NEPHROGENIC
DIABETES
INSIPIDUS
424
By James R. West, M.D., and James G. Kramer, M.D.*
D
IABETES insipidus is a rare diseasecilaracterized in the classical instance
i)y polydipsia, polyuria, and an inability to
excrete a concentrated urine. The syndrome
is usually the result of damage to or
func-tional impairment of the supraoptic-neurohypophyseal mechanism which gov-ems the rate of urille flow through the nlediation of ADH (anti-diuretic hormone).
ADH, originating in the neurohypophysis,
exerts its effect on the cells of the renal
tubules causing increased reabsorption of
water from the glomerular filtrate during
its passage through the distal portions of
the nephron.1 Thus during the periods of
water deprivation the normal individual is
able to produce a concentrated urine and
conserve body water. Tile patient with diabetes insipidus, lacking in ADH, is
un-able to do so and continues to excrete large quantities of dilute urine despite the drain
on his body economy and fluid balance.
Symptomatology in these patients is well-controlled by the administration of potent extracts of posterior pituitary body tissue.
A less common form of diabetes insipidus
occurs Wilich seems to stem from primary renal rather than pituitary dysfunction. The presence of a basic developmental defect or persistent immaturity of the renal tubules
has been postulated in tilis variety.2 As a
consequence of the “end-organ” anomaly
there results an inability to conserve water
despite the presence of adequate quantities
of ADH. Waring, Kajdi, and Tappan3
re-ported such a case in 1945 and described
the clinical syndrome as characterized by
onset shortly after birth with bouts of un-explained fever, persistent constipation,
Irow the Pediatric Department of the Children’s
Hospital, Akron, Ohio.
(Submitted for publication October 8, 1954;
re-vision accepted January 14, 1955.)
* ADDRESS: 716 Second National Bldg., Akron 8,
Ohio.
vomiting during the first 3 months of life,
polydipsia and polyuria not responding to
pitressin. Also noted were high serum
sodium and chloride values, high skin
re-sistance, rapid dehydration with reduction
of fluid intake, inability to excrete a urine
of high specific gravity, familial incidence
and questionable occurrence in males only.
Williams and Henry2 introduced the term
“nephrogenic diabetes insipidus” and
con-eluded from their study of 7 cases in one
family that the condition was hereditary
with transmission as a sex-linked recessive
by
females to their male offspring.The authors of the present paper have
recently observed infant male cousins who were hospitalized simultaneously as
prob-lems of pyrexia of unknown cause and who
proved to have pitressin-resistant diabetes
insipidus. This report includes detailed
accounts of studies of these patients, a
dis-cussion of methods used and information
obtained which might be of value to others
faced with a similar problem.
The family history of these infants is of
particular interest in that transmission of
the disease appears to depart from the
sex-linked recessive pattern observed in the
past, predicating its occurrence in males
only. The finding of the trait in the Illothers,
maternal grandmother, and a maternal
uncle of the patients to be described
sug-gests the operation of either a Mendelian
dominant or simple recessive genetic
mechanism in this particular family. The
report by Dancis et al., describing a
6-month-old female so afflicted, lends support
to this concept.
CASE REPORTS
CASE No. 1: SN. (Unit No. 28065), a
3%-month-old white male, was admitted to the Children’s Hospital on 3/13/54 because of poor weight gain and repeated unexplained bouts
of fever dating from shortly after birth. It
be-ORIGINAL ARTICLES 425
tween 38.9#{176}and 40.5#{176}C. had occurred even
while ill the new-born nursery of another
hos-pital. Febrile episodes had recurred
subse-(juently at irregular intervals without apparent
cause and antibiotics had been administered
Vitil equivocal results. Unsatisfactory weight
gain was reflected in the admission weight of 4320 gm. as compared with a birth weight of 2900 gm. Cow’s milk formula, later
supple-mented by cereal and strained vegetables had
been veIl-taken except during periods of fever
when appetite tended to diminish. An unusual
willingness to take water between feedings had
l)een noted by the mother and had been
dis-couraged in the belief that such intake might
replace more nutritious foods.
