Injection Of Lanreotide Research Articles

Altered biodistribution of [68Ga]Ga-DOTA-TOC during somatostatin analogue treatment.

The need for an interval between the administration of long-acting Somatostatin Receptor Analogues (SSA) and the [68Ga]Ga-DOTA-TATE PET has been questioned based on recent literature in the new EANM guidelines. Here an earlier studies showed that SSA injection immediately before SSTR PET had minimal effect on normal organ and tumor uptake (1). However, data are scarce and there are (small) differences between [68Ga]Ga-DOTA-TATE and [68Ga]Ga-DOTA-TOC binding affinity, and it remains unknown whether these findings can be directly translated to scans with [68Ga]Ga-DOTA-TOC as well. The purpose of this study was to assess the effect of SSA use on the biodistribution in a subsequent [68Ga]Ga-DOTA-TOC PET/CT and compare this intra-individually across several cycles of SSA treatments. Retrospectively, 35 patients with NENs were included. [68Ga]Ga-DOTA-TOC PET at staging and after the 1st and 2nd cycle of SSA were included. SUVmean and SUVmax of blood, visceral organs, primary tumor and two metastases were determined. Also, the interval between SSA therapy and the PET scan was registered. Treatment with SSA resulted in a significantly higher bloodpool activity and lower visceral tracer uptake. This effect was maintained after a 2nd cycle of SSA therapy. Furthermore, there was an inverse relationship between bloodpool tracer availability and visceral tracer binding and a positive correlation between bloodpool tracer availability and primary tumor tracer uptake. With an interval of up to 5days, there was a significantly higher bloodpool activity than at longer intervals. Absolute comparison of the SUV on [68Ga]Ga-DOTA-TOC PET should be done with caution as the altered biodistribution of the tracer after SSA treatment should be taken into account. We recommend not to perform a scan within the first 5days after the injection of lanreotide.

THU029 Subcutaneous Self-injections Of Lanreotide Is a Good Alternative For Acromegalic Patients With Long COVID Treated With Anticoagulants

Abstract Disclosure: I.N. Rosa: None. L.A. Naves: None. Background: Acromegaly control during pandemics was an important challenge. Telemedicine was a resource to provide health care, associated to electronic prescription sent directly to central pharmacy and drugs delivered to patients' home avoided treatment disruption in 2020 and 2021. The concomitant use of anticoagulants in Covid patients is a major concern because of risk of muscle hematomas. We describe here the replacement of Octreotide LAR to Somatuline Autogel in long Covid acromegalic patients with thromboembolic co-morbidities. Methods: We describe a sample of acromegalic patients, diagnosed with long Covid and thromboembolic co-morbidities. All patients were previously submitted to transsphenoidal surgery for somatotropic tumors and were controlled by mensal injections of octreotide LAR. Outpatient management was remodeled to simplify access to care by (1) adoption of virtual meetings; (2) collection of blood samples at home; (3) abolishment of printed prescription and provision of electronic files directly to central pharmacy; and (4) replacement of intramuscular injections for subcutaneous self injection of Lanreotide- Autogel. Results: From our cohort of 128 acromegalic patients, coronavirus disease (COVID-19) was confirmed in18%, although, long COVID, and use of anticoagulant drugs for more than 4 months was observed in 8 cases, 5 women, median age 68 years. Patients adopted self injections monthly and maintained disease control in 75% of cases with good adherence. Local side-effects, as injection-site pain, equimosis were observed less frequently than reported by the patients in previous use of Octreotide LAR. Conclusion: Telemedicine was a feasible tool in acromegalic patients with Long Covid. The replacement of intramuscular injections of Octreotide LAR for Lanreotide Autogel self injected subcutaneously allowed stability of disease control and provided an alternative to injections administered in the health care Presentation: Thursday, June 15, 2023

SAT139 Non-insulinoma Pancreatogenous Hypoglycemia Syndrome In A Patient With 1p36 Deletion Syndrome

