15. Secondary endocrine HT (primary aldosteronism, pheocromocytoma)

Question 1

What are some causes of secondary hypertension?

Answer 1

• Non-endocrine origin (renal, cardiac)
• endocrine origin such as acromegaly, Cushing syndrome, thyroid, congenital adrenal hyperplasia, primary hyperaldosteronism, and phaeochromocytoma.

Question 2

When should we suspect secondary hypertension and who should be examined?

Answer 2

We should suspect secondary hypertension in patients with
- hypertension in youth
- malignant hypertension (180/120 Hgmm),
- sudden onset with high blood pressure value hypertension,
- patients with hypertension and adrenal tumor,
- patients with hypertension and OSAS,
- and therapy-refractory hypertension (insufficient blood pressure with >3 antihypertensive medications).

Question 3

What are some screening examinations for secondary hypertension?

Answer 3

• Family history, inherited diseases
• physical examination (blood pressure in 4 limbs, “typical” signs),
• lab results (routine lab: creatinine, BUN, GFR, Sodium).
• radiology (tumors, arteries)

Question 4

What is primary hyperaldosteronism?

Answer 4

Independant adrenal overexpression of aldosterone with suppressed renin value, hypertension and hypokalemia

Question 5

What is the classification of primary hyperaldosteronism?

Answer 5

• > 50% aldosterone-producing adenoma,
• 35-50% bilateral adrenal hyperplasia,
• < 1 % familial hyperaldosteronism,
• < 1% aldosterone-producing adrenal cancer.

Question 6

What is the epidemiology of primary hyperaldosteronism?

Answer 6

• most frequent secondary hypertension cause: 5-10%,
• highest incidence between 30-50 Y.

Question 7

What is the most frequent endocrine cause of secondary hypertension?

Answer 7

Primary hyperaldosteronism (Conn-syndrome).

Question 8

What are the clinical signs of primary hyperaldosteronism?

Answer 8

• Hypertension - moderate/severe, hard to adjust, headache
• hypokalemic (50%) : spontaneous, diuretics induced, fatigue, weakness, muscle cramp, arrhythmia.

Question 9

What are the complications of hypertension in primary hyperaldosteronism?

Answer 9

Stroke, cardiac failure, MI, atrial fibrillation, kidney failure (proteinuria), metabolic syndrome/(Pre)diabetes mellitus.

Question 10

What is the primary goal in the diagnosis of primary hyperaldosteronism?

Answer 10

To differentiate between essential hypertension and primary hyperaldosteronism.

Question 11

What is the next step in finding the cause of primary hyperaldosteronism?

Answer 11

Adrenal adenoma vs. bilateral hyperplasia.

Question 12

What is the recommendation for a morning sample used in screening for primary hyperaldosteronism?

Answer 12

At least 20-30 minutes in rest (sitting, lying), fasting

Question 13

What is the essential condition for accurate screening of primary hyperaldosteronism?

Answer 13

Normokalemia.

Question 14

Which medications should be temporarily left out during screening for primary hyperaldosteronism?

Answer 14

ACE-blockers, ARB, other diuretics, dihydropyridine calcium-channel blockers, and estrogens.

Question 15

What is the mechanism of action of spironolactone and eplerenone?

Answer 15

They block the action of aldosterone on its receptors.

Question 16

Which medication can cause a false-positive result in the calculation of the ARR ratio?

Answer 16

Beta-blockers, NSAIDS

Question 17

Which medication can cause a false-negative result in the calculation of the ARR ratio?

Answer 17

ACE-blockers and ARB.

Question 18

What is the recommended duration of medication withdrawal before calculating the ARR ratio?

Answer 18

At least 6 weeks.

Question 19

What is the recommended ratio used in screening for primary hyperaldosteronism?

Answer 19

Ratio of plasma aldosterone concentration and plasma renin activity (ARR).

Question 20

What is the recommended antihypertensive medication for primary hyperaldosteronism (Conn-syndrome)?

Answer 20

Doxazosin, Prazosin, Verapamil, Hidralazin.

Question 21

What is the screening criteria for primary hyperaldosteronism (Conn-syndrome)?

Answer 21

Screening is positive if ARR > 30 and the plasma aldosterone concentration > 15 ng/dl (416 pmol/L) and the PRA is suppressed (< 0.2 ng/ml/H) in most cases.

