Nephrogenic Diabetes Insipidus: Transmitted by Females and Appearing During Infancy in Males
| Title: | Nephrogenic Diabetes Insipidus: Transmitted by Females and Appearing During Infancy in Males |
|---|---|
| Authors: | Williams, Robert H.; Henry, Cole |
| Publisher: | Annals of Internal Medicine |
| Date Published: | January 01, 1947 |
| Reference Number: | 289 |
N/A
| |
This paper reports an unusual type of diabetes insipidus. This entity has most likely existed before, but we have not found any evidence of its recognition as such. Before discussing the characteristics of the syndrome, a presentation of our studies is given, chiefly in the order that they were conducted.
Patient C. H. A physician, aged 35, was recently admitted to the Boston City Hospital with pneumonia. His past health had been good, but he stated that he had had diabetes insipidus since infancy. In the course of treating the pneumonia with sulfadiazine it was observed that the concentration of this compound in the blood was unusually high in spite of a daily urine volume of about 12 liters. This observation and the fact that several members of the family had had diabetes insipidus since childhood aroused special interest.
This patient, like six others in five generations of his family, was told that he was a "water baby." When he was one month of age, or younger, his parents noticed that he desired excessive amounts of fluid and that he had a large urine volume. In spite of the persistence of these symptoms, his growth and development proceeded fairly well. However, he never appeared to be very strong and he did not grow to be as large as the average individual, although he had good stamina. His appetite has not been very remarkable, but he never has had much desire for sweets or salt. He has had a great desire for fruit and he has used black pepper freely. He likes meat moderately well.
He has known for eight years that he had hypertension, the systolic blood pressure ranging from 130 to 140 mm. of mercury and the diastolic pressure from 90 to 95. During this time his urine has been examined many times, but it has never been found to contain albumin, sugar or formed elements. The daily urine volume has been determined occasionally and it has been found to vary from 8 to 24 liters per day, with a specific gravity of about 1.001. The ingestion of sodium chloride caused a moderate increase in thirst. On two occasions water was denied for about seven hours and the patient developed a circulatory collapse each time. In 1940 he was given, intramuscularly, 1 c.c. of pitressin tannate in oil every two days for eight days, but this treatment caused no decrease in the urine volume. Large doses of sodium bicarbonate caused a slight decrease in the amount of urine excreted.
He occasionally has had headaches, but these do not tend to be severe. There have been no visual complaints, sensitivity to cold, brittleness of hair or nails, drowsiness nor gonadal disturbances. A careful systemic review elicited no additional complaints.
On physical examination the patient was found to be smaller than average. His weight was 120 pounds and his height was 5 feet and 6 inches. He appeared somewhat older than his age of 35 years. The skin was quite unusual in texture and appearance, being pale, shiny, scaly, very dry, coarse, inelastic and parchment-like. The epidermal layer was distinctly thickened. Systolic blood pressure varied from 130 to 175 and the diastolic pressure ranged from 80 to 125. The fundi, thyroid, heart, lungs, abdomen, sexual hair, gonads and neurological examination appeared to be normal.
The urine was pale and the specific gravity was 1.001-1.002. It contained no albumin, sugar, or formed elements. The hemoglobin varied from 82 to 95 per cent of normal. The red blood cell count was 4,300,000 and the volume of packed red blood cells was 42 per cent. Four estimations of the non-protein nitrogen of the blood yielded normal values. The carbon dioxide combining power of the plasma was 42 volume per cent on two occasions. Estimations of creatinine yielded 1.1 and 1.2 mg. per 100 c.c. of blood. The concentration in the serum of sodium, potassium and chloride was normal or slightly elevated (table 1).
