ACTH stimulation test

• often confirms the diagnosis (Table 20-3).

1. Other laboratory abnormalitiesinclude

• hyponatremia.
• hyperkalemia.
• azotemia.
• hypoglycemia.
• low plasma.
• urinary cortisol.

5. Treatmentincludes

• saline and glucose administration
• glucocorticoid replacement.
• mineralocorticoid replacement for chronic disease.

Table 20-3. Characteristics of Adrenal Insufficiency

Primary Adrenal Insufficiency Secondary Adrenal Insufficieny ACTH levels Increased Decreased Aldosterone levels Increased Decreased ACTH stimulation test Increased ACTH levels Decreased cortisol levels Decreased ACTH levels Decreased cortisol levels Skin pigmentation Hyperpigmentation Normal pigmentation Headaches, vision loss Rare Frequent ACTH = adrenocorticotropic hormone.

1. Adrenocortical carcinoma
2. Overview
3. These are rare tumors occurring with a bimodal age distribution (before age 5 and during the fifth decade).

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1. Sixty percent secrete hormones.
2. Fifty percent present as a large mass, and approximately 50% have metastases.
3. Clinical manifestations
4. Presenting symptoms in adultstypically include

• abdominal pain.
• increased abdominal girth.
• weight loss.
• weakness.
• anorexia.
• nausea.

1. Children display

• virilization over 90% of the time.

3. Evaluation and staging

• should include CT, MRI, and a bone scan.

4. Treatmentinvolves

• attempted complete resection, in addition to medical therapy for control of symptoms.

1. Recurrencesmay be treated with reoperation.
2. Debulking and chemotherapy, involving mitotane, are beneficial in controlling symptomsand prolonging survival.
3. Physiology of the Adrenal Medulla
4. Cells of the adrenal medulla

• produce biologically active catecholamines including epinephrine (80%), norepinephrine (20%), and dopamine.

1. Catecholamine secretion
2. Secretion is stimulatedby

• sympathetic activation.
• anorexia.
• endotoxins.
• body temperature changes.

2. Secretion is inhibitedby prostaglandins.
3. Diseases of the Adrenal Medulla
4. Pheochromocytoma
5. Overview
6. These tumors

• are slow-growing, catecholamine-secretingtumors.

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• arise from chromaffin cells of the adrenal medulla(85%) or sympathetic ganglia.
• usually presentin the fourth to fifth decades.
• are rarewith fewer than 0.1% per year, but there is an increased frequency in association with multiple endocrine neoplasia (MEN) II syndromes (see VI C).

1. The “Rule of Tens”associated with pheochromocytomas include:

• 10% are malignant.
• 10% are familial(associated with MEN syndrome).
• 10% are found in children.
• 10% are bilateral(50% in children and 100% in familial forms).
• 10% are extra-adrenal.

1. Malignancy

• is more common in women (3:1), children, and extra-adrenal locations.

2. Clinical manifestationsinclude

• hypertension(95%) that is frequently episodic.
• headache(80%).
• diaphoresis(70%).
• palpitations(60%).

3. The differential diagnosesinclude

• essential hypertension.
• migraines.
• tachycardia.
• endocrine abnormalities.
• central nervous system (CNS) disorders.
• tumors.
• pregnancy.
• renal artery stenosis.

4. Evaluation of pheochromocytoma

• involves confirmation of catecholamine excess and tumor localization.

1. Laboratory evaluation
2. Urinary vanillylmandelic acid(VMA) and metanephrine levels may be elevated.
3. Urinary free or serum catecholaminelevels may be useful markers in equivocal cases.
4. The clonidine suppression testmay be useful if urinary catecholamines are equivocal and the diagnosis is strongly suspected because clonidine will not suppress norepinephrine levels in affected patients.
5. Radiologic assessment
6. CTor MRI may help to localize tumors.

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1. Metaiodobenzylguanidine (MIBG) radionuclide scanningis particularly helpful in identifying extra-adrenal tumors.
2. Arteriography or fine needle aspiration (FNA) is not indicated.
3. Treatment

• involves both medical and surgical therapy.

1. Medical treatment

• should precede surgical resection.

