Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement

The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach.

Tumor neuroendocrino ileal con síndrome carcinoide de difícil control / Neuroendocrine ileal tumor with difficult to control carcinoid syndrome

Resumen Los tumores neuroendocrinos son neoplasias infrecuentes y de abordaje complejo. Actualmente se necesitan más ensayos clínicos aleatorizados para establecer el manejo óptimo de los pacientes afectados por metástasis hepáticas no resecables. Aportamos un caso de TNE metastásico en el que se indicó trasplante hepático por sintomatología derivada del síndrome carcinoide no controlable con el tratamiento médico habitual. (Acta Med Colomb 2018; 43: 161-164).

Abstract Neuroendocrine tumors are infrequent neoplasms with a complex approach. Currently, more randomized clinical trials are needed to establish the optimal management of patients affected by unresectable liver metastases. A case of metastatic NET in which hepatic transplantation was indicated due to symptoms derived from the carcinoid syndrome that cannot be controlled with the usual medical treatment is provided.

Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors / 대한핵의학회잡지

Peptide receptor radionuclide therapy (PRRT) is a systemic cytotoxic radiation therapy using a compound of β-emitting radionuclide chelated to a peptide for the treatment of tumor with overexpressed specific cell receptor such as somatostatin receptor subtype 2 (SSTR2) of neuroendocrine tumor (NET). Surgical resection should be performed for the curative treatment for NETs when it is feasible; however, a multi-disciplinary approach is needed when locally advanced or metastasized disease. PRRT with lutetium-177 (Lu-177)-labeled somatostatin analogues, as a new treatment modality targeting metastatic or inoperable NETs expressing the SSTR2, have been developed and successfully used for the past two decades. As Lu-177 emits both β- and γ-radiation, it has the ability as a theragnostic agent for NETs compared with only β-emitting yttrium-90 labeled PRRT. Several recent studies reported that Lu-177 gave an overall positive response and improved the patients' quality of life. To fully exploit its potential, large comparative studies are needed for the assessment of distinct efficacies of Lu-177 labeled PRRT. Additionally, for extending the indications and developing new regimens of Lu-177-based PRRT, more dedicated clinical research is required.

1-methylhydantoin inhibits secretion of growth hormone in rabbits / 中国药理学通报

Aim Toexplorewhether1-methylhydan-toin(MH)could inhibit the basal secretion of growth hormone (GH ) and suppress the promoting effect of growth hormone-releasing hormone (GHRH ) in rab-bits.Methods Thirty-sixrabbitswererandomlydi-vided into six experimental groups according to the kind of dosing drugs,namely normal saline group(A), MH group (B ),octreotide group (C ),GHRH group (D),GHRH +MH group(E),GHRH +octreotide group(F),with 6 rabbits in each group.Blood was sampled (1. 0 mL each time)from each rabbit before injecting drugs and 5,15,30,45,60 min after drug administration.Clotting spontaneously,rabbits blood samples were centrifugated for 20 minutes at approxi-mately 1000 ×g and the supernatant was collected. Serum GH concentrations were determined by enzyme linked immunosorbent assay kit(ELISA Kit).Mean-while,the behavior of rabbits in each group after injec-tingdrugswascloselyobserved.Results TheGH level of rabbits in group A at each time point had no significant differences(P>0. 05 ).Group B and group C rabbit GH levels were significantly lower than those of group A (P<0. 05 ),while GH levels in group D were obviously higher than those of group A (P <0. 05 ).Compared with group D,rabbit GH levels in group E and group F decreased markedly(P<0. 05 ). No obvious toxic and side effects had been observed within one week after the experimental rabbits were ad-ministered corresponding drugs by intravenous injec-tion.Conclusions 1-methylhydantoincouldinhibit the basal secretion of GH in rabbits.1-methylhydan-toin could suppress the promoting effect of GHRH in rabbits.

Advances in drug treatment of acromegaly / 中国生化药物杂志

Acromegaly is mostly caused by a pituitary adenoma secreting growth hormone ( GH ) , which leads to a wide range of endocrine morbidities, with an insidious onset and slow progression.A long-term overproduction of GH results in elevated insulin-like growth factor-1 ( IGF-1 ) level, which in turn, would cause target organ damage and an increased risk for mortality and decreased quality of life.Herein, the literature regarding the progress of drug therapy for acromegaly in recent five years is reviewed.

Análogos de la somatostatina en el tratamiento de la retinopatía diabética / Somatostatin analogues in the treatment of diabetic retinopathy

La retinopatía diabética constituye un importante problema de salud por la discapacidad visual que provoca. El tratamiento de elección continúa siendo la fotocoagulación láser, pero en ocasiones hay formas avanzadas en que la respuesta es pobre y la evolución tórpida. Se continúan buscando otras alternativas de tratamiento que puedan mejorar la evolución, como son los esteroides y antiangiogénicos. Con el objetivo de reagrupar información actual sobre este grupo de medicamentos (análogos de la somatostatina), los cuales tienen efectos antiangiogénicos y han sido usados en el tratamiento de la retinopatía diabética proliferativa y el edema macular diabético, se realizó esta revisión. Los análogos de la somatostatina han mostrado ser eficaces, fundamentalmente, en el control de los fenómenos hemorrágicos y proliferativos en la retinopatía diabética proliferativa, y al mejorar también la integridad de la barrera hematoretiniana, ofrecen una alternativa de tratamiento para el edema macular diabético, fundamentalmente, cuando la respuesta al láser no resulta favorable(AU)

