Diabetes Insipidus

DIABETES INSIPIDUS (diabetes insipidus), a disease characterized by intense thirst and excessive excretion of transparent, sugar-free urine with a low specific gravity. The occasion for the correct division of diabetes into mellitus and insipidus was the discovery by Willis in 1674 of the fact that the urine of certain diabetics has a sweet taste. Lister in 1694 and Oostedyck Schacht in 1747 already described seemingly cases of diabetes insipidus, since the symptoms in these cases consisted of excessive thirst and frequent excretion of urine in a very large quantity, while the urine was watery, pale, odorless, and tasteless (insipida). Further studies by Pool and Dobson in 1775, Cowley in 1778, and Frank in 1794 finally established the division of diabetes into mellitus and insipidus. Etiology and pathogenesis. There are several theories attempting to explain the mechanism of the onset of diabetes insipidus. According to the renal theory, the symptom complex of diabetes insipidus is the result of primary renal insufficiency regarding the concentration of NaCl, and polyuria in diabetes insipidus represents a phenomenon compensating for the decrease in the concentration capacity of the kidneys. A number of authors consider the cause of diabetes insipidus to be the increased excitability of the renal epithelium regarding water excretion. Both assumptions are possible in view of the works of Jungmann, Rhode, and Meyer, which showed that the concentration work of the kidneys and their ability to excrete water can be disturbed completely independently of one another. However, most researchers lean toward the view that the essence of diabetes insipidus lies in pathological polyuria. Since the end of the 19th century, numerous indications of the onset of diabetes insipidus after traumatic injuries of the hypophysis and lesions by gumma, sarcoma, cancerous metastasis, glioma, cystadenoma, and other neoplasms are encountered in the literature. The effect of hypophyseal extracts on diuresis was confirmed by numerous experimental and clinical observations, noting in most cases a sharp decrease in polyuria and polydipsia when using hypophyseal therapy in sufferers of diabetes insipidus, and since 1911 diabetes insipidus has already been linked to a disease of the hypophysis, at first involving its probable hyperfunction in the given disease (Sharpey-Schafer), but after the successes of treatment with extracts from the hypophysis (van den Velden) the cause of the disease began to be considered hypofunction of the pituitary gland. Russian (Rossiysky) in 1914 experimentally established that under the influence of pituitrin in animals, a decrease in diuresis and retention of chlorides in the organism occur with a decrease in their excretion in the urine. Experiments by Molitor and Pick on dogs with a urinary bladder fistula showed that subcutaneous and intravenous injections of pituitrin in doses of 0.0001 per 1 kg and higher regularly inhibit diuresis during a water test. This antidiuretic effect lasts, depending on the dose of pituitrin, from 2 to 10 hours and can be prolonged for any period by repeated administration of the drug, since habituation or weakening of the effect of pituitrin upon repeated injections is not observed. Oehme observed the effect of pituitrin upon disruption of all neural connection with the kidneys, which in his opinion testifies to the direct action of pituitrin on the secretory cells of the kidney. At present, most researchers (Frank, Romer, Eisner, Simmonds) recognize the middle lobe of the hypophysis as playing a prevailing role in the pathogenesis of diabetes insipidus, and view the posterior lobe of the hypophysis as an organ serving to conduct the secretion of the middle lobe into the cavity of the cerebral ventricle. There are descriptions in the literature of cases of diabetes insipidus with damage to the pineal gland without any damage to the hypophysis. Such are the cases of diabetes insipidus: Hymans—embryoma of the pineal gland; Massaff and Gierke—carcinomatous metastases in the pineal gland; Hoesslin—sarcoma of the pineal gland. The occurrence of diabetes insipidus in these cases is explained by proponents of the hypophyseal theory of diabetes insipidus by the possibility of a disorder of internal secretory correlations between the pineal gland and the hypophysis, while others believe that the occurrence of diabetes insipidus in disease of the pineal gland is a consequence of damage to the interbrain by compression from its pathologically altered pineal gland. Facts of the development of diabetes insipidus in diseases of other endocrine glands, e.g., the ovaries (Umber), are also known. Parallel to the hypophyseal theory of the origin of diabetes insipidus, a theory of the purely nervous origin of this disease developed. Thus, traumas and skull tumors, concussion of the brain, cerebrospinal lues, syphilitic meningitis of the base of the brain, gummas or tuberculosis