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). Postgrad Med J: first published as 10.1136/pgmj.26.294.214 on 1 April 1950. Downloaded from 2I6 POSTGRADUATE MEDICAL JOURNAL April I950 The Hypothalamus the other hand, the concentration of chloride in The confusion as to the role ofthe hypothalamus the urine rises until it reaches a maximum of about in the causation of diabetes insipidus was finally 1,200 mg. per cent. (as CI), which implies that ended by the work of Fisher, Ingram and Ranson for every cc. of water reabsorbed less chloride (1938) who conclusively proved that bilateral in- passes back. This appears to be the specific terruption of the supraoptico-hypophysial tracts effect of the hormone but it is often said that it produces the disease in the cat and monkey. No increases the output of chloride by the human other lesion has consistently been shown to do this. kidney. This question has recently been further Nearly complete destruction of the gland or tracts investigated and it has been shown that in normal is necessary to produce diabetes insipidus; in the men the hormone increases the concentration of cat subtotal lesions produce less severe degrees of chloride in the urine leaving the minute output un- the disease. This appears to be true in man also. changed, or reducing it slightly (Chalmers, Lewis A temporary phase of polyuria and a brief normal and Pawan, 1950). There is in fact no evidence interval occur before the polyuria becomes per- that ADH has any other action in normal men established. than to stimulate the renal tubule to reabsorb more manently water. The factor that limits the tubular re- The Normal Processes of Urine Formation absorption of water, and therefore determines the The nephrons elaborate urine by a process of minimum urine flow that can occur under the glomerular filtration, followed by the reabsorption action of ADH, appears to be the total osmotic of the greater part of this filtrate by the tubules. pressure exerted by the urine solutes. In a normal man about I,ooo to I,400 cc. of blood Suggestions that the posterior pituitary hor- flow through the kidneys per minute, the glomeruli mones might have other actions, e.g. on a hypo- filtering off I30 cc. of plasma water with its dis- thetical water regulating centre in the mid- solved crystalloids. Of this, more than I00 cc. are brain or hypothalamus, on the hydration of the always reabsorbed, probably in the proximal half tissues or on the osmotic pressure of the plasma of the tubule (Smith, I947). It is believed that the proteins are not supported by the evidence. by copyright. final concentration of the urine takes place in the Renal function has been investigated in diabetes distal tubule (probably mainly in the thin segment insipidus by Winer (1942) who found the filtration of Henle's loop) where varying quantities of water rate to be normal before and after treatment with are reabsorbed under the control of ADH re- pituitrin, though there was a sharp, temporary de- leased into the blood stream by the neuro- crease just after the injection. hypophysis. Under ordinary conditions the glomerular Factors Influencing the Production of ADH filtration rate (measured by the inulin or sodium (Pickford, 1945; O'Connor, I947) thiosulphate clearances) remains remarkably con- Claude Bernard showed that emotion could in- http://pmj.bmj.com/ stant and variations in the rate of urine flow are hibit the flow of urine. Emotional changes seem to thought to be effected by varying blood levels of be responsible for the release of ADH brought ADH, to which the renal tubules are extremely about by exercise (Rydin and Verney, I938) and by sensitive. Secretion of urine ceases if the pain (Kelsall, 1949). Various sensory stimuli will glomerular filtration rate falls to very low levels inhibit a water diuresis in animals, and the (as with very low arterial pressures) and at very stimulus can be so conditioned that the inhibition rates of urine flow the filtration rate rises, can be the mere of the high produced by preparation on September 30, 2021 by guest. Protected possibly from dilution of the plasma proteins by animal for the experiment, or even by a musical the large water load ingested. Between these ex- note. In man, a water diuresis can be initiated by tremes, however, there is no evidence that varia- suggestion under hypnosis (Marx, 1926). tions