Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendocrine tumors that arise from chromaffin cells. PHEOs arise from the adrenal medulla, whereas PGLs arise from the neural crest localized outside the adrenal gland. Approximately 40% of all cases of PPGLs (pheochromocytomas/paragangliomas) are associated with germline mutations and 30–40% display somatic driver mutations. The mutations associated with PPGLs can be classified into three groups. The pseudohypoxic group or cluster I includes the following genes: SDHA, SDHB, SDHC, SDHD, SDHAF2, FH, VHL, IDH1/2, MHD2, EGLN1/2 and HIF2/EPAS; the kinase group or cluster II includes RET, NF1, TMEM127, MAX and HRAS; and the Wnt signaling group or cluster III includes CSDE1 and MAML3. Underlying mutations can help understand the clinical presentation, overall prognosis and surveillance follow-up. Here we are discussing the new genetic insights of PPGLs.
Background and Objective Recombinant human thyrotropin (rhTSH) is currently not FDA-approved for the treatment of high-risk patients with differentiated thyroid cancer (DTC). The goal of our study was to compare the outcomes in higher risk patients with metastatic DTC prepared for radioiodine (RAI) therapy with rhTSH versus thyroid hormone withdrawal (THW). Methods Retrospective chart review of patients with metastatic DTC in follow-up at MedStar Washington Hospital Center and MedStar Georgetown University Hospital from 2009 to 2017. Patients were divided according to their preparation for RAI therapy, with assessment of progression free survival (PFS) and overall survival (OS). Results Fifty-five patients with distant metastases (16 men, 39 women) were prepared for RAI therapy exclusively either with rhTSH (n= 27) or with THW (n= 28). There were no statistically significant differences between the groups regarding clinicopathological features and history of RAI therapies. The median follow-up time for patients with rhTSH-aided therapies was 4.2 yr (range 3.3 – 5.5 yr) and for patients with THW-aided therapies was 6.8 yr (range 4.2- 11.6 yr) (p=0.002). Multivariate analysis showed that the method of TSH stimulation was not associated with a difference in PFS or OS. Conclusion As has been shown previously for low-risk DTC, this study indicates that the mode of preparation for RAI therapy does not appear to influence the outcomes of patients with metastatic DTC. PFS and OS were similar for patients with THW-aided or rhTSH-aided RAI therapies.
Summary Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant condition characterized by parathyroid, anterior pituitary and enteropancreatic endocrine cell tumors. Neuroendocrine tumors occur in approximately in 5–15% of MEN1 patients. Very few cases of ovarian NETs have been reported in association with clinical MEN1 and without genetic testing confirmation. Thirty-three-year-old woman with MEN1 was found to have right adnexal mass on computed tomography (CT). Attempt at laparoscopic removal was unsuccessful, and mass was removed via a minilaparotomy in piecemeal fashion. Pathology showed ovarian NET arising from a teratoma. Four years later, patient presented with recurrence involving the pelvis and anterior abdominal wall. She was treated with debulking surgery and somatostatin analogs (SSAs). Targeted DNA sequencing analysis on the primary adnexal mass as well as the recurrent abdominal wall tumor confirmed loss of heterozygosity (LOH) at the MEN1 gene locus. This case represents to our knowledge, the first genetically confirmed case of ovarian NET arising by a MEN1 mechanism in a patient with MEN1. Extreme caution should be exercised during surgery as failure to remove an ovarian NET en masse can result in peritoneal seeding and recurrence. For patients with advanced ovarian NETs, systemic therapy options include SSAs, peptide receptor radioligand therapy (PRRT) and novel agents targeting mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF). Learning points: Ovarian NET can arise from a MEN1 mechanism, and any adnexal mass in a MEN1 patient can be considered as a possible malignant NET. Given the rarity of this disease, limited data are available on prognostication and treatment. Management strategies are extrapolated from evidence available in NETs from primaries of other origins. Care should be exercised to remove ovarian NETs en bloc as failure to do so may result in peritoneal seeding and recurrence. Treatment options for advanced disease include debulking surgery, SSAs, TKIs, mTOR inhibitors, PRRT and chemotherapy.