of the floor of the 4th ventricle, hemorrhages, internal hydrocephalus, epidemic encephalitis, and various inflammatory processes of the brain membranes are sometimes accompanied by clinical symptoms of diabetes insipidus. A whole series of clinical cases in which diabetes insipidus was observed without lesion of the hypophysis, and studies by Aschner, Camus, Roussy, and Leschke, which showed that damage or irritation of the intermediate brain can cause the symptom complex of diabetes insipidus, forced many authors to conclude that the cause of the origin of diabetes insipidus must be sought not in lesions of the hypophysis, but in changes in the region of the intermediate brain, where the centers of water and salt metabolism are located. According to Eckhard, Aschner, and Leschke, these centers are located in the mammillary body and are in connection with nerve cells located in the medulla oblongata, in the reticular formation, since from these places it is possible to obtain experimental hydruria and hyperchloruria. Through the vagus nerve and the splanchnic nerve, the nerve centers regulating water and salt metabolism are in connection with the kidneys, influencing not so much the secretory function of the renal cells as the lumen of the blood vessels supplying the kidneys (Sirotinin). According to Aschner's data, the vagus nerve stimulates urination and causes polyuria with hyperchloruria, while the sympathetic nerve is an inhibitory nerve causing oliguria with hypochloruria. Other authors believe that between the nuclei of the intermediate brain and the posterior lobe of the hypophysis there is a neural connection regulating water metabolism in the organism. The pathogenesis of diabetes insipidus, consisting of a disturbance in the regulation of water and salt metabolism in the tissues, depends either on damage to the centers directing this regulation and located in the intermediate brain, or on an interruption of the pathway from these centers to the hypophysis, or on the fact that the hypophysis itself, due to one or another pathological processes occurring in it, is incapable of producing its specific incretion. Etiological moments causing damage to the hypophysis and intermediate brain and the appearance of the symptom complex of diabetes insipidus can be divided into genotypic and phenotypic; the latter include mechanical and toxic factors. Mechanical factors include neoplasms growing into or compressing individual more or less extensive areas of the hypophysis or brain, increased intracranial pressure, and sclerosis of cerebral vessels causing a disturbance in the nutrition of the hypophysis and intermediate brain. Toxic moments include syphilis and acute infectious diseases (malaria, scarlet fever, etc.), which can also present the picture of diabetes insipidus. At the base of so-called idiopathic forms of diabetes insipidus and diabetes-like diseases there undoubtedly lies a genotypic weakness of the hypophyseal-diencephalic apparatus, which is proven by the existence of hereditary forms of diabetes insipidus. Such congenital weakness of these apparatuses naturally also contributes to the development of toxic forms. Cases of hereditary diabetes insipidus are observed by no means rarely. Thus, Weil described an entire family of diabetics, where in five generations out of 220 people, 35 suffered from diabetes insipidus. The pedigree tree of this family was scientifically developed by Nest, who proved with evidence the dominant inheritance pattern of this affliction. Symptoms of diabetes insipidus were noted in the family in one child already from the age of 5; in some family members upon more thorough examination, phenomena of diabetes insipidus were noted to such a mild degree that they would not have been paid any attention at all had there not been a special examination. Lancereaux observed hereditary disease of diabetes insipidus in 11 out of 51 cases observed by him. Diabetes insipidus is observed more often in men at a young and middle age, but cases of the disease have even been described in children aged from 1.5 years to 12 years. Pathoanatomical studies of cases of diabetes insipidus not infrequently reveal changes in the hypophysis, most often manifesting as malignant tumors or syphilitic and tubercular processes in the hypophysis itself or in adjacent tissues. In some cases, during autopsies of patients suffering from diabetes insipidus, lesions of the celiac ganglion and splanchnic nerves were found (Shapiro). The kidneys in cases of diabetes insipidus sometimes turn out to be hypertrophied; in some cases, hyperemia, dilatation of the renal tubules, and fatty degeneration were observed in the kidneys. Clinical picture. The main symptoms of diabetes insipidus are extremely strong constant thirst and polyuria. Patients with diabetes insipidus introduce colossal amounts of liquids into their organism. The daily amount of excreted urine frequently reaches from 5, 10 to 40 and more liters.

