In a recent study published in Hypertension Research, scientists examine the endocrine causes of hypertension (HTN) and investigate the efficacy of treatments to alleviate HTN.

Study: Endocrine causes of hypertension: Literature review and practical approach. Image Credit: Hodoimg / Shutterstock.com

What’s HTN?

About 30% of the worldwide population is affected by HTN. HTN is a modifiable cardiovascular (CV) risk factor that’s related to a major variety of deaths worldwide.

There are two sorts of HTN often called primary and secondary HTN. As in comparison with primary HTN, secondary HTN causes greater morbidity and mortality. 

Essentially the most common endocrine causes of HTN include primary aldosteronism (PA), paragangliomas and pheochromocytomas (PGL), Cushing’s syndrome (CS), and acromegaly. Other causes include congenital adrenal hyperplasia, mineralocorticoid excess, cortisol resistance, Liddle syndrome, Gordon syndrome, and thyroid and parathyroid dysfunction. 

What’s PA?

PA is essentially the most common endocrine reason for hypertension, which is related to excessive aldosterone secretion by the adrenal gland and low renin secretion. It’s difficult to estimate the true prevalence of PA as a consequence of the complexity of its diagnosis.

Typically, the plasma aldosterone-to-renin ratio (ARR) is measured to diagnose PA. The diagnosis of PA can be confirmed using other diagnostic tools like chemiluminescent enzyme immunoassays (CLEIAs) and radio immune assay (RIA).

Continuous aldosterone secretion is related to organ damage as a consequence of chronic activation of the mineralocorticoid (MR) receptor in lots of organs, including fibroblasts and cardiomyocytes. An elevated level of aldosterone causes diastolic dysfunction, endothelial dysfunction, left ventricular hypertrophy, and arterial stiffness.

Increased aldosterone secretion also results in obstructive sleep apnea and increases the chance of osteoporosis. For this reason individuals with PA are at a better risk of cardiovascular events (CVDs), including heart failure, myocardial infarction, coronary artery disease, and atrial fibrillation.

PA is treated by specializing in normalizing potassium and optimizing HTN and aldosterone secretion. Unilateral adrenalectomy is a surgical operation proposed to treat PA.

Young patients who’re willing to stop medication are advisable surgical procedure. Essentially the most common pharmaceutical treatment for PA includes mineralocorticoid receptor antagonists resembling spironolactone and eplerenone.

Pheochromocytomas and paragangliomas

PGL are tumors that develop on the thoracic-abdominal-pelvic sympathetic ganglia, that are present along the spine, in addition to within the parasympathetic ganglia positioned at the bottom of the skull. The incidence rate of PGL is about 0.6 for each 100,000 individuals annually. PGL tumors synthesize excessive catecholamines (CTN), which induce HTN.

A few of the common symptoms linked to HTN related to PGL are palpitations, sweating, and headache. PGL could be diagnosed by determining metanephrines (MN) levels, that are degraded products of CTN. Bio-imaging tools also play a vital role in confirming the diagnosis of PGL.

Excessive secretion of CTN increases the chance of CVDs, including Takotsubo adrenergic heart disease, ventricular or supraventricular rhythm disorders, hypertrophic obstructive or ischaemic cardiomyopathy, myocarditis, and hemorrhagic stroke. Excessive CTN secretion also causes left ventricular systolic and diastolic dysfunction.

Typically, PGL treatment is related to surgical procedures. Two weeks before the surgery, patients are treated with alpha-blockers. For these patients, beta-blockers should not used as the primary line of treatment without prior use of alpha-adrenergic receptors.

Patients with high CTN secretion are treated with metyrosine, as this may inhibit tyrosine hydroxylase. Hydroxylase converts tyrosine into dihydroxyphenylalanine, which is expounded to CTN synthesis.

What’s CS?

CS, which arises as a consequence of persistent exposure to glucocorticoids, is a rare disease with an incidence rate of 1 in five million individuals annually. Essentially the most common symptoms of CS include weight gain, purple stretch marks, muscle weakness, pimples, and hirsutism. A high cortisol level causes cardiovascular complications resembling HTN, hypercholesterolemia, and diabetes.

CS is diagnosed based on the presence of two or more biomarkers that could be identified through pathological tests, resembling salivary nocturnal cortisol, 24-hour urinary-free cortisol, and dexamethasone suppression tests. 

CS is treated through surgical procedures based on the detected lesions. Patients with severe CS are treated with steroidogenic inhibitors, resembling metyrapone, ketoconazole, osilodrostat, and mitotane. Pituitary radiotherapy and bilateral adrenalectomy are performed when other treatments should not effective.

Acromegaly

Acromegaly arises as a consequence of chronic exposure to growth hormone (GH), resulting in excessive insulin-like growth factor 1 (IGF1) synthesis. This condition has a comparatively higher incidence rate of three.8 million person-years. Clinical symptoms of acromegaly include thickened lips, widened nose, an oblong face, distinguished cheekbones, soft tissue overgrowth, or skeletal deformities.

Prolonged exposure to GH results in increased water and sodium retention, insulin resistance, reduced glucose uptake, and increased systemic vascular resistance. These conditions increase the chance of HTN and diabetes in patients with acromegaly. Acromegalic patients are also at a better risk of cancer, particularly those affecting the thyroid and colon.

Acromegaly is diagnosed using the IGF1 assay, which determines IGF1 levels in serum. After confirming the presence of high IGF1 levels, a GH suppression test should be performed to verify the diagnosis. Bioimaging can also be conducted to locate adenoma.

Acromegaly is often treated through surgical procedures. Patients who refuse this line of treatment are treated with somatostatin receptor ligands, growth hormone receptor antagonists, dopaminergic agonists, or radiotherapy.