IN 25% CASES INSULINOPENIA DEVELOPS.
Medical management is the treatment of choice for the IAH variant of primary hyperaldosteronism (PH).
Among the major goals of therapy are (1) normalization of blood pressure, (2) normalization of serum potassium and other deranged electrolytes levels, and (3) normalization of serum aldosterone levels. Evidence exists to show that chronic hyperaldosteronism in and of itself in the absence of elevated blood pressure (eg, as occurs in secondary hyperaldosteronism) is associated with increased risk for cardiac injury including ischemic and fibrotic injury. Furthermore, studies show that patients with PH are more likely to have left ventricular hypertrophy, stroke, and acute coronary syndromes than patients with similar degrees of hypertension from other causes.
Aldosterone antagonism, by both spironolactone and eplerenone, in patients with heart failure who have secondary hyperaldosteronism has been demonstrated to confer survival benefit.
By inhibiting the intracellular calcium flux in the adrenocortical cells, the dihydropyridine calcium channel blockers reduce the production of aldosterone in response to a variety of stimulants, including potassium, ACTH, and angiotensin-II. Nifedipine is the most extensively studied of these medications; however, while causing a significant improvement in patients with HTN, it does not address the pathophysiology of the condition. The PRA, aldosterone levels, plasma volume, and serum potassium concentrations remain essentially unchanged while using nifedipine.
ACE inhibitors and angiotensin receptor blockers (ARBs) are also potential treatment options.
Mineralocorticoid antagonists, such as spironolactone, achieve remarkable blood pressure control and normalization of the above-mentioned parameters, particularly in patients with aldosteronomas. The salutary effects of spironolactone appear to be mainly due to the effects on salt and water balance rather than to its antagonism of aldosterone in the kidney. The combination of spironolactone and thiazides often provides even better blood pressure control than spironolactone alone. Because of the estrogenlike adverse effects of spironolactone, including impotence and gynecomastia, the incentive to develop a similarly effective antialdosterone agent without these adverse effects is considerable. Eplerenone is a new selective antialdosterone agent that may fulfill this promise, as it is a specific aldosterone receptor antagonist without the additional antiandrogen effects associated with spironolactone.
Other less ideal medical treatment options include other potassium-sparing diuretics, such as triamterene and amiloride. Amiloride acts at the level of the distal convoluted tubule (DCT) but does not bind to mineralocorticoid receptors.
Medical therapy is also a viable treatment option in patients who have lateralizable disease but who are poor surgical candidates because of other coexisting comorbidities. It is also a viable treatment option in the rare setting of bilateral functional adrenal adenomas that would otherwise require bilateral adrenalectomy.
In the subgroup of patients with GRA, the treatment of choice is to use the lowest possible dose of glucocorticoid to achieve adequate blood pressure control. Because of the potential adverse effects that can result from even subtle glucocorticoid excess, using short-acting glucocorticoids, such as prednisone and hydrocortisone (rather than dexamethasone), is generally best.
Surgical Care
Surgery is the treatment of choice for the lateralizable variants of PH, including typical aldosteronomas, RRAs, and PAH.
Preoperatively, once the biochemical and anatomical diagnoses are made and confirmed, the patient should be started on a 3- to 5-week course of spironolactone. This serves both as an additional diagnostic tool (in confirming the diagnosis of PH) and as a means of predicting the response of the blood pressure that can be expected postsurgery.
An adrenalectomy can be performed either via a formal laparotomy or, increasingly commonly, by a laparoscopic technique. The laparoscopic option now makes it possible to offer surgical therapy to relatively frail patients who would be unable to withstand formal laparotomies. Ongoing studies are systematically evaluating the place of adrenal-conserving operations versus total unilateral adrenalectomy in these patients.
Among the options being studied are partial adrenalectomy, in which a wedge resection of the gland with the adenoma is performed along with aldosteronoma enucleation, and medulla-sparing adrenalectomy, where an attempt is made to retain the adrenal medullary tissue while removing the cortex.
About 60-70% of patients are rendered normotensive following curative surgery for aldosteronomas when evaluated 1 year postoperatively. The percentage of patients who remain normotensive 5 years postoperatively is about 53%. Resolution of hypertension following adrenalectomy invariably occurs in the setting of absent family history of hypertension and/or preoperative use of two or fewer antihypertensives. Virtually all patients with an aldosteronoma, however, have significant reductions in aldosterone secretion, blood pressure, and correction of hypokalemia following surgery.
Adrenalectomy has very little utility in the setting of IAH. In reported cases where this had been done unintentionally, the effects on blood pressure, hypokalemia, and aldosterone hypersecretion have been found to be minimal further underpinning the necessity of making a correct diagnosis before making a case for adrenalectomy.
Persistence of HTN following apparent surgical treatment of lateralizable disease is most common in patients older than 45 years, in those who have had HTN for more than 5 years prior to surgery, and in those who did not respond preoperatively to spironolactone.
Other possibilities to consider are an incomplete resection of the adenoma with remaining remnant hyperplastic tissue or the possibility that the patient may have coexistent essential HTN (which is a prevalent condition). The coexistence of hypertensive nephrosclerosis in some of these patients is also a distinct possibility. The coexistence of other secondary causes of HTN also needs to be considered; renal artery stenosis is an important consideration.
Prior to surgery, patients should receive at least 8-10 weeks of medical therapy, both to decrease blood pressure and to correct the metabolic syndromes that are often associated with PH. Postoperatively, metabolic profiles should be closely monitored. Most patients do not develop permanent hypomineralocorticoidism and, thus, do not require fludrocortisone replacement.
For patients who develop hypoaldosteronism, the symptoms may persist for a long time and may be akin to the delay observed in adrenal glucocorticoid recovery following chronic ACTH suppression by exogenous steroids (see Image 3). However, if significant hyperkalemia develops, potassium supplements should be discontinued, and the patient can be started on furosemide at doses of 80-160 mg daily.
A few reports of using percutaneous injection of ethanol or acetic acid into aldosteronomas as a treatment modality exist, usually in patients for whom surgery is contraindicated. This technique is neither popular nor well validated. Furthermore, it requires the technical expertise of a highly skilled interventional radiologist.
Diet
A low-salt diet, though helpful in achieving blood pressure control in this condition, may be associated with false-negative results on biochemical testing.
A high-salt diet makes achievement of blood pressure control more difficult and may cause false-positive results on biochemical testing.
DRUG THERAPY :
1. SPIRONOLACTONE OR EPLERENONE : VERY IMPORTANT TO BLOCK THE DELETERIOUS EFFECTS OF ELEVATED SERUM ALDOSTERONE LEVELS.
CONTRAINDICATIONS - CHR RENAL FAILURE
2. ANTIHYPERTENSIVE AGENTS :
- CALCIUM CHANNEL BLOCKERS
- TRIAMTERENE & AMILORIDE
* GLUCOCORTICOID-REMEDIABLE ALDOSTERONISM CAN BE TREATED WITH LOW DOSES OF A GLUCOCORTICOID.