1. Reversal of vasoconstrictionwith α-blockade (e.g., phenoxybenzamine, prazosin) is essential.
2. α-Blockade should be administered 1 week preoperatively to prevent vascular instability.
3. Phenoxybenzamine is also indicated if blood pressure is over 200/130 mm Hg, there are uncontrolled hypertensive attacks, hematocrit is over 50%, or with anticipated use of β blockers.
4. Administer fluids and restore blood volume.
5. Following appropriate α-blockade, administration of β-blockersis often indicated (e.g., propranolol).
6. This is indicated for heart rate over 130, for arrhythmias, or if the tumor secretes large amounts of epinephrine.
7. β Blockers should never be administered before α blockadebecause unopposed α activity may result, causing vasoconstriction and cardiac failure.
8. Metyrosineinhibits tyrosine hydroxylase, causing decreased synthesis of catecholamines; this may also be beneficial.
9. Morphineand meperidine should be avoided preoperatively because they may stimulate catecholamine release or cause hypotension.
10. Surgical treatment

• involves resection or debulkingto control symptoms.
• Negative localization still warrants exploratory laparotomy.

6. Complicationsinclude

• hypertension.
• hypotension.
• intracranial bleeding.
• arrhythmias.
• congestive heart failure.
• myocardial infarction.

1. A neuroblastoma

• is an embryonal tumor of neural crest origin that arises in the sympathetic chain (see BRS Surgical Specialties, Chapter 3).

1. A ganglioneuroma

• is a rare, benign, often asymptomatic tumor of neural crest origin involving the adrenal gland or sympathetic trunk.

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1. Incidental Finding of an Adrenal Mass (Incidentaloma)
2. Incidentalomas

• are unsuspected adrenal masses identified during evaluation of other processes (Figure 20-4).
• are frequently benign(e.g., adenomas), but a portion of incidentalomas may be metastatic disease or adrenal carcinomas (5%).

1. Evaluation of incidentalomas

• is necessary to identify a hormonally active lesion or an adrenocortical carcinoma.

1. Laboratory studiesinclude

• serum potassium.
• 24-hour urinary free cortisol.
• urine 17-hydroxycorticosteroids, VMA, and metanephrines.
• plasma aldosterone and renin levels, if hypertensive or hypokalemic.

2. Radiologic assessment

• includes a chest radiograph and abdominal CT scan.
• may also include an MRIor MIBG scan for suspicious or symptomatic lesions.

Figure 20-4. Incidental finding of an adrenal mass on an abdominal computed tomography (CT) scan performed for trauma evaluation.

1. Surgical resection

• is indicated for lesions with significant malignant potential.

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1. Tumorswith a higher potential for malignancy include

• functional tumors(e.g., hormone-producing tumors).
• tumors that are enlarging over time.
• tumors larger than 5 cm.
• Tumors that meet these criteriagenerally require surgical resection.

2. Nonfunctional, stable tumors smaller than 3 cm

• have a lower potential for malignancy.
• may be managed with close follow-up and serial CT scans.

3. Tumors 3–6 cm

• may require additional diagnostic work-up.
• should be treated individually.

Table 20-4. Multiple Endocrine Neoplasia (MEN) Syndromes

Syndrome Components MEN I (Wermer's) Parathyroid hyperplasia (90%) Pancreatic islet tumors (80%) Pituitary tumors (65%) MEN IIA (Sipple's) Medullary thyroid carcinoma (100%) Pheochromocytoma (50%) Parathyroid hyperplasia (40%) MEN IIB Medullary thyroid carcinoma (100%) Pheochromocytoma (50%–90%) Mucosal neuromas (100%) Marfanoid habitus (70%)

VII. Multiple Endocrine Neoplasia (MEN) Syndromes

(Table 20-4)

1. Overview
2. MEN syndromes are a group of familial disorders

characterized by the development of neoplasms in multiple endocrine glands.

2. They are derived from APUD(amine precursor uptake decarboxylation) cells.
3. The neoplasms may developsynchronously or metachronously.
4. These syndromes are inheritedin an autosomal dominant fashion with 100% penetrance but variable expressivity.
5. MEN I syndrome (i.e., Wermer's syndrome)

• is caused by a defect in chromosome 11, which involves a tumor suppressor gene.

1. Common components of MEN I syndromeinclude

• primary hyperparathyroidism(see Chapter 19 VI B).

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• pancreatic islet cell tumors(see Chapter 17 IV B).
• pituitary tumors.

2. Most patients presentwith pancreatic hypersecretion.
3. The most common tumors

• include gastrinomas(60%) and insulinomas (30%). These present with symptoms of peptic ulcer disease or hypoglycemia, respectively.

1. Neoplasms

• are usually malignant, multicentric, and microadenomas.

3. Hyperparathyroidism

• presents similarlyto sporadic hyperparathyroidism with hypercalcemia (see Chapter 19 VI B, C).
• usually presents in the third to fourth decade of life, but rarely before age 10.

4. Pituitary neoplasm

. Pituitary tumors are associated with

• headaches.
• visual field defects.
• galactorrhea and amenorrhea in women.
• hypogonadism in males.