Electrolytes in Serum
| Date | |
| |
| 6/20 11/24 11/26 11/28 |
140.0 136.5 142.2 146.0 | 4.2 4.6 5.0 | 108.5 102.2 110.5 115.0 |
| *All of the specimens were taken while the patient was in a fasting state, but the amount of water previously ingested varied. | |||
The basal metabolic rate was plus 26 per cent of normal. With the patient in a fasting state there were 120 mg. of glucose per 100 c.c. of blood. After the administration of 75 gm. of glucose, orally, the blood glucose concentration after 30, 60, and 120 minutes was 170, 210, and 180 mg. per 100 c.c., respectively. Another test was conducted, administering 75 gm. of glucose, orally, and 0.1 unit of insulin per kilogram of body weight, intravenously. There were 100 mg. of glucose per 100 c.c. of blood before this treatment was given and after 60, 120, and 220 minutes were 140, 120, and 100 mg., respectively. No sugar appeared in the urine. These tests can be interpreted as indicating the existence of diabetes mellitus with possibly slight insulin resistance. There were 8.9 mg. of 17-ketosteroids excreted in the urine per 24 hours. Roentgenograms of the skull, lumbar vertebrae, pelvis, chest, and abdomen revealed no abnormalities.
The average daily excretion of urine during an interval of 17 days was 10,600 c.c. Several compounds were administered, consecutively, in an effort to modify the volume of urine. The quantity of the latter was determined at frequent intervals throughout the day in order to detect any brief effect that might be exerted. Twenty mg. of desoxycorticosterone acetate in oil when injected, intramuscularly, had no effect. Ten c.c. of adrenal cortical extract was without effect. Potassium chloride, given in doses of 2 gm. six times daily, caused a slight decrease in thirst and in the urine volume.
When 1 c.c. of pitressin tannate in oil was given, intramuscularly, no definite decrease in urine volume resulted, but within 30 minutes after the injection the patient had a slight chill and a rise in his temperature to 101°F. A few days subsequently he was given 0.1 c.c. of pitressin, intradermally, in the forearm. Within 30 minutes a violent local reaction had developed. At the site of injection there was a firm, white wheal, about 10 by 6 cm. Extending towards the shoulder was an edematous streak which was about 15 cm. long. The reaction was soon inhibited by the injection of 15 c.c. of saline containing 1/2 c.c. of 1 : 1,000 dilution of adrenalin.
The marked allergic reaction to pitressin was considered as possibly accounting for the absence of its antidiuretic effect. In order to test the antidiuretic effect of large doses of pitressin, the patient was desensitized to this solution. Beginning with 0.1 unit of pitressin and progressively increasing the dosage, 17 injections of this drug were given within 30 hours. At the end of this time no local or general allergic reaction to pitressin resulted, even in doses of 1 c.c. (20 pressor units), but there was only a very slight, if any, antidiuretic effect. The phenomenon was regarded as possibly analogous to that observed in three patients with diabetes mellitus, seen by one of us (R. H. W.), who had local inflammatory reactions to insulin and showed no response in the blood sugar to injections of more than 100 units of insulin.
The question for consideration was whether antibodies had been produced which were capable of destroying the pitressin. Studies were conducted with rats to test this hypothesis.
To 0.9 c.c. of the patient's serum was added 0.1 c.c. of pitressin and the mixture, after sitting at room temperature for one hour, was injected, intravenously, into rats. The antidiuretic effect of this solution was tested by the method of Ham and Landis.1 The control solutions for the experiment consisted of: (a) 0.9 c.c. of serum from a normal man plus 0.1 c.c. of pitressin (2 pressor units), (b) 1 c.c. of normal serum, (c) 1 c.c. of patient's serum, (d) 0.9 c.c. of saline and 0.1 c.c. of pitressin, and (e) 1 c.c. of saline. Each of these solutions was given intravenously to a group of three male rats, each weighing approximately 300 gm. The animals given sera with pitressin added excreted 25 per cent less urine than those given any of the other solutions. Therefore, it was concluded that under the conditions of the experiment the serum did not inactivate the pitressin.
The next question was whether pitressin was inactivated in the patient's body at an abnormally rapid rate. To test this possibility 1 c.c. of pitressin was administered subcutaneously to the patient and a similar injection was given to a normal individual. Thirty minutes later blood was withdrawn and a few minutes thereafter 2 c.c. of serum was injected intraperitoneally into rats. The urine flow was then followed for the next three hours. The serum from the untreated normal subject had no antidiuretic effect whereas the sera of the subjects injected with pitressin had a marked antidiuretic effect.
