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
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 [2]. 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 [3,4]. 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) [5]. 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 [6]. 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) [7]. 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 'Closed-loop insulin pumps' and "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Insulin-only, completely automated system (bionic pancreas)'.)
Lifestyle intervention in older adults with type 2 diabetes (September 2022)
Lifestyle modification is important for improving glycemia in type 2 diabetes mellitus, but there have been few randomized trials evaluating glycemic benefits in older adults. In a recent trial, 100 older adults (mean age approximately 72 years) were randomly assigned to an intensive lifestyle intervention (diet and exercise to achieve a 10 percent body weight loss) for six months or a control intervention (monthly educational group sessions) [8]. After one year, intensive lifestyle modification led to greater reductions in A1C (mean difference 0.9 percent) and body weight (mean difference 8.1 kg), but also caused more episodes of mild hypoglycemia than the control intervention. This trial supports our practice of providing older adults with counseling regarding lifestyle modification, provided the risk of hypoglycemia is minimized through close monitoring and empiric reductions in glucose-lowering therapy in selected individuals. (See "Treatment of type 2 diabetes mellitus in the older patient", section on 'Lifestyle modification'.)
Open-source automated insulin delivery systems in type 1 diabetes (September 2022)
The use of do-it-yourself automated insulin delivery (AID) systems is increasingly common among individuals with type 1 diabetes, but evidence regarding the effectiveness and safety of these systems has been limited. In a 24-week trial in 97 patients (48 children and 49 adults) on insulin pump therapy for type 1 diabetes, an open-source AID system conferred greater improvement in percentage of time spent in target glucose range than sensor-augmented insulin pump therapy (adjusted difference 14 percentage points) [9]. These findings support the potential utility of open-source AID algorithms for selected individuals with type 1 diabetes who are willing to invest in learning these systems. (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Do-it-yourself automated insulin delivery systems'.)
Intravitreal vascular endothelial growth factor (VEGF) inhibitors for diabetic macular edema (August 2022)
Intravitreal vascular endothelial growth factor (VEGF) inhibitors are initial therapy for most patients with diabetic macular edema and impaired visual acuity. The selection of a particular agent depends on cost of care (given the wide disparity in cost between the anti-VEGF agents) as well as treatment efficacy and specific details of the ophthalmic history and retinal examination. In a recent trial comparing aflibercept with a progressive regimen (bevacizumab first, with a switch to the more costly aflibercept if specific ophthalmic criteria for suboptimal response were met), the mean improvement in visual acuity over two years was similar in the two groups [10]. During the two-year trial, 70 percent of eyes in the bevacizumab group were switched to aflibercept. This cost-saving step-up approach may be suitable for some patients with diabetic macular edema. (See "Diabetic retinopathy: Prevention and treatment", section on 'Anti-VEGF agents'.)
Combination pharmacotherapy for painful diabetic neuropathy (August 2022)
Combination pharmacotherapy is frequently used for patients with painful diabetic neuropathy that does not respond to initial monotherapy, despite limited data to support the efficacy of this practice. In a multicenter trial of 130 patients with painful diabetic neuropathy who were given initial monotherapy with amitriptyline, pregabalin, or duloxetine, those whose pain did not improve at six weeks were given a second agent from a different pharmacologic class [11]. At 16-week follow-up, combination strategies consisting of pregabalin added to amitriptyline, amitriptyline added to pregabalin, or pregabalin added to duloxetine all provided greater benefit than monotherapy, and each strategy provided similar (approximately 50 percent) pain reduction relative to baseline pain. These results support the strategy of combination pharmacotherapy for patients with painful diabetic neuropathy that does not respond to initial monotherapy. (See "Management of diabetic neuropathy", section on 'Inadequate response to initial therapy'.)
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'.)
OBESITY
Tirzepatide for obesity treatment (June 2022)
Treatment of obesity with glucagon-like peptide-1 (GLP-1) agonists is very effective, but treatment with a dual-acting GLP-1 and gastric inhibitory polypeptide (GIP) receptor agonist may be more effective. In a randomized controlled trial including over 2500 adults with obesity (but without diabetes), the dual GIP/GLP-1 receptor agonist tirzepatide once weekly was compared with placebo [13]. At 72 weeks, reduction in body weight at all tirzepatide doses (5, 10, and 15 mg administered subcutaneously once weekly) was greater compared with placebo (-16.1, -22.2, and -23.6 kg, respectively, versus -2.4 kg). While tirzepatide is effective for obesity management in patients with and without diabetes, it does not have regulatory approval for the treatment of obesity alone. (See "Obesity in adults: Drug therapy", section on 'Dual-acting GLP-1 and GIP receptor agonists'.)
THYROID DISORDERS
Risk factors for persistent hyperthyroidism after radioiodine treatment of Graves' disease (August 2022)
Radioiodine is one of the effective treatment options for Graves' disease. Approximately 10 to 20 percent of patients have persistent hyperthyroidism six months following radioiodine treatment. Accepted risk factors for persistent hyperthyroidism include more severe hyperthyroidism and large goiter. In a meta-analysis of 4822 patients with Graves' disease, treatment failure also correlated with male sex, administration of radioiodine more than six months after diagnosis, prior use of thionamides, and 24-hour radioiodine uptake ≥60 percent, as well as thyroid volume ≥35.8 mL [14]. These findings may help guide choice of therapy for Graves’ disease. (See "Radioiodine in the treatment of hyperthyroidism", section on 'Persistent hyperthyroidism'.)
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 [15].
●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 [16].
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'.)
Vitamin D supplementation in community-dwelling individuals did not show a fracture benefit (August 2022)
In the VITAL trial, in which 25,871 community-dwelling men and women (mean age 67 years) were randomly assigned to vitamin D (2000 units daily) or placebo, the two groups had similar rates of total fractures (5.9 versus 6 percent), nonvertebral fractures (5.6 versus 5.7 percent), and hip fractures (0.44 versus 0.43 percent) [17]. The participants were not selected on the basis of vitamin D deficiency, low bone mass, or osteoporosis; approximately 10 percent of the total group had a history of a fragility fracture, and approximately 5 percent were taking osteoporosis medications. The mean 25-hydroxyvitamin D level (in a subset of participants) was 30 ng/mL (75 nmol/L). Community-dwelling adults who are getting adequate vitamin D and calcium from dietary intake as well as sun exposure do not need to take additional supplements. Vitamin D supplementation is typically suggested as part of the treatment of osteoporosis, particularly for patients who are receiving osteoporosis medications. (See "Calcium and vitamin D supplementation in osteoporosis", section on 'Calcium and/or vitamin D'.)
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 [18]. 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'.)
