Dose Of Octreotide Research Articles

Initiation of Patients onto Long-Acting Somatostatin Analogue Therapy for Neuroendocrine Tumors: A Single-Center Review of Practice

Neuroendocrine tumors (NETs) are being seen increasingly frequently, and recent data show that long-acting somatostatin analogues have become a major initial treatment, regardless of whether the tumors are functioning or not. However, test dosing with subcutaneous (sc) octreotide is usually advised to assess longer-term tolerability, although this advice is mainly based on results with functioning tumors. The aim of the study was to assess the value of an initiating test dose of sc octreotide on the prediction of subsequent adverse events after treatment with the long-acting analogue. In a single, large Centre of Excellence for NETs, a first cohort of patients (n = 24) was admitted overnight after an sc injection of octreotide, and then administered the analogue; a subsequent group (n = 53) had the test dose performed on an outpatient basis. Side effects were recorded after the test dose and subsequent treatment with the long-acting analogue. The test dose injection was of little value in predicting adverse events following the long-acting somatostatin analogue. Unless there are serious symptoms associated with a functioning NET, it is unnecessary to carry out a test dose; a change to this procedure will improve resource allocation and should enhance early initiation onto maintenance therapy. CLARINET = Controlled study of lanreotide antiproliferative response in neuroendocrine tumors LAR = long-acting repeatable NET = neuroendocrine tumor PROMID = Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with meta-static neuroendocrine midgut tumors.

Assessing Readmissions for Gastrointestinal Bleeding in Patients With Left Ventricular Assist Devices Treated With Octreotide

Introduction: Left ventricular assist device (LVAD) implantation has been associated with a high rate of gastrointestinal bleeding (GIB) that results in costly hospital readmissions for monitoring, transfusions, and endoscopy. Angiodysplasia (AVM) is a common cause of GIB found in these patients. Our institution's heart failure (HF) team has attempted to use octreotide to treat obscure or refractory GIB secondary to AVM in LVAD recipients. We set out to assess the clinical outcomes and hospitalization frequency of these patients. Methods: Retrospective analysis of LVAD patients with one or more admissions to a single academic center for GIB and history of octreotide use (March 2012-November 2016). Patients identified in a HF database of LVAD patients hospitalized for GIB. Medication reconciliation records interrogated for octreotide orders. The hospitalization in which octreotide was initiated was defined as the index stay and used as a marker to compare data before and after therapy. Patients excluded if death occurred during index stay. Number of readmissions within days 30, 60, and 90 from discharge or last octreotide dose were assessed. Results: 128 patients were identified (17 met criteria; one excluded due to death). Among 16 patients (mean age 67.5±7.4, 4 females): one patient treated with only intramuscular (IM) octreotide (dose 20mg, every 4 weeks), 5 patients with only subcutaneous (SQ) injections (dose 50-100mcg, every 8-12 hours), and 10 patients with combination IM and SQ (similar ranges). Most common endoscopic results were AVMs (35.6%) and no findings (37.9%). Mean number of admissions were 2.43 ±2.78 before index stay and 1.75 ±2.3 afterward (P=0.45), not significantly different. However, time between admissions lengthened after octreotide therapy (88.9 ±122.4 vs 216.6 ±313.8 days; P<0.05). Average length of stay per admit shortened after therapy trending towards statistical significance (10.3 ±8.9 vs 7.0 ±5.0; P=0.06). Number of endoscopies performed (P=0.08), admit Hgb (P=0.47) and INR (P=0.89) were not changed by octreotide. Readmissions in 30 and 60 days following index stay decreased significantly (P<0.05), but not in 90 days (P=0.9). Conclusion: Our study reveals that octreotide therapy for GIB in LVAD patients can lengthen the intervals between admissions and lower readmissions for GIB in 30 and 60 days. Octreotide shows potential to improve clinical outcomes but results need to be validated in a prospective study.

Budget impact of somatostatin analogs as treatment for metastatic gastroenteropancreatic neuroendocrine tumors in US hospitals.

