Does Lisinopril Increase Cortisol?
No, lisinopril does not increase cortisol levels. There is no evidence in the medical literature that lisinopril, an ACE inhibitor, affects cortisol production or secretion.
Mechanism and Pharmacology
- Lisinopril inhibits angiotensin-converting enzyme (ACE), which blocks the conversion of angiotensin I to angiotensin II, thereby reducing peripheral vascular resistance and blood pressure 1
- The drug is not metabolized and is excreted unchanged in the urine, with no hepatic metabolism required for its pharmacologic effect 2, 3
- Lisinopril's mechanism of action involves the renin-angiotensin-aldosterone system (RAAS), reducing plasma angiotensin II and aldosterone while increasing plasma renin activity 1
- There is no interaction between ACE inhibitors and the hypothalamic-pituitary-adrenal (HPA) axis or cortisol synthesis pathways 4, 5
Clinical Evidence
- Multiple comprehensive reviews of lisinopril's pharmacology and clinical effects make no mention of cortisol elevation or HPA axis effects 4, 2, 3, 1, 5
- In diabetic patients treated with lisinopril, the drug does not adversely affect glycemic control or metabolic parameters, which would be expected if cortisol were elevated 4
- Large-scale trials including ALLHAT, GISSI-3, and EUCLID that evaluated lisinopril in thousands of patients did not report cortisol-related adverse effects 6, 4, 5
Important Distinction from Other Medications
- Etomidate, an anesthetic induction agent, is known to suppress the HPA axis and reduce cortisol response, but this is unrelated to ACE inhibitors 6
- The Surviving Sepsis Campaign guidelines specifically warn about etomidate's adrenal suppression effects when used before steroid therapy, but make no such warnings about ACE inhibitors 6
Clinical Implications
- If a patient on lisinopril presents with elevated cortisol, investigate other causes of hypercortisolism using standard diagnostic approaches including 24-hour urinary free cortisol, late-night salivary cortisol, and dexamethasone suppression testing 7, 8
- Do not attribute elevated cortisol to lisinopril therapy, as this would delay appropriate workup for Cushing's syndrome or other causes of hypercortisolism 6, 7
- Lisinopril can be safely continued during evaluation for hypercortisolism, as it does not interfere with cortisol measurement or HPA axis testing 8