After giving the patient as much as 3 c.c. of pitressin (60 pressor units) within six hours, no more than a very slight antidiuretic effect was observed. The above experiments with the rats had indicated that inactivation did not seem to take place abnormally rapidly. Furthermore, after the injection of 0.5 c.c. or more of pitressin, there was generalized blanching of the skin and abdominal cramps, as well as an increase in the blood pressure. Therefore, it was evident that the pitressin was exerting several of its systemic effects, but was failing to affect the reabsorption of water by the kidneys.
These observations suggested that there might be an anatomical, or at least a physiological, defect in a specific segment of the renal tubules. At this point the possibility that there was an even greater production of posterior pituitary principle was considered, since it was believed that the patient often was in a state of dehydration, which Gilman and Goodman2 found usually leads to an increased availability of the antidiuretic hormone. Moreover, the patient's pallor and hypertension might possibly have been related to increased function of the posterior pituitary lobe. His serum was given to rats, intravenously, in doses of 1 c.c. and its antidiuretic effect was tested in the manner described above. Control specimens of serum were taken from two normal individuals. Another sample of serum was obtained from a normal subject who had drunk 7,000 c.c. of water during the 24 hours previously. Saline was injected into other animals to serve as additional controls. However, no antidiuretic effect was found to be exerted by the serum of any of the subjects.
A series of tests was conducted to establish the extent and site of impairment of renal function. The patient and a normal individual who was essentially the same size were compared in their capacity to excrete sodium chloride. The control subject had a normal blood pressure and phenolsulphonphthalein excretion; routine examination of the urine revealed no abnormalities. Each individual was in a fasting state and had had no water for one hour. The subjects were asked to void and this specimen was discarded, but hourly collections of urine were made during the next four hours. No treatment was given during the first hour, but throughout the next 45 minutes an intravenous infusion of 1,500 c.c. of normal saline was given at a fairly constant rate. Specimens of blood were taken at hourly intervals. Estimations were made of the sodium and chloride in the blood and urine (table 2). During the one hour control interval each subject excreted about the same amount of sodium and chloride, although the patient excreted more than twice as much urine as did the normal subject. During the hour following the beginning of the saline infusion the patient excreted distinctly less of these electrolytes than did the normal individual, but during each of the subsequent two hours the reverse was found. Throughout the entire four hours the patient excreted about 32 per cent more sodium and chloride than did the normal individual, yet the urine volume was about 300 per cent greater. The chloride concentration of the serum increased markedly in the patient, but it did not show any significant change in the normal subject. During the course of this test the individual with diabetes insipidus became pale, weak and intensely thirsty. He also had a slight drop in his blood pressure.
(After the infusion intravenously of 1,500 c.c. of normal saline)
| Subject | Hourly Intervals | | | |||||
| Volume, c.c. | Sodium | Chloride | Sodium, m.eq./l. | Chloride, m.eq./l. | ||||
| m.eq./l. | total m.eq. | m.eq./l. | total m.eq. | |||||
| Normal Patient C. H. | Control 1 2 3 Control 1 2 3 | 150 135 145 142 380 480 810 680 | 20.4 96.2 66.4 101.9 6.9 12.1 25.8 35 | 3.1 13.0 9.7 14.5 2.62 5.8 20.9 23.8 | 41.8 111.2 85.0 132.1 16.7 23 30.3 40.3 | 6.3 15.1 12.3 18.7 6.3 11.0 24.5 27.4 | 140 138.5 141 — 142 140 143 140.8 | 110 108.9 107 — 106.2 118.5 122 117.5 |
Following the injection, intravenously, of 1 c.c. of phenolsulphonphthalein, there was found: none in the urine within 15 minutes, 5 per cent after 30 minutes, 15 per cent after 60 minutes, and 20 per cent after 120 minutes. There was also impairment in the clearance of the blood of urea and of creatinine from the plasma (table 3). Despite the marked diuresis, sodium and potassium were eliminated from the body less rapidly than normal, probably indicating increased tubular reabsorption of these elements. In three patients with diabetes insipidus of the "pituitary type," studied by Dr. John Talbott at the Massachusetts General Hospital, the sodium and potassium clearances were found to be normal.3
| Subject | Urine, c.c./min. | | ||||
| Plasma | ||||||
| Urea | Creatinine | Sodium | Potassium | Chloride | ||
| Normal | 1 | 75 | 175 | 3.0 | 20 | |
