Mg Of Octreotide Research Articles

THU025 Acromegaly And Central Hyperthyroidism

Abstract Disclosure: A. Akhtar: None. M.A. Mahmood: None. Introduction: Pituitary adenomas are usually benign neoplasms that are the third most common type of central nervous system tumors. Although TSH releasing tumor accounts for 1% of pituitary adenomas, about one-third of the time it co-secretes Growth Hormone. Co-secretion of TSH and GH can further promote the prognosis of the tumor, therefore, must be immediately treated medically or surgically. Case Report: The case is of a 42 years old male patient who presented to his orthodontist with the complaint of loosening teeth and was referred to a primary care physician. According to the patient, he has observed an increase in his ring size up to 3 times his usual size, one and a half increase in his shoe size, some degree of joint pain, occasional visual blurriness, no weight loss, and snoring. He has no history of headaches, breast tenderness, or discharge. He works at a farm and has no family history of pituitary tumors. His laboratory findings in May 2021 show IGF-1 1028 ng/mL (normal less than 278 ng/mL), ACTH 72.2 pg/mL (normal <60pg/mL), Prolactin, TSH, LH and FSH levels were normal. These findings suggested an IGF-producing pituitary adenoma. During further workup, he had high levels of free T4 and free T3, 2.7 ng/dL and 8.2pg/mL (Normal 2.3 - 4.2pg/mL), respectively, along with elevated TSH levels, which were 8.1mIU/L (normal 0.27-4.2mIU/L). Magnetic resonance imaging showed a pituitary mass of 1.8cm x 2.0cm x 1.6cm in the suprasellar region, abutting the optic chiasm, and showed heterogeneous enhancement. There were no signs of hemorrhage. His visual field examinations were normal. He was prescribed to take 50mg of octreotide every 8 hours. In six weeks, the patient had improved levels of serum TSH which was lowered to 0.785mIU/L, and free T4 and free T3, which were 1.62pmol/L and 3.45pmol/L, respectively. He had transsphenoidal pituitary surgery. Pathology showed a 2.6 x 2.0 x 0.3 cm tumor of somatotropic type. Post-surgery MRI showed no tumor residues. Discussion: We report a middle-aged man with a rare case of the pituitary tumor with acromegaly and central hyperthyroidism. Thyrotropinomas, also known as TSHomas, are benign pituitary adenoma that produces thyroid stimulating hormones. Although rare, they are macroadenomas 80% of the times and 20-25% of the time co-secrete other pituitary hormones. These tumors may show elevated fT3, fT4, and TSH, and increased alpha-subunit. There is not enough evidence to proof the exact origin of the pathology, however, immunohistologically, the tumor cells arise from PIT1-lineage adenohypophyseal cells and could be associated with MEN 1 mutation on chromosome 11q13. Surgical removal of the tumor is a preferred approach to TSHomas, but recent studies have shown a significant improvement with medial therapy of somatostatin analogs by interacting with somatostatin receptors. Octreotide, a somatostatin analog has been clinically shown to bring the thyroid hormones to a normal level in 80% if cases and shrinkage of tumor size in pituitary adenoma in 60% of cases. It can be used as a pre-operative therapy to reduce the levels of free thyrotropin. It also reduces GH and serum IGF-1 levels. Co-secretion of TSH and GH promotes the prognosis of tumors which may be prevented with early diagnosis and treatment. Presentation: Thursday, June 15, 2023

Combination of pasireotide and octreotide: effects on GH and IGF-I secretion and glucose metabolism in healthy volunteers.

