Evaluation of adrenal function

Question 1

What fraction of circulating cortisol is active for signaling?

At what concentration does it begin binding to albumin?

Answer 1

Free cortisol is active

Normally less than 5% of circulating cortisol is free.

When the concentration of cortisol is >700 nmol/l (25 ug/dl) part of the excess binds to albumin, and a greater proportion than ususal circulates unbound.

Question 2

What are the common measured compounds of adrenal cortex function?

Why and when are they measured?

Answer 2

Adlosterone

Cortisol

DHEAS

Androstendione

Measured for DDx of hypertension, obesity, hyperandrogenism.

Measured in the morning

Question 3

Clinical symptoms of Cushing’s

Answer 3

• Obesity
• Moon face
• Thin, easy bruising skin, purplish, striae, acne, hirsutism
• polyglobulia
• Proximal muscle weakness,
• Proximal muscle weakness, muscle atrophy
• osteoporosis, fractures ( growth failure in children)
• Hypokalemia, alkalosis
• hypertension, diabetes mellitus, lipid metabolism disorders
• Menstrual irregularities, amenorrhoea, infertility
• Infektion-risk
• depression
• Compression fractures from bone loss
• osteonecrosis of femur head
• hypercalciuria and nephrolithiasis.

Question 4

Test to diagnose cushings syndrome

Answer 4

Urine cortisol measured at least twice.

Midnight salivary cortisol measurement twice

Dexamethasone suppression test, low dose no suppression, high dose suppression.

Measure ACTH in Plamsa

Imaging,

• MRI of pituitary
• CT for pituitary

Question 5

Test for adrenal cortex Cortisol producing function. What zone produces cortisol?

Answer 5

CRH administration, measure cortisol and ACTH levels 5, 15, 30 mins measures the zona fasciculata function

Synacthen administration, Measure cortisol.

Question 6

Test for aldosterone production?

What zone produces it?

Answer 6

Synacthen test: ACTH analog, should stimulate both cortisol and aldosterone production, measured 30 minutes later. Cortisol should exceed 495 nM, 18 ug/dL, aldosterone should be above 5 ng/dL

Saline loading test: administer IV isotonic NACl oiver 2 hours. The increased volume and Na content should decrease aldosterone in patients with normal function. Will not decrease if they have primary hyperaldosteronism.

Question 7

Signs and ymptoms of hypertension, hyperaldosteronism

When should you check for hyperaldesteronism?

Answer 7

Left ventricular hypertrophy, by EKG, X-ray, Ultrasound.

Low potassium, U waves on EKG, arrythmias PVCs

When to screen

• Hypertension and hypokalemia
• Hypertension and adrenal tumor
• Resistant hypertension (20% incidence)
• In a young hypertensive patient, < 20 years of age
• Severe hypertension ( > 160/100 Hgmm)
• Whenever considering secondary hypertension

Question 8

Causes of secondary hypertension

Answer 8

Apnea, Aldosteronism, presence of renal artery Bruits (suggesting renal artery stenosis), renal parenchymal disease (Bad kidneys), excess Catecholamines, Coarctation of the aorta, Cushing’s syndrome, Drugs, Diet, excess Erythropoietin, and Endocrine disorder

• Aorta
  
  • Aortic Regurgitation
  • Aortic Coarctation
• Kidney
  
  • Glomerular disease
  • Renal Artery Stenosis
  • Polycystic Kidney Disease
• Adrenal
  
  • Cushing’s and Conn’s
  • Pheochromocytoma
• Thyroid
  
  • Hyperthyroidism - isolated systolic hypertension
  • Hypothyroidism - isolated diastolic from sodium retention
  • Hyperparathyroidism - hypercalcemia
• Drug induced,
  
  • oral contraceptive increase angiotensinogen synthesis
  • cocaine, other rec drugs
• Pregnancy

Question 9

Screens for hyperaldosteronism

Answer 9

Plasma aldosterone concentration

Plasma Renin Activity (PRA)- enzyme measurement in vitro

Measured in the morning from a seated patient that has normal potassium to prevent suppression of aldosterone.

Measure Aldosterone-Renin Ratio (ARR).

• Ratio above 30 (when both are in ng/mL) and aldosterone levels above 15 ng/dL indicates primary hyperaldosteronism, Conn syn.
• Ratio below 30, indicates increased Renin, inducing increased hyperaldosteronism.
• Confirmed by 24 hr urine aldosterone level
• Or confirmed by Adrenal vein sampling

Adrenal vein sampling: Used to check for lateralization, if one adrenal is hyperfunctioning, the contralateral should be suppressed. Lateralization exists if the aldosterone or cortisol ratio is 4 fold higher in one vein than the other. For the test to be valid, the adrenal vein to IVC cortisol ratio must be above 2.

Question 10

What are the aldosterone suppression tests?

Answer 10

IV saline suppression test - 500 ml phys saline for 4 hours infusion. Measure plasma aldosterone concentration (PAC), at 0 minutes and at the end of the 4th hour.

Oral sodium chloride suppression test - give 10 g NaCl orally every day for 4 days. On day 4, do a 24 hour urine collection. measure aldosterion and sodium. Aldosterone is suppressed if it is below 14 mg and sodium mis above 200 mM.

Fludrocortisone suppression test - An Aldosterone agonist. A high salt diet and large doses of Astonin H. Should cause Aldosterone suppression. Serum aldosterone > 140 pmol/L indicates a failed test and primary hyperaldosteronism.

All of these tests must be performed in the seated position as this has strong effect on aldosterone levels.

Question 11

What drugs influence/invalidate the ARR test results?

Answer 11

ARR can’t be assessed: spironolacton, eplerenon amilorid

ARR false positive: Béta blockers, alphaa-methyldopa clonidin, NSAIDs

ARR false negative: ACE inhibitors, AII receptorblockers

Question 12

What suppresses DHEA and DHEAS expression

Answer 12

Cortisol, in CAH.