Campbell Adrenal Disorders 2021

Question 1

Cells of this tissue zone are the sole source of aldosterone

Answer 1

Zona glomerulosa

** Aldosterone regulates electrolyte metabolism by stimulating epithelial cells of the distal nephron to reabsorb Na+ and Cl−, while secreting H+ and K+.

Question 2

Site of glucocorticoid production.

Expression of enzymes: 17alpha-hydroxylase, 21-hydroxylase, and 11beta-hydroxylase.

Answer 2

Zona fasciculata

** Cortisol: primary glucocorticoid in humans, controlled by ACTH

Question 3

Production of DHEA, sulfated DHEAS, and androstenedione

Answer 3

Zona reticularis

Question 4

Lies at the center of the adrenal;
Integral part of the autonomic nervous system;
Secretes catecholamines;
Source of metanephrine and normetanephrine

Answer 4

Adrenal medulla

Question 5

Catalyzes conversion of NE to epineprhine

Expressed in the adrenal medulla, brain, and organ of Zuckerkandl

Answer 5

Phenyethanolamine-N-methyltransferase (PNMT)

Question 6

Hypercortisolism secondary to excessive production of glucocorticoids by the adrenal cortex.

Answer 6

Cushing syndrome

Question 7

Three main groups of causes of Cushing syndrome

Answer 7

Exogenous: iatrogenic glucocorticoid administration

ACTH dependent: elevated serum corticotropin level by pathology extrinsic to adrenal (85% of Cushing syndrome)

ACTH independent: unregulated overproduction of glucocorticoids by the adrenal (rare)

Question 8

Most common cause of hypercortisolism in the West.

Answer 8

Exogenous Cushing syndrome

Question 9

85% of endogenous Cushing syndrome
Majority: primary pituitary pathology
Other causes: Ectopic ACTH production, ectopic CRH production

Answer 9

ACTH dependent Cushing Syndrome

Question 10

Cushing Syndrome vs. Cushing Disease vs. Cushing Triad

Answer 10

Syndrome: Hypercortisolism secondary to excessive production of glucocorticoids

Disease: hypercortisolism through excessive secretion of ACTH by the pituitary gland/macroadenoma

Triad: triad of elevated intracranial pressure (widened pulse pressure, irregular respiration, bradycardia)

Question 11

ACTH-producing nonpituitary tumors
Almost always malignant
10% of Cushing syndrome

Answer 11

Ectopic ACTH Syndrome

Question 12

Extremely reare
<1% of Cushing syndrome
Bronchial carcinoma most common culprit

Answer 12

Ectopic CRH

Question 13

Uncontrolled hypersecretion of cortisol by adrenal tissues

Answer 13

ACTH-independent Cushing syndrome

** Adrenal neoplasms and bilateral adrenal disease are in this group

Question 14

Multiple large (4cm) nodules replacing the glands
Each gland weighs > 60 g
<1% of Cushing syndrome

Answer 14

ACTH-independent Macronodular Adrenal Hyperplasia (AIMAH)

Question 15

Normal-sized adrenals
Black or brown cortical nodules
<1% of Cushing syndrome
Autosomal Carney complex (50%): spotty skin and mucous membrane lesions

Answer 15

Primary pigmented nodular adrenocortical disease (PPNAD)

Question 16

Cushing syndrome

Answer 16

Central obesity
Moon facies
Buffalo hump
Proximal muscle weakness
Easy bruisability
Abdominal striae

Metabolic syndrome (dyslipidemia, insulin resistance, hypertension

**These are non-specific

Question 17

___% of patients with Cushing syndrome exhibit ___.

Answer 17

50%
Urolithiasis

** Stone formers with cushingoid features also should receive a hypercortisolemia evaluation

Question 18

Hypercortisolemia inbsence of an overt cushingoid phenotype.

Answer 18

Autonomous Cortisol Secretion (subclinical Cushing syndrome)

Question 19

Explain:

Low-dose dexamethasone suppression test

Answer 19

Low-dose dexamethasone should act on corticotropic cells of ant. pituitary gland –> suppresses ACTH production –> decreases serum cortisol

Failure to suppress cortisol levels: Cushing syndrome

DOES NOT delineate cause of hypercortisolism and cannot reliably detect subclinical Cushing syndrome

Question 20

Explain:
Late night salivary cortisol
Midnight plasma cortisol

Answer 20

Cushing syndrome causes disruption of diurnal variation of cortisol levels

Normal: Cortisol peaks in the AM, decreases in the PM
Cushing: Persistent elevation in the PM

Question 21

If (+) Cushing syndrome screening:

How do you differentiate between ACTH dependent vs independent?

Answer 21

Test for serum ACTH:

Low ACTH: ACTH independent

** The true diagnostic difficulty lies in distinguishing Cushing disease from the ectopic ACTH syndrome for patients who have high serum ACTH levels.

