Campbell Adrenal Disorders 2021 Flashcards
Cells of this tissue zone are the sole source of aldosterone
Zona glomerulosa
** Aldosterone regulates electrolyte metabolism by stimulating epithelial cells of the distal nephron to reabsorb Na+ and Cl−, while secreting H+ and K+.
Site of glucocorticoid production.
Expression of enzymes: 17alpha-hydroxylase, 21-hydroxylase, and 11beta-hydroxylase.
Zona fasciculata
** Cortisol: primary glucocorticoid in humans, controlled by ACTH
Production of DHEA, sulfated DHEAS, and androstenedione
Zona reticularis
Lies at the center of the adrenal;
Integral part of the autonomic nervous system;
Secretes catecholamines;
Source of metanephrine and normetanephrine
Adrenal medulla
Catalyzes conversion of NE to epineprhine
Expressed in the adrenal medulla, brain, and organ of Zuckerkandl
Phenyethanolamine-N-methyltransferase (PNMT)
Hypercortisolism secondary to excessive production of glucocorticoids by the adrenal cortex.
Cushing syndrome
Three main groups of causes of Cushing syndrome
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)
Most common cause of hypercortisolism in the West.
Exogenous Cushing syndrome
85% of endogenous Cushing syndrome
Majority: primary pituitary pathology
Other causes: Ectopic ACTH production, ectopic CRH production
ACTH dependent Cushing Syndrome
Cushing Syndrome vs. Cushing Disease vs. Cushing Triad
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)
ACTH-producing nonpituitary tumors
Almost always malignant
10% of Cushing syndrome
Ectopic ACTH Syndrome
Extremely reare
<1% of Cushing syndrome
Bronchial carcinoma most common culprit
Ectopic CRH
Uncontrolled hypersecretion of cortisol by adrenal tissues
ACTH-independent Cushing syndrome
** Adrenal neoplasms and bilateral adrenal disease are in this group
Multiple large (4cm) nodules replacing the glands
Each gland weighs > 60 g
<1% of Cushing syndrome
ACTH-independent Macronodular Adrenal Hyperplasia (AIMAH)
Normal-sized adrenals
Black or brown cortical nodules
<1% of Cushing syndrome
Autosomal Carney complex (50%): spotty skin and mucous membrane lesions
Primary pigmented nodular adrenocortical disease (PPNAD)
Cushing syndrome
Central obesity Moon facies Buffalo hump Proximal muscle weakness Easy bruisability Abdominal striae
Metabolic syndrome (dyslipidemia, insulin resistance, hypertension
**These are non-specific
___% of patients with Cushing syndrome exhibit ___.
50%
Urolithiasis
** Stone formers with cushingoid features also should receive a hypercortisolemia evaluation
Hypercortisolemia inbsence of an overt cushingoid phenotype.
Autonomous Cortisol Secretion (subclinical Cushing syndrome)
Explain:
Low-dose dexamethasone suppression test
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
Explain:
Late night salivary cortisol
Midnight plasma cortisol
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
If (+) Cushing syndrome screening:
How do you differentiate between ACTH dependent vs independent?
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.
If (+) ACTH dependent:
Differentiate ectopic ACTH vs. Cushing disease
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
Consequence of bilateral adrenalectomy for refractory hypercorstiolism due to Cushing disease
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
Single best therapeutic approach to normalizing cortisol levels in patients with ectopic ACTH syndrome
Resection of the primary ACTH-producing tumor
Most common form of secondary hypertension
Primary aldosteronism
Aldosterone secretion independent of RAAS
Suppressed plasma renin levels
Primary aldosteronism
Elevated renin levels –> elevated aldosterone secretion
Secondary aldosteronism
Aldosterone increases sodium ___ and potassium ___ in the distal nephron, BUT does NOT cause hypernatremia (reabsorption is accompanied by water uptake)
Na reabsorption
K secretion
Causes of Conn syndrome
Bilateral adrenal hyperlasia 60% Adenoma 35% Unilateral adrenal hyperplasia 2% Carcinoma <1% Ectopic aldosterone secreting tumor <1% Familial hyperaldosteronism <1%
Indications for Primary Aldosterone Screening (Box 106.2)
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
Screening for primary aldosteronism
8AM-10AM
Plasma aldosterone concentration (PAC)
PRA
Direct renin concentration (DRC)
Then calculate aldosterone-renin-ratio (ARR)
Confirmatory tests for primary aldosteronism
Fludrocortisone suppression test
Oral sodium loading test
IV saline infusion test
Captopril suppression test
Fludrocortisone suppression test
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
Oral sodium loading test
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.
