hyperaldosteronism- SB

Question 1

In which patient population should Familial hyperaldosteronism type 1 (GRA) be suspected?

Answer 1

It should be suspected in young patients presenting with early-onset hypertension and hypokalemia.

Question 2

What is the definitive diagnostic test for Glucocorticoid-Remediable Aldosteronism (GRA)?

Answer 2

Genetic testing is the definitive diagnostic test due to high false-positive rates with other tests.

Question 3

Glucocorticoid-remediable aldosteronism is an autosomal dominant disorder caused by a chimeric gene consisting of the _____ promoter and _____ coding sequences.

Answer 3

CYP11B1; CYP11B2

Question 4

In Glucocorticoid-Remediable Aldosteronism (GRA), aldosterone production is regulated by what hormone, leading to a circadian rhythm?

Answer 4

Aldosterone production is regulated by ACTH.

Question 5

What is the appropriate management for patients with Glucocorticoid-Remediable Aldosteronism (GRA)?

Answer 5

Treatment involves physiologic glucocorticoids or mineralocorticoid receptor antagonists to manage hypertension and hypokalemia.

Question 6

Patients with Glucocorticoid-Remediable Aldosteronism (GRA) should be monitored for hemorrhagic strokes related to what condition?

Answer 6

They should be monitored for intracranial aneurysms.

Question 7

In the context of mineralocorticoid receptor overactivation, what enzyme normally inactivates cortisol to cortisone in mineralocorticoid receptor-expressing tissues?

Answer 7

The enzyme is 11ß-dehydrogenase type 2 (HSD11B2).

Question 8

What substance found in black licorice can mimic mineralocorticoid excess by inhibiting the HSD11B2 enzyme?

Answer 8

Glycyrrhizic acid (metabolized to glycyrrhetinic acid) inhibits the HSD11B2 enzyme.

Question 9

What is the recommended next step for a patient over 35 with a unilateral adrenal nodule and confirmed primary aldosteronism who is considering surgery?

Answer 9

The patient should undergo adrenal vein sampling (AVS) to confirm lateralization.

Question 10

For a patient younger than 35 with marked primary aldosteronism and a clear unilateral adrenal adenoma on CT, what is the next step if they agree to surgery?

Answer 10

The patient can proceed directly to unilateral laparoscopic adrenalectomy without AVS.

Question 11

What is the primary cause of a false-negative screening test for primary aldosteronism that should be corrected before re-screening?

Answer 11

Hypokalemia should be corrected before rescreening, as it can suppress aldosterone secretion.

Question 12

List two risk factors for developing hyperkalemia after an adrenalectomy for primary aldosteronism.

Answer 12

Older age, longer duration of hypertension, proteinuria, or impaired renal function.

Question 13

What plasma aldosterone concentration is considered positive in a saline infusion test for primary aldosteronism?

Answer 13

A serum aldosterone level greater than 10 ng/dL after a 2 L saline infusion over 4 hours is positive.

Question 14

Renal tubular acidosis (RTA) type 4 is characterized as a state of _____.

Answer 14

hyporeninemic hypoaldosteronism

Question 15

Which condition can present with hypertension, hypokalemia, and subnormal plasma renin and aldosterone levels, mimicking mineralocorticoid excess?

Answer 15

Ectopic ACTH syndrome.

Question 16

According to screening guidelines, surgically curable primary aldosteronism is unlikely if the plasma aldosterone concentration (PAC) is less than _____ or plasma renin activity (PRA) is more than _____.

Answer 16

PAC <10 ng/dL; PRA >1 ng/mL/hr

Question 17

Under what specific lab conditions can primary hyperaldosteronism be diagnosed without confirmatory testing?

Answer 17

When there is spontaneous hypokalemia, plasma renin is suppressed (<1 ng/mL/hr), and plasma aldosterone is >20 ng/dL.

Question 18

What is the recommended management for a patient with confirmed primary aldosteronism if adrenal vein sampling (AVS) does not lateralize?

Answer 18

The patient should be treated with medical therapy, such as mineralocorticoid receptor antagonists.

Question 19

In individuals with a positive screening test for primary aldosteronism but negative confirmatory testing, what clinical finding suggests the need for repeat testing in the future?

Answer 19

Blood pressure that becomes increasingly difficult to control over time.

Question 20

Why are mineralocorticoid receptor (MR) antagonists most likely to interfere with screening for primary aldosteronism?

Answer 20

Because these drugs have a strong tendency to raise renin levels.

Question 21

A potential complication after the surgical resection of an aldosterone-producing adenoma is transient _____.

Answer 21

hypoaldosteronism

Question 22

What are the three key goals of MR antagonist therapy in primary aldosteronism, used as proxies for adequate cardiovascular risk reduction?

Answer 22

To normalize blood pressure, normalize potassium, and increase renin activity from a suppressed to an unsuppressed level.

Question 23

What is the interpretation of a decreased estimated glomerular filtration rate (eGFR) after starting MR antagonist therapy for primary aldosteronism?

Answer 23

It is an expected effect from reducing glomerular hyperfiltration and unmasking underlying kidney disease, not an adverse effect requiring discontinuation.

Question 24

Why might eplerenone be preferred over spironolactone as an MR antagonist, particularly in male patients?

Answer 24

Eplerenone is preferred due to its lack of antiandrogenic side effects (e.g., gynecomastia).

Question 25

What is the biochemical mechanism by which licorice ingestion leads to hypertension and hypokalemia?

Answer 25

Licorice contains glycyrrhetinic acid, which inhibits the enzyme 11ß-HSD2, allowing cortisol to activate mineralocorticoid receptors.

