Therapeutic options in the management of acromegaly: focus on lanreotide Autogel®

In acromegaly, expert surgery is curative in only about 60% of patients. Postoperative radiation therapy is associated with a high incidence of hypopituitarism and its effect on growth hormone (GH) production is slow, so that adjuvant medical treatment becomes of importance in the management of many patients. To delineate the role of lanreotide in the treatment of acromegaly. Search of Medline, Embase, and Web of Science databases for clinical studies of lanreotide in acromegaly. Treatment with lanreotide slow release and lanreotide Autogel((R)) normalized GH and insulin-like growth factor-I (IGF-I) concentrations in about 50% of patients. The efficacy of 120 mg lanreotide Autogel((R)) on GH and IGF-I levels was comparable with that of 20 mg octreotide LAR. There were no differences in improvement of cardiac function, decrease in pancreatic beta-cell function, or occurrence of side effects, including cholelithiasis, between octreotide LAR and lanreotide Autogel(R). When postoperative treatment with somatostatin analogs does not result in normalization of serum IGF-I and GH levels after noncurative surgery, pegvisomant alone or in combination with somatostatin analogs can control these levels in a substantial number of patient

Testosterone in men with hypogonadism and transgender males: a systematic review comparing three different preparations

Testosterone therapy is the cornerstone in the care of men with hypogonadism and transgender males. Gel and intramuscular injections are most frequently used and are registered and included in the international guidelines. The specific preparation should be selected according to the patient’s preference, cost, availability, and formulation-specific properties. As the majority of men with hypogonadism and transgender males require lifelong treatment with testosterone, it is important to utilize a regimen that is effective, safe, inexpensive, and convenient to use with optimal mimicking of the physiological situation. This systematic review reviews current literature on differences between the three most used testosterone preparations in adult men with hypogonadism and transgender males. Although it appeared hardly any comparative studies have been carried out, there are indications of differences between the preparations, for example, on the stability of testosterone levels, hematocrit, bone mineral density, and patient satisfaction. However, there are no studies on the effects of testosterone replacement on endpoints such as cardiovascular disease in relation to hematocrit or osteoporotic fractures in relation to bone mineral density. The effect of testosterone therapy on health-related quality of life is strongly underexposed in the reviewed studies, while this is a highly relevant outcome measure from a patient perspective. In conclusion, current recommendations on testosterone treatment appear to be based on data primarily from non-randomized clinical studies and observational studies. The availability of reliable comparative data between the different preparations will assist in the process of individual decision-making to choose the most suitable formula

New medical therapies on the horizon: oral octreotide

Somatostatin analog treatment is first line medical treatment in patients with acromegaly. This drug is currently mainly administered by monthly depot preparations of octreotide and lanreotide. With the innovative transient permeability enhancer, a technology enabling the absorption of drug molecules via transient opening of the tight junctions of the gut epithelium, it is possible to achieve therapeutic octreotide levels after oral ingestion. The present review summarized the preclinical work and the recently reported phase I and III study on oral octreotide capsules in patients with acromegaly. Maintenance of control in 155 participating patients was achieved in 65% at the end of core period. Once controlled on oral octreotide, the response was maintained to the end of the extension phase in 85%. Side effects were comparable to currently available preparations. There was a profound suppression of growth hormone levels, and significant symptom reduction. Currently available parental somatostatin analogs are generally well tolerated and are able to achieve longstanding biochemical control in patients with somatostatin sensitive tumors. Potential advantages of an oral alternative is the lack injection-related side effects, but there will be an ongoing need for a very strict compliance with the 2 daily dose regimen and fasting around drug administrations. A second phase III study is currently being conducted. The potential place in the treatment of acromegaly is discussed

Limited effects of growth hormone replacement in patients with GH deficiency during long-term cure of acromegaly

The aim of this study was to assess the effects of replacement with recombinant human growth hormone (rhGH) in patients with GH deficiency (GHD) after treatment of acromegaly. Intervention study. Sixteen patients (8 men, age 56 years), treated for acromegaly by surgery and radiotherapy, with an insufficient GH response to insulin-induced hypoglycaemia, were treated with 1 year of rhGH replacement. Study parameters were assessed at baseline and after 1 year of rhGH replacement. Study parameters were cardiac function, body composition, bone mineral density (BMD), fasting lipids, glucose, bone turnover markers, and Quality of Life (QoL). During rhGH replacement IGF-I concentrations increased from −0.4 ± 0.7 to 1.0 ± 1.5 SD (P = 0.001), with a mean daily dose of 0.2 ± 0.1 mg in men and 0.3 ± 0.2 mg in women. Nonetheless, rhGH replacement did not alter cardiac function, lipid and glucose concentrations, body composition or QoL. Bone turnover markers (PINP and β crosslaps) levels increased (P = 0.005 and P = 0.021, respectively), paralleled by a small, but significant decrease in BMD of the hip. The beneficial effects of rhGH replacement in patients with GHD during cure from acromegaly are limited in this study

Patient-reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly.

