This handout is for cushing syndrome htn crisis (cortisol-excess–driven severe htn with hypokalemic alkalosis). Your care team identified this based on: cushingoid phenotype (moon facies, dorsocervical fat pad, central obesity, purple striae, proximal myopathy, easy bruising) + severe htn (newell-price lancet 2006 pmid 16713505).
Other reasons your team may use this plan: severe hypokalemia (k <3.0) + metabolic alkalosis + htn — high-cortisol or ectopic acth suspicion; chronic supraphysiologic glucocorticoid exposure (prednisone ≥7.5 mg ≥3 wk, dexamethasone, megestrol, intra-articular/inhaled high-dose) — exogenous cushing; pituitary microadenoma or adrenal incidentaloma + htn + hypokalemia → biochemical cushing screen.
Take these medications exactly as prescribed. Do not stop or change a dose without talking to your provider.
| Medication | Starting dose | How | When | What it does |
|---|---|---|---|---|
| nicardipine | 5 mg/h IV titrate by 2.5 mg/h q5-15 min, max 15 mg/h | IV | continuous | ACC/AHA 2025 — predictable titration; safe in Cushing with renal involvement; CCB preferred acute |
| spironolactone | 25-50 mg PO daily, titrate to 100-400 mg/d | PO | daily | Endocrine Society 2008/2015 (PMID 18334580/26222757) — blocks MR activation by cortisol; addresses K wasting + HTN simultaneously; gynecomastia limit (use eplerenone if concern) |
| eplerenone | 25-50 mg PO daily, titrate to 100-200 mg/d | PO | daily or BID | Selective MR antagonist — no androgen receptor blockade → no gynecomastia; less potent than spironolactone, requires higher doses; PATHWAY-2 PMID 26414968 demonstrated MRA efficacy in resistant HTN |
| potassium chloride | KCl IV 10-20 mEq/h via central line if K <3 (peripheral max 10 mEq/h); KCl PO 40-80 mEq divided | IV + PO | continuous IV or QID PO | Severe hypokalemia from cortisol-driven K wasting; replace to ≥3.5 with continuous ECG monitoring |
| magnesium sulfate | 2-4 g IV load + 1-2 g/h infusion | IV | continuous | Mg almost always coexisting low; refractory hypokalemia without Mg correction; Torsades prophylaxis |
| ketoconazole | 200 mg PO TID, titrate to 400-1200 mg/d divided | PO | TID-QID | Endocrine Society 2015 (PMID 26222757) — CYP17 + CYP11B inhibitor; rapid cortisol-lowering; HEPATOTOXICITY (monitor LFTs weekly initial then monthly); QT prolongation; CYP3A4 interactions |
| metyrapone | 250 mg PO QID, titrate to 500-1000 mg q6h | PO | QID | Endocrine Society 2015 — 11β-hydroxylase inhibitor; rapid effect; can cause hirsutism + hypoadrenalism; alternative when ketoconazole hepatic concern |
| osilodrostat | 2 mg PO BID, titrate q2 wk to max 30 mg BID | PO | BID | LINC-3 trial (Fleseriu Lancet Diabetes Endocrinol 2019 PMID 31523029) — newer 11β-hydroxylase inhibitor + aldosterone synthase inhibitor; FDA approved Cushing disease 2020; hyperandrogenism + adrenal insufficiency monitor |
| mifepristone | 300 mg PO daily, titrate to 600-1200 mg/d | PO | daily | FDA approved (Korlym) for Cushing-induced hyperglycemia; SEEKING-2 trial; cortisol levels rise (GR antagonism not synthesis inhibition) — cannot use cortisol to titrate; symptom-based + glucose-based titration; HYPOKALEMIA worsens (need MRA + K) |
| mitotane | 0.5 g PO BID titrate to 4-8 g/d (target plasma 14-20 mg/L) | PO | BID-TID | Endocrine Society 2015 — adrenolytic agent specific for adrenocortical carcinoma; slow onset (weeks); GI + neuro toxicity; mandatory cortisol replacement during therapy; long terminal half-life |
| AVOID isolated ACEi/ARB acutely | AVOID | N/A | N/A | Cushing patients have aldosterone-like activity but renin-suppressed RAAS → ACEi alone less effective; coexisting hypokalemia + risk of hyperK if MRA also added → start MRA + K replacement first, then ACEi/ARB once K stable |
| STOP exogenous glucocorticoid (taper if iatrogenic) | Taper (do not stop abruptly — adrenal suppression risk) | PO/inhaled/topical | taper | Iatrogenic Cushing from chronic supraphysiologic GC — taper with stress-dose coverage during illness; CRH-stim or AM cortisol to confirm HPA recovery before full stop |
Plan: Cushing syndrome HTN crisis — MR-blockade FIRST (spironolactone or eplerenone) + K replacement + nicardipine; cortisol-lowering bridge (ketoconazole, metyrapone, osilodrostat, mifepristone, mitotane) for surgical bridge
Contact your care team if any of the following happen:
Call 911 or go to the nearest emergency room right away if you have:
Postop morning cortisol day 1-3 (suppression to <1.8 mcg/dL = remission); if <5 — physiologic hydrocortisone replacement 15-25 mg/d divided BID (or 10/5 split); follow ACTH stim test annually until HPA recovery (usually 6-18 mo); annual UFC + ACTH for recurrence (10-15% recurrence at 10 years for Cushing disease); cardiovascular risk reassessment (cardiometabolic legacy effect persists years after cure); bone density DEXA + osteoporosis treatment; psychiatric follow-up (mood symptoms slow recovery); diabetes management (often resolves but chronic GI insulin resistance may persist)
Guideline: Endocrine Society 2008 Cushing Syndrome Diagnosis CPG (Nieman JCEM 2008 PMID 18334580) + 2015 Treatment CPG (Nieman JCEM 2015 PMID 26222757) + 2025 ACC/AHA HTN (Whelton)