Adrenal Cortical Tumors1

Question 1

What ia a key surgical anatomic fact about adrenal glands?

Answer 1

The adrenal vein is inferomedial to the gland on the left side and drains into the left renal vein, and it is superiomedial on the right side and drains directly into the inferior vena cava posterolaterally.

Question 2

What are the layers of the adrenal gland and what they produce?

Answer 2

About 80% of the adrenal gland consists of the adrenal cortex, which is subdivided into the zona glomerulosa, which produces aldosterone, the zona fasciculata, which makes glucocorticoids, and the zona reticularis, which produces sex hormones.

Question 3

Which are usually the patients referred for an adrenalectomy?

Answer 3

1. functional tumor causing a clinical syndrome due to hormonal excess, which includes aldosteronoma, Cushing syndrome, and virilizing/feminizing tumors
2. adrenocortical cancer
3. adrenal metastasis
4. incidentaloma

Question 4

On whom should you suspect primary hyperaldoteronism?

Answer 4

Should be suspected in any patient with hypertension and hypokalemia, persistent hypertension refractory to medical treatment, or hypertension and an adrenal mass.ﾠ

Question 5

How is primary aldosteronism diagnosed?

Answer 5

Diagnosed by an elevated plasma aldosterone concentration (PAC >15 ng/dL) with a suppressed plasma renin activity (PRA 14 g/day) during IV saline infusion confirm the diagnosis.

Question 6

How is secondary hypoaldosteronism diagnosed?

Answer 6

Increased plasma renin activity and a PAC/PRA less than 30 may indicate secondary hyperaldosteronism, which is treated medically.

Question 7

What test is diagnostic of a unilateral functioning adenoma?

Answer 7

An adrenal vein aldosterone/cortisol ratio on one side that is five times higher than the contralateral side is diagnostic of unilateral functioning adenoma.

Question 8

What preoperative preparation is needed for a patient with aldosteronoma?

Answer 8

Hypertension and hypokalemia should be managed preoperatively with a 3 to 5 week course of spironolactone (100 to 400 mg daily) and/or oral potassium. Preoperative normalization of blood pressure with spironolactone is a good predictor of a successful outcome after adrenalectomy.

Question 9

What is one of the first laboratory signs of Cushing syndrome?

Answer 9

Loss of diurnal variation in cortisol levels is one of the first signs of Cushing syndrome.ﾠ

Question 10

What is the most sensitive and specific test for diagnosing Cushing syndrome?

Answer 10

Elevated 24-hour urinary free cortisolﾠ

Question 11

What is the most common cause of Cushing syndrome?

Answer 11

Exogenous steroid use

Question 12

What is the most common cause of endogenous excess cortisol production?

Answer 12

Pituitary tumor or hyperplasia (Cushing disease, 60% to 70%); ectopic ACTH (10% to 20%); or an adrenal adenoma or adrenocortical carcinoma (10% to 20%).

Question 13

What tumors can produced ACTH?

Answer 13

Bronchial carcinoids, small cell lung cancer, pancreatic islet cell cancers, and thymomas

Question 14

Are stress glucocorticoids needed perioperatively for patients undergoing surgery for Cushing syndrome?

Answer 14

They should receive stress glucocorticoids perioperatively, usually 100 mg IV hydrocortisone preoperatively followed by 100 mg every 6 hours postoperatively. These doses are gradually transitioned to oral steroids, which are tapered once the ACTH-stimulation test normalizes, and the contralateral gland is no longer suppressed. Patients undergoing bilateral adrenalectomy will require lifelong replacement therapy.

Question 15

How can you control cortisol excess preoperatively?

Answer 15

Cytochrome P-450 inhibitors such as ketoconazole (600 to 1200 mg daily).ﾠ

Question 16

What % of virilizing and feminizing tumors are malignant?

Answer 16

80%

Question 17

What physical exam findings are characteristic of a virilizing tumor?

