Insulinoma in a Patient with Normal Results from Prolonged Fast and Glucagon-Induced Hypoglycemia

ObjectiveTo describe a man with a functioning insulinoma and normal results from two 72-hour fasts who developed hypoglycemia secondary to exaggerated insulin response following glucagon stimulation.MethodsWe report the patient’s clinical findings, laboratory findings, and clinical course. We also review the literature for previously reported cases and possible mechanisms.ResultsA 49-year-old man presented with hypoglycemic symptoms initially occurring after jogging and well-documented symptomatic hypoglycemia occurring during an evening meal. A 72-hour fast was associated with a serum glucose concentration of 50 mg/dL, suppressed insulin and C-peptide levels, and mildly elevated β-hydroxybutyrate. Another documented episode of hypoglycemia occurring 3 hours postprandially was associated with elevated insulin and C-peptide and suppressed β-hydroxybutyrate. A second 72-hour fast provoked asymptomatic hypoglycemia (glucose concentration at 60 hours: 32 mg/dL) with suppressed insulin and measurable β-hydroxybutyrate. After 72 hours of fasting, glucagon administration led to a decrease in glucose from 50 to 18 mg/dL, elevations in insulin and C-peptide, and suppression of β-hydroxybutyrate. Computed tomography revealed a mass lesion in the pancreatic tail. Distal pancreatectomy was performed, and the resected specimen demonstrated immunostaining for insulin. Hypoglycemic symptoms resolved postoperatively.ConclusionsNormal results from a prolonged fast do not preclude an insulinoma and may demonstrate exaggerated insulin secretion from the insulinoma following glucagon administration. In addition to examining the glucose response to glucagon as a surrogate for insulinoma diagnosis, measurement of serum insulin levels following glucagon administration may provide a further clue to the diagnosis of insulinoma. (Endocr Pract. 2010;16:838-841)     

Ectopic Acromegaly due to A Pancreatic Neuroendocrine Tumor Producing Growth Hormone-Releasing Hormone

ObjectiveTo present a case of acromegaly due to ectopic growth hormone-releasing hormone (GHRH) secretion from a pancreatic neuroendocrine tumor in the context of multiple endocrine neoplasia type 1 (MEN 1).MethodsWe describe the clinical, imaging, and pathologic findings of the study patient.ResultsA 46 year old woman presented with clinical and biochemical findings diagnostic of acromegaly. Magnetic resonance imaging showed a 1.2-cm sellar mass. Following resection of the macroadenoma, serum insulinlike growth factor 1 (IGF-1) and growth hormone (GH) levels remained unchanged. Pathologic examination revealed adenomatous changes, including a nonsecretory focus and a prolactin immunopositive area (GH stain negative in both). Octreotide long-acting release was ineffective. Search for an ectopic tumor included normal octreoscan and abdominal computed tomography. GHRH was greater than 1000 pg/mL. Repeated abdominal computed tomography documented a 6.2-cm mass in the tail and body of the pancreas. Distal pancreatectomy revealed a pancreatic neuroendocrine tumor that stained positive for GHRH. Postoperatively, serum GHRH and IGF-1 normalized. Re-evaluation of the initial pituitary pathologic specimen revealed additional somatotroph hyperplasia of the adjacent, normal pituitary gland. Primary hyperparathyroidism was diagnosed, and multigland parathyroid hyperplasia was noted at surgery. Genetic testing was positive for a mutation in the MEN1 gene.ConclusionThis patient’s acromegaly was resistant to somatostatin analogue therapy, reflecting the negative octreoscan imaging. In addition, this case is novel because the patient presented with pituitary adenomatous changes, which were presumably associated with MEN 1 and/or possibly the elevated GHRH levels. (Endocr Pract. 2011; 17:79-84)     

Calcitonin-Secreting Pancreatic Neuroendocrine Tumors: A Case Report and Review of the Literature

