Identifying Endocrine-Related Hypertension

Secondary HTN can result from changes in the endocrine system, including those brought on by cortisol mimicking medications. If correctly identified, treatment for endocrine-related HTN cures or reduces a patient’s high blood pressure.

Hypertension (HTN) may be the initial presentation for at least 15 different endocrine-related disorders,1 according to a scientific statement from the Endocrine Society. HTN is a prominent condition in nearly 30% of all adults in the United States.2 How, then, might clinicians determine if elevated blood pressure arises as an idiopathic or endocrine condition?

Aldo Murillo @ iStockAccording to George Bakris, MD, professor of medicine and director of the ASH Comprehensive Hypertension Center at the University of Chicago School of Medicine in Illinois, "Although secondary causes of hypertension comprise about 10-12% of all hypertension, it is important that clinicians are aware of endocrine causes. Keep in mind that there are 40 genes that determine all facets of hypertension. A full 21 of those are linked to the endocrine system.”

Identifying endocrine-driven HTN by resistant HTN

In a recent review article, Irina Benenson, DNP, FNP-C, assistant professor of Advanced Nursing at Rutgers School of Nursing in Newark, New Jersey and her team demonstrate that this is an effective approach to navigate the considerations essential to sort out which patients are presenting with endocrine-related HTN rather than other causes of high blood pressure.3

Some patients with hypertension, even after multiple pharmacotherapeutic attempts to control for high blood pressure, remain at or above their targeted goals.4 As a frame of reference, the prevalence of endocrine-related HTN in resistant or persistent patients is estimated to be as high as 20%.4

For these unresponsive patients, Benenson and her colleagues suggest that in patients with persistent elevated high blood pressure (BP > 150/100 mm Hg) and/or resistant HTN (BP > 140/90 mm Hg despite therapy with three medications from different drug classes, including diuretics), clinicians should look for possible endocrine dysfunctionality.

Once identified, the authors offer focus on the best course of management for patients who have one of three central endocrine disorders, for which hypertension is a dominant indicator: Primary aldosteronism, Cushing’s disease, and pheochromocytoma.

Poor sodium reabsorption is predominant in primary aldosteronism  

The single most common cause of secondary HTN is primary aldosterone (PA).  Aldosterone is released by the adrenal cortex to regulate sodium reabsorption in the renal ducts. When conditions arise that prohibit adequate aldosterone production, patients will experience altered blood plasma osmolality, leading to a rise in blood pressure. Common causes of this include adrenal hyperplasia and aldosterone-producing adenomas. 

Primary aldosteronism (PA) resulting from hyperplasia is best treated with mineralocorticoid receptor blockers, such as spironolactone, which prevent aldosterone from binding to its receptor. Aldosterone-releasing adenomas are also removed surgically, thus removing the source of the overproduction. Once PA is adequately treated, blood pressure lowers considerably, often to normal levels.  

If PA is suspected, the current review paper suggests a screening workup that includes measuring the aldosterone-renin ratio (ARR). An ARR of > 20 hg/dL per hg/mL/h is a strong indicator of PA. The authors point out to bear in mind that several HTN medications can mask an accurate ARR result. Diuretics, ACE inhibitors, and angiotensin blockers may all raise renin levels even as they lower blood pressure. Benenson and her team suggest a 2-4 week washout period for all HTN medications before measuring ARR. However, they acknowledge that this is not always possible. In such cases, they suggest serial ARR testing.

Cushing Syndrome (CS), an excess of cortisol

Cortisol over-exposure, which can bring about a condition called Cushing Syndrome, can be caused by frequent use of cortisol-like medications such as prednisone, or endogenously through over-activated cortisol-producing cells. A pituitary adenoma or hyperplasia can also produce surplus adrenocorticotropic hormone (ACTH). Excess ACTH stimulates cells in the adrenal glands to produce excess cortisol.

The authors state that HTN results when cortisol triggers the aldosterone receptors in the renal ducts. As in PA, sodium does not get re-absorbed, and blood pressure elevates. Surgical removal of the cells producing cortisol results in a cure rate of 60-90% when diagnosed early. CS patients with untreated HTN have a poor five year prognosis3, so it is essential to identify this patient.

High blood pressure is common in CS, even though the syndrome itself is not. In addition to the physical characteristics of CS – hirsutism, obesity, and facial rounding – two  tests can help determine if elevated blood pressure is caused by excess cortisol1,4. For the primary care provider, Benenson and colleagues suggest using a late-night salivary cortisol test or a 24-hour urine test. Normal cortisol levels follow a diurnal pattern, elevated in the morning and low at night. A patient with CS will have elevated cortisol even at night5.

Pheochromocytoma, an excess of catecholamines

The catecholamines, epinephrine and norepinephrine, act on the sympathetic nervous system, including the renin-angiotensin-aldosterone system6. Tumors secreting catecholamines, usually on the adrenal cortex, are typically the source of these excess hormones. Surgical removal of the tumor may not cure HTN, but it reduces high blood pressure to a manageable level.

Pheochromocytoma is recognizable by its paroxysmal nature. Elevated blood pressure can be transient, as are headaches, sweating, and heart palpitations. Dr. Bakris points out, “A key diagnostic feature of pheochromocytoma, when present, is awakening out of a sound sleep with sweats, a headache and blood pressure well above 180. This does not happen with anxiety disorders, the most common misdiagnosis.” A urine test for catecholamine metabolites can help identify it.

Most importantly, pheochromocytoma is genetic with an autosomal dominant inheritance. Dr. Bakris says, “Pheochromocytoma is distinctly uncommon and should always be accompanied by genetic testing for other endocrine problems like multiple endocrine neoplasias (MEN) syndromes.” Concordantly, the Benenson review suggests that patients with a family history of pheochromocytoma, even if asymptomatic, should be tested. Early diagnosis reduces the detrimental effects of long-term untreated HTN.

Thyroid dysfunction

Because thyroid disorders are common, Benenson et al. include a short comment on the relationship between high blood pressure and both hyperthyroidism and hypothyroidism. In hyperthyroidism, the excess hormone increases cardiac output, putting strain on the heart, and elevating the blood pressure. Thyroid deficiency in hypothyroidism can cause arterial stiffness, also triggering an elevation in blood pressure. Once treated and euthyroidal states are achieved, blood pressure usually returns to normal.  

Final advice to primary care providers

The authors conclude that endocrine-related HTN is uncommon. However, considering the harmful effects of long-term HTN4 and the relatively effective methods of treating it, endocrine-related HTN must be a pathology that clinicians keep in mind when seeing a hypertensive patient, especially if they have persistent or resistant HTN. Screening tests for any of these conditions are best interpreted within the broad spectrum of a patient’s medical history and current medications. If there is strong evidence of endocrine involvement, then the patient should be referred to an endocrinologist or nephrologist for more definitive diagnostic testing.

The authors report no competing financial conflicts with regard to their involvement in conducting or discussing this study.


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