Arch Dis Child 1998;79:431–434 431 Hypertonic saline test for the investigation of Arch Dis Child: first published as 10.1136/adc.79.5.431 on 1 November 1998. Downloaded from posterior pituitary function Angelika Mohn, Carlo L Acerini, Timothy D Cheetham, StaVord L Lightman, David B Dunger Abstract (ADH) concentrations. The test is well estab- The hypertonic saline test is a useful tech- lished in adults56 yet there is little reported nique for distinguishing partial diabetes experience of its use in children. insipidus from psychogenic polydipsia, We describe five cases in which the hyper- and for the diagnosis of complex disorders tonic saline test provided a clear diagnosis of of osmoreceptor and posterior pituitary various disorders of water balance where function. However, there is little infor- standard diagnostic procedures had failed or mation concerning its use in childhood. were deemed unreliable. The experience of using this test in five children (11 months to 18 years) who pre- Methods and materials sented diagnostic problems is reported. In All the tests were performed at the John two patients, in whom water deprivation RadcliVe Hospital, Oxford and informed con- tests were equivocal or impractical, an sent was obtained from the patients and/or inappropriately low antidiuretic hormone their parents. Before testing, each patient was (ADH) concentration (< 1 pmol/l) was assessed to exclude the presence of any demonstrated in the presence of an ad- confounding factor such as hypercalcaemia, equate osmotic stimulus (plasma osmola- hypokalaemia, glycosuria or any other cause of lity > 295 mosmol/kg). In two children— a solute diuresis. Free access to food and fluids, one presenting with adipsic hyper- to maintain adequate hydration, was allowed natraemia and the other with hyponatrae- until the morning of the tests. mia complicating desmopressin treat- ment of partial diabetes insipidus— WATER DEPRIVATION TEST defects of osmoreceptor function were A seven hour water deprivation test was carried identified. Confirming a diagnosis of idio- out between 08:30 and 15:30 using a standard pathic syndrome of inappropriate ADH procedure.7 The test was terminated before secretion (SIADH) was possible in a seven hours if urine osmolality concentrated to patient with no other evidence of pituitary > 750 mosmol/kg, if weight loss exceeded 5% dysfunction. The hypertonic saline test of initial body weight, or if the patient http://adc.bmj.com/ was well tolerated, easy to perform, and developed intolerable thirst. diagnostic in all cases. (Arch Dis Child 1998;79:431–434) DESMOPRESSIN TEST Keywords: hypertonic saline test; disorders of water An eight hour desmopressin test (DDAVP; balance; diabetes insipidus Ferring, Middlesex, UK) was carried out between 08:00 and 16:00. The child was weighed and urine osmolality was measured on September 23, 2021 by guest. Protected copyright. Department of The diVerential diagnosis of polyuric states before an intramuscular injection of desmo- Paediatrics, John using standard diagnostic procedures such as pressin (0.1 µg/kg, maximum 4 µg). For the RadcliVe Hospital, the short and long water deprivation tests following hours the child was encouraged to Oxford, UK A Mohn (WDT) are usually reliable in distinguishing void hourly. All urine was collected for C L Acerini severe central diabetes insipidus and nephro- measurement of urine osmolality. D B Dunger genic diabetes insipidus from primary polydip- sia. However, both central and nephrogenic HYPERTONIC SALINE TEST Department of diabetes insipidus may be partial,1 and polyuria Intravenous saline (0.85 mol/l) was adminis- Paediatrics, Royal associated with compulsive water drinking may tered continuously (0.05 ml/kg/min) through Victoria Infirmary, 2 Newcastle, UK limit the ability to concentrate urine. Diagnos- an indwelling catheter for up to a maximum of T D Cheetham tic confusion between these conditions may three hours, or until a plasma osmolality of arise as all are capable of producing a similar 300 mosmol/kg was achieved. The patient Department of rise in urine osmolality using standard diagnos- remained supine from 30 minutes before and Medicine, University tic procedures.3 Furthermore, complex disor- throughout the test. Blood samples were taken of Bristol, Bristol, UK S L Lightman ders of osmoreceptor function such as essential 30 minutes before and at 30 minute intervals hypernatraemia are rarely diagnosed using from the start of the test into lithium heparin Correspondence to: WDTs, as a hypovolaemic stimulus may result containers for measurement of plasma sodium, Dr D B Dunger, Department in apparently normal urinary concentrating ADH concentrations, and osmolality. Urine of Paediatrics, Level 4, John 4 RadcliVe Hospital, Oxford ability. samples were also collected before the start of OX3 9DU, UK. The hypertonic saline test oVers an alterna- the test and at 60 minute intervals, where pos- email: david.dunger@ tive