Chapter 78: Paraneoplastic Endocrine Syndromes
Both benign and malignant tumors of nonendocrine tissue can secrete a variety of hormones, principally peptide hormones, and many tumors produce more than one hormone (Table 78-1). At the clinical level, ectopic hormone production is important for two reasons.
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 |
Consumptive hypothyroidism | Type 3 deiodinase | Hepatic hemangiomas |
First, endocrine syndromes that result may either be the presenting manifestations of the neoplasm or occur late in the course. The endocrine manifestations in some instances are of greater significance than the tumor itself, as in pts with benign or slowly growing malignancies that secrete corticotropin-releasing hormone and cause fulminant Cushing’s syndrome. The frequency with which ectopic hormone production is recognized varies with the criteria used for diagnosis. The most common syndromes of clinical import are those of adrenocorticotropic hormone (ACTH) hypersecretion, hypercalcemia, and hypoglycemia. Indeed, ectopic ACTH secretion is responsible for 15–20% of pts with Cushing’s syndrome, and ∼50% of pts with persistent hypercalcemia have a malignancy rather than hyperparathyroidism. Because of the rapidity of development of hormone secretion in some rapidly growing tumors, diagnosis may require a high index of suspicion, and hormone levels may be elevated out of proportion to the manifestations.
Second, ectopic hormones serve as valuable peripheral markers for neoplasia. Because of the broad spectrum of ectopic hormone secretion, screening measurements of plasma hormone levels for diagnostic purposes are not cost effective. However, in pts with malignancies that are known to secrete hormones, serial measurements of circulating hormone levels can serve as markers for completeness of tumor excision and for effectiveness of treatment. Likewise, tumor recurrence may be heralded by reappearance of elevated plasma hormone levels before mass effects of the tumor are evident. However, some tumors at recurrence do not secrete hormones, so hormone measurements cannot be relied on as the sole evidence of tumor activity.
There's more to see -- the rest of this topic is available only to subscribers.