Multiple Endocrine Neoplasia (MEN)

Rule out pheochromocytoma before any anesthetic - Plasma fractionated metanephrines drawn supine after at least 30 minutes recumbent, or 24-hour urine fractionated metanephrines with a urine creatinine to confirm collection. Pheochromocytoma occurs in 40 to 50% of MEN2A and MEN2B, is usually bilateral and multicentric, and presents at a mean age of 25 to 32 — as young as 8 to 12. MEN2 patients run high metanephrines and are more symptomatic than VHL patients.

Alpha blockade before beta blockade, never the reverse - Phenoxybenzamine 10 mg PO twice daily started 7 to 14 days preop, titrated up to a maximum of 1 mg/kg/day; doxazosin is an alternative with a better side-effect profile. Add a beta blocker only 3 to 4 days after alpha blockade is established — starting one first risks a hypertensive crisis from unopposed alpha stimulation. Amlodipine or nifedipine are add-on agents.

Fill the tank - Catecholamine excess contracts intravascular volume. A high-sodium diet begun a few days after alpha blockade starts reduces the hypotension that follows tumor devascularization.

Drugs and stimuli that set off a crisis - Dopamine receptor antagonists, non-selective beta blockers, tricyclics, corticosteroids, sympathomimetics and neuromuscular agents have all precipitated severe hypertension, as have surgery and induction of anesthesia itself. Abdominal palpation, coughing, pain and cold can trigger a crisis in a tumor that was otherwise silent.

Check calcium and intact PTH - Multigland nodular hyperplasia is typical of MEN1 hyperparathyroidism and the PTH may be only minimally elevated or within the upper limits of normal, so a normal PTH does not exclude it. MEN1-related disease carries more severe bone disease than sporadic hyperparathyroidism despite the milder numbers.

Pad and position for fragile bone - Osteoporosis is part of MEN1 hyperparathyroidism and may still be under treatment at the time of surgery. Take the extra minute on transfers and limb positioning.

Expect a distorted neck in MEN2 - Medullary thyroid carcinoma has essentially 100% penetrance in MEN2A and MEN2B and is usually the first manifestation, presenting as a solitary thyroid nodule with cervical lymphadenopathy. Review prior anesthetic records and any neck ultrasound or CT before you commit to a plan.

MEN2B habitus - Marfanoid habitus, kyphoscoliosis or lordosis, joint hyperlaxity, and mucosal neuromas on the lips and tongue. Unlike Marfan syndrome these patients lack lens dislocation and aortic abnormalities. The neuromas can be visible at laryngoscopy, and the joint laxity and spinal curvature change positioning and neuraxial technique.

Insulinoma means intraoperative hypoglycemia - A functioning pancreatic neuroendocrine tumor can secrete enough insulin to cause hypoglycemia, and general anesthesia hides every symptom of it. Run point-of-care glucose on a schedule, not on suspicion.

Gastrinoma means a full stomach - Gastrin-secreting tumors drive gastric acid hypersecretion and peptic ulcer disease (Zollinger-Ellison syndrome). Plan aspiration prophylaxis and RSI.

Pituitary panel before an elective case - Prolactin, GH and IGF-1, ACTH, TSH, T4 and cortisol, with contrast MRI of the pituitary. Prolactinomas are the most common secretor, GH-secreting adenomas next, and non-secreting tumors compress the gland and cause hypopituitarism — the cortisol result is the one that changes your day.

Bilateral adrenalectomy leaves a steroid-dependent patient - Bilateral total adrenalectomy commits the patient to lifelong glucocorticoid replacement, so stress-dose coverage is mandatory for every subsequent anesthetic. Cortical-sparing adrenalectomy preserves adrenocortical function and reduces that dependence.

Hirschsprung disease travels with MEN2A - Aganglionic segment, chronic obstruction and megacolon. Factor that into fasting status and aspiration risk in a patient presenting for anything abdominal.

Multiple endocrine neoplasia is a group of autosomal dominant syndromes that produce tumors across several endocrine glands. MEN1 (Wermer syndrome) comes from inactivating mutations of the MEN1 (menin) gene on chromosome 11 and causes primary hyperparathyroidism in about 90%, gastro-entero-pancreatic neuroendocrine tumors in about 60%, and anterior pituitary adenomas in about 40%. MEN2 (Sipple syndrome) comes from gain-of-function RET proto-oncogene mutations: MEN2A is medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism, while MEN2B is medullary thyroid carcinoma, pheochromocytoma, marfanoid habitus, and mucosal neuromas of the lips and tongue. MEN4 arises from CDKN1B mutation and looks like MEN1.

Perioperatively the syndrome matters through its secretory products — catecholamines from a pheochromocytoma, insulin or gastrin from a pancreatic tumor, and calcium from multigland parathyroid hyperplasia.