ObjectiveWe report the presentation and novel therapy of a calcitonin-secreting pancreatic neuroendocrine tumor (PNET) and review the literature on this unusual neoplasm.Methods:We cite the history of a 38-year-old male who presented with fatigue, weight loss, and diarrhea and was found to have a pancreatic head mass on cross-sectional imaging, as well as liver metastases.Results:The patient’s laboratory evaluation was notable for a >100-fold elevation of the peptide hormone calcitonin in serum. As calcitonin is typically secreted by thyroid C-cells, hypercalcitoninemia is considered a marker for medullary thyroid cancer (MTC) or C-cell hyperplasia, but it may be present in several physiologic or pathologic conditions or may be ectopically secreted in rare PNETs. An octreotide scan confirmed the presence of somatostatin (SST) receptors on the pancreatic mass and liver metastases, leading to the diagnosis of a calcitonin-secreting PNET. We initiated treatment with long-acting SST analogs and peptide receptor radionuclide therapy (⁹⁰Yttrium-DOTATOC) and achieved disease regression while maintaining a high quality of life.Conclusion:Functional PNETs that secrete calcitonin are exceedingly rare, but they are important to consider in the differential diagnosis of nonthyroid-mediated hypercalcitonemia or pancreatic tumors that present with diarrhea, as the management differs markedly from both MTC and other pancreatic malignancies. (Endocr Pract. 2014;20:e140-e144)     

Failure of Multiple Therapies in the Treatment of a Type 1 Diabetic Patient with Insulin Allergy: A Case Report

ObjectiveTo describe the clinical manifestations of insulin allergy and explain a systematic management approach.MethodsWe present the clinical, laboratory, and pathologic findings of a type 1 diabetic patient with allergy to subcutaneous insulin and briefly review the related literature.ResultsAn 18-year old woman with type 1 diabetes mellitus had an insulin allergy and developed subcutaneous nodules after insulin administration. Human and analogue insulins were used, but painful nodule formation persisted. Treatment with antihistamines, steroids, and omalizumab and insulin desensitization were ineffective. The patient required pancreatic transplant because glycemic control could not be achieved due to the insulin allergy.ConclusionsInsulin allergy is not a common condition and can be challenging in patients with type 1 diabetes. Therefore, identifying patients with true insulin allergy and applying a stepwise approach to their treatment is important. (Endocr Pract. 2011;17:91-94)     

Everolimu Resolving Hypoglycemia,Producing Hyperglycemia,and Necessitating Insulin Use in A Patient With Di Etes and Nonresectable Malignant Insulinoma

ObjectiveTo present a case of management of refractory hypoglycemia due to malignant insulinoma with use of everolimusresulting in recurrent insulin-requiring diabetes.MethodsThis report describes a case of a nonresectable malignant insulinoma in a 78-year-old patient with long-standing type 2 diabetes mellitus. Endogenous hyperinsulinism was confirmed by a fasting test, which revealed a glucose level of 35 mg/dL and an insulin value of 23.7 μIU/mL. Endoscopic ultrasonography, magnetic resonance imaging, and computed tomography identified a pancreatic mass, infiltration of the superior mesenteric vein, and metastatic lesions in the liver.ResultsAfter chemoembolization of the metastatic lesions, hypoglycemia recurred, despite combined treatment with somatostatin analogues, dexamethasone, and diazoxide. Everolimus, an orally administered mammalian target of rapamycin, was used at a daily dose of 5 mg. After 6 months, the hypoglycemia was controlled, and the patient presented with a C-peptide level of 0.2 ng/mL and secondary hyperglycemia that necessitated insulin treatment.ConclusionThe orally administered drug everolimus controlled hypoglycemia due to a malignant insulinoma in a patient with prior insulinrequiring diabetes. Secondary hyperglycemia was an acceptable drug effect (to the patient and managing physicians), in light of the complex and often poorly tolerated treatments available for this rare condition. (Endocr Pract. 2011;17:e17-e20)     

Endoscopic Ultrasonography - A Sensitive Tool in the Preoperative Localization of Insulinoma