Physical examination on admission revealed
an irritable, frail white male who appeared
poorly Ilourished and unhappy. The tempera-ture was 38.4#{176}C. rectally. Moderate general-ized mottling of the skin was evident and
turgor was poor. The circumference of the
head (occipito-frontal) was 38.7 cm., the chest
36.7 cm. and the body length 57.5 cm. The
blood pressure was 104/80. The remainder of
the physical examination was normal.
Laboratory findings: The red blood cell
count was 3,140,000 and the hemoglobin was
10 gm. The white blood cell count was 11,900
with 30 per cent segmented PMN’s, 68 per cent lymphocytes and 2 per cent monocytes.
Urinalysis on admission showed a pH of 5,
no albumin or sugar, and 2 to 3 white blood cells/HPF. The specific gravity was not re-ported because an insufficient quantity had been submitted for examination. Tuberculin test with old tuberculin 1 : 1000 and Kahn and
Kline tests for syphilis were negative.
The subsequent hospital course was
char-acterized by daily temperature elevations
be-tween 38.5#{176}and 40.5#{176}C. Agglutinations for
typhoid, paratyphoid, undulant fevers and heterophiie antibody were negative. Repeated cultures of urine, blood and stool were nega-tive. Dynamics and chemistry of the spinal
fluid were normal except for a high chloride
value of 842 mg. per 100 ml. The total serum proteins were 6.0 gm. with 4.0 gm. albumin
and 2.0 gm. globulin per 100 ml. Blood urea
nitrogen was 15.6 mg. per 100 ml. Repeated
blood counts failed to show significant devia-tion from the admission values.
On the fourth hospital day a cousin of this
patient was admitted to the hospital with a
history similar to that described above:
CASE No. 2: D.H. (Unit No. 28144), a
12-month-old white male, was admitted to the
Children’s Hospital on 3/17/54. He had gained
weight poorly and there had been recurrent
episodes of fever since birth. Appetite had been
good except during febrile bouts but the
ad-mission weight of only 5550 gm. as compareci
with a birth weight of 3040 gm. indicates the
poor nutritional state at the time he was first
seen. The patient was unable to sit without
support and could not stand. Temperature
elevations had occurred frequently and
er-ratically. Antibiotics had been administered
empirically during the febrile episodes without convincing effect on the patient’s course.
The temperature on admission was 38.9#{176}C.
by rectum. The skin appeared sallow and was
of poor turgor. The child was observed to
perspire freely, particularly about the head.
The head measured 41 cm. in circumference,
the chest 35 cm., and the body length 67.5 cm.
Blood pressure in the arms averaged 90/50.
The remainder of the physical examination was
normal and no cause for the temperature
dc-vation was found.
Laboratory findings: On admission the red
blood cell count was 3,390,000 and the
hemo-globin 10.5 gm. The white blood cell count
was 8600 with 50 per cent PMN’s, 47 per cent
lymphocytes, and 3 per cent eosinophils.
Ad-mission urinalysis: pH was 5, negative albumin,
sugar and acetone, white blood cells 1-2/HPF,
no red blood cells. The specific gravity was
not reported because of insufficient quantity
collected. The tuberculin test with old
tuber-culin 1:1000 and Kahn and Kline tests for
syphilis were negative as were typhoid, para-typhoid and undulant fever agglutinations. The
heterophile antibody agglutination test was
positive in a dilution of 1 : 16. A glucose
toler-ance test resulted in an elevated curve with
a 1-hour peak of 280 mg, per 100 ml. with
return to 180 mg. per 100 ml. at 2 hours and
110 mg. per 100 ml. at 3 hours. Repeated
examinations of the urine for sugar were
nega-tive. Blood urea nitrogen on admission was
58.4 mg. per 100 ml., non-protein nitrogen
81.4 mg. per 100 ml. Vitamin A absorption
and serum cholesterol studies were within
nor-mal limits. Roentgenograms of the skull and
chest were negative as was an intravenous
diges-426 \VEST - NEPHROGENIC DIABETES INSIPIDUS
tion Studlies suggested normal trypsin in the feces.