Abstract Disclosure: E.D. Auckley: None. M.A. Arosemena: None. L. Philipson: None. Background: 1p36 deletion syndrome comprises a phenotypic presentation that includes central nervous system, cardiac, and craniofacial anomalies. There has been no report of associated hypoglycemia with this syndrome. Nesidioblastosis, also known as non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS), is understood as a rare condition defined by diffuse pancreatic hypertrophy with subsequent hyperinsulinemic hypoglycemia. Diagnosis requires serologic workup consistent with endogenous hyperinsulinemic hypoglycemia, intraarterial calcium stimulation positive for inappropriately elevated insulin secretion, and imaging studies without identified masses. Clinical Case: A 21-year-old female with 1p36 deletion syndrome (seizure disorder, cerebral palsy, vision loss and heart failure) was admitted to the hospital due to persistent falls. On admission vital signs were within normal limits, and physical exam revealed a thin non-verbal patient without significant other findings. During hospitalization and prolonged fasting periods of approximately 14-18 hours related to poor appetite she developed several episodes of hypoglycemia with serum glucose as low as 57 mg/dl. As patient was non-verbal at baseline, symptoms of hypoglycemia such as sweating, lightheadedness or shakiness were not confirmed. Even when she started to eat, hypoglycemic events continued to occur. Dextrose containing fluids (Dextrose 5% and later 10%) were added to try to maintain blood sugars within the normal range. Nevertheless, she continued to develop hypoglycemia. Endocrinology service was consulted and recommended to obtain a critical sample. A critical sample revealed serum glucose of 59 mg/dl, insulin level of 20.6 mcU/mL, proinsulin of 33 pmol/L, and beta-hydroxybutyrate of <0.10 mmol/L. Insulin antibodies was negative. Adrenal insufficiency was unlikely due to a normal 9 am cortisol level of 13.7 ug/dl. Due to the presence of hyperinsulinemic hypoglycemia further workup was conducted. A CT of the abdomen with a pancreatic protocol and 68Ga-DOTATATE PET/CT scan was negative for a pancreatic mass. Endoscopic ultrasound did not reveal a clear pancreatic mass either. This was followed by a calcium stimulation test which showed a two-fold increase in insulin levels in all 3 catheterized pancreatic territories. In the absence of a discrete mass, non-surgical management was recommended. For hypoglycemia management patient was started on octreotide injections with resolution of hypoglycemia. Prior to discharge she was switched to lanreotide and was discharged to continue monthly lanreotide injections. Conclusion: To our knowledge, this is the first case reported of NIPHS in a patient with a mutation in 1p36 deletion. Hyperinsulinism in the setting of diabetes has been reported in this syndrome1 but to our knowledge no cases of hypoglycemia with NIPHS have been reported. Presentation: Saturday, June 17, 2023

Abstract #1395486: Uncontrolled Acromegaly Resulting in the Need for LVAD as Bridge to Heart Transplant

Acromegaly is an uncommon pituitary disorder with an incidence of six per million persons. While hypertension is often encountered in these patients, heart failure rarely is seen with an incidence rate under 10%. We describe a case of an individual who was diagnosed with acromegaly after an acute exacerbation of heart failure with subsequent management requiring an LVAD to perform Transsphenoidal Surgery (TSS). 37-year-old male otherwise healthy initially presented to an emergency room and was found to be in acute heart failure exacerbation. Concerning acromegaly features included macrognathia, enlarged hands and feet, swollen phalanges, widened spacing of teeth, and frontal bossing. IGF-1 level was found 455 ng/mL. MRI showed a 10mm macroadenoma. A right heart catheterization showed elevated filling pressures. Cardiac MRI showed no defects or enhancement. Endomyocardial biopsy showed no inflammatory infiltrates or evidence of infiltrative diseases. Patient had an ejection fraction of 15% corroborated by cardiac MRI along with the presence of aortic root dilatation and mitral regurgitation. The patient started on 0.5mg of Cabergoline twice weekly and 120mg weekly Lanreotide injections. Patient stabilized with plans for further close monitoring and outpatient neurosurgical evaluation. The COVID-19 pandemic and insurance gaps led the patient to spend two years off his medicines and he was unable to be seen by his medical team. Patient was seen by our system after recurrent hospitalizations for heart failure at our sister hospital, AICD was unable to be placed due to the patient’s anatomy, he was placed on wearable cardiac defibrillator and required milrinone infusion for progression to end-stage heart failure with cardiac cachexia. At our institution, the patient was evaluated for Orthotopic Heart Transplant (OHT) but due to active GH secreting macroadenoma there was concern for OHT failure without TSS. Decision was made to utilize LVAD as Bridge-to-Transplant for OHT so the patient could be stabilized and safely undergo TSS. The patient tolerated surgeries well and is currently on the active transplant list. Heart failure is an uncommon presentation of severe acromegaly requiring multidisciplinary management. We describe a case of a patient who initially presented with heart failure too unstable for surgery. Due to the COVID-19 pandemic the patient’s disease progressed resulting in end-stage heart failure requiring LVAD placement for further treatment. We would like to draw attention to the use of LVAD placement in acromegalic patients who develop severe cardiovascular disease who are not candidates for OHT.

ODP303 Cushing's Syndrome Due to Ectopic Adrenocorticotropic Hormone-Secreting Metastatic Neuroendocrine Tumor

