THE HYPODIPSIA-HYPERNATRAEM|A SYNROME PRESENTING WITH OBESITY

David Powell, Mary Codd, Petr Skrabanek and Edward Tempany*

Endocrine Unit, Mater Misericordiae Hospitat, and *Our Lady's Hospital for Sick Children, Dublin.

Summary

Following a suspected viral infection 4 years previously, a 9~year-old boy developed obesity, hypodipsia, hypernatraemia, hyperosmolality and hyperprolactinaemia. The renal handling of sol- ute and water was normal, but there was a decreased sensitivity of hypothalamic osmorecep- tors to both hypernatraemia and water loading. Therapeutic trials with a thiazide diuretic, an aldosterone antagonist, bromocriptine, and. long- term sodium restriction with high fluid intake failed to maintain serum sodium and plasma osmolality within the normal range.

Introduction

The hypodipsia-hypernatraemia syndrome is a rare cause of chronic hypernatraemia. In adults, this hypothalamic syndrome usually follows vascular or infiltrative lesions. In children, con- genital CNS malformations (e.g., absent corpus callosum), tumours, histiocytosis, diffuse neur- onal degeneration of the hypothalamus and subarachnoida! haemorrhage have been associa- ted with this syndrome, which is frequently accompan.iec! by lethargy, retardation, attacks of muscular weakness, eating disorders, and lability of body-temperature regulation. (For a literature review of the hypodipsia-hypernatraemia synd- rome, see Shaad et al, 1979).

We report a case of hypodipsia-hypernatraernia in a 9-year-old boy, who presented with obesity.

Case Report

C.C., was born to a French father and an Irish mother. The family history was unremarkable. Two sisters, age 14 and 15, were normal. Birth weight was 7 Ib 3 oz. Patient's developmental milestones were normal. The patient presented at the age of 4 with a history of sudden weight gain. Immediately before the weight gain, the patient had a "viral infection" accompanied by lethargy, anorexia, and hypodipsia. Since this episode, the patient has had an impaired thirst sensation and drank only when encouraged to do so. By the age of 5 his weight was 29 kg (an increment of 12 kg in 12 months). Between ages 5 and. 9 his growth rate remained within the the high normal range and his bone age has become advanced by 1�89 years. The weight has remaine~ above the 97th percentile and at pre-

sent his weight is 46 kg. He is a bright boy who does well in school. The blood pressure has remained in the range 90/60-110/80 mm Hg. He has striae on the thighs, loins and abdomen. E.E.G. was abnormal, showing generalised dis- turbances (high voltage spikes and irregular slow waves) without Iocalising features. Except for a divergent strabismus there has been no other neurological abnormality.

The serum sodium has varied between 145 and 165 mmol/I and plasma osmolality between 305 and 341 mOsm/I. Serum potassium has been in the low normal range (2.8-3.7 mmol/ I ) . The initial haematocrit was 44.6%. The full blood count was normal, except for a lymphocytosis of 53%. Serum proteins, serum calcium and serum phosphate were normal. Serum urate was eleva- ted at 597 umol/I (normal = 120-420). Serum creatinine, urea, bilirubin, alkaline phosphatase, blood gases, and cholesterol were normal. SGOT was elevated on several occasions, with values between. 40 and' 97 IU/I (normal less than 40 IU/I) and, SGPT varied between. 60 and 102 IU/I (normal less than 35 IU/I). Serum, triglycerides were elevated at 2-2.5 mmol/I (normal 0.5-1.5).

Anterior pituitary function was normal, except for a mild elevation of basal plasma prolactin (300-400 mlU/I, normal less than 300 IU). There was a normal circadian variation in plasma cor- tisol. Urinary ketogenic corticosteroids and keto- steroids were normal. Thyroid function was normal. Urinary aldosterone was on one occasion 59 nmol/24 hours (normal 14-56). Growth hor- mone, follicle-stimulating hormone, luteinising hormone, thyrotrophin, prolactin and cortisol responded normally to stimulation with combined insulin/LH-RH/TRH.

Investigations in a neurosurgical unit, including skull X-rays, tomography of the sella turcica, pneumoencephalogram, carotid angiography, and CAT scan, showed no abnormality.

The creatinine clearance was normal (78 ml / min/m2). The concentration ability of the kidneys was normal. Urinary osmolality exceeded 1000 mOsm/I at a time when plasma osmolality was mildly elevated (300 mOsm/I), suggesting that there was adequate production of ADH. During the pitressin test (5 U, i .m) , there was an in- crease in urinary osmolality from 427 to 957 mOsm/I, while plasma osmolality remained in the range 339-343 mOsm/I.

357

358 Powel! e ta l .

W A T E R L O A D 150.o,~ODIUM mmol/I

130 OSMOLALITY rnOsrn/kg

305 295 285,

1100 t

700

30C

m I"--

o o o

r

=r

ill

300 "URINARY OUTPUT

200 m ~

100

P M A M

Fig. 1--The response of serum sodium plasma osmolality, and urinary output following a water load of 500 ml c4 5% glucose administered orally. The hatched areas for sodium and osmolality

represent the normal range.