Special Studies of the Patients
Intermittent elevations of temperature con-tinned and in botil cases a marked intolerance to water restriction was noted in connection
with blood chemistry studies requiring fasting specimens. Under sucil circumstances signs of serious dehydration bordering on shock with temperature elevations as higIl as 40.5#{176}C. were
observed. Hydration following these episodes
1roved difficult with continued poor tissue turgor and fever despite the administration of apparently adequate quantities of fluids, orally
and intravenously. The skin of Case No. 2 car-ned an unmistakable yellow tint although the total serum i)ilirubin was only 0.2 trig. per ml.
and the serum carotene 90 lU. In view of 24-hour oral intakes of fluid measuring up to 2 liters for both patients the presence of a
diabetic state was considered. Neither case
cx-hibited a reducing substance in the urine on
repeated examinations although Case No. 2 had shown a diabetic-type of curve in the oral
glucose tolerance test. Specimens of urine were
obtained by means of external catheters in (luantities sufficient to permit specific gravity determinations; low values (varying from
1.006 to 1.008 and 1.009 in the 2 cases) were
observed even though the patients were mark-edly dehydrated.
Serum electrolyte studies carried out on
322/54 ill Case No. 1 revealed a serum
so-dium of 170 mEq./l. and chlorides of 140
mEq.’l. Two days later, despite attempts at
forcing fluids by mouth the sodium was still 163
mEq./l., chlorides 140 mEq./l., potassium
5.1 mEq./i., CO combining power 17.6
mEq./l., and pH 7.45. Similarly Case No. 2
was found on 3/22/54 to have a serum sodium
of 165 mEq./l., cillorides 140 mEq./l.,
potas-sium 5.5 mEq./l., CO2 combining power of 21.6 mEq./I. The blood urea nitrogen which had been elevated in Case No. 2 at the time of
admission had fallen to 13.8 mg. per 100 ml.
when repeated on 3; 26/54.
Phenosulpho-phthalein excretion during the 2-hour collecting
period following intramuscular injection of 2 ml. of the dye was 60 and 80 per cent in Cases No. 1 and No. 2 respectively. Urea clearance determined after the method of Behrendt5 was
7.95 mi./min./M2 for Case No. 1 (normal =
13.8 to 31.3) and 10.5 mi./min./M2 for Case
No. 2 (normal = 23 to 55). The 24-hour
excre-tion of 17-ketosteroids was 0.20 mg. for Case
No. 1 and 0.22 mg. for Case No. 2.
Family Histories
Additional questioning of the mothers
re-vealed that 1)0th babies had seemed to pass
large quantities of urine since birth insofar as
could be judged from their keeping diapers persistently wet. Stools tended to be hard and dry in both cases. The mothers of the patients were sisters and, when questioned specifically, gave histories of excessive thirst and passing large volumes of urine dating from early life as did their brother, an uncle of the patients.
Initial morning urine specimens were obtained
on these individuals, and specific gravities ranged from 1.002 to 1.003. A similar speci-men from the maternal grandmother of the patients gave a specific gravity of 1.003 despite
the absence of any history of polyuria or
polydipsia. Urine specimens from the fathers
of the patients showed normal concentration.
Case No. 1 was an only child. Case No. 2 had 2 female siblings, both of whom were asympto-matic. A careful review of the family tree as far
back as 7 generations failed to uncover any additional suggestive histories.
Studies Relative to Antidiuretic Hormone
In the light of these findings the patients
were placed on low-protein, low-solute
formu-las and posterior pituitary hormone was ad-ministered in a suspension as nose drops. It
was found that by urging fluids there was
im-provement in the hydration of both patients
and febrile episodes could be controlled. No
reduction in thrist or urinary output was noted
in response to posterior pituitary medication,
however. Case No. 2 was observed to take
as much as 2400 ml. by mouth in 24 hours.