Question 22

What is the confirmatory testing for primary hyperaldosteronism (Conn-syndrome)?

Answer 22

• Intravenous sodium loading test,
• Oral sodium loading test

Question 23

What is the purpose of the Intravenous sodium loading test?

Answer 23

To evaluate primary hyperaldosteronism (Conn-syndrome) by measuring plasma aldosterone levels after intravenous infusion of sodium chloride.

Question 24

What is the cutoff value for plasma aldosterone concentration after the Intravenous sodium loading test to confirm the diagnosis of primary hyperaldosteronism?

Answer 24

Plasma aldosterone concentration > 5 ng/dl.

Question 25

What is the significance of plasma aldosterone concentration between 5-10 ng/dl after the Intravenous sodium loading test?

Answer 25

It might refer to bilateral hyperplasia.

Question 26

What is the significance of plasma aldosterone concentration > 10 ng/dl after the Intravenous sodium loading test?

Answer 26

It might refer to aldosterone-producing adrenal adenoma.

Question 27

What is the first choice for localizing the subtype of primary hyperaldosteronism?

Answer 27

Adrenal CT (MR).

Question 28

What is the gold-standard for confirming the subtype of primary hyperaldosteronism?

Answer 28

Adrenal vein sampling.

Question 29

What is the sensitivity and specificity of adrenal vein sampling?

Answer 29

Sensitivity: 95%, specificity: 100%.

Question 30

How is the correct catheter localization confirmed during adrenal vein sampling?

Answer 30

Adrenal vein cortisol concentration is 2-3x higher vs. cortisol concentration in vena cava.

Question 31

What does a 3-4x higher aldosterone/cortisol ratio on one side during adrenal vein sampling suggest?

Answer 31

Aldosterone-producing adenoma on that side.

Question 32

What does less or no difference in ratio between the two sides during adrenal vein sampling suggest?

Answer 32

Bilateral adrenal hyperplasia.

Question 33

What is the difference between one-sided aldosterone-producing adenoma and bilateral hyperplasia in primary hyperaldosteronism?

Answer 33

One-sided adenoma has a higher aldosterone/cortisol ratio on one side compared to the other, while bilateral hyperplasia has less or no difference in ratio between the sides.

Question 34

What is the treatment for one-sided aldosterone-producing adenoma in primary hyperaldosteronism?

Answer 34

Surgical resection, specifically adrenalectomy.

Question 35

What is the postoperative effect of adrenalectomy in one-sided aldosterone-producing adenoma?

Answer 35

Temporarily "hypoaldosteronism" and hyperkalemia.

Question 36

What is the treatment for bilateral hyperplasia or aldosterone-producing adenoma in primary hyperaldosteronism if no operation is done?

Answer 36

Mineralocorticoid-receptor antagonist therapy, specifically spironolactone or eplerenone.

Question 37

What are the side effects of spironolactone in primary hyperaldosteronism treatment?

Answer 37

Progesterone/androgen-receptor effect, leading to dysmenorrhea, breast tension, gynecomastia, and impotence.

Question 38

What is phaeochromocytoma?

Answer 38

It is a catecholamine-producing neuroendocrine adrenal tumor.

Question 39

What are the forms of phaeochromocytoma?

Answer 39

Extraadrenal-paraganglioma, pediatric cases, one-sided/bilateral adrenal, and benign/malignant.

Question 40

What is the genetic involvement in phaeochromocytoma?

Answer 40

It is involved in 50% of cases, with 35% being germline and 15% being somatic.

Question 41

What is the prevalence of phaeochromocytoma?

Answer 41

0.3-0.8/100 000.

Question 42

What is the mechanism of action of PNMT?

Answer 42

PNMT stands for phenyletanolamine-N-methyltransferase, which is an enzyme that converts norepinephrine to epinephrine.

Question 43

What are the three types of catecholamines produced by phaeochromocytoma?

Answer 43

Epinephrine, norepinephrine, and dopamine.

Question 44

What are the two pathways involved in phaeochromocytoma pathogenesis?

Answer 44

The VHL and SDH pathway, and the Ret and NF1 pathway.

Question 45

What is the prevalence of pheochromocytoma in the hypertension population?

Answer 45

0.1-0.6%.

Question 46

What are the signs of pheochromocytoma?

Answer 46

- Headache, - palpitation, - perspiration, pallor, - hypertension / paroxysmal hypertension, - fatigue, - weight loss, - panic attack, anxiety, - orthostatic hypotension.