ObjectiveWith the introduction of new therapies, hospitals have to plan spending limited resources in a cost-effective manner. To assist in identifying the optimal treatment for patients with locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors, budget impact modeling was used to estimate the financial implications of adoption and diffusion of somatostatin analogs (SSAs).Patients and methodsA hypothetical cohort of 500 gastroenteropancreatic neuroendocrine tumor patients was assessed in an economic model, with the proportion with metastatic disease treated with an SSA estimated using published data. Drug acquisition, preparation, and administration costs were based on national pricing databases and published literature. Octreotide dosing was based on published estimates of real-world data, whereas for lanreotide, real-world dosing was unavailable and we therefore used the highest indicated dosing. Alternative scenarios reflecting the proportion of patients receiving lanreotide or octreotide were considered to estimate the incremental budget impact to the hospital.ResultsIn the base case, 313 of the initial 500 gastroenteropancreatic neuroendocrine tumor patients were treated with an SSA. The model-predicted per-patient cost was US$83,473 for lanreotide and US$89,673 for octreotide. With a hypothetical increase in lanreotide utilization from 5% to 30% of this population, the annual model-projected hospital costs decreased by US$488,615. When varying the inputs in one-way sensitivity analyses, the results were most sensitive to changes in dosing assumptions.ConclusionResults suggest that factors beyond drug acquisition cost can influence the budget impact to a hospital. When considering preparation and administration time, and real-world dosing, use of lanreotide has the potential to reduce health care expenditures associated with metastatic gastroenteropancreatic neuroendocrine tumor treatments.

Posterior Reversible Encephalopathy Syndrome Due To Carcinoid Crisis Complicating Transarterial Chemoembolization for Metastatic Carcinoid Tumour

Posterior Reversible Encephalopathy Syndrome Due To Carcinoid Crisis Complicating Transarterial Chemoembolization for Metastatic Carcinoid Tumour

Escalated dose somatostatin analogues (SSAs) in management of neuroendocrine tumors (NETs): A systematic review.

422 Background: SSAs are effective in controlling NET symptoms and more recently have been shown to have anti-proliferative properties. PROMID and CLARINET have established “standard” doses of octreotide and lanreotide, but dose escalation is often employed both for symptom relief and tumor control. Methods: We searched MEDLINE, EMBASE, Cochrane CENTRAL and abstracts of major conferences. Studies investigating patients treated with doses of octreotide higher than 30mg/28d or lanreotide higher than 120mg/28d were eligible for inclusion. Data extracted included patient population, interventions and prior SSA use. The primary endpoint was disease control rate; secondary endpoints included response rate, symptom control, biochemical response, progression-free survival and toxicity. Results: 19 studies (12 prospective; 981 patients) were identified from 609 search results. Of the 13 studies that mandated prior treatment, the reasons for dose escalation were tumor progression (5), symptoms (3), either (2) and not listed (3). SSAs used were octreotide LAR (10), lanreotide ATG (1), short-acting octreotide (3), short-acting lanreotide (3), and mixtures (2). Significant heterogeneity existed in dosing schedules as well as reporting of efficacy data. Disease control rates ranged from 40-100% (pooled rate 248/396) with response rates from 0-42% (pooled rate 24/396). Dose escalation was associated with improvement in carcinoid symptoms in at least 50% of patients. Biochemical response was variably defined but reported rates ranged from 33% to 100% (pooled rate 55/78). Median PFS ranged from 6 months to 30 months. Dose escalation was generally well tolerated with side effect profile and frequency comparable to normal dose SSA. Conclusions: Escalated dose SSA is well tolerated and results in significant rates of disease control and symptomatic improvement. Compared to a prior systematic review (Broder WJG 2015), this review includes studies of lanreotide, includes 721 additional patients, and restricts inclusion to clinical studies. Prospective randomized trials of escalated SSA therapy are warranted.

