Comparison between somatostatin analog injections

SUMMARY OBJECTIVE: Long-acting depot formulations of somatostatin analogs, i.e., octreotide and lanreotide, are the first-line medical therapies for patients with acromegaly to whom surgery/radiotherapy cannot be performed or who have inadequate response. In this study, we aimed to evaluate the short-term local and systemic adverse reactions developed after the somatostatin analogs injections in the patients with acromegaly, in order to compare the side effects of somatostatin analogs injections. METHODS: Patients diagnosed with acromegaly who were referred to our endocrinology clinic for monthly somatostatin analogs injections were questionnaired. Wong-Baker Faces Pain Rating Scale was used to evaluate the injection-site pain at the time of injection. The existence of leg pain, nausea, diarrhea, and abdominal pain following the previous injection was also investigated during the next injection. RESULTS: A total of 49 patients were included in the study. The statistical difference could not be shown between the injection-site pain, anorexia, and leg pain frequencies of the groups, while the frequency of gastrointestinal disturbances, i.e., diarrhea and abdominal pain, was significantly lower in the octreotide group (p<0.001 and p=0.015, respectively). CONCLUSIONS: This is the first prospective study that compared the severity of the injection-site pain by using a scoring scale, following the long-acting somatostatin analogs injections. We have shown that there was no significant association of the injection-site pain severity with the somatostatin analogs regimen nor the dose differences within each somatostatin analogs treatment.

Lanreotide and diazoxide have comparable effects on glucose levels in an elderly Japanese insulinoma patient: a case report / Journal of Rural Medicine

An insulinoma is a pancreatic neuroendocrine tumor that causes hypoglycemia. In the elderly, as surgery is not always possible, drugs are an important alternative. However, the effects of lanreotide on insulinomas have not yet been elucidated. We report the case of an 85-year-old Japanese woman who was admitted for loss of consciousness and hypoglycemia, which was resolved after intravenous glucose infusion. Insulin secretion was not inhibited during hypoglycemia. Enhanced computed tomography and OctreoScan scintigraphy revealed a pancreatic tumor (diameter, 13 mm) with radiotracer accumulation. Thus, clinical insulinoma was confirmed. However, the patient refused further examination and surgery. Diazoxide (150 mg/day) therapy resolved hypoglycemia but caused fluid retention. Consequently, we switched to lanreotide (120 mg/6 weeks). Continuous glucose monitoring revealed that both drugs had comparable effects on interstitial glucose normalization. Furthermore, 447 days after the initiation of lanreotide treatment, the patient had no hypoglycemic symptoms. Therefore, lanreotide may be a useful alternative treatment option for inoperable insulinomas in elderly individuals.

Diabetes Insipidus Induced by Combination of Short-acting Octreotide and Lanreotide for Recurrent Carcinoid Crisis of Neuroendocrine Tumour: A case report / Journal of the ASEAN Federation of Endocrine Societies

@#Somatostatin analogue is useful in carcinoid crisis for symptom control. Optimal dosing of somatostatin analogues for carcinoid symptoms is not known. This case highlighted management issues using combination short-acting octreotide infusion with long-acting lanreotide during carcinoid crisis. The patient had left lung neuroendocrine tumour that metastasized to his liver and bone, post left lobectomy. Due to extensive metastasis to the liver causing recurrent carcinoid crisis, he required shorter interval long-acting lanreotide with continuous infusion of short-acting octreotide, which led to transient diabetes insipidus. Symptoms resolved with discontinuation of treatment. Somatostatin analogues, especially in combination, may inhibit the posterior pituitary resulting in diabetes insipidus. Prompt withdrawal of short-acting somatostatin analogue and initiation of desmopressin can reverse the complication. It is important to recognize this complication with combination of octreotide and lanreotide injections to avoid serious complications.

Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement / 대한내과학회지

Acromegaly is a chronic disorder caused by excessive growth hormone (GH) secretion. In most cases, the excess GH originates from GH-producing pituitary adenomas. Surgery is the preferred first-line treatment for patients with acromegaly, but medical management is considered when the disease persists after surgery or in cases where patients refuse surgery or are poor candidates for surgery. Somatostatin analogues are commonly used to treat acromegaly. The Korean Endocrine Society and the Korean Neuroendocrine Study Group have developed a position statement for the use of somatostatin analogues in the medical treatment of acromegaly. This position statement is based on evidence from the current literature and expert opinions. In the case of discrepancies among expert opinions, the experts voted to determine the recommended approach.

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.

Macrodenoma hipofisario productor de TSH y GH tratado con dosis mensuales del análogo de somatostatina lanreotide. Caso clínico / Pituitary macroadenoma cosecreting thyrotropin and somatotropin treated with monthly doses of the somatostatin analog lanreotide. A case report

Los tirotropinomas son una causa rara de hipertiroidismo, con una prevalencia de un caso por millón de habitantes. Representanmenos del 2% de todos los adenomas pituitarios. Se caracterizan por la secreción autónoma de tirotrofina (TSH) y la refractariedada la retroalimentación negativa de las hormonas tiroideas. Los adenomas mixtos se diferencian por la hipersecreción concomitantede otra hormona de la hipófisis anterior, y se encuentran hasta un 25% de los pacientes, siendo el 15% productoresde somatotrofina (GH).Debido a su infrecuencia, presentamos el caso de una mujer de 62 años, con antecedente de enfermedad de Graves diagnosticadaa los 28 años de edad, tratada con dos dosis de iodo radioactivo. Es derivada a nuestro servicio a la edad de 62 años conel siguiente laboratorio: TSH 38 µUI/ml (0,3-4,2), T4 12.8 µg/ml (4,5-12,5) e IGF-1 445 ng/ml (81-230) y una resonanciamagnética nuclear (RMI) que informaba un macroadenoma hipofisario invasivo. Tras la actualización de los estudios y laconfirmación diagnóstica se inició tratamiento médico con lanreotide intramuscular, 120 mg cada 28 días, obteniendo buenarespuesta bioquímica.

Thyrotropin secreting pituitary adenomas (TSH-omas) are a rare cause of hyperthyroidism with a prevalence of about one case permillion. They account for less than 2% of all pituitary adenomas. TSH secretion is autonomous and refractory to the negative feedbackof thyroid hormones. Mixed adenomas are characterized by concomitant hypersecretion of other anterior pituitary hormones, and arefound in about 25% of patients; approximately 15% secrete somatotropin (GH).Because of their rarity, we report the case of a 62 year old women with a history of Graves’ disease diagnosed at 28 years of age,treated with two doses of I-131, and referred to our service with the following laboratory: TSH 38 µIU/ml (0.3-4.2), T4 12.8 µg/ml(4.5-12.5) and IGF-1 445 ng/ml (81-230). RMI showed an invasive pituitary macroadenoma. After updating and confirming thecomplementary studies, medical treatment was started with the somatostatin analog lanreotide, 120 mg i.m. every 28 days; there wasgood biochemical response.

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.

Therapeutic effects of a long-acting formulation of lanreotide in Korean patients with acromegaly / 대한내과학회지

BACKGROUND: The present study was conducted to examine the effects of a long-acting formulation of lanreotide (Somatulin-Autogel(R)) in Korean acromegalic patients who had undergone surgery. METHODS: The subjects in the study were 11 acromegalic patients (5 men and 6 women) who had undergone transsphenoidal tumor resection at Korea University Guro Hospital. The anthropometric parameters, blood pressure, fasting blood glucose (FBG), IGF-1, HbA1C, mass size and GH level following a 75 gm oral glucose tolerance test (OGTT) were measured in each subject before and after treatment with a long-acting formulation of lanreotide. RESULTS: The median age of the subjects was 41 yrs (range: 28-52 yrs) (Table 1). The mean pre-operative levels of serum IGF-1 in the 11 patients was 1185+/-323.58 ng/mL, and post-operatively it was 862+/-314.06 ng/mL. The mean serum IGF-1 concentration decreased from 862+/-314.06 ng/mL to 549+/-371.62 ng/mL after 6 months treatment with the long-acting formulation of lanreotide (p=0.003, vs baseline, n=11), and it decreased further to 439+/-342.53 ng/mL after 12 months treatment (p=0.005 vs baseline, n=10) (Table 3). Two patients achieved the target level of IGF-1. The HbA1C measured before and after lanreotide treatment was 5.8+/-0.5% and 5.9+/-0.3%, respectively. CONCLUSIONS: This study showed that a long-acting formulation of lanreotide decreased the IGF-1 and GH levels without significant side effects. In spite of the small number of subjects in this study, these findings suggest that this formulation of lanreotide is effective for the post-operative management of acromegaly.

