CASE REPORT

Niger J Paed 2014; 41 (2): 147 –150

Okpere AN

Anochie IC

Yarhere I

Central Diabetes insipidus in a

Nigerian child : A case report

DOI:http://dx.doi.org/10.4314/njp.v41i2,16

Accepted: 24th November 2013

Abstract Background: Central

diabetes insipidus (CDI) is rare in

children. About 30 - 50% of cases

are idiopathic. Early and accurate

diagnosis are crucial for safe and

effective treatment. This is the

first report of Central diabetes

insipidus in a child in Nigeria.

deprivation test followed by an in-

crease in urine osmolality from

59mOsm/kg to 158mOsm/kg and

serum osmolality from 286mOsm/kg

to 321Osm/kg following intravenous

administration of desmopressin. The

patient responded well to oral des-

mopressin.

(

)

Okpere AN

Anochie IC, Yarhere I

Department of Pediatrics,

University of Port Harcourt Teaching

Hospital,

PMB 6173, Port-Harcourt,

Rivers State, Nigeria.

E-mail:anokpere@yahoo.com

Tel: +2348059150818

Case report: We report a case of

central diabetes insipidus in a

female toddler who presented at

the University of Port Harcourt

Teaching Hospital with polydipsia

and polyuria with a urine specific

gravity of 1.000 and normal blood

sugar. The diagnosis of CDI was

confirmed by her inability to

Conclusion: Central diabetes in-

sipidus occurs in Nigerian children

and responds to oral desmopressin.

We recommended high index of sus-

picion in children with polyuria and

polydipsia.

Key words: Central diabetes

insipidus, polyuria, polydipsia, des-

mopressin, Nigerian child

concentrate urine after a water

Introduction

knowledge of the authors, no of case CDI has been re-

ported in children in Nigeria. We therefore report the

first case of CDI in a toddler in our centre in order to

share our experience and also to review available litera-

ture.

Central diabetes insipidus (CDI)is a heteregenous condi-

tion characterized by polyuria and polyd_-₃ipsia due to

1

deficiency of arginine vasopressin (AVP). It is a

rareendocrine disorder in children and results from the

destruction or degeneration of AVPsecreting neurons in

the supraoptic and paraventricular nuclei of the hypo-

thalamus or from impairment to the release or transport

of AVP. CDI may be idopathic, inherited or acquired.

Approximately 30 to 50% of cases of CDI are consid-

ered idiopathic. Congenital or inherited forms which are

very rare and may be due to genetic defects in the syn-

thesis of AVP that are inherited as autosomal dominant

or X-linked recessive traits. Acquired or secondary

causes include head trauma resulting from surgery or

accident; central nervous tumors such as germinoma and

craniopharyngioma; Langerhans’cell histiocytosis; cen-

tral nervous infections such as tuberculosis, meningitis;

autoimmune disorders andvascular lesio₁n_-₃s such as aneu-

rysms and arteriovenous malformations.

Case report

C.N was a two year eight month old female referred

from Federal Medical Centre, Yenegoa, Bayelsa State to

the Children’s Emergency Room of the University of

Port Harcourt Teaching Hospital (UPTH), Port

Harcourt, Rivers State with complaints of excessive

ingestion of water and urination of two months duration.

Onset of symptoms was gradual with excessive inges-

tion of water increasing from about 500mililitre (ml) per

day to 9- 10Litres (L) per day. She wakes up about 6-7

times at night to drink water and this usually disturbs

sleep. There was also increase in both frequency of uri-

nation and volume of urine voided; from1- 2 times to 10

-15 times during the day and from nil to 5-7 times at

night. There was no history of body swelling, poly-

phagia, fever, head trauma, chronic cough, weight loss,

seizures, use of nephrotoxic drugs or surgery prior to

onset of symptoms. She was initially treated in a private

clinic for malaria but with persistence of symptoms, she

was taken to the referral hospital. Random blood sugar

(RBS) done was 6.4mmol/L; urinalysis showed a low

specific gravity (S.G) of 1.005. She was subsequently

referred to UPTH with a presumed diagnosis of Diabetes

insipidus (DI). Pregnancy, birth, neonatal and develop-

mental histories were essentially uneventful. She is the

Deficiency of AVP causes excessive and uncontrolled

loss of water from the kidneys with resultant hypos-

thenuria, inordinate thirst and an increase in serum

osmolality. The complications which include dehydra-

4

tion, hypernatraemia and seizures are usually fatal.

