Postgrad Med J: first published as 10.1136/pgmj.26.294.214 on 1 April 1950. Downloaded from 214 POSTGRADUATE MEDICAL JOURNAL April 1950 BIBLIOGRAPHY ALBRIGHT, F., SMITH, P. H., and FRASER, R. (1942), J. Clin. GO]LDB)ERG, M. B., and LISSER, H. (1942), J. Ciin. Endo- Endocrinology, 2, 37. crinology, 2, 477. ATKINSON, F. R. B. (193I), Brit. J. of Children's Diseases, 28, HURXTHAL, L. M., HARE H. F. E., HORRASE, G., and 121. POPPEN J. L. (1949) .. Clin. Endocrinology, 9, 126. BAUER, W., and AUB, J. C. (1941), . Clin. Invest., 20, 295. JOSEPHSON, B. Acta. Med. Scand., go, 38s. CHUTE, A. L., ROBINSON, G. C., and DONOHUE, W. L. KINSELL, L. W.,(1936),MICHAELS, G. D., LI, C. H., and LARSEN (I949), . Paediatrics, 34, I. W. E. (1948), J. Clin. Endocrinology, 8, 1013. COGGESHALL, C., and ROOT, H. F. (1940), Endocrinology, LI, C. H. (I950), Lancet, , 213. 26, I. MAINZER, F., and YALAUSIS, E. (I937), Folia Clin. Orient., CROOKE, A. C., and CALLOW, R. K. (I939), Quart.7. Med., I, 37. 8, 233. McNEE J. W. (95o), Brit. Med. J., I, 113. CUSHING, H. (1912), 'The Pituitary Body and its Disorders,' NORTHFIELD,D . W. C. (949), Proc. Roy. Soc. Med., 42. 84 J. B. Lippincott & Co. Philadelphia. OPPENHEIMER, B. S., and FISHBERG, A. M. (I924), Arch. CUSHING, H., and DAVIDOFF, L. M. (1927), 'Rockefeller Int. Med., 34, 631. Institute for Medical Research Monographs,' New York. SCHRIRE, J., and SHARPEY-SCHAFER, E. P. (1938), Clinical DAVIDOFF, L. M. (1926), Endocrinology, 10, 461. Science, 3, 413. DAVIS, A. C. (1940), 'Transactions of Amer. Assoc. for Study SCHRIRE, J. (1948), J. Endocrinology (Gt. Britain), 5, 274. of Goitre. SIMPSON, S. L. (1948), 'Major Endocrine Disorders,' Oxford ELLINGER, P., HARE, D. C., and SIMPSON, S. L. (I937), University Press, London. Quart. Y. Med., 6, 241. TURNER, H. H. (1938), Endocrinology, 23 566. ELLIS F. (949), Proc. Roy. Soc. Med., 42, 853. WALTERS, W., WILDER, M., and KEPLER, E. J. (1934), FORBES, J. E., GUSTINA, F. G., and POSTOLOFF, A. V. Annals of Surgery Oct. p. 670. (I943), Amer. J. Dis. Child., 45, 593. YOUNG, F. G. (1937), Lancet, 2, 372. DIABETES INSIPIDUS By A. A. G. LEWIS, B.Sc., M.D., M.R.C.P. Saltwell Research Fellow, the Royal College of Physicians From the Medical Professorial Unit, The Middlesex Hospital by copyright. Thomas Willis, in I682, distinguished between when and where their illness began and may say saccharine and non-saccharine diabetes. Frank (in that the thirst occurred after some particular 1794) defined diabetes insipidus as a long-continued, food had been eaten. Sometimes a shock or an abnormally-increased secretion of non-saccharine accident may be blamed. urine, not caused by renal disease. It is now In severe cases the thirst is extreme, the patient known to be due to a failure of water reabsorption developing a dry mouth if he abstains from fluid by the renal tubules as the result of an ineffective for more than an hour or so. Very often the http://pmj.bmj.com/ level of circulating anti-diuretic hormone (ADH). thirst seems to be abnormal in quality as well. It Cases where the renal tubules can be shown to be may be described in dramatic terms, the patient insensitive to the action of the hormone occur emphasizing the 'burning sensation' in the extremely rarely (Williams, I946). mouth and throat. Sipping water is only a tem- porary palliative however; the patient often feels Clinical Picture compelled to drink a large quantity of water- Diabetes insipidus may occur at any age, but is he feels he must' drain the glass to the dregs' or more common in the young. In Jones' series of 'get it right down inside.' Water is often pre- on September 30, 2021 by guest. Protected 42 cases (I944), 17 occurred in the first ten years of ferred to all other fluids and some patients be- life. Males are more often affected than come connoisseurs of water, preferring that from females. one source to that from another in flavour. Many The onset is usually insidious, the patient find iced water more satisfying. noticing a tendency to thirst and dryness of the Deprived of water, the sufferer may go to any mouth, with polyuria and nocturia. There may lengths to get fluid, drinking from flower vases, be some loss of appetite, and the dryness of the puddles or fountains, or filling his mouth with mouth may make mastication difficult and food snow, or even drinking his own urine. It is not less appetizing. Loss of weight may occur, though surprising that some of these patients, constantly some cases gain. Loss of appetite and exhaustion tortured by thirst, unable to follow any normal from loss of sleep may lead to emaciation in severe occupation on account of the polyuria and pre- cases. Occasionally the appetite is increased. vented from sleeping for more than an hour or so In a few cases the onset is sudden and dramatic at