15. Secondary endocrine HT (primary aldosteronism, pheocromocytoma) Flashcards
What are some causes of secondary hypertension?
- Non-endocrine origin (renal, cardiac)
- endocrine origin such as acromegaly, Cushing syndrome, thyroid, congenital adrenal hyperplasia, primary hyperaldosteronism, and phaeochromocytoma.
When should we suspect secondary hypertension and who should be examined?
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).
What are some screening examinations for secondary hypertension?
- Family history, inherited diseases
- physical examination (blood pressure in 4 limbs, “typical” signs),
- lab results (routine lab: creatinine, BUN, GFR, Sodium).
- radiology (tumors, arteries)
What is primary hyperaldosteronism?
Independant adrenal overexpression of aldosterone with suppressed renin value, hypertension and hypokalemia
What is the classification of primary hyperaldosteronism?
- > 50% aldosterone-producing adenoma,
- 35-50% bilateral adrenal hyperplasia,
- < 1 % familial hyperaldosteronism,
- < 1% aldosterone-producing adrenal cancer.
What is the epidemiology of primary hyperaldosteronism?
- most frequent secondary hypertension cause: 5-10%,
- highest incidence between 30-50 Y.
What is the most frequent endocrine cause of secondary hypertension?
Primary hyperaldosteronism (Conn-syndrome).
What are the clinical signs of primary hyperaldosteronism?
- Hypertension - moderate/severe, hard to adjust, headache
- hypokalemic (50%) : spontaneous, diuretics induced, fatigue, weakness, muscle cramp, arrhythmia.
What are the complications of hypertension in primary hyperaldosteronism?
Stroke, cardiac failure, MI, atrial fibrillation, kidney failure (proteinuria), metabolic syndrome/(Pre)diabetes mellitus.
What is the primary goal in the diagnosis of primary hyperaldosteronism?
To differentiate between essential hypertension and primary hyperaldosteronism.
What is the next step in finding the cause of primary hyperaldosteronism?
Adrenal adenoma vs. bilateral hyperplasia.
What is the recommendation for a morning sample used in screening for primary hyperaldosteronism?
At least 20-30 minutes in rest (sitting, lying), fasting
What is the essential condition for accurate screening of primary hyperaldosteronism?
Normokalemia.
Which medications should be temporarily left out during screening for primary hyperaldosteronism?
ACE-blockers, ARB, other diuretics, dihydropyridine calcium-channel blockers, and estrogens.
What is the mechanism of action of spironolactone and eplerenone?
They block the action of aldosterone on its receptors.
Which medication can cause a false-positive result in the calculation of the ARR ratio?
Beta-blockers, NSAIDS
Which medication can cause a false-negative result in the calculation of the ARR ratio?
ACE-blockers and ARB.
What is the recommended duration of medication withdrawal before calculating the ARR ratio?
At least 6 weeks.
What is the recommended ratio used in screening for primary hyperaldosteronism?
Ratio of plasma aldosterone concentration and plasma renin activity (ARR).
What is the recommended antihypertensive medication for primary hyperaldosteronism (Conn-syndrome)?
Doxazosin, Prazosin, Verapamil, Hidralazin.
What is the screening criteria for primary hyperaldosteronism (Conn-syndrome)?
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.
What is the confirmatory testing for primary hyperaldosteronism (Conn-syndrome)?
- Intravenous sodium loading test,
- Oral sodium loading test
What is the purpose of the Intravenous sodium loading test?
To evaluate primary hyperaldosteronism (Conn-syndrome) by measuring plasma aldosterone levels after intravenous infusion of sodium chloride.
What is the cutoff value for plasma aldosterone concentration after the Intravenous sodium loading test to confirm the diagnosis of primary hyperaldosteronism?
Plasma aldosterone concentration > 5 ng/dl.
What is the significance of plasma aldosterone concentration between 5-10 ng/dl after the Intravenous sodium loading test?
It might refer to bilateral hyperplasia.
What is the significance of plasma aldosterone concentration > 10 ng/dl after the Intravenous sodium loading test?
It might refer to aldosterone-producing adrenal adenoma.
What is the first choice for localizing the subtype of primary hyperaldosteronism?
Adrenal CT (MR).
What is the gold-standard for confirming the subtype of primary hyperaldosteronism?
Adrenal vein sampling.
What is the sensitivity and specificity of adrenal vein sampling?
Sensitivity: 95%, specificity: 100%.
How is the correct catheter localization confirmed during adrenal vein sampling?
Adrenal vein cortisol concentration is 2-3x higher vs. cortisol concentration in vena cava.
What does a 3-4x higher aldosterone/cortisol ratio on one side during adrenal vein sampling suggest?
Aldosterone-producing adenoma on that side.
What does less or no difference in ratio between the two sides during adrenal vein sampling suggest?
Bilateral adrenal hyperplasia.
