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Adrenal hypertension is when blood pressure is too high resulting from an increase of hormones from the adrenal glands. It is part of secondary hypertension and contributes to 5% of hypertension cases (Figure 1). This can be down to 3 major areas that result from excessive production of mineralocorticoids, glucocorticoids, or catecholamines. I will look at the underlying causes of adrenal hypertension including primary aldosteronsism, Cushing's syndrome and pheochromocytoma.
Cases of adrenal hypertension
Primary aldosteronism (PA) is causes by the autonomous production of aldosterone by the adrenal cortex. This can be due to bilateral idiopathic adrenal hyperplasia or an aldosterone secreting adrenal adenomas called Conn's tumour. Normal regulation of aldosterone secretion is mediated by renin, potassium and sodium levels, intravascular volume status, and ACTH.
Autonomous hypersecretion of aldosterone leads to the increase in extracellular fluid volume expansion and also elevated tubular sodium content. These raised levels are a result of increased sodium and water reabsorption at the expense of potassium and hydrogen ion excretion into the urine. The rise in sodium and ECF volume increase the systemic blood pressure and renal perfusion pressure and sodium content. This suppresses further renin release and the production of angiotensin 2. By measuring the plasma aldosterone/renin activity ratio as a screening test. This ratio increases along with the severity of the disease
Excess levels of either exogenously administrated glucocorticoids or endogenous overproduction of cortisol causes Cushing syndrome. Endogenous glucocorticoid overproduction that is independent of ACTH is usually due to a primary adrenocortical neoplasm. Bilateral macro and micronodular hyperplasia are rare causes of Cushing syndrome.
There are three different types of Cushing's syndrome: a pituitary tumour making ACTH, ectopic ACTH and an adrenal tumour.
- Pituitary Cushing's disease results from a benign adenoma in the pituitary producing excessive amounts of ACTH. Excess ACTH stimulates both adrenals to produce excessive amounts of cortisol and results in bilateral adrenal hyperplasia. The increased cortisol production does not suppress ACTH release because the pituitary tumor is unresponsive to the normal feedback suppression of increased cortisol levels.
The diagnosis usually is made by demonstration of elevated levels of ACTH in the face of elevated cortisol levels in afternoon, representing loss of the normal circadian rhythm .
- Ectopic ACTH can come from a malignant tumour, often in the lung .
- Adrenal Cushing's syndrome typically is caused by a solitary adrenal adenoma (rarely by carcinoma) producing excessive amounts of cortisol autonomously. The increased levels of cortisol feed back to suppress release of ACTH and corticotropin-releasing factor. The finding of very low ACTH levels in the face of elevated cortisol values and a loss of the circadian pattern of cortisol verify the diagnosis. Surgical removal usually is very effective .
The increase in the amount of cortisol being produced causes an increase in the activation of the mineralcorticoid receptor and increases the concentration of angiotensin II. This causes vasoconstriction and therefore increased peripheral resistance. There is expansion of extracellular fluid due to sodium and water retention. Together these cause increased blood pressure .
The low dose dexamethasone suppression test is the best screening test for Cushing's syndrome and can help to distinguish between excess production of ACTH due to pituitary adenomas from those with ectopic ACTH-producing tumours .
Phaeochromocytoma is an adenoma of the adrenal medulla causing the excess production of catecholamines like adrenaline. About 10% grow in chromaffin cells outside the adrenal glands.
A minority of pheochromocytomas occur because someone has an inherited susceptibility to them. Inherited pheochromocytomas are linked with four separate syndromes: type 2A and B Multiple Endocrine Neoplasia, von Hippel-Lindau disease and Neurofibromatosis . Adrenaline produces hypertension as it is a vasoconstrictor and increases heart rate thereby increasing blood pressure by increasing the peripheral resistance and the cardiac output. Phaeochromocytoma is diagnosed by doing a 24-hour urinary metadrenaline normametadrenline test.
Due to the fact that tumours cause part of adrenal hypertension, surgical removal can bring blood pressure back to a normal level. The treatment for hyperaldosteronism depends on the cause. In patients with a single benign tumor (adenoma), surgical removal (adrenalectomy) is curative. For patients with hyperplasia of both glands, successful treatment is often achieved with spironolactone or eplerenone, drugs that block the effect of aldosterone.
Adrenal hypertension is caused by the excess release of aldosterone, cortisol and adrenaline. This causes an increase in blood pressure by increased reabsorption of sodium and water producing extracellular fluid expansion or vasoconstriction and increased heart rate. Adrenal hypertension plays a small but important role in overall worldwide hypertension. The good thing is that most cases can be treated with surgical removal of the tumour or with medication whereas primary hypertension is harder to control due to the many other factors involved.
- National Endocrine and Metabolic Diseases Information Service: Cushing's syndrome. 2008
- Adrenal Endocrinology Lecture Notes. Edinburgh University. 2008
- Weinberger MH. Adrenal Causes of Hypertension. Chapter 4. 2008.