Abstract Introduction Cushing's syndrome (CS) due to ectopic ACTH secretion (EAS), is an infrequent form of ACTH-dependent CS. EAS results from unregulated ACTH secretion by neuroendocrine tumors (NETs) of various locations resulting in severe hypercortisolism. The progression of CS is usually precipitous. To improve outcomes, it is imperative to recognize early so that treatments of cortisol-induced comorbidities and targeted treatments can be initiated. Case Presentation A 74-year-old female presented to an outside hospital with fatigue, bilateral lower extremity edema and intractable hypokalemia. She was later transferred to our facility, where workup of CS was initiated. She underwent a 1mgdexamethasone suppression test (DST)which resulted in an unsuppressed 8amcortisol of 34.7 ug/dL (<2 ug/dL). This was followed by a 4mgDST, again resulting in an unsuppressed 8amcortisol of25.4 ug/dL. A 24-hour urine cortisol level was collected and resulted at 2,108.9 ug/d (<45 ug/d). ACTH level was elevated at 136 pg/ml (7.2-63.3 pg/ml). CT abdomen/pelvis identified liver lesions concerning for metastatic disease. PET DOTATATE revealed multiple liver lesions and a few pulmonary nodules. Biopsy of liver lesions demonstrated strongly positive staining of synaptophysin and chromogranin confirming NET, with a weak TTF-1 positivity suggestive of pulmonary origin. Lanreotide injections were initiated for tumor control and ketoconazole for treatment of persistent hypercortisolism. Despite titration of ketoconazole, symptoms and labs showed minimal improvement. Osilodrostat was then added as a third line and examethasone was initiated in a block and replace approach. The regimen of lanreotide, osilodrostat and ketoconazole improved her24-hoururine cortisol to 15 from 2,109 ug/24hr. Subsequently patient underwent trans-arterial chemoembolization (TACE) of the liver lesions with resolution of hypercortisolism. She is currently only on Lanreotide for tumor control. Discussion NET with ectopic ACTH production is rare. While primary tumor location was not definitively identified, multiple lung lesions and histopathology suggested primary lung tumor with hepatic metastases. 20-40% of all NETS originate in the chest. Patient management necessitates a multidisciplinary approach not only for the diagnosis and treatment of CS but also for the specific management of neuroendocrine tumors (NET). This case highlights a rare presentation of EAS, and aggressive treatment modalities needed to treat symptoms of excess cortisol production and tumor progression. Presentation: No date and time listed

Efficacy of lanreotide 120 mg primary therapy on tumour shrinkage and ophthalmologic symptoms in acromegaly after 1 month.

Few studies have attempted to evaluate the early efficacy of first-generation somatostatin analogues in somatotroph macroadenomas. To investigate the short-term efficacy of primary therapy with lanreotide 120 mg at 1 and 3 months on tumour shrinkage and ophthalmologic symptoms in newly diagnosed patients with acromegaly. This single-centre retrospective study included 21 patients with de novo acromegaly resulting from pituitary macroadenoma, with optic chiasm compression (Grade ≤ 2) and/or cavernous sinus invasion, treated with a monthly injection of lanreotide 120 mg. Clinical, hormonal, ophthalmologic and magnetic resonance imaging scan evaluations were conducted after the first and the third months of treatment. Tumour volume reduction was more pronounced at 1 month; mean volume change: -31.4 ± 19.5%, p < .0001than between the first and third month of treatment; mean volume reduction: -20.6 ± 13.4%, p = .0009. The mean volume change between baseline and the third month was - 46.4 ± 21.6, (p < .0001). A significant volume reduction (≥25%) was observed in 61.9% of individuals (13/21) at the first month. Among 14 individuals with optic chiasm compression and visual field defects, visual field normalization or improvement were observed in seven cases (50%), stabilization in four cases (28.5%), and mild worsening in three cases (21.4%) at 1 month. The decrease in growth hormone and IGF-1 serum values was significant at 1 month. Primary treatment with lanreotide 120 mg in patients with somatotroph macroadenomas provides early significant tumour shrinkage with rapid improvement of visual symptoms at the end of the first month in 50% of patients.

A Rare Case of Adult Nesidioblastosis Causing Persistent Hypoglycemia in Patient With Atrial Fibrillation and Chronic Kidney Disease

Abstract Nesidioblastosis is a very rare adult disorder in the absence of gastrointestinal surgery. Nesidioblastosis is a disorder of the endocrine pancreas causing hyperinsulinemic hypoglycemia. We describe a case of 83 year-old Caucasian male, with a 3-year history of severe refractory hypoglycemia with glucose level below 2.1 mmol/L. Confusion and sleepiness were reported as his neuroglycopenic symptoms. According to his family, his symptoms improved within 30 minutes of drinking orange juice. Hypoglycemia episodes mostly occurred while fasting and post exercise (after playing golf). His work up included low venous plasma glucose levels, high insulin and C-peptide levels that were consistent with an insulinoma. His history is remarkable for chronic kidney disease stage 3, penicillin allergy and atrial fibrillation with loop recorder for cardiac rhythm monitoring, which precluded him from undergoing CT with IV contrast or MRI studies. Abdominal computed tomography with oral contrast did not reveal any lesion. In an attempt to localize the suspected Insulinoma, he had celiac angiogram and portal vein sampling, which were inconclusive. He had a PET scan with dotatate that showed increased amount activity in the uncinate process of the pancreas. He was diagnosed with insulinoma and placed on monthly lanreotide injections, however continued to have severe hypoglycemia episodes. Due to persistent refractory hypoglycemia, patient underwent distal pancreatectomy and splenectomy and the histological findings were consistent with nesidioblastosis. Patient developed hyperglycemia in the post-operative course which was controlled with a carb consistent diet. This case demonstrates that differentiation between insulinoma and nesidioblastosis is very challenging, and in most cases, the diagnosis is made post operatively based on histologic findings.

