Hyperaldosteronism Clinical Presentation
- Author: George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London); Chief Editor: Stephen Kemp, MD, PhD more...
Primary hyperaldosteronism may be asymptomatic, particularly in its early stages. When symptoms are present, they may be related to hypertension (if severe), hypokalemia, or both.
The spectrum of hypertension-related symptoms includes the following:
If hypertension is severe, weakness, visual impairment, impaired consciousness, and seizures (hypertensive encephalopathy)
Hypokalemia can be precipitated by non–potassium-sparing diuretics or sodium loading. Symptoms of hypokalemia include the following:
Polyuria and polydipsia (because of impaired renal concentrating ability)
If the serum potassium is low enough, paralysis and disturbances of cardiac rhythm 
Hyperglycemia or frank diabetes mellitus is possible because insulin secretion is a potassium-dependent process that may be impaired by hypokalemia.
If secondary hyperaldosteronism is suspected as the cause of hypertension, the history should include questions about flushing, diaphoresis, anxiety attacks, and headaches (pheochromocytoma) and about hematuria and abdominal fullness (Wilms tumor or other renal tumor), in addition to the above symptoms.[26, 27]
For patients in whom secondary hyperaldosteronism is suggested, questions should be specifically directed at potential causes (eg, the presence and duration of swelling, the child’s exercise tolerance).
Information should be sought about a family history of essential hypertension and familial syndromes, including the following:
Neurofibromatosis (associated with renal artery stenosis and pheochromocytoma)
Multiple endocrine neoplasia (MEN) type 2 – This includes MEN 2A (parathyroid adenoma, medullary thyroid carcinoma [MTC], and pheochromocytoma) and MEN 2B (mucosal neuromas of eyelids, lips, and tongue with a long thin face, pheochromocytoma, and MTC)
von Hippel-Lindau syndrome - Cerebellar hemangioblastoma; renal and pancreatic cysts and carcinoma; hemangiomas of the retina, liver, and adrenal glands; and pheochromocytomas
In any child or adolescent with significant hypertension, a thorough investigation into the cause is warranted. Hypermineralocorticoidism should be considered in any patient with associated hypokalemia, though it should not be excluded in the absence of hypokalemia. In patients with significant hypertension, blood pressure should be measured several times, preferably with an automated device after a supine rest.
Examination of the hypertensive patient should include the following:
General examination – Be alert for dysmorphic features (eg, MEN 2B), evidence of neurofibromatosis type 1 (NF-1; ie, café-au-lait lesions, axillary freckling, short stature, and evidence of disease in parents), and features of Cushing syndrome (ie, obesity, short stature, striae, and hirsutism)
Neck examination – Assess for a thyroid mass (MTC associated with MEN 2)
Cardiovascular examination - Assess left ventricular muscle mass and exclusion of murmurs and pulse differential (eg, coarctation of the aorta); check for abdominal bruits (renal artery stenosis) and peripheral edema (secondary hyperaldosteronism)
Abdominal examination – Look for masses (Wilms tumor), hepatomegaly (cardiac failure or liver disease), splenomegaly, and ascites
Neurologic examination - Examine the eyes, and assess visual acuity (severe hypertension may interfere with vision); examine the eye grounds (looking for retinal angiomas [von Hippel-Lindau syndrome]); be alert for hypertensive retinopathy, which is of prognostic significance, including arterial narrowing, hemorrhages, cotton-wool spots, and papilledema; assess for Lisch nodules of the iris (NF-1)
Strength assessment - Evaluation for weakness, focal neurologic signs, or impaired conscious state in a patient with severe hypertension, which requires urgent treatment and central nervous system (CNS) imaging to exclude infarction or hemorrhage
Skin examination - In patients who have secondary hyperaldosteronism, look for evidence of NF-1
The main complications of primary hyperaldosteronism are hypertension and hypokalemia.
Hypertension due to hyperaldosteronism can damage many organs and organ systems, including the heart (hypertrophy and myocardial fibrosis), the blood vessels (vascular remodeling with medial and intimal hypertrophy and acceleration of atherogenesis), the eyes (arterial narrowing, retinal ischemia, and papilledema), the kidneys (progressive deterioration with nephrosclerosis), and the brain (hemorrhage).