The 24-hour urine output measured 913 ml.
and 1092 ml. for Cases No. 1 and No. 2
respec-tively. Specific gravities determined carefully by one of us varied from 1.001 to 1.003 on
specimens obtained at 2-hour intervals over the
24-hour period.
Response to the administration of hyper-tonic saline intravenously was measured. This procedure has been variously referred to as
the Carter-Robbins#{176} or Hickey-Hare test.
Fluids are withheld for 8 hours and the effect
CHART II.
EFFECT5 OF WATER DEPRIVPTI0N AND ADMiNiSTRATION
OF I-%YPERTONIC 51LlNE ON URINE SPECIFIC GRAVIIY, URINE OUTPUT, AND BLOOD AND URINE CHEMISTRIES
CASE NO.1 SN.
FLUID ROUTE
INTAKE tYPE.
AMOUNT
URINE SPECIFIC GRAVITY
c_A1 c?:.: .!L
k!i.9 Hj 2#{176}/
N.c!
1.001 %.OOZ 1.002
-uOO 1007
9:4cc
‘ %.O7
9.Q.c
‘IO? .00’
URIWE0UTPUT3’
(
cc’s) 2ebODY WIGWr(GRAM$
-
-S
- - - .7’
-k! 4iP 4i4
BLOOD CHEMISTRIES
EPIATOC1
HcL(Mt4k K(MeQ.AJ
a&i
i
41.
-
-35% 3O#{149}/
!_. -
-r.i(M&.’ !.!I l! Ii -
-0p(it.#{241} !:
PH :7:±
NPN(MgvnV 332 URiNE
CHEP4ISTRIES
P4a(11t4/F :.±
-:1(rle/i) 3J5
4PN(M9m 37
TITlE I4OUR a 3 S 6 7 8
?
CHART I.
EFFECTS OF WATER DEPRIVATION AND ADMINIS1RPTION
OF HYPERTONIC SALINE ON URINE SPECIFIC GRPIV%T’I’, URINE OUTPUT, AND BLOOD AND URINE CHEMISTRIES
CASE No2,D.H.
FLUID IR0UT( 1NTA(E FIYE
IAMOUNT
2! ..J-
&___
- --
c-I4z0
la4cc
.j’ ‘1ICC
L
URINE 5PECIFI( GRAVITY i.oo %004 1004 QQ4
3C----URINEOUTP%JT
----;--(cc’s) 2C___-\_
0
---j
0
BODY dEIGHT (Gp.ris) 5950 5790
::::z
LT
TIME #{216}.iouRs) I 2 3 4 5
- ._,- - 4- LQ.27 ‘&QF.,
,,
-.
6
-5790
.
;4#{176}L’T’’r
PIT RESSIN TEST, CASE No. I (S. N.)
20
8o
..1
Ui
:40
20
L00L
1.004
I-,
Ui
-J
0
>
Ui
z
HOURS
CHART IV.
428 WEST - NEPHROGENIC DIABETES INSIPIDUS
SPEcIFIc GPAVTY DETERMINATIONS ARE
RECORDED AT HOURLY INTERVALS ON THE CURVE
La
PITRE3SI4UNITS1/
-tM.
OO3
t004 1.002
P IT P #{163}IN
8UNITS LM.
I 5 6
CHART III.