SUN-291 Presence of Aberrant Adrenocorticotropic Hormone Precursors in Two Cases of McCune- Albright Syndrome

Background: McCune-Albright syndrome (MAS) is a rare disorder. MAS is caused by an activating postzygotic somatic mutation in the GNAS, and, is classically defined by the occurrence of fibrous dysplasia (FD), café-au-lait skin macules, and precocious puberty. Autonomous GH and/or PRL production in MAS has been reported. However, there have been no reports of ACTH excess in MAS. Method: Plasma ACTH and serum cortisol (F) levels were assessed using electrochemiluminescence immunoassays (Eclusys ACTHTM and Eclusys Cortisol IITM, respectively; Roche Diagnostics K.K., Tokyo, Japan).Clinical Cases: Case1; 42-year-old man showed craniofacial deformities and suffered from multiple bone fractures. He was diagnosed with FD at the age of 23 years. Café-au-lait macules were found on his back. He had slightly acromegaloid features. He showed no cushingoid features. Pituitary adenoma or hyperplasia was not detected by MRI. The diagnosis of GH excess was confirmed by no suppression of serum GH levels by a 75-g oral glucose tolerance test (nadir GH: 2.34 ng/mL) and an elevated serum IGF-I level (307 ng/mL; normal range: 92-257 ng/mL). The patient was treated with monthly subcutaneous lanreotide injection and then GH excess was well controlled. Basal ACTH and F levels in blood were 40.6-63.4 pg/mL and 8.0-10.5 μg/dL, respectively. The urinary free cortisol (UFC) level was 53 μg/day. Autonomous F excess was excluded by the level of midnight F (1.2 μg/dL) and the level of F (0.2 μg/dL) after a low-dose (1 mg) dexamethasone suppression test (DST). Case2; A 32-year-old man was diagnosed with MAS and gigantism at the Pediatrics Department at the age of 5 years. Treatment of GH excess was well controlled by monthly octreotide depot. He had no acromegaloid features and no cushingoid features. Café-au-lait macules were observed from the left flank to the back. Pituitary adenoma or hyperplasia was not detected by MRI. Basal ACTH and F levels in blood were 35.5-73.1 pg/mL and 7.0-11.7 μg/dL, respectively. The UFC level was 61 μg/day. Autonomous F excess was excluded by the level of F (<0.2 μg/dL) after a low-dose (0.5 mg) DST.Possibility of primary adrenal insufficiency was excluded by ACTH stimulation test and/or insulin tolerance test in both cases. The involvement of 11β-HSD1 by GH excess and PC1/3 deficiency were also excluded. Gel exclusion chromatography was then performed. POMC and pro-ACTH were detected and the aberrant ACTH/normal ACTH ratio was 42% in both cases. Conclusion: This is the first report of the presence of aberrant ACTH precursors, particularly POMC, in MAS. A high ratio of circulating ACTH to F may suggest secretion of inactive ACTH precursors in MAS. Further investigations are required to determine whether GNAS mutations or other mechanisms are involved in the presence of aberrant ACTH precursors in MAS.

Lanreotide Reduces Liver Growth In Patients With Autosomal Dominant Polycystic Liver and Kidney Disease.

Polycystic liver disease is the most common extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). There is need for robust long-term evidence for the volume-reducing effect of somatostatin analogues. We made use of data from an open-label, randomized trial to determine the effects of lanreotide on height-adjusted liver volume (hTLV) and combined height-adjusted liver and kidney volume (hTLKV) in patients with ADPKD. We performed a 120-week study comparing the reno-protective effects of lanreotide vs standard care in 305 patients with ADPKD (the DIPAK-1 study). For this analysis, we studied the 175 patients with polycystic liver disease with hepatic cysts identified by magnetic resonance imaging and liver volume ≥2000 mL. Of these, 93 patients were assigned to a group that received lanreotide (120 mg subcutaneously every 4 weeks) and 82 to a group that received standard care (blood pressure control, a sodium-restricted diet, and antihypertensive agents). The primary endpoint was percent change in hTLV between baseline and end of treatment (week 120). A secondary endpoint was change in hTLKV. At 120 weeks, hTLV decreased by 1.99% in the lanreotide group (95% confidence interval [CI], -4.21 to 0.24) and increased by 3.92% in the control group (95% CI, 1.56-6.28). Compared with the control group, lanreotide reduced the growth of hTLV by 5.91% (95% CI, -9.18 to -2.63; P < .001). Growth of hTLV was still reduced by 3.87% at 4 months after the last injection of lanreotide compared with baseline (95% CI, -7.55 to -0.18; P= .04). Lanreotide reduced growth of hTLKV by 7.18% compared with the control group (95% CI, -10.25 to -4.12; P < .001). In this subanalysis of a randomized trial of patients with polycystic liver disease due to ADPKD, lanreotide for 120 weeks reduced the growth of liver and combined liver and kidney volume. This effect was still present 4 months after the last injection of lanreotide. ClinicalTrials.gov, Number: NCT01616927.

