Arginine-stimulated copeptin for Central Diabetes Insipidus diagnosis in children

Flavia Napoli; Emilio Casalini; Angelica Pisati; Mirna Balsamo; Tiziana Camia; Silvia Bianchin; Alice Zucconi; Giordano Spacco; Giulia Simiele; Silvia Marcenaro; Daniela Fava; Maria Allegri Anna Elsa; Alessia Angelelli; Giuseppa Patti; Iorgi Natascia Di; Mohamad Maghnie

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ESPE Abstracts (2024) 98 P1-183

ESPE2024 Poster Category 1 Pituitary, Neuroendocrinology and Puberty 3 (9 abstracts)

Arginine-stimulated copeptin for Central Diabetes Insipidus diagnosis in children.

Flavia Napoli ¹ , Emilio Casalini ² , Angelica Pisati ² , Mirna Balsamo ³ , Tiziana Camia ² , Silvia Bianchin ² , Alice Zucconi ² , Giordano Spacco ² , Giulia Simiele ² , Silvia Marcenaro ² , Daniela Fava ^1,2 , Anna Elsa Maria Allegri ¹ , Alessia Angelelli ^1,2 , Giuseppa Patti ^1,2 , Natascia Di Iorgi ^1,2 & Mohamad Maghnie ^1,2

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¹Pediatric Endocrinology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy. ²DINOGMI, Università degli Studi di Genova, Genova, Italy. ³Medicine Laboratory, Irccs San Martino Polyclinic Hospital, Genova, Italy

Introduction: Central diabetes insipidus (CDI) diagnosis is challenging, since water deprivation test has sub-optimal sensitivity and specificity and carries an important burden for patients and care-givers. Several authors have investigated arginine as a stimulus for AVP secretion – evaluated by dosing copeptin, a pre-pro AVP cleavage product - and normal values for adult patients have already been established.

Aims and Methods: Aim of our study was to evaluate arginine-stimulated copeptin in a cohort of children and adolescents (age 0-18 years) with CDI, and to compare it to stimulated copeptin in patients with primary polydipsia. Both conditions have been ascertained by means of standard water deprivation test and confirmed by clinical follow up. Copeptin was measured at baseline, after an overnight fast - and after withdrawing DDAVP for 24 hours in CDI patients who had already started DDAVP replacement therapy -, and 60 minutes after starting a 30-minute arginine infusion (0.5g/Kg body weight).

Results: Baseline and stimulated copeptin were analysed in 14 patients with CDI (5M, 9F) and in 8 children with primary polydipsia (5M, 3F); 11 CDI patients had an idiopathic or genetic form, while 3 patients were affected by a pituitary stalk neoplasm (germinoma or Langerhans cell histiocytosis). Median age at testing was 12.48 years in CDI patients (IQR: 9.73-13.75) and 13.17 (9.90-14.53) years in primary polydipsia patients. Median baseline copeptin was significantly lower in CDI patients (1.60pmol/l; 1.08-1.93 vs 2.20; 1.50- 2.75; P = 0.021). Stimulated copeptin was significantly lower in patients as well (1.95; 1.48-2.20 vs 4.70; 3.80-6.20; P = 0.002). Delta copeptin (stimulated minus baseline was lower in CDI patients, even though, due to missing values, this parameter did reach statistical significance. Baseline and stimulated copeptin did not differ in females and males in our cohort, nor in pre-pubertal (Tanner stage I) vs pubertal (Tanner II-V) children, and had only a weak correlation with BMI SDS; one patient (5%) presented nausea and vomiting after arginine infusion, with prompt resolution of symptoms after medical treatment.

Conclusion: Preliminary data showed that arginine test is a safe and reliable in differentiating CDI from primary polydipsia in children. Further investigations are needed to establish a diagnostic cut-off for copeptin in children; these evaluations should also consider differences due to age, anthropometric measures and pubertal stage.