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Maturity-onset diabetes of the young, or MODY-monogenic diabetes, is a not-so-rare collection of inherited disorders of non-autoimmune diabetes mellitus that remains insufficiently diagnosed despite increasing awareness. These cases are important to efficiently and accurately diagnose, given the clinical implications of syndromic features, cost-effective treatment regimen, and the potential impact on multiple family members. Proper recognition of the clinical manifestations, family history, and cost-effective lab and genetic testing provide the diagnosis. All patients must undergo a thorough history, physical examination, multigenerational family history, lab evaluation (glycated hemoglobin A1c [HbA1c], glutamic acid decarboxylase antibodies [GADA], islet antigen 2 antibodies [IA-2A], and zinc transporter 8 [ZnT8] antibodies). The presence of clinical features with 3 (or more) negative antibodies may be indicative of MODY-monogenic diabetes, and is followed by genetic testing. Molecular genetic testing should be performed before attempting specific treatments in most cases. Additional testing that is helpful in determining the risk of MODY-monogenic diabetes is the MODY clinical risk calculator (>25% post-test probability in patients not treated with insulin within 6 months of diagnosis should trigger genetic testing) and 2-hour postprandial (after largest meal of day) urinary C-peptide to creatinine ratio (with a ≥0.2 nmol/mmol to distinguish HNF1A- or 4A-MODY from type 1 diabetes). Treatment, as well as monitoring for microvascular and macrovascular complications, is determined by the specific variant that is identified. In addition to the diagnostic approach, this article will highlight recent therapeutic advancements when patients no longer respond to first-line therapy (historically sulfonylurea treatment in many variants). LEARNING OBJECTIVES: Upon completion of this educational activity, participants should be able to: Identify risk factors and learn when to suspect MODY-monogenic diabetes. Obtain appropriate diagnostic testing and evaluation prior to treatment. Determine appropriate monitoring and treatment for microvascular and macrovascular comorbidities. Recognize the recommended approach to treatment and monitoring that was performed in a patient with MODY-monogenic diabetes. TARGET AUDIENCE: This continuing medical education activity should be of substantial interest to endocrinologists and all health care professionals who care for people with diabetes mellitus.

Objective: To identify novel prognostic risk factors and compare them with other known prognostic risk factors in follicular-cell-derived thyroid carcinoma (FDTC) with distant metastases. Methods: A retrospective review was conducted of adult patients with metastatic FDTC seen at a tertiary care center between January 1990 and December 2010. A 15-year Kaplan–Meier survival estimate was created for overall survival (OS) and cancer-specific survival (CSS). Hazard ratios (HR) and P values from Cox proportional hazard models were used with a 95% CI. Results: There were 143 patients (60.1% male, 39.9% female), of whom 104 (72.7%) patients had papillary, 30 (21.0%) had follicular, 5 (3.5%) had poorly differentiated, and 4 (2.8%) had Hürthle cell cancers. Median length of follow-up was 80.0 months (range 1.0–564.0). The 15-year mortality rate was 32.2% and cancer-specific mortality was 25.2%, with OS and CSS having the same risk factors. Lung was the most common site of metastases in 53 patients (37.1%), and patients with pleural effusions had significantly lower CSS (HR = 5.21, CI = 1.79–15.12). Additional risk factors for a decreased CSS included: older age upon diagnosis (>45 years, HR = 4.15, CI = 1.43–12.02), multiple metastatic locations (HR = 3.75, CI = 1.32–10.67), and incomplete/unknown tumor resection (HR = 2.35, CI = 1.18–4.67). Conclusion: This study is the first to demonstrate that pleural effusion is a poor prognostic sign in patients with FDTC with distant metastases and compare this risk with other accepted prognostic variables.