| Patient C. H.* Test No. 1 Test No. 2 |
6.3 (630%) 7.0 (700%) | 29.8 (39.7%) 35.4 (47.1%) | 105 (60%) 99 (57%) | 0.312 (10.4%) 0.379 (12.6%) | 4.54 (22.7%) 8.85 (44.2%) | 0.932 1.24 |
| Diabetes Insipidus (Pituitary) | 3.2 | 21 | ||||
| * Patient in a fasting state; no fluid during test and none for 2 hours before it. | ||||||
Special studies of renal function4 were conducted to determine the chief site of impairment.* The renal plasma flow was measured by the diodrast clearance and the glomerular filtration by the mannitol clearance. Diodrast and glucose were used to study, respectively, the maximal excretory and reabsorptive capacities of the tubules. There was shown to be a decrease in renal plasma flow without much change in glomerular filtration (table 4).
(*The authors are very grateful to Dr. Stanley Bradley of the Evans Memorial Hospital, Boston, who very kindly performed these tests and aided in interpreting the results.)
| Normal | Patient C. H. | Diabetes Insipidus (Pituitary)* | |
| Renal Plasma Flow, c.c./min. Glomerular Filtration, c.c./min. Filtration Fraction, % Diodrast Tm, mg./min. Glucose Tm, mg.min. | 697 (‡136) 130 (‡20) 19 (‡2) 52 (‡9) 375 (‡79) | 450 106 23.6 27.7 417.3 | 480 113 26 43 — |
| *These data are taken from Winer.5 | |||
The resulting increase in the glomerular filtration fraction may imply that efferent arteriolar constriction exists. The maximal rate of glucose reabsorption (glucose Tm) was normal, while maximal tubular diodrast excretion (diodrast Tm) was reduced by about 50 per cent. These changes in renal function are similar to those found in diabetes insipidus of the "pituitary type," and are consistent with the pattern found in essential hypertension. Dissociation between glucose and diodrast Tm is frequently seen in the course of hypertensive disease, but not of the magnitude seen in this case. The marked impairment in the secretion of diodrast and phenolsulphonphthalein is apparently due to impairment of active tubular excretion, but the normal glucose Tm indicates a normal mass of functioning proximal tubular tissue. This interpretation would explain the defect in water reabsorption which has led to continuous polyuria in this patient. In the course of the special studies the urine flow was observed to be between 14 and 28 c.c. per minute, which is about four times the volume in normal individuals under the same circumstances.
After making the foregoing observations an effort was made to study six other members of the family affected with diabetes insipidus. It was not possible to examine any of these patients, but some information, given below, was obtained from hospital records, from the patients or from their relatives.
Patient M. R. A clerk, aged 53, has been admitted to a veterans' hospital in Tuscaloosa, Alabama, on six occasions during the past 12 years. We are grateful to Dr. Dave Robertson for submitting to us the pertinent information that has been accumulated in this case. The patient stated that he had drunk an excessive amount of water since birth. The volume of his urine has been estimated many times and was found to average about 18 liters per day. He grew fairly well, but he has always been somewhat shorter than the average individual. He has had hyperorexia for many years, apparently eating a balanced diet with an average amount of salt. Occasionally he has severe diffuse headaches and feels dizzy and weak. The accumulated diagnoses are: diabetes insipidus, hypertrophic arthritis, blindness of right eye, corneal scar on the left eye, chronic otitis media, myocardial disease, complete atrophy of the right testicle, and chronic prostatitis. His height is 68 inches and he weighs 193 pounds. The hemoglobin determinations and the red blood cell counts were normal repeatedly. The examination of many specimens of urine revealed a specific gravity which varied from 1.000 to 1.003 and usually a neutral reaction. Albumin was sometimes present in small amounts and at other times none was found. Occasionally many white blood cells were present, but usually there were no formed elements in the urine. No glycosuria was ever found, but six fasting blood sugar estimations yielded values ranging from 105 to 147 mg. per 100 c.c. The concentrations in the blood of non-protein nitrogen, creatinine and urea nitrogen were normal. Eighty-five per cent of phenolsulphonphthalein injected intravenously was excreted in the urine within two hours. Two dilution and concentration (Mosenthal) tests revealed a maximal range in specific gravity of from 1.000 to 1.005. During these tests the patient developed circulatory collapse as a result of dehydration, and during one of them he became unconscious. Although he excreted only 724 c.c. of urine during one interval of 12 hours and 755 c.c. during another such period, the maximal specific gravity was 1.006.