in renal blood flow or glomerular filtration Pickford (I947) has shown that acetylcholine rate affect the urine flow. It is possible that will cause the release of ADH in the dog when in- ADH, by acting on the glomerular arterioles, may jected into the supraoptic nucleus, and Burn, produce small changes in the filtration rate but Truelove and Bur (I945) showed that in man these probably play no part in its essential action. intravenous injections of nicotine, or smoking The greater the tubular reabsorption of water cigarettes, will do so (Walker, I949). Estimations the more concentrated does the urine become. Its of the inulin clearance in this laboratory have specific gravity and osmotic pressure rise, though shown that this is due to increased tubular re- not all the constituents are equally affected. More absorption of water. urea is reabsorbed for instance (this is probably a Dehydration appears to be the 'normal' process of passive back-diffusion) so that less urea stimulus increasing the output of hormone. It is removed from the blood per minute at low rates has frequently been shown that the urine of de- of urine flow (that is, the urea clearance falls). On hydrated animals contains an anti-diuretic sub- Postgrad Med J: first published as 10.1136/pgmj.26.294.214 on 1 April 1950. Downloaded from April I950 LEWIS: Diabetes Insipidus 217 stance. This disappears after destruction of the the mouth and throat. If this were true, extirpa- supraoptico-hypophysial tracts. (These results tion of the salivary glands should lead to increased should not all be accepted without reserve. Other drinking, but Montgomery (I931) found that this anti-diuretic substances might be present in did not follow in dogs. Gregersen and Cannon urine, and the methods of assay have not always (1932) repeated this work, drying the buccal been above criticism. As an example, the urine of mucosa as well by exposing it to warm air, but smokers contains nicotine, which will inhibit a even then the dogs only drank twice as much as water diuresis when injected into rats unless care before. Cannon found that atropine made him is taken to remove it.) thirsty when it made his mouth dry: most people It is this stimulus that has been so fully in- who have tried this would probably say that the vestigated by Verney and his co-workers at Cam- dryness leads to a desire to wet the mouth, not to bridge (Verney, 1946). They have shown in dogs drink large quantities of water. Nervous women that it is the osmotic pressure exerted by some of with xerostomia, or patients with ureo-parotid the plasma crystalloids which controls the release tuberculosis or with Sj6gren's syndrome (Ellman of the hormone. Changes can be brought about, and Parkes Weber, I949) do not develop diabetes with subsequent inhibition of a water diuresis, insipidus, though they may drink more often than by injections of hypertonic solutions into the other people. common carotid artery, and the amount liberated Gilman (I937) has suggested that thirst is the can be estimated by comparing the duration of result of the loss of intracellular fluid, which is the inhibition with that produced by injecting a older view in modern terminology, and this does known quantity of hormone. Changes in the not seem inconsistent with the known facts. It osmotic pressure of the carotid blood of about 2 would explain why thirst should occur after per cent. are effective. Verney believes that haemorrhage, which reduces the extracellular fluid special ' osmoreceptors' are responsible for con- volume, and after infusions of hypertonic saline, trolling the output of ADH from moment to which increase it. It seems probable that thirst moment, and has very tentatively suggested that arises from intracellular dehydration, while extra- by copyright. the small vesicles which can be seen in sections cellular fluid loss, by reducing the blood flow through the supraoptic nucleus may be the re- through the salivary glands (Gregersen), reduces ceptors themselves. According to Verney, a water the salivary flow. Usually, of course, the two diuresis only occurs when, following the ingestion occur together. of water, dilution of the blood leads to the cessa- Holmes and Gregersen (1948) investigated the tion of the activity of the osmoreceptors (' physio- origin of the thirst in diabetes insipidus by study- logical diabetes insipidus '). There