Sirolimus in the treatment of three infants with diffuse congenital hyperinsulinism

Congenital hyperinsulinism (CHI) is a major cause of persistent hypoglycemia and brain damage. Therapeutic strategies to avoid near total pancreatectomy in patients who are unresponsive to maximum doses of diazoxide and octreotide remain to be identified, although sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used successfully to treat diffuse type CHI. We used sirolimus to treat three infants with diffuse CHI. Diagnosis was confirmed clinically, biochemically and by genetic testing. Homozygous mutations in KCNJ11, ABCC8 and KCNJ11 were identified in infants 1, 2 and 3, respectively. Each infant had received the therapy for at least 2 months with close monitoring of glycemic response, serum insulin and C-peptide. None of the infants responded to the therapy. We conclude that sirolimus is less effective in the treatment of diffuse CHI in patients with severe mutations in the homozygous state compared with those with the mutations in the heterozygous.

Principles «cliff» pancreatic necrosis in a first-aid hospital

Pancreatic necrosis - acute surgical disease accompanying high rates of mortality and complications. The analysis of the treatment of 256 patients with pancreatic necrosis moderate and severe degrees. In the control group was conducted basic therapy, the main (n=158), which further were administered high doses of octreotide and endoscopic stenting of the main pancreatic duct to decrease the intraductal pressure, prevention and treatment of internal pancreatic fistula. In the main group in contrast to the control is marked by a more rapid decline in the level of amylase, lipase and leukocyte index of intoxication. The infection occurred in the basic - 11%, control 20% died in the study group - 3%, control - 9%.

Octreotide use in post-cardiac surgery chylothorax: a 12-year perspective.

Background Chylothorax following cardiothoracic surgery is a rare condition in pediatric patients with significant morbidity and mortality. Pharmacological management with octreotide suggests possible efficacy; however, current evidence is inadequate. The objective of this study was to assess the safety and efficacy of octreotide as a therapeutic option in this clinical setting. Methods This was a 12-year single-center retrospective cohort study of all patients (birth to 18-years old) who received octreotide for management of post-cardiac surgery chylothorax between January 2003 to August 2015. The primary efficacy endpoint was resolution of chylothorax, categorized as complete (<2 mL·kg-1·day-1), partial (based on physician's judgement), or failed. The primary safety endpoint was any significant adverse drug reaction leading to discontinuation of octreotide therapy. Of the 46 patients identified as receiving octreotide for post-cardiac surgery chylothorax, 29 were included in efficacy and safety analyses. Results Resolution of chylothorax was achieved in 62% (complete in 28%, partial in 34%) of the total sample. The 38% who did not respond to octreotide therapy required thoracic duct ligation. The mean initial dose and duration of octreotide was 4 ± 3 µg·kg-1·h-1 and 10 ± 5 days, respectively. Besides minor side-effects including transient hyperglycemia (45%), abdominal distension (3%), and tachycardia (>150 beats·min-1; 10%), no patient developed a significant side-effect that required discontinuation of therapy. Conclusions Pharmacological management of post-cardiac surgery induced chylothorax with octreotide shows promising benefits with an acceptable safety profile.

High Dose Octreotide for the Treatment of Chylothorax in Three Neonates

Chylothorax is an abnormal condition of lymphatic fluid collection in thea€€pleural space, and the somatostatin analog octreotide is thought to have a beneficial effect on chylothorax. However, the octreotide dosage and administration route for chylothorax have been inconsistent to date. We report three neonatal cases of persistent chylothorax successfully treated with high-dose octreotide infusion therapy (20 μg/kg/h). Case 1 was congenital chylothorax, Case 2 was secondary chylothorax after an operation for congenital diaphragmatic hernia, and Case 3 was chylothorax after a cardiac operation. In all cases, the chylothorax was not decreased by a low-dose octreotide infusion, but after a high-dose octreotide infusion, the chylothorax decreased and eventually vanished, with no side effects. Conclusion: We suggest that the dose of octreotide in neonatal chylothorax can be safely increased to a maximum of 20 µg/kg/h.

Octreotide and Lanreotide in Gastroenteropancreatic Neuroendocrine Tumors.