Lanreotide Therapy in Graves' Ophthalmopathy / 대한내분비학회지

BACKGROUND: Graves' ophthalmopathy (GO) is an autoimmune process that affects the orbital tissues. Patients with GO are usually treated with high doses of corticosteroids, retrobulbar irradiation, or by surgical decompression, however, those have some adverse effect. Recently, a synthetic somatostatin analogue has been reported for the treatment of GO. This study was performed prospectively to evaluate the therapeutic effects of lanreotide, a potent long acting synthetic somatostatin analogue, in patients that have GO. METHODS: Eight patients with moderate to severe GO (M:F=1:7, age 39.0+/-11.8 years) were included. Patients who had been treated with other modalities than GO, or had a systemic illness such as diabetes were excluded. Eight patients were given lanreotide, 40mg IM every 2 weeks over a period of 8 weeks. Their therapeutic responses were evaluated using an orbital CT or MRI and by ophthalmologic examinations. RESULTS: After 8 weeks' of lanreotide treatment, 4 patients showed decreased scores in the NOSPECS classification (p=0.059) as well as 5 patients in their clinical activity scores(p=0.109). All of the 8 patients showed improvements according to clinical evaluation criteria (p=0.008). Significant changes in the thickness of both the lateral rectus and superior rectus muscles were observed (p<0.05). No patient showed serious adverse effects related to lanreotide therapy during the follow-up periods. CONCLUSION: We conclude that lanreotide therapy has clinical benefits and show radiologic improvements in GO. Considering the minimal side-effects of lanreotide compared to those of corticosteroid, lanreotide therapy should be considered for use in selected patients that have Graves' ophthalmopathy

The Clinical Result of Somatuline(R) Therapy in Thyroid Ophthalmopathy

PURPOSE: Octreotide, a potent synthetic somatostatin (SM) analogue, was recently evaluated and found to have a beneficial effect in thyroid eye disease (TED). Lanreotide (LRT: Somatuline(R)), a new SM analogue, is more active and has a much longer duration of action. The aim of this study was to report the therapeutic effect of LRT on the treatment of TED. METHODS: Four patients of mean age 42.5 years had severe acute thyroid-related ophthalmopathy symptoms. The NOSPECS system was applied in this study to evaluate the response to treatment. They received 40 mg LRT i.m. every 2 weeks over a period of 3 months. RESULTS: All of them showed a significant improvement of acute inflammatory symptoms in both eyes. The average of TED score was 3.6, while it was 6.3 before the injection. Average clinical activity score of pre-injection was 4.1 and it markedly decreased to 1.3, and the self assessment score was 1.4, which means a moderate satisfaction. The amount of proptosis was found to decrease about 3.0 mm. CONCLUSIONS: We report our clinical experience that LRT has a beneficial effect on active TED and it is a good therapeutic modality for medical treatment.