OIl hourly specimens obtained by means of indwelling catheters. Following the fast the patient receives orally 20 ml. water/kg. of body
weight over a period of 1 hour and during
this time output is measured at 15-minute inter-vals to determine the diuretic effect of the oral
fluids. In adults this should amount to at
least 5 ml. urine/minute. There are no pub-lished data Oil the degree of diuresis necessary
for valid interpretation of this particular test
in infaiits. A 2.5 per cent solution of NaCl
is then administered intravenously at the rate of 0.25 ml./kg. of body weight/minute over a period of 45 minutes and urinary output
measured at 15, 30, 45, 60, and 75 minutes following completion of the infusion. The
re-suits of these tests are presented in Charts
I and II. It will be noted that the saline
infu-SiOIl in Case No. I was delayed until after the
administration of water by mouth a second time because the output following the first such feeding was inadequate. Failure to cx-crete a concentrated urine during the 8-hour
period of water deprivation is evident in both
cases. Although urinary output did diminish
and an increase in sodium, chloride and NPN
content of tile urine was observed, the high-est specific gravity achieved in either case
was 1.007. The normal response to administra-tion of hypertonic saline under the circum-stances in this test is a marked antidiuresis.6’ Neither of our patients exhibited such a
re-sponse. No claims are made for the validity of this test in assessing ADH effect in infants
be-cause the procedure for its administration is based on studies in adults.
The patients were then hydrated and
ob-served for response to the administration of
pitressin. Fluids were urged at hourly intervals
since it has been demonstrated that a water
diuresis must be in progress before the anti-diuretic effect of posterior pituitary hormone can be demonstrated.8 The patients were re-strained comfortably on Bradford frames at the beginning of the test and #10 Fr. catheters
passed into the urinary bladders where they
were firmly anchored by means of adhesive
strips extending from the abdominal wall
out-ward over the penis and catheter. After a
1-hour rest period to allow for recovery from
the stress of catheterization a 1-hour control
specimen of urine was collected and pitressin
administered intramuscularly. Initially a
gen-erous dosage of 4 units was administered to these patients and when this failed to produce a response 8 units were administered. Pallor, a shock-like appearance, the passage of flatus and several loose stools followed the latter dose
in both cases and were considered
manifesta-tions of toxicity. Effects on urine output and
specific gravity are depicted in Charts III and
IV. Commercial pitressin (Parke-Davis)
con-taming 20 units pressor activity and less than
1 unit oxytocic activity/mi. was used in these
and subsequent tests requiring administration
of hormone.
For purposes of comparison the pitressin test was also performed on 10 normal infants rang-ing in age from 12 days to 14 months, utilizing
a 2-unit test dose. In none of these was the
response identical to that encountered in the
TABLE I
EFFECT OF TEN UNITS PITRESSIN J.M. ON URINE OUTPUT AND SPECIFIC
GRAVITY OF MOTHERS OF PATIENTS DESCRIBED
Subject
1-hr. Control Urine
1-hr. Test Urine
2nd-hr. Test Urine
Vol.
ml. Sp. Ge.
Vol.
ml. Sp. Ge.
3rd-hr. Test Urine
Vol.
nil. Sp. Ge.
iol.
ml. S. (;r.
Mrs. N., mother of Case No. L SN.
Wt.1571hs.,ht.634in. 446 1.003 29 1.004 57 1.003 344 1.004
Mrs. H., mother of Case No. 2, D.H.
Wt.l49lhs.,ht.631in. 410 1.003 165 1.004 239 1.004 100 1.003
ORIGINAL ARTICLES 429
2 cases reported and all exhibited definite in-crease in urine concentration with only 1 fail-nrc to achieve a specific gravity of 1.020 or higher.
The mothers of the cases reported were
similarly tested. One of these, Mrs. N., was in the first trimester of her second pregnancy at
the time. Specific gravities of control
speci-mens from both women were 1.003, and in response to the intramuscular injection of 10
units pitressin neither excreted a urine of
spe-cific gravity higher than 1.004 (Table I). Un-fortunately the maternal grandmother and
af-fected uncle were not available for testing.
It is apparent from the charts that neither patient conserved water in response to the intravenous administration of hypertonic saline.
In the pitressin test Case No. 1 showed a
some-what erratic output following administration of the hormone but no significant increase in concentration as reflected by specific gravity. Urinary output for Case No. 2 actually in-creased following administration of pitressin
and specific gravities were essentially
changed.