When patients with untreated PA are compared with patients who have essential hypertension, the risk of previous myocardial infarction or acute coronary syndrome is increased approximately 2.5-fold, cerebrovascular event or transient ischemic attack is increased approximately 3–4-fold, sustained cardiac arrhythmia is increased approximately 5-fold, and peripheral arterial disease is increased approximately 3-fold. Renal disease is also increased in patients with PA. The frequency of 24-hour microalbuminuria in patients with PA (both APA and IHA) is twice that of patients with essential hypertension. Renal insufficiency has been reported to occur in 7-29% of patients with PA, and proteinuria has been reported in 8-24%.
Aggressive blood pressure control and early diagnosis and treatment of the underlying hyperaldosteronism minimize the risk.
Hypokalemia initially results in weakness, constipation, and polyuria; when it is more severe, it may cause cardiac arrhythmias. Patients receiving cardiac drugs are at greater risk for this complication. Hypokalemia also impairs insulin secretion and can promote the development of diabetes mellitus. Of note, hypokalemia should not be considered a diagnostic feature of primary hyperaldosteronism. In some studies, only a minority of patients with PA (9-37%) had hypokalemia. Thus, normokalemic hypertension constitutes the most common presentation of the disease; hypokalemia is probably present in only the more severe cases.
Patients with adenomas are more likely to develop this complication, as are patients who have milder disease but receive treatment with diuretics for their hypertension before the hyperaldosteronism is diagnosed.
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|False Negative Results|
|K-wasting diuretics (Non-K-sparing diuretics, such as thiazides, induce renal potassium losses and reduce plasma potassium concentrations, leading to decreased aldosterone secretion.)||→↑||↑↑||↓|
|Angiotensin receptor blockers||↓||↑↑||↓|
|DHPs (It is a shared opinion that dihydropyridinic calcium channel blockers do not significantly affect aldosterone secretion, mainly causing an increase in PRA, which rarely gives false negatives.)||→↓||↑||↓|
|False Positive Results|
|Central alpha-2 agonists (eg, clonidine, alpha-methyldopa)||↓||↓↓||↑|
|Luteal phase of menstrual cycle||↑||PRA: Unchanged||↑|
|Antihypertensive Medications With Minimal Effect on the ARR|
|Prazosin, doxazosin, terazosin||←→|
|Renin inhibitors (Renin inhibitors raise the ARR if renin is measured as PRA [false positive] and lower it if measured as DAR concentration [false negative.])||↓||↑↓||↑↓|
|OCPs (OCPs have little effect on ARR when renin is measured as PRA. Use of immunometric measurements of DAR rather than PRA may give false positive results. Subdermal etonogestrel has no effect on ARR.)||↑||↓DAR||↑|
ARR, aldosterone-renin ratio; NSAIDs, non-steroidal anti-inflammatory drugs; K, potassium; ACE, angiotensin converting enzyme; ARBs, angiotensin II type 1 receptor blockers; DHPs, dihydropyridines; PHA-2, pseudohypoaldosteronism type 2; PRA, plasma renin activity; DAR, direct active renin; OCPs, oral contraceptive agents; SSRIs, selective serotonin reuptake inhibitors
|Spironolactone||Aldosterone antagonist||0-10 kg: 6.25 mg/dose PO q12h
11-20 kg: 12.5 mg/dose PO q12h
21-40 kg: 25 mg/dose PO q12h
>40 kg: 25 mg PO q8h
|Potassium canrenoate||Aldosterone antagonist||3-8 mg/kg IV qd; not to exceed 400 mg|
|Amiloride||Potassium-sparing diuretic||0.2 mg/kg q12h|
|Triamterene||Potassium-sparing diuretic||2 mg/kg/dose q8-24h|
|Nifedipine||Dihydropyridine calcium channel antagonist||0.25-0.5 mg/kg PO q6-8h|
|Amlodipine||Calcium channel antagonist||0.05-0.2 mg/ day PO|
|Doxazosin||Alpha1 -specific adrenergic antagonist||0.02-0.1 mg/day; not to exceed 4 mg|
|Prazosin||Alpha1 -specific adrenergic antagonist||0.005 mg/kg test dose, then 0.025-0.1 mg/kg/dose q6h; not to exceed 0.5 mg/dose|