The diabetic retinopathy is an important health problem due to visual disability provoked. The choice treatment still remains the laser photocoagulation, but sometimes there is advanced ways in which the response is poor and the course is torpid. Other alternatives of treatment are look for to improve the course including the steroids and anti-angiogenic. The aim of present review was to regroup the current information on this group of drugs (somatostatin analogues), which has a anti-angiogenic effect and used in the treatment of proliferative diabetic retinopathy and the diabetic macular edema. The somatostatin analogues have shown to be effective, mainly in the control of hemorrhagic and proliferative phenomena and to also improve the integrity of the hematoretinal barrier, offer an alternative of treatment for diabetic macular edema, mainly when the response to laser is not favorable(AU)

Cost-effectiveness analysis of somatostatin analogues in the treatment of acromegaly in Brazil / Análise de custo-efetividade de análogos da somatostatina no tratamento de acromegalia no Brasil

This study aims to compare economic and patient impacts of the treatment of acromegaly with two different somatostatin analogues (octreotide LAR and lanreotide SR) in Brazil. A cost-effectiveness analysis was carried out under the Brazilian Public Health Care System (SUS) perspective. A decision analytical model was developed based on the Brazilian Public Health Care System Clinical Guideline for Acromegaly. A hypothetical cohort of 276 patients was followed for two years. Data were extracted from literature and administrative databases. Based on the analytical model, treatment with octreotide LAR would avoid 12 and 17 cases of GH and IGF-I elevated serum levels, respectively. Octreotide LAR was a cost-saving strategy, with net savings of R$10,448,324 (US$4,465,096) to SUS. Annual net savings per patient were R$ 18,928 (US$8,089). Treatment of acromegaly with octreotide LAR is a dominant strategy when compared to the treatment with lanreotide SR in Brazil. Sensitivity analysis did not alter the cost-saving status.

O objetivo deste estudo é comparar o impacto econômico e o impacto nos pacientes com acromegalia do tratamento com dois diferentes análogos de somatostatina (octreotida LAR e lanreotide SR) no Brasil. Um estudo de custoefetividade foi realizado a partir da perspectiva do Sistema Único de Saúde (SUS). Foi desenvolvido um modelo analítico de decisão baseado no Protocolo Clínico e Diretrizes Terapêuticas de Acromegalia do SUS. Uma coorte hipotética de 276 pacientes foi seguida por dois anos. Dados foram obtidos da literatura e bases de dados oficiais do SUS. Baseado no modelo analítico, o tratamento com octreotida LAR evitaria 12 e 17 casos com níveis elevados de GH e IGF-I, respectivamente. Octreotida LAR foi uma estratégia econômica, gerando economia de R$10.448.324 (US$4.465.096) para o SUS. A economia anual por paciente foi de R$18.928 (US$8.089). O tratamento de acromegalia com octreotida LAR é estratégia dominante quando comparado com o tratamento com lanreotida SR no Brasil. A análise de sensibilidade não alterou seu status de econômica.

Effects of somatostatin analogues on pancreatic tissue TGF ?_1 expression in acute pancreatitis in rats and its mechanisms / 中华消化杂志

Objective To determine the effects and mechanisms of somatostatin analogues (sandostatin) on pancreatic repair and regeneration in caerulein induced pancreatitis. Methods Acute pancreatitis was induced by intra abdominal infusion of caerulein in rats, sandostatin was administered intra abdominally at the time of induction of pancreatitis and 24, 48 and 72 hours after. Rats were sacrificed at 6, 24, 48, 72 and 96 hours after the operation. The mRNA expression for Transforming growth factor ? 1 (TGF ? 1) was evaluated by reverse transcription polymerase chain reaction, pancreatic tissue DNA synthesis was measured by 3H thymidine method in vitro and protein content was detected by Lowry's method. Results The serum amylase level was decreased significantly in the sandostatin treated group. Expression of TGF ? 1 mRNA was undetectable in the normal pancreas and the treated group at 6 hours. TGF ? 2 was observed at 24 hours after the induction of pancreatitis, reaching maximum at 72 hours. It could be detected in the sandostatin treated group at 6 hours, reaching maximum at 24 hours, the expression of TGF ? 1 was increased significantly in the sandostatin treated group as compared with the non treated group at 24, 48 hours. Pancreatic tissue DNA synthesis showed a significant decrease during the first 72 hours following the induction of pancreatitis and a marked increase was observed at 96 hours after treatment with sandostatin. Within 48 hours of the induction of pancreatitis, total protein content in pancreatic tissue declined, and there was a significant increase in the sandostatin treated group at 48 hours, reaching maximum at 96 hours. Conclusions Effects of somatostatin analogues (sandostatin) on pancreatic tissue regeneration in acute pancreatitis in rats might be attributed to the enhancement of TGF ? 1 gene expression which subsequently stimulates formation of extracellular matrix components, increases protein content and DNA synthesis, thus accelerates pancreatic repair and regeneration.

A Meta-analysis of somatostatin analogues in treatment of Graves ophthalmopathy / 第二军医大学学报

Objective:To examine whether somatostatin analogous(SSAs) have effect on Graves ophthalmopathy and to compare its effects with that of glucocorticoid.Methods: Both a computer aided search of MEDLINE and Chinese Biological Medicine disc and an intensive search by hand were conducted to identify all controlled studies assessing the effect of SSAs on Graves ophthalmopathy.Results: Five studies were finally included.Three of them found SSAs to be significantly more effective than placebo;2 of them found SSAs to be able to reduce proptosis; 2 of them found SSAs to be equally effctive as glucocorticoid.The pooled OR, pooled mean difference, pooled OR were 0.070.02,0.23],-1.47 -2.10,-0.84] and 0.95 0.25,3.59] respectively.Conclusion: This Meta analysis demonstrates that SSAs are effective in treatment of Graves ophthalmopathy and in reduction of proptosis, and it is equally effctive as glucocorticoid.