Neuroendocrine tumors are heterogeneous, rare malignancies that arise most commonly in the gastrointestinal tract and pancreas. They often secrete vasoactive substances resulting in carcinoid syndrome and the tumor cells exclusively express somatostatin receptors. Octreotide and lanreotide are the two synthetic somatostatin analogs used for the control of carcinoid symptoms and tumor progression in advanced inoperable disease. Recent pivotal trials (PROMID and CLARINET studies) established their antitumor activity. We discuss the available data to support their use as symptom controlling and antiproliferative agents. This article also reviews the guidelines (National Comprehensive Cancer Network and North American Neuro Endocrine Tumor Society), cost-analysis (suggesting the cost-effectiveness of lanreotide autogel compared to higher doses of octreotide long acting release formulation in refractory patients), and future directions of somatostatin analogs in the management of patients refractory to conventional doses of octreotide and lanreotide.

Outcomes of the major pancreatic duct stenting and high Octreotide doses administration for acute pancreatitis

Outcomes of the major pancreatic duct stenting and high Octreotide doses administration for acute pancreatitis

Experience of Octreotide Therapy for Hyperinsulinemic Hypoglycemia in Neonates Born Small for Gestational Age: A Case Series

Aims: Hyperinsulinemic hypoglycemia (HH) is common in small-for-gestational-age (SGA) neonates. Diazoxide is often used as the first-line medication for HH in SGA neonates. Unfortunately, diazoxide is not authorized in China. We examined the effectiveness of octreotide as an alternative therapy to treat HH in SGA neonates. There is limited data on the use of octreotide in HH of SGA neonates. Methods: Seven SGA neonates with HH who were admitted to the Department of Neonatology at the Third Affiliated Hospital of Sun Yat-sen University between January 2013 and December 2014 received octreotide at an initial dose of 5 μg/kg/day through subcutaneous injection at 8-hour intervals. Depending on the glycemic control, the dose of octreotide was increased in increments of 2-5 μg/kg/day every 3-5 days to the maximum dose of 30 μg/kg/day. Results: The age of neonates with HH diagnosis ranged from 1 to 4 days. The maximum dose of octreotide ranged from 8 to 18 μg/kg/day. The duration of octreotide therapy ranged from 9 to 45 days. All patients had a clear glycemic response to octreotide, and no major adverse events were observed during the treatment. Conclusions: Octreotide may be a useful alternative therapy in HH of SGA neonates when diazoxide is unavailable.

Idiopathic Chylothorax in Infants - Is Octreotide Alone Enough?

Five month old female baby presented to us for evaluation of asymptomatic right sided pleural effusion. Pleural fluid analysis revealed it as chylous effusion. Radiological investigations revealed gross right side pleural effusion with partial collapse of right lung. After investigations, diagnosis of asymptomatic idiopathic chylothorax was made. Baby was treated with Inj. Octreotide alone. Pleural drain was not placed. After three doses of Octreotide, there was complete clearance of pleural effusion.J Nepal Paediatr Soc 2015;35(1):64-66

Management of Left Ventricular Assist Device (LVAD)-Related Gastrointestinal Bleeding (GIB): A Retrospective Case Series: Presidential Poster