1. Neoplasms are usually prolactinomas(40%).
2. Diagnosis

• begins with biochemical confirmation of hypersecretory states.

6. Treatment

• involves attention to all neoplastic changes.

1. If hypercalcemia is present, total parathyroidectomy with autotransplantation

• is recommended over subtotal parathyroidectomy because of a high incidence of recurrence.

1. Resection of pancreatic tumors

• depends on the type of tumor present.

1. Bromocriptine

• is often used to decrease the size and inhibit hormone production of prolactinomas, and is followed by surgical ablation, irradiation, or both.

1. Cabergoline or pergolide may also be used to decrease the size of pituitary prolactinomas.
2. Differences exist

• between the neoplastic disorders in familial (MEN) forms and sporadic forms.

1. Gastrinomas

• are usually malignant with MEN I, but benign with sporadic forms.

1. Insulinomas

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• are multiple with MEN I, but generally solitary with sporadic forms.

1. MEN II syndrome
2. These disorders can be dividedinto MEN IIA (Sipple's syndrome) and MEN IIB.

• Both MEN IIA and IIB are highly associated with medullary thyroid carcinoma and pheochromocytomas.
• Additional associations are listed in Table 20-4.

2. Clinical manifestations
3. Medullary thyroid carcinoma
4. These tumors arisefrom C-cells that secrete calcitonin, which inhibits bone resorption and decreases calcium levels.
5. These tumors usually presentin the second to third decade, as opposed to the fifth to sixth decade in sporadic forms.
6. This is often the earliest expressed defectin MEN II syndromes.
7. Diarrheais the most common symptom.
8. Tumors are often bilateral.
9. Pheochromocytoma
10. These tumors usually presentin the second to third decades.
11. Sixty to eighty percent are bilateral (only 10% of sporadic forms are bilateral).
12. These tumors are nearly always benign (90%), unless they are extra-adrenal (50%).
13. Hyperparathyroidism(see Chapter 19 VI).
14. Evaluation

. Evaluation begins with confirmation of a hypersecretory state and tumor localization.

1. Laboratory findingsmay include

• elevated calcium levels.
• elevated calcitonin levels (> 300 pg/mL).
• increased calcitonin with pentagastrin challenge.
• elevated urinary catecholamines and metabolites.
• presence of the retoncogene

4. Treatment

. Unilateral or bilateral adrenalectomy

• should be performed for unilateral and bilateral pheochromocytomas, respectively.

1. Thyroidectomy and parathyroidectomy

• can be performed simultaneously 1–2 weeks after adrenalectomy.

1. A total thyroidectomy with central lymph node dissection

• is generally performed for medullary thyroid tumors.
• Many surgeons advocate total thyroidectomy with a radical neck dissection for MTC associated with MEN II.

1. A total parathyroidectomy with autotransplantation

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• is generally performed for hypercalcemia or an enlarged parathyroid gland.

5. Differences between familial (MEN) and sporadic forms

. Medullary thyroid carcinoma

• is usually bilateral with MEN.
• is often more aggressive when associated with MEN.
• is unilateral with sporadic forms.

1. Pheochromocytomas

• are usually bilateral (60%–80%) with MEN.
• are unilateral (90%) with sporadic forms.

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Review Test

Directions: Each of the numbered items or incomplete statements in this section is followed by answers or by completions of the statement. Select the ONE lettered answer or completion that is BEST in each case.

1. A 26-year-old woman presents with anxiety and hypertension, and is diagnosed with a presumed pheochromocytoma based on preliminary laboratory studies. Which of the following diagnostic tests is contraindicated for pheochromocytoma?

(A) Computed tomography (CT)

(B) Magnetic resonance imaging (MRI)

(C) Metaiodobenzylguanidine (MIBG) radionuclide scanning

(D) Selective arteriography

(E) Ultrasound

1–D. Computed tomography (CT), magnetic resonance imaging (MRI), metaiodobenzylguanidine (MIBG) scans, and ultrasound can all be used in the work-up of a suspected adrenal mass. Ultrasound is the least useful of these tests owing to limited resolution and limited visualization of surrounding anatomy. In addition, ultrasound can only visualize tumors larger than 2 cm. CT scan provides more information about surrounding anatomical structures and is useful for detecting tumors as small as 1 cm. MIBG selectively accumulates in chromaffin tissue and will do so more rapidly in a pheochromocytoma than in normal tissue. Selective angiography is contraindicated because a sudden increase in intraglandular pressure can cause a massive release of catecholamines and precipitate a hypertensive crisis.