ObjectiveA number of imaging modalities have been used in the preoperative localization of insulinomas. Computed tomography (CT) is the most commonly employed modality. Endoscopic ultrasound (EUS) allows the transducer to be placed in close proximity to the pancreas, thereby yielding higher quality images, which facilitates accurate localization, minimally invasive surgery, and a lower occurrence of residual tumors, all of which contribute to a better clinical outcome.MethodsWe analyzed the hospital records of all adult patients (age >18 years) diagnosed with insulinoma between October 2004 and September 2010. The diagnosis was based on the clinical practice guidelines of the American Endocrine Society. We compared the sensitivities of EUS and multidetector computed tomography (MDCT) in lesion.ResultsEighteen patients were seen over a period of 6 years, and all underwent EUS. MDCT scans were carried out in 17 patients. EUS had greater sensitivity (89%) in localizing insulinomas compared to CT (69%). In this series, the lesions that were missed on CT but picked up on EUS were smaller (<12 mm, P<.001). Lesions that were near mesenteric vessels and those located in the head of the pancreas were more likely to be missed on CT.ConclusionsEUS has a greater sensitivity in identifying and localizing insulinomas. As availability increases, EUS should be part of a preoperative insulinoma workup. (Endocr Pract. 2013;19:602-608)     

Cushing’s Syndrome Due to a Corticotropin-releasing Hormone- and Adrenocorticotrophic Hormone-producing Neuroendocrine Pancreatic Tumor

Objective: To our knowledge, only 2 cases of pancreatic neuroendocrine tumors have been described as the source of corticotropin-releasing hormone (CRH) in Cushing’s syndrome. Here, we describe a case of ectopic adrenocorticotrophic hormone (ACTH-) and CRH-production caused by a pancreatic neuroendocrine tumor.Methods:We analyzed and summarized the patient’s medical history, physical examination results, laboratory data, imaging studies, and histopathologic results.Results: An endocrinologic workup revealed massive ACTH-dependent hypercortisolism. Pituitary magnetic resonance imaging (MRI) showed no pathologic findings and led to extensive imaging in search of the suspected ectopic lesion. Ketoconazole treatment was initiated. Rapid deterioration of the patient’s clinical condition due to escalating cortisol levels and resulting sepsis required an emergency adrenalectomy to control the hypercortisolism. A positron emission tomography-computed tomography (PET-CT) scan revealed a hepatic lesion, which was biopsied. Histology of the lesion showed a well-differentiated endocrine tumor. Subsequent scintigraphy with octreotide (a somatostatin [SMS] analog) detected a pancreatic tumor, which was endosonographically confirmed. The initiated SMS therapy was followed by a distal splenopancreatectomy and a right hemihepatectomy. Immunostaining of the specimen showed positive expression for CRH and ACTH.Conclusion: We conclude that SMS-scintigraphy did have an additional diagnostic benefit compared to PET-CT. In hypercortisolemic patients, rapid endocrinologic evaluation is crucial to prevent rapid deterioration and a possible fatal outcome. (Endocr Pract. 2014;20:e53-e57)     

Complete clinical remission and disappearance of liver metastases after treatment with somatostatin analogue in a 40-year-old woman with a malignant insulinoma positive for somatostatin receptors type 2

Insulinoma is the most common pancreatic endocrine tumor, accounting for 40% of all pancreatic functional neoplasm, and is characterized by hypersecretion of insulin and hypoglycemia. Elective treatment for insulinomas is surgical enucleation. Medical therapy with diazoxide, followed by somatostatin analogues in some cases, may be necessary to treat the hypoglycemic symptoms. We report a case of a patient affected by metastatic insulinoma with severe hypoglycemia. After surgery, histopathology confirmed the presence of a malignant insulinoma with multiple metastases in the liver. Due to the persistence of hypoglycemia, the patient was started on octreotide LAR treatment, which determined a complete clinical remission with regression of the metastatic lesions in the liver after one year. Repeated CT scans 2 and 3 years after surgery confirmed the remission. To our knowledge, the complete regression of the disease in insulinomas treated with long-standing somatostatin analogue therapy has never been reported. Immunohistochemical analysis in tissue specimens showed a strong membrane immunoreactivity for somatostatin receptors type 2 (SSTR2) in both the primary nodule and the metastases. The capacity of somatostatin analogues to negatively regulate cell proliferation through indirect and direct mechanisms has been experimentally demonstrated. Furthermore, SSTR2 activation may exert pro-apoptotic effects in neoplastic cells. Thus, both mechanisms may have been responsible of the remission of the disease in this patient. This case underlies the potential impact of the treatment of pancreatic insulinomas with somatostatin analogues, and, if confirmed, the usefulness of SSTR determination in these neoplastic specimens.     

