Conn’s syndrome

1. Case capsule
Zeeshan

2. •Mrs X/34 yrs
•Recurrent episodes of muscle cramps for 1
year
•Polyuria and nocturia for 5 months.

3. •Dx- Hypertension for 6 years on 4
antihypertensives
•Persistent hypokalemia for 1 year
•Frequent change of antihypertensives once
every 3 months for 1 year

4. Other significant H/O?

5. On examination
•HR - 80 per minute BP – 170/90 mm Hg.
•General and systemic examination was
unremarkable.

6. Investigations?

7. 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)

8. Differential diagnosis?

9. DD for Hypertension + Hypokalemia
•Renovascular disease
•Cushing’s syndrome
•Renin secreting tumors
•Congenital adrenal hyperplasia
•Primary aldosteronism

14. Diagnosis?

16. Most common subtypes
•Bilateral idiopathic hyperaldosteronism(IHA)
•Aldosterone producing adenomas (APA)

17. Clinical presentation
•Uncontrolled hypertension
•Unexplained hypokalemia

18. 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

19. •HTN with adrenal incidentaloma
•HTN+ family history of early onset HTN
•All hypertensive first degree relatives of
patients with primary hyperaldosteronism.

20. RAA cascade

21. 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

22. Drugs interfering with PAC/PRC ratio
•Mineralocorticoid receptor antagonist
- Spironolactone
- Eplerenone
•ACE inhibitors & ARB
- Low PAC/PRC level does not exclude Conn’s

24. 24 hour urine test
•24 hour urine potassium
-Potassium wasting (>30 mEq/day)
•24 hour urine aldosterone measurement

25. Why one needs to confirm diagnosis
•Mr. X
-Hypertension
-Hypokalemia
-PAC/PRA – Borderline

26. 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

27. Results
-Check 24 hour urine Na for checking adequate
loading
-Check urine Aldosterone levels ( > 12 ng/dl
diagnostic)

28. Saline infusion test
•Administer 2 litres of isotonic saline over 4
hours
•Normal individuals – PAC < 5 ng/dl
•Primary hyperaldosteronism – PAC > 10 ng/dl

29. Diagnostic dillema

30. Bilateral adrenal
hyperplasia
Aldosterone
producing
adenoma
Incidence60 % 35%
Aldostn
rate
Lower rate of
production
Higher rate
Hypokale
mia
Mild Profound
Age > 50 yrs < 50 yrs

31. CT abdomen
Presence of unilateral mass does NOT confirm Adenoma
Presence of bilateral lesion – NOT diagnostic of hyperplasia

32. Systematic review of 38 studies
•Ann Intern Med. 2009;151(5):329.

33. 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

34. Adrenal vein sampling
•Measurement of aldosterone sample in
adrenal venous blood.
•Unilateral four fold increase of aldosterone
diagnostic

35. Role for adrenal venous sampling in primary aldosteronism.
AU
Young WF, Stanson AW, Thompson GB, Grant CS, Farley DR, van Heerden JA
SO
Surgery. 2004;136(6):1227.
APA - Aldosterone producing adenoma
IHA – Idiopathic hyperplasia of adrenals
PAH – Unilateral adrenal hyperplasia

37. Operation
•Retroperitoneoscopic/ Laparoscopic
adrenalectomy

38. 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

39. 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