Context Preoperative imaging is performed routinely to guide surgical management in primary hyperparathyroidism, but the optimal imaging modalities are debated. Objective Our objectives were to evaluate which imaging modalities are associated with improved cure rate and higher concordance rates with intraoperative findings. A secondary aim was to determine whether additive imaging is associated with higher cure rate. Design, Setting, and Patients This is a retrospective cohort review of 1485 adult patients during a 14-year period (2004-2017) at an academic tertiary referral center that presented for initial parathyroidectomy for de novo primary hyperparathyroidism. Main Outcome Measures Surgical cure rate, concordance of imaging with operative findings, and imaging performance. Results The overall cure rate was 94.1% (95% confidence interval, 0.93-0.95). Cure rate was significantly improved if sestamibi/single-photon emission computed tomography (SPECT) was concordant with operative findings (95.9% vs. 92.5%, P = 0.010). Adding a third imaging modality did not improve cure rate (1 imaging type 91.8% vs. 2 imaging types 94.4% vs. 3 imaging types 87.2%, P = 0.59). Despite having a low number of cases (n = 28), 4-dimensional (4D) CT scan outperformed (higher sensitivity, specificity, positive predictive value, negative predictive value) all imaging modalities in multiglandular disease and double adenomas, and sestamibi/SPECT in single adenomas. Conclusions Preoperative ultrasound combined with sestamibi/SPECT were associated with the highest cure and concordance rates. If pathology was not found on ultrasound and sestamibi/SPECT, additional imaging did not improve the cure rate or concordance. 4D CT scan outperformed all imaging modalities in multiglandular disease and double adenomas, and sestamibi/SPECT in single adenomas, but these findings were underpowered.

Objective The coexistence of insulinoma and insulin antibodies is extremely rare. The aim of this novel case report is to inform physicians of the possibility of an insulinoma with concomitant insulin antibodies. Methods In this report, we describe a patient with symptomatic hypoglycemia confirmed with a 72-hour fast, who was subsequently found to have an insulinoma with concomitant elevation in his immunoglobulin G insulin antibody titer. Results The patient presented with initial symptoms of diaphoresis, confusion, and disorientation and was found unresponsive by a bystander. He had a fingerstick blood glucose of 36 mg/dL (reference 74-99 mg/dL), without exogenous insulin or sulfonylurea use. His symptoms resolved with administration of glucose. He was subsequently admitted for a 72-hour fast in which he developed neuroglycopenic symptoms 4 hours into the fast with fingerstick glucose of 47 mg/dL and serum glucose of 44 mg/dL (reference 74-99 mg/dL), C-peptide of 10.8 ng/mL (reference 0.5-2.7 ng/mL), insulin level of 106 μIU/mL (reference

Machine learning (ML) is increasingly being studied for the screening, diagnosis, and management of diabetes and its complications. Although various models of ML have been developed, most have not led to practical solutions for real-world problems. There has been a disconnect between ML developers, regulatory bodies, health services researchers, clinicians, and patients in their efforts. Our aim is to review the current status of ML in various aspects of diabetes care and identify key challenges that must be overcome to leverage ML to its full potential. ML has led to impressive progress in development of automated insulin delivery systems and diabetic retinopathy screening tools. Compared with these, use of ML in other aspects of diabetes is still at an early stage. The Food & Drug Administration (FDA) is adopting some innovative models to help bring technologies to the market in an expeditious and safe manner. ML has great potential in managing diabetes and the future is in furthering the partnership of regulatory bodies with health service researchers, clinicians, developers, and patients to improve the outcomes of populations and individual patients with diabetes.

Objective: Clomiphene citrate-induced hypertriglyceridemia causing acute pancreatitis is rare. The aim of this case report is to alert physicians to the possibility of clomiphene citrate-induced hypertriglyceridemia that can lead to acute, and even chronic, pancreatitis.Methods: We describe a patient with known mild hypertriglyceridemia who presented with acute pancreatitis and severe hypertriglyceridemia after initiation of clomiphene citrate.Results: The patient had mid-epigastric tenderness with radiation around her bilateral flanks in a band-like distribution. Lab studies showed a triglyceride level greater than 4,425 mg/dL, a lipase level greater than 3,000 U/L, and computed tomography of the abdomen showed acute interstitial edematous pancreatitis. The patient's Naranjo Adverse Drug Reaction score was calculated to be a 7, and was therefore probable as clomiphene being the causative agent. The patient's triglyceride levels improved after initiation of fibrate therapy and discontinuation of clomiphene at first; however, she continued to develop acute episodes of pancreatitis that progressed to chronic pancreatitis despite stopping clomiphene citrate. This is the second report of recurrent pancreatitis with hypertriglyceridemia induced by clomiphene citrate and, in this case specifically, each episode of pancreatitis was associated with hypertriglyceridemia.Conclusion: Clomiphene citrate-induced hypertriglyceridemia rarely occurs and can progress to acute, and even chronic, pancreatitis with significant morbidity. Clomiphene citrate should be used with caution in patients with elevated triglycerides, and should be avoided in patients with triglyceride levels greater than 400 mg/dL.

