Central diabetes insipidus as a complication of neonatal pathology: Report of three cases

Acta Paediatrica Japonica (1 998) 40, 146-1 49

Patient Report

Central diabetes insipidus as a complication of neonatal pathology: Report of three cases VERA LGCIA JORNADA KREBS. DURVAL DAMIANI, EDNA MARIA DE ALBUQUERQUE DINIZ. MARIA ESTHER CECCON, CKISTINA YOSHIMOTO, IARA FLAVIA AGUIAR, NCVARTE SETIAN. JOSE LAURO A R A U J O RAMOS AND FLAVIO ADOLFO COSTA VAZ Nrc~nrrftrllritrri 511 11 Coie Urirr triirl Perlrtiri i i Eiidoc riiie Uiirt, h i \trtuto { ( h0Ol Of

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Abstract

Three patient\. I 1. 17 and 41 days old with mrious degrees of central nervous system (CNS) lesions dz\ eloped central diabetes insipidus a s ii complication of hypothalamic damage. Two of the children had congenital CNS malfomiations including meningomyelocele, hydrocephalus. and prosencephaly, while the third child presented Sfr-~,~el,toc.oc.c.ir.rc c g d m i o r meningitis. complicated with CNS hemorrhage and h! pertensive dilatation of the lateral ventricles. All of them fulfilled the criteria for central diabetes insipidus, reaching high le\els of serum sodium and osmolality. along with hypotonic urine. The responses to intran were prompt. nornialiiing the serum levels of sodium and increasing urinary osmolality, ~irzininc-~a.lopressin allou ing ii better metabolic balance. avoiding continuing damage to the already compromised CNS. The neonatologist must he aware of the pos4bility of this kind o f complication even in a normal child with CNS infection. Imaging studies showing hemorrhage in the region of the posterior hypothalanius must be a sign that this type of complication is able to occur.

Key words

antidiuretic hormone. diabete4 insipidus. hydrocephalus. meningitis. neonate.

Central cliabetes inhipidus (('DI) i h ;I distrirbance characrel-i/eci b\ cxcesi\e renal \barer loss causcd by antidiuretic hormone ( A D H ) deficiency. I i can be primary (idiopathic. sporadic o r f;rmilial) or follow diseases that affect the li!pothalamc~-lii~iilar) axis. namely brain tumors. central ner\wis \ystem tC"SI tnalf~~rmations. inflammatory lesion\. or infections.' I n the neonatal period. there h a w been reports . a\sociated Lvith CNS pathologies. Giacoia P I ( I / . . ' i n ;I rc\ ie\v from 197-1 to 1984. reported nine patients itli ihc clinical picture of C'DI between 1 and 30 days of azc. Wxis P I "[..' i n ;i I -3-b~iirretrospectiw stud!. carried ~ i i i n 1904. reportccl 35 CDI children xlmitted ;it the Children's Hospital of' BufiJo. 8.5% o f whom nwe neonates. Although i t i \ lei-> rare in the neonatal period or in i n t h c y . bein2 repoitrd onl> i n c x s e i n Lvliich there is dcstruction of magnocrllular neurons in the neurohypophysis. it c;tn \iorwn the prognosi4 of the basic disease. 2s the hyperosinolali th often induce\ pemianent neurologic sequelae.

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An early diagnosis, together with proper management, will avoid maintenance of a hypernatremic state that. in this age group. leads to brain damage. Eventually, the clinical maniiestations are not limited to ADH insufficiency but involve other neuroendocrine and hypothalamic filnctions, giving rise to a great variety of clinical presentationsi and even imposing some extra risks when thernioregulation o r appetite control are at stake. The aim of the present paper is to report three cases of CDI in young children, emphasizing the risk of this complication in congenital CNS inalforniation andor bacterial meningitis. Early recognition o f the disorder and its proper iiianagement are of extreme importance because of the great metabolic liability of children in this age group. Informed consent was obtained from all parents.

Patient report Case 1

Corrc~pontleric~: Lcr;i L cia Jornada Krehs. Rua Crisriano Viana. KO 150.AP. 127 Jardim A n 1 rica. S o f'aulu. SP. Brasil. Kecci\cJ X J a n i i a i - > 1907: revijion 5 August 1997: accepted 8 .Atlgu\t 1907.

