PRIMARY HYPERALDOSTERONISM

Question 1

What is the function of the adrenal cortex?

three

Answer 1

1. steroid hormone function biosynthesis and regulation
2. diagnostic testing
3. adrenocortical insufficiency states (acute and chronic adrenal insufficiency)

Question 2

What are the 2 adrenocortical excess states?

Answer 2

1. cushing’s syndrome
2. conn syndrome

Question 3

Adrenal medulla:

what does it do and what can occur at that level?

Answer 3

catecholamine synthesis, metabolism, receptors and functions

pheochromocytoma/paragangliomas occur here

Question 4

What is the definitive zone of the fetal adrenal gland?

Answer 4

the principal site of glucocorticoid and mineralcorticoid synthesis

Question 5

What is the fetal zone of the fetal adrenal gland?

Answer 5

androgenic precursors, which the placenta converts to various types of estrogens

Question 6

what are the cortexes of the mature adrenal gland?

Answer 6

1. zona glomerulosa
2. zona fasciculata
3. zona reticularis

Question 7

Where is the medulla?

Answer 7

at the very bottom of both fetal and mature adrenal gland gradient

Question 8

What is the function of the zona glomerulosa?

two things

Answer 8

1. MINERALCORTICOIDS
2. sodium resorption in the kidney, thus electrolyte balance, intravascular volume, and blood pressure

Question 9

What is the function of the zona fasciculata?

Answer 9

1. GLUCOCORTICOIDS
2. named for their carbohydrate-mobilizing activity
3. ubiquitous physiologic regulators, influencing a wide variety of bodily functions

Question 10

What is the function of the zona reticularis?

Answer 10

1. SEX STEROIDS
2. no known physiologic role
3. secondary characteristics in women, overproduction can result in virilization

Question 11

Biosynthesis of Aldosterone:

Answer 11

pregnenolone-> progesterone-> 11- deoxycorticosterone-> corticosterone-> aldosterone

Question 12

biosynthesis of cortisol:

Answer 12

17-hydroxyoregnenolone-> 17-hydroxyprogesterone-> 11-deoxycortisol-> cortisol

Question 13

biosynthesis of androstenedione:

Answer 13

Dehydroepiandrosterone (DHEA)-> Androsteneidone

Question 14

How is aldosterone regulated?

Answer 14

renin-angiotensin system

Question 15

what is primary hyperaldosteronism also known as?

Answer 15

conn syndrome

Question 16

significance of primary hyperaldosteronism?

four things

Answer 16

1. inappropriately high aldosterone production, autonomous of major regulators of secretion (angi II, potassium)
2. causes HTN, CV damage, Na retention, suppression of plasma renin, increased K excretion (hypokalemia 9-37%)
3. increasingly recognized, >5% and possibly >10% of hypertensive patients
4. higher CV morbidity and mortality than age and sex matched patients with essential HTN and same degree BP elevation

Question 17

Who should be screened ?

Answer 17

1. sustained BP >150/100 on each of 3 measurements on different days
2. HTN (BP >140/90) resistant to 3 conventional antihypertensive drugs (including a diuretic)
3. controlled BP (<140/90) on 4+ antihypertensive agents
4. HTN plus spontaneous or diuretic-induced hypokalemia, adrenal incidentaloma, sleep apnea, FMHx of early onset HTN or cerebrovascular accident at young age (<40 years), first degree relatives of pt w/ primary hyperaldosteronism (PA)

Question 18

Patho of hyperaldosteronism:

Answer 18

1. MOST COMMON: ADRENAL ADENOMA
2. uni or bilat adrenal hyperplasia
3. adrenal carcinoma
4. inherited conditions of familial hyperaldosteronism -> familial hyperaldosteroniam T1 (FH-I),aka glucocorticoid remediable aldosteronism —> recombination between 11betahydroxylase (CYP11B1) and aldosterone synthase (CYP11B2), expression of mutant form of CYP 11B2 drives transcription under control of ACTH
5. there also exists FH-II and FH-III

Question 19

screening: what is the screening for hyperaldosteronism?

Answer 19

1. PLASMA ALDOSTERONE/RENIN RATIO (ARR)
   - collect samples in morning after patients out of bed for at least 2 hours, usually after they have been seated for 5-15 min
   - unrestricted dietary salt intake, ideally K+- replete
   - mineralcorticoid receptor anatagonists withdrawn for atleast 4 weeks
   - complete cessation of all interfering antihypertensives is usually not necessary

Question 20

increased renin and decreased aldosterone indicates what?

Answer 20

a kidney problem

Question 21

decreased renin and increased aldosterone indicates what?

Answer 21

conn syndrome

Question 22

increased renin and normal aldosterone indicates what?

Answer 22

salt sensitivity (AA)

Question 23

What are the confirmatory tests for hyperaldosteronism?

Answer 23

1. oral Na loading test -checking sodium sensitivity
2. saline infusion test (seated better sensitivity than recumbent)
3. furosemide upright test -checks pressure
4. captopril challenge test - inhibits ace. if still high after test, confirmatory

Question 24

what is the choice of test based on?

Answer 24

pt safety, cost, pt compliance, local experience/expertise

Question 25

when is confirmatory testing not needed?

Answer 25

spontaneous hypokalemia, plasma renin below detection level + plasma aldosterone concentration >20 ng/dL

Question 26

What test do you start with in diagnosing hyperaldosteronism and why?

Answer 26

1. CT. This is to exclude large masses that may represent adrenocortical carcinoma, can also help interventional radiology before adrenal venous sampling (AVS)

Question 27

What is pre-op treatment?

Answer 27

HTN and hypokalmeia should be well controlled

Question 28

What is post-op treatment?

Answer 28

1. measure plasma aldosterone and renin activity shortly after surgery 2. Day 1: d/c K supplementation and Spiro, and reduce antihypertensive therapy if u can 3. generous sodium diet to avoid hyperkalemia that can develop from hyperaldosteronism d/t chronic contralat. adrenal glands suppression 4. BP normalizes or shows improvement in 1-6 months, but can continue to fall for up to 1 year.

Question 29

Hyperaldosteronism medical management:

Answer 29

-MINERALCORTICOID RECEPTOR ANTAGONISTS- 1. Spironolactone 1st gen ; reduces SBP 25%, DBP 22%; half of patients can manage w/ spiro monotherapy; non-selective and has anti-androgen and progesterone agonist effects 2. Eplerenone 2nd gen- shorter half life and lower MR affinity compared to spiro; 25 mg; new and more expensive; selective MR antagonist 3. 3rd gen MR antagonists and aldosterone synthase inhibitors are new to market/in development

Question 30

look at physio slide

Answer 30

...

Question 31

medical management of FH-1/GRA

Answer 31

1. glucocorticoid to partially suppress pituitary ACTH secretion - dosage varies in kids by age and body weight; taken at bedtime to suppress early morn ACTH surge; use lowest possible dose to normalize BP and/or serum K; avoid over-treatment/iatrogenic Cushing syndrome 2. long acting glucocorticoids preferred - dexa and prednisone

Question 32

what are the 2 things found in the mature adrenal gland?

Answer 32

1. cortex 2. medulla