Cushing’s syndrome

Learning objectives

Cushing’s syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids (i.e., cortisol)
Cushing’s disease is a specific type of Cushing’s syndrome caused by a pituitary tumor leading to excessive production of adrenocorticotropic hormone (ACTH) → excessive ACTH stimulates the adrenal cortex to produce high levels of cortisol

Exogenous

Patients taking prescribed glucocorticoids (e.g., prednisone) to treat other diseases (i.e., asthma and rheumatoid arthritis) or for immunosuppression after organ transplants = iatrogenic Cushing’s syndrome
Adrenal glands may gradually atrophy due to lack of stimulation by ACTH, which’s production is reduced by the glucocorticoid medication
Resolves when the patient stops the glucocorticoid medication

Endogenous

Derangement of the body’s system to secrete cortisol
Hormone-secreting tumors of the adrenal glands or pituitary
Pituitary Cushing’s: Benign pituitary adenoma secretes ACTH = Cushing’s disease
Adrenal Cushing’s: Excess cortisol production by adrenal glands tumors, hyperplastic adrenal glands, or adrenal glands with nodular adrenal hyperplasia
Tumors (e.g., small cell lung cancer) outside the pituitary-adrenal system can also produce ACTH = ectopic or paraneoplastic Cushing’s disease

Transsphenoidal microadenomectomy and radiotherapy for pituitary-dependent Cushing’s disease
Adrenal adenoma or carcinoma requires surgical removal of the affected gland
Hypercortisolism can be controlled with adrenal enzyme inhibitors, such as ketoconazole, metyrapone, mitotane, or aminoglutethimide, given alone or in combination → drugs to inhibit release and synthesis of glucocorticoids

Patients with Cushing’s syndrome are classified as ASA 2 or 3
Airway evaluation: Mallampati score, mouth opening, neck extension, tireomental and sternomental distances, and Wilson score
Careful cardiovascular evaluation: ECG, echo
Careful respiratory evaluation: X-ray, blood gases, PFT
Stabilize glycemia: Stop oral therapy and start insulin regimen

Regular insulin	Type 1 DM (male)	Type 1 DM (female)	Type 2 DM
Initial bolus infusion	0.05-0.1 U/kg 1 U/h	0.05-0.1 U/kg 0.5 U/h	0.05-0.1 U/kg 1 U/h

Correct acid-base and electrolytes imbalances: Spironolactone, potassium
Continue antihypertensive drugs until the morning of surgery except for the angiotensin-converting enzyme inhibitors (i.e., captopril, enalapril, lisinopril, enalaprilat, and ramipril) and angiotensin II receptor blocks (i.e., valsartan)
Discontinue clopidogrel 5-7 days before surgery, except in coronary-stent patients (risk of stent occlusion)
Continue glucocorticoid inhibitors (i.e., ketoconazole, metyrapone, mitotane, or aminoglutethimide)
Prevent perioperative venous thromboembolism and pulmonary embolism: LMWH (i.e., enoxaparin, dalteparin) or fondaparinux
Avoid deep preoperative sedation → Premedication drugs: Midazolam 1 mg i.v.

Positioning and taping: Careful and gentle positioning to avoid fractures
Standard monitoring: Non-invasive blood pressure, temperature, end-tidal carbon dioxide, pulse oximetry, and ECG
Invasive monitoring: Invasive blood pressure via arterial catheter cannulation and Swan-Ganz pulmonary artery catheter (if necessary)
Venous access: Large bore peripheral and central venous catheters
Maintain the glucose blood level within normal values (i.e., 120-180 mg/dL) → insulin regimen

Prevent gastric aspiration: Metoclopramide 10 mg, ranitidine 50 mg i.v., and sodium citrate 30 mL P.O.
Induction of anesthesia and endotracheal intubation: Rapid induction sequence
Blunt sympathetic response (i.e., hypertension and arrhythmias) during induction: Opioids, lidocaine, clonidine, and esmolol
Avoid ketamine because of its sympathetic effects
Extubate if the patient is alert, warm, hemodynamically stable, and fully reversed from muscle relaxants

Prevent respiratory complications (i.e., atelectasis, hypoxemia): Effective postoperative pain relief, early mobilization, and respiratory exercises
Postoperative acute pain treatment: Systemic analgesic drugs (i.e., patient-controlled analgesia pumps or epidural analgesia)
Routinely check cortisol, glucose, and electrolytes blood levels
Continue replacement of cortisol, guided by cortisol blood levels
Use insulin regimen to maintain the glucose blood level within recommended levels
Continue antihypertensive drugs based on the patient’s hemodynamic status

The anesthesiologist has to deal with difficult ventilation and intubation, hemodynamic disturbances, volume overload and hypokalemia, glucose intolerance, and diabetes, maintain the blood cortisol level, and prevent glucocorticoid deficiency in the perioperative period