is a time lag ing the weight, thirst, salivary flow, plasma of some 15 minutes after the peak of the water ' available fluid' and rate of flow is volume, thiocyanate plasma load before the maximum urine proteins and sodium in five cases under three sets http://pmj.bmj.com/ attained, presumably because this is the time taken of conditions: (I) when fluids were allowed ad lib. for the circulating hormone to be removed or (2) when pitressin was given to control the inactivated. polyuria, and (3) when fluids were forced until thirst disappeared and the salivary flow approached Thirst in Diabetes Insipidus that observed in period (2). In the last two There is no doubt that this experimental work periods, compared with the first, changes were offers a of the nature observed identical with those found

very convincing explanation consistently on September 30, 2021 by guest. Protected of the clinical condition, and there might seem to in dehydrated men after the ingestion of water- be little room for further argument. It deals, the weight, salivary flow, plasma volume and however, solely with the factors controlling water 'thiocyanate space' rose, while the plasma pro- output and only indirectly with that sensation teins and sodium fell. They believed that which must ultimately regulate the organism's Cannon's theory of thirst could be applied to water exchange, namely, thirst. If water loss did diabetes insipidus, the dehydration leading to a not rapidly lead to thirst and the ingestion of water, dry mouth and so to thirst. These results do not death would soon follow, while diabetes insipidus, rule out the possibility of over-hydration in as defined above, would certainly be the result if periods (2) and (3), as no figures for normal some prolonged and abnormal increase in thirst estimations are given. They believed this was were to occur. excluded since pitressin and forced fluids will not The problem of thirst has been discussed by increase the salivary flow in normally hydrated 'Gregersen (I94I). The older view is that it is a men. Theobald (I934), however, found that if a sensation arising centrally, from changes in the water diuresis in a hydrated dog were inhibited by hydration of the tissues. Cannon suggested that pituitrin, excessive salivation did occur. That it is purely local in origin, arising from dryness of pitressin can lead to chronic over-hydration is 2I8 POSTGRADUATE MEDICAL JOURNAL April 1950Postgrad Med J: first published as 10.1136/pgmj.26.294.214 on 1 April 1950. Downloaded from shown by the results of fluid restriction in a case been criticized by Fisher, Ingram and Ranson reported recently at the Royal Society of Medicine (I938). Bellows and van Wagenen (1938) repeated (Lewis, Ward and Bishop, I949). Fluids were re- an earlier experiment of Claude Bernard, making stricted on two occasions, once after daily doses oesophageal fistulas in dogs so that the water in- of pitressin or pituitrin snuff and once four clear take could be completely dissociated from the out- days after any treatment had been given. On the put, the dogs being given a measured quantity of first occasion, in the course of the 12 hours that fluid into the lower end of the oesophagus. followed the end of the anti-diuresis produced by Diabetes insipidus was then produced by bperation the last dose of pituitrin, nearly 5 litres of fluid on the hypothalamus or pituitary. In the tem- were lost, yet the urine flow remained above 5 cc. porary phase a marked polydipsia occurred, with per minute and the specific gravity was less than polyuria only on the first day. In the permanent I005' On the second occasion 19 hours' de- phase polydipsia was the sole abnormality, the privation reduced the urine flow to less than i cc. dogs suffering no ill effects from losing, through per minute with a specific gravity of Io1o.5, in the fistula, all the excess water drunk. If they spite of a total loss of less than 3 litres of fluid. were given more water into the stomach, the The mouth was not really dry on either occasion, polydipsia was reduced but not abolished. The though thirst was great (see also Thorn and Stein, dogs could, however, pass a fairly concentrated I941). urine. Though there was no obvious evidence of dehydration, there may have been sufficient to The Role of Polydipsia stimulate both the thirst and the production of The view that thirst is