Objective: To determine predictors of prolonged length of stay (LOS), 30-day readmission, and 30-day mortality in a multihospital health system. Methods: We performed a retrospective review of 531 adults admitted with diabetic ketoacidosis (DKA) to a multihospital health system between November 2015 and December 2016. Demographic and clinical data were collected. Linear regression was used to calculate odds ratios (ORs) for predictors and their association with prolonged LOS (3.2 days), 30-day readmission, and 30-day mortality. Results: Significant predictors for prolonged LOS included: intensive care unit (ICU) admission (OR, 2.12; 95% confidence interval [CI], 1.38 to 3.27), disease duration (nonlinear) (OR, 1.28; 95% CI, 1.10 to 1.49), non-white race (OR, 1.73; 95% CI, 1.15 to 2.60), age at admission (OR, 1.03; 95% CI, 1.01 to 1.04), and Elixhauser index (EI) (OR, 1.21; 95% CI, 1.13 to 1.29). Shorter time to consult after admission (median [Q1, Q3] of 11.3 [3.9, 20.7] vs. 14.8 [7.4, 37.3] hours, P

Tetratricopeptide repeat domain-7A (TTC7A) deficiency causing combined immunodeficiency with inflammatory bowel disease (IBD) is rare. This case report alerts physicians to the possibility of TTC7A deficiency causing combined immunodeficiency with IBD and also highlights some of the current treatment options. We describe a 19-year-old patient with a compound heterozygote TTC7A mutation causing combined immunodeficiency, IBD, and multiple intestinal atresia. Compound heterozygote TTC7A mutations are known to cause combined immunodeficiency and IBD. Although rare, clinicians should be alerted to this variant and should understand the general approach to treatment.

In this review, we have highlighted work that has clearly demonstrated that mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), a negative regulator of MAPKs, is an important signaling mediator in bone, muscle, and fat tissue homeostasis and differentiation. Further, we examined recent studies with particular focus on MKP-1 overexpression or deletion and its impact on tissues connected to bone. We also summarized regulation of MKP-1 by known skeletal regulators like parathyroid hormone (PTH)/PTH-related peptide (PTHrP) and bone morphogenic proteins. MKP-1's integration into the pathophysiological state of osteoporosis, osteoarthritis, rheumatoid arthritis, obesity, and muscular dystrophy are examined to emphasize possible involvement of MKP-1 both at the molecular level and in disease complications such as sarcopenia- or diabetes-related osteoporosis. We predict that understanding the mechanism of MKP-1-mediated signaling in bone-muscle-fat crosstalk will be a key in coordinating their activities and developing therapeutics to improve clinical outcomes for diseases associated with advanced age.

Maturity-onset diabetes of the young (MODY) is an inherited form of diabetes caused by a mutation in a single gene. The frequency of mutation carriers for HNF4A-MODY has been reported to be 1.2% (1). Our group has previously published on the successful use of glucagon-like peptide 1 receptor agonist (GLP-1 RA) therapy in three consecutive generations of a family with an HNF1A-MODY (2). Although GLP-1 RA therapy has been studied in patients with HNF1A-MODY (3), it has not been studied in patients with HNF4A-MODY. In this father-son cohort, we demonstrate successful use of GLP-1 RA therapy in two patients with c.790:1 bp deletion of G; codon:264 mutations of HNF4A. The son first presented with neonatal hypoglycemia, then later developed diabetes and …