Localization and Origin of Antidiuretic Principle in Para-Endocrine-Active Malignant Tumors

Abstract

Studies performed on 5 cancer patients (3 bronchogenie carcinomas, 1 pancreatic carcinoma, 1 female choriocarcinoma) resulted in evidence that (1) some malignant tumors may contain a small amount of antidiuretic activity identical or very similar to posterior pituitary antidiuretic hormone (ADH) even in the absence of the syndrome of inappropriate ADH secretion; (2) the zone of active tumor growth contained most (50–100%) of the antidiuretic activity; (3) para-endocrine-active tumor cells can release ADH into Krebs-Ringer incubation solution, and they may be capable of synthesizing a substance identical or very similar to posterior pituitary ADH; (4) ADH levels measured in blood plasma and urine reflect the overall ADH production rate in tumor tissue.

Antidiuretic Hormone in Bronchogenic Carcinoma

“…The possibility that the tumour levels may determine the plasma concentration has been suggested by Vorherr et al (1974) and it is supported by the observation here of a relationship between tumour and plasma concentration of ADH immunoactivity. This relationship was restricted to the last plasma estimation and its existence may seem surprising in view of the observation (Robertson et al, 1976) that plasma ADH can fluctuate widely in some patients with carcinoma of the bronchus and syndrome of inappropriate ADH.…”

“…Since the original demonstration of antidiuretic activity in lung tumour tissue by Amatruda et al (1963), a number of studies (George et al, 1972;Lipscomb et al, 1968;Martin et al, 1972;Vorherr et al, 1974;Vorherr, 1974) appear t o suggest that tumour cells, especially those of the small anaplastic or oat-cell type, may have the ability to synthesize and secrete ADH or an ADH-like substance. In this investigation, all ten patients with bronchial carcinoma, hyponatraemia and elevated plasma ADH had small oat-cell tumours which contained detectable levels of ADH immunoactivity.…”

“…Whether this antidiuretic material is identical t o the naturally occurring hormone, arginine vasopressin, is not known. Both pharmacological and biological studies suggest a close similarity (Barraclough et al, 1966;Sawyer, 1967;Vorherr et al, 1968Vorherr et al, , 1974. While complete chemical characterization has been prohibited by lack of sufficient purified material, a number of studies reporting the behaviour of tumour extracts on Sephadex chromatography have been published (Utiger, 1966;Lipscomb et al, 1968;Sawyer, 1967).…”

Para-Endocrine Tumor Activity with Emphasis on Ectopic ADH Secretion

“…I. table VI); (2) antidiuretic activity was released from tumor cells into the incubation medium [99,103]; (3) synthesis of ADH possibly occurred in tissue culture of lung cancer cells [99,103]; (4) neurovesicle-like structures found in lung cancer cells, showed great similarity to neurohypophysial neurovesicles [29,37,106]; (5) incubation of tissue slices of bronchogenic carcinoma with phenylalanine-'H yielded synthesis of radioactive arginine vasopressin-'H [37]; (6) neurophysin synthesis and storage in lung cancer cells parallels that of neurohypophysial neurophysin in connection with ADH and oxytocin storage [45], and (7) inappropriate elevation of ADH levels in plasma and urine in some patients with malignant disease (tables VII, VIII).…”

“…It is anticipated, however, that in the future, broader application of X-ray polytomography, lung blood flow scintigram, sputum cytology, bronchoscopy with catheter biopsy, bronchography with tantalum dust, bronchial cytology brushing technique under X-ray television, fluoros copy, mediastinoscopy or even exploratory thoracotomy may facilitate earlier lung cancer diagnosis, especially when applied to high risk suspects such as heavy smokers above 45 years with a 'smoker's cough' [27,46,52]; in some instances, early lung tumor detection is accomplished because of appearance of a para-endocrine syndrome. Since malignant lung tumors may contain small amounts of ADH, in the absence of clinical SIADH [103] it appears that during any stage of cancerous disease sufficient amounts of ADH or another hormone may be produced which can be detected in blood and urine before other clinical and laboratory findings indicate lung cancer disease or its progression. This is in analogy to female choriocarcinoma diagnosis by HCG measurement in plasma and urine.…”