Clinical Diabetes and Endocrinology最新文献

Background: We intended to estimate the proportion hypoglycemic/hyperglycemic emergency episodes in treated diabetes mellitus (DM) patients admitted to a hospital ward, and calculate the prevalence of risk factors for hypoglycemia and diabetic complications.

Methods: In this cross-sectional, multicentered study, the observational data was collected by physicians from patient's hospitalization to discharge/death. Statistical tests were 2-tailed considering 5% significance level.

Results: There were 646 ward admissions due to hyperglycemic emergencies and 176 hypoglycemic episodes with a ratio hypoglycemia/hyperglycemia 0.27 for all DM patients. In T2DM patients the ratio was 0.38. These were mainly female (55.1%), functionally dependent (61.4%) and retired/disabled (73.1%). Median age was 75 years and median duration of disease 11 years. Half the patients were on insulin-based therapy and 30.1% on secretagogue-based therapy. Approximately 57% of patients needed occasional/full assistance to manage the disease. The most frequent risk factor for hypoglycemia was polypharmacy (85.0%). Hypoglycemia in the 12 months before admission was higher in insulin-based therapy patients (66.1%; p = 0.001).

Conclusions: Hyperglycemic emergencies are the most frequent cause of hospitalization in Portugal, although severe hypoglycemic events represent a health and social problem in elderly/frail patients. There is still the need to optimize therapy in terms of the potential for hypoglycemia in this patient group and a review of anti-hyperglycemic agents to add on to insulin.

Background: Evidence suggests that insulin therapy of patients with type 2 diabetes mellitus (T2DM) is frequently discontinued. However, the reasons for discontinuing insulin and factors associated with insulin discontinuation in this patient population are not well understood.

Methods: We conducted a retrospective cohort study of adults with T2DM prescribed insulin between 2010 and 2017 at Partners HealthCare. Reasons for discontinuing insulin and factors associated with insulin discontinuation were studied using electronic medical records (EMR) data. Natural language processing (NLP) was applied to identify reasons from unstructured clinical notes. Factors associated with insulin discontinuation were extracted from structured EMR data and evaluated using multivariable logistic regression.

Results: Among 7009 study patients, 2957 (42.2%) discontinued insulin within 12 months after study entry. Most patients who discontinued insulin (2121 / 71.7%) had reasons for discontinuation documented. The most common reasons were improving blood glucose control (33.2%), achieved weight loss (18.5%) and initiation of non-insulin diabetes medications (16.7%). In multivariable analysis adjusted for demographics and comorbidities, patients were more likely to discontinue either basal or bolus insulin if they were on a basal-bolus regimen (OR 1.6, 95% CI 1.3 to 1.8; p <  0.001) or were being seen by an endocrinologist (OR 2.6; 95% CI 2.2 to 3.0; p <  0.001).

Conclusions: In this large real-world evidence study conducted in an area with a high penetration of health insurance, insulin discontinuation countenanced by healthcare providers was common. In most cases it was linked to achievement of glycemic control, achieved weight loss and initiation of other diabetes medications. Factors associated with and stated reasons for insulin discontinuation were different from those previously described for non-adherence to insulin therapy, identifying it as a distinct clinical phenomenon.

The COVID-19 pandemic has prompted the rapid transition of in-person outpatient care to telemedicine, and clinical training to remote learning. The endocrinology fellows at the University of Michigan maintain their own continuity-of-care clinics and rotate in the Ann Arbor Veterans Affairs (VA) Healthcare System. For these clinics, we sought to preserve patient staffing with expert attending physicians and continue the clinical training experience in a remote setting. We have adapted the online conferencing platform, Zoom, to integrate learners into a virtual teaching clinic environment. By using the Zoom "breakout room" feature, fellows are able to match staffing attending physicians to different patient cases, according to attending physicians' areas of specialty. Similar to the traditional teaching clinic environment, our remote staffing strategy has ensured that fellows continue to provide excellent patient care and fulfill educational aims across our University and VA facilities. Outpatient clinics in other University of Michigan departments and other academic centers have inquired about or have begun utilizing our method. Even beyond COVID-19, our paradigm potentially provides a convenient virtual staffing platform to serve patient populations with geographic or transportation challenges. Following implementation, stakeholders can regularly evaluate the approach to continually improve both patient care and medical education.

