What's new in endocrinology and diabetes mellitus

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

ADRENAL DISORDERS

Contrast medium washout in lipid-poor adrenal masses (November 2022)

Computed tomography (CT) with contrast medium washout is often used to distinguish benign adrenal adenomas from nonbenign lesions. However, few studies have examined the utility of contrast washout for evaluating indeterminate, lipid-poor adrenal masses. In a retrospective study of 336 masses with attenuation value >10 Hounsfield units, contrast washout ≥60 percent had a sensitivity of 77 percent and specificity of only 70 percent for benign adenoma in adrenal masses <4 cm in size [1]. Among adrenal masses at least 4 cm in size, the prevalence of malignancy was similar between those with (17 percent) and without (23 percent) contrast washout ≥60 percent. Further, three of nine pheochromocytomas exhibited contrast washout of 60 percent or greater. These findings suggest that contrast medium washout may have limited utility in lipid-poor adrenal masses for excluding malignancy and pheochromocytoma. (See "Evaluation and management of the adrenal incidentaloma", section on 'Delayed contrast-enhanced CT'.)

DIABETES MELLITUS

International consensus guidelines for the use of automated insulin delivery systems in type 1 diabetes (March 2023)

In individuals with type 1 diabetes, automated insulin delivery (AID; hybrid closed-loop) systems improve glycemia. AID therapy is now widely available, but formal guidance for implementing AID systems in clinical practice has been limited. An international panel convened by the Advanced Technologies & Treatments for Diabetes (ATTD) Congress has issued guidelines for the use of AID systems in diabetes management [2]. These guidelines provide recommendations for identifying candidates for AID therapy, providing requisite education and training for users, and selecting initial insulin delivery settings. They also emphasize the importance of creating structured and individualized treatment plans and reducing disparities in access to AID therapy. Adequate resources and infrastructure are critical for individuals with type 1 diabetes to derive benefit from AID systems. These guidelines are largely consistent with the UpToDate approach for the optimization of AID therapy in diabetes care. (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Patient selection'.)

Automated insulin delivery systems for young children with type 1 diabetes (March 2023)

Increasing evidence supports the benefits of automated insulin delivery systems groups for young children with type 1 diabetes. In a 13-week randomized trial in 102 children two to five years old that compared glycemic outcomes for a hybrid closed loop (HCL) system with standard type 1 diabetes care (continuous insulin pump or multiple daily injections with continuous glucose monitoring), patients assigned to the HCL system had substantially increased time in target range (approximately three more hours daily) with the greatest improvement at night [3]. Episodes of hyperglycemia (including one episode of diabetic ketoacidosis) were more common in the HCL group and were primarily related to infusion set failure. Severe hypoglycemia was uncommon in both groups. These findings and experience with other HCL devices in young children support our suggestion for a HCL system, if available, rather than insulin pumps for most pediatric patients with type 1 diabetes, including young children. Education of parents/primary caregivers regarding recognition and management of infusion set failures is essential to their safe use. (See "Insulin therapy for children and adolescents with type 1 diabetes mellitus", section on 'Automated insulin delivery (hybrid closed-loop insulin pumps)'.)

ADA guidelines for hypertension treatment in individuals with diabetes (January 2023)

Hypertension management is a cornerstone of cardiovascular risk reduction in patients with diabetes, but society guidelines have been discordant in their recommended treatment targets for medical therapy. In its recently published guidelines, the American Diabetes Association (ADA) recommends treatment targets for systolic and diastolic blood pressures of <130 mmHg and <80 mmHg, respectively, for most patients with diabetes [4]. These treatment targets should be implemented only if they can be achieved safely, and treatment goals should be individualized based on cardiovascular risk, patient preferences, and possible adverse effects of therapy. These ADA guidelines are now consistent with those of the American College of Cardiology/American Heart Association and support our current recommendations for medical management of hypertension in patients with diabetes. (See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Blood pressure control' and "Goal blood pressure in adults with hypertension", section on 'Patients with diabetes mellitus'.)

Immunotherapy to delay type 1 diabetes (December 2022)

Immunotherapies have been investigated extensively as a means of preserving pancreatic beta cell function and thereby delaying or preventing progression to type 1 diabetes in high-risk individuals. Teplizumab is the first disease-modifying immunotherapy for type 1 diabetes to receive regulatory approval in the United States [5]. Teplizumab, administered as a single 14-day course of daily intravenous infusions, delays the diagnosis of type 1 diabetes by a median of two years in individuals at high risk for developing the disease (ie, abnormal glucose tolerance and presence of at least two diabetes autoantibodies). Adverse effects include transient lymphopenia, rash, anemia, and fever. The clinical use of teplizumab remains uncertain and will require additional data regarding its benefits and risks, as well as the development of clearly delineated strategies for identifying optimal candidates for treatment. (See "Prevention of type 1 diabetes mellitus", section on 'Teplizumab'.)