Roentgenograms of the skull showed slight calcification in the region of the pineal body and the sella turcica was normal.
He was given 1 c.c. of pituitrin daily for four days, but there was no antidiuresis. However, he developed a marked febrile reaction following the last injection.
During the last 11 years his blood pressure has gradually risen from 115 to 160 systolic and from 84 to 106 diastolic.
Patient R. L. A veteran of the Army Air Force, aged 33, has been hospitalized for most of the past year with a urinary tract infection.
During the first month or two after birth it was observed that he drank an excessive amount of fluid and he urinated frequently. After a few years his symptoms largely disappeared, but he continued to drink as much as four quarts of water per day and got out of bed from one to three times per night to urinate.
His growth and development were normal. He had several examinations on entering the Air Force, but apparently no abnormalities were found. About one year ago he received an injury in the region of the left kidney on landing with a parachute. Since then he has not felt well. He was found to have dilation of his ureters and a urinary tract infection, which has not responded satisfactorily to prolonged treatment with penicillin and sulfonamides. The non-protein nitrogen has remained at about 70 to 100 mg. per 100 c.c. of blood. He has never received pituitrin therapy.
Patient W. M. A boy, 17 months of age, was apparently normal at birth. By the end of two months he stopped gaining weight, so breast feedings were discontinued and a formula was given. He became fretful and varied a great deal in his desires for milk and water. At four months he developed a fever which rose to 107° within a few days. He was then taken to the University of Virginia Hospital, where many studies were conducted, a report of which was kindly supplied to us by Dr. William Waddell. Numerous urine examinations were made, but at no time was there any albumin, sugar, or cellular elements. The specific gravity varied from 1.006 to 1.010. The blood ureas were 45 and 37 mg. per 100 c.c. Numerous blood cultures were negative. The blood chloride was 655 mg. per 100 c.c.
In view of the uncertainty of the diagnosis, an exploratory operation was performed, but nothing remarkable was found; the kidneys seemed normal grossly. Two pyelograms, made after intravenous injection of the opaque medium, revealed normal appearing kidneys.
The amount of fluid ingested and excreted was not abnormal. Roentgen-rays of the chest, skull, long bones and sinuses showed nothing remarkable.
At six months of age he was taken to the Duke University Hospital, under the care of Dr. Wilbur C. Davison, who has supplied us with the pertinent information. The child's weight was only about one-half that of normal and he was 2.5 inches shorter than normal. There was generalized hypotonicity of all the muscles. There was slight fever and moderate leukocytosis. Urinalysis was negative, except for from one to three white blood cells per microscopic field. One blood culture and four urine cultures grew out a staphylococcus. The blood chemical studies revealed the following contents per 100 c.c.: phosphorus 3.6 mg., calcium 9.4 mg., non-protein nitrogen 45 mg., albumin 4.2 gm., globulin 3.5 gm. Many other studies failed to explain the child's illness.
He continued to have fever throughout the 45 days of his hospitalization, in spite of therapy with penicillin, staphylococcus antitoxin and streptomycin.