Introduction: GIB complicates 17-30% of postoperative LVAD placements. Despite attempts to modulate anticoagulation and prescreening to prevent bleeding, there is no consensus on treatment for these patients. Our objective is to evaluate the potential role of octreotide LAR in patients with an LVAD for secondary prevention of GIB. Methods: Forty patients underwent LVAD implantation at our institution between 12/2012 and 12/2014. Ten developed GIB during their postoperative course (25%). Eight had bleeding secondary to arteriovenous malformations (AVMs) in the small bowel and two secondary to ulcers. Four patients suffered a recurrent GIB which was not controlled by endoscopy and were placed on octreotide. Three of the four were placed on octreotide LAR. We evaluated the clinical scenarios of these patients. Results: Three patients (2 men and 1 woman; ages 60-72) received octreotide LAR. None had a GIB prior to LVAD implantation. Post implantation, patients had a median of 5 endoscopic procedures for GIB prior to starting octreotide(range 2-9). AVMs were the cause of GIB in all 3 cases. The first patient had 7 GIBs with 36 units of packed red blood cells (pRBCs) transfused over the course of 12 months. After octreotide was started, she had 3 GIBs with 16 units of pRBCs transfused over the following 16 months. One GIB was after a missed octreotide dose and required 8 of the 16 units of pRBC. The second patient had 4 GIBs with 32 units of pRBCs transfused over 2 months. After octreotide he had 2 GIBs requiring 8 units of pRBCs over 6 months. The third patient had 2 GIBs with 33 units of pRBC transfused over 11 months. After octreotide he had no further GIBs and no transfusions for 12 months. Overall, these patients required a median of 2 endoscopic procedures (range 0-3) and a median of 8 units pRBCs (0-16) after octreotide LAR was started. In the two patients with GIBs despite octreotide, dosing was increased to twice monthly with no further bleeding. There were no thrombotic events after starting octreotide. Discussion: In post-LVAD patients, octreotide appears to markedly decrease the frequency of GIB with a reduction in transfusion requirements and endoscopic procedures. Octreotide reduces mesenteric blood flow and portal venous pressure, and has been used for treatment of small bowel AVMs with an excellent safety profile. Octreotide may be an effective therapy for secondary prevention of GIB in patients with an LVAD and warrants further prospective investigation.Table 43: Summary of Findings

Persistent Hyperinsulinemic Hypoglycemia of Infancy: A Rare Case with Multiple Anomalies

Background: Few cases of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) have been reported, so far. The main concern in the management of PHHI is to prevent severe hypoglycemia, which can lead to coma, brain damage and mental retardation. Total or subtotal pancreatectomy is normally required for the infants, despite the availability of medical therapies. Case report: In this report, we present the case of a three-day-old male infant with hypoglycemia and seizure, admitted to a hospital in Mashhad with the diagnosis of PHHI. Further evaluations revealed multiple congenital disorders including dextrocardia, posterior communicating aneurysm, atrial septal defect, ventricular septal defect, situs inversus and asplenia. Maximal doses of diazoxide, octreotide and intravenous glucose were prescribed for the infant. The patient was referred to our hospital and subtotal pancreatectomy was performed. In addition, due to frequent hypoglycemic episodes, a near-total pancreatectomy was conducted six days after the first surgery. The patient died eight months after total pancreatectomy at the age of nine months with no follow-ups. Conclusion: Infants with PHHI are at a high risk of severe neurological damage due to severe hypoglycemia, unless immediate and adequate medical interventions are carried out. Considering the co-occurrence of different congenital anomalies and PHHI in the present case, further assessment of concomitant congenital disorders is highly recommended in PHHI patients.

Patients with Active Acromegaly are at High Risk of 25(OH)D Deficiency.

Acromegaly is a chronic disease characterized by hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Electrolyte disturbances such as hypercalcemia and hyperphosphatemia are reported in patients with this disorder. There is limited data on vitamin D status in subjects with acromegaly. The aim of the study was to determine calcium, inorganic phosphate, magnesium, alkaline phosphatase, and 25(OH)D levels with regard to the activity of the disease. We also studied correlations of 25(OH)D and IGF-1, GH, body mass, body mass index, and age. A study group consisted of 55 acromegalic patients, and was divided into three subgroups: active acromegaly (AA), well-controlled acromegaly (WCA), cured acromegaly (CA). We enrolled 29 healthy subjects to a control group (CG). Vitamin D deficiency was recorded in all AA patients, 13 WCA patients (92.86%), 10 CA patients (62.5%), and 13 controls (54.17%). The highest 25(OH)D levels were found in the CG group and the lowest in the AA group (p = 0.012). The dose of octreotide did not influence serum 25(OH)D levels. A significant positive correlation between IGF-1 and 25(OH)D levels was observed in the AA group (r = 0.58, p = 0.024). Inorganic phosphate levels were the highest in the AA group. In conclusion, active acromegalic patients have lower 25(OH)D levels in comparison with the CG and are at higher risk of vitamin D deficiency.