The urine is very pale, transparent, of weakly acidic reaction, contains no sugar, protein, or any other pathological constituents; the specific gravity of the urine is very low (1.005-1.001), the freezing point is -0.2 to -0.4; the excretion of nitrogen (urea) in the majority of cases does not deviate from the norm. A feeling of hunger is noted rarely, more often the appetite is even diminished. Besides polydipsia and polyuria, patients exhibit dry skin, weakness, emaciation, headaches, a constantly depressed mood, decline in sexual energy, lowering of body temperature, and sometimes nocturnal enuresis. The heart and circulatory system most often do not reveal any deviations; blood pressure is ordinarily normal or low. In diabetes insipidus, a concentration insufficiency of the kidneys regarding NaCl is always observed, even under a load of NaCl on the organism and the administration of the smallest possible amount of water. Polyuria in diabetes insipidus does not decrease from the administration of NaCl, but increases, since the kidneys cannot excrete NaCl in an increased concentration, and for the removal of NaCl the elimination of a large amount of water from the organism is necessary (the so-called "pathological" reaction to salt). It is very characteristic that during dry feeding, blood concentration and an increase in its molecular concentration are observed, while the specific gravity of the urine and the concentration (percentage content) of chlorides in it continue to remain low, and the amount of excreted urine is significant. In connection with this, the weight of the patient towards the end of the experiment drops sharply (sometimes by 1-1.5 kg). Believing that diabetes insipidus is a consequence of a disturbance in water and mineral metabolism, manifested in the loss by tissues of the ability to bind water, Weil distinguishes two types of diabetes insipidus: the hyperchloremic-hypochloruric type and the hypochloremic-hyperchloruric type. Both types, according to Weil, have common symptoms in the form of polyuria, polydipsia, and a decrease in the concentration capacity of the kidneys, but while in the hyperchloremic type of diabetes insipidus there is a high molecular concentration of the blood and hyperchloremia with a normal content of water, sugar, and nitrogen, in the hypochloremic type of diabetes insipidus either a normal or reduced molecular concentration of the blood is noted with hyperchloruria, i.e., increased excretion of chlorides by the urine. In the hyperchloremic type, the water test proceeds with insufficient fluid excretion and with a specific gravity of the urine not falling below 1.002, which can be explained by the fact that with existing hyperchloremia, the high level of NaCl in the blood, altering the conditions of absorption and excretion of fluid through the kidneys, leads to a decrease in diuresis. The salt test in cases of hyperchloremic diabetes gives a retention in the organism of up to 50% of the introduced NaCl, causing a sharp rise in the concentration of NaCl in the blood. In cases of hyperchloremic diabetes, the use of a salt-free diet and especially the use of pituitary therapy (pituitrin) causes a very favorable therapeutic effect, leading to a sharply expressed decrease in the feeling of thirst, a lowering of diuresis and the level of chlorides in the blood, and an improvement in the patient's well-being. In the hypochloremic (or rather normochloremic, not recognized by all authors) type of diabetes insipidus, the water and salt tests in some cases give even excessive excretion of NaCl and H₂O, and a salt-free diet and the use of pituitary therapy allegedly do not give a therapeutic effect. The prognosis in diabetes insipidus quoad vitam must be considered favorable, since diabetes insipidus, if some other disease is not joined to it, can drag on for decades. Cases of diabetes insipidus lasting 30 (Eichhorst) and even 50 (Willis) years have been described. Cases have even been observed in which patients reached the age of 80 and more years (Weil). Regarding complete recovery, the prognosis is mostly unfavorable. Temporary improvement sets in not infrequently; sometimes