PRIMARY HYPERALDOSTERONISM Flashcards
What is the function of the adrenal cortex?
three
- steroid hormone function biosynthesis and regulation
- diagnostic testing
- adrenocortical insufficiency states (acute and chronic adrenal insufficiency)
What are the 2 adrenocortical excess states?
- cushing’s syndrome
- conn syndrome
Adrenal medulla:
what does it do and what can occur at that level?
catecholamine synthesis, metabolism, receptors and functions
pheochromocytoma/paragangliomas occur here
What is the definitive zone of the fetal adrenal gland?
the principal site of glucocorticoid and mineralcorticoid synthesis
What is the fetal zone of the fetal adrenal gland?
androgenic precursors, which the placenta converts to various types of estrogens
what are the cortexes of the mature adrenal gland?
- zona glomerulosa
- zona fasciculata
- zona reticularis
Where is the medulla?
at the very bottom of both fetal and mature adrenal gland gradient
What is the function of the zona glomerulosa?
two things
- MINERALCORTICOIDS
- sodium resorption in the kidney, thus electrolyte balance, intravascular volume, and blood pressure
What is the function of the zona fasciculata?
- GLUCOCORTICOIDS
- named for their carbohydrate-mobilizing activity
- ubiquitous physiologic regulators, influencing a wide variety of bodily functions
What is the function of the zona reticularis?
- SEX STEROIDS
- no known physiologic role
- secondary characteristics in women, overproduction can result in virilization
Biosynthesis of Aldosterone:
pregnenolone-> progesterone-> 11- deoxycorticosterone-> corticosterone-> aldosterone
biosynthesis of cortisol:
17-hydroxyoregnenolone-> 17-hydroxyprogesterone-> 11-deoxycortisol-> cortisol
biosynthesis of androstenedione:
Dehydroepiandrosterone (DHEA)-> Androsteneidone
How is aldosterone regulated?
renin-angiotensin system
what is primary hyperaldosteronism also known as?
conn syndrome
significance of primary hyperaldosteronism?
four things
- inappropriately high aldosterone production, autonomous of major regulators of secretion (angi II, potassium)
- causes HTN, CV damage, Na retention, suppression of plasma renin, increased K excretion (hypokalemia 9-37%)
- increasingly recognized, >5% and possibly >10% of hypertensive patients
- higher CV morbidity and mortality than age and sex matched patients with essential HTN and same degree BP elevation
Who should be screened ?
- sustained BP >150/100 on each of 3 measurements on different days
- HTN (BP >140/90) resistant to 3 conventional antihypertensive drugs (including a diuretic)
- controlled BP (<140/90) on 4+ antihypertensive agents
- 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)
Patho of hyperaldosteronism:
- MOST COMMON: ADRENAL ADENOMA
- uni or bilat adrenal hyperplasia
- adrenal carcinoma
- 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
- there also exists FH-II and FH-III
screening: what is the screening for hyperaldosteronism?
- 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
increased renin and decreased aldosterone indicates what?
a kidney problem
decreased renin and increased aldosterone indicates what?
conn syndrome
increased renin and normal aldosterone indicates what?
salt sensitivity (AA)
What are the confirmatory tests for hyperaldosteronism?
- oral Na loading test -checking sodium sensitivity
- saline infusion test (seated better sensitivity than recumbent)
- furosemide upright test -checks pressure
- captopril challenge test - inhibits ace. if still high after test, confirmatory
what is the choice of test based on?
pt safety, cost, pt compliance, local experience/expertise
when is confirmatory testing not needed?
spontaneous hypokalemia, plasma renin below detection level + plasma aldosterone concentration >20 ng/dL
What test do you start with in diagnosing hyperaldosteronism and why?
- CT. This is to exclude large masses that may represent adrenocortical carcinoma, can also help interventional radiology before adrenal venous sampling (AVS)
What is pre-op treatment?
HTN and hypokalmeia should be well controlled
What is post-op treatment?
- measure plasma aldosterone and renin activity shortly after surgery
- Day 1: d/c K supplementation and Spiro, and reduce antihypertensive therapy if u can
- generous sodium diet to avoid hyperkalemia that can develop from hyperaldosteronism d/t chronic contralat. adrenal glands suppression
- BP normalizes or shows improvement in 1-6 months, but can continue to fall for up to 1 year.
Hyperaldosteronism medical management:
-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
look at physio slide
…
medical management of FH-1/GRA
- 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
- long acting glucocorticoids preferred
- dexa and prednisone
what are the 2 things found in the mature adrenal gland?
- cortex
- medulla
