When tumors travel in families
Multiple endocrine neoplasia (MEN) is a group of inherited syndromes in which a single germline mutation predisposes several endocrine glands to tumors over a lifetime. Because every cell carries the mutation, the disease shows up as patterns of glands, not one isolated tumor. Recognizing the pattern in one patient can save the lives of relatives who haven't yet developed disease.
The classic clusters are worth memorizing as recipes. MEN1 favors the parathyroids, the pancreatic islets, and the pituitary — so a young person with hyperparathyroidism plus an islet tumor plus a pituitary adenoma should make you think MEN1. MEN2 pairs medullary thyroid cancer with pheochromocytoma and parathyroid disease. Tumors here often start as diffuse endocrine hyperplasia — the whole gland is primed to grow — before any single mass appears.
Hormone from the wrong place
A different surprise is ectopic hormone secretion: a tumor that is not endocrine at all starts manufacturing a hormone. A lung cancer, for instance, can switch on the gene for ACTH and pour it into the blood. The adrenal glands obediently make cortisol, and the patient develops Cushing's syndrome — from a hormone source that has nothing to do with the pituitary. This is a paraneoplastic syndrome: a remote, hormonal effect of cancer.
Ectopic secretion has a tell. Because the rogue source ignores the normal axis, the feedback looks impossible. In ectopic-ACTH Cushing's, both cortisol and ACTH are sky-high — yet they refuse to suppress even with high-dose dexamethasone, because the lung tumor neither knows nor cares about the feedback rules. Whenever the numbers break the usual logic, suspect a source outside the gland.
- Find an excess that's impossibly high or stubbornly unsuppressible.
- Ask whether the source could be outside the normal gland — an ectopic, paraneoplastic tumor.
- If a young patient has multiple endocrine tumors, screen for MEN and inform the family.