Continuous glucose monitoring for hospitalized patients with diabetes (December 2022)

Continuous glucose monitoring (CGM) is increasingly used in hospitalized patients with diabetes, but whether it offers benefit over conventional glucose monitoring remains uncertain for the inpatient setting. In a trial in 185 hospitalized adults with type 1 and type 2 diabetes on general medicine and surgery services, time spent in target glucose range (70 to 180 mg/dL [3.9 to 10 mmol/L]) and mean daily glucose did not differ between participants randomly assigned to CGM and those who underwent conventional monitoring with fingerstick and glucose meter [6]. Among participants who experienced at least one episode of hypoglycemia, CGM led to a small reduction in hypoglycemia reoccurrence. These findings demonstrate that CGM and conventional glucose monitoring yield comparable glycemic management in the inpatient setting. CGM may be beneficial in selected hospitalized patients at high risk of hypoglycemia. (See "Management of diabetes mellitus in hospitalized patients", section on 'Blood glucose monitoring'.)

Finerenone in patients with diabetic kidney disease (November 2022)

Sodium-glucose co-transporter 2 (SGLT2) inhibitors and finerenone (a nonsteroidal mineralocorticoid receptor antagonist) prevent important adverse kidney and cardiovascular outcomes in patients with diabetic kidney disease (DKD). The 2022 guidelines from the American Diabetes Association (ADA) and the Kidney Disease: Improving Global Outcomes (KDIGO) on the treatment of patients with DKD advise the use of SGLT2 inhibitors in all patients with DKD; they also advise the use of finerenone in patients who have increased albuminuria despite treatment with an angiotensin inhibitor and an SGLT2 inhibitor [7,8]. We agree with these guidelines and now suggest use of finerenone in patients with albuminuria despite other recommended therapies, except when serum potassium is elevated (serum potassium >4.8 mEq/L or estimated glomerular filtration rate <25 mL/min/1.73 m²). (See "Treatment of diabetic kidney disease", section on 'Type 2 diabetes: Treat with additional kidney-protective therapy'.)

Choice of second diabetes medication in patients with low cardiovascular risk (October 2022)

In a recent comparative effectiveness trial evaluating the choice of a second medication for treatment of type 2 diabetes, 5047 patients (mean A1C 7.5 percent) on metformin monotherapy and with low baseline cardiovascular risk were randomly assigned to treatment with glargine, glimepiride, liraglutide, or sitagliptin. Glycemic and vascular outcomes over a mean follow-up of five years were reported, as follows:

● The proportion of participants with an A1C ≥7 percent was modestly lower with glargine (67.4 percent) or liraglutide (68.2 percent) than with glimepiride (72.4 percent) or sitagliptin (77.4 percent) [9]. The rate of severe hypoglycemia was highest with glimepiride (2.2 percent) and body weight gain of ≥10 percent lowest with liraglutide (6.1 percent).

● In this cohort with low baseline prevalence of cardiovascular or kidney disease, treatment assignment did not affect the rate of prespecified microvascular and cardiovascular secondary outcomes including peripheral neuropathy, moderately or severely increased albuminuria, reduced kidney function (estimated glomerular filtration rate <60 mL/min per 1.73 m²), major adverse cardiovascular events (MACE), hospitalization for heart failure, or all-cause mortality [10]. However, liraglutide treatment conferred benefit relative to the other three treatments for the incidence of any cardiovascular disease (composite of MACE, hospitalization for unstable angina or heart failure, or any arterial revascularization).

These findings support the selection of a glucagon-like peptide 1 (GLP-1) receptor agonist or basal insulin as second-line treatment for type 2 diabetes in patients without established cardiovascular or kidney disease, with preferential choice of a GLP-1 receptor agonist for patients who wish to avoid weight gain. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Without established cardiovascular or kidney disease'.)