Therefore, early recognition and accurate diagnosis are-

crucial to limit morbidity and mortality.

In Nigeria, Diabetes insipidus has been reported in

5

adults following burns andsurgery. To the best of the

1

48

second of three children (all females) in a monogamous

family. Mother is a 26 year old nurse and father is a 38

year old business man with tertiary education. There was

no history of similar symptoms in the parents, siblings

or close relatives.

was made based on the symptoms of excessive water

intake and urination, craving for water; persistent hypos-

thenuria, passage of large volume (11ml/Kg/hour) of

urine despite lack of oral input during the water depri-

vation test, absence of urine concentration on water dep-

rivation followed by an increase in urine and serum

osmolalilty following the administration of desmo-

pressin. The urinary tract infection was treated with oral

nitrofurantoin 25mg three times a day for 10 days.

On examination, she was conscious, calm, a febrile, well

hydrated with moist buccal mucosa with no loss of skin

tugor. Her weight was 15kg (115% of expected); height

was 96cm (108% of expected). Her radial pulse was

regular, full volume with a rate of 110beats per minute;

blood pressure was 80/50mmHg (which was normal).

Examination of the systems were essentially normal. A

bedside dipstick urinalysis showed a colourless urine

with a pH 6 and a very low S.G of 1.000 without glyco-

suria or proteinuria. Random blood sugar was 5.4mmol/

L (which was within normal range). An initial diagnosis

of Diabetes insipidus was made.

She was allowed free access to water and received des-

mopressin tablets (25mg twice a day initially then in-

creased to 50mg twice a day due to poor response. There

was reduction of urine volume to 2.5L during the day

and nil at night noticed on the second day of commence-

ment of desmopressin. Urine specific gravity also in-

creased ranging from 1.010 - 1.016 throughout the dura-

tion of hospitalisation. She was discharged after three

weeks of admission on oral desmopressin. She came for

follow up once one week after discharge. On follow up

visit, polyuria and polydipsia had reduced; urine fre-

quency had reduced to 1 -2 times during the day and nil

to once at night. Telephone conversations with the

mother revealed that child is alive, still on desmo-

pressin; polyuria and polydipsia had greatly subsided.

Serum electrolytes, urea and creatinine done on admis-

sion showed Sodium of 139mmol/L (normal range: 128

-

3

142mmo/L); Potassium of 3.7mmol/L(normal range:

.4 - 4.8mmol/L); Bicarbonate of 22mmol/L (normal

range: 24 - 30mmol/L); Urea of 2.2mmol/L (normal

range: 2.4 - 6mmol/L) and Creatinine of 40µmol/L

(

[

mOsm/Kg = 2 × serum Sodium (mmo/L) + serum Glu-

cose (mmol/L) + serum Urea (mmol/L)] was 286mOsm/

kg. Serum calcium was 2.2mmol/L (normal range: 2.1 -

2

limits showed a packed cell volume of 31%; white

blood cell of 6.2 × 10 ; neutrophils of 44%; lymphocyte

5

normal range: 60 - 120µmol/L). Serum Osmolality

calculated from the formula : serum osmolality in

6

Table 1: Biochemical parameters before and after water

deprivation test and desmopressin administration in the

patient with Central diabetes insipidus

Urine

.6mmol/L). Full blood count which was within normal

specific Urine

Plasma

Total volume

of urine

Parameter

gravity

osmolality osmolality

9

(

kg)

mOsmol/

(mOsmol/

kg)

6%; normal electrolyte sedimentation rate of 8mm/

voided

hour. Blood film was essentially normal. Urine micros-

copy and culture showed heavy growth of E.coli sensi-

tive to nitrofurantoin and ceftazidine.

Before water

deprivation

10 - 20ml/

kg/hr

1.000

-

286

After water

deprivation

After IV des-

mopressin

2030ml

(17ml/kg/hr)

125ml

1.000

1.010

59

289

321

Abdominal ultrasonography was normal showed that

both kidneys were normal in size, position and echo-

genicity with good corticomedulary differentiation.