Pancreatic Neuroendocrine Tumor in a Child with a Tuberous Sclerosis Complex 2 (TSC2) Mutation

ObjectivePancreatic neuroendocrine tumors (PanNETs) are rare in children with tuberous sclerosis complex (TSC). The objective of this report is to describe a case of PanNET in a boy with TSC.MethodsWe describe the patient’s clinical presentation, biochemical workup, and laboratory tests.ResultsA 10-year-old boy with a TSC2 mutation presented with a nonsecretory PanNET discovered during routine annual abdominal ultrasound. Surgical distal pancreatectomy with spleen preservation was undertaken. The excised tumor appeared nodular, whitish, and encapsulated. The tumor was composed of pancreatic endocrine monomorphic cells, and the solid appearance of the tumor was interrupted by areas of cystic degeneration. Mitoses were rare; the proliferation index was estimated around 4%. Local lymph nodes showed hyperplasia but were free of metastatic disease. Immunohistochemical examinations were positive for the neuroendocrine markers chro-mogranin, neurospecific enolase, synaptophysin, CAM52, and vimentin and were negative for CD 10 and alpha-1 antitrypsin. The immunohistochemistry also showed a lack of hyperactivation of mammalian target of rapamycin (mTOR) mTOR pathway. All data supported the diagnosis of a grade II well-differentiated neuroendocrine neoplasm, according to the World Health Organization (WHO).ConclusionThirteen non-secretory PanNET cases associated with TSC have been reported, including our patient (9 men and 4 women; 7 with TSC2 mutation). These tumors are usually asymptomatic and can be associated with metastasis; therefore, early diagnosis is crucial for prompt treatment. It is still unclear whether PanNETs should be considered a feature of TSC; however due to this association, we suggest that pancreas investigation should be included in routine examinations in men with TSC2 mutation. (Endocr. Pract. 2013;19:e124-e128)     

Insulinoma in a Young Female Patient With Systemic Lupus Erythematosus: A Case Report

ObjectiveFasting hypoglycemia may occur in subjects with systemic lupus erythematosus (SLE) when accompanied with insulin-binding antibodies or insulin-receptor antibodies. However, insulinoma has not been reported in SLE subjects with hypoglycemia.MethodsWe present a case report and review the relevant literature.ResultsA 26-year-old female with underlying SLE experienced several episodes of neuropsychiatric symptoms in a fasting state. The steroid dosage was titrated up, but in vain. Timely imaging studies showed a pancreatic tumor, and insulinoma was proven by pathology. Hypoglycemia did not recur after surgery.ConclusionPhysicians should distinguish insulinoma from autoimmunity-mediated hypoglycemia in SLE patients with fasting hypoglycemia. (Endocr Pract. 2014; 20:e256-e259)     

Hyperinsulinism Presenting In Childhood and Treatment by Conservative Pancreatectomy

