ESPE Abstracts

Six-year-old female, diagnosed with GH deficiency at another Center (H: -3.13SDS; H peak with clonidine 5.7ng/mL, with insulin 1.2ng/mL). Brain MRI at diagnosis: small pituitary gland, ectopic neurohypophysis, normal stalk, right internal carotid artery aplasia. At 10 years onset of polyuria-polydipsia syndrome (PPS) (4L/day–154ml/kg/die); mood disorders and ADHD diagnosis were also reported. A fluid deprivation test was performed, lasting 22 hours (pre: S-Osm 275mOsm/L, U-Osm 346mOsm/kg, Na⁺ 142.4mmol/L; post: S-Osm 277mOsm/L, U-Osm756 mOsm/kg, Na⁺ 143.5mmol/L, weight loss <5%). Conclusions: primary polydipsia, water restriction recommended. At 12 years worsening of PPS was reported (5L/day–138ml/kg/die). A fluid deprivation test was repeated (pre: S-Osm 285mOsm/L, U-Osm 409mOsm/kg, Na⁺ 141.3mmol/L; post: S-Osm 285mOsm/L, U-Osm 750mOsm/kg, Na⁺ 144mmol/L, weight loss <5%), overlapping with the previous one. At 14 years of age the patient reached her final height (H: -0.29SDS, ΔH pre-post-therapy +2.84SDS, menarche at 13 years, bone age 15 years old). Retesting with insulin was pathological (GH peak 2.4ng/mL). IN-OUT water balances 6L/day–120ml/kg/day. (S-osm 289mOsm/L, U-Osm 155mOsm/kg, Na⁺ 143.3mmol/L). Familiarity in the maternal line for PPS emerged during a visit, never previously reported nor investigated. Therefore, the patient underwent NGS for short stature, currently ongoing, and diabetes insipidus: a heterozygous mutation in exon 1 of the AVP gene (c. 55G>A p. /Ala19Thr) was found, associated with neurohypophyseal diabetes insipidus (DI). Therapy with desmopressin was started, with expected clinical response.

Conclusions: the differential diagnosis between DI and primary polydipsia is complex, especially in adolescence when psychosocial problems are more common. Fluid deprivation test, the pediatric gold standard for the diagnosis of DI, can be falsely negative in partial forms, due to the persistence of vasopressin secretory capacity and the alteration of the renal osmolar gradient, especially in the chronic forms of PPS. In particular, the aforementioned mutation is associated with a later onset of disease and may not show any frank biochemical alteration due to progressive loss of vasopressin neurons. This can mislead the diagnosis towards forms of primary polydipsia, as in our case. In the diagnostic-therapeutic process it is therefore always necessary to investigate familiarity, which may not be mentioned, and to consider genetic analysis as well as neuroimaging. The peculiarity of the reported case is the genetic origin of neurohypophyseal DI despite the presence of a concomitant picture of congenital hypopituitarism, delineated by the anatomical alteration of the hypothalamic-pituitary region and by the permanent GH deficiency.