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The Clinical Significance Of Non-Metastatic Endocrine Manifestations Of Malignancy

Updated on February 17, 2014



A General Overview And Syndromes

Many substances with hormonal activity may be elaborated by several malignant tumours. They are peptide in nature. Different neoplasms elaborate different hormones or their analogues. These endocrine abnormalities may precede other overt manifestations of the neoplasm or they may appear along with the other signs of tumour. Removal of the tumours promptly alleviates the endocrinological abnormality in many cases.

Hyponatremia (Syndrome of inappropriate ADH Secretion):In this condition, hyponatremia, hypervolemia, and high sodium content of urine occur. Several malignant lesions give rise to this syndrome. Oat cell carcinoma of the lung, carcinoma prostate, carcinoma of the adrenal cortex and Hodgkin’s disease are well known among them. Clinical features include mental changes and other symptoms of water intoxication. Treatment consists of restriction of fluids and removal of the primary malignant lesion.

Hypoglycemia: Several tumours give rise to hypoglycemia which may precede or follow the onset of signs of overt malignancy. Most often, the underlying neoplasm is peritoneal or retroperitoneal mesothelioma. Hepatomas, leukemias and fibrosarcomas may also give rise to bypoglycemia. Some of these tumours elaborate insulin like substances or somatomedin. In the case of others, excessive utilization of glucose may be the abnormal mechanism.

Hypophosphatemia: Tumours like pleomorphic sarcomas and giant cell tumour of bone may give rise to excessive phosphaturia, but with normal levels of serum calcium and parathyroid hormone. Symptoms include weakness, muscle cramps and osteomalacia. It is possible that 1- hydroxylation of vitamin D is inhibited by the products of the tumour. This results in impairment of proximal renal tubular reabsorption of phosphorus, glucose and aminoacids.

Hypercalcemia: This is a common manifestation of several tumours. In many cases there are extensive metastases, but even without extensive spread some produce hypercalcemia. Carcinomas of the breast, lungs, kidneys and cervix, and lymphosarcoma produce hypercalcemia. These tumours may elaborate substances with activity similar to parathormone, prostaglandins or osteoclast stimulating factor.

Hyperthyroidism: Trophoblastic tumours such as hydatidiform mole and choriocarcinomas may produce hyperthyroidism because of the production of TSH like substances.

ACTH/MSH syndrome: Cushing’s syndrome may develop not infrequently in association with oat cell carcinoma of the lung. Marked hyperpigmentation may develop. The tumour may elaborate large amounts of ACTH and MSH. Other tumours of the thymus, pancreatic islet cell carcinoids and adenocarcinomas may give rise to Cushing’s syndrome. The typical picture of Cushing’s syndrome may be present only in a few cases. Others present with predominant muscle wasting, edema, mental changes, hyperpigmentation and extreme weakness. Persistent hypokalemia is an important feature suggestive of ectopic ACTH production.

Growth hormone and growth hormone releasing hormone: Bronchial carcinoids may produce growth hormone releasing factor (GHRF).

Zollinger Ellison Syndrome


Gastrointestinal Peptide Hormones

(a). Zollinger Ellison syndrome: This syndrome caused by excessive production of gastrin may develop in tumours arising from the duodenal wall, ovarian cystadenomas and islet cell tumours.

(b) Pancreatic cholera (WDHA): Watery diarrhea with hypokalemia and achlorhydria may occur in pancreatic islet cell carcinoma which produces excessive amounts of vasoactive intestinal polypeptide (VIP), glucagon and other substances.

In addition to these well recognized syndromes, less well-defined endocrine abnormalities may develop.

  1. Chorionic gonadotropins may be produced by malignant melanoma, carcinoma of the lungs, renal carcinoma and breast carcinoma.
  2. The free alpha chains of chorionic gonadotropins may be produced by carcinomas of the lung and stomach.
  3. Lipotropic factors may be elaborated by carcinoma lung.
  4. Carcinomas of breast, lung, pancreas and colon may give rise to elevated levels of calcitonin.

In summary, non metastatic endocrine manifestations of malignancy includes hyponatremia, hypoglycemia, hypophosphatemia, hypercalcemia, hyperthyroidism, growth hormone and growth hormone releasing hormone and gastrointestinal peptide hormones syndromes.

© 2014 Funom Theophilus Makama


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