Background: Acromegaly is associated with higher morbidity and mortality mainly due to cardiovascular disease. Data on the incidence and evolution of thyroid cancer in acromegaly are controversial. Our objective was to describe the characteristics of a group of acromegalic patients with differentiated thyroid carcinoma (DTC) and analyze their evolution.

Methods: This is a retrospective multicenter study of 24 acromegalic patients with DTC. The AJCC Staging System 8th Edition was used for TNM staging, and the initial risk of recurrence (RR), initial response and response at the end of follow-up (RFU) were defined according to the 2015 ATA Guidelines. As a control group, 92 patients with DTC without acromegaly were randomly included. Statistical analyses were done using SPSS Statistics 20.0.

Results: Median age of patients at diagnosis of acromegaly was 49.5 years (range 12-69). The median delay in diagnosis of acromegaly was 3 years (range 0.5-23). Mean baseline IGF-1 level was 2.9 ± 1.1 ULN. Median age at DTC diagnosis was 51.5 years (18-69). At the moment of diagnosis of DTC, 58.3% of the patients had active acromegaly. Median time from DTC diagnosis to acromegaly control was 1.25 years (0.5-7). Mean DTC tumor diameter of the biggest lesion was 14.6 ± 9.2 mm, being multifocal in 37.5%. All tumors were papillary carcinomas, two cases being of an aggressive variety. Lymph node dissection was performed in 8 out of 24 patients and 62.5% had metastases. Only one patient had distant metastases. Radioiodine ablation was given to 87.5% of patients. Nineteen patients (79%) were stage I, four (17%) stage II and one (4%) stage IVb. Initial RR was low in 87% (21/24), intermediate in 9% (2/24) and high in 4% (1/24) patient. RFU was: 83% (19/23) patients with no evidence of disease, 9% (2/23) with indeterminate response, 4% (1/23) with biochemical incomplete response and 4% (1/23) with structural incomplete response, at a median time of FU of 36.5 months. When comparing RFU between acromegalics and controls no statistically significant differences were found.

Conclusions: Patients with acromegaly and DTC mostly had a low initial RR. When compared with the control group, we found that DTC patients with acromegaly did not have a worse evolution.

Background: Central pontine myelinolysis (CPM) is a non-inflammatory demyelinating lesion of the pons. CPM and extrapontine demyelination (EPM) are together termed osmotic demyelination syndrome (ODS), a known and serious complication of acute correction of hyponatremia. Conversely, hyperglycemic hyperosmolarity syndrome (HHS) develops in patients with type 2 diabetes who still have some insulin secretory ability due to infection, non-compliance with treatment, drugs, and coexisting diseases, and is often accompanied by ketosis. HHS represents a life-threatening endocrine emergency (mortality rate, 10-50%) associated with marked hyperglycemia and severe dehydration. HHS may develop ODS, and some cases have been associated with hypernatremia.

Case presentation: The patient was an 87-year-old woman with hyperglycemia, dehydration, malnutrition, and potential thrombus formation during long-term bed rest. HHS was suspected to have developed due to progression of hyperglycemia and dehydration caused by pneumonia. Furthermore, ketoacidosis developed from ketosis and prerenal renal failure associated with circulating hypovolemia shock, which was also associated with disseminated intravascular coagulation. Treatment was started with continuous intravenous injection of fast-acting insulin and low-sodium replacement fluid. In addition, ceftriaxone sodium hydrate, heparin sodium, thrombomodulin α, human serum albumin, and dopamine hydrochloride were administered. Blood glucose, serum sodium, serum osmolality, and general condition (including vital, infection/inflammatory findings, and disseminated intravascular coagulation) improved promptly, but improvements in disturbance of consciousness were poor. Diffusion-weighted imaging of the brain 72 h after starting treatment showed no obvious abnormalities, but high-intensity signals in the midline of the pons became apparent 30 days later, leading to definitive diagnosis of CPM.

Conclusions: Fluctuation of osmotic pressure by treatment from hyperosmolarity due to hyperglycemia and hypernatremia in the presence of risk factors such as malnutrition, severe illness, and metabolic disorders may be a cause of CPM onset. When treating HHS with risk factors, the possibility of progression to ODS needs to be kept in mind.