There were no renal cysts or calculi. Radiograph of the

skull showed normal bones and sella turcica; there was

no abnormal lucency or calcification. Assay for serum

levels of AVP, Magnetic Resonance Imaging (MRI) and

genetic studies were not done due to unavailability of

such studies in our centre and environs.

158

(4.2ml/kg/hr)

Discussion

CDI is a form of polyuric polydipsic disorder which

occurs mainly due to lesions of the neurohypophysis or

the hypothalamuc median eminence resulting in defi-

A water deprivation test was done over six hours. She

was weighed two hourly throughout the duration of the

test. There was no change in the weight pre and post

water deprivation at 15Kg. Total volume of urine voided

was 2,030mls (11ml/kg/hour) and the urine S.G re-

mained 1.000.Serum and urine samples for osmolality

analysed at Pathcare laboratory showed that urine os-

molality was 59 mOsm/Kg and serum osmolality was

7

cient synthesis and or release of AVP. The clinical

manifestation of CDI is variable, depending on the ex-

tent of neuronal destruction. Usually 80 to 90% of the

magno- cellular neurones in the hypothalamus need to

7

be damaged before symptoms of DI arise. Polyuria and

4

polydipsia which are the essential features were present

2

86mOsm/Kg. Intravenous desmopressin 2µg was given

in the index patient. The onset of symptoms is usually

abrupt or sudden in CDI due to head trauma or neurosur-

gical interventions and gradual in other forms of non-

after the water deprivation test. Total volume of urine

voided 2hours later was 125ml (2.6mls/kg/hour); urine

SG increased to 1.010. There was increase in the urine

osmolality and serum osmolality to 158mOsm/kg and

8

trauma conditions. However, in some cases, CDI may

be a chronic complication of head injury or subarach-

3

21Osm/kg

9

noid haemorrhage. In the index patient, the onset of

respectively. The diagnosis of CDI in the index patient

symptoms was gradual and there was no history of

1

49

trauma or surgery. The age at present₄a_,t₈ion also varies

depending on the underlying aetiology. Severe neona-

tal forms are rarely described in children. In contrast,

hereditary Nephrogenic DI manifests in early infancy,

that plasma copeptin is a valuable surrogate of AVP

release in patients w₁₆ith the DI, exhibiting a promising

diagnostic potential.

4

,8

often before the age of 1 week. The familial autosomal

recessive formmay manifest at infancy while that due to

developmental_,₁d₀efects of midline brain structure may

MRI of the pituitary gland has emerged as another use-

ful addition to the biochemical tests in the diagnosis of

CDI. The physiological bright spot in the posterior pitui-

tary o the sella turcica is persistent in patients with Pri-

8

present early. Symptoms in the index patient devel-

17

oped at the age of 2 years and 6 months. Maghnie at

mary polydipsia and is absent inCDI. However, indi-

vidual cases of CDI with persistent pituitary bright spot

have been r₁e₈ported most likely due to an early stage of

the disease. Also, anage-related absence of the signal

1

al in Italy in a study of children with CDI reported that

the mean age at presentation were 6.4 years, 7.5 years

and 1.4 years for the idiopathic, secondary form due to

intracranial tumor and the familial forms respectively.

1

9

has been described in up to 20% of normal subjects.

Conversely in NDI, the brigh₀t spot is present in some

2

The clinical manifestations of CDI are due to deficiency

of AVP and disturbance in water metabolism. Excessive

loss of water from the kidney (polyuria) will result in

dehydration, hypernatraemia and a corresponding in-

patients and absent in others. Consequently, the role of

MRI as a diagnostic test in patients with DI remains to

be clarified. It has been suggested that MRI is a more

usefu₂l₁tool for ruling out than for ruling in a diagnosis of

CDI. A very similar conclusion also seems to apply to

measurements of thepituitary stalk, whose enlargement

beyond 2–3 mm has been considered to be pathological,

4

crease in serum osmolality. However, in ambulatory

patients with intact thirst mechanism and free access to

water, hypernatraemia and dehydration do not oc-

1

22

cur. This may explain the absence of dehydration, nor-

mal serum sodium levels and serum osmolality in the

index patient.

but not necessarily specific for idiopathic CDI. MRI

was not done in the index patient due unavailability of

the services in the hospital.