An 1 I-day-old white girl born weighing 3150 g presented with hydrocephalus, meningomyelocele, and congenital clubfoot. The meningomyelocele was infected, leaking pus

C D I in neonates

147

Table 1 Serum sodium, serum and urinary osmolality, urinary output, and urinary specific gravity before and after desmopressin therapy

Case ( s t d e n d ) 1

Serum sodium (mEqL) Serum osmolality (mOsm/kg H,O) Urinary output (mL/kg/h) Urinary osmolality (mOsdkg H,O) Urinary specific gravity (g1rnL)

1511147 3 121296

9.015.0 -1100511010

for 2 days and antibiotics were started, followed by surgical correction. In the follow-up she had ventriculitis, externally derived. On the 25th hospital day she was dehydrated, with a serum sodium of 151 mEq/L, osmolality of 312 mOsmkg H,O, urine output of 9 m L k g per h, urine specific gravity of 1005 and urinary sodium of 5 mEq/L. Started on intranasal arginine vasopressin (DDAVP), 0.0125 mL (0.25 p g k g per dose) every other day, she normalized serum sodium levels as well as urinary output 4 days later. The medication could be stopped on the 33rd hospital day and she was discharged at 84 days of life. On cranial computed tomography (CT) there was dilatation of the lateral ventricles, and a wide inter-hemispheric cysternae. Case 2

A 17-day-old white girl was born weighing 2950 g and admitted because of cyanosis from 3 days of life. She presented prenatally diagnosed with hydrocephaly, low-set ears, cleft palate, and malformed hand and foot digits. Cranial ultrasound and CT scan displayed prosencephaly. Dehydration, cyanosis, and hypothermia followed, with Na = 156 rnEq/L, serum osmolality of 324 mOsmkg H,O, urine output of 7.2 m L k g per h, urine osmolality of 128 mOsm/kg H,O, urinary Na = 18 mEq/L. Besides dehydration, hypernatremia and polyuria persisted and she was started on intranasal DDAVP on the 10th hospital day (0.0125 mL or 0.25 pg/kg per dose). After 48 h, sodium levels normalized and she was discharged on the 42nd postnatal day, receiving alternate-day doses of DDAVP.

2 1561137 3241283 7.214.9 1281314 100511005

3

1651148 34 I I298 5.412.8 1611100011010

days, respectively. Cranial ultrasound was normal on the first hospital day but, on the seventh hospital day, showed hemorrhage in the basal ganglia and, on the 17th hospital day, dilatation of lateral ventricles. The C T scan on the 20th hospital day showed hypertensive dilatation of lateral ventricles, faded cortical convolutional impressions, mainly on the right side, sub-dural bilateral fronto-temporal and left interhemispheric effusion, as well as hypo-attenuated areas in the basal ganglia, mainly on the left side. On the ninth day of admittance, Na = 155 mEq/L and rose to 171 mEq/L on the 10th hospital day, with a urine output of 5 m L k g per h. Hydration with a 15 mEq/L solution was ineffective in lowering the sodium level that, on the 28th hospital day, was 165 mEq/L, serum osmolality = 341 mOsmkg H,O, urinary sodium of 9 mEq/L, urinary osmolality of 161 mOsmkg H,O, and urine output of 5.4 m L k g per h. Started on intranasal DDAVP 0.0125 mL (0.25 p g k g per dose) once a day, sodium levels lowered to 148 mEq/L, urine output became 2.8 m L k g per h with a urinary specific gravity of 1010. She was discharged on the 120th postnatal day, receiving DDAVP twice a week. The criteria for CDI used in these newborn infants were the following: dehydration, hypernatremia, polyuria, high serum osmolality and hypotonic urine. The response to intranasal arginine-vasopressin was analyzed to confirm the diagnosis. Each of the patients had evidence of CNS involvement on CT; magnetic resonance imaging of the posterior pituitary was not available. Serum sodium levels, serum and urinary osmolality, urinary output, and urinary specific gravity before and after desmopressin treatment are shown in Table I .

Case 3

A 41-day-old white girl was born weighing 3990 g and came to the hospital because of fever, vomiting and irritability since the previous day, being diagnosed Streptococcus agalactiae (group B) meningitis. Having been started on penicillin and ceftriaxone, she presented with seizure spells from the first day of admittance, and was non-responsive to phenobarbital. Continuous intravenous infusion of midazolan and mechanical ventilation were needed for 12 and 10

Discussion Central diabetes insipidus is a rare clinical condition characterized by polyuria, thirst, polydipsia, and serum hyperosmolality. Because of ADH deficiency, the renal collector system is not permeable to water, avoiding the osmotic equilibrium between the hyperosmolar renal medulae and the hypo-osmolar urine. Magnocellular neurons from supra-