What is the difference between one-sided aldosterone-producing adenoma and bilateral hyperplasia in primary hyperaldosteronism?
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.
What is the treatment for one-sided aldosterone-producing adenoma in primary hyperaldosteronism?
Surgical resection, specifically adrenalectomy.
What is the postoperative effect of adrenalectomy in one-sided aldosterone-producing adenoma?
Temporarily “hypoaldosteronism” and hyperkalemia.
What is the treatment for bilateral hyperplasia or aldosterone-producing adenoma in primary hyperaldosteronism if no operation is done?
Mineralocorticoid-receptor antagonist therapy, specifically spironolactone or eplerenone.
What are the side effects of spironolactone in primary hyperaldosteronism treatment?
Progesterone/androgen-receptor effect, leading to dysmenorrhea, breast tension, gynecomastia, and impotence.
What is phaeochromocytoma?
It is a catecholamine-producing neuroendocrine adrenal tumor.
What are the forms of phaeochromocytoma?
Extraadrenal-paraganglioma, pediatric cases, one-sided/bilateral adrenal, and benign/malignant.
What is the genetic involvement in phaeochromocytoma?
It is involved in 50% of cases, with 35% being germline and 15% being somatic.
What is the prevalence of phaeochromocytoma?
0.3-0.8/100 000.
What is the mechanism of action of PNMT?
PNMT stands for phenyletanolamine-N-methyltransferase, which is an enzyme that converts norepinephrine to epinephrine.
What are the three types of catecholamines produced by phaeochromocytoma?
Epinephrine, norepinephrine, and dopamine.
What are the two pathways involved in phaeochromocytoma pathogenesis?
The VHL and SDH pathway, and the Ret and NF1 pathway.
What is the prevalence of pheochromocytoma in the hypertension population?
0.1-0.6%.
What are the signs of pheochromocytoma?
- Headache,
- palpitation,
- perspiration, pallor,
- hypertension / paroxysmal hypertension,
- fatigue,
- weight loss,
- panic attack, anxiety,
- orthostatic hypotension.
What are the life-threatening situations associated with pheochromocytoma?
- Angina pectoris, malignant arrhythmia, cardiac failure, aorta dissection,
- high blood glucose,
- catecholamine crisis,
- mechanic irritation of the tumor,
- and thyramine and beta-blockers.
When should we rule out pheochromocytoma?
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.
What is the recommended approach for screening hypertension in all hypertensive patients?
Rare case of hypertension, screening is not recommended in all hypertensive patients.
What are the unusual cases where hypertension screening is recommended?
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.
What are the confirmatory tests for catecholamine overproduction in phaeochromocytoma?
(nor)metanephrine excretion (plasma/24H urine) in low pH, in dark bowl, positive if 3x > ULN, vanilin mandelic acid, 3-metoxithyramine (malignant?), chromogranine A.
What is the common neuroendocrine tumor marker for phaeochromocytoma?
Chromogranine A, serum level is proportional with tumor size.
What are the imaging tests used for diagnosis and localization of phaeochromocytoma?
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.
What is the recommended imaging technique for detecting hereditary phaeochromocytoma?
18F-fluorodopamine/18fluoroDOPA -PET/CT.
What is the sensitivity of 131I-metaiodine-benzil-guanidine (131I-MIBG) scintigraphy in detecting phaeochromocytoma?
95-100%.
What is the differential diagnosis for phaeochromocytoma?
Thyrotoxicosis, carcinoid syndrome, medullary thyroid cancer (high calcitonin), perimenopausal syndrome, migraine, epilepsy, panic attack, anxiety disorders, drugs, mastocytosis, porphyria.
What is the recommended preoperative treatment for phaeochromocytoma?
Alpha-blocker, such as doxazosine, urapidil, or prazosine, for at least two weeks.
What is the first step during the operation for phaeochromocytoma?
Adrenal vein ligature, to avoid mechanical irritation.
What is the first step during an operation to remove a pheochromocytoma?
Adrenal vein ligature, avoiding mechanical irritation.
What is the typical postoperative blood pressure change in patients who have had a pheochromocytoma removed?
Temporarily hypotension is usual, but in many cases, long-term hypertension can occur.
What is the first treatment for pheochromocytoma?
Removal of the tumor.
What is the incidence of malignant pheochromocytoma?
In 5-26% of cases.
What is the recommended follow-up for all patients with pheochromocytoma?
Lifelong follow-up is recommended.
What are the common sites of metastasis for malignant pheochromocytoma?
Liver, bone, lung, and skull.
What is the role of SHDB gene mutations in the development of malignant pheochromocytoma?
They increase the risk of developing malignant pheochromocytoma.
Can histology provide a diagnosis of malignant pheochromocytoma?
No, it can only confirm the presence of distant metastasis.
What are the treatment options for malignant pheochromocytoma?
Operation, alpha-methyl-parathyrosine treatment, and 131I-MIBG treatment.
