Indian]. I'ediat. 31~: 279, I97t

CHLORPROPAMIDE IN DIABETES INSIPIDUS*

Report o f a Case

V.P. CHOUm~RV

New Delhi

Diabetes insipidus of the cenlral (t~eurohypophyseal) type is treated with replacement therapy by vasopressin. Its repeated administration as injections cztuses discomfort and anxiety, parti-

t:ularly in children, while other routes of administration are unsatisfactory. File drug, unfortunately, is not readily available in Ind ia . The introduction of thiazide derivatives marked an advance in the m a n a g e m e n t of diabe- tes insipidus. Recent ly Ardunio et a l

(1966) showed a beneficial action of the antidiabetie drug chlorpropamide

in this disorder. Successflfl symptomatic

management of diabetes insipidus with ehlorwopamide in an eleven-year-old girl is reported here.

Report of a Case

S.B., an l l -year-old gM, was

admit ted on 19th J anua ry , 1970, to the

All-India Institute of Medical Sciences

Hospital, with the history of polyuria

and polydipsia of 3 years ' duration. She used to drink about 3-4 litres of water per day and had to go to the toilet several

times during the night. These symptoms had started following a short febrile

illness, lasting for 3-4 days, which was unassociated with headache and visual or neurological symptoms. The past and family history was insignificant.

*From the Department of Pediatrics, All-India !nstitutc of Medical Sciences, New Delhi-16. [(cceived on January 15, x 97 I.

Examinat ion revealed a well-nou-

rished young girl weighing 30 kg. with a height of 128 cm. Systemic examina-

tion was essentially unremarkable except

that her bladder was palpable 3 cm. above the pubic symphysis even after

voiding urine. The optic fundi were

normal . Perimetry was also normal.

Her fluid intake varied between 3-4

litres/day while the output was between

2.5-3.5 litres/day. The urine specitic

gravity varied between 1002 and 1004. The haemoglobin was 11.2 G.~ total and differential leukocyte c o u n t s were normal. Serum sodium varied between

140-142 mEq/litre while serum potassium varied between 4.2-4.5 mEq/litre. Fast- ing and postprandial blood sugar values

were 80 mg.% and92 rag.% respectively.

Serum calcium was 10 rag.%, phosphorus 3.1 rag.% and alkaline phosphatase 15.0 K.A. units. Liver function tests were normal. Intravenous pyelography showed a distended bladder with dilated ureters

on both sides. An X-ray of the skull was

normal .

Following water deprivation for 18

hours, during which the child lost 1.7 kg. in weight, the urine specific gravity remained at 1004. During a hypertonic saline infusion (Carter and Robins 1947) there was no change in the urine flow and urine specific gravity. On adminis- tration of 5 units of Pitressin tannate

(Parke-Davis and Co.) subcutaneously tho,

280 INDIAN JOURNAL OF PEDIATRIGS VOL, 38, No. 281

24-hour urine volume came down to

500 ml. and the specific gravity rose to

1020. The child was administered 375

rag. of chlorpropamide daily before

breakfast. The daily urine output was

reduced by about 60% and there was a

significant rise in urine osmolality. Both

of these returned to the pretreatment

values on withdrawal of the drug (Fig. 1).

She was advised to take 375 rag. of

chlorpropamide daily. She has been

followed for the last one year, during

which the symptomatic improvement has

been maintained. No symptoms of hypo-

glycaemia or drug toxicity were seen

and he blood sugar values have been

normal.

Discussion

The patient presented herself with vasopressin sensitive diabetes insipidus for which no apparent cause was found. Chlorpropamide administration resulted in a reduction of urine volume with an increase in urine osmolality. The delay in the peak antidiuretic action was presumably because of oral administra- tion of the drug, The antidiuretic effect of chlorpropamide in pitressin deficient

patients is now well established (Vallet el al. 1970) but the mechanism of anti- diuresis remains unknown. A decrease in urine output along with a rise in urine

osmolality to values slightly more than that of plasma can be achieved by an extreme reduction in glomerular filtra-

300

uRiNE 2O0

OSMOLALtTY 100

(~ Osm/k~l) 0,

4 '

3. Z4-hr. URINE

2, VOLUME

(ti~,.) t ,

30.5- WEIGHT 30. (wg)

29,5,

HOSPITAL DAY

Fig. I.

-t

29. CHLORPROPAMIDE

375 ,~. DAILY

The effect of chlorpropamid.e on the urine volume and urine osmolality.

CI-IOUDHRY~CHLORPROPAMIDE IN DIABETES INSIPIDUS 281

tion rate even in the absence of anti- diuretic hormone (Berliner and Davidson 1957). However, Ehrlick and Kooh (1970) showed that the glomerular filtra- tion rate increased during chlorpropa- mide therapy because of improved hydra- tion. Recently Vallet et al. (1970) pro- posed that the antidiuretic action of chlorpropamide may be due to an en- hancement of the sensitivity of the renal tubules to small amounts of vasopressin which might still be present. The drug could also act by inhibiting the enzyme system responsible for degradation of the antidiuretic hormone. It is note- worthy that chlorpropamide is without any effect in nephrogenic diabetes insi- pidus (Ardunio et al. 1966), in whch condition the thiazide derivatives have a significant antidiuretic action.

Summary Chlorpropamide effectively con-

trolled the symptoms of diabetes insipidus

in an eleven-year-old girl. No side effects were encountered over a one-year period of follow up.

I am thankful to Dr. R.N. Srivastava and Professor O.P. Ghai for constant guidance and encouragement.

R eferen ces

Arduino, F., Ferraz, F.P. and Rodrigues, J.

(I966). Antidiuretic action of chlorpr0pamide in diabetes insipidus. 07. Glin. Endoer. 26, I325.

Berliner, R.W. and Davidson, D.G. (x957). Production of hypertonic urine in the absence of pituitary antidiuretic hormone 07. Clin. Invest. 36, I416.

Carter, A.C. and R)bins, J. (t9-t7). The use of hypertonic saline infusion in the differen- tial diagnosis of diabetes inslpidus and psychO- genic polydypsia. 07. Clin. Endocr. 7, 753.

Ehrllch, R.M. and Kooh, S.W. (x97o). The use of chlorpropa~nide in diabetes iasipidus

in children. Pediatrics, 459 236. Vallet, H.C., Prasad, M. and Goldbloo, B.

Richard (i97o). Chlorpropamide treatment of diabetes insipidus in children. Pediatrics. 45,

246.