To assess the pharmacokinetics, pharmacodynamics and tolerability of different doses of octreotide and pasireotide (subcutaneous [sc] and long-acting release [LAR]) when co-administered in healthy volunteers. This was an exploratory, Phase I, single-centre study. Healthy adults were enrolled in a staggered approach into seven cohorts to receive octreotide and pasireotide (sc and LAR formulations), alone or in combination. Plasma drug concentrations, growth hormone (GH), insulin-like growth factor I (IGF-I), and plasma glucose were assessed at baseline, immediately after sc treatment, and 21 and 28 days after LAR treatment. Of 88 enrolled subjects, 52 and 82 participated in sc and LAR dosing phases, respectively. There were no relevant pharmacokinetic interactions between octreotide and pasireotide. In combination, pasireotide sc (150 µg) and octreotide sc (100/300 µg) resulted in numerically greater reductions in insulin levels and a higher incidence of AEs than either single agent; the rapid (within 1 h) increase in plasma glucose after pasireotide was delayed with combination treatment. Octreotide sc and pasireotide sc, alone or in combination, reduced IGF-I levels and led to undetectable GH levels in most subjects. During the LAR phase, addition of a low dose of pasireotide (5 mg) to a standard dose of octreotide (20 mg) resulted in an ~2-fold reduction in median IGF-I versus octreotide 20 mg 21 days post-dose; this effect was numerically greater than seen for pasireotide 20 mg alone. Peak plasma glucose was substantially lower after LAR than sc dosing. Interestingly, glucose levels were also numerically lower in the pasireotide 5 mg plus octreotide 20 mg group than for 20 mg of octreotide or pasireotide alone. AEs were less frequent after LAR than sc dosing. Combined low doses of pasireotide LAR (5 mg) and octreotide LAR (10-30 mg) provided greater suppression of IGF-I than either single agent and did not increase blood glucose or incidence of AEs versus either agent alone.

The Dose of Somatostatin Analogues during Pre-Surgical Treatment Is a Key Factor to Achieve Surgical Remission in Acromegaly

Purpose: to determine whether pre-surgical treatment using long-acting somatostatin analogues (SSAs) may improve surgical outcomes in acromegaly. Methods: retrospective study of 48 patients with acromegaly operated by endoscopic transsphenoidal approach and for first time. Surgical remission was evaluated based on the 2010 criteria. Results: most patients, 83.3% (n = 40), harbored macroadenomas and 31.3% (n = 15) invasive pituitary adenomas. In this case, 14 patients were treated with lanreotide LAR and 6 with octreotide LAR, median monthly doses of 97.5 [range 60–120] and 20 [range 20–30] mg, respectively, for at least 3 months preoperatively. Presurgical variables were comparable between pre-treated and untreated patients (p > 0.05). Surgical remission was more frequent in those pre-treated with monthly doses ≥90 mg of lanreotide or ≥30 mg of octreotide than in untreated or pre-treated with lower doses (OR = 4.64, p = 0.025). However, no differences were found between pre-treated and untreated patients when lower doses were included or between those treated for longer than 6 months compared to those untreated or pre-treated for shorter than 6 months. Similarly, no differences were found either in terms of surgical or endocrine complications (OR = 0.65, p = 0.570), independently of the doses and the duration of SSA treatment (p > 0.05). Conclusions: the dose of SSAs is a key factor during pre-surgical treatment, since the beneficial effects in surgical remission were observed with monthly doses equal or higher than 90 mg of lanreotide and 30 mg of octreotide, but not with lower doses.

Presurgical somatostatin receptor ligand treatment does not affect tumor consistency in GH-secreting pituitary macroadenomas.

PurposeTo evaluate whether presurgical treatment using long-acting somatostatin receptor ligands (SRL) may change pituitary tumor consistency and improve surgical outcome in GH-secreting pituitary macroadenomas.MethodsRetrospective study of 40 patients with GH-secreting pituitary macroadenomas operated for the first time by endoscopic transsphenoidal approach. Tumor consistency was evaluated intraoperatively and then correlated with histopathological fibrosis parameters and surgical outcomes. Surgical remission was reported based on the 2010 criteria.ResultsThe mean tumor size of GH-secreting macroadenomas was of 16.9 ± 8.2 mm and 25 were invasive pituitary adenomas (PAs). Presurgical treatment with long-acting SRL was performed in 17 patients (11 lanreotide, 6 octreotide). The cure rate was higher in those patients pre-treated with monthly doses ≥30 mg of octreotide or ≥90 mg of lanreotide than in those treated with lower doses or untreated (8/11 (72.7%) vs 11/29 (37.9%), P = 0.049). However, although the proportion of soft tumors increased as higher doses of SRL were considered in the pre-treated group, no statistical significance was reached, even when the highest approved monthly doses were used (6/6 (100%) vs 23/34 (67.7%), P = 0.102). Moreover, we found that the remission rate was similar between fibrous and soft tumors (P = 0.873) and also of surgical complications (P = 0.859), despite of the higher prevalence of Knosp >2 (P = 0.035) and very large PA (P = 0.025) in fibrous tumors than in soft tumors.ConclusionsAlthough presurgical treatment with high doses of SRL was associated with a 2.2-fold greater chance of surgical remission, this benefit was not related with changes in tumor consistency induced by the presurgical treatment.