The Effect of Slow Release Lanreotide in Korean Acromegalic Ratients / 대한내분비학회지

BACKGROUND: Previous studies have shown that somatostatin analogues such as octreotide are effective in suppressing GH and IGF-I levels in acromegaly. The recent availability of slow release lanreotide could avoid the inconveniences associated with either repeated subcutaneous injections or continuous infusions. We investigated the effects of the SR-lanreotide on clinical, biochemical and safety responses in five patients with acromegaly. And we investigated whether the response of the GH level to acute adrninistration of octreotide predicts the response after 12 weeks of treatment with the SR-lanreotide and whether the identification of gsp oncogene could be used as a therapeutic and prognostic clue in treatment with the SR-lanreotide. METHODS: We studied the effects of SR-lanreotide 30 mg administered intramuscularly biweekly for 12 weeks in five Korean acromegalic patients. Subjective improvements in the clinical symptoms of acromegaly and adverse reactions were recorded. During SR-lanreotide treatment, serum GH, IGF-I and IGFBP-3 concentrations were evaluated just before the next injection of the SR-lanreotide. Before the start of SR-lanreotide therapy the sensitivity of GH secretion to the octreotide was tested by measuring the effect of the acute response to 0.1 mg intravenously on plasma GH levels followed until 6 hours after administration of octreotide. Direct polymerase chain reaction sequencing of the gsp oncogene were performed. We compared the responses to SR-lanreotide in patients harboring gsp-positive and gsp-negative somatotroph adenomas. RESULTS: The treatment with SR-lanreotide for 12 weeks could suppress the GH level by more than 50% in four of five patients and normalize the IGF-I in two patients. No correlation was found between the GH level and IGF-I level at the end of the study. The IGFBP-3 level correlated with the IGF-I level in three of five patients. Although the initial GH response to octreotide tended to correlate with the IGF-I response after SR-lanreotide treatment, the results were statistically insignificant. The patients with gsp-positive tumor tended to show a better response to SR-lanreotide. During treatment, there was a reduction in the percentage of patients complaining of joint pain, fatigue, digital paresthesia, and hyperhydrosis. Changes in soft tissue swelling were documented by decreases in finger circumference. The common adverse events were abdominal discomfort, loose stool, and diarrhea. These events were decreased progressively. No patients discontinued the treatment of SR-lanreotide due to adverse events. CONCLUSION: This study showed that SR-lanreotide is effective in controlling acromegalic symptoms as well as GH and IGF-I hypersecretion. This treatment was well tolerated and more convenient for the patients. Further studies are required for clinical outcome of long-term SR-lanreotide treatment and cost-effective analysis.

SR (Slow-Replase) Lanreotide Treatment in Acromegalic Patients / 대한내분비학회지

BACKGROUND: Several clinical studies reported the efficacy of the long-acting SRIH analog, octreotide (Octreotide, Sandoz) in the treattnent of acromegaly. Recently, another SRIH analog (BIM 23014, Ipsen Biotech) was shown to decrease plasma GH levels in acromegalic patients. The recent availability of a long-acting formulation of BIM 23014 [slow release (SR) lanreotide] could avoid repeated sc injections or continuous sc infusions. The objective of this study was to determine the tolerability and effectiveness of the slow release (SR) somatostatin analog, SR lanreotide in active acromegaly. METHOD: Between March 1998 and May 1998, 10 patients were recruited in the prospective study carried out at Yonsei University. The effects of 6 weeks of SR lanreotide, given every 14 days at a dosage of 30 mg, im, were analyzed. All the patients completed the 6-week period of therapy. RESULTS: SR lanreotide injection produced 45% suppression of area under the curve of GH levels from the basal value on oral glucose tolerance test(OGTT). GH values on OGTT were normalized (< 2ng/mL) in 30% of patients after 6 weeks, whereas insulin-like growth factor I (IGF-I) levels were normalized in 50% of patients. No correlation was found between pretreatment GH levels and GH response to SR lanreotide or between changes in GH and IGF-I during therapy, The significant differences in response to SR lanreotide were shown between the patients with residual mass and no visible mass. During treatment, there was the significant reduction in the percentage of patients complaining of joint pain, hyperhydrosis, and paresthesias. Changes in soft tissue swelling were documented by a significant decrease in the diameter of fingers. Mild diarrhea and fatigue were the most frequent side-effects (20 30%) when SR lanreotide therapy was started. However, these side effects decreased progressively. Significant changes were noted in carbohydrate tolerance. CONCLUSIONS: These data indicate that SR lanreotide at a dose of 30 mg, im, every 14 days is an effective treatment in most unselected acromegalic patients, especially in patients with no visible mass. Tolerability to SR lanreotide therapy is high. The use of a new sustained release formulation of somatostatin analog is clearly advantageous in improving patient compliance with medical treatment for acromegaly.