Following a water load (500 ml of 5% glucose, orally) serum sodium and plasma osmolality became normal and urinary osmolality dropped from the initial value of 1100 mOsm/I to 80 mOsm/I. However, there was a marked delay in this response and an increased urinary output appeared only after 8 hours (see Fig. 1), sug- gesting a delayed shut-off of ADH secretion.

Stimulation of volume receptors by an infusion of 500 ml of normal saline had no effect on urinary osmolality or urinary output.

I . J . M S . September, lC83

Effects of Therapies

Diet severely restricted in sodium had no long- term effect on the hypernatraemia or plasma hyperosmolatity. A trial ot benzofluazide (2.5 mg on alternate days; Centyl K) was discontinued after 3 weeks when the initial sodium-lowering effect of the diuretic wore off. A course of

spironolactone (100 mg daily; Aldactone) brought serum sodium and plasma osmolality to within the normal range, but again, the effect was temporary and disappeared within a month. Bromocriptine (2.5 mg B.D.; Parlodel) lowered plasma prolactin to 40-50 mlU/I, but had no effect on serum sodium. Intranasal pitressin (30 ADH units T.I.D.; Di-Sipidin) increased the ex- cretion of urinary electrolytes, but had, no effect on serum sodium and plasma osmolality. Long- term increased fluid' intake, encouraged by the patient's mother at home, had no effect and the serum sodium has remained in the range 150-165 mmol/I.

Oiscusslon

It appears that the primary abnormality in this patient is an occult hypothalamic lesion, arising in the wake of a viral infection. Hypodipsia, obesity and hyperprolactinaemia are compatible with a hypothalamic d~sorder. Water load studies suggested: that there was an increased osmotic threshold, of hypothalamic osmoreceptors and a sluggish response of the osmoreceptors to a reduction in plasma osmolality.

We have found only 4 cases in the literature, in which obesity was a part of the hypodipsia- hypernatraemia syndrome, in the absence of an obvious anatomic hypothalamic lesion. Goldberg et al (1967) described" a 14-year-old girl with a sudden onset of obesity. The only evidence of a CNS abnormality was an elevation of CSF proteins and a diffusely abnormal EEG. In con- trast to our patient, the diluting ability of the kidneys was impaired. Travis et al (1967) stud- led a 6-year-old boy, who rapidly gained weight at the age of two. Autopsy revealed neuronal degeneration and' chronic inflammatory cells in the hypothalam,Js, and generalised organomeg- aly. Renal studies showed slightly impaired diluting capacity (max. dilution of 200 mOsm/l). The patient of Shaad et a~ was a 6-year-old boy, who developed obesity at the age of 3. However, he had psychomotor retardation since birth. The concentrating and diluting abilities of the kidneys were normal, but there was a delay in ADH inhibition following a water load. The hypernat- raemia was corrected by forced intake of 1500 ml water daily, which also ameliorated obesity, lethargy, hyperhidrosis and body-temperature labUHy. Blank and Farnsworth (1974) studied a 9-year-old boy, who had also a blunted response to water loading, similar to the patient of Shaad et at and the present patient.

The elevation of liver enzyme serum levels on our patient may be a part of the hypodipsia- hypernatraemia syndrome. Shaad et af (1979) reported elevated blood SGPT and SGOI" in their patient, who also had an abnormal liver biopsy. Liver dysfunction was also described in one adult case of hypernatraemia-hypodipsia (Maddy and Wintemitz, 1971 ). Hayek et al (1983) showed

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that hypernatraemia may by itself cause a fatty liver and hypertriglyceridaemia.

The hypothalamic abnormality in our patient probably involves the area of the ventromedial nucleus, since Stevenson et at (1950) showed that experimental lesions of this area in rats induce a similar syndrome, consisting of hypo- dipsia, hyperphagia, increased concentration of urine and delayed excretion of a water load.

References

Blank, M. S. and Farnsworth, P. B. 1974. Idio- pathic symptomatic hypernatremia in a 9-year- old boy. A clinical and physiological evaluation. J. Pediatr. 85, 215-219.

Goldberg, M., Weinstein, G., Adesman, J. and' Bleicher, S. J. 1967. Asymptomatic hypovol- emic hypernatremia. A variant of essential hypernatremia. Am. J. Meal. 43, 804-810.

The hypodipsia-hypernatraemia syndrome 359

Hayek, A., Bryant, P. D. and Woodside, W. F. 1983. Hyp.ernatraemia induces hyperlipaemia and a fatty liver. Metabolism 32, 1-3.

Maddy, J. A. and Winternitz, W. W. 1971. Hypo- thalamic syndrome with hypernatraemia and muscular paralysis. Am. J. Meal. 51, 394-402.

Shaad, U., Vassella, F., Zuppinger, K. and Oet- liker, O. 1979. Hypodipsia-hyponatremia syn- drome. Helv. Paediat. Acta 34, 63-76.

Stevenson, J. A F., Welt, L. G. and Orloff, J. 1950. Abnormalities of water and electrolyte metabolism in rats with hypothalamic lesions. Am. J. Physiol. 161, 35-39.

Travis, L. B., Dodge, W. F., Waggener, J. D. and Kashemsant, C. 1967. Defective thirst mechan- ism secondary to a hypothalamic lesion: Studies ir~ a child with adJpsia, poiyphagia, obesity, and persistent hyperosmolality. J. Pediat. 70, 915-926.