Everolimus, lutetium-177 DOTATATE and sunitinib for advanced, unresectable or metastatic neuroendocrine tumours with disease progression: a systematic review and cost-effectiveness analysis.

Neuroendocrine tumours (NETs) are a group of heterogeneous cancers that develop in cells in the diffuse neuroendocrine system. To estimate the clinical effectiveness of three interventions [everolimus (Afinitor®; Novartis International AG, Basel, Switzerland), lutetium-177 DOTATATE (177Lu-DOTATATE) (Lutathera®; Imaging Equipment Ltd, Radstock, UK) and sunitinib (Sutent®; Pfizer Inc., New York, NY, USA)] for treating unresectable or metastatic NETs with disease progression and establish the cost-effectiveness of these interventions. The following databases were searched from inception to May 2016: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Daily, Epub Ahead of Print, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. We systematically reviewed the clinical effectiveness and cost-effectiveness literature on everolimus, 177Lu-DOTATATE and sunitinib for treating advanced, unresectable or metastatic progressive NETs. The following NET locations were considered separately: pancreas, gastrointestinal (GI) tract and lung, and GI tract (midgut only). We wrote a survival partition cohort-based economic evaluation in Microsoft Excel® 2013 (Microsoft Corporation, Redmond, WA, USA) from the UK NHS and Personal Social Services perspective. This comprised three health states: (1) progression-free survival (PFS), (2) progressed disease and (3) death. Three randomised controlled trials (RCTs), RADIANT-3 [RAD001 in Advanced Neuroendocrine Tumors, Third Trial; pancreatic NETs (pNETs): everolimus vs. best supportive care (BSC)], A6181111 (pNETs: sunitinib vs. BSC) and RADIANT-4 (RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial; GI and lung NETs: everolimus vs. BSC), met the inclusion criteria for the clinical effectiveness systematic review. The risk of bias was low. Although the NETTER-1 (Neuroendocrine Tumors Therapy) RCT, of 177Lu-DOTATATE plus 30 mg of octreotide (Sandostatin®, Novartis) compared with 60 mg of octreotide, was excluded from the review, we nonetheless present the results of this trial, as it informs our estimate of the cost-effectiveness of 177Lu-DOTATATE. The pNETs trials consistently found that the interventions improved PFS and overall survival (OS) compared with BSC. Our indirect comparison found no significant difference in PFS between everolimus and sunitinib. Estimates of OS gain were confounded because of high rates of treatment switching. After adjustment, our indirect comparison suggested a lower, but non-significant, hazard of death for sunitinib compared with everolimus. In GI and lung NETs, everolimus significantly improved PFS compared with BSC and showed a non-significant trend towards improved OS compared with BSC. Adverse events were more commonly reported following treatment with targeted interventions than after treatment with BSC. In the base case for pNETs, assuming list prices, we estimated incremental cost-effectiveness ratios (ICERs) for everolimus compared with BSC of £45,493 per quality-adjusted life-year (QALY) and for sunitinib compared with BSC of £20,717 per QALY. These ICERs increased substantially without the adjustment for treatment switching. For GI and lung NETs, we estimated an ICER for everolimus compared with BSC of £44,557 per QALY. For GI (midgut) NETs, the ICERs were £199,233 per QALY for everolimus compared with BSC and £62,158 per QALY for a scenario analysis comparing 177Lu-DOTATATE with BSC. We judge that no treatment meets the National Institute for Health and Care Excellence's (NICE) end-of-life criteria, although we cannot rule out that sunitinib in the A6181111 trial does. A RCT with included comparators was not identified for 177Lu-DOTATATE. The indirect treatment comparison that our economic analysis was based on was of a simple Bucher type, unadjusted for any differences in the baseline characteristics across the two trials. Given NICE's current stated range of £20,000-30,000 per QALY for the cost-effectiveness threshold, based on list prices, only sunitinib might be considered good value for money in England and Wales. Further analysis of individual patient data from RADIANT-3 would allow assessment of the robustness of our findings. The data were not made available to us by the company sponsoring the trial. This study is registered as PROSPERO CRD42016041303. The National Institute for Health Research Health Technology Assessment programme.

