Paraneoplastic Syndromes Caused by Ectopic Hormone Production
| Paraneoplastic Syndrome | Ectopic Hormone | Typical Tumor Typesa |
|---|---|---|
| Common | ||
| Hypercalcemia of malignancy | PTHrP | Squamous cell (head and neck, lung, skin), breast, genitourinary, gastrointestinal |
| 1,25 dihydroxyvitamin D | Lymphomas | |
| PTH (rare) | Lung, ovary | |
| PGE2 (rare) | Renal, lung | |
| SIADH | Vasopressin | Lung (squamous, small cell), gastrointestinal, genitourinary, ovary |
| Cushing's syndrome | ACTH | Lung (small cell, bronchial carcinoid, adenocarcinoma, squamous), thymus, pancreatic islet, medullary thyroid carcinoma |
| CRH (rare) | Pancreatic islet, carcinoid, lung, prostate | |
| Ectopic expression of GIP, LH/hCG, other G protein-coupled receptors (rare) | Macronodular adrenal hyperplasia | |
| Less common | ||
| Nonislet cell hypoglycemia | IGF-II | Mesenchymal tumors, sarcomas, adrenal, hepatic, gastrointestinal, kidney, prostate |
| Insulin (rare) | Cervix (small cell carcinoma) | |
| Male feminization | hCGb | Testis (embryonal, seminomas), germinomas, choriocarcinoma, lung, hepatic, pancreatic islet |
| Diarrhea or intestinal hypermotility | Calcitoninc | Lung, colon, breast, medullary thyroid carcinoma |
| VIP | Pancreas, pheochromocytoma, esophagus | |
| Rare | ||
| Oncogenic osteomalacia | Phosphatonin (FGF23) | Hemangiopericytomas, osteoblastomas, fibromas, sarcomas, giant cell tumors, prostate, lung |
| Acromegaly | GHRH | Pancreatic islet, bronchial and other carcinoids |
| GH | Lung, pancreatic islet | |
| Hyperthyroidism | TSH | Hydatidiform mole, embryonal tumors, struma ovarii |
| Hypertension | Renin | Juxtaglomerular tumors, kidney, lung, pancreas, ovary |
aOnly the most common tumor types are listed. For most ectopic hormone syndromes, an extensive list of tumors has been reported to produce one or more hormones.
bhCG is produced eutopically by trophoblastic tumors. Certain tumors produce disproportionate amounts of the hCG α or hCG β subunit. High levels of hCG rarely cause hyperthyroidism because of weak binding to the TSH receptor.
cCalcitonin is produced eutopically by medullary thyroid carcinoma and is used as a tumor marker.
Abbreviations: ACTH, adrenocorticotropic hormone; CRH, corticotropin-releasing hormone; FGF23, fibroblast growth factor 23; GH, growth hormone; GHRH, Growth hormone-releasing hormone; GIP, gastric inhibitory peptide; hCG, human chorionic gonadotropin; IGF, insulin-like growth factor; LH, luteinizing hormone; PGE2, prostaglandin E2; PTH, parathyroid hormone; PTHrP, parathyroid hormone-related protein; SIADH, syndrome of inappropriate antidiuretic hormone secretion; TSH, thyroid-stimulating hormone; VIP, vasoactive intestinal peptide.