High blood pressure (hypertension) is a common condition, but in most cases, the cause remains unknown (primary hypertension). A smaller percentage of cases result from an identifiable underlying disease, termed secondary hypertension. Endocrine hypertension is a form of secondary hypertension caused by disorders of the hormone-producing glands. Identifying the hormonal origin is important because it allows for targeted treatment that can often cure the hypertension or significantly improve its management.
How Hormones Regulate Blood Pressure
Hormones play a large role in regulating blood pressure stability. One primary mechanism is the Renin-Angiotensin-Aldosterone System (RAAS), which manages fluid and electrolyte balance. When blood pressure drops, the kidneys release renin, triggering a cascade that produces angiotensin II, a powerful blood vessel constrictor. Angiotensin II also stimulates the adrenal glands to release aldosterone, which instructs the kidneys to retain sodium and water. This retention of salt and fluid increases blood volume, raising blood pressure.
Another system involves catecholamines, such as epinephrine and norepinephrine, produced by the adrenal medulla. These hormones rapidly increase heart rate and the force of heart contractions. Catecholamines also constrict blood vessels, increasing resistance to blood flow and quickly elevating blood pressure. Dysregulation in these pathways can lead to sustained high blood pressure, defining endocrine hypertension.
Specific Hormonal Conditions Causing Hypertension
The most common form of endocrine hypertension is Primary Aldosteronism (PA), characterized by the overproduction of aldosterone from the adrenal glands. This excess aldosterone occurs autonomously, unregulated by the RAAS system. The resulting mechanism involves the unnecessary retention of sodium and water by the kidneys, leading to expanded blood volume and persistent hypertension. PA affects 5% to 10% of all hypertensive patients and carries a higher risk of cardiovascular events.
Cushing’s Syndrome is another significant cause, resulting from prolonged exposure to high levels of cortisol. Cortisol excess is typically caused by a tumor in the pituitary or adrenal gland. High cortisol levels enhance the body’s sensitivity to catecholamines and activate the mineralocorticoid receptor, mimicking aldosterone’s effects. This dual action contributes to fluid retention and increased vascular tone, resulting in elevated blood pressure.
Pheochromocytoma and Paraganglioma are rare tumors that cause the release of excessive amounts of catecholamines (epinephrine and norepinephrine). These tumors are found either in the adrenal gland (pheochromocytoma) or outside it (paraganglioma). The over-secretion of these hormones leads to severe, often episodic, hypertension characterized by symptoms like headaches, palpitations, and excessive sweating. Identifying these tumors is important due to the high risk of cardiovascular complications if left untreated.
Screening and Diagnostic Procedures
Identifying endocrine hypertension requires recognizing clinical signs suggesting a secondary cause. Screening is recommended for patients with hypertension resistant to standard medication, hypertension that began at a young age, or those presenting with abnormally low potassium levels (hypokalemia). Hypokalemia is a strong indicator of Primary Aldosteronism due to increased potassium excretion driven by excess aldosterone.
Primary Aldosteronism (PA)
For suspected PA, the initial screening test is the Aldosterone-to-Renin Ratio (ARR), which compares Plasma Aldosterone Concentration (PAC) to Plasma Renin Activity (PRA). An elevated ARR (high PAC and suppressed PRA) suggests that aldosterone production is inappropriate and independent of the RAAS feedback loop. A positive ARR requires confirmation using suppression tests, such as the oral sodium loading test or the saline infusion test, to determine if the high aldosterone secretion can be suppressed.
Pheochromocytoma and Cushing’s Syndrome
Screening for pheochromocytoma or paraganglioma involves measuring fractionated metanephrines, the breakdown products of catecholamines, in plasma or a 24-hour urine collection. Measuring these metabolites is preferred because their secretion is continuous, offering a reliable detection method. Imaging, such as a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen, is then used to locate tumors. For Cushing’s Syndrome, diagnosis relies on measuring cortisol levels in a 24-hour urine sample or performing a low-dose dexamethasone suppression test.
Targeted Management of Endocrine Hypertension
Diagnosing endocrine hypertension allows for targeted management that addresses the underlying hormonal excess.
Primary Aldosteronism Treatment
For patients with a unilateral aldosterone-producing adenoma, surgical removal of the affected adrenal gland (adrenalectomy) is the preferred first-line treatment. Adrenalectomy offers the potential for complete cure and significant improvement in blood pressure control. For PA caused by bilateral adrenal hyperplasia, or for patients unable to undergo surgery, medical therapy uses mineralocorticoid receptor antagonists (MRAs). Medications like spironolactone or eplerenone block the aldosterone receptor in the kidneys, promoting sodium and water excretion. This pharmacological approach improves blood pressure and corrects potassium imbalance.
Other Conditions Treatment
Surgical resection is the treatment of choice for pheochromocytoma or paraganglioma, often curing the hypertension and preventing hypertensive crises. Patients require careful pharmacological preparation, typically involving alpha-blockers, before surgery to control blood pressure. For Cushing’s Syndrome, treatment focuses on normalizing cortisol levels. This may involve surgery to remove a tumor in the pituitary or adrenal gland, or the use of specific medications to inhibit cortisol synthesis.