the cause and not the ADH from some residual tissue. The findings in result of diabetes insipidus, in spite of the im- Dandy's case might be explained along similar pressive weight of evidence to the contrary, cannot lines, for there may have been a greatly increased be lightly dismissed. This was certainly the extra-renal fluid loss following the operation. opinion of many of the older clinicians, who con- The view that there might be two types of sidered the disease as psychopathic in origin or diabetes insipidus was put forward by Veil (I9I6). referred to it as 'nervous polyuria.' Later, He believed that polydipsic and polyuric formsby copyright. hysterical thirst was considered in France to be a existed, but his final division was into hypo- separate condition and was termed ' potomanie.' chloraemic and hyperchloraemic types. In France, Cushny (1926) and Cushing (I932) both suggested Veil's earlier view has been greatly extended by that the polydipsia was primary. Many patients Kourilsky (I947) who has studied the effects of are absolutely convinced that their thirst began prolonged fluid deprivation on 30 patients. He before their polyuria, and there are several case divided them into:--(I) Pure polydipsia: five reports in the literature (Nothnagel, I88I; cases. The urine is reduced in volume and Futcher, I904; Kennaway and Mottram, I9I9; normally concentrated if the fluid deprivation is Weir, Larson and Rowntree, 1922; Kourilsky, prolonged. The symptoms and signs arise from http://pmj.bmj.com/ 1947). In Dandy's case (1940), the pituitary stalk excessive water ingestion (see below). Two was deliberately cut at operation: thirst appeared showed a normal hypothalamo-hypophysial system soon after the return of consciousness and was at necropsy (Roussy, Kourilsky and Mosinger, quickly followed by a very high output of urine. I946). (2)Pure polyuria: six cases. This corres- The water intake greatly exceeded the urine ponds in every respect to the disease produced in volume for ten days. cats by Fisher, Ingram and Ranson. There is Other clinical evidence sometimes advanced to constant polyuria of low specific gravity, little support the theory of primary polydipsia is per- affected by fluid restriction, the gravity remaining on September 30, 2021 by guest. Protected haps less convincing. Patients will often maintain below IOIO even when a fluid deficit of 3 litres that injections of pituitrin relieve their thirst very has developed. Dehydration and haemocon- rapidly, long before much effect on body hydration centration occur. (3) Mixed forms: 19 cases. could have occurred, or declare that pituitrin These may be due to partial lesions of the neuro- promptly increases their salivation. Both these hypophysis. Here the urine volume and specific effects may be psychological, however, and even gravity can be influenced to some extent by the control water injections may not decide this, for intake, but the thirst seems to be the dominant patients can sometimes tell from bladder sensations symptom and the effects of excessive fluid intake when the injection' begins to work.' complicate the picture. Experimental evidence in favour of the theory of The effects of excessive water drinking have polydipsia was given by Bailey and Bremer (I921) been studied by Veil and by Kourilsky, the latter who believed that polydipsia and polyuria occurred emphasizing that different changes in the blood simultaneously and independently, by Curtis chemistry occur in different subjects. Kunst- (1924) and by Swann (i939). These findings have mann, for example, in 1933 drank between IO and Postgrad Med J: first published as 10.1136/pgmj.26.294.214 on 1 April 1950. Downloaded from April 1950 LEWIS: Diabetes Insipidus 219 I8 litres a day for 127 days. After the first eight specific gravity or fall in the urine flow. The days there was an active desire for water and he had gravity never exceeds ioio and rarely reaches even to drink during the night, even if he had done so this figure. Cases of polydipsia will be able to before retiring. If water was not drunk, dryness form a much more concentrated urine without any ofthe mouth and difficulty in mastication occurred. signs of dehydration, though the urine flow falls to His weight remained constant and the plasma much lower levels than in the first group and the chloride rose in spite of a negative chloride test may