148 V Krebs et (11. optic and paraventricular hqpothalamic nuclei may be destroyed by malt'ormations. hemorrhage. infiltration, or infections and give rise to a clinical picture easier to detect on an older child than o n a neonate. Central nervous system sequelae and even death ma) follow prolonged hyperosmolality. After a tirst phase of destruction. a second phase where ADH is inappropriately secreted can follow, giving rise to a dangerous hyponatremia with cerebral edema. A third phase puts the child back to a state of ADH deficiency.' In neonates, as well as in adults, the three-phase response may be seen. and deserves special attention to avoid. in the phase of eucessivc ADH release. cerebral edema. In children, intracranial tumors, especially after surgical removal. are the most frequent etiology. Greger et a / . studied 73- CDI children (none of whom were in the neonatal period) retrospectively from 1962 to 1983 and showed CNS tumors in 49.6%. intracranial malformation in 13.7%. idiopathic causes i n 12.4%. CNS infections in 11%. histiocytosis in 8.2%. cranial traunia and mixed etiologies in 2.7% of cases.' Some authors have reported CDI in children under I year of ape. with severe CNS lesions or brain death secondary to metabolic encephalopathy." sudden infant death syndrome.' herpetic encephalitis o r traumatic brain hemorrhage.x In the neonatal period CDI is 3 rare occurrence, with sporadic case reports. more often caused by congenital CNS malformations." intra-ventricular hemorrhage."'-" perinatal asphyxia.?.12.1;cytomepaly," toxoplasmosis,' and bacterial meningitis.".." In all of the present cases. structural CNS lesions were demonstrated on ultrasound and computed axial tomography. I n 1974. Fenton and Kleinman described a Listri-iti i i i o i z o c ~ t o ~ e isepsis i ~ . ~ on a newborn. associated with CDI.Ix Since then. there have been isolated reports of B meningitis and CDI."-" '').'" neonatal Stre~~t~)(,~)(,~,i/.r One patient. case I , had tivo risk factors for CDI: CNS malformation and infection. The clinical picture began on the 25th day of hospitalization. with prompt commencement of desniopressin that elicited a good response (Table 1). with resolution of the process on the 33rd hospital day, characterizing a transient CDI. Patient number 2 showed hypernatremia from admission. when she was 17 days old. characteri/ing an early presentation of CDI. Similar to patient number 1. this child had hydrocephalus, a condition very often associated with ADH deficiency. Jackson and Carson"' reported one case of CDI in a 7-month-old infant with marked dilatation of the lateral ventricles and fusion of the anterior horns with a porencephalic cyst close to the right frontal horn in the absence of obstruction to cerebrospinal Ruid flow. In cases of midline defects. the affected structures have included hypophy\is. hypothalamus. septum pellucidum. optic nerLe. c o i p s callowin. and Sylvius aqueduct." As the anterolateral region of the third ventricle is the osmoreceptor site. anomalies involving this region have given the anatomic

basis for osmoreception d e r e g ~ l a t i o n .Prosencephaly, ~ also present in this patient. was reported by Wang' in three children. Hydration with hypotonic solutions on the first 10 days did not improve the hypernatremia and polyuria, which reached normal values 48 h after desmopressin treatment, maintained after hospital discharge, and characterizing a permanent CDI. The third patient, case 3, had Streptococcus ngalactiae meningitis. with stormy evolution caused by seizures and the need for mechanical ventilation. She had hypernatremia and polyuria from the 9th admittance day. There was no response to hydration with hypotonic solutions and treatment with desmopressin after 19 days normalized serum levels of sodium and the urinary output. She was discharged at 4 months of age, receiving DDAVP twice a week. Bacterial meningitis is a very rare cause of CDI, with the exception of tuberculous etiology." There have been some reports in children 1-5 years old with Henuiphilus in.ueiizae, StreptococcLis piieumoriiae and group €3 Streptococcus meningitis developing CDI.'.?'.23 It has been suggested that Sri-eptococcvs B causes hypothalamic infarction" and this could be the cause of CDI. Pai et al.I7 describe a neonate with hydrocephalus and external ventricle-peritoneal derivation leading to hypothalamic dysfunction characterized by defective thermoregulation and endocrine abnormalities. One of the present patients (case number 3) had CNS hemorrhage in basal ganglia as well as ventricular dilatation along with other brain lesions. Signs and symptoms of CDI may be difficult to recognize in neonates, which makes a diagnosis very difficult in this age group. The disease has been reported in full-term neonates as well as in prematures, with similar clinical manifestations. The combination of significant weight loss, hypernatremia, and increased urinary output with low urine osmolality strongly suggest ADH deficiency.' The short w'ater deprivation test as well as vasopressin concentrations in blood or urine may be done to determine the etiology of the process. In the current patients we analyzed the DDAVP response, avoiding water restriction because it poses risk of dehydration to children at this age. There was a rapid improvement in sodium levels, urinary volume, as well as urinary specific gravity or urinary osmolality after DDAVP. It is important to pay close attention to the association of CDI with other pituitary deficiencies, especially those involving adrenocorticotropic hormone (ACTH), leading to adrenal insufficiency. In this situation, the diabetes insipidus is somehow attenuated by the lack of cortisol, a hormone responsible for free water clearance. The adrenal insufficiency is a life threatening situation per se and needs to be treated as soon as diagnosed. Otherwise, at the moment we supplement glucocorticoid, the diabetes insipidus will become more evident. with increased urine output and greater risk of hyperosmolar dehydration. It is wise not t o have wide

CDI in neonates oscillations in plasma osmolality, and a variation of up to 12 mOsm/kg H,O per day is admittedly safe in this respect. Although some- authors did not advise the use of desmopressin supposing it to cause transient defects,24 we have seen that the metabolic consequences are sufficiently important to warrant prompt correction, and can be safely achieved with appropriate doses of desmopressin.

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