Question 22

If (+) ACTH dependent:

Differentiate ectopic ACTH vs. Cushing disease

Answer 22

Direct measurements of ACTH in a downstream venous plexus that drains the pituitary gland—the inferior petrosal sinus—after CRH stimulation has become the gold standard approach for distinguishing ectopic ACTH production from Cushing disease

Question 23

Consequence of bilateral adrenalectomy for refractory hypercorstiolism due to Cushing disease

Answer 23

Nelson-Salassa Sydrome

** progressive growth of their pituitary adenoma, mainly resulting in complications such as ocular chiasm compression, oculomotor deficiencies, and, rarely, a rise in intra- cranial pressure

Prophylactic radiation therapy may prevent phenomenon

Question 24

Single best therapeutic approach to normalizing cortisol levels in patients with ectopic ACTH syndrome

Answer 24

Resection of the primary ACTH-producing tumor

Question 25

Most common form of secondary hypertension

Answer 25

Primary aldosteronism

Question 26

Aldosterone secretion independent of RAAS | Suppressed plasma renin levels

Answer 26

Primary aldosteronism

Question 27

Elevated renin levels --> elevated aldosterone secretion

Answer 27

Secondary aldosteronism

Question 28

Aldosterone increases sodium ___ and potassium ___ in the distal nephron, BUT does NOT cause hypernatremia (reabsorption is accompanied by water uptake)

Answer 28

Na reabsorption | K secretion

Question 29

Causes of Conn syndrome

Answer 29

``` Bilateral adrenal hyperlasia 60% Adenoma 35% Unilateral adrenal hyperplasia 2% Carcinoma <1% Ectopic aldosterone secreting tumor <1% Familial hyperaldosteronism <1% ```

Question 30

Indications for Primary Aldosterone Screening (Box 106.2)

Answer 30

Hypertension with hypokalemia Resistant hypertension (three or more oral agents including a diuretic) Controlled hypertension on four or more antihypertensives Adrenal incidentaloma with hypertension Hypertension with sleep apnea Early-onset hypertension (<20 years) or stroke (<50 years) Severe hypertension (≥150/≥100) measured on 3 different days Whenever considering secondary causes of hypertension (i.e., pheochromocytoma or renovascular disease) Unexplained hypokalemia (spontaneous or diuretic induced) Evidence of target organ damage disproportionate to degree of hypertension Hypertension with family history of primary aldosteronism

Question 31

Screening for primary aldosteronism

Answer 31

8AM-10AM Plasma aldosterone concentration (PAC) PRA Direct renin concentration (DRC) Then calculate aldosterone-renin-ratio (ARR)

Question 32

Confirmatory tests for primary aldosteronism

Answer 32

Fludrocortisone suppression test Oral sodium loading test IV saline infusion test Captopril suppression test

Question 33

Fludrocortisone suppression test

Answer 33

Fludrocortisone (0.1 mg every 6 hours) + sodium chloride (2 g every 8 hours) x 4 days After 4 days: PAC is measured in the upright position ** Failure to suppress PAC to less than 6 ng/dL is diagnostic of primary aldosteronism

Question 34

Oral sodium loading test

Answer 34

High-sodium diet for 3 days, then 24-hour urine measurements of aldosterone, sodium (at least 12.8 g a day), and creatinine **Diagnosis of primary aldosteronism is then made when the 24-hour aldosterone is greater than 12 μg/day.

Question 35

Patients with confirmed PA should undergo ___ when adrenalectomy is being considered. Exceptions: <40 yo, clear unilateral adrenal adenoma, normal contralateral adrenal gland

Answer 35

Adrenal vein sampling

Question 36

Medical management for PA who are not surgical candidates

Answer 36

Aldosterone receptor antagonists spironolactone and eplerenone are successful in lowering blood pressure and are the antihypertensive agents of choice in patients with primary aldosteronism.

Question 37

Chromaffin bodies in between the aortic bifurcation and the root of the inferior mesenteric artery

Answer 37

Organ of Zuckerkandl ** Common site of paragangliomas

Question 38

Components of the 10% tumor (pheochromocytoma)

Answer 38

``` 10% extra-adrenal, 10% familial, 10% bilateral, 10% pediatric, and 10% malignant ```

Question 39

Pheochromocytoma on imaging

Answer 39

Well-circumscribed Rich vascularity, low lipid content > 10 HU attenuation on unenhanced CT (vs. lipid rich adenomas) DO NOT exhibit rapid contrast washout on delayed imaging Classically: light bulb sign (T2 weighted bright signal intensity)

Question 40

Most common alpha-blocker for preoperative catecholamin blockade of pheochromocytoma

Answer 40

Phenoxybenzamine ** 7-14 days preop, 10 mg OD, titrated to 10-20 to maintain BP 120-130/80 sitting

Question 41

Life-threatening condition Preceded by hypotension unresponsive to fluid resuscitation Acute abdomen, abdominal pain, nausea, vomiting, and fever