Objectives To identify risk factors for severe disease and death among patients with diabetes and coronavirus disease 2019 (COVID-19) infection. Methods This retrospective cohort study conducted at three hospitals included 733 consecutive patients with DM admitted with confirmed COVID-19 (March 1 – December 31, 2020). Multivariable logistic regression was performed to identify predictors of severe disease and death. Results The mean age was 67.4 ± 14.3 years, 46.9% were males and 61.5% were African American. Among all patients, 116 (15.8%) died in the hospital. A total of 317 (43.2%) patients developed severe disease, 183 (25%) were admitted to an ICU and 118 (16.1%) required invasive mechanical ventilation. Increasing BMI (OR, 1.13; 95% CI, 1.02–1.25), history of chronic lung disease (OR, 1.49; 95% CI, 1.05–2.10) and increasing time since the last HbA1c test (OR, 1.25; 95% CI, 1.05–1.49) were the preadmission factors associated with increased odds of severe disease. Preadmission use of metformin (OR, 0.67; 95% CI, 0.47–0.95) or GLP-1 agonists (OR, 0.49; 95% CI, 0.27–0.87) was associated with decreased odds of severe disease. Increasing age (OR, 1.21; 95% CI, 1.09–1.34), co-existing chronic kidney disease greater than stage 3 (OR, 3.38; 95% CI, 1.67–6.84), ICU admission (OR, 2.93; 95% CI, 1.28–6.69) and use of invasive mechanical ventilation (OR, 8.67, 95% CI, 3.88–19.39) were independently associated with greater odds of in-hospital death. Conclusion Several clinical characteristics were identified to be predictive of severe disease and in-hospital death among patients with underlying diabetes hospitalized with COVID-19.
Introduction Neuroendocrine tumors (NETs) are neoplasms that can arise from the neuroendocrine cells distributed widely throughout the body. Majority of NETs overexpress somatostatin receptors (SSTR) on their cell surface. This biologic characteristic is exploited in the SSTR-based imaging such as 111 In octreotide scintigraphy and 68 Ga DOTATATE positron emission tomography (PET)/CT. These modalities are currently considered standard for initial evaluation of suspected NETs. Although highly sensitive and specific, recent reports demonstrate a concerning incidence of “false-positive” physiologic uptake of these tracers in the pancreatic head - a confounding common site of NET involvement. Case report: A 78 year-old woman presented to clinic with a year-long history of diarrhea. Serum vasoactive intestinal peptide (VIP) levels were slightly elevated at 134.2 pg/mL. CT showed a mildly enhancing 2.5x1.8x2.8 cm area in the pancreatic uncinate process which corresponded to moderate focal uptake with 68 Ga DOTATATE PET/CT. A presumptive diagnosis of NET was made, and the patient was scheduled to undergo Whipple’s surgery. She sought a second opinion at our institution. A subsequent MRI showed no lesion in the uncinate process and the patient’s surgery was deferred. Thereafter, her VIP levels spontaneously normalized. Endoscopic ultrasound (EUS) with fine needle aspiration cytology of the uncinate process showed normal pancreatic acini with no evidence of NET. Conclusion Conspicuous physiological uptake has been reported in the pancreatic head on 16-70% of 68 Ga DOTATATE or 68 Ga DOTANOC PET/CT scans, and 26% of the 111 In octreotide scintigraphy scans. 1 Image-based quantitative attempts to distinguish physiologic from pathologic uptake using SUVmax have rendered mixed results. When evaluating SSTR-based imaging uptake in the pancreatic head, patients can benefit from a higher index of suspicion of false positive uptake. Such cases require additional confirmation by means such as MRI or EUS. The patient described above also had mild contrast enhancement on CT, but an MRI didn’t show any corresponding lesion. Because of potential morbidity and mortality related to false positive uptake, a systematic review with evidence-based recommendations for imaging may benefit patient care. 1. Brabander T, et al. Physiological Uptake in the Pancreatic Head on Somatostatin Receptor Scintigraphy Using [111In-DTPA]Octreotide: Incidence and Mechanism. Clin Nucl Med 2017;42:15-9. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserv...