a time, should develop neurotic symptoms. with intense, unquenchable thlrst and polyuria. Headaches, apathy, weakness, inability to con- These patients may remember for years exactly centrate, irritability and insomnia may be com- Postgrad Med J: first published as 10.1136/pgmj.26.294.214 on 1 April 1950. Downloaded from April 1950 LEWIS: Diabetes Insipidus 25I plained of, though in some cases these symptoms ) ...: PARAVENTRICULAR are probably associated with loss of salt. .' NUCLEUS In severe cases the urine volume may exceed io litres a day and much higher figures have been NCLEUS MAMILLAY recorded. Trousseau's famous case passed 43 OPTIC litres in 24 hours. While it is probably true that CHIASMA P E W \ INFUNDIBULAR STEM the more severe cases tend to have a more constant TUBER output of urine, variations do occur from time to CINEREM \ time. The day volume is greater than the night or reduced in an and may be increased by anxiety IFWUNDIWULAR intercurrent infection. Since the renal tubules PROCESS cannot concentrate the urine in the absence of ADH, any call for the increased excretion of osmotically active substances (especially salt and urea) will increase the volume of urine (Beaser, 1947). ADENOHYPOPHYSIS The specific gravity of the urine is always low, Diagrammatic representation of the course of the usually below o005. The significance of the supraoptico-hypophysial tracts in man. variations in urine volume and specific gravity (Drawn bi' Professor E. W. Walls.) which occur with fluid restriction will be discussed later. Diabetes insipidus is a symptom complex and the underlying cause must be carefully sought. optico-hypophysial tract) passes from the supra- Hyperparathyroidism should be remembered as optic nucleus in the hypothalamus, with some an occasional cause of fibres from the nucleus, to the polyuria. paraventricular by copyright. neurohypophysis. The mode of termination of The Anti-Diuretic Hormone these fibres is uncertain. It is thought that the This is formed by the neurohypophysis. It is pituicytes, large glial cells found throughout the generally believed to be identical with vasopressin, neurohypophysis, may actually elaborate the hor- and it is doubtful whether this has any other mone. They degenerate after section of the action normally in the body, though Heller (1940) supraoptico-hypophysial tracts, and retrograde de- has reported separating the anti-diuretic from the generation occurs in the two hypothalamic nuclei. pressor effect. Pitressin is the proprietary name given to a preparation of vasopressin which is said The von Hann Theory (x918) http://pmj.bmj.com/ to be practically free of the oxytocic factor. In spite of the fact that posterior pituitary ex- The hormone can be adsorbed and inactivated tracts were shown to control the polyuria of by blood and tissue extracts. It is probably re- diabetes insipidus in 1913, the role of the hypo- moved from the blood stream partly by destruction thalamus and of the anterior lobe remained in in the liver and, to a lesser extent, by excretion in dispute for many years. In I9I8 von Hann first the urine, in which it can be assayed by suitable reconciled the conflicting results of animal ex- techniques 1931; Heller and Urban, that some continued func- (Bur, I935; periments, suggesting on September 30, 2021 by guest. Protected Grollman and Woods, 1949). In cirrhosis of the tion of the anterior lobe, in the absence of the liver it has been suggested that slow destruction of secretion of the posterior lobe, was necessary for the hormone may be partly responsible for water the maintenance of the polyuria. Complete hypo- retention (Ralli, et al., I945). physectomy does not lead to diabetes insipidus, nor, clinically, does Simmond's disease, in which The Neurohypophysis the water exchange is reduced. Exactly how the The terminology introduced by Rioch, Wislocki anterior lobe is responsible for this is not known. and O'Leary (I940) for the more accurate descrip- It may produce an actively diuretic principle, but tion of the pituitary gland is now being generally it seems more likely that it is the maintenance of adopted. The gland is divided into adeno- normal metabolism and activity, by the thyroid hypophysis and neurohypophysis, the latter con- and the adrenals, that is essential. Thus thyroid- sisting of the median eminence of the tuber ectomy greatly reduces the severity of the polyuria cinereum, the infundibular stem and the in- in diabetes insipidus, and there is a failure of the fundibular process, which together form, histo- normal response to the ingestion of water in logically and functionally, a single unit (see fig.). adrenal insufficiency. This has been further in- A dense bundle of unmyelinated fibres (the supra- vestigated in dogs by Pickford and Ritchie (I945).