therefore have to be prolonged for more balance. At the end of the experiment he had than 24 hours. There remains a number of inter- great difficulty in reducing his water intake. It is, mediate cases where there is probably sufficient of course, well known that continuous drinking hypophysial function left to form small amounts of has a dehydrating effect (Wolf, I945; see also ADH when dehydration is moderate; in these the references to earlier literature by Schemm, there may be a rise of urinary specific gravity I944, who based his treatment of oedema on this above ioio when some litres of fluid have been principle). This may be due to loss of sodium lost. The thirst and dryness of the mouth may and of extra cellular fluid. It is difficult to believe be misleading indications of the degree of de- that Kunstmann was dehydrated during this ex- hydration, as noted earlier. It is the urine flow periment, as his weight remained constant. The and specific gravity considered against the fluid rise in plasma chloride, with a negative chloride deficit that are of diagnostic importance. balance, indicates a marked loss of extra cellular Nicotine may also be valuable as a diagnostic water, which might have reduced the salivary flow. aid. In the case previously referred to (Lewis, Kourilsky maintains that the polydipsia in his Ward and Bishop, I950) there was no response to cases was not a hysterical manifestation, though he hypertonic saline but smoking a cigarette pro- does not deny the existence of' potomanie.' This duced a marked anti-diuresis. Further work on is bound to be the subject of controversy, though this test is now in progress in this unit. recent additions to our knowledge of the control of autonomic functions by specific cortical areas Lesions Associated with Diabetes Insipidus by copyright. make this view seem less improbable than it Cases occur where other signs of damage to the would have done a few years ago. One of his hypothalamus are present-emotional changes, cases was a young girl with a subarachnoid cyst adiposo-genital dystrophy, impotence, dis- which was stretching the pituitary stalk. While turbances of sleep or of sweating and diabetes this was being aspirated she suddenly exclaimed mellitus. The polyuria found in acromegaly may that her thirst had gone. This resembles results sometimes be due to pressure on the neuro- sometimes produced by leucotomy. hypophysis by the enlargement in the anterior Whether or not it is accepted that pathological lobe. thirst may be the result of lesions elsewhere than in These symptoms are the exception, however, http://pmj.bmj.com/ the neuro-hypophysis or may arise from its partial and in the majority of cases diabetes insipidus is an destruction, the experiments of Kunstmann isolated finding. and others show that the excessive ingestion of Fink (1928) analysed 107 post-mortem reports water can produce a symptom complex identical of cases with diabetes insipidus. In 63 per cent. with diabetes insipidus. there was a tumour at the base or in the posterior fossa, in 13 per cent. basal syphilitic meningitis or Diagnostic Tests gumma, in 6 per cent. tuberculous meningitis or a The tendency in Britain and America has been tuberculoma and in 8 per cent. some other in- on September 30, 2021 by guest. Protected to divide these cases into two groups-diabetes flammatory process in this area, while in io per insipidus and 'psychogenic polydipsia.' Carter cent. trauma was responsible. and Robbins (1947) suggested that a rapid intra- Jones (1944) reviewed the records of 42 cases venous infusion of hypertonic saline, after pre- treated in the University of Michigan Hospital liminary hydration, will reduce the urine flow in between 1926 and 1943. Tumours involved the the second group. This begs the question of the pituitary gland in 11; one was a medulloblastoma, origin of the polydipsia, but they claim that the four were cystic adamantinomas and the others three cases so diagnosed were freed of their secondary deposits. There was a tumour involv- symptoms by psychotherapy. ing the hypothalamus in two. Four suffered from Prolonged restriction of fluid is the usual Hand-Schiiller-Christian disease, seven from diagnostic procedure. Sucking small pieces of ice chronic encephalitis, three from syphilis, three or decicaine lozenges makes the ordeal more from the effects of head injury and three possibly tolerable, but the patient will still complain of from the results of vascular accidents. No cause thirst. Severe cases become obviously dehydrated could be found in eight, which were classed as in a few hours, with little rise in the urinary ' idiopathic.' 