ALDOSTERONISM, PRIMARY

ALDOSTERONISM, PRIMARY - Mark C. Horattas, MD, FACS
BASICS
DESCRIPTION
• The clinical syndrome of excess secretion of aldosterone is classically manifested by hypertension, hypokalemia, and depressed plasma renin activity (patients often present as normokalemic).
• Unilateral aldosterone-producing adenoma (APA): Cured with unilateral adrenalectomy
• Idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia: Not cured with surgery, medical management
• System(s) Affected: Endocrine/metabolic
• Synonym(s): Conn syndrome; Aldosteronoma; Hyperaldosteronism
ALERT
Pregnancy Considerations
Can be associated with toxemia during pregnancy or persistent hypertension following delivery. Treat hypertension with agents proven to be safe during pregnancy; avoid spironolactone and ACE inhibitors.
EPIDEMIOLOGY (1)[A]
Incidence
Involves 1% of the hypertensive population
Prevalence
• Usually diagnosed during 4th to 6th decades
• More common in women
RISK FACTORS
Genetics
Can be associated rarely with familial multiple endocrine neoplasia (MEN) syndromes.
ETIOLOGY
• Unilateral aldosterone-producing adenoma (APA)
• Idiopathic hyperaldosteronism (IHA)
• Other rare subtypes


DIAGNOSIS
(2)[A]
SIGNS AND SYMPTOMS
Physical Exam
• Usually asymptomatic
• Most patients are normokalemic.
• Marked hypokalemia may be associated with muscle weakness and cramping, intermittent paralysis, headaches, palpitations, polydipsia, polyuria, or nocturia.
• Mild to severe hypertension, one of the causes for secondary hypertension
• Funduscopy: Benign or grade 1-2
• Edema (rare)
• Hypokalemia (not required)
• Metabolic alkalosis
• Relative "hypernatremia"
• Impaired glucose tolerance
TESTS
• Screen for primary aldosteronism
- Patients with hypertension and spontaneous hypokalemia
- Patients with treatment-resistant hypertension
• Plasma aldosterone levels, plasma renin activity
• Special tests
- Aldosterone suppression test with either a high salt diet or saline infusion
- Spironolactone treatment trial
Lab
• Hypokalemia with inappropriate kaliuresis
• Insuppressible urine or plasma aldosterone levels
• Low ambulatory plasma renin activity
• High plasma aldosterone to renin ratio (>20 in ng/dL [>55 nmol/L] and ng/mL/h, respectively)
• Normal glucocorticoid excretion
• Drugs that may alter lab results: Diuretics, ACE inhibitors, spironolactone
• Disorders that may alter lab results: Malignant hypertension
Imaging
• Adrenal CT (preferred over MRI) with fine cuts
• Iodocholesterol (NP-59) scan with dexamethasone suppression
• Adrenal vein sampling (3)[A]
Diagnostic Procedures/Surgery (4)[A]
• Laparoscopic adrenalectomy if localized on CT scan
• Adrenal venous sampling for lateralization preoperatively if not localized by CT scan.
Pathological Findings
• Aldosteronoma usually a benign solitary adenoma.
• Idiopathic hyperaldosteronism (IHA) due to bilateral adrenal (zona glomerulosa) hyperplasia
• Aldosterone-producing adrenocortical carcinoma rarely
DIFFERENTIAL DIAGNOSIS
• Diuretic use
• Renovascular hypertension
• Pheochromocytoma
• Renin-secreting tumor
• Malignant hypertension
• Congenital adrenal hyperplasia
• Deoxycorticosterone-producing tumor
• Exogenous mineralocorticoid
• High-dose glucocorticoid therapy
• Apparent mineralocorticoid excess syndrome (congenital or acquired due to licorice ingestion)
• Liddle syndrome
TREATMENT
STABILIZATION
• Appropriate health care
- Unilateral APA: Unilateral adrenalectomy
- Bilateral IHA: Chronic medical therapy
• Unilateral APA: Correct hypokalemia preoperatively with spironolactone
• Bilateral IHA: Low-sodium diet, regular isotonic exercise, maintenance of ideal body weight, tobacco avoidance, mineralocorticoid receptor antagonist, antihypertensive agent (e.g., calcium channel antagonist, ACE-inhibitor, low-dose thiazide diuretic)
Diet
Low sodium
MEDICATION (DRUGS)
• Potassium-sparing agent: Spironolactone (Aldactone) or amiloride (Midamor)
• Antihypertensive agent: Calcium channel antagonist, ACE inhibitor, angiotensin-II receptor antagonist, or low-dose thiazide diuretic
• Contraindications: Potassium-sparing agent and ACE inhibitors in renal failure, hyperkalemia, and pregnancy
• Precautions: Monitor serum potassium closely after any adjustment in potassium replacement or potassium-sparing agent.
• Significant possible interactions: Lithium and diuretics, NSAIDs with diuretics, and ACE inhibitors
SURGERY
The treatment of choice for patients with unilateral APA is adrenalectomy. Patients with bilateral IHA are treated medically.
FOLLOW-UP
PROGNOSIS
• Surgical removal of an APA results in a cure of hypertension in ~30-60% of the cases.
• Hypertension does not resolve immediately postoperatively, but rather over 1-4 months.
COMPLICATIONS
Cardiac arrhythmia associated with severe hypokalemia
PATIENT MONITORING
• BP checks
• Serum potassium check
• 24-hour urine aldosterone following surgery
REFERENCES
1. Clark OH, Duh QY. Textbook of Endocrine Surgery. Philadelphia; WB Saunders, 2005.
2. Mulatero P, Stowasser M, Loh KC, et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. 2004;89:045 [PMID 15001583].
3. Young WF, Stanson AW, Thompson GB, et al. Role for adrenal venous sampling in primary aldosteronism. Surgery. 2004;136:1227 [PMID 15657580].
4. Mansmann G, Lau J, Balk E, et al. The clinically inapparent adrenal mass: update in diagnosis and management. Endocr Rev. 2004;25:309.