Question 47

What are the life-threatening situations associated with pheochromocytoma?

Answer 47

- Angina pectoris, malignant arrhythmia, cardiac failure, aorta dissection, - high blood glucose, - catecholamine crisis, - mechanic irritation of the tumor, - and thyramine and beta-blockers.

Question 48

When should we rule out pheochromocytoma?

Answer 48

Unusual presence of symptoms such as headache, palpitations, sweating, and weight loss, hypertension that is difficult to control with medication, hypertension that develops at a young age or in a patient with a family history of pheochromocytoma, and hypertension that is associated with other endocrine disorders such as hyperthyroidism or hyperparathyroidism.

Question 49

What is the recommended approach for screening hypertension in all hypertensive patients?

Answer 49

Rare case of hypertension, screening is not recommended in all hypertensive patients.

Question 50

What are the unusual cases where hypertension screening is recommended?

Answer 50

Unusual presence of hypertension, hypertension in youth or in young adults, therapy-resistant hypertension, blood-pressure lability, paroxysmal hypertension, adrenal incidentalom + hypertension, unknown cause of dilatative cardiomyopathy, unknown cause of shock, paradox blood-pressure elevation after beta-blocker initiation.

Question 51

What are the confirmatory tests for catecholamine overproduction in phaeochromocytoma?

Answer 51

(nor)metanephrine excretion (plasma/24H urine) in low pH, in dark bowl, positive if 3x > ULN, vanilin mandelic acid, 3-metoxithyramine (malignant?), chromogranine A.

Question 52

What is the common neuroendocrine tumor marker for phaeochromocytoma?

Answer 52

Chromogranine A, serum level is proportional with tumor size.

Question 53

What are the imaging tests used for diagnosis and localization of phaeochromocytoma?

Answer 53

Adrenal CT/MR scans, 20% are extra-adrenal, full-body scan is needed, hereditary phaeochromocytoma can be multifocal, 131I-metaiodine-benzil-guanidine (131I-MIBG) scintigraphy, sensitivity.

Question 54

What is the recommended imaging technique for detecting hereditary phaeochromocytoma?

Answer 54

18F-fluorodopamine/18fluoroDOPA -PET/CT.

Question 55

What is the sensitivity of 131I-metaiodine-benzil-guanidine (131I-MIBG) scintigraphy in detecting phaeochromocytoma?

Answer 55

95-100%.

Question 56

What is the differential diagnosis for phaeochromocytoma?

Answer 56

Thyrotoxicosis, carcinoid syndrome, medullary thyroid cancer (high calcitonin), perimenopausal syndrome, migraine, epilepsy, panic attack, anxiety disorders, drugs, mastocytosis, porphyria.

Question 57

What is the recommended preoperative treatment for phaeochromocytoma?

Answer 57

Alpha-blocker, such as doxazosine, urapidil, or prazosine, for at least two weeks.

Question 58

What is the first step during the operation for phaeochromocytoma?

Answer 58

Adrenal vein ligature, to avoid mechanical irritation.

Question 59

What is the first step during an operation to remove a pheochromocytoma?

Answer 59

Adrenal vein ligature, avoiding mechanical irritation.

Question 60

What is the typical postoperative blood pressure change in patients who have had a pheochromocytoma removed?

Answer 60

Temporarily hypotension is usual, but in many cases, long-term hypertension can occur.

Question 61

What is the first treatment for pheochromocytoma?

Answer 61

Removal of the tumor.

Question 62

What is the incidence of malignant pheochromocytoma?

Answer 62

In 5-26% of cases.

Question 63

What is the recommended follow-up for all patients with pheochromocytoma?

Answer 63

Lifelong follow-up is recommended.

Question 64

What are the common sites of metastasis for malignant pheochromocytoma?

Answer 64

Liver, bone, lung, and skull.

Question 65

What is the role of SHDB gene mutations in the development of malignant pheochromocytoma?

Answer 65

They increase the risk of developing malignant pheochromocytoma.

Question 66

Can histology provide a diagnosis of malignant pheochromocytoma?

Answer 66

No, it can only confirm the presence of distant metastasis.

Question 67

What are the treatment options for malignant pheochromocytoma?

Answer 67

Operation, alpha-methyl-parathyrosine treatment, and 131I-MIBG treatment.