ObjectiveTo describe the uncommon presentation of hyperinsulinism in an 8-year-old boy.MethodsWe describe the patient’s clinical findings, results from biochemical and imaging studies, surgical approach, and outcome. The discussion encompasses a review of literature that provided the basis for the diagnostic and surgical approach applied to this patient’s case.ResultsAn obese 8.5-year-old boy initially presented with hypoglycemic seizures after initiation of dietary changes to treat obesity. Biochemical analysis indicated hyperinsulinism. Endoscopic ultrasonography showed no pancreatic lesions suggestive of insulinoma. Genetic studies identified no known mutations in the ABCC8, KCNJ11, GCK, or GLUD1 genes. Selective arterial calcium stimulation and hepatic venous sampling did not document a focal source for hyperinsulinism in the pancreas, and positron emission tomography with 18-fluoro-L-3,4-dihydroxyphe-nylalanine showed diffusely increased uptake in the pancreas. The patient ultimately required partial pancreatectomy because of continued hypoglycemia while taking diazoxide and octreotide. Intraoperative glucose monitoring directed the extent of surgical resection. A 45% pancreatectomy was performed, which resolved the hypoglycemia but led to impaired glucose tolerance after surgery.ConclusionThe unusual presentation of hyperinsulinism in childhood required a personalized approach to diagnosis and surgical management using intraoperative glucose monitoring that resulted in a conservative pancreatectomy. (Endocr Pract. 2012;18:e52-e56)     

GSK-3β Protein Phosphorylates and Stabilizes HLXB9 Protein in Insulinoma Cells to Form a Targetable Mechanism of Controlling Insulinoma Cell Proliferation

Insulinomas (pancreatic islet β cell tumors) are the most common type of functioning pancreatic neuroendocrine tumors that occur sporadically or as a part of the MEN1 syndrome that is caused by germ line mutations in MEN1. Tissue-specific tumor predisposition from germ line mutations in ubiquitously expressed genes such as MEN1 could occur because of functional consequences on tissue-specific factors. We previously reported the proapoptotic β cell differentiation factor HLXB9 as a downstream target of menin (encoded by MEN1). Here we show that GSK-3β inactivates the proapoptotic activity of HLXB9 by phosphorylating HLXB9 at Ser-78/Ser-80 (pHLXB9). Although HLXB9 is found in the nucleus and cytoplasm, pHLXB9 is predominantly nuclear. Both pHLXB9 and active GSK-3β are elevated in β cells with menin knockdown, in MEN1-associated β cell tumors (insulinomas), and also in human sporadic insulinomas. Pharmacologic inhibition of GSK-3β blocked cell proliferation in three different rodent insulinoma cell lines by arresting the cells in G₂/M phase and caused apoptosis. Taken together, these data suggest that the combination of GSK-3β and pHLXB9 forms a therapeutically targetable mechanism of insulinoma pathogenesis. Our results reveal that GSK-3β and pHLXB9 can serve as novel targets for insulinoma treatment and have implications for understanding the pathways associated with β cell proliferation.     

Clinical Management of Malignant Insulinoma: a single Institution’s experience over three decades

Background

Malignant insulinoma is extremely rare and accounts for only 10% of total insulinoma cases. The goal of this study is to retrospectively analyze clinical data from 15 patients with malignant insulinoma treated at Peking Union Medical College Hospital (PUMCH) from 1984 to April 2017.

Methods

“Malignant insulinoma” was used as the keywords in the PUMCH medical record retrieval system to search and obtain patients’ clinical information. We identified subjects diagnosed with malignant insulinoma based on clinical or surgical pathological signs and subsequently analyzed their clinical data.

Results

Eight males and seven females with a median age at diagnosis of 40?years (38–54?years) were included. Eight patients (53%) had developed metastases at diagnosis, while the others (46.67%) developed metastases during the follow-up visits. The major sites of metastasis were the liver (86.7%), local tissues and blood vessels (33%) and abdominal lymph nodes (13%). All patients displayed neuroglycopenic (100%) and/or autonomic (60%) symptoms, mostly during fasting periods (73.3%), with an average blood glucose level of 1.66?±?0.51?mmol/L. A total of 93% of the patients had one primary pancreatic lesion, 53% had a lesion in the head of the pancreas, and 47% had a lesion in the tail of the pancreas, with diameters ranging between 0.9 and 6.0?cm. Most liver metastases were multiple lesions. Selective celiac arteriography yielded 100% sensitivity for both primary pancreatic lesions and liver metastases. Most patients received synthetical treatments, including surgery, chemoembolization, and octreotide.