The water deprivation test (Miller-Moses test) together

with the intravenous administration of desmopressin are

useful in the confirmation of the diagnosis of CDI and

also to distinguish between Nephrogenic DI and Primary

The therapeutic goals of treatment of CDI are primarily

to reduce polyuria and decrease thirst so that the child is

able to grow adequately and maintain a normal life style.

Free access to water will facilitate maintenance of tonic-

4

8

polydipsia. In CDI, urine osmolality is usually less than

ity if the thirst mechanism is intact. The index patient

3

00 mOsm/kg after dehydrationand greater than 750

was allowed free access to water. Excess fluid intake in

the long te₃rm may lead to hydronephrosis and hy-

1

2

mOsm/kg following desmopressin administration. In

the index patient, the diagnosis of CDI was confirmed

based on the absence of urine concentration on water

deprivation followed by an increase urine and serum

osmolalilty following the administration of desmo-

pressin. Although, the urine osmolality was less than

2

droureters. The index patient did not have clinical or

radiologic evidence of hydronephrosis or hydroureters.

Desmopressin (1-deamino-8-D-arginine vasopressin,

dDAVP), an analogue of vasopressin, is the current drug

4

of choice for long-term therapy of CDI. It increases the

7

was more than a double-fold increase in urine osmola-

50 mOsm/kg after desmopressin administration, there

cellular permeability of the collecting ducts resulting in

an increase in water reabsorption and therefore mini-

mises water excretion. The index patient responded well

to oral desmopressin.

lilty from 59mOsm/kg to 158mOsm/kg. Simil₃ar finding

1

has been reported in children by Wong et al in Hong

Kong where the urine osmolality was less than 750

mOsm/kg post desmopressin administrationin all ten

children with CDI. A possible explanation to this is that

in long standing polyuria there is partial washout of the

medullary interstitial gradient and downward regulation

of AV₂ P release leading to defect in urinary concentra-

Conclusion

1

tion.

CDI would occur in Nigerian children and responds well

to oral desmopressin. We recommend a high index of

suspicion in children with polyuria and polydipsia as

early recognition and accurate diagnosis is crucial to

both safe and effective disease treatment.

The urinary concentration test is an indirect measure of

AVP activity. The combination of the water deprivation

test and direct AVP determination would allow the

diagnos₄is of more than 95% of all cases of CDI cor-

1

rectly. However, AVP assay has failed to be a diagnos-

tic reference standard to date due to its methodological

limitations of a very short half life of 10 -30 minutes,

high pre analytical ins₅tability and high turnaround time

Authors' contributions

All three authors participated in the management of this

patient; prepared and approved the final version of the

manuscript.

1

in most laboratories. More recently plasma copeptin

levels have been studied as a surrogate marker of AVP

in the differential diagnosis of DI. Copeptin, the

Conflict of Interest: None

Funding: None

1

6

C-terminal part of the AVP precursor, co-secreted with

AVP is much easier to measure. It was demonstrated

1

50

References

1

.

Maghnie M, Cosi G, Genovese E,

Manca-Bitti ML, Cohen A, Zecca

S, et al. Central diabetesin-

sipidusinchildrenandyoung adults.

NEJM 2000; 343:998–1007

Wang LC, Cohen ME, Duffner

PK. Etiologies of central diabetes

insipidus in children. Pediatr Neu-

rol 1994; 11:273–277

Hansen LK, Rittig S, Robertson

GL. Genetic basis of familial neu-

rohypophyseal diabetes insipidus.

Trends Endocrinol Metab

10. Siggaard C, Christensen JH, Cory-

don TJ, Rittig S, Robertson GL,

Gregersen N, et al. Expression of

three different mutations in argin-

ine vasopressin gene suggests

genotype-phenotype correlation in

familial neurohypophyseal diabe-

tes insipidus kindreds. Clin Endo-

crinol (Oxf) 2005;63:207–16.