SAT-473 Acromegaly and Drug-Induced Parkinsonism Were Controlled by Lanreotide

BACKGROUND Serum IGF-1 is reported as possible marker for risk and early diagnosis of Parkinson's disease in Neurology. Acromegaly is a disease that causes organ symptoms as a result of the high level of IGF-1. Despite the elevation of IGF-1 in acromegaly patients, there is little report on Parkinson's syndrome of acromegaly. A clinical course of acromegaly with co-morbidity of diabetes mellitus and depression suggested a possible relationship between IGF-1 transition and drug-induced Parkinsonism. CASE A 55-year-old woman with co-morbidity of diabetes mellitus and depression was diagnosed as acromegaly. Her HbA1C was 14.4% because of untreated diabetes. Her GH was elevated to 777 ng/mL and MRI indicated macroadenoma of pituitary gland. Contrary to GH elevation, her IGF-1 was in the normal range of 103 ng/mL (normal range: 75-210 ng/mL), that was a false negative result due to untreated diabetes. The continuation of insulin therapy produced a gradual rise in IGF-1 as a result of glycemic control. Antidepressants were continued by psychiatrists. Three months after starting insulin treatment, her IGF-1 increased to 305 ng/mL . From then on, her coarse tremor was observed and she was not capable to write letters at all. 111In-pentetreotide scintigraphy (Octreoscan) showed radiotracer accumulation in her pituitary gland, excluding the existence of ectopic GHRH-producing tumors. For the treatment of pituitary tumor and Parkinsonism, bromocriptine was tried but stopped because of liver dysfunction. After checking the safety and response of octreotide, monthly injection of lanreotide was started. Fourteen months after starting lanreotide, her IGF-1 was decreased to 71 ng/mL and her coarse tremor disappeared. She also became capable of writing and self-monitoring of blood glucose for diabetes. Disappearance of her tremor improved her activity of daily life. A woman with acromegaly with comorbidity of depression and diabetes was treated. An elevation of IGF-1 produced coarse tremor and lowering of IGF-1 improved the symptom. Lanreotide controlled drug-induced Parkinsonism by lowering IGF-1 level. CLINICAL LESSONS This clinical course and transition of IGF-1 suggested the involvement of IGF-1 in parkinsonism. There has been no report of drug-induced Parkinsonism with comorbidity of acromegaly of which IGF-1 and symptoms were observed chronologically. This case suggested a possibility that an elevation of IGF-1 lowers the threshold of drug-induced Parkinsonism.

MON-329 Calcitonin-Secreting Neuroendocrine Tumor Raising Concern for Medullary Thyroid Carcinoma in a Patient with Thyroid Nodules

Background: Calcitonin elevation is a characteristic feature of medullary thyroid carcinoma, but can also be secreted by other neuroendocrine tumors. Pancreatic neuroendocrine tumor is a rare entity, with most functioning tumors secreting insulin and gastrin, while other hormones such as calcitonin are not commonly evaluated. Case: A 63 year old woman with stage 4, well differentiated pancreatic neuroendocrine tumor was referred for evaluation of a thyroid nodule and rising calcitonin level concerning for possible medullary thyroid cancer. She presented with persistent diarrhea and weight loss, and found to have a 10 cm pancreatic mass, liver metastasis and common bile duct obstruction requiring a biliary drain. Pathology showed grade 2, well differentiated neuroendocrine neoplasm with 5/10 mitoses/high power field, immunopositive for chromogranin, synaptophysin and Cam5.2, very faint, rare staining for gastrin and negative for somatostatin. Chromogranin A was 21 (Nl 25-140 ng/mL), serotonin 641 (Nl 56-244 ng/mL), gastrin 16 (Nl <100pg/mL), 24 hr 5HIAA 3.3 (Nl <6mg/24h), pancreatic polypeptide <50 pg/mL (Nl <1823 pg/mL), vasoactive intestinal peptide <5 pg/mL (Nl <75 pg/mL) and somatostatin 33 (Nl <30). She was treated with radioablation of the liver lesions and monthly lanreotide injections. An Octreoscan showed a questionable focus of abnormal uptake within the right thyroid lobe, triggering a calcitonin level that was elevated at 722 pg/mL (Nl <5pg/mL). She was referred for thyroid nodule biopsy to rule out medullary thyroid cancer. Ultrasound of the thyroid gland showed bilateral thyroid nodules with a dominant, right mid thyroid nodule measuring 13.9 x 16. 4 x 18.5 mm, hyperechoic, spongiform with regular, smooth and well defined margins and no calcifications. FNA biopsy of the right mid thyroid nodule was negative for malignant cells, consistent with benign follicular nodule with cystic degeneration, and immunohistochemical staining for calcitonin of the cell block was negative. Immunostaining of the prior pancreatic tumor biopsy for calcitonin was performed and positive. Conclusion: Although elevation in calcitonin raises concern for medullary thyroid cancer, it is rarely secreted by other neuroendocrine tumors. Thus, a, calcitonin-secreting pancreatic neuroendocrine tumor is an important entity to consider as a cause of elevated calcitonin, especially in a patient with benign appearing thyroid nodules. Reference: 1 Jensen, R et al, ENETS Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Neoplasms: Functional Pancreatic Endocrine Tumor Syndromes. Neuroendocrinology. 2012;95:98-119.

