P08 - Hypertonic saline test: anterior pituitary response and electrolytic alterations

Background Over the years, various procedures have been proposed for the evaluation of polyuria–polydipsia syndrome (PPS), including the arginine stimulation test, glucagon stimulation test, and insulin-induced hypoglycemia test. Although originally designed to assess anterior pituitary function, recent evidence suggests that these tests are also triggers for arginine vasopressin (AVP) secretion, thereby offering potential utility in the diagnostic work-up of PPS. The hypertonic saline test (HST) emerged as the new gold-standard for the differential diagnosis of PPS, strongly stimulating AVP secretion by increasing plasma osmolality (pOsm). Additionally, it induces a significant stress response, requiring corticosteroid supplementation in patients with adrenal insufficiency. However, it remains unclear whether HST can also elicit a stimulatory effect on anterior pituitary function. Purpose To assess whether HST may represent a valid tool for evaluating anterior hypopituitarism, focusing on somatotropic and corticotropic axes and describe possible electrolytic alterations during the test. Methods Nineteen patients (16F; age 38.9[31.3]yrs; BMI 22.3[6.9]kg/m2) with PPS underwent HST between 12/2023 and 03/2025 at two third-level centers in Northern- Italy. GH, cortisol, ACTH, glucose, s-Na+, s-K+, s-Ca2+, pOsm and copeptin were measured at baseline and upon achieving hypernatremia (s-Na >149mmol/L) via 3% saline bolus (250 mL at 500 mL/h) followed by continuous infusion (9 mL/Kg/h). Results HST induced significant increases in s-Na+ (137[5.0] vs 150.0[2.5]mmol/L, p<0.0001), pOsm (282[11.0] vs 304.0[20.8]mOsm/Kg, p<0.0001) and copeptin concentrations (1.8[0.5] vs 9.9[34.3]pmol/L, p=0.0008). Glucose levels remained unchanged. ACTH significantly increased (14.9[10.5] vs 22.6[25.4]ng/L, p=0.03), while cortisol showed a non-significant trend towards elevation (119.0[34.0] vs 144.5[62.0]μg/L, p=0.18). GH levels remained stable. s-K+ levels significantly increased (3.9[0.2] vs 4.3[0.4]mmol/L, p=0.0001), whereas s-Ca2+ significantly decreased (1.16[0.11] vs 1.10[0.08]mmol/L, p=0.0002) in response to HST. Conclusion This study confirms HST as a valid trigger for copeptin release. However, the test did not show a clinically relevant stimulatory effect on the somatotropic or adrenal axis, despite a moderate increase in ACTH. These preliminary findings warrant further investigation. The observed changes in s-K+ and s-Ca2+ levels highlight the need for a baseline assessment of electrolyte status and careful ECG monitoring should be considered in cases where significant electrolyte disturbances occur in response to HST.