Question 26

In the differential diagnosis of low renin hypertension, what condition is caused by activating pathogenic variants in the epithelial sodium channel?

Answer 26

Liddle syndrome.

Question 27

What is the most common cause of primary aldosteronism, accounting for about 60% of cases?

Answer 27

Bilateral idiopathic hyperplasia (IHA).

Question 28

What is the underlying cause of familial hyperaldosteronism (FH) type I, also known as Glucocorticoid-Remediable Aldosteronism (GRA)?

Answer 28

It is caused by a CYP11B1/CYP11B2 germline chimeric gene.

Question 29

What is the underlying genetic cause of familial hyperaldosteronism (FH) type III?

Answer 29

It is caused by germline KCNJ5 mutations.

Question 30

In congenital adrenal hyperplasia, deficiency of which two enzymes can cause low renin and low aldosterone hypertension?

Answer 30

11ß-Hydroxylase deficiency and 17α-Hydroxylase deficiency.

Question 31

Term: Resistant Hypertension

Answer 31

Definition: Blood pressure that remains above target despite the use of three different classes of antihypertensive agents, or BP controlled with four or more medications.

Question 32

According to the 2017 ACC/AHA guidelines, what blood pressure range defines Stage 1 Hypertension?

Answer 32

Systolic 130–139 mm Hg or diastolic 80–89 mm Hg.

Question 33

According to the 2017 ACC/AHA guidelines, what blood pressure defines Stage 2 Hypertension?

Answer 33

Systolic $\geq$140 mm Hg or diastolic $\geq$90 mm Hg.

Question 34

For primary aldosteronism screening, what are the plasma aldosterone concentration (PAC) and plasma renin activity (PRA) cutoffs that suggest the diagnosis?

Answer 34

A PAC of $\geq$10 ng/dL and a suppressed PRA of <1 ng/mL/hr.

Question 35

How do ß-blockers affect renin, plasma aldosterone concentration (PAC), and the aldosterone-to-renin ratio (ARR), potentially causing a false positive?

Answer 35

They markedly decrease renin (↓↓) more than PAC (↓), causing the ARR to increase (↑).

Question 36

How do ACE inhibitors and ARBs affect renin, PAC, and the ARR, potentially causing a false negative?

Answer 36

They markedly increase renin (↑↑) and decrease PAC (↓), causing the ARR to decrease (↓).

Question 37

How do potassium-losing diuretics affect renin, PAC, and the ARR, potentially causing a false negative?

Answer 37

They markedly increase renin (↑↑) more than they increase PAC (↑), causing the ARR to decrease (↓).

Question 38

The mechanism by which NSAIDs can cause a false positive on an ARR screen involves the inhibition of _____, which reduces prostaglandin synthesis and subsequent renin release.

Answer 38

cyclooxygenase (COX) enzymes

Question 39

For how long should mineralocorticoid receptor antagonists like spironolactone be discontinued before testing for primary aldosteronism?

Answer 39

They should be discontinued for at least 4 weeks prior to testing.

Question 40

Which classes of antihypertensive medications are considered to have minimal impact on the ARR and can be used during the washout period before testing?

Answer 40

Non-dihydropyridine calcium channel blockers (e.g., verapamil), alpha-adrenergic antagonists (e.g., doxazosin), and vasodilators (e.g., hydralazine).

Question 41

When is adrenal vein sampling (AVS) considered unnecessary in a patient with biochemically confirmed primary aldosteronism?

Answer 41

AVS may be unnecessary in patients younger than 35 with marked primary aldosteronism and a clear unilateral adenoma on CT.

Question 42

Can adrenal vein sampling (AVS) be reliably performed while a patient is on MRA therapy?

Answer 42

Yes, recent studies suggest AVS can be reliable if plasma renin remains suppressed despite MRA therapy.

Question 43

What is the primary purpose of performing an adrenal CT scan once primary hyperaldosteronism is biochemically confirmed?

Answer 43

To exclude rare adrenocortical carcinoma and provide anatomical information for potential surgical planning.

Question 44

What is the key difference between Type 1 and Type 2 genetic Apparent Mineralocorticoid Excess (AME)?

Answer 44

Type 1 AME is severe with early onset due to HSD11B2 deficiency, while Type 2 AME has a milder phenotype with later onset due to partial loss of enzyme function.

Question 45

In Cushing syndrome, mineralocorticoid excess occurs because the high levels of _____ overwhelm the capacity of the 11ß-HSD2 enzyme.

Answer 45

cortisol

Question 46

A high 24-hour urinary cortisol-to-cortisone ratio is indicative of what condition?

Answer 46

Apparent mineralocorticoid excess (AME).

Question 47

What finding supports a diagnosis of Glucocorticoid-Remediable Aldosteronism (GRA) when comparing morning and afternoon aldosterone levels?

Answer 47

Morning aldosterone levels are higher than afternoon levels, consistent with ACTH's diurnal rhythm.

Question 48

The _____ test for primary aldosteronism is considered positive if urinary aldosterone is >10–12 µg/day after ensuring urinary sodium is >200 mmol/day.

Answer 48

3–5 Day Oral Salt Loading

Question 49

Four biomarkers suggestive of adequate renal MR blockade in primary aldosteronism include decreased blood pressure, increased serum potassium, increased renin activity, and decreased _____.

Answer 49

estimated glomerular filtration rate (eGFR)

Question 50

Mutations in the NR3C1 gene cause tissue insensitivity to glucocorticoids, leading to compensatory ACTH hypersecretion and a condition known as _____.

Answer 50

Glucocorticoid Resistance Syndrome