approach to the diagnosis of polyuric sible, for measurement of urinary sodium and paediatrics.ox.ac.uk states, as it defines the relation between plasma osmolality. Thirst behaviour and blood press- Accepted 22 April 1998 osmolality and plasma antidiuretic hormone ure were recorded at 30 minute intervals 432 Mohn, Acerini, Cheetham, Lightman, Dunger Arch Dis Child: first published as 10.1136/adc.79.5.431 on 1 November 1998. Downloaded from 6.0 ioural problems. He was diagnosed as having 5.5 insulin dependent diabetes mellitus at the age 5.0 of 8 years. His metabolic control had been poor 4.5 over the previous year (mean HbA1c 11%). At 4.0 15 years of age he developed a severe episode of 3.5 diabetic ketoacidosis complicated by cerebral 3.0 oedema and cerebral infarction, which had 2.5 resulted in loss of short term memory. 2.0 Because of serious behavioural problems a 1.5 WDT was impossible and a hypertonic saline Plasma ADH (pmol/l) 1.0 test was performed. He had a small maximal 0.5 increase of ADH (0.4 pmol/l) during the test 0 (fig 1), which was inappropriately low for the 280 285 295290 300 305 310 320315 corresponding plasma osmolality (314 Plasma osmolality (mosmol/kg) mosmol/kg). A diagnosis of diabetes insipidus Figure 1 Plasma ADH related to plasma osmolality was made and treatment with intranasal during hypertonic saline infusion in two patients (triangles, desmopressin (10 µg bid) was started. case 1; squares, case 2) with diabetes insipidus. The shaded area represents the normal range. CASE 3 throughout. If the ADH response to a hypo- This boy presented at 11 months old with an tonic stimulus was to be assessed the hyper- afebrile, generalised tonic clonic seizure. tonic challenge was preceded by an intravenous On admission, hyponatraemia (sodium water load (20 ml/kg of 5% dextrose) given 129 mmol/l) was detected, which persisted over two to three hours. despite fluid restriction. All preliminary inves- Plasma sodium and urine sodium were tigations, including renal function, thyroid measured using standard laboratory methods. function (thyroid stimulating hormone 2 mU/l, Urine and plasma osmolality were measured by total thyroxine 123 nmol/l), and adrenal func- freezing point depression (Microosmometre; tion (random cortisol 426 nmol/l, adreno- Advanced Instruments, Vetech Scientific Ltd, corticotrophic hormone 29 ng/l, aldosterone West Sussex, UK). Blood for determination of 295 pmol/l) were normal. Random plasma plasma ADH was separated in a refrigerated osmolality and urine osmolality were centrifuge and stored at −20°C. Plasma ADH 259 mosmol/kg and 955 mosmol/kg, respec- was measured by radioimmunoassay as previ- tively, and plasma ADH was 2.98 pmol/l. He ously described.8 The limit of detection of the had a low plasma osmolality (272 mosmol/kg) immunoassay was 0.02 pg/ml (coeYcient of at the beginning of the hypertonic saline test variation intra-assay 9.7% and interassay with inappropriately high plasma ADH 15.3%). All samples from each patient were (3.01 pmol/l) and an exaggerated ADH re- measured in the same assay run. sponse (maximum 27.38 pmol/l) during the osmotic challenge (fig 2). The syndrome of http://adc.bmj.com/ Case reports inappropriate ADH secretion (SIADH) was CASE 1 diagnosed and treatment with water restriction A 14 year old girl presented with a three month (500 ml/day) and demeclocycline (150 mg history of polydipsia (up to 14 l/day) and bid) was started. However, the hyponatraemia polyuria. Significant emotional problems were was corrected only after oral sodium supple- identified. A frontal head injury with skull frac- ments were added. Magnetic resonance imag- ture had been sustained at the age of 13 years, ing of the brain remained normal but second- and nine months before presentation a further ary hypothyroidism developed and he is now on September 23, 2021 by guest. Protected copyright. minor head injury had occurred. All prelimi- receiving treatment with thyroxine (50 µg/day). nary investigations were normal, except for a random prolactin concentration, which was CASE 4 raised to 2387 mU/l. The WDT resulted in A 4 year old boy presented with erratic maximum urinary and plasma osmolalities of drinking characterised by intermittent polydip- 287 and 289 mosmol/kg, respectively. Re- sia (up to 5 l/day) and polyuria. Episodic head- sponses to desmopressin were equivocal with aches and aggressive behaviour had been baseline urinary osmolality 135 mosmol/kg noted. He had been diagnosed three years ear- reaching a maximum of 331 mosmol/kg. lier with histiocytosis X with histologically During the osmotic challenge with hyper- confirmed lesions of the skin, ear, and lung, tonic saline (fig 1), a low maximal ADH which had been treated with prednisolone. A (1 pmol/l) with raised plasma osmolality WDT suggested partial central diabetes insip- (312 mosmol/kg) was detected and established idus (maximum urine osmolality 630 mosmol/ the diagnosis of partial diabetes insipidus.