Endocrine Abstracts

Introduction: Resistant hypertension(RHTN) is an increasingly prevalent clinical condition associated with target organ damage and a poor prognosis, encompassing endocrine hypertension(EH). In this report, we describe a rare case of EH complicated by the application of a cytochrome P450(CYP450) enzyme inducer, which manifested as RHTN.

Case summary: A 56-year-old man with an 18-year history of hypertension and one month documented spontaneous hypokalemia(K+, 3.01 mmol/l),was admitted to the Endocrinology Department. The patient had undergone a 2-week washout period with double doses of doxazosin and diltiazem before admission. Physical examination revealed a BP of 170/85 mmHg and overweight. Screening investigations for EH showed abnormal response to the overnight 1 mg dexamethasone suppression test (DST) and low-dose 2-day dexamethasone test (cortisol of 113 nmol/l and 193 nmol/l, respectively), indicating Cushing’s syndrome(CS) probably; secondly, a positive aldosterone–renin ratio(ARR) and a positive captopril challenge test(CCT) demonstrating primary aldosteronism(PA). Adrenal CT revealed slight nodular thickening of the bilateral adrenal glands. Pituitary MRI and renal artery ultrasound showed normal findings, leading to suspicion of EH as the underlying cause. Although spironolactone and amlodipine at near-maximum doses were added for the treatment of PA, there was no response. The BP sometimes still could achieve 200/100 mmHg. Subsequent treatment involved bisoprolol, terazosin, clonidine and olmesartan. However, systolic blood pressure had no significant change. MDT discussion and a review of medical history revealed that the patient had been taking rifampicin for brucellosis before being hospitalized. Previous research showed that almost all antihypertensive medications are substrates of CYP450 enzymes, which can be induced by rifampicin. This induction may lead to decreased blood concentration, diminished medicinal efficacy, and elevated BP. And the CYP-induction effect of rifampicin accelerates the metabolism of dexamethasone, rendering a false-positive DST. Consequently, we discontinued rifampicin, causing an improvement in BP control. During the 1-month follow-up, the patient’s ARR and CCT were positive, and the overnight 1 mg DST (cortisol of 17.6 nmol/l) was negative. Further AVS supported idiopathic hyperaldosteronism (IHA). Thus, the etiology of the patient’s RHTN was confirmed as IHA complicated by drug–drug interactions due to the CYP450 enzyme inducer, with CS excluded. Three months later, his BP was well controlled with serum potassium levels normal. The defined daily doses of antihypertensive medications had decreased by more than 50% compared with the previous treatment.

Conclusion: Drug–drug interactions caused by CYP450 inducers is prone to be neglected, especially when combined with another cause of EH, which complicates the etiology of RNTH further.