Endocrinology & Metabolism Command Center

Order ≥ 2 initial screening tests: 24-hour urinary free cortisol (↑), late-night salivary cortisol (↑), or low-dose (1 mg) overnight dexamethasone suppression test (cortisol fails to suppress < 1.8 μg/dL).

• ACTH < 5 pg/mL (ACTH-Independent): Adrenal adenoma, adrenal carcinoma, or exogenous glucocorticoids. Order Abdominal CT/MRI.
• ACTH > 20 pg/mL (ACTH-Dependent): Pituitary adenoma vs. Ectopic ACTH production. Proceed to Step 3.

• Cortisol Suppresses > 50%: Cushing Disease (Pituitary ACTH Adenoma). Order pituitary MRI.
• Cortisol Fails to Suppress: Ectopic ACTH secretion (most commonly Small Cell Lung Cancer or bronchial carcinoid). Order chest/body CT.

• • Pathophysiology: Absolute insulin deficiency → uncontrolled lipolysis → free fatty acids converted to β-hydroxybutyrate and acetoacetate in liver.
• • Blood Glucose: Typically 250–500 mg/dL (lower than HHS).
• • Arterial pH & HCO3-: pH < 7.30, HCO3- < 18 mEq/L (High anion gap metabolic acidosis).
• • Clinical Hallmarks: Kussmaul respirations (deep rapid breathing to blow off CO2), fruity breath (acetone), nausea, vomiting, abdominal pain (mimics acute peritonitis).

• • Pathophysiology: Relative insulin deficiency (enough portal insulin to suppress hepatic lipolysis/ketogenesis, but insufficient to facilitate peripheral glucose uptake).
• • Blood Glucose: > 600–1000+ mg/dL with profound osmotic diuresis (8–10 L fluid deficit).
• • Effective Serum Osmolality: > 320 mOsm/kg with normal pH (> 7.30) and normal bicarbonate (> 18).
• • Clinical Hallmarks: Severe dehydration, focal neurological deficits, lethargy, stupor, coma; higher mortality than DKA!

Initial: 1 to 1.5 L/hr of 0.9% Normal Saline during first 1–2 hours. Switch to 0.45% Saline once corrected sodium is normal or high.

Crucial Pivot: When blood glucose reaches < 200 mg/dL (DKA) or < 300 mg/dL (HHS), add 5% Dextrose (D5W) to IV fluids to prevent hypoglycemia while continuing insulin infusion to close the anion gap!

Check K+ BEFORE Starting Insulin!

• • If K+ < 3.3 mEq/L: HOLD INSULIN and aggressively replete K+ (insulin shifts K+ into cells and can trigger lethal cardiac arrest / arrhythmias!).
• • If K+ 3.3–5.2 mEq/L: Add 20–30 mEq K+ to each liter of IV fluids while running insulin.
• • If K+ > 5.2 mEq/L: Start insulin, check K+ every 2 hours.

Continuous IV regular insulin infusion at 0.1 units/kg/hr. Target glucose decrease of 50–75 mg/dL/hr.

Resolution of DKA: Defined by closure of the serum anion gap (≤ 12) and serum HCO3- ≥ 18 mEq/L (NOT by glucose normalization!). Overlap subcutaneous basal insulin by 1–2 hours before stopping the IV drip.

Genetics: Autosomal dominant mutation in MEN1 tumor suppressor gene on chromosome 11 (encodes menin).

• • 1. Parathyroid: Hyperplasia or adenomas (95%, hypercalcemia).
• • 2. Pituitary Adenomas: Prolactinoma (galactorrhea, amenorrhea) or GH adenoma.
• • 3. Pancreatic Endocrine Tumors: Gastrinoma (Zollinger-Ellison recurrent refractory duodenal/jejunal ulcers), Insulinoma (hypoglycemia), VIPoma, Glucagonoma (necrolytic migratory erythema).

Genetics: Autosomal dominant gain-of-function mutation in RET proto-oncogene (receptor tyrosine kinase) on chromosome 10.

• • 1. Medullary Thyroid Carcinoma (100%): Calcitonin production, amyloid stroma.
• • 2. Pheochromocytoma (50%): Often bilateral paroxysmal hypertension, sweating, palpitations.
• • 3. Parathyroid Hyperplasia (20–30%): Hypercalcemia.

Board Rule: Resect Pheochromocytoma FIRST before thyroid surgery to prevent fatal intraoperative hypertensive crisis!

Genetics: Autosomal dominant RET codon M918T mutation.

• • 1. Medullary Thyroid Carcinoma: Highly aggressive; develops in infancy.
• • 2. Pheochromocytoma: Bilateral adrenal medullary tumors.
• • 3. Mucosal Neuromas: Benign neural tumors on lips, tongue, and eyelids; intestinal ganglioneuromatosis (chronic constipation/megacolon).
• • 4. Marfanoid Habitus: Long limbs, pectus excavatum, arachnodactyly (with NO lens dislocation or aortic dissection!).

Zero parathyroid disease in MEN 2B!