Answer 41

Acute adrenal insufficiency or adrenal crisis TX: Hydrocortisone Fludrocortisone

Question 42

Hereditary disorders associated with ACC

Answer 42

Li-Fraumeni syndrome | Beckwith-Wiedemann syndrome

Question 43

Most common hormone secreted by ACC: ____ Second most common: ___

Answer 43

Cortisol (50-80% of functional tumors) Androgens (40-60% of functional tumors)

Question 44

Imaging characteristics of ACC

Answer 44

Larger than benign tumors (avg. size 10-12 cm) 90% of ACC are larger than 5 cm Irregular borders Irregular enhancement Calcifications Necrotic areas with cystic degeneration Mean attenuation (39HU) higher than adenomas (8HU)

Question 45

Preferred surgical management for adrenal tumors > 6 cm or those with evidence of local invasion

Answer 45

Open adrenalectomy/surgery ** Metastatic: consider cytoreductive removal and debulking metastasectomy IF >90% disease burden can be removed

Question 46

Mitotane MOA

Answer 46

Direct cytotoxicity of cells in adrenal cortex Oxidative damage via free radicals Inhibition of enzymes involved in steroid synthesis

Question 47

Most valuable imaging study for diagnosis of adrenal adenoma

Answer 47

Non-contrast CT: measures density, uniformity, and size ** Attenuation < 10 HU = strongly suggestive of benign adrenal adenoma

Question 48

NIH Consensus: Adrenal lesions > 1cm should undergo ___. Metabolically active adenomas should undergo: ___

Answer 48

Metabolic evaluation Resection

Question 49

Incidentaloma CT evaluation: request washot films IF: ___

Answer 49

> 10 HU on CT or lack of signal dropout on chemical shift MR

Question 50

Absolute and relative percent washout

Answer 50

Absolute: (E - D)/(E-U) x 100 Relative: (E - D)/(E) x 100 If > 60% absolute and >40% relative --> adenoma If <60% absolute and <40% relative --> adenoma unlikely

Question 51

The 5-way Test for Adrenal Mass Biopsy

Answer 51

Can the mass be characterized with imaging? NO. Metabolically active? NO. Will biopsy change management? YES. ACC strongly suspected? NO. Benefit of biopsy justify risks inc. making lap adrenalectomy difficult? YES. If these are your answers, then PERFORM BIOPSY (pheo must be ruled out before doing so).

Question 52

Indications of Surgery/Adrenalectomy

Answer 52

• Functional adrenal mass • Cortisol hypersecretion • Pheochromocytoma • Aldosterone hypersecretion • Mass >4 cm with the exception of myelolipoma (see discussion on size and growth under the Imaging of Adrenal Masses section in text) • Mass with imaging findings that are suggestive of malignancy (e.g., lipid poor, heterogeneous, irregular borders, infiltrates surrounding structures) • Adrenal incidentaloma that grows more than 1 cm on follow-up imaging • Extremely large and/or symptomatic myelolipoma (see discussion on myelolipoma in the Adrenal Lesions section in text) • Isolated adrenal metastasis (multidisciplinary decision making required) • During renal surgery for renal cell carcinoma if: • Adrenal abnormal or not visualized because of large renal tumor size on imaging • Vein thrombus to level of adrenal vein • Failed neurosurgical treatment of Cushing disease, necessitating bilateral adrenalectomy • Select patients with ectopic adrenocorticotropic hormone (ACTH) syndrome, requiring bilateral adrenalectomy • ACTH-independent macronodular adrenal hyperplasia (AIMAH) • Primary pigmented nodular adrenocortical disease (PPNAD)

Question 53

Contraindications to LAP adrenalectomy

Answer 53

CONTRAINDICATIONS Relative Large tumor Localized adrenal cortical carcinoma without evidence of local invasion, adrenal vein, or vena caval involvement or lymph node metastases (>12 cm) Morbid obesity Malignant pheochromocytoma Virilizing adrenal tumor (70%–80% of these tumors are actually functional adrenal cortical carcinoma) Significant abdominal adhesion History of recurrent pyelonephritis Pregnancy ABSOLUTE Local recurrence of a previously resected adrenal mass Invasive adrenal cortical carcinoma with evidence of invasion of neighboring organs or renal vessels or vena caval involvement Severe cardiopulmonary disease

Question 54

Oncologic Principles of Resection for ACC

Answer 54

1. No touch technique 2. Preservation of the intact peritoneum on the anterior surface of the adrenal gland if no evidence of invasion through the overlying peritoneal layer 3. En bloc resection of tumor with a wide margin of surrounding benign tissue outside the tumor capsule 4. Strict preservation of an intact tumor capsule 5. Exclusion of the remainder of the peritoneal cavity as much as possible using barriers such as laparotomy pads, plastic barriers, or drapes 6. Minimizing of bleeding and fluid spillage into the peritoneal cavity 7. Extraction of specimen in a bag 8. Change of gloves, gowns, and instruments after removal of the tumor and before closure of the abdomen