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Context: Hypothalamic injury often leads to rapid, intractable weight gain causing hypothalamic obesity, which is associated with increased risk of cardiovascular and metabolic morbidity and mortality. There are no approved or effective pharmacological treatments for hypothalamic obesity, and conventional lifestyle management remains ineffective. Objective: Investigate the safety and efficacy of Tesomet (0.5mg tesofensine/50mg metoprolol) in adults with hypothalamic obesity. Methods: Twenty-one adults with hypothalamic obesity (16 females) were randomized to Tesomet (0.5mg/50mg) or placebo for 24 weeks. Patients also received diet/lifestyle counselling. The primary endpoint was safety; secondary endpoints included measures of body weight, appetite-scores, quality of life, and metabolic profile. Results: Eighteen patients completed 24-weeks. Consent withdrawal, eligibility, and serious adverse events (SAE) unrelated to treatment resulted in dropouts. One patient experienced a Tesomet-related SAE of exacerbated pre-existing anxiety leading to treatment discontinuation. Tesomet-related adverse events were otherwise mostly mild, and included sleep disturbances (Tesomet 50%, Placebo 13%), dry mouth (Tesomet 43%, Placebo 0%), and headache (Tesomet 36%, Placebo 0%). No significant differences in heart rate or blood pressure were observed between groups. Compared to placebo, Tesomet resulted in additional mean (95% CI) weight change of -6.3% ([-11.3; -1.3]; p=0.017), increased the number of patients achieving ≥5% weight loss (Tesomet 8/13, Placebo 1/8; p=0.046), and tended to augment the reduction in waist circumference by 5.7cm ([-0.1; 11.5]; p=0.054). Conclusion: Tesomet was well-tolerated, did not affect heart rate or blood pressure, and resulted in significant reductions in body weight compared to placebo in adults with hypothalamic obesity.

ObjectivesRecent large cohort studies suggest an association between high plasma prolactin and cardiovascular mortality. The objective of this systematic review was to systematically assess the effect of reducing prolactin with dopamine agonist on established cardiovascular risk factors in patients with prolactinomas.DesignBibliographical search was done until February 2019 searching the following databases: PubMed, EMBASE, WHO and LILAC. Eligible studies had to include participants with verified prolactinomas where metabolic variables were assessed before and after at least 2 weeks treatment with dopamine agonists.MethodsBaseline data and outcomes were independently collected by two investigators. The study was registered with PROSPERO (registration number CRD42016046525).ResultsFourteen observational studies enrolling 387 participants were included. The pooled standardized mean difference of the primary outcome revealed a reduction of BMI and weight of −0.21 (95% CI −0.37 to −0.05; P = 0.01; I2 = 71%), after treatment. Subgroup analysis suggested that the reduction of weight was primarily driven by studies with high prolactin levels at baseline (P = 0.04). Secondary outcomes suggested a small decrease in waist circumference, a small-to-moderate decrease in triglycerides, fasting glucose levels, HOMA-IR, HbA1c and hsCRP, and a moderate decrease in LDL, total cholesterol and insulin.ConclusionThis systematic review suggests a reduction of weight as well as an improved lipid profile and glucose tolerance after treatment with dopamine agonist in patients with prolactinomas. These data are based on low-quality evidence.

BackgroundA 20-year-old Danish woman with melorheostosis in her right femoral shaft and disabling pain in the affected area, whose symptoms did not in the long term respond to zoledronic acid, experienced continuous remission of pain after treatment with denosumab. To the best of our knowledge, this is the first case report on denosumab treatment for melorheostosis.Case presentationRadiologic findings and bone biopsy showed irregular cortical hyperostosis in the right femoral shaft with increased tracer uptake on Tc99-bone scan.The diagnosis of melorheostosis was made based on the radiological findings. There was a good initial response to zoledronic acid administration, but after relapse of pain, the second and third administrations had a poor effect. As a second line of treatment denosumab was administered at 8-week intervals, the frequency was based on our patient’s symptoms and on biochemical markers of bone turnover.ConclusionThis is the first report indicating that denosumab has a place in the treatment of melorheostosis when the effect of bisphosphonate treatment is insufficient.