220 POSTGRADUATE MEDICAL JOURNAL April 1950 Postgrad Med J: first published as 10.1136/pgmj.26.294.214 on 1 April 1950. Downloaded from Kourilsky (I947) has emphasized the importance and it is possible that some cases have a selective of upper respiratory tract infections as a cause, and degeneration of the supraoptico - hypophysial cases following sphenoidal sinusitis have been re- tracts. ported (Yaskin, Lewey and Schwarz, 1942; The number of cases for which no cause at all Ball and Thackray, 1948). can be found at any time must be comparatively Bollack, et al. (i937), found 15 cases of diabetes small. A few of these may be found to be re- insipidus among 129 of chiasmal arachnoiditis. sistant to pitressin. The remainder probably in- Sinusitis or rhinitis were noted in 15 of the latter. cludes those cases described by Kourilskv as Colover (1948), reviewing the reports of II5 pure polydipsias,l if it is indeed the case that they cases of sarcoidosis involving the central nervous are not wholly psychological in origin. system, states that polydipsia and polyuria were present in 20. Several showed other. symptoms Treatment due to lesions of the hypothalamus. Apart from the treatment of the underlying Porter and Miller (1948) have reviewed the condition, the polyuria can be controlled by re- cases occurring at the Head Injury Centre at placement therapy. Oxford. They reported I8 cases, 13 occurring in Implantations of pellets and grafts of animal 5,ooo admissions with non-fatal closed head in- glands have been made, but have been un- juries. The majority had severe injuries with successful. more than seven days' post-traumatic amnesia. Injections of posterior pituitary extracts will Symptoms were noticed between the ninth and control the polyuria in the majority of cases, but thirty-first day after the injury. Of the I8 cases, this effect only lasts for a few hours. Occasionally only 12 had fractured skulls and these were not they cause such unpleasant sensations, particu- all basal. 'Eleven cases recovered within nine larly abdominal cramps, that they have to be months. abandoned. Warkany and Mitchell (1939) have reviewed Intramuscular injection of pitressin tannate in the condition in childhood. oil, which delays the absorption, is usually much Blotner (1942) and Williams (1946) have re- more successful. Many patients need only i orby copyright. ported families with hereditary diabetes insipidus. 2 cc. every two or three days and unpleasant side effects are fewer (Court and Taylor, I943). Idiopathic Diabetes Insipidus Nasal insufflations of the dried gland are also The diagnosis of this condition calls for an ex- effective for short periods. Patients can take a tremely detailed case history and clinical examina- pinch of this snuff when they need to control the tion, with X-rays of the skull and sinuses, lumbar polyuria for a few hours and can judge the quantity puncture and perhaps encephalography to deter- without having to measure it accurately, or they mine the underlying condition. In a small num- may prefer to have it measured out in capsules. ber, no evidence of one will be .found and these Some find it too irritating to the mucous http://pmj.bmj.com/ are usually termed 'idiopathic.' A progressive membrane. lesion may declare itself even in some of these Thyroidectomy has been recommended, par- after time has elapsed. A primary growth was ticularly for those cases associated with post- found in one of Jones' cases six years after the encephalitic Parkinsonism (Blotner and Cutler, onset of polyuria, and in this unit a case has I941). Thiouracil was given to one ' idiopathic' recently been seen to develop papilloedema after case in the Middlesex Hospital by Dr. K. P. Ball, seven years. It has even been suggested but without effect.

(Bern- on September 30, 2021 by guest. Protected stein, Moore and Fishback, 1938) that 'idio- Restriction of salt and protein in the diet will pathic' cases should be given deep X-ray therapy reduce the polyuria and increase the effectiveness to the pituitary area on an empirical basis. of pituitary extracts, but it must not be forgotten Isolated lesions destroying the supraoptic that salt deficiency may occur and be responsible nuclei have been reported (Baker and Craft, I940) for some of the symptoms in untreated cases.