Background: Nelson's syndrome is a well-described complication following bilateral adrenalectomy for management of Cushing's disease. There is no consensus on optimal management of Nelson's syndrome, characterized by the triad of pituitary corticotroph adenoma growth, elevated serum adrenocorticotropic hormone, and skin hyperpigmentation. Medical therapy with a variety of drug classes have been studied. One potentially promising drug already approved for Cushing's disease is pasireotide, a somatostatin analog with affinity for multiple somatostatin receptors, including subtype 5, the most highly expressed receptor on corticotroph tumors.

Case presentation: A 24-year-old female was diagnosed with Cushing's disease with initial ACTH levels around 700-800 pg/mL. She underwent transsphenoidal surgery without remission, followed by bilateral adrenalectomy. Over the subsequent 3 years, the patient developed skin hyperpigmentation, recurrent elevations of ACTH, and tumor recurrence requiring two additional transsphenoidal surgeries. After her third transsphenoidal resection, ACTH normalized, no residual tumor was seen on radiology, and the patient's skin hyperpigmentation improved. She then had an uncomplicated full-term pregnancy, during which ACTH levels remained within normal limits. One month after delivery, ACTH levels began rising to a peak at 5,935 pg/mL. Imaging revealed two new bilateral pituitary adenomas, measuring 14 mm on the left, and 7 mm on the right. She was then started on pasireotide. After two months of therapy, ACTH decreased to 609 pg/mL, and repeat pituitary MRI showed interval decrease in size of both pituitary adenomas to 13 mm on the left and 6 mm on the right.

Conclusion: We report the protracted course of a young female with several recurrences of Nelson's syndrome following bilateral adrenalectomy and multiple transsphenoidal surgeries, who ultimately responded to pasireotide. Unique features of her case not described previously are the response to pasireotide in a radiotherapy-naive patient, as well as the rapid radiologic response to therapy. Her history illustrates the unresolved challenges of Nelson's syndrome and the continued need for additional studies to identify optimal management.

Background: Diabetes mellitus (DM) is one of the most common chronic diseases. Individuals with DM are more likely to be hospitalised and stay longer than those without DM. Inpatient hypoglycemia and hyperglycemia, which are associated with adverse outcomes, are common, but can be prevented through hospital quality improvement programs.

Methods: We designed a multi-faceted intervention program with the aim of reducing inpatient hypoglycemia and hyperglycemia. This was implemented over seven phases between September 2013 to January 2016, and covered all the non-critical care wards in a tertiary hospital. The program represented a pragmatic approach that leveraged on existing resources and infrastructure within the hospital. We calculated glucometric outcomes in June to August 2016 and compared them with those in June to August 2013 to assess the overall effectiveness of the program. We used regression models with generalised estimating equations to adjust for potential confounders and account for correlations of repeated outcomes within patients and admissions.

Results: We observed significant reductions in patient-days affected by hypoglycemia (any glucose reading < 4 mmol/L: OR = 0.71, 95% CI: 0.61 to 0.83, p <  0.001), and hyperglycemia (any glucose reading > 14 mmol/L: OR = 0.84, 95% CI: 0.71 to 0.99, p = 0.041). Similar findings were observed for admission-level hypoglycemia and hyperglycemia. Further analyses suggested that these reductions started to occur four to 6 months post-implementation.

Conclusions: Our program was associated with sustained improvements in clinically relevant outcomes. Our described intervention could be feasibly implemented by other secondary and tertiary care hospitals by leveraging on existing infrastructure and work force.

Background: Differentiated thyroid cancer uncommonly presents with distant metastases. Adrenal metastasis from differentiated thyroid cancer presenting as the initial finding is even less common.