11. Schulman SL. Polyuria and Uri-

nary Frequency.In: Scfwartz MW,

editor. Clinical Handbook of Pedi-

atrics, Maryland: Lippincott Wil-

liams and Wilkins:2003: 293 - 321

12. Baylis PH, Cheetham T. Diabetes

insipidus. Arch Dis Child

18. Maghnie M, Genovese E, Bernas-

coni S, Binda S, Arico` M. Persis-

tent highMRsignal of the posterior

pituitary gland in centraldiabetes

insipidus. Am J Neuroradiol 1997;

18:1749–1752

19. Brooks BS, el Gammal T, Allison

JD, Hoffman WH. Frequencyand

variation of the posterior pituitary

bright signal onMRimages. AJR

Am J Roentgenol 1989; 153:1033–

1038

20. Maghnie M, Villa A, Arico M,

Larizza D, Pezzotta S, Beluffi G,

Genovese E, Severi F. Correlation

between magnetic resonance imag-

ing of posterior pituitary and neu-

rohypophyseal function in children

with diabetes insipidus. J Clin

Endocrinol Metab 1992; 74:795–

800

21. Verbalis JG. Disorders of water

balance. In: Taal MW, Cher-

towGM, Marsden PA, Skorecki K,

Yu ASL, Brenner BM, eds.Brenner

and Rector’s The Kidney, 9th ed,

Philadelphia:Saunders;2011: 552–

569

22. Leger J, Velasquez A, Garel C,

Hassan M, Czernichow P. Thick-

ened pituitary stalk on magnetic

resonance imaging in childrenwith

central diabetes insipidus. J Clin

Endocrinol Metab1999; 84:1954

1960

23. Muglia LJ, Majzoub JA. Disorders

of the posterior pituitary. In: Sper-

ling MA, editor. Pediatric Endocri-

nology. 3rd ed. Philadelphia: Saun-

ders; 2008: 356–73.

2

3

.

1

997;8:363-72

4

.

Harris WH. Diabetes insipidus. In:

Behrman RE, Kliegman RM,

Jenson HB, editors. Nelson Text-

book of Pediatrics, WB Saunders

Company, Pennsylvania, 2000:

1998;79:84 – 89.

13. Wong LM, Man SS. Water depri-

vation test in children with polyu-

ria. J Pediatr Endocrinol Metab.

2012; 25: 869-74

1

681-1683

5

6

.

Onilede DA, Olawoye OA,

Ipadeola A. Diabetes insipidus - a

rare complication of flame burn: a

case report. NJPS 2013; 9: 42-45

Kennedy TL. Electrolyte Distur-

bances. In: Schwartz WM, editor.

Clinical Handbook of Pediatrics,

Maryland:Lippincott Williams and

Wilkins;2003: 293 - 321

1

4. Verbalis JG. Disorders of body

water homeostasis. Best Pract Res

J Clin Endocrinol Metab

2

003;17:471–503

1

5. Katan M, Morgenthaler NG, Dixit

KC, Rutishauser J, Brabant GE,

Muller B, et al. Anterior and poste-

rior pituitary function testing with

simultaneous insulin tolerance test

and a novel copeptin assay. J Clin

Endocrinol Metab. 2007;92:2640–

7

8

.

Heinbecker P, White HL. The role

of the pituitary gland in water bal-

ance. Ann Surg 1939; 110:1037–

1

049

Mishra G,Chandrashekhar SR.

Management of diabetes insipidus

in children. Indian J Endocrinol

Metab 2011; 15(Suppl3): S180–

S187.

Hannon MJ, Sherlock M, Thomp-

son CJ. Pituitary dysfunction fol-

lowing traumatic brain injury or

subarachnoid haemorrhage - in

3

.

1

6. Morgenthaler NG, Struck J,

Jochberger S, Du¨ nser MW. Co-

peptin:clinical use of a new bio-

marker. Trends Endocrinol Me-

tab2008; 19:43–49

9

.

1

7. Moses Am, Clayton B,

Hochhauser L. Use of T1-weighted

MR imaging to differentiate be-

tween primary polydipsia and cen-

tral diabetes insipidus. AJNR Am J

Neuroradiol 1992; 13:1273–1277

"Endocrine Management in the

Intensive Care Unit". Best Pract

Res Clin Endocrinol Metab2011;

2

5:783-98