Completely automated insulin delivery systems for type 1 diabetes (October 2022)

For patients with type 1 diabetes (T1D), completely automated insulin delivery systems promise enhanced glycemic management without the substantial time and training required for use of partially automated systems. In a 13-week unblinded trial in which 219 patients with T1D (ages 6 to 79 years, A1C 5.5 to 13.1 percent) were randomly assigned to a fully automated insulin delivery system or standard care (any mode of insulin delivery coupled with continuous glucose monitoring), the fully automated system led to a greater reduction in A1C (mean adjusted difference in A1C -0.5 percent) [11]. Participants assigned to fully automated insulin delivery also had a higher percentage of time spent in the target glucose range without increased frequency of hypoglycemia. Completely automated insulin delivery systems may enable expanded use of continuous insulin therapy among patients with T1D. (See "Insulin therapy for children and adolescents with type 1 diabetes mellitus", section on 'Automated insulin delivery (hybrid closed-loop insulin pumps)' and "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Insulin only, fully automated system'.)

FEMALE REPRODUCTION

Use of ovulation induction drugs does not affect colon cancer risk (September 2022)

Ovulation induction drugs are used for anovulatory infertility. While these drugs increase circulating estradiol levels, no increased risk of estrogen-sensitive cancers, such as breast and ovarian cancers, has been observed. In addition, the risk of colon cancer, which may also be impacted by hormonal factors, does not appear to affected. This was demonstrated in a population-based cohort study of nearly 150,000 women where no significant change in colon cancer risk was observed with the use of clomiphene citrate, exogenous gonadotropins, human chorionic gonadotropin, or gonadotropin-releasing hormone agonists [12]. (See "Overview of ovulation induction", section on 'Cancer risks'.)

MENOPAUSE

Geographical variability in the prevalence of menopausal hot flashes (February 2023)

There is considerable geographic variability in the prevalence of menopausal hot flashes. Among American and Japanese females, the prevalence of moderate-to-severe hot flashes is 35 and 15 percent, respectively. In a survey of menopausal females in five European countries, the overall prevalence of moderate-to-severe hot flashes was slightly higher than in the United States (40 versus 35 percent), ranging from a low of 31 percent in France to a high of 52 percent in Italy [13]. The reasons for the variation are unclear; smoking rates were similar in each country and body mass indexes were not provided. (See "Clinical manifestations and diagnosis of menopause", section on 'Hot flashes'.)

OSTEOPOROSIS

Abaloparatide for men at high risk for osteoporotic fracture (January 2022)

Abaloparatide is a synthetic analog of parathyroid hormone-related protein (PTHrP) administered as a daily subcutaneous injection, which increases spine and hip bone mineral density (BMD) and reduces the risk of vertebral and nonvertebral fractures in postmenopausal women. It recently received regulatory approval in the United States to increase bone density in men at high risk for osteoporotic fracture based on the results of a 12-month trial comparing abaloparatide with placebo in 228 men with osteoporosis, approximately 35 percent of whom had prevalent vertebral fractures [14]. Abaloparatide increased BMD at the lumbar spine and total hip more than placebo; fractures were infrequent in both groups. Anabolic agents like abaloparatide are options for osteoporosis treatment in men with severe osteoporosis or for those who have contraindications or intolerance to bisphosphonates. (See "Treatment of osteoporosis in men", section on 'Contraindications/intolerance to any bisphosphonates'.)

PITUITARY DISORDERS

MRI monitoring of nonfunctioning pituitary microincidentalomas (March 2023)

In a retrospective, longitudinal cohort of 177 patients with incidentally discovered nonfunctioning pituitary microadenomas (median size 4 mm) monitored with an average of four magnetic resonance images (MRIs) over a median follow-up period of five years, 63 percent of patients experienced no change or a decrease in size of their microadenomas [15]. However, 49 patients (28 percent) did experience an increase in size, but growth was slow, with a maximal increase of 6 mm. These findings support the approach of less frequent imaging (every three to five years) if the first follow-up MRI after initial diagnosis shows no change in size. (See "Pituitary incidentalomas", section on 'Natural history'.)

Diabetes insipidus terminology change (February 2023)

Confusion between diabetes insipidus and diabetes mellitus has led to occasional medication errors resulting in patient-safety concerns; in addition, the name "diabetes insipidus" does not reflect the underlying pathophysiology of disease. As a result, the Endocrine Society, European Society of Endocrinology, Pituitary Society, Society for Endocrinology, European Society for Paediatric Endocrinology, Endocrine Society of Australia, Brazilian Endocrine Society, and Japanese Endocrine Society all proposed to change the names of these disorders [16]. Arginine vasopressin deficiency (AVP-D) is the new name for central diabetes insipidus, and arginine vasopressin resistance (AVP-R) is the new name for nephrogenic diabetes insipidus. (See "Arginine vasopressin deficiency (central diabetes insipidus): Clinical manifestations and causes" and "Arginine vasopressin deficiency (central diabetes insipidus): Treatment" and "Arginine vasopressin resistance (nephrogenic diabetes insipidus): Clinical manifestations and causes" and "Arginine vasopressin resistance (nephrogenic diabetes insipidus): Treatment".)