Soon after discharge from the Duke University Hospital, he began to drink excessive quantities of fluid and he developed polyuria. He drank 24 ounces of milk and 36 ounces of water daily. With a phenolsulphonphthalein test only a trace of the dye was excreted in the urine. The specific gravity of the urine was only 1.002, but after spraying pituitary powder in the nostrils it was 1.010 and it was thought that there was possibly some decrease in thirst and urine volume. This pituitary powder was used two or three times daily for about four months. On stopping this treatment no definite change in the polydipsia or polyuria was observed. His mouth always seemed to be dry and he never drooled saliva. At the age of one year the child weighed 13 pounds. At this time he could sit up, unsupported. At present the child is 17 months of age, weighs 15.7 pounds and ingests about 2,400 c.c. of fluid per day.
Not very much is known about the other three patients because they died many years ago. However, each of these individuals was a male and had polydipsia and polyuria which appeared soon after birth. One of the subjects died of kidney disease at the age of about 35. The causes of death in the other cases are not known; one of them died in infancy and the other one died during early adult life.
It would seem probable that each of the seven individuals described had the same basic disease, but there apparently was a variation in the extent of the disturbance or in the patient's reaction to it. As seen in figure 1, the disease has appeared only in males, but has been transmitted only by females. The manifestations of water imbalance appeared within the first few months of life. As long as an adequate supply of water was given, fairly satisfactory progress was made, although some retardation in growth occurred in all cases and two of the patients died early in life.
|
Marked restriction of fluid was found to produce pronounced thirst, irritability, depression, weakness and circulatory collapse. It is not surprising that such reactions should result when one considers the marked shift in water and electrolytes that occur. The ingestion of sodium chloride caused a moderate increase in thirst. On the other hand, several grams daily of potassium chloride given to one patient either had no effect or slightly decreased the quantity of urine. This patient noticed no definite effect from 20 mg. of desoxycorticosterone, or from 10 c.c. of adrenal cortical extract. None of three subjects treated with pitressin experienced a significant antidiuretic effect. In one of these patients it was demonstrated that neither his serum nor his cells inactivated pitressin within 30 minutes. Since he responded to pitressin with generalized blanching of the skin and abdominal cramps, it was suspected that his kidneys were at fault. Renal function studies revealed an impairment in the renal plasma flow and in the tubular excretion of diodrast and phenolsulphonphthalein. The glomerular filtration was slightly decreased and the filtration fraction was slightly increased. There was a marked decrease in the sodium, potassium and creatinine clearances, and a moderate decrease in the urea clearance. The patient excreted larger quantities of sodium and chloride within three hours after the intravenous infusion of normal saline than did a normal individual.
It seems likely that this patient has a physiological defect, and possibly a congenital malformation, in the loop of Henle and/or the distal convoluted tubules, thereby causing an inadequate reabsorption of water, as well as some of the other disorders of renal function mentioned in the previous paragraph. Moreover, it is presumable that a similar pathogenesis existed in the six relatives with "diabetes insipidus."
Four of the subjects had marked impairment of kidney function; in two it was not tested and in one the phenolsulphonphthalein excretion was normal. In the three subjects in which the blood pressure was estimated there was hypertension. In two individuals there was an increase in the fasting blood sugar and the brother of patient C. H. has diabetes mellitus, but not diabetes insipidus.