Conclusions

Malignant insulinomas have a similar diagnostic process to that of benign insulinomas but require far more comprehensive therapies to alleviate hypoglycemic symptoms and extend patients’ survival.

     

Use of A Continuous Glucose Monitor in the Management of Inoperable Meta Static Insulinoma: A Case Report

ObjectiveTo describe the successful use of a continuous glucose monitor in the management of a patient with inoperable metastatic insulinoma.MethodsWe present a case of inoperable recurrent metastatic insulinoma in which medical therapy failed to relieve symptoms of dangerous hypoglycemia. We describe how the use of a continuous glucose monitor has assisted in avoiding hypoglycemia and improving her quality of life.ResultsA 70-year-old woman with a history of recurrent surgically treated insulinoma presented with recurrent hypoglycemia secondary to multiple metastases in the liver. Diazoxide therapy decreased the frequency of symptoms, but she continued to have hypoglycemic episodes resulting in frequent visits to the emergency department. Since starting to use a continuous glucose monitor, she has been able to avoid hypoglycemia with associated neuroglycopenic symptoms. While the accuracy of the device was poor when compared with conventional fingerstick monitors, the sensor tended to read higher than the meter in the hypoglycemic range. Although this led to more frequent false-positive hypoglycemic alarms, true episodes of severe hypoglycemia were rare.ConclusionsMalignant insulinomas are rare tumors. Many affected patients have disease that is unresectable, and medical therapy is limited in its ability to prevent hypoglycemic episodes. We have demonstrated that a continuous glucose monitor can be a useful adjunct to therapy to reduce hypoglycemic episodes by alerting the patient to low glucose concentrations before the development of neuroglycopenic symptoms. (Endocr Pract. 2008;14:880-883)     

Medullary Thyroid Carcinoma Manifesting as an Ovarian Mass: Case Report and Review of Literature

ObjectiveTo report the uncommon case of a woman with abdominal pain and a complex adnexal mass, who was subsequently found to have medullary thyroid carcinoma (MTC) metastatic to the ovary.MethodsWe present the clinical history, physical findings, laboratory and imaging studies, and pathologic findings in a woman with metastatic MTC and locally aggressive disease. The genetic associations, variable clinical course, and histopathologic findings in MTC are reviewed.ResultsA 38-year-old woman with abdominal and pelvic pain underwent a computed tomographic scan of the abdomen, which showed a complex left adnexal mass. After laparoscopic left oophorectomy, histopathologic analysis of the resected ovary suggested the presence of a metastatic neuroendocrine tumor. The patient recovered but was referred to the surgery clinic 3 months later because of hoarseness, a left neck mass, and left-sided vocal cord paralysis. Further work-up was suggestive of MTC, which prompted RET testing for multiple endocrine neoplasia. The patient underwent left thyroid lobectomy and selective lymph node dissection but later required tracheostomy because of tumoral invasion of the trachea, laser debulking of the tumor, and external beam radiation therapy. One year postoperatively, development of a metastatic lesion in her right ovary necessitated a second oophorectomy.ConclusionMTC usually manifests as a solitary thyroid nodule but should be considered in patients with metastatic lesions characterized by neuroendocrine features. This unusual case highlights the biologic and clinical variability of this often aggressive thyroid cancer, which necessitates an attentive work-up, a rigorous operative strategy, and a periodic postoperative surveillance program. (Endocr Pract. 2008;14:351-357)     

Malignant Somatostatinoma Presenting with Diabetic Ketoacidosis and Inhibitory Syndrome: Pathophysiologic Considerations