The Role of the Acute Octreotide Suppression Test in Detecting Patients with Neuroendocrine Neoplasms

Background: Serum chromogranin A (CgA) is routinely used as a biomarker in patients with neuroendocrine neoplasms (NENs). Several conditions and comorbidities may be associated with falsely elevated CgA, often leading to extensive diagnostic evaluation, which may be costly and harmful. The aim of this study was to analyze the effectiveness of the acute octreotide suppression test (AOST) in differentiating falsely elevated serum CgA. Methods: Our prospective study enrolled 45 patients from two different patient cohorts: (1) 29 patients with suspicion or presence of NENs (extensive workup and subsequent biopsy confirmed 16 NENs); (2) 16 consecutive patients admitted via the Emergency Department without NENs (non-NENs). AOST was performed after an overnight fast. Baseline CgA was measured, after which 0.25 mg of octreotide was administered subcutaneously. CgA was measured 3 and 6 h after administration. Results: Baseline CgA levels were similar in NENs and non-NENs. At the end of the AOST, CgA decreased by a median of 83.3% (41.0–127.4) in non-NENs and 13.8% (0.0–43.6) in NENs (p < 0.001). In patients with increased baseline CgA, a decrease in CgA at the 6th hour of < 51.3% had 90.0% sensitivity and 88.9% specificity in detecting NENs. In patients with normal baseline serum CgA, a decrease in CgA at the 3rd hour of < 17.6% had 83.3% sensitivity and 81.8% specificity in detecting patients with NENs. The diagnostic accuracy of the AOST in the entire study population was 86.7%. Conclusions: AOST is a promising tool to increase the diagnostic accuracy of serum CgA.

Effect of Octreotide Administration in the Prophylaxis of Post-ERCP Pancreatitis and Hyperamylasemia: A Multicenter, Placebo-Controlled, Randomized Clinical Trial

Since the introduction of endoscopic retrograde cholangiopancreatology (ERCP) in clinical use, pancreatitis has become a common complication of ERCP. Octreotide is an inhibitor of pancreatic enzyme secretions. Several studies have evaluated the effect of octreotide on the incidence of clinical pancreatitis after ERCP, but with different results. The aim was to determine the efficacy of prophylactic administration of octreotide for the prevention of post-ERCP pancreatitis (PEP) and hyperamylasemia. In this study, patients with scheduled ERCP were randomized to receive either octreotide (0.3 mg) via intramuscular injection or a placebo. The study was conducted in 12 digestive endoscopic units in China. Patients were randomized into two groups: an octreotide group (N = 414) and a control group (N = 418). In the octreotide group, octreotide (0.3 mg) was dissolved in 500 mL of 0.9% saline solution and administered by continuous intravenous infusion, beginning 1 h before endoscopic examination and continued for 6 h thereafter; 0.1 mg of octreotide was injected subcutaneously at 6 and 12 h after the intravenous injection was stopped. The control group was given a placebo intravenously. The end point was the development of acute pancreatitis. The overall incidence of acute pancreatitis was 3.85%; this included 2.42% (10/414) in the octreotide group and 5.26% (22/418) in the control group (P = 0.046). The overall incidence of hyperamylasemia was 14.9%; 12.32% (51/414) in the octreotide group and 17.46% (73/418) in the control group (P = 0.041). No side effects were found. The results indicate that octreotide can prevent PEP and hyperamylasemia.