Patients with confirmed PA should undergo ___ when adrenalectomy is being considered.
Exceptions: <40 yo, clear unilateral adrenal adenoma, normal contralateral adrenal gland
Adrenal vein sampling
Medical management for PA who are not surgical candidates
Aldosterone receptor antagonists spironolactone and eplerenone are successful in lowering blood pressure and are the antihypertensive agents of choice in patients with primary aldosteronism.
Chromaffin bodies in between the aortic bifurcation and the root of the inferior mesenteric artery
Organ of Zuckerkandl
** Common site of paragangliomas
Components of the 10% tumor (pheochromocytoma)
10% extra-adrenal, 10% familial, 10% bilateral, 10% pediatric, and 10% malignant
Pheochromocytoma on imaging
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)
Most common alpha-blocker for preoperative catecholamin blockade of pheochromocytoma
Phenoxybenzamine
** 7-14 days preop, 10 mg OD, titrated to 10-20 to maintain BP 120-130/80 sitting
Life-threatening condition
Preceded by hypotension unresponsive to fluid resuscitation
Acute abdomen, abdominal pain, nausea, vomiting, and fever
Acute adrenal insufficiency or adrenal crisis
TX:
Hydrocortisone
Fludrocortisone
Hereditary disorders associated with ACC
Li-Fraumeni syndrome
Beckwith-Wiedemann syndrome
Most common hormone secreted by ACC: ____
Second most common: ___
Cortisol (50-80% of functional tumors)
Androgens (40-60% of functional tumors)
Imaging characteristics of ACC
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)
Preferred surgical management for adrenal tumors > 6 cm or those with evidence of local invasion
Open adrenalectomy/surgery
** Metastatic: consider cytoreductive removal and debulking metastasectomy IF >90% disease burden can be removed
Mitotane MOA
Direct cytotoxicity of cells in adrenal cortex
Oxidative damage via free radicals
Inhibition of enzymes involved in steroid synthesis
Most valuable imaging study for diagnosis of adrenal adenoma
Non-contrast CT: measures density, uniformity, and size
** Attenuation < 10 HU = strongly suggestive of benign adrenal adenoma
NIH Consensus: Adrenal lesions > 1cm should undergo ___.
Metabolically active adenomas should undergo: ___
Metabolic evaluation
Resection
Incidentaloma CT evaluation: request washot films IF: ___
> 10 HU on CT or lack of signal dropout on chemical shift MR
Absolute and relative percent washout
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
The 5-way Test for Adrenal Mass Biopsy
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).
Indications of Surgery/Adrenalectomy
• 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)
Contraindications to LAP adrenalectomy
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
Oncologic Principles of Resection for ACC
- No touch technique
- Preservation of the intact peritoneum on the anterior surface
of the adrenal gland if no evidence of invasion through the
overlying peritoneal layer - En bloc resection of tumor with a wide margin of
surrounding benign tissue outside the tumor capsule - Strict preservation of an intact tumor capsule
- Exclusion of the remainder of the peritoneal cavity as much
as possible using barriers such as laparotomy pads, plastic
barriers, or drapes - Minimizing of bleeding and fluid spillage into the peritoneal
cavity - Extraction of specimen in a bag
- Change of gloves, gowns, and instruments after removal of
the tumor and before closure of the abdomen