Treatment and Course
Following discharge from the hospital the
patients have received formulas and diets
de-signed to increase fluid intake and reduce renal
solute-load as recommended by Talbot9 and
both have shown improvement although bouts
of fever continue to occur in conjunction with
varying degrees of dehydration and both are
below the normals for their age for weight and
mental development.
DISCUSSION
The occurrence of diabetes insipidus in
infancy resistant to replacement therapy
had been observed and reported by
Forss-man1#{176}in 1945 as affecting 3 male members
of one family. Biggart,’1 in 1937, reported
2 cases of diabetes insipidus developing in
unrelated males during adulthood which
failed to respond to posterior pituitary
ex-tract and stated that 5 to 15 per cent of
cases of diabetes insipidus are refractory to therapy. Biggart did not record the data
whereby he arrived at this figure. In
addi-tion to the cases previously mentioned in
this article, other reports of
pitressin-resist-ant diabetes insipidus appearing in the
lit-erature are those of Kao and Steiner,’2
Macdonald” 13a and Luder and
Bur-nett.’4
Macdonald described a white male
1105-pitalized at 3 months of age and on whom
the serum titre of ADH was determined
and found to be “high normal.” The basic
pathology was thought to be either a
de-velopmental defect of the renal tubules or
an intrinsic enzymatic deficiency causing
inability to respond to the hormone. The
only example of this condition known to
have come to autopsy failed to exhibit any
demonstrable anatomical defect in the renal
tubules ‘5
Renal function, aside from the specific
430 WEST - NEPHROGENIC DIABETES INSIPIDUS
quite well-preserved in this disease. Blood
urea nitrogen values are generally normal
although they may be slightly elevated in
tile presence of dehydration. Both of our
patients exhibited reduction in clearance
values for urea and in Case No. 2 the blood
urea nitrogen was elevated during a period
of extreme dehydration but returned to
normal \Vitll the administration of fluids.
Case No. 2, it may be noted, demonstrated sufficient dye excretion and concentrating capacity for normal intravenous
pyelogra-pily. Williams and Henry’ studied renal plasma flow, glomerular filtration, tubular
excretion and tubular reabsorption in their
patient, wilO was 35 years old at the time,
i)y means of Diodrast#{174} clearance, mannitol
clearance, Diodrast#{174} Tm and glucose Tm.
Normal results were obtained with the cx-ception of Diodrast Tm which was re-duced to approximately 50 per cent of
IlOrIT)al and was interpreted as reflecting
impairment of tubular excretion. Their
pa-tient exhibited a mildly elevated oral
glu-cose tolerance curve without glycosuria as did our Case No. 2.
Routine evaluation of renal capacity for
concentration or dilution is generally
de-pendent upon the determination of urine
specific gravity rather than the more
complicated and time-consuming
measure-ments of osmolar concentration of total urine solids. This seemingly simple test is not always an easy procedure in infants
where volumes of specimens obtained over
short intervals of time are generally so
scanty as to make determinations difficult. We have found that the so-called Squibb-type urinometer routinely used in many
laboratories is often inaccurate and may
give misleading results unless care is taken
to avoid error. The calibration figures for
these instruments are often printed on
paper inserts fitted into the glass stem which
protrudes above the surface of the
speci-men. The insert may loosen and slip up or
clown within its glass Ilousing, thus causing
faulty readings. Testing the instrument
against distilled water as a control prior to
each determination will help reveal such
artefacts. Reading should be carried out in
a consistent fashion with respect to
manipu-lation of the apparatus and eye position in
relation to the meniscus. For special
accuracy marked deviations in temperature
of the specimens from that at which the
instrument is calibrated (usually 25#{176}C.)may
be allowed for by adding 0.001 to the
read-ing for each 3#{176}C.by which the specimen
differs from the calibration temperature.’6
By making appropriate dilutions with
distilled water as suggested by Heplar,’6
volumes as small as 4 to 6 ml. may be tested
although such dilutions were not necessary
in evaluating the urines of our patients with
diabetes insipidus. The falling-drop method
of determining specific gravities of small
quantities of urine described by Barbour
and Hamilton’7 might be utilized nicely in
studies of this type on infants.