Introduction MEN1 is an autosomal dominant condition characterized by parathyroid, anterior pituitary and enteropancreatic endocrine cell tumors. Carcinoids occur in 5-15% patients, majority of which are of foregut origin (thymus, bronchus, stomach and duodenum). Only 1 case of ovarian carcinoid has been reported in association with MEN1, and was not confirmed with genetic testing. Case report A 33-year-old female with a macroprolactinoma and primary hyperparathyroidism was referred to us with a presumptive diagnosis of MEN1. Genetic testing showed a heterozygous germline mutation in the MEN1 gene, c.219_220delCG (frameshift leading to premature protein truncation). She had no family history consistent with MEN1. EGD showed two submucosal nodules in the duodenum with confirmed histology of gastrinomas. CT demonstrated 8.7 x 7.7 cm right adnexal mass containing foci of soft tissue density and calcification. Laparoscopic resection was attempted but the mass was too large to be delivered en-bloc. Operative approach was changed to a minilaparotomy and the mass was delivered in a piecemeal fashion. Pathology demonstrated a benign dermoid cyst with neuroendocrine tumor consistent with carcinoid extending into peri-ovarian tissues. 4 years later, she presented with a lower abdominal palpable mass. CT showed an irregular, avidly enhancing 11.7 x 8.7 cm pelvic mass, extending through the anterior abdominal wall into the subcutaneous fat with satellite lesions within the anterior subcutaneous abdomen. The CT abnormalities corresponded to abnormally elevated In-111 pentetreotide uptake. Biopsy of one of the subcutaneous lesions showed metastatic neuroendocrine neoplasm with Ki67 index of 2%. Targeted genetic analysis for the patient’s MEN1 mutation using DNA samples isolated from the primary adnexal mass as well as the recurrent abdominal wall tumor demonstrated predominantly mutant sequence in both specimens, confirming LOH at the MEN1 gene locus. 5 months later, the patient presented with obstructive uropathy from nodal metastases. She underwent debulking surgery via exploratory laparotomy, panniculectomy, resection of metastatic abdominal wall tumors and abdominal wall reconstruction. Post operatively, FDG-PET scan showed few scattered disease foci. She was commenced on monthly octreotide injections. Conclusions This case represents to our knowledge, the first genetically confirmed case of ovarian carcinoid arising by a MEN1 mechanism. Ovarian carcinoid should be considered as a differential in MEN1 patients with adnexal mass. Extreme caution should be exercised during surgical resection, as failure to remove an ovarian carcinoid en masse can result in peritoneal seeding and recurrence. For patients with advanced disease, systemic therapy options include somatostatin receptor analogs, peptide receptor radioligand therapy, and novel agents targeting mTOR and VEGF. Unless otherwise noted, all abstracts presented at ENDO are embargoed until...
Rationale: Neuroendocrine tumors (NETs) are neoplasms that can arise from the neuroendocrine cells distributed widely throughout the body. Majority of NETs overexpress somatostatin receptors (SSTR) on their cell surface. This biologic characteristic is exploited by SSTR-based imaging such as 111In octreotide scintigraphy and 68Ga DOTATATE positron emission tomography (PET)/computed tomography (CT), which are considered standard for initial evaluation of NETs. Although highly sensitive and specific, recent reports demonstrate a concerning incidence of “false-positive” physiologic uptake of these tracers in the pancreatic head – a common site of neuroendocrine tumor (NET) involvement. We present false positive uptake on 68Ga DOTATATE PET/CT along with false positive CT findings. Role of other imaging modalities is discussed. Patient concerns: A 78-year-old woman presented with a year-long history of diarrhea. Diagnosis: Serum vasoactive intestinal peptide (VIP) levels were slightly elevated at 134.2 pg/mL (normal <75 pg/mL). CT showed a mildly enhancing 2.5 cm × 1.8 cm × 2.8 cm area in the pancreatic uncinate process which corresponded to focal uptake with 68Ga DOTATATE PET/CT. A presumptive diagnosis of pancreatic NET (vipoma) was made, and the patient was scheduled to undergo Whipple's surgery. Interventions: She sought a second opinion and a subsequent magnetic resonance imaging (MRI) showed no lesion and the patient's surgery was deferred. Thereafter, her VIP levels spontaneously normalized. Endoscopic ultrasound (EUS) with fine needle aspiration cytology of the uncinate process showed normal pancreatic acini with no evidence of NET. Outcomes: Patient is currently pursuing workup for alternative etiologies for chronic diarrhea. Lessons: Conspicuous physiological uptake has been reported in the pancreatic head on 16% to 70% of 68Ga DOTATATE or 68Ga DOTANOC PET/CT scans, and 26% of the 111In octreotide scintigraphy scans. Image-based quantitative attempts to distinguish physiologic from pathologic uptake using SUVmax have rendered mixed results. When evaluating SSTR-based imaging uptake in the pancreatic head, patients can benefit from a higher index of suspicion of false positive uptake. Such cases require additional confirmation by MRI or EUS. Interestingly, the patient described also had mild contrast enhancement on CT, but without an MRI correlate. Because of potential morbidity and mortality related to false positive uptake, a systematic review with evidence-based recommendations for imaging may benefit patient care.
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