Safety of octreotide in hospitalized infants

BackgroundOctreotide is used off-label in infants for treatment of chylothorax, congenital hyperinsulinism, and gastrointestinal bleeding. The safety profile of octreotide in hospitalized infants has not been described; we sought to fill this information gap. MethodsWe identified all infants exposed to at least 1 dose of octreotide from a cohort of 887,855 infants discharged from 333 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012. We collected laboratory and clinical information while infants were exposed to octreotide and described the frequency of baseline diagnoses, laboratory abnormalities, and clinical adverse events (AEs). ResultsA total of 428 infants received 490 courses of octreotide. The diagnoses most commonly associated with octreotide use were chylothorax (50%), pleural effusion (32%), and hypoglycemia (22%). The most common laboratory AEs that occurred during exposure to octreotide were thrombocytopenia (47/1000infant-days), hyperkalemia (21/1000infant-days), and leukocytosis (20/1000infant-days). Hyperglycemia occurred in 1/1000infant-days and hypoglycemia in 3/1000infant-days. Hypotension requiring pressors (12%) was the most common clinical AE that occurred during exposure to octreotide. Necrotizing enterocolitis was observed in 9/490 (2%) courses, and death occurred in 11 (3%) infants during octreotide administration. ConclusionRelatively few AEs occurred during off-label use of octreotide in this cohort of infants. Additional studies are needed to further evaluate the safety, dosing, and efficacy of this medication in infants.

Sirolimus treatment of severe congenital hyperinsulinism

Sirolimus treatment reduced dependence on octreotide and frequent feeding in 4 infants with CHI in a recent study [1]. We report our experience in a 1 year-old boy with presumed diffuse disease due to a de novo heterozygous ABCC8 missense mutation (p.D1506E). This macrosomic infant (term birth weight 5.676kg) presented with hypoglycaemia in the first hours of life. Critical sample results were consistent with CHI (blood glucose 0.9mmol/L, insulin 41mU/L, free fatty acids 0.2mmol/L[RR 0.1-0.6]). The family history was significant for type 2 diabetes in both grandmothers, and CHI in his maternal second cousin. No ABCC8 missense mutation was identified in either parent or his second cousin. Initial management included intravenous glucose (12mg/kg/min) and glucagon infusions. Maximal dose diazoxide (20mg/kg/day for 5 days) was ineffective so subcutaneous octreotide infusion was initiated (26mcg/kg/day). At discharge from hospital (age 10 weeks) he was overweight (height SDS 1.11, weight SDS 3.1), receiving octreotide 27mcg/kg/day, nocturnal gastrostomy Polyjoule® feeds (equivalent to 11mg/kg/min glucose) plus 3-hourly daytime bolus feeds. Sirolimus (0.5mg/m2/day) was added at age 7 months because of continued weight gain and intermittent mild hypoglycaemia while receiving octreotide 37mcg/kg/day. The dose was increased to 6mg/m2/day, aiming for trough levels 15-20ng/ml. After 3 months, the octreotide dose has stabilised (36mcg/kg/day) and the intensity of feeds has been reduced (3.5mg/kg/minute glucose overnight), resulting in weight loss; however, he has also developed linear growth failure (height velocity 6cm/year over 3 months). At 1 year of age his length and weight SDS are 0.48 and 1.21 respectively, and he is developmentally appropriate for age. Apart from one mild episode of respiratory syncytial virus, he has had no significant illnesses during sirolimus treatment. In conclusion, treatment with sirolimus has improved our patient’s blood glucose concentrations, decreased his dependence on hypercaloric nocturnal continuous feeds and decreased his weight gain; however the burden of care remains more significant than reported in the 4 published cases, 2 of whom had heterozygous mutations in ABCC8. The combination of high-dose octreotide and sirolimus may not be sustainable long-term in view of their likely combined contribution to his growth failure and the potential for immunosuppression due to sirolimus. Written informed consent was obtained from the patient's parent or guardian for publication of this Case report (and any accompanying images). A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Sirolimus therapy following subtotal pancreatectomy in neonatal hyperinsulinemic hypoglycaemia: a case report

