Hyperaldosteronism

This is a summary of the Endo Soc guideline in JCEM 2008 93 3266.

Some notes for later digestion. Mayo Clinic don't do AVS if <40 and definite single nodule (Kloos 1995 - autopsy prevalence adrenal nodules). But otherwise would not rely on CT as incidentalomas too frequent. Spiro/eplerenone titrated to K+.


Background stuff

Frequency

Perhaps 10% of people with hypertension, or 20% with resistant hypertension.

Consider Liddle syndrome, liquorice, steroids etc. as alternative causes of hypertension with hypokalaemic alkalosis.

Who to screen?

  • Resistant hypertension
  • Hypertension with hypokalaemia
  • Hypertension with adrenal incidentaloma
  • Hypertension with family history of early hypertension or CV disease

Screening test: aldosterone:renin ratio

Conversion for units and methods of measurement
  Traditional
units
= SI units
Aldosterone 1 ng dl-1 = 27.7 pmol l-1
PRA 1 ng ml-1 h-1 = 12.8 pmol l-1 min-1
Direct renin conc. (DRC)
equiv. to PRA 1 ng ml-1 h-1
5.2 ngl l-1 = 8.2 mU l-1

ARR cut-off values by different methods & units
PRA
ng ml-1h-1
PRA
pmol l-1min-1
DRC
mU l-1
DRC
ng l-1
PAC ng dl-1 20 1.6 2.4 3.8
30 2.5 3.7 5.7
40 3.1 4.9 7.7
PAC pmol l-1 750 60 91 144
1000 80 122 192
Drugs to be totally avoided
Spironolactone, eplerenone, amiloride, triamterene, liqourice, potassium-wasting diuretics
(Bill Young argues that stopping diuretics is unnecessary - should cause renin to rise but in PA renin is immovable)
Drugs with significant effect on RAA system
Beta-blockers, ACEI, ARB, DRI, dihydropyridine CCBs, clonidine, methyldopa, NSAIDs
Drugs with little effect on RAA system
Verapamil M/R, hydralazine, alpha-blockers

  • Liberalise sodium intake
  • Correct hypokalaemia
  • Withdraw red drugs
  • If ARR non-diagnostic, repeat after withdrawing orange drugs
  • Oestrogen-containing mediations may lower renin and raise ARR
  • Age>65 and renal failure can also raise ARR

Confirmatory tests

Saline infusion test

Method
  • start 0830-0900
  • recumbent position 1hr before and during test
  • infusion 2 litres 0.9% saline over 4 hours
  • measure renin, aldo, cortisol, U&E at 0 and 4 hours
  • monitor BP and pulse throughout
Interpretation
  • PA unlikely if postinfusion aldo <5 ng/dl (138.5 pmol/l)
  • PA likely if postinfusion aldo >10 ng/dl (277 pmol/l)
Contraindications
  • severe uncontrolled hypertension
  • cardiac or renal failure
  • severe hypokalaemia

Fludrocortisone challenge test

Method
  • 100mcg fludrocortisone every 6hr for 4 days
  • slow-release K+ every 6hr at dose to keep plasma K+ close to 4 mmol/l (measured 4 times/day!)
  • slow-release NaCl 30 mmol tds with meals, plus sufficient dietary salt to maintain urine sodium excretion rate at least 3 mmol/kg
  • measurements on day 4:
    • plasma cortisol and U&E 0700h and 1000h
    • plasma aldo and PRA at 1000h in upright seated posture
Interpretation

Upright seated plasma aldo >6 ng/dl (166 pmol/l) at 1000h confirms PA provided:
  • PRA <1 ng ml-1 h-1 (12.8 pmol l-1 min-1)
  • cortisol falls from 0700h to 1000h to exclude confounding ACTH effect
  • normal K+

Diagnostic tests

Adrenal vein sampling

Purpose is to exclude BAH - bilateral adrenal hyperplasia. If due to technical failure, cannulation of only one adrenal occurs, an elevated aldosterone level from that adrenal is not helpful; the goal of AVS was to show suppression of the contralateral adrenal.