MON-332 Metastatic Pancreatic Neuroendocrine Tumor: A Very Rare Cause of Ectopic ACTH Production (ACTHoma)

Introduction Ectopic ACTH syndrome (EAS)is responsible for 10% of Cushing’s syndrome. Multiple tumors, most commonly small cell carcinoma of lung are associated with EAS. Pancreatic neuroendocrine tumors (pNETs) are usually associated with secretion of pancreatic polypeptide, gastrinomas, insulinomas, glucagonomas and vasoactive intestinal peptide (VIPomas). EAS or “ACTHomas” are rarely associated with pNETs. Case 76y/o man with ah/o hairy cell leukemia, bladder cancer (both in remission), and stage M1 unresectable pNET tumor with liver metastases presented with generalized weakness. Discovery of his pNET was incidentally noted during routine surveillance with CT monitoring following successful bladder cancer treatment six years ago. Treatment of his pNET initially began with Everolimus and then switched to Lanreotide injections. No evidence of Cushing’s Syndrome at the time of diagnosis. The lesions remained stable in size and patient was doing well. Physical exam was notable for lethargy, frailty, and absence of Cushingoid features. Labs showed serum glucose 231mg/dl, sodium 141mEq/L, potassium 2.4mEq/L, AM cortisol 116 ug/dL (range 6.7-22.6ug/dl) and ACTH was 209.6pg/mL (range 7.2-63.3pg/mL). Renin-aldosterone levels were normal. Cortisol level did not suppress with low dose or high dose dexamethasone. His hospital course was significant for persistent hypokalemia despite aggressive supplementation, difficult to control blood glucose, and worsening kidney function. EAS with pNET is very refractory to management and may be rapidly progressive. They occasionally demonstrate classic manifestations of Cushingoid features. However, they often lack the traditional phenotypic features of Cushing syndrome. Treatment options for EAS in the setting of an unresectable tumor include medical management versus bilateral adrenalectomy. Metyrapone, a cortisol synthesis inhibitor, can be an effective therapy. Ketoconazole, an antifungal that inhibits cortisol production can be an alternative, but may need weeks to achieve control. Etomodate can rapidly reduce cortisol levels, but requires intensive care monitoring. Somatostatin analogs may be effective by reducing ectopic ACTH production and stabilize tumor growth. Medical versus surgical management of Cushing’s syndrome was discussed with the patient and family, but they opted for hospice care. Conclusion We present a case of pNET associated with late onset EAS without obvious signs of Cushing’s syndrome. To our knowledge this late presentation of ACTH secretion in the setting of a stable pNET has not been previously reported in the literature. EAS due to pNET is rare and metabolic abnormalities can occur rapidly without other Cushingoid manifestations which can pose significant management challenges. High index of suspicion is required for early diagnosis. Due to the aggressive nature, the 5 years survival rate is 16%.

Metastatic atypical lung carcinoid treated with combined therapeutic modalities

Introduction. Lung carcinoids are considered a rare and uncommon group of lung tumors, making about 1% of all primary lung tumors. Atypical carcinoids are more aggressive than typical ones, with higher metastatic potential and worse prognosis and a 10-year survival rate of less than 60%. Case outline. In 2012, a 61-year-old male underwent the right lower lobectomy and the histopathological finding was an atypical lung carcinoid tumor. At the beginning of 2016, radiological and bronchoscopic progression of the disease was reported. Magnetic resonance imaging revealed enhanced nodular lesions compatible with liver metastases. The patient received endoluminal brachytherapy. Subsequently, the first line chemotherapy according to the cisplatin/etoposide (PE) protocol was applied. In August 2016, the somatostatin receptor scintigraphy (SRS) revealed secondary deposits with somatostatin receptor (SR) expression in the liver and lungs. The treatment with lanreotide injections was initiated. After five treatment courses, progression of the disease in the bronchial tree was verified and electro-cauterization and argon plasma cauterization of the tumor in the right main bronchus were performed. In September 2017, progression of the disease was verified again. The Oncology Board introduced the third line therapy with everolimus. Conclusion. The evidence supporting optimal treatment strategies for an atypical lung carcinoid tumor is lacking, but some recent publications indicate that multimodal treatment is associated with prolonged survival.

Triple Valve Replacement in a Rare Case of Left-sided Carcinoid Heart Disease

Carcinoid heart disease (CHD) is characterised by plaque-like deposits of fibrous tissue on the endocardium as a result of production of vasoactive substances by carcinoid tumours. CHD typically affects the right-sided valves of the heart. Involvement of the left-sided valves rarely occurs, as it is thought that the pulmonary circulation inactivates the vasoactive substances. Left-sided CHD has been reported in patients with a patent foramen ovale and/or bronchial carcinoid lesions. We present a rare instance of left-sided CHD, occurring without an intracardiac shunt or bronchial carcinoid lesions. This 66-year-old male was diagnosed with a metastatic small bowel carcinoid tumour with liver metastases in 2014, and was managed with lanreotide injections. He was found to have CHD involving his tricuspid, pulmonic, and aortic valves. Initially, he was medically managed; however, following multiple presentations and worsening heart failure he was referred for surgical management. A successful elective triple valve replacement (and one coronary artery bypass grafting) was performed, with replacement of the tricuspid, pulmonary, and aortic valves with bioprosthetic valves. Histology of the resected valves was suggestive of chronic carcinoid valvulopathy. At a 2-month follow-up appointment after his surgical admission his heart failure symptoms had improved markedly. There are very few case reports in the literature documenting management of left-sided CHD and the pathophysiology is not well established. All valves should be assessed and patients with CHD should be undergo close surveillance, with consideration of valvular surgery in patients with severe valvular dysfunction to potentially improve prognosis and long-term functional status.

