Primary Aldosteronism Flashcards
What Potassium channel is involved in 1/3 of aldosterone producing adenomas?
KCNJ5
What is the mechanism that leads to aldosterone overproduction in somatically mutated KCJN5 channels?
The mutation leads to loss of potassium selectivity and leads to influx of na+ and depolarisation of the cell. This leads to calcium influx and activation of aldosterone synthase and cell proliferation
What voltage gated Ca Channel that has been identified in adrenal adenomas?
CACNA1D - leads to similar phenotype.
What might be the clinical implication of identifying the KCNJN5 mutation?
Small study has shown better Bp control on patients with the mutation
What is the typical triad of hyperaldosteronism?
Hypertension, Hyperkalemia (but less than 50% might have this) and metabolic alkalosis
What are the most common subtypes of primary aldosteronism?
- Aldosterone producing adenomas APAs
- Bilateral idioptahic hyperaldosteronis
less common
- Familial Hyperadosteronism Type 1 GRA (glucocortocoid remediable aldosteronism) or Type III familial occurrence of APA or bilateral hyperaldosteronism
- Pure aldosterone producing carcinomas
- Ectopic aldosterone producing tumours
Who should be screened for primary hyperaldosteronism?
- Hypertensive and hypokalemic
- Resistant hypertension (3 agents) and severe Ht Bp more than 160 systolic or diastolic 100
- HT with adrenal incidentaloma
- Hypertension and famiy history of early onset HT and CVA (age less than 40)
- All hypertensive first degree relatives of patients with primary aldosteronism
Describe the algorithm used to investigate HT and hypokalemia using the PAC and PRA ratio?
What does beta blockers do the PAC/PRA ratio and does it matter?
Betal blockers lower PRA and PRC measurements and raise the PAC/PRA ratio BUT it does not increase the PAC levels
How long should mineralocorticoid receptor blockers be stopped prior to performing screening for primary aldosteronism?
6 weeks
How does ACE inhibitors effect PAC/PRA ratios?
ACE inhibitors might increase PRC levels or renin levels. So a detectable PRA level or a low PAC/PRA ratio does not exclude primary aldosteronism.
However, if PRA is undetectable this is a string predictor.
Whats PAC/Pra ratio is normal in essential hypertension and what is found in primary aldosteronism?
4-10 vs 30 to 50
So what are the typical features in PAC/PRA in primary aldosteronism?
- Undetectable PRA or PRC
- PAC/PRA ratio above 20
- PAC above 416 pmol/l
What are the confirmatory tests available if screening tests is suggestive of primary aldosteronism?
Oral sodium loading 5000 mg of sodium a day or two 1 gram Nacl tablets tds (be vary of na loading in severe hypertensives, hypokalemia - might need replacament)
Saline infsuion test - 2 l of isotonic Nacl over 4 hrs. then measure 24 hr urine collection for na excertion needs to be above 200 mEq urine aldosterone above 33 nmol/day.
What is the diagnostic criteria used in AVS?
a four fold difference in sides of PAC