Ames8 has relied upon volume changes
of urine-output alone in demonstrating
existence of an antidiuretic response to
in-travenous pitressin in infants over 3 days of
age. We have found such volume changes
very difficult to evaluate because of the extreme variability in volume-output
some-times seen during a control period or
fol-lowing administration of pitressin without
concomitant changes in specific gravity to
signify ability of the kidneys to concentrate.
The observation that a decrease in volume
of urine-output can occur in the absence of
appropriate rise in concentration suggests the possibility that these 2 aspects of renal activity may function independently of one
another in the infantile kidney even though,
as Heller’8 points out, no such dissociation
has been observed in normal subjects. As
urine volume may be expected to vary
in-versely with tubular solute reabsorption and
concentrating capacity and directly with
glomerular filtration, it is somewhat
diffi-cult to assess output changes in the light of
any one of these factors without due regard
to the others.
ORIGINAL ARTICLES 431
the nephrogenic type whereas true diabetes
insipidus is usually acquired after infancy.
This is in contrast to the observations of
Forssman’#{176} who writes that the hereditary
type of true diabetes insipidus is also a
lifetime disease present in most instances
from birth. Blotner’9 states that true
dia-betes insipidus is commonly observed in children at 2 or 3 years of age. In his cx-tensive review of 112 cases only 2 were
oh-served during the first 2 months of life. In
either type the condition may go
un-noticed or undiagnosed in small infants because of the unavailability to such
pa-tients of large quantities of fluids and the
difficulty in assessing the volume of urine output during tile diaper-wearing stage. Such were the circumstances with tile
pa-tients described in this report and the
his-tory of polydipsia and polyuria was
ob-tamed in retrospect only after the diagnosis
had been established. It is not unlikely
that the condition may occur with
con-siderably greater frequency than is now appreciated.
SUMMARY
1. Two cases of congenital diabetes
illsi1)idus resistant to pitressin, or diabetes
insipidus of the nephrogenic type, occurring
in male cousins during infancy have been
described in which the most striking
mani-festations were recurrent pyrexia, polyuria, polydipsia, poor weight gain and develop-ment, and hyperelectroiytemia.
2. The basic defect in these patients
ap-pears to be renal; in the nature of an
end-organ failure to respond to the antidiuretic
hormone of the posterior pituitary body.
3. The demonstration of the trait in the
mothers of the patients and probably an
uncle and maternal grandmother suggests genetic transmission by means other than the previously postulated sex-linked re-cessive pattern.
4. The literature pertinent to this
condi-tion is reviewed and some of the clinical
features and diagnostic problems are dis-cussed.
NOTE: Since this paper was submitted for
publication, Mrs. N., the mother of Case
No. 1 has given birth to another male child.
Dr. Robert Reiheld of Orrville, Ohio,
re-ported that the baby was having bouts of
fever and dehydration. After the baby was
placed on a dilute high volume formula
containing low fat and protein with high
carbohydrate, the fever and dehydration
disappeared. The baby’s general condition
is reported good with a satisfactory weight
gain.
REFERENCES
1. Smith, H. W. : The Kidney. Structure and
Function in Health and Disease. New
York, Oxford, 1951, p. 241.
2. Williams, R. H., and Henry, C. : Nephro-genie diabetes insipidus transmitted by females and appearing early during in-fancy in males. Ann. Int. Med., 27:84, 1947.
3. Waring, A.
J.,
Kajdi, L., and Tappan, V.:A congenital defect of water
metabo-lism. Am.
J.
Dis. Child., 69:323, 1945.4. Dancis,
J.,
Birmingham,J.
R., and Leslie,S. : Congenital diabetes insipidus
resis-tant to treatment with pitressin. Am.
