Chapter 096. Paraneoplastic Syndromes: Endocrinologic/Hematologic (Part 2)

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Ectopic hormone production would only be an epiphenomenon associated with cancer if it did not result in clinical manifestations. Excessive and unregulated production of hormones such as ACTH, PTHrP, or vasopressin can lead to substantial morbidity and can complicate the cancer treatment plan. Moreover, the paraneoplastic endocrinopathies are sometimes the presenting feature of underlying malignancy and may prompt the search for an unrecognized tumor. A large number of paraneoplastic endocrine syndromes have been described, linking overproduction of particular hormones with specific types of tumors. However, certain recurring syndromes emerge from this group (Table 961). The most common paraneoplastic endocrine syndromes...

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Chapter 096. Paraneoplastic Syndromes: Endocrinologic/Hematologic (Part 2) Ectopic hormone production would only be an epiphenomenon associated with cancer if it did not result in clinical manifestations. Excessive and unregulated production of hormones such as ACTH, PTHrP, or vasopressin can lead to substantial morbidity and can complicate the cancer treatment plan. Moreover, the paraneoplastic endocrinopathies are sometimes the presenting feature of underlying malignancy and may prompt the search for an unrecognized tumor. A large number of paraneoplastic endocrine syndromes have been described, linking overproduction of particular hormones with specific types of tumors. However, certain recurring syndromes emerge from this group (Table 96- 1). The most common paraneoplastic endocrine syndromes include hypercalcemia from overproduction of PTHrP and other factors, hyponatremia from excess vasopressin, and Cushing's syndrome from ectopic ACTH.
Table 96-1 Paraneoplastic Syndromes Caused by Ectopic Hormone Production Paraneoplastic Ectopic Hormone Typical Tumor Syndrome Typesa Common Hypercalcemia Parathyroid Squamous cell (head of malignancy hormone-related protein and neck, lung, skin), breast, (PTHrP) genitourinary, gastrointestinal 1,25 Lymphomas dihydroxyvitamin D Parathyroid Lung, ovary hormone (PTH) (rare) Prostaglandin E2 Renal, lung
(PGE2) (rare) Syndrome of Vasopressin Lung (squamous, small inappropriate cell), gastrointestinal, antidiuretic hormone genitourinary, ovary secretion (SIADH) Cushing's Adrenocorticotropic Lung (small cell, syndrome hormone (ACTH) bronchial carcinoid, adenocarcinoma, squamous), thymus, pancreatic islet, medullary thyroid carcinoma Corticotropin- Pancreatic islet, releasing hormone (CRH) carcinoid, lung, prostate (rare) Ectopic expression Macronodular adrenal of gastric inhibitory hyperplasia peptide (GIP), luteinizing hormone (LH)/ human
chorionic gonadotropin (hCG), other G protein– coupled receptors (rare) Less Common Non-islet cell Insulin-like growth Mesenchymal tumors, hypoglycemia factor (IGF-II) sarcomas, adrenal, hepatic, gastrointestinal, kidney, prostate Insulin (rare) Cervix (small cell carcinoma) Male hCGb Testis (embryonal, feminization seminomas), germinomas, choriocarcinoma, lung, hepatic, pancreatic islet Diarrhea or Calcitoninc Lung, colon, breast, intestinal hypermotility medullary thyroid carcinoma
Vasoactive Pancreas, intestinal peptide (VIP) pheochromocytoma, esophagus Rare Oncogenic Phosphatonin Hemangiopericytomas, osteomalacia [fibroblast growth factor osteoblastomas, fibromas, 23 (FGF23)] sarcomas, giant cell tumors, prostate, lung Acromegaly Growth hormone– Pancreatic islet, releasing hormone bronchial and other carcinoids (GHRH) Growth hormone Lung, pancreatic islet (GH) Hyperthyroidism Thyroid-stimulating Hydatidiform mole, hormone (TSH) embryonal tumors, struma
ovarii Hypertension Renin Juxtaglomerula tumors, kidney, lung, pancreas, ovary a Only 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. b hCG is produced eutopically by trophoblastic tumors. Certain tumors produce disproportionate amounts of the hCG α or hCG β subunits. High levels of hCG rarely cause hyperthyroidism because of weak binding to the TSH receptor. c Calcitonin is produced eutopically by medullary thyroid carcinoma and is used as a tumor marker. Hypercalcemia Caused by Ectopic Production of PTHrP (See also Chap. 347)