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Hypertension affects 30% of adults in Australia with most cases being primary (essential or idiopathic). A subgroup of approximately 15% have secondary hypertension for which there is an identifiable cause.
Head of Biochemistry.
Aaron gained his MBBS at the University of Sydney and proceeded to complete fellowships in both Chemical Pathology and Endocrinology. He has been widely published in both disciplines with particular interests in endocrine hypertension, adrenal, pituitary, and calcium metabolism disorders. Aaron is Clinipath Pathology’s Head of Biochemistry.
Causes of secondary hypertension include renal causes (e.g. renal parenchymal disease) and endocrine causes with hypertension, often initial clinical presentation for other endocrine disorders. Diagnosis of endocrine hypertension provides clinicians with an opportunity to render a surgical cure or an optimal clinical response with targeted pharmacologic therapy.
Endocrine hypertension is commonly caused by adrenal gland disorders, including primary hyperaldosteronism, Cushing syndrome and pheochromocytoma. While nonadrenal endocrine disorders are less common, they pose significant health issues, including growth hormone excess, thyroid disorders, obesity, insulin resistance and metabolic syndrome.
Primary aldosteronism
This occurs in 5-10% of all hypertensive patients and is a common cause of secondary hypertension. Historically, primary aldosteronism was considered rare and not generally included in a differential diagnosis for patients presenting with resistant hypertension. However, recent research indicates that it is more prevalent than previously thought.
Patients develop this condition when there is increased aldosterone production independent of the renin-angiotensin system. As a result, sodium retention can lead to hypertension, hypokalemia, and high plasma aldosterone/renin ratio (ARR). Clinical findings and symptoms can be vague, increasing the difficulty of identifying primary aldosteronism. Patients may be asymptomatic with the only abnormal lab finding being hypokalemia which affects a third of patients. If hypokalemia is present, symptoms can include nocturia, polyuria, muscle weakness, cramps, paresthesias and palpitations.
The most common screening test for primary aldosterone is ARR. It should be noted that both false-negative and false-positive results are possible. False-negative results can be caused by dietary salt restriction, hypokalemia and medication including diuretics, ACE inhibitors, calcium channel blockers, and angiotensin receptor antagonists. ß-blockers, α-methyldopa or NSAIDs can cause false-positive results.
Patients should be encouraged to follow a liberal sodium diet before ARR testing and efforts to correct hypokalemia should be implemented. Before ARR is measured, diuretics (specifically spironolactone) should be stopped for at least six weeks; other possible interfering medications stopped for four weeks.
The ARR should be obtained on several occasions to confirm elevated readings. As the ARR is purely a screening method, further testing is required. Of the methods available, the seated saline suppression test (performed at Clinipath) is commonly used. It aims to suppress plasma aldosterone to < 170 nmol/L following an infusion of isotonic saline over four hours.
Cushing syndrome
Cushing syndrome, caused by chronic glucocorticoid excess, affects around one case per million a year. Signs and symptoms include centripetal obesity, moon facies, facial plethora, easy bruising, posterior cervical fat pad, hirsutism and peripheral striae. Up to 80% have hypertension.
If Cushing syndrome is suspected, these screening tests apply: 24-hour urine-free cortisol, 1mg overnight dexamethasone suppression test or late-night salivary cortisol. Society guidelines recommend two of these tests be performed. If a patient has clinical features suggestive of Cushing syndrome but test results are normal, referral to an endocrinologist should be considered. Abnormal screening tests require follow-up.
Phaeochromocytoma
These are catecholamine-producing tumours located in the adrenal medulla and sympathetic ganglia and accounts for only 0.2-0.6% of all causes of hypertension. Hypertension (persistent or paroxysmal) is the most common finding for patients with pheochromocytoma, with 80-90% presenting with this sign. The classic triad of symptoms are headache, sweating, and palpitations.
If left untreated, there is risk for hypertensive retinopathy, nephropathy, myocardial infarction, stroke from cerebral infarction, intracranial haemorrhage or embolism. Due to the high rate of morbidity and mortality with untreated phaeochromocytoma, testing should be initiated upon suspicion of this diagnosis or if the patient has relevant family history.
Pheochromocytoma is diagnosed by plasma metanephrines or 24-hour urine metanephrines. Some medications can interfere with the accuracy of lab results and therefore may need to be temporarily stopped. It is important to check the specific lab guidelines and review the patient’s medication lists before testing.
Always screen
Although the causes of endocrine-related hypertension are rare, screening patients who present with signs and symptoms is important. The endocrine disorders discussed here can be cured or controlled with appropriate diagnosis and treatment.
Further reading
ISH Global Hypertension Practice Guidelines: Information and resources related to the 2020 ISH Global Hypertension Practice Guidelines. https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.120.15026
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