This work is licensed under a Creative Commons Attribution 3.0 Unported LicenseBACKGROUND: Long-acting somatostatin analogues delivered parenterally are the most widely used medical treatment in acromegaly. This patient-reported outcomes survey was designed to assess the impact of chronic injections on subjects with acromegaly. METHODS: The survey was conducted in nine pituitary centres in Germany, UK and The Netherlands. The questionnaire was developed by endocrinologists and covered aspects of acromegaly symptoms, injection-related manifestations, emotional and daily life impact, treatment satisfaction and unmet medical needs. RESULTS: In total, 195 patients participated, of which 112 (57%) were on octreotide (Sandostatin LAR) and 83 (43%) on lanreotide (Somatuline Depot). The majority (>70%) of patients reported acromegaly symptoms despite treatment. A total of 52% of patients reported that their symptoms worsen towards the end of the dosing interval. Administration site pain lasting up to a week following injection was the most frequently reported injection-related symptom (70% of patients). Other injection site reactions included nodules (38%), swelling (28%), bruising (16%), scar tissue (8%) and inflammation (7%). Injection burden was similar between octreotide and lanreotide. Only a minority of patients received injections at home (17%) and 5% were self-injecting. Over a third of patients indicated a feeling of loss of independence due to the injections, and 16% reported repeated work loss days. Despite the physical, emotional and daily life impact of injections, patients were satisfied with their treatment, yet reported that modifications that would offer major improvement over current care would be 'avoiding injections' and 'better symptom control'. CONCLUSION: Lifelong injections of long-acting somatostatin analogues have significant burden on the functioning, well-being and daily lives of patients with acromegaly.Chiasma, Inc. 60 Welles Ave, Newton, MA 02 459, USA

Multi-generational House

BUTOROVÁ, H.: Dvougenerační rodinný dům: Bakalářská práce. Ostrava: VŠB-Technická univerzita Ostrava, Fakulta stavební, Katedra architektury 226, 2017, 49 s. Vedoucí práce: Student, A. Předmětem bakalářské práce „Dvougenerační rodinný dům“ je vypracování částečné projektové dokumentace pro provádění stavby podle vyhlášky 499/2006 Sb., o dokumentaci staveb. Jako podklad bakalářské práce slouží architektonická studie vypracovaná v rámci předmětu Ateliérová tvorba I a dokumentace pro stavební povolení vypracovaná v předmětu Ateliérová tvorba Va. Rodinný dvougenerační dům je navržen v lázeňské oblasti Karviná-Darkov. Stavba je složena z části pro mladou rodinu a z části pro starší rodiče. Cílem bylo vytvořit společné zázemí obou rodin, avšak i dostatek soukromí. Koncepce domu je založena na přízemní části staršího páru a na dvoupodlažní části mladé čtyřčlenné rodiny.BUTOROVÁ, H.: Multi-generational House: Bachelor´s thesis. Ostrava: VŠB-Technical university of Ostrava, Faculty of Civil Engineering, Department of Architecture 226, 2017, 49 p. Thesis head: Student, A. The subject of bachelor’s thesis „Multi-generational House‟ is preparation of partial project documentation for construction of a building according to notice 499/2006 Sb., about documentation of buildings. As resource materials serves architectural study worked out from Studio Work I and a documentation for building permit worked out from Studio Work Va. Multi-generational House is projected in the spa area Karviná-Darkov. The building consists of a part for young family and a part for grandparents. The goal was to make a common base for both families, but also to secure enough privacy. The philosophy of the house is based on the ground part for older couple and on the two-floor part for young four-member family.226 - Katedra architekturyvelmi dobř

Cushing's Syndrome and Hypothalamic-Pituitary-Adrenal Axis Hyperactivity in Chronic Central Serous Chorioretinopathy

Clinical epidemiolog

Time-restricted feeding improves adaptation to chronically alternating light-dark cycles

Disturbance of the circadian clock has been associated with increased risk of cardio-metabolic disorders. Previous studies showed that optimal timing of food intake can improve metabolic health. We hypothesized that time-restricted feeding could be a strategy to minimize long term adverse metabolic health effects of shift work and jetlag. In this study, we exposed female FVB mice to weekly alternating light-dark cycles (i.e. 12 h shifts) combined with ad libitum feeding, dark phase feeding or feeding at a fixed clock time, in the original dark phase. In contrast to our expectations, long-term disturbance of the circadian clock had only modest effects on metabolic parameters. Mice fed at a fixed time showed a delayed adaptation compared to ad libitum fed animals, in terms of the similarity in 24 h rhythm of core body temperature, in weeks when food was only available in the light phase. This was accompanied by increased plasma triglyceride levels and decreased energy expenditure, indicating a less favorable metabolic state. On the other hand, dark phase feeding accelerated adaptation of core body temperature and activity rhythms, however, did not improve the metabolic state of animals compared to ad libitum feeding. Taken together, restricting food intake to the active dark phase enhanced adaptation to shifts in the light-dark schedule, without significantly affecting metabolic parameters