HDCN Ask the Professor:

Hypertension, hypokalemia, equivocally high aldosterone excretion


Question:
A 22 year old male was seen for evaluation of hypertension. At age 19 after a tonsillectomy and adenoidectomy, he was hospitalized briefly in intensive care for hypertension. He was started on beta-blocker therapy, which he took briefly and discontinued. When evaluated several months ago, blood pressure was 135/95. K 3.3, bicarbonate 32.5 with the rest of the SMAC, CBC, and urinalysis all normal. The patient was taking no diuretics, denied laxative ingestion, nausea, vomiting, and diarrhea. There was no family history of hypertension or cerebrovascular accident.

When reevaluated while eating a normal sodium diet, his blood pressure was 135/95, K 3.6, HCO 38.3, plasma renin activity after 2h of upright posture was 3.6 ng/ml/h (normals 1.3-4.0). Aldosterone 30 ng/dl. Random urine Na was 67 mEq/l, urine K 76 mEq/24h. VMA 6 mg/24 h (nl 2-10). Aldosterone 19 mcg/24h (nl 2-19). He was begun on Procardia XL. Subsequently, the blood pressure was 120/90, K 4.1, HCO 33.2. Other studies done included CT scan of the abdomen and pelvis which were normal. Captopril renal scan was normal, no lateralization.

I thought this was and interesting case and would like thoughts on this and work-up of hypertension with hypokalemia in this setting.
Dr. Alvin E. Brent, M.D., Jackson, MI


Response by Dr. Stuart L. Linas, M.D., Denver, CO
The work-up of the hypokalemic hypertensive patient is first directed at determining the role of mineralocorticoid. Mineralocorticoid-like hypertension can occur in the absence of increased aldosterone in Liddle's syndrome or 11- beta-hydroxysteroid dehydrogenase deficiency. Liddle's syndrome is mediated by a constiutively active sodium channel. 11-beta-hydroxysteroid dehydrogenase deficiency as occurs after licorice or in hereditary variants results from decreases in the renal enzyme which converts cortisol to cortisone.

Cortisone is unable to activate mineralocorticoid receptors while cortisol is able to activate mineralocorticoid receptors but is prohibited from this activation by 11-beta-hydroxysteroid dehydrogenase. Thus, decreases in this enzyme result in increases in cortisol and activation of mineralocorticoid receptors follo wed by hypertension and hypokalemia.

However, this patient had increases in aldosterone. Aldosteronism can be primary or secondary. Primary aldosteronism is caused by aldosterone producing adenomas, idiopathic adrenal hyperplasia, or glucocorticoid-remedial hyperaldosteronism. All are associated with decreases in plasma renin activity.

Aldosterone producing adenomas and idiopathic adrenal hyperplasia are associated with increases in aldosterone levels which are not suppressible by exogenous mineralocorticoids or glucocorticoids. In contrast, glucocorti coid- remedial hyperaldosteronism is reversed by exogenous glucocorticoid but not mineralocorticoid.

Surprisingly, this patient has increases in PRA. Thus, he had secondary rather than primary aldosteronism. Secondary aldosternonism is associated with hypertension under several conditions including primary reninism and malignant hypertension. Renal artery stenosis has been effectively excluded. However, in primary reninism and malignant hypertension, renin levels are generally much higher than in this individual. In this patient, the renin is not high enough to account for his hypertension or aldosteronism. I would proceed by questioning the renin values. It may be appropriate to perform renin determinations under more controlled conditions such as high and low salt diets. In addition, I would infuse sodium chloride to be certain aldosteronism is secondary rather than primary. My hunch is that this individual does not have secondary but primary aldosteronism and I would proceed with a more extensive work-up for an aldosterone producing adenoma or idiopathic adrenal hyperplasia.


Response by Dr. Lawrence R. Resnick, M.D., Wayne State University Hospital, Detroit, MI
Suggest most likely possibilities, without erudite discussion:
1) segmental/branch renal artery stenosis
2) coarctation of the aorta, partial
3) weird syndromes such as Moya-Moya syndrome, or noninflammatory/nonarteritis variations of Takayasu's, etc.
4) small pheo/Cushing's, etc; any other lytes abnormal: Mg, Ca, P ?
5) I don't know - always a good bet

Renal vein renins in a good institution, pre/post captopril, with segmental sampling; IVC sampling supine and upright, and/or appropriate other hormone measurements will help distinguish among the above. At this young age, and with the negative family history of hypertension. I wouldn't give up on secondary hypertension just yet.

April, 1996



I agree that renal arery stenosis is a definite consideration. However there have been cases of both hyperaldosteronism(primary) and renal artery stenosis co-existing.
George Mansoor
Farmington, CT USA-Tuesday, July 23, 1996 at 16:15:12 (CDT)


In terms of ruling out primary hyperaldosteronism,have other aldo/renin ratios been done?Will he agree to a fludrocortisone suppression test? In terms of renal artery stenosis, which isotope was used,was it done in a dept experienced in the area.Have you access to reliable renal artery doppler?
paul martin (docmartin@gpo.pa.uq.edu.au)
brisbane, queensland australia-Friday, August 09, 1996 at 01:09:06 (CDT)


The very easy control of hypertension in this patient is good for him, but a little bit easy for me! HypoK,with alkalosis,would get me a little suspicious of either diuretic abuse or repeated vomiting. Both diagnoses are sometimes difficult to make.
A.Korzets (aradmt@.netvision.net.il)
Kfar Saba, Israel-Saturday, April 04, 1998 at 12:44:06 (PST)