THYROID DISORDERS

Treatment of anaplastic thyroid cancer (March 2023)

Anaplastic thyroid cancer is a rare and aggressive tumor with management based on case series and clinical experience. In a recent successfully completed randomized trial, 89 patients with anaplastic thyroid cancer (stage IVA to IVC) were randomly assigned to the addition of pazopanib, an oral antiangiogenic multikinase inhibitor, or placebo to chemoradiation therapy (concurrent paclitaxel and intensity-modulated radiation therapy) [17]. The median overall survival was not significantly different (5.7 and 7.3 months). We continue to use chemoradiation therapy without additional agents. Other targeted therapies remain under investigation. (See "Anaplastic thyroid cancer", section on 'Chemoradiation'.)

Assisted reproductive technology outcomes in euthyroid women with thyroid peroxidase (TPO) antibodies (March 2023)

A 2022 meta-analysis of observational studies showed higher rates of adverse assisted reproductive technology (ART) outcomes in euthyroid women with, compared to without, thyroid peroxidase (TPO) antibodies, although the findings were limited by the low quality of the evidence [18]. In a subsequent retrospective study of 449 TPO antibody-positive and 2945 antibody-negative Chinese women undergoing in vitro fertilization or intracytoplasmic sperm injection, there was no difference in oocyte retrieval, fertilization, embryo utilization, blastocyst formation, pregnancy rate, or live birth rate between the two groups [19]. Although the new study was larger than most previous studies and attempted to control for numerous potential confounding factors, it was retrospective in design and has similar limitations as previous observational studies. The association between thyroid autoimmunity and adverse ART outcomes remains uncertain. (See "Overview of thyroid disease and pregnancy", section on 'Pregnancy outcomes'.)

VITAMIN D

Vitamin D trials do not show benefit for COVID-19 outcomes (October 2022)

There is growing interest in the role of vitamin D as a facilitator of the innate immune response during SARS-CoV-2 infection. However, two recent trials evaluating the effect of vitamin D supplementation on COVID-19 outcomes did not show a benefit:

●In a trial from the United Kingdom, in which 6200 adults were randomly assigned to testing of serum 25-hydroxyvitamin D followed by daily low (800 units) or high (3200 units) dose vitamin D supplementation when the concentration was <30 ng/mL (<75 nmol/L) versus no testing/supplementation, there was no difference in the incidence or severity of COVID-19 during six months of follow-up [20].

●In a trial from Norway, in which 34,601 adults were randomly assigned to 5 mL of cod liver oil (400 units vitamin D) or placebo daily for six months, there was no difference in the incidence or severity of COVID-19 during six months of follow-up [21].

In patients with COVID-19, vitamin D supplementation may be necessary to meet the recommended intake or to treat deficiency; however, doses exceeding the upper level intake with the intention of improving COVID outcomes are not advised. (See "Vitamin D and extraskeletal health", section on 'COVID-19'.)

OTHER ENDOCRINOLOGY

Autosomal dominant hypocalcemia type 1 (November 2022)

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism caused by an activating mutation of the CaSR gene. A recent systematic review analyzed reports from 1994 to 2021 to characterize the clinical findings [22]. Among 191 patients with clinical data, 27 percent were asymptomatic at presentation, whereas 32 percent had moderate and 41 percent had severe symptoms (predominantly seizures). Among the 91 patients with biochemical data, mean calcium levels correlated with symptom severity (6.8, 7.4, and 7.6 mg/dL in those with severe, moderate, and no symptoms, respectively). The usual biochemical tests do not reliably discriminate ADH1 from other forms of hypoparathyroidism. The major clinical clue to this syndrome is its familial nature and the tendency of patients to develop renal complications (eg, nephrocalcinosis, nephrolithiasis, kidney impairment) during treatment with calcium and vitamin D supplementation. The diagnosis can be confirmed by analysis for mutations in the CaSR gene. (See "Disorders of the calcium-sensing receptor: Familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia", section on 'Clinical manifestations'.)