2. Which of the following adrenal masses could be treated with observation and follow-up after a complete metabolic work-up?

(A) Nonfunctioning, 3-cm, solid adrenal mass in a 38-year-old man

(B) Nonfunctioning, 7-cm, cystic adrenal mass in a 25-year-old woman

(C) Functioning, 2-cm, cystic mass in a 45-year-old woman

(D) Nonfunctioning, solid mass that has doubled in size in 1 year in a 67-year-old man

(E) A 10-cm, solid adrenal mass in a 56-year-old man

2–A. General criteria that are considered indications for surgical intervention for an adrenal mass include functional tumors of any size, tumors that increase in size during follow-up, and nonfunctional tumors that are 6 cm or larger. These tumors are at greatest risk for harboring malignancy. Nonfunctioning adrenal tumors smaller than 6 cm are unlikely to harbor malignancy and some surgeons advocate simple observation and follow-up computed tomography (CT) scans in 3 to 6 months. Some surgeons use 3–4 cm as the upper limit instead of 6 cm.

3. A 45-year-old man presents with a 4-cm adrenal mass that has been diagnosed as a pheochromocytoma by preoperative testing. Preoperative preparation in this patient should initially include which of the following?

(A) Administration of phenoxybenzamine

(B) Administration of propranolol, followed by phenoxybenzamine

(C) Administration of furosemide

(D) Fluid restriction

(E) Administration of propranolol

3–-A. The physiologic effects seen in a patient with a pheochromocytoma are a result of α- and β-adrenergic stimulation. α-Receptor blockade (e.g., phenoxybenzamine, phentolamine) should be instituted before surgery to counteract the diffuse vasoconstriction seen in patients with an active pheochromocytoma. The vasodilation that ensues after α blockade will result in a functional hypovolemia, making diuretic therapy (e.g., furosemide) and fluid restriction contraindicated before surgery. β-antagonist therapy (e.g., propranolol) is often needed after α antagonist therapy is instituted to counteract the reflex tachycardia that may result. However, β-antagonist therapy should never be started before α blockade, as it can result in unopposed α stimulation from the pheochromocytoma, causing malignant hypertension and congestive heart failure.

4. A 40-year-old woman who has been treated with prednisone for 2 years for rheumatoid arthritis undergoes emergent splenectomy after a motor vehicle accident. Postoperatively, the patient develops fever, abdominal pain, nausea, and vomiting. Laboratory data reveal hyperkalemia, hypoglycemia, and hyponatremia. Immediate measures should include which of the following?

(A) Rapid correction of hyponatremia

(B) Administration of saline, glucose, and dexamethasone

(C) Saline infusion and fludrocortisone

(D) Intravenous hydrocortisone alone

(E) Plasma adrenocorticotropic hormone (ACTH) and cortisol levels after initiation of therapy

4–B. Emergency measures in the treatment of acute adrenal insufficiency include establishment of intravenous (IV) access, immediate assessment of serum electrolyte, glucose, and adrenocorticotropic hormone (ACTH) levels, and subsequent infusion of 2–3 liters of isotonic saline. Treatment with IV dexamethasone should also be instituted. Initiation of therapy before measuring plasma ACTH and cortisol may interfere with assessment of these hormones. Rapid correction of hyponatremia is rarely indicated, as central pontine myelinolysis can result. Fludrocortisone has no role in the acute management of acute adrenal insufficiency, although it is used in the treatment of chronic insufficiency. Hydrocortisone alone without adequate administration of fluids is inadequate therapy.

5. A 45-year-old man presents to the emergency room after having fallen from a height of 12 feet. He complains only of abdominal pain, and a computed tomography (CT) scan is eventually performed to evaluate his abdomen. No injuries are noted but a 5-cm solid adrenal mass is detected. Which of the following studies is inappropriate in the work-up of this lesion?

(A) Serum potassium

(B) Serum aldosterone

(C) Fine needle aspiration (FNA)

(D) Chest radiograph

(E) Urine metanephrines

5–C. The work-up of adrenal incidentalomas should include serum and urine testing to assess the possibility of a functional tumor. A chest radiograph should also be obtained to rule out the possibility of a metastatic lesion from the chest. Fine needle aspiration (FNA) has no place in the work-up of a new adrenal lesion because the information obtained is rarely helpful unless the lesion is metastatic. In addition, FNA may be dangerous because of the risk of precipitating a hypertensive crisis in a patient with a pheochromocytoma.

6. A 62-year-old man presents with an 8-cm, nonfunctioning adrenal tumor. Which of the following statements is true regarding the surgical approach in this patient?

