Context There are growing reports of dopamine agonist (DA)-induced impulse control disorders (ICDs) in hyperprolactinemic patients. However, the magnitude of this risk and predictive factors remain uncertain. Objective To determine ICD prevalence and risk factors in DA-treated hyperprolactinemic patients compared to community controls. Design, Setting and Participants Multicenter cross-sectional analysis of 113 patients and 99 healthy controls. Main Outcome Measures Participants completed a neuropsychological questionnaire consisting of the Depression Anxiety Stress Scale (DASS21), Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP-S), Hypersexual Behavior Inventory (HBI), Hypersexual Behavior Consequences Scale and Social Desirability Response Set Scale. Demographic and clinical data were collated to determine ICD risk factors. Patients testing positive for an ICD were offered a semistructured psychological interview. Results Patients were more likely than controls to test positive by QUIP-S for any ICD (61.1 vs 42.4%, P = .01), hypersexuality (22.1 vs 8.1%, P = .009), compulsive buying (15.9 vs 6.1%, P = .041) and punding (18.6 vs 6.1%, P = 0.012), and by HBI for hypersexuality (8.0 vs 0.0%, P = 0.004). Independent risk factors were male sex (odds ratio [OR] 13.85), eugonadism (OR 7.85), Hardy’s tumor score and psychiatric comorbidity (OR 6.86) for hypersexuality, and age (OR 0.95) for compulsive buying. DASS21 subset scores were higher in patients vs controls and in patients with vs without different ICDs. Only 19/51 (37.3%) interviewed patients were aware of the relationship between DAs and ICDs before the study. Conclusions DA therapy poses a high, previously underestimated risk of ICDs, especially in the form of hypersexuality in eugonadal men.

Summary Objective Measurement of hypertonic saline‐stimulated copeptin has recently been described for the differentiation of polyuria‐polydipsia syndrome. This study aims to determine the copeptin response to intravenous 3% hypertonic saline, including evaluation of adverse effects, in a local cohort of healthy adults >18 years in Australia. Design Prospective clinical study. Methods Twenty healthy volunteers (10 males and 10 females) were recruited. Participants underwent infusion of 3% hypertonic saline via a previously described standardized protocol, until the plasma sodium was ≥150 mmol/L, with measurement of plasma copeptin. Results Mean peak sodium was 152 mmol/L ± SD 1.4 with osmolality 315 mmol/kg ± SD 3.9. Median volume of hypertonic saline infused to reach target sodium ≥ 150 mmol/L was 1536 mL (IQR 1362, 1992). Mean rate of plasma sodium rise was 5.9 mmol/L/hour ± SD 1.5. Hypertonic saline‐stimulated copeptin had non‐parametrical distribution with median of 33.8 pmol/L (IQR 27.6, 63.6). Overall median symptom burden was 6/10 (range 3/10‐9/10). Copeptin was significantly higher for those who experienced nausea and/or vomiting (n = 13) (median 39.0 pmol/L; IQR 32.5, 90), compared to those participants who did not experience either (median 20.0 pmol/L; IQR 13.0, 31.0) (P = 0.003). There were no serious adverse events. Conclusion Hypertonic saline‐stimulated copeptin measurements were similar in our population compared with previously reported reference intervals in healthy volunteers. There is a wide range of stimulated copeptin measurements in the healthy population. Nausea and vomiting are common adverse effects which enhance the copeptin response.

No abstract

Differentiating between primary polydipsia and central diabetes insipidus (DI) can be challenging. The water deprivation test has traditionally been used to diagnosis DI, however has poor diagnostic accuracy (1). Direct measurement of anti-diuretic hormone (ADH) is limited clinically. Copeptin is the C-terminal glycoprotein moiety of ADH prohormone, and correlates well with plasma ADH. Unlike ADH, copeptin is easy to measure (2). Hypertonic saline stimulated copeptin measurements have recently been described for the diagnosis of central DI. A copeptin cut-off of >4.9 pmol/L has a diagnostic accuracy of 96.5% for distinguishing primary polydipsia from central DI (3). A copeptin assay has recently been established in our laboratory. Validation of hypertonic saline-stimulated copeptin concentrations in our local population is needed before this test can be used with confidence in patients presenting to our institution with polyuria-polydipsia syndrome. The aim of this study was to develop a local reference range for hypertonic saline-stimulated copeptin in healthy volunteers. Twenty healthy volunteers (10 male and 10 female) were recruited. Subjects underwent a hypertonic saline test, as previously described (3). Hypertonic saline (3%) was administered as an initial 250 mL bolus followed by 0.15 mL/kg/minute until a target serum sodium of ≥150 mmol/L was reached. At this time, blood was drawn for copeptin. Twelve healthy volunteers (7 females; 5 males) have undergone the study to date. Median age was 28 years (range 26-50); median body weight 75.7 kg (range 57.9 -94.5); median baseline plasma sodium 138 mmol/L (range 136 - 140) and median serum osmolality 289.5 (range 281-297). Median peak sodium was 152 mmol/L (range 150-154) with osmolality 314.5 mmol/kg (range 306-320). Median volume of hypertonic saline infused was 1583 mL (1230-2177) and median hypertonic saline stimulated copeptin was 29.2 pmol/L (9.6-167.4). Overall symptom burden was 5/10 (range 3/10-9/10). There were no serious adverse events. Development of a local reference range for hypertonic saline stimulated copeptin measurements will assist in interpretation of the test in our local population of patients presenting with polyuria-polydipsia syndrome. References 1. Fenske W, Quinkler M, Lorenz D, Zopf K, Haagen U, Papassotiriou et al. Copeptin in the differential diagnosis of the polyuria-polydipsia syndrome- revisiting the direct and indirect water deprivation tests. JCEM. 2011;96:1506-1515 2. Timper K, Fenske W, Kuhn F, Frech N, Arici B, Rutishauser J et al. Diagnostic accuracy of copeptin in the differential diagnosis of the polyuria-polydipsia syndrome: a prospective multicenter study. JCEM. 2015;100:2268-2274 3. Fenske, W, Refardt J, Chifu I, Schnyder I, Winzeler B, Drummond J. A copeptin-based approach in the diagnosis of diabetes insipidus. NEJM. 2018;379:428-439