Analysis of Peripheral Blood T-Cell Subsets in Active Thyroid-Associated Ophthalmopathy: Absence of Effect of Octreotide-LAR on T-Cell Subsets in Patients with Thyroid-Associated Ophthalmopathy

Thyroid-associated ophthalmopathy (TAO) is thought to be a T-cell-mediated autoimmune disorder. We sought to characterize abnormalities in the peripheral blood T-cell subsets in patients with TAO, and examine whether the long-acting somatostatin analogue, octreotide-LAR, treatment affects these cells. We analyzed peripheral blood T-cell subsets by flow cytometry in 26 euthyroid patients with moderately severe active TAO and 24 controls. Twenty-five of the patients with TAO were enrolled in a randomized trial to receive either 30 mg of octreotide-LAR (n = 11) or placebo (n = 14) every 4 weeks for 16 weeks; all 25 patients subsequently received octreotide-LAR 30 mg every 4 weeks from week 16 to 32. T-cell subsets were analysed at baseline, week 16, and week 32. At baseline, the relative percentage of CD4+ helper T-cells (p = 0.0003) and the CD4+/CD8+ ratio (p = 0.008) were significantly higher in patients with TAO compared to controls. Patients with TAO had higher naïve active T cells (CD45RA+, CD45RA+ CD4+) and lower memory T cells (CD45RO+, CD45RO+ CD4+) than controls. At weeks 16 and 32, there were no significant differences in any T-cell subsets between the octreotide-LAR-treated and placebo groups. These results support a role of T cell in the pathogenesis of TAO, and show that octreotide-LAR has no effect on T-cell subsets during 32-weeks of treatment.

The use of long-acting somatostatin analogue (octreotide) for prophylaxis of acute pancreatitis after endoscopic sphincterotomy

Acute pancreatitis is a serious complication of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST). In addition, serum pancreatic enzymes increase without clinical symptoms in about 40-50% of patients undergoing these endoscopic procedures. We evaluated the potential of octreotide, a long-acting somatostatin analogue, to prevent these complications in patients who underwent EST for choledocholithiasis. 151 patients were randomly allocated to two groups (A and B). Group A was given 0.1 mg of octreotide subcutaneously 120 and 30 min before EST and four hours after; group B was given a placebo. Serum amylases (normal range 20-220 IU/l) were measured before premedication and 4, 24, and 48 hours after the end of endoscopy. After EST, the increase in the mean serum amylase was greater in the control group, but the difference was statistically significant only at the 48-hour measurement. There were five cases of acute pancreatitis in each group, with a trend (but not statistically significant) toward less severe pancreatitis in the treated group. In the control group, one patient with acute pancreatitis died. In conclusion, octreotide does not seem to prevent acute post-EST pancreatitis.

Hyperinsulinemia Is Not a Cause of Cortisol-Induced Hypertension

There is much interest in the relationship of hypertension to hyperinsulinemia. Six male volunteers received cortisol, 50 mg orally four times daily, for 5 days. Plasma insulin concentration increased from 11.8 +/- 3.0 mU/L to 16.1 +/- 4.0 mU/L (P = .034). Fasting glucose increased from 4.7 +/- 0.3 to 5.8 +/- 0.1 mmol/L (P = .001). The insulin-to-glucose ratio was unchanged. Octreotide has been reported to lower blood pressure in obese, hyperinsulinemic, hypertensive patients. The hypothesis that cortisol-induced hypertension might be secondary to steroid-induced hyperinsulinemia was examined by determining whether reversal of hyperinsulinemia by octreotide would reverse cortisol-induced hypertension. Five healthy men were given two subcutaneous injections of 0.05 mg of octreotide before and on the fifth day of cortisol administration. Cortisol increased blood pressure, weight, plasma glucose concentration, and white cell count, with decreases in plasma potassium concentration and packed cell volume. Plasma cortisol concentrations were unchanged following octreotide in the control period but decreased after cortisol treatment. Insulin concentrations were reduced profoundly after octreotide, both in the control period (12.5 +/- 3.7 mU/L, falling to 1.1 +/- 0.3 mU/L at 30 min) and on cortisol (22.3 +/- 4.5 to 2.3 +/- 0.5 mU/L at 30 min). Octreotide did not lower pressure before or after cortisol treatment. Thus, octreotide was effective in lowering plasma insulin concentrations but di not lower blood pressure in normal subjects with cortisol-induced hypertension. These data do not support the notion that steroid-induced hyperinsulinemia is responsible for steroid-induced hypertension.