Endocrine Abnormalities in Bronchial Carcinoma
It is now known that undifferentiated cancer cells some- times produce substances with properties indistinguishable from those of hormones. The mechanism of production of these substances is unknown, though possibly the cancer cells produce a wide variety of polypeptides, some of which have biological activity.1 This phenomenon is well illustrated by some syndromes found in the bronchial carcinoma.
Rarely oat-cell carcinoma of the bronchus may be compli- cated by bilateral adrenocortical hyperplasia, also called the ectopic corticotrophin syndrome. The signs of this include oedema, muscle weakness, polyuria, thirst, and hypertension, though features of Cushing’s syndrome are usually absent, . presumably because these patients do not live long enough for their full development. The principal biochemical abnor- mality is hypokalaemic alkalosis, while glycosuria and hyper- glycaemia may also occur. The plasma-cortisol concentra- tion is high-usually higher than in Cushing’s syndrome- and, as in the latter disease, the characteristic diurnal varia- tion in plasma cortisol is lost. The urinary excretion of cortisol and 17-ketogenic steroids is increased.2 3 A cortico- trophin-like substance has been isolated from the primary tumour and its metastases, and excess of corticotrophin activity can be demonstrated in the plasma of these patients.4 Removal or irradiation of the tumour may result in regres- sion of the endocrine abnormality.5
Another substance that has been obtained from oat-cell bronchial carcinoma is one with an action resembling anti- diuretic hormone.6 The continued release of this substance by the tumour in the presence of a low serum-sodium level and reduced plasma osmolality is unphysiological, and hence the condition has been called ” inappropriate secretion of anti- diuretic hormone.”7 The secretion of this substance leads to an increase in plasma volume, which in its turn leads to secretion of aldosterone, and hence an excessive loss of sodium in the urine. Thus the reduced plasma-sodium level has two causes-firstly, an increased plasma volume (” dilutional ” hyponatraemia), and, secondly, excessive excretion in the urine (” depletional ” hyponatraemia).
Some patients with dilutional hyponatraemia may be lethargic, drowsy, or disorientated, but others show no distinguishing features and are diagnosed only when hypo- natraemia is found unexpectedly. Treatment with fludro-
1 Ross, E. J., in Symposium on Some Aspects of Carcinoma of the Bronchus, D. Teare and J. Fenning, 1967, p. 74. Midhurst.
? Friedman, M., Marshall-Jones, P., and Ross, E. J., Quart. }. Med., 1966, 35, 193.
3 Ross, E. J., Proc. roy. Soc. Med., 1966, 59, 335.
’ Liddle, G. W., Island, D. P., Ney, R. L., Nicholson, W. E., and Shimizu, N., Arch. intern. Med., 1963, 111, 471.
5 Engel, F. L., and Kahana, L., Amer. }. Med., 1963, 34, 726.
6 Lee, J., Jones, J. J., and Barraclough, M. A., Lancet, 1964, 2, 729.
1 Schwartz, W. B., Bennett, W., Curelop, S., and Bartter, F. C., Amer. 7. Med., 1957, 23, 529.
” Ross, E. J., Quart. }. Med., 1963, 32, 297.
9 Linton, A. L., and Hutton, I., Brit. med. 7., 1965, 2, 277.
10 Anderson, H. C., Rothschild, E. O., and Meyers, W. P. L., Clin. Res., 1962, 10, 238.
11 Rothschild, E. O., Meyers, W. P. L., and Lawrence, W., Clin. Res., 1964, 12, 462.
12 Tashjian, A. H., Levine, L., and Munson, P. L., 7. exp. Med., 1964, 119, 467.
13 Goldberg, M. F., Tashjian, A. H., Order, S. E., and Dammin, G. J., Amer. f. Med., 1964, 36, 805.
14 Meyers, W. P. L., Tashima, C. K., and Rothschild, E. O., Med. Clin. N. Amer., 1966, 50, 763.
15 Daughtry, DeW. C., Chesney, J. G., Spear, H. C., Gentsch, T. O., and Larsen, P. B., Dis. Chest, 1967, 52, 632.
16 Williams, E. D., and Azzopardi, J. G., Thorax, 1960, 15, 30.
17 Liddle, G. W., Givens, J. R., Nicholson, W. E., and Island, D. P., Cancer Res., 1965, 25, 1057.
”$ Fusco, F. D., and Rosen, S. W., New Engl. }. Med., 1966, 275, 507.
cortisone may relieve symptoms and correct serum sodium. Some patients also show defective function of the proximal renal tubule, the urine containing appreciable amounts of amino-acids and potassium, and they require additional treat- ment with large sodium and potassium supplements.8 Cor- rection of these metabolic abnormalities has been observed after treatment of the tumour with cytotoxic drugs.9
Hypercalcaemia, hypophosphataemia, and hypercalciuria occur in some patients with bronchial carcinoma who have no evidence of bony metastases. The symptoms of this syndrome include thirst, polyuria, nocturia, abdominal cramps, constipation, drowsiness, and mental confusion. The hypercalcaemic state resembles hyperparathyroidism, though the parathyroid glands have usually been found to be normal,10 and hypercalcaemia has persisted after parathyroid- ectomy.11 This condition may be caused by the secretion of parathyroid-hormone-like substances, which have been found to be present in some cancers, including carcinoma of the bronchus.12 13 It is important to recognize this syndrome, since hypercalcaemia and its symptoms may be relieved by giving the patient cortisone or by removing or irradiating the tumour. 14
Other endocrine disturbances reported in association with bronchial carcinoma15 include the carcinoid syndrome, in association with serotonin-producing tumours16 ; increased skin pigmentation with tumours containing melanophore- stimulating hormone-like substances17; gynaecomastia in men with tumours containing gonadotrophins18 ; and thyro- toxicosis and hypoglycaemia.
These metabolic abnormalities in bronchial carcinoma probably occur more commonly than has been realized. A survey of 100 consecutive admissions of patients with bronchial carcinoma revealed two patients with bilateral adrenal hyperplasia, two with dilutional hyponatraemia, and one with hypercalcaemia without apparent bony metastases.1 These metabolic complications may be identified by fairly simple screening tests, and, though treatment may not neces- sarily prolong life, it may make the patient’s remaining days more comfortable. Moreover, occasionally detection of the metabolic abnormality has led to the discovery of a previously unsuspected bronchial carcinoma.
Obstruction by Tonsils and Adenoids
Respiratory failure caused by nasopharyngeal obstruction from large tonsils and adenoids provides a dramatic clinical picture that has recently been recognized.1-6 Now L. E. Ainger, of Tennessee, has reported six more cases in the British Heart Journal to emphasize the rapidly changing clinical state and potentially lethal outcome.”
All the children came from poor Negro families in Memphis, Tennessee, and all but one were very young,
1 Menashe, V. D., Farrehi, C., and Miller, M., 7. Pediat., 1965, 67, 198. 2 Cox, M. A., Schiebler, G. L., Taylor, W. J., Wheat, M. W., and Krovetz, L. J., 7. Pediat., 1965, 67, 192.
$ Noonan, J. A., American Pediatric Society Inc., 6-8 May 1965, Abstracts No. 95. Philadelphia.
’ Luke, M. J., Mehrizi, A., Folger, G. M., and Rowe, R. D., Pediatrics, 1966, 37, 762.
5 Levy, A. M., Tabakin, B. S., Hanson, J. S., and Narkewicz, R. M., New Engl. }. Med., 1967, 277, 506.
6 Brit. med. 7., 1968, 1, 658.
” Ainger, L. E., Brit. Heart 7., 1968, 30, 356.