In analyzing the pathogenesis of diabetes insipidus, many factors must be considered, especially: (1) injury to the supraoptic nuclei, supra-optico-hypophyseal nerve tracts, or to the posterior lobe of the pituitary gland, (2) injury to the posterior portion of the hypothalamus, with particular reference to the nuclei of the tuber cinereum, and the mammillary bodies, and (3) anatomical or physiological defects in the tubules of the kidneys. On the basis of present data, which are incomplete, the clinical picture of patients with diabetes insipidus is similar in many respects regardless of the site of pathology. Moreover, the type of lesion has often remained occult. That there are variations in the characteristics of the syndrome is indicated by the many classifications that have been given.6, 7 Veil8 divided the cases into two groups: (a) hyperchloremic-hypochloruric, and (b) hypochloremic-hyperchloruric. The former type is the one seen more commonly and is often due to a lesion in the diencephalon. The latter type has been produced experimentally by a lesion of the fourth ventricle. In the hypochloremic-hyperchloruric type pitressin is said to have no effect.9 Biggart10 reported three cases of diabetes insipidus which were refractory to pitressin. He observed lesions in the tuber cinereum and he suggested that damage to tuberal nuclei might result in diabetes insipidus which is not controlled by pitressin. Moreover, some of the cases with hereditary diabetes insipidus have failed to respond to the posterior lobe principle. In view of studies on the mechanism of pitressin,11 it is difficult to see why such cases fail to respond to this hormone, unless there is a coexisting structural defect in the kidneys. In such cases there have not been a sufficient number of reports on the physiological reactions and histological appearances of the kidneys to determine whether they contain the significant abnormality. To be sure, it is well known that polyuria may be associated with kidney disease and in some instances of tubular damage there may be such a marked loss of water and salt that a state of vascular collapse results. These patients usually do not excrete more than four or five liters of urine per day and they have a marked impairment of renal function in many respects. However, an abnormality in the loop of Henle is conceivable, which would impair reabsorption of water and which might not affect other renal functions to a significant extent. A congenital absence of the loop of Henle would seem possible since, phylogenetically, it was the last segment of the nephron to be added. It is present in birds and mammals, but is absent in frogs, fish and alligators. Moreover, the latter species of animals do not have a significant antidiuretic response to pitressin.12 Since these lower animals possess all of the segments of the nephron except the loop of Henle, there is a possibility that the facultative reabsorption of water13 that occurs in birds and mammals takes place in the loop of Henle, against osmotic gradients, as the result of a specific action by pitressin.
Therefore, it appears feasible to assume that in the cases reported above there was a congenital defect in the loop of Henle, as well as in the distal convoluted tubules, but the glomerular and proximal convoluted tubular functions were essentially normal.
Many cases of hereditary diabetes insipidus have been reported.6 This entity is more common in boys, usually responds satisfactorily to pitressin and has not been known to be associated, etiologically, with kidney disease. Males and females have transmitted the disease. In general, hereditary diabetes insipidus has not markedly reduced l
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
In this report, Williams and Henry describe in detail the condition of a 35-year-old male Jewish physician admitted as a patient to the Boston City Hospital. Since birth, this patient had experienced polyuria (the chronic passage of large volumes of urine) and polydipsia (chronic, excessive thirst). The authors determined the patient's urine contained no albumin, sugar or formed elements. The concentration in the blood serum of sodium, potassium and chloride was normal or slightly elevated.
Vasopressin (VP) is the antidiuretic hormone. It initiates a molecular sequence that enables the kidneys to concentrate urine by reabsorbing the body water flowing through the kidney tubules and collecting ducts. Pitressin is a synthetic form of VP that is used by physicians to enable the kidneys of patients suffering from pituitary diabetes insipidus (because they can't synthesize VP) to reabsorb body water.
But injections of Pitressin had no antidiuretic effect on their patients; nor did any other compound the authors tried. This indicated that their patient might have an anatomical or physiological defect in the tiny tubes (tubules) that help form the main working unit of the kidney: the nephron. They undertook a series of tests to establish the extent and site of the kidney impairment that prevented their patient from reabsorbing body water. Analyzing the maximal excretory and reabsorptive capacities of the tubules revealed a normal tubular reabsorption capacity while maximal tubular excretion was reduced by about 50%. This indicates impairment of active tubular excretion but a normal mass of tubular tissue.
Six other members of the patient's extended family (covering five generations) were affected with this newly recognized form of diabetes insipidus. All were male and all had polydipsia and polyuria which appeared soon after birth. It appears that all seven had the same basic disease, but apparently some had less severe symptoms than others. The disease only appeared in males, but was transmitted only by females. As long as an adequate supply of water was given, there was fairly satisfactory development although some retardation in growth occurred in all cases and two of the patients died early in life. Three of these patients were treated with Pitressin, to no avail in each case.
The authors speculate that in all seven cases, there might have been a congenital defect in two contiguous segments of the kidney: the loop of Henle and the distal tubules.