(A) The anterior approach is usually used for patients with potential bilateral disease

(B) The posterior approach is used for lesions larger than 5 cm because of greater exposure of the retroperitoneum

(C) The lateral approach is the preferred method for patients with bilateral adrenal disease

(D) Laparoscopic adrenalectomy is contraindicated in right-sided lesions because of the short adrenal vein

(E) Laparoscopic adrenalectomy is contraindicated in lesions larger than 4 cm

6–A. Adrenal tumors can be removed by a variety of surgical approaches. An anterior approach is preferred for suspected bilateral tumors because it allows for inspection of both glands through a single incision. The posterior approach is generally better tolerated postoperatively but gives only limited exposure. The lateral approach is used for large, unilateral tumors or for bilateral tumors in obese or high-risk patients, although it is not generally the preferred method because of the postoperative pain and morbidity associated with bilateral subcostal flank incisions. Laparoscopic adrenalectomy is more difficult in right-sided and large lesions, but is not contraindicated in either scenario.

Directions: Each set of matching questions in this section consists of four to twenty-six lettered options followed by several numbered items. For each numbered item, select the appropriate lettered option(s). Each lettered option may be selected once, more than once, or not at all.

Questions 7–11

1. Cushing's disease
2. Ectopic adrenocorticotropic hormone (ACTH) syndrome
3. Adrenal carcinoma/adenoma
4. Hyperaldosteronism
5. Adrenogenital syndrome
6. Pheochromocytoma
7. Primary hyperparathyroidism
8. Multiple endocrine neoplasia (MEN) II syndrome

Match the following surgical causes of hypertension with their respective clinical scenarios.

7. A 30-year-old man presents with truncal obesity, hypertension, and weakness. Work-up reveals increased urine cortisol and decreased plasma ACTH. (SELECT 1 CAUSE)

7–C. This patient exhibits the signs and symptoms of plasma cortisol excess. Possible causes include Cushing's disease, ectopic adrenocorticotropic hormone (ACTH) syndrome, adrenal cancer, adrenal adenoma, and iatrogenic causes. However, the fact that this patient's plasma ACTH is decreased rules out Cushing's disease (primary pituitary source). Although not one of the choices listed, it should be noted that ACTH may be decreased in the presence of signs and symptoms of Cushing's syndrome with exogenous administration of corticosteroids.

8. A 65-year-old man presents with truncal obesity, hypertension, and weight loss. Work-up reveals increased urinary cortisol and ACTH. (SELECT 2 CAUSES)

8–A, B. There are numerous potential causes of Cushing's syndrome. Both ectopic adrenocorticotropic hormone (ACTH) production and Cushing's disease would produce elevated cortisol and ACTH. These two possible causes can usually be differentiated from one another with the aid of a dexamethasone suppression test.

9. A 30-year-old man presents with hypertension and weakness. Work-up reveals the following laboratory values: Na¹= 153, K¹ = 1.9, blood pressure = 150/98, central venous pressure = 15. (SELECT 1 CAUSE)

9–D. Elevated serum sodium, decreased serum potassium, and hypertension are the classic signs of hyperaldosteronism (i.e., Conn's syndrome). Work-up of this patient would include 24-hour urine aldosterone as well as plasma renin activity. Diagnostic studies are needed to differentiate adrenal hyperplasia from an adenoma because the treatments differ for these two possible causes (medical therapy for hyperplasia versus surgical treatment for an adenoma).

10. A 26-year-old man presents with episodic hypertension and anxiety. Work-up reveals increased urinary vanillylmandelic acid (VMA) and metanephrines. (SELECT 1 CAUSE)

10–F. Complaints of episodic hypertension should raise suspicion for a pheochromocytoma, especially in young patients. Increased levels of catecholamine breakdown products (vanillylmandelic acid and metanephrines) in the urine essentially confirms the diagnosis. Further localization studies include abdominal computed tomography (CT), magnetic resonance imaging (MRI), or metaiodobenzylguanidine (MIBG) scan.

11. A 30-year-old woman presents with a 4-month history of hypertension and a thyroid mass. Work-up reveals hypercalcemia. (SELECT 1 CAUSE)

11–H. The diagnosis of pheochromocytoma should be considered in any young patient who presents with hypertension. Furthermore, the additional finding of a thyroid mass should raise suspicion for the multiple endocrine neoplasia (MEN) II syndrome (pheochromocytoma, medullary thyroid cancer, and hyperparathyroidism). Preoperative work-up should include serum calcium levels in patients with suspected MEN II syndrome because any parathyroid dysfunction can be addressed at the same time as the thyroid mass. Should a pheochromocytoma also be present, it should be addressed first at a separate procedure.