BIBLI:;OG:RAPHY BAILEY, P., and BREMER, F. (I921), Arch. Int. Med., 28, 773. BLOTNER, H., and CUTLER, E. C. (I941), J. Amer. Med. Ass., BAKER, A. B., and CRAFT, C. B. (1940), Endocrinology, 26, 8ox. ir6, 2739. BALL, K. P., and THACKRAY, A. C. (1948), Lancet, I, 637. BOLLACK, J., DAVID, M., and PUECH, P. (I937), 'Les BEASER, S. B. (I947), Amer. J. Med. Sci., 213, 441. arachnoidites optochiasmatiques,' Paris. BELLOWS, R., and Van WAGENEN, W. P. (1938), J. Nerv. BURN, J. H. (I931), Quart. J. Pharm., 4, 57. Ment. Dis., 88, 417. BURN, J. H., TRUELOVE, L. H., and BURN, I. (I945), Brit. BERNSTEIN, M., MOORE, M. T., and FISHBACK, D. B. Med. Y., I, 403. (1938), Arch. Ijt. Med., 62, 604. CANNON, W. B. (19I8), Proc. Roy. Soc. B., 90, 283. BLOTNER, H. (1942), Amer. J. Med. Sd., 204, 261. CARTER, A. C., and ROBBINS, J. (1947), J. Clin. Endo., 7,752. Postgrad Med J: first published as 10.1136/pgmj.26.294.214 on 1 April 1950. Downloaded from April 1950 LEWIS: Diabetes Insipidus 221 CHALMERS, T. M., LEWIS, A. A. G., and PAWAN, G. L. MARX, H. (1926), Klin. Wchnschr., 5, 92 ( 95o), Y. Physiol. (in press). MONTGOMERY, M. (193I), Amer. J. Physiol., 96,'221. COLOVER, J. (I948), Brain, 71, 45I. NOTHNAGEL, H. (1887), Virchow's Arch., 86, 435. COUTT, D., and TAYLOR, S. (1943), Lancet, I, 265. O'CONNOR, W. J. (I947), Biol. Rev., 22, 30. CURTIS, G. M. (1921), Arch. Int. Med., 34, 8oi. PICKFORD, M. (1945), Physiol. Rev., 25, 573. CUSHING, H. (1932), 'Papers relating to the Pituitary Body, M. .. xo6, Hypothalamus and Parasympathetic Nervous System,' PICKFORD, (I947), Physiol., 264. Charles C. Thomas, Springfield. PICKFORD, M., and RITCHIE, A. E. (1945), J. Physiol., 04,. ' o05. CUSHNY, A. R. (I926), The Secretion of the Urine,' Longman's PORTER, R. J., and MILLER, R. A. (1948), 7. Neurol., Neurosurg. Green & Co., London. and Psychiat., I,, 258. DANDY, W. E. (I940), J. Amer. Med. Ass., 114, 3I2. RALLI, E., ROBSON, J. G., CLARK, D., and HOAGLAND, ELLMAN. P., and PARKES WEBER. F. (I949), Brit. Med. J., C. L. (I945), J. Clin. Invest., 24, 316. 1, 304. RIOCH, D., WISLOCKI, G. B., and O'LEARY, J. L. (1940), FINK, E. B. (1928), Arch. Path., 6, Io2. Res. Publ. Ass. Nerv. Ment. Dis., 20, 3. FISHER, C., INGRAM, W. R., and RANSON, S. W. (1938), ROUSSY, G., KOURILSKY, R., and MOSINGER, M. (I946), 'Diabetes Insipidus and the Neuro-Hormonal Control of Rev. Neurol., 78, 313. Water Balance,' Edwards Bros., Ann. Arbor. RYDIN, H., and VERNEY, E. B. (1938), Quart. J. exper. Physiol., FUTCHER, T. B. (I904), Tr. A. Amer. Physicians, 19, 247. 27, 343. GILMAN, A. (I937), Amer. J. Physiol., 120, 323. SCHEMM, F. R. (1944), Ann. Int. Med., 21, 937. GREGERSEN, M. I. (I94I), in Macleod's 'Physiology in Modern SMITH, HOMER W. (1947), Bull. N.Y. Acad. Med., 23, I77. Medicine,' 9th edition, Henry Kimpton, London. SWANN, H. G. (1939), Endocrinology, 25, 288. GREGERSEN, M. I., and CANNON, W. B. (I932), Amer. J. THEOBALD, G. W. (1934), J. Physiol., 81, 243. Physiol., o02, 336. THORN, G. W., and STEIN, K. E. (I941), .7 Clin. Endoc., I,. GROLLMAN, A., and WOODS, B. (1949), Endocrinology, 44, 409. 680. VON HANN, F. (I918), Ztschr. f. Path., 21, 337. VEIL, R. (I916), Deutch. Arch. f. Klin. Med., 119, 376. HELLER, H., and URBAN, F. (1935), J. Physiol., 85, 502. VERNEY, E. B. (1946), Lancet, 2, 739 and 781. HOLMES, J. H., and GREGERSEN, M. (1948), Amer. J. Med., WALKER, J. M. (I949), Quart. J. Med., I8, 5I. 4, 503. WARKANY, J., and MITCHELL, A. G. (1939), Amer. J. Dis. JONES, G. M. (1944), Arch. Int. Med., 74, 8I. Child., 57, 603. KELSALL, A. R. (1949), J. Physiol., 109, 150. WEIR, J. F., LARSON, E. E., and ROWNTREE, L. G. (1922), KENNAWAY, E. L., and MOTTRAM, J. C. (1919), Quart. J. Arch. Int. Med., 29, 306. Med., 12, 225. WILLIAMS, R. H. (1946), J. Clin. Invest., 25, 937. KOURILSKY, R. (I947), Ann. Med., 48, 288. WINER, N. J. (1942), Arch. Int. Med., 70, 6I. KUNSTMANN, R. (1933), Arch. J Erp. Path., 170, 701. WOLF, A. V. (1945), Amer. J. Physiol., 143, 567. LEWIS, A. A. G., WARD, C. S., and BISHOP, P. M. F. (1950), YASKIN, J. C., LEWEY, F. H., and SCHWARZ, G. (1942), J. Endocrinol. (in press). Arch. Neurol. and Psychiat., 48, 19. by copyright.

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