ObjectiveTo describe a patient with diabetic ketoacidosis secondary to a malignant somatostatinoma.MethodsWe present the clinical, laboratory, radiologic, and pathologic findings of a patient with diabetic ketoacidosis secondary to a malignant somatostatinoma. We also review the potential effects of somatostatin on glucose homeostasis and discuss the underlying pathophysiologic mechanisms.ResultsA 30-year-old woman presented with diabetic ketoacidosis and had a malignant somatostatinoma with hepatic, bone, and lymph node metastasis. She exhibited features of somatostatinoma “inhibitory syndrome” characterized by mild nonketotic hyperglycemia, hypochlorhydria, cholelithiasis, steatorrhea, anemia, and weight loss. In these tumors, the absence of ketoacidosis is thought to arise from the somatostatin-induced simultaneous suppression of the secretion of insulin and glucagon. The patient’s primary tumor could not be located.ConclusionsDiabetic ketoacidosis may occur in somatostatinomas. The secretion of larger molecular weight forms of somatostatin from the tumor may contribute to the ketogenesis. (Endocr Pract. 2010;16:835-837)     

Clinical and Radiological Features of Pheochromocytoma/Ganglioneuroma Composite Tumors: A Case Series with Comparative Analysis

ObjectiveTo describe and compare the clinical, biochemical, radiologic, and pathologic features of adrenal pheochromocytoma-ganglioneuroma (PC-GN) composites with the features of isolated pheochromocytomas (PCs) and adrenal ganglioneuromas (AGNs).MethodsWe reviewed data for PC-GN composite cases seen at a single tertiary center between 1993 and 2012 and compared them with cases of isolated AGN and relatively similar median-size PCs.ResultsNine PC-GN composites were included. The median age at diagnosis was 52 years (range, 28 to 83 years) for PC-GN compared with 55 years (range, 24 to 78 years) for PC patients and 40 years (range, 18 to 64 years) for AGN patients. Similar to PCs, all PC-GN composites were associated with catecholamine overproduction, whereas AGNs were nonfunctioning. On pathology, the median tumor sizes were 7 cm (range, 2.5 to 13 cm) for PC-GN tumors, 6.5 cm (range, 3.5 to 7 cm) for PCs, and 8 cm (range, 3.2 to 20 cm) for AGNs. On computed tomography (CT) imaging, PC-GN composites and PCs were heterogeneous, with both having significantly higher postcontrast density values than AGNs, which typically looked homogeneous and had a progressive enhancement pattern without contrast washout in most cases.ConclusionThe presence of a PC component significantly increases tumor heterogeneity and postcontrast density values. CT imaging could be very helpful in distinguishing AGNs from both PC-GN and PC tumors, but only pathologic examination can yield the diagnosis. Clinically and radiologically, PC-GN composites are indistinguishable from PCs and need to be managed similarly. (Endocr Pract. 2014;20:864-869)     

A Novel Deletion Mutation in the Men1 Gene in a Patient with Prolactinoma and a Family History of Pancreatic Tumors

ObjectiveMultiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant tumor syndrome caused by mutations in the MEN1 gene. Mutations in this tumor suppressor gene are often associated with neuroendocrine tumors. Here we describe a novel deletion mutation at codon 304 in the MEN1 gene of a patient with a prolactinoma and strong family history of pancreatic tumors.MethodsWe describe the patient’s clinical course and mutational analysis and review the relevant literature. Results: A 30-year-old pregnant female was referred to our institution’s psychological department for treatment of depression. She had developed a prolactinoma at age 17 and was being treated with 1 mg/week of cabergoline. A medical interview revealed a family history of pancreatic islet cell and other tumors; her mother died of pancreatic cancer, her brother is living with gastrinoma, and her sister died of leiomyosarcoma. Extensive examinations performed after delivery, including laboratory tests and computed tomography (CT) scans, did not reveal any other tumors. Mutational analysis of the MEN1 gene identified a heterozygous deletion mutation (c911_914delAGGT) at codon 304. This mutation produces a frameshift at p.304Lys and might disturb the splicing of intron 6 due to the lack of a donor site. The predicted menin protein from the mutated allele is truncated at amino acid 328.ConclusionWe report a novel deletion mutation (c911_914delAGGT) in the MEN1 gene that was likely associated with the patient’s prolactinoma and her strong family history of pancreatic tumors. (Endocr Pract. 2014; 20:e162-e165)