Case Report: Persistent Acromegaly – Effective Therapy with Lanreotide and Weekly Pegvisomant Injections

Abstract Objective Therapeutic options for persistent acromegaly after surgery include another surgical approach, radiotherapy, medical therapy or a combination of these procedures. We describe a patient with persistent acromegaly despite heavy pre-treatment who was in need of a simplified mode of effective therapy. Methods In a 45-year old patient after transsphenoidal pituitary surgery followed by linear accelerator irradiation of the residual tumor two years later acromegaly could not be controlled by a tolerable dosage of intramuscular octreotide LAR. For professional reasons the patient requested a simplified mode of treatment. Results In order to improve efficacy and treatment convenience, we combined subcutaneous injections of lanreotide up to 120 mg monthly performed by the patient’s spouse and of pegvisomant 80 mg weekly conducted by the patient himself. This therapy was well tolerated and satisfactory endocrine control was achieved. Magnetic resonance imaging did not show any remaining tumor within a year. 5 years following surgery and 3 years following irradiation pegvisomant could be stopped and levels of insulin growth factor 1 and growth hormone remained in the normal range. The interval of lanreotide given subcutaneously by the patient’s spouse could be extended stepwise and somatostatin analog treatment was terminated after 7.5 years when the patient was cured. Conclusions Excessive growth hormone secretion persisting after pituitary surgery and irradiation can be controlled in a convenient way for the patient with acromegaly by combining monthly lanreotide and weekly pegvisomant injections, if monotherapy with a somatostatin analog fails.

012-Short Term Pain for Long Term Gain: Nursing Implications with Lanreotide Use in Patients with Hyperinsulinism

Background: Congenital Hyperinsulinism (CH) is caused by unregulated, increased secretion of insulin from the pancreatic beta cells. This results in severe persistent hypoglycemia which can lead to brain injury. Diffuse disease can be treated medically. Previous practice at SickKids was to treat patients with diffuse disease who did not respond to oral diazoxide and who declined pancreatectomy or had persistent hyperinsulinism post-pancreatectomy with subcutaneous octreotide injected every 8 h. There have been some studies that conclude long acting somatostatin analogue (Lanreotide) is a safe and effective alternative to octreotide therapy in CH patients with a significant improvement in blood glucose (BG) control and quality of life. As a result, the new standard of care at SickKids is monthly deep subcutaneous Lanreotide injections. Purpose: To describe the new practice of injecting Lanreotide to children. To aim to educate pediatric endocrine nurses in its use, and understand the nursing implications involved. Description of Topic: We did a Literature review and emailed Great Ormond Street Hospital (GOSH) to obtain their experience. Patients came in monthly for Lanreotide injections. Pain management and distraction techniques were utilized. Octreotide was weaned by 25% each week following the second Lanreotide injection and ceased by third Lanreotide injection. Other therapies (e.g. sirolimus) weaned after octreotide discontinued if BG stable. Communicated with community partners to coordinate care for patients in their home town. Clinical Implications: The following nursing implications should be considered when patients are treated with Lanreotide: 1) Nursing Practice (dosing, injection technique, land marking, pain management, illness management) 2) Monitoring (GI upset, TFT, yearly ultrasound for cholelithiasis, BG, weaning of Octreotide/Sirolimus during treatment) 3) Patient/Family satisfaction.

Lanreotide in the management of small bowel angioectasias: seven-year data from a tertiary centre

Background and aims: Haemorrhage from small bowel angioectasias (SBAs) can be debilitating to patients who are very often elderly and have multiple comorbidities. Our aim was to assess the use of lanreotide in addition to endotherapy in patients with SBAs.Method: Patients with SBAs on capsule endoscopy (CE) who received lanreotide injections from January 2010 to till the present day at the Royal Hallamshire Hospital in Sheffield were included. Baseline demographics were recorded. Efficacy was evaluated in terms of improvement in mean haemoglobin, transfusion requirements and bleeding episodes.Results: Twelve patients (67% males, mean age 74 SD ± 15.5 years) were included. All patients had multiple comorbidities. Lanreotide was given at a dosage of 60 mg (42%), 90 mg (33%) or 120 mg (25%). It was given at a four-week interval in 75% of patients and at a six-week interval in 17% of patients. One patient (8%) received a single dose. The mean duration of treatment was 19 months SD ± 14.5. Only 17% of patients had their lanreotide stopped due to cholelithiasis.There was a significant improvement in mean haemoglobin: 86.8 versus 98.0 (131–166 g/L, p = .012). The mean number of bleeding episodes (4.18 versus 1.09, p = .010) and packed red cells (323 versus 152, p = .006) received improved. Patients required less DBEs ± APCs after starting lanreotide (19 versus 11 p = .048).Conclusion: Lanreotide is a useful adjuvant treatment to therapeutic enteroscopy in patients with refractory obscure gastrointestinal bleeding due to SBAs. It improves haemoglobin levels, reduces transfusion requirements, bleeding episodes and number of DBEs. Overall, it has a good safety profile.