J.
Dis. Child., 75:316, 1948.
5. Behrendt, H. : Diagnostic Tests for Infants
and Children. New York, Interscience,
1949, p. 368.
6. Carter, A. C., and Robbins,
J.
: The use ofhypertonic saline infusions in the
dif-ferential diagnosis of diabetes insipidus
and psychogenic polvdipsia.
J.
Clin.Endocrinol., 7:753, 1947.
7. Hickey, R. C., and Hare, K. : The renal
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432 WEST - NEPHROGENIC DIABETES INSIPIDUS
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SPANISH ABSTRACT
Diabetes
InsIpida
Nefrog#{233}nica
La diabetes insIpida es un padecimiento
raro generalmente debido a lesion o alteraci#{243}n
funcional del mecanismo
supra#{243}ptico-neurohi-pofisiario que regula Ia excreci#{243}n urinaria a
trave de Ia hormona antidiur#{233}tica; cuando
#{233}stafalta, ci paciente no concentra Ia orina ni
conserva ci agua corporal durante los perlodos de deshidrataci#{243}n sino que contin#{241}a eliminando
grandes cantidades de orina diluIda.
La forma nefrog#{233}nica de Ia diabetes insIpida es ann menos comun; parece resultar de una
disfunci#{243}n primaria renal, m#{225}sque pituitaria,
por defecto b#{225}sicode desarrollo o inmadurez persistente de los tnbulos renales y como
con-secuencia ci organismo no retiene ci agua ni
responde a cantidades adecuadas de Ia hor-mona antidiur#{233}tica. El sindrome se caracteriza
por brotes incxplicables de ficbrc, constipaci#{243}n
persistente, v#{243}mitos durante los primeros mcses
de Ia vida, polidipsia, y poliuria que no
res-ponde a Ia pitresina. Tal es ci caso de los dos
pacientes que en este artIculo presentan los
autores; dos ni#{241}osdcl sexo masculino, primos
hermanos, con antecedentes familiares de
par-ticular inter#{233}spues el padecimiento se
en-contr#{243} en las madres (hermanas entre sI), Ia
abuela materna y un tb materno, dato que
sugiere transmisi#{243}n del rasgo como car#{225}cter gen#{233}ticoMendeliano dominante o simplemente
recesivo, no unido ai sexo como antes se
suponha. Ambos casos se hospitalizaron por Ia
persistencia inexplicable de la fiebre y escaso
aumento de peso; ya en estudio, se cncontr#{243}
adem#{225}s hipcrelcctrolitemia. Se Ics sujet#{243}a
dietas hipoproteinadas e hiposolutas, y
ad-ministr#{243} por via oral hormona pituitaria
pos-tenor; al forzar lIquidos se mejoraba Ia
hidrataci#{243}n y controlaban los episodios febriles
pero no se reducla Ia sed ni Ia cxcreci#{243}n
urinaria como corresponde a Ia medicaci#{243}n
hormonal. La respuesta a Ia administraci#{243}n de soluciones salinas hipert#{243}nicas por via
intra-venosa se resume en las figuras 1 y 2; en niflos
normales se observa antidiuresis marcada, lo que no mostr#{243}ninguno de estos dos pacientcs. La respucsta a Ia administraci#{243}n de pitresina se resume en las figuras 3 y 4; tambi#{233}n con-trasta con la observada en diez niflos normales estudiados con fines comparativos. Las madres de ambos ni#{241}os,ante Ia misma prucba de Ia
pitresina, no excretaron orina con gravedad
especIfica superior a 1.004.
Los ni#{241}oshan estado recibiendo formulas y
dietas que aumenten la ingestion de lIquidos y reduzcan Ia carga renal de solutos, segnn lo recomienda Talbot; ambos han mostrado mejorla, pero los brotes febrilcs continOan
apareciendo segnn ci grado de deshidrataciOn
que presenten. Actualmente se cncuentran
