Monitoring patients receiving dopamine agonist therapy for hyperprolactinaemia.

The surveillance strategy for patients taking low dose cabergoline for hyperprolactinaemia is controversial. As more evidence has emerged that the risks of cardiac valvulopathy in this population of patients are low, fewer and fewer endocrinologists adhere strictly to the original medicines and healthcare products agency MHRA guidance of "at least" annual echocardiography. Strict adherence to this guidance would be costly in monetary terms (£5.76 million/year in the UK) and also in resource use (90,000 extra echocardiograms/year). This article reviews the proposed pathophysiological mechanism underlying the phenomenon of dopamine agonist valvulopathy, the characteristic echocardiographic changes seen, summarises the published literature on the incidence of valvulopathy with low dose cabergoline and examines the previous and current evidence-based screening guidelines.

A meta-analysis of the prevalence of cardiac valvulopathy in hyperprolactinemic patients treated with Cabergoline.

CONTEXT: Cabergoline is first line treatment for most patients with lactotrope pituitary tumors and hyperprolactinemia. Its use at high-dose in Parkinson's disease has largely been abandoned, because of its association with the development of a characteristic restrictive cardiac valvulopathy. Whether similar valvular changes occur in patients receiving lower doses for treatment of hyperprolactinemia is unclear, although stringent regulatory recommendations for echocardiographic screening exist. OBJECTIVE: To conduct a meta-analysis exploring any link between the use of cabergoline for the treatment of hyperprolactinemia and clinically-significant cardiac valvulopathy. DATA SOURCES: Full-text papers published up to and including January 2017 were found via PubMed and selected according to strict inclusion criteria. STUDY SELECTION: All case-control studies were included where patients had received ≥6 months cabergoline treatment for hyperprolactinemia. Single case reports, previous meta-analyses, review papers and papers pertaining solely to Parkinson's disease were excluded. 13/76 originally selected studies met inclusion criteria. DATA EXTRACTION: A list of desired data were compiled and extracted from papers by independent observers. Each also independently graded for paper quality (bias) and met to reach consensus. DATA SYNTHESIS: More tricuspid regurgitation was observed (OR 3.74; 95% CI 1.79-7.8 p<0.001) in the cabergoline treated patients compared to controls. In no patient was tricuspid valve dysfunction diagnosed as a result of clinical symptoms. There was no significant increase in any other valvulopathy. CONCLUSIONS: Treatment with low dose cabergoline in hyperprolactinemia appears to be associated with an increased prevalence of tricuspid regurgitation. The clinical significance of this is unclear and requires further investigation. 51.

De novo HNF1 homeobox B mutation as a cause for chronic, treatment-resistant hypomagnesaemia.

29-year-old female presenting with an 8-year history of unexplained hypomagnesaemia, which was severe enough to warrant intermittent inpatient admission for intravenous magnesium. Urinary magnesium was inappropriately normal in the context of hypomagnesaemia indicating magnesium wasting. Ultrasound imaging demonstrated unilateral renal cysts and computed tomography of kidneys, ureters and bladder showed a bicornuate uterus. Referral to genetic services and subsequent testing revealed a de novo HNF1B deletion. LEARNING POINTS: HNF1B loss-of-function mutations are one of the most common monogenic causes of congenital anomalies of the kidney and urinary tract.Those with HNF1B mutations may have some of a constellation of features (renal and hepatic cysts, deranged liver function tests, maturity onset diabetes of the young type 5 (MODY5), bicornuate uterus, hyperparathyroidism, hyperuricaemic gout, but presenting features are highly heterogeneous amongst patients and no genotype/phenotype correlation exists. HNF1B mutations are inherited in an autosomal dominant pattern but up to 50% of cases are de novo.HNF1B mutations can be part of the Chr17q12 deletion syndrome, a contiguous gene deletion syndrome.Inorganic oral magnesium replacements are generally poorly tolerated with side effects of diarrhoea. Organic magnesium compounds, such as magnesium aspartate, are better absorbed oral replacement therapies.

A cross-sectional study of the prevalence of cardiac valvular abnormalities in hyperprolactinemic patients treated with ergot-derived dopamine agonists.

CONTEXT: Concern exists in the literature that the long-term use of ergot-derived dopamine agonist drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease. OBJECTIVE: The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking dopamine agonists as treatment for lactotrope pituitary tumors and to explore any associations with the cumulative dose of drug used. DESIGN: A cross-sectional echocardiographic study was performed in a large group of patients who were receiving dopamine agonist therapy for hyperprolactinemia. Studies were performed in accordance with the British Society of Echocardiography minimum dataset for a standard adult transthoracic echocardiogram. Poisson regression was used to calculate relative risks according to quartiles of dopamine agonist cumulative dose using the lowest cumulative dose quartile as the reference group. SETTING: Twenty-eight centers of secondary/tertiary endocrine care across the United Kingdom participated in the study. RESULTS: Data from 747 patients (251 males; median age, 42 y; interquartile range [IQR], 34-52 y) were collected. A total of 601 patients had taken cabergoline alone; 36 had been treated with bromocriptine alone; and 110 had received both drugs at some stage. The median cumulative dose for cabergoline was 152 mg (IQR, 50-348 mg), and for bromocriptine it was 7815 mg (IQR, 1764-20 477 mg). A total of 28 cases of moderate valvular stenosis or regurgitation were observed in 24 (3.2%) patients. No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality. CONCLUSION: This large UK cross-sectional study does not support a clinically concerning association between the use of dopamine agonists for the treatment of hyperprolactinemia and cardiac valvulopathy.

Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density.

An in vivo study was conducted to assess the sensitivity of fibrous capsule thickness and macrophage density to polymer fiber diameter. Single polypropylene fibers of diameters ranging from 2.1 to 26.7 microm were implanted in the subcutaneous dorsum of Sprague-Dawley rats. Results at 5 weeks demonstrated reduced fibrous capsule thickness for small fibers. Capsule thickness was 0.6 (+/-1.8) microm, 11.7 (+/-12.0) microm, 20.3 (+/-11.6) microm, and 25.5 (+/-10.0) microm for fibers in the ranges of 2.1 to 5.9, 6.5 to 10.6, 11.1 to 15.8, and 16.7 to 26.7 microm, respectively. Fibers very near to blood vessels had smaller capsules than did those with local vasculature further away. The macrophage density in tissue with fiber diameters 2.1 to 5.9 microm (23.03 +/- 8.67%) was comparable to that of unoperated contralateral control skin (18.72+/-10.06%). For fibers with diameters in the ranges of 6.5 to 10.6, 11.1 to 15.8, and 16.7 to 26.7 microm, macrophage densities were 33.90+/-13.08%, 34.40+/-15.77%, and 41.68+/-13.98%, respectively, all of which were significantly larger (p<0.002) than that for the control. The reduced fibrous capsule thickness and macrophage density for small fibers (<6 microm) compared with large fibers could be due to the reduced cell-material contact surface area or to a curvature threshold effect that triggers cell signaling. A next step will be to extend the analysis to meshes to evaluate fiber-spacing effects on small-fiber biomaterials.