Lanreotide depot deep subcutaneous injection: a new method of delivery and its associated benefits

Acromegaly is a rare disease characterized by excessive growth hormone secretion, usually from a pituitary tumor. Treatment options include surgery, medical therapy, and in some cases, radiation therapy. Current medical therapy consists of treatment with somatostatin analog medications or a growth hormone receptor antagonist. There are two somatostatin analogs currently in use, octreotide and lanreotide. Both are supplied in long-acting formulations and are of comparable biochemical efficacy. Lanreotide is supplied in a prefilled syringe and is injected into deep subcutaneous tissue. Studies have been conducted to assess the efficacy of self- or partner administration, and have demonstrated that injection of lanreotide can be accomplished reliably and safely outside a physician’s office. For patients who have achieved biochemical control with lanreotide, the FDA has recently approved an extended dosing interval. Selected patients may be able to receive the medication less frequently with injections of 120 mg administered every 6 or 8 weeks. This review focuses on the use of lanreotide in the treatment of acromegaly, the safety and efficacy of the drug, and the benefits afforded to patients because of unique aspects of the delivery of lanreotide.

Randomized, Placebo-Controlled, Double-Blind Study of the Efficacy of Lanreotide 30 mg PR in the Treatment of Pancreatic and Enterocutaneous Fistulae

Continuous intravenous infusion of somatostatin improves the natural course of digestive fistulae. Lanreotide 30 mg PR is a synthetic analogue of somatostatin with pharmacological activity extending to at least 10 days after intramuscular administration. Its effectiveness was assessed in patients with simple externalized digestive fistulae in a randomized, doubleblind, placebo-controlled study. Patients demonstrating a reduction of at least 50% of fistula output within 72 hours after a first double-blind intramuscular injection of lanreotide or placebo were considered to be responders (primary end point) and continued the double-blind treatment to a maximum of 6 injections at 10-day intervals. Other endpoints included fistula closure rate and time to closure. Blind was lifted for nonresponders, and those initially on placebo were then treated with open-label lanreotide. Following the first double-blind injection, 35 of 54 patients (64.8%) on lanreotide were responders versus 20 of 53 (37.7%) on placebo, ie, a 3.1 times higher response likelihood on lanreotide compared with placebo (P = 0.006). Group mean reduction of fistula output at 72 hours was 45.1% and 8.9%, respectively (P = 0.005). Lanreotide compared with placebo had no effect on closure rate which averaged 77% but median time to fistula closure was shorter on lanreotide, based on Kaplan-Meier analysis, although no statistical significance was achieved. Compared with placebo, intramuscular lanreotide 30 mg PR significantly decreases digestive fistulae output at Day 3 and shortens time to fistula closure by 9 days. ClinicalTrials.gov registration number: NCT00729313.

Effectiveness of self- or partner-administration of an extended-release aqueous-gel formulation of lanreotide in lanreotide-naïve patients with acromegaly

Surgical resection is often not curative in patients with acromegaly and long-acting somatostatin analogues (lanreotide or octreotide) are often needed. This study assessed the efficacy and safety of self- or partner-administration of lanreotide in patients with acromegaly. This was a six-month, single-arm, open-label study conducted at 13 endocrinology clinics. Fifty-nine patients received deep subcutaneous lanreotide injections every 28 days. Twelve patients started on 120 mg lanreotide and forty-seven started on 90 mg lanreotide. At week 16, the dose was adjusted to 60, 90 or 120 mg based on insulin-like growth factor-1 (IGF-1) levels at week 12. Fifty-nine patients with acromegaly either switched from long-acting octreotide (switch; n = 33) or were somatostatin analogue treatment-naïve or not currently taking long-acting octreotide (“other”; n = 26). The key endpoints included the percentage of patients/partners able to self- or partner-inject lanreotide and those with normal IGF-1 or growth hormone (GH) levels at week 24/early termination. 100% of patients/partners correctly self- (n = 41) or partner-injected (n = 18) lanreotide by week 4. By week 24/early termination, IGF-1 levels were controlled in 93.7% of switch and 46.2% of “other” patients, while GH levels were controlled in 76.9% and 39.1% of patients, respectively. Both IGF-1 and GH were controlled in 73.1% of switch and 30.4% of “other” patients. Most switch patients (81%) reported they preferred lanreotide over long-acting octreotide for future use (P = 0.0001). Self- or partner-administration of lanreotide is generally well tolerated and associated with IGF-1 and GH control in many lanreotide-naïve patients with acromegaly.