Hyperinsulinemic hypoglycaemia (HH) occurs due to an unregulated insulin production from the pancreatic β-cells in the presence of low blood glucose. Mutations in ABCC8 and KCNJ11 are associated with severe HH that is unresponsive to conventional medical treatment. The only treatment for patients with medically unresponsive diffuse HH is a subtotal pancreatectomy. However, following surgery, hypoglycaemia may persist and some patients develop diabetes and malabsorption. Overexpression of the mTOR pathway is contributory to HH. Sirolimus, an mTOR inhibitor, is currently used in the treatment of congenital hemangiomas and in post renal transplant. Senniappan et al [1] recently reported efficacy of sirolimus in four surgically naive patients with diffuse HH unresponsive to diazoxide and octreotide. We present a patient who was treated with sirolimus due to persistent hypoglycaemia following subtotal pancreatectomy. A term neonate with a birth weight of 4.67kg had persistent hypoglycaemia since birth secondary to hyperinsulinism and was unresponsive to treatment with maximal doses of diazoxide and octreotide with a glucose infusion requirement (GIR) of 38mg/kg/min. Genetic testing revealed a homozygous ABCC8 nonsense mutation, p.Gln1020Ter. A subtotal pancreatectomy was performed on day 40. Post-surgery, he had a GIR of 20mg/kg/min and was recommenced on daily subcutaneous (SC) octreotide, with monthly long acting (LA) octreotide. At 3 months, he was commenced on oral sirolimus. The dose was adjusted to maintain serum trough levels between 5 and 15ng/ml. Parenteral fluids and SC octreotide were weaned over a month. He was discharged home at 4.5 months on sirolimus (2.5mg/m2/day) and LA octreotide. He was monitored with capillary blood glucose testing twice a day with the aim to maintain levels above 3.5mmol/L. Further surgery has been deferred. His growth and development are appropriate at 6 months of age with no side effects from sirolimus. The clinical response in our patient supports sirolimus as a new therapeutic strategy in patients with HH which may facilitate deferment of surgery. Written informed Consent for this patient has been taken including results of the genetic analyses and histopathological images according to the Institutional Ethics Committee procedures of our health service

Prolonged life-threatening hypoglycaemia following dose escalation of octreotide LAR in a patient with malignant polysecreting pancreatic neuroendocrine tumour.

SummaryThis paper details the case of a 77-year-old male with refractory hypoglycaemia due to inoperable metastatic pancreatic neuroendocrine tumour (pNET) co-secreting insulin and gastrin. Multiple medical therapies were trialled with limited success, and we describe the complications experienced by our patient. Somatostatin analogues can ameliorate hypoglycaemia and may have tumour-stabilising effects; however, in our case resulted in paradoxical worsening of hypoglycaemia. This rendered our patient hospital dependent for glycaemic support including continuous dextrose infusion. Although this is a reported adverse effect with initiation of therapy, we describe successful initiation of short-acting octreotide as an inpatient followed by commencement of long-acting octreotide. Hypoglycaemic collapse occurred only after dose titration of long-acting octreotide. We outline the pitfalls of somatostatin analogue therapy and the mechanisms that may contribute to worsening hypoglycaemia. This rare side effect cannot be reliably predicted, necessitating close supervision and glucose monitoring during therapy. Our patient achieved disease stabilisation and gradual resolution of hypoglycaemia with peptide receptor radionuclide therapy (PRRT), an emerging therapeutic option for metastatic neuroendocrine tumours with high efficacy and low toxicity. We present a brief but comprehensive discussion of currently available and novel therapies for insulin secreting pNETs.Learning points Hypoglycaemia due to malignant insulin secreting pNET is frequently severe and may be life-threatening despite supportive therapies.Octreotide can ameliorate hypoglycaemia, and may have anti-proliferative and tumour-stabilising effects in malignant pNETs that are surgically unresectable.Paradoxical worsening of hypoglycaemia may occur with octreotide initiation and dose titration, necessitating close supervision and glucose monitoring.PRRT is emerging as a therapeutic option with high efficacy and low toxicity.