Case presentation: A 71-year-old male was incidentally found on chest CT to have bilateral thyroid nodules, which were confirmed on ultrasound. Fine needle aspiration of the dominant right 3.3 cm nodule contained histologic features most consistent with Bethesda classification III, and repeat fine needle aspiration revealed pathology consistent with Bethesda classification II. Follow-up thyroid ultrasound showed 1% increase and 14% increase in nodule volume at one and two years, respectively, compared to baseline. Prior to the second annual thyroid ultrasound, the patient was incidentally found to have a 4.1 cm heterogeneously enhancing mass in the right adrenal gland on CT of the abdomen and pelvis. Biochemical evaluation was unremarkable with the exception of morning cortisol of 3.2 µg/dL after dexamethasone suppression. The patient then underwent laparoscopic right adrenal gland excision, which revealed metastatic follicular thyroid carcinoma. Total thyroidectomy was then performed, with pathology showing a 4.8 cm well-differentiated follicular thyroid carcinoma of the right lobe, a 0.5 cm noninvasive follicular thyroid neoplasm with papillary-like nuclear features of the left lobe, and a 0.1 cm papillary microcarcinoma of the left lobe. Thyrotropin-stimulated whole body scan showed normal physiologic uptake of the remnant thyroid tissue without evidence of other iodine avid disease. The patient then received radioactive iodine. At follow-up 14 months after total thyroidectomy, he remains free of recurrent disease.

Conclusion: Despite following the recommended protocol for evaluation and surveillance of thyroid nodules, thyroid cancer can be challenging to diagnose, and may not be diagnosed until distant metastases are identified.

Background: The most common type of monogenic diabetes is maturity-onset diabetes of the young (MODY), a clinically and genetically heterogeneous group of endocrine disorders that affect 1-5% of all patients with diabetes mellitus. MODY is characterized by autosomal dominant inheritance but de novo mutations have been reported. Clinical features of MODY include young-onset hyperglycemia, evidence of residual pancreatic function, and lack of beta cell autoimmunity or insulin resistance. Glucose-lowering medications are the main treatment options for MODY. The growing recognition of the clinical and public health significance of MODY by clinicians, researchers, and governments may lead to improved screening and diagnostic practices. Consequently, this review article aims to discuss the epidemiology, pathogenesis, diagnosis, and treatment of MODY based on relevant literature published from 1975 to 2020.

Main body: The estimated prevalence of MODY from European cohorts is 1 per 10,000 in adults and 1 per 23,000 in children. Since little is known about the prevalence of MODY in African, Asian, South American, and Middle Eastern populations, further research in non-European cohorts is needed to help elucidate MODY's exact prevalence. Currently, 14 distinct subtypes of MODY can be diagnosed through clinical assessment and genetic analysis. Various genetic mutations and disease mechanisms contribute to the pathogenesis of MODY. Management of MODY is subtype-specific and includes diet, oral antidiabetic drugs, or insulin.

Conclusions: Incidence and prevalence estimates for MODY are derived from epidemiologic studies of young people with diabetes who live in Europe, Australia, and North America. Mechanisms involved in the pathogenesis of MODY include defective transcriptional regulation, abnormal metabolic enzymes, protein misfolding, dysfunctional ion channels, or impaired signal transduction. Clinicians should understand the epidemiology and pathogenesis of MODY because such knowledge is crucial for accurate diagnosis, individualized patient management, and screening of family members.

Background: While surgery is the first-line treatment for patients with endogenous hypercortisolism (Cushing syndrome [CS]), mifepristone has been shown to be a beneficial medical treatment option, as demonstrated in the SEISMIC (Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing Syndrome) trial. Mifepristone is a competitive glucocorticoid receptor antagonist and progesterone receptor antagonist that is associated with several treatment effects and adverse events that clinicians need to be aware of when considering its use. The objective of this review was to provide updated clinical management recommendations for patients with CS treated with mifepristone.

Methods: A panel of endocrinologists from the US with extensive experience in treating patients with CS, including with mifepristone, convened as part of a clinical advisory board to develop a consensus on the practical, real-world clinical management of patients on mifepristone.

Results: Comprehensive considerations and recommendations are provided for managing mifepristone-associated effects, including symptoms of cortisol withdrawal, hypokalemia, and change in thyroid function; effects related to its antiprogesterone activity; and rash. Additional management strategies to address concomitant medications and special clinical situations, such as surgery and use in specific populations, are also provided.

Conclusion: Safe and effective use of mifepristone requires clinical judgment and close patient monitoring to ensure optimal clinical outcomes. These consensus recommendations provide useful, practical guidance to clinicians using mifepristone.