Conn’s syndrome

Case capsule

Zeeshan

• Mrs X/34 yrs

• Recurrent episodes of muscle cramps for 1 year

• Polyuria and nocturia for 5 months.

• Dx- Hypertension for 6 years on 4 antihypertensives

• Persistent hypokalemia for 1 year

• Frequent change of antihypertensives once every 3 months for 1 year

Other significant H/O?

On examination

• HR - 80 per minute BP – 170/90 mm Hg.

• General and systemic examination was unremarkable.

Investigations?

Investigation Value

Hb 12.2 gm%

Total counts 10,600 / mm3

Electrolytes Na- 140mmol/l K- 2.5mmol/l

Urine metanephrine/ normetanephrine

105mcg/24hrs (<350ng/24hrs)533 mcg/24 hrs (<600ng/24hrs)

Creatinine 0.62

Renin <0.1 ng/ml/hr (At rest–.05-2.3) (Upright – 1.3-4)

Aldosterone 2.78 nanogm/ml (0.40 – 3.10ng/ml )

Serum Cortisol (8AM) 7mcg/dL (6-23 mcg/dL)

Cortisol post-dexa suppression

0.31 mcg/dl (<1.8mcg/dl)

Differential diagnosis?

DD for Hypertension + Hypokalemia

• Renovascular disease

• Cushing’s syndrome

• Renin secreting tumors

• Congenital adrenal hyperplasia

• Primary aldosteronism

Diagnosis?

Most common subtypes

• Bilateral idiopathic hyperaldosteronism(IHA)

• Aldosterone producing adenomas (APA)

Clinical presentation

• Uncontrolled hypertension

• Unexplained hypokalemia

Who to screen for Hyperaldosteronism

• HTN + Spontaneous/ low dose diuretic induced hypokalemia

• Severe HTN( Systolic> 160mm Hg and Diastolic > 100 mm Hg) / Drug resistant hypertension

J Clin Endocrinol Metab. 2008

• HTN with adrenal incidentaloma

• HTN+ family history of early onset HTN

• All hypertensive first degree relatives of patients with primary hyperaldosteronism.

RAA cascade

Plasma aldosterone conc/Plasma renin activity ratio

• PAC > 15 ng/dl Diagnostic of • Ratio of PAC/PRC > 20 Conn’s

• Test to be performed in the morning 8:00 AM• Paired random sample to be collected• Certain drugs contraindicated prior to test

Drugs interfering with PAC/PRC ratio

• Mineralocorticoid receptor antagonist - Spironolactone - Eplerenone

• ACE inhibitors & ARB - Low PAC/PRC level does not exclude Conn’s

24 hour urine test

• 24 hour urine potassium- Potassium wasting (>30 mEq/day)

• 24 hour urine aldosterone measurement

Why one needs to confirm diagnosis

• Mr. X- Hypertension- Hypokalemia- PAC/PRA – Borderline

Test for confirmation

• Oral Na loading test- Correct hypertension and hypokalemia

- Avoid Spironolactone/ Eplerenone

- Achieve 5000mg Na diet over 3 days/ Two 1 gram Na tablets taken three times daily

Results

- Check 24 hour urine Na for checking adequate loading

- Check urine Aldosterone levels ( > 12 ng/dl diagnostic)

Saline infusion test

• Administer 2 litres of isotonic saline over 4 hours

• Normal individuals – PAC < 5 ng/dl

• Primary hyperaldosteronism – PAC > 10 ng/dl

Diagnostic dillema

Bilateral adrenal hyperplasia

Aldosterone producing adenoma

Incidence 60 % 35%

Aldostn rate

Lower rate of production

Higher rate

Hypokalemia

Mild Profound

Age > 50 yrs < 50 yrs

CT abdomen

Presence of unilateral mass does NOT confirm Adenoma

Presence of bilateral lesion – NOT diagnostic of hyperplasia

Systematic review of 38 studies

• Ann Intern Med. 2009;151(5):329.

If Management was based on CT/MRI

• 139 patients (14.6%) - inappropriately undergone unilateral adrenalectomy

• 181 patient (19.1) - medical management instead of curative adrenalectomy

• 37 patients (3.9%) – adrenalectomy on the wrong side

Adrenal vein sampling

• Measurement of aldosterone sample in adrenal venous blood.

• Unilateral four fold increase of aldosterone diagnostic

Role for adrenal venous sampling in primary aldosteronism.AUYoung WF, Stanson AW, Thompson GB, Grant CS, Farley DR, van Heerden JASOSurgery. 2004;136(6):1227.

APA - Aldosterone producing adenomaIHA – Idiopathic hyperplasia of adrenalsPAH – Unilateral adrenal hyperplasia

Operation

• Retroperitoneoscopic/ Laparoscopic adrenalectomy

Postoperative persistent hypertension

• Long term cure rate – 69%

• 60 % become normotensive• 40% improve markedly but remain

hypertensive

• Normalisation of blood pressure DOES NOT occur immediately after operation – 1 year

Risk factors for persistent HTN

• Age- Older age group associated with lesser

chances of reversal to normotensive• Gender• Duration of HTN preop• Positive family history of HTN