a decrease in polyuria is especially noted after undergoing infectious diseases. Complete recovery is very rare: it is observed in cases that developed on a syphilitic basis and sometimes in traumatic forms. Death occurs mostly on the basis of progressive exhaustion. Differential diagnosis of diabetes insipidus from diseases accompanied by a significantly increased amount of urine—diabetes mellitus, primary and secondary contracted kidney—in the majority of cases does not present difficulties. In diabetes mellitus, the presence of sugar in the urine and its high specific gravity, and in chronic interstitial nephritis, elevated blood pressure, resp. hypertrophy of the left ventricle, provide definite data for making a diagnosis. For the differential diagnosis of true diabetes insipidus from secondary polyuria developed on the basis of primary polydipsia, the fact is important (E. Meyer, H. Strauss) that an increase in the introduction of a sodium chloride load in healthy people and in the case of primary polydipsia causes an increase in urine concentration, whereas in cases of true diabetes insipidus this phenomenon is not noted (see above). For the differential diagnosis between true diabetes insipidus and primary polydipsia, the dry feeding and water tests are also very important. For true diabetes insipidus during the dry feeding test, an almost complete absence of changes on the part of diuresis and urine concentration is characteristic, with an simultaneously noted extremely severe reaction on the part of the patient's general well-being. For primary polydipsia, on the contrary, a rapid drop in the amount of urine and an increase in the specific gravity of the urine to normal with good general well-being of the patient during the dry feeding test are characteristic. Therapy. In the treatment of diabetes insipidus, a large number of the most diverse remedies have been used, mainly exerting a symptomatic short-term effect in the sense of reducing polydipsia and polyuria. Opium, belladonna preparations, ergot, bromides, arsenic, quinine, valerian preparations, and antipyrine have been used for this disease for a long time. Meyer, Filosofov, and Romanenko point to good results from the use of diuretics (Theocinum natrio-aceticum); recently, the newest diuretics—novasurol (0.5-1.0 each) and salyrgan—have been used with success in diabetes insipidus. In cases of diabetes insipidus caused by syphilitic processes at the base of the brain or in the region of the pituitary gland, antisyphilitic treatment not infrequently gives striking results in the sense of the complete disappearance of all disease symptoms. Pituitary preparations in diabetes insipidus not infrequently exert a brilliant therapeutic effect, sharply reducing thirst and polyuria and improving the well-being of the patients. The action of pituitrin in various etiological moments that caused the appearance of diabetes insipidus will not be the same. In lesions of the pituitary gland itself (when there is an absence or lack of a stimulator with completely healthy centers of water and salt metabolism), the action of pituitrin will be brilliant, although short-lived. In cases of lesions of the centers with complete integrity of the pituitary gland, pituitrin will not exert a sharp action. In view of the fact that pituitary preparations can be modified under the influence of the action of digestive juices, it is preferable to prescribe them subcutaneously. In diabetes insipidus, simultaneously with the prohibition of excessive physical labor and mental overwork, it is extremely important to establish an appropriate dietary regimen with a restriction of the introduction of meat and sodium chloride into the organism. A diet containing many fats and carbohydrates is recommended mainly. A sharp restriction of fluid intake is undesirable, since this restriction in the majority of cases causes patients, along with agonizing thirst, various mental symptoms in the form of an anxiety state, headache, a feeling of heat in the body, etc. Of the beverages, it is best to use pure cold water. To reduce thirst, sucking on pieces of ice or sour lemonades can be recommended.