Answer 17

Women with hirsutism, alopecia, irregular menses, and other virilizing signs may have a hypersecreting adrenal tumor or a functioning ovarian tumor.ﾠ

Question 18

What lab values are concerning for virilizing tumors?

Answer 18

Elevated serum testosterone, dehydroepiandrostenedione (DHEA-S), and 24-hour urinary 7-hydroxysteroids and 17-ketosteroids establish the diagnosis of a virilizing tumor.

Question 19

What physical exam findings are characteristic of a feminizing tumor?

Answer 19

Men with gynecomastia, gonadal atrophy, impotence, or loss of libido may have an estrogen-secreting adrenal tumor, which may be adrenocortical carcinoma, or a testicular tumor.ﾠ

Question 20

What lab values are concerning for feminizing tumors?

Answer 20

Elevated serum estrogen levels with suppressed gonadotropins, follicle stimulating hormone (FSH), and luteinizing hormones suggest a feminizing tumor.ﾠ

Question 21

What percentage of all adrenal masses accounts for sdrenocortical carcinoma?

Answer 21

1%

Question 22

What are the most frequent sites of metastasis for adrenocortical carcinoma?

Answer 22

Lung and Liver

Question 23

Which is more helpful between MRI and CT to plan an excision of adrenocortical carcinoma?

Answer 23

Although CT and MRI are equally effective, MRI may be more useful than CT in determining extension of tumor into the renal vein and inferior vena cava (IVC). Invasion into the IVC and/or the presence of thrombus are considered regional involvement and are not contraindications to resection.

Question 24

What are two most important prognostic factors of adrenocortical carcinoma?

Answer 24

completeness of resection and stage of disease

Question 25

What is the TNM staging for adrenocortical carcinoma?

Answer 25

TNM
T1: 5 cm, no invasion
T3: Any size, locally invading (but not adjacent organs)
T4: Any size, locally invading adjacent organs
N0: No regional positive nodes
N1: Positive regional nodes
M0: No distant metastatic disease
M1: Distant metastasis present
Stage
I: T1N0M0
II: T2N0M0
III: T1N1M0, T2N1M0, T3N0M0
IV: T3N1M0, T4N1M0, TXNXM1

Question 26

What marker has been associated with poor clinical outcome in adrecortical carcinoma?

Answer 26

Ki67 expression

Question 27

What is the single most important drug for adjuvant ACC treatment?

Answer 27

Mitotane is the single most important drug for adjuvant ACC treatment for patients with residual, recurrent, or metastatic ACC. Some centers use mitotane after complete R0 resection if the tumor is large (>8 cm), or if it appears aggressive (Ki67 >10%). Prolonged mitotane treatment is limited by gastrointestinal and neurologic toxicity. Since mitotane can induce adrenal insufficiency, patients may need glucocorticoid and mineralocorticoid supplementation during treatment. Up to 80% of mitotane-treated patients with functioning tumors will show significant decreases in hormone production.

Question 28

Does radiotherapy has any role in ACC?

Answer 28

Radiotherapy is recommended in patients with incomplete resection or, in some centers, with advanced local disease (stage III) or aggressive tumors (Ki67 >20%).

Question 29

Which are the most common tumor to metastasize to the adrenal glands?

Answer 29

Lung carcinoma (especially small cell), renal cell carcinoma, melanoma, gastric adenocarcinoma, hepatocellular carcinoma, esophageal adenocarcinoma, and breast adenocarcinoma.

Question 30

What findings on CT or MRI are characteristics of adrenal metastases?

Answer 30

Irregular borders, hemorrhage, tumor necrosis, and a region of interest (ROI) greater than 20 HU on unenhanced CT.

Question 31

What can be used to confirm the diagnosis of adrenal metastases?

Answer 31

Fine needle aspiration may be required to confirm the diagnosis, but only after pheochromocytoma has been ruled out to avoid potentially life-threatening hypertensive crisis.