UpToDate Endocrinology and Diabetes PDF

10/10/23, 8:56 PM What's new in endocrinology and diabetes mellitus - UpToDate Official reprint from UpToDate® www.uptodate.com © 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. What's new in endocrinology and diabetes mellitus AUTHORS: Kathryn A Martin, MD, Jean E Mulder, MD All...

10/10/23, 8:56 PM What's new in endocrinology and diabetes mellitus - UpToDate Official reprint from UpToDate® www.uptodate.com © 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. What's new in endocrinology and diabetes mellitus AUTHORS: Kathryn A Martin, MD, Jean E Mulder, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Sep 2023. This topic last updated: Sep 26, 2023. Please read the Disclaimer at the end of this page. 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 Influence of cortisol assay technique on diagnosis of adrenal insufficiency (May 2023) The diagnosis of adrenal insufficiency depends on the demonstration of inappropriately low cortisol production. Early morning serum cortisol levels are typically used to exclude the diagnosis of chronic adrenal insufficiency and to select patients for additional evaluation with corticotropin (ACTH) stimulation testing. With newer cortisol assays that use more specific monoclonal antibodies, the morning cortisol threshold to exclude chronic adrenal insufficiency is approximately 25 to 30 percent lower than that used with older immunoassays (eg, 13 to 14 mcg/dL instead of 18 mcg/dL [360 to 390 nmol/L instead of 500 nmol/L]) [1]. When evaluating patients for chronic adrenal insufficiency, the interpretation of the serum cortisol result depends on the type of assay that is used to measure it. (See "Diagnosis of adrenal insufficiency in adults", section on 'Suspected chronic adrenal insufficiency'.) DIABETES MELLITUS Investigational once-weekly basal insulin therapy (insulin icodec) for the treatment of type 2 diabetes (July 2023) https://www.uptodate.com/contents/whats-new-in-endocrinology-and-diabetes-mellitus/print?search=endocrinology&source=search_result&select… 1/8 10/10/23, 8:56 PM What's new in endocrinology and diabetes mellitus - UpToDate In a trial in 588 adults with type 2 diabetes (mean A1C approximately 8.6 percent) who had not previously used insulin, participants were randomly assigned to basal insulin therapy with once-weekly insulin icodec or daily insulin degludec [2]. After 26 weeks, icodec treatment led to slightly greater A1C reduction (estimated treatment difference -0.2 percentage points). The number of level 2 hypoglycemic episodes (glucose <54 mg/dL [3 mmol/L]) was numerically higher in the icodec group (53 versus 23 in the degludec group over 31 weeks). Similar findings were reported in a 78-week trial comparing weekly insulin icodec with daily insulin glargine U-100 [3]. Icodec modestly improved A1C but increased the rate of level 2 hypoglycemia. Further studies are needed to define the potential role of onceweekly basal insulin in clinical practice. (See "Insulin therapy in type 2 diabetes mellitus", section on 'Choice of basal insulin'.) Glucagon-like peptide 1 (GLP-1) receptor agonists may increase risk of aspiration during anesthesia (July 2023) Patients who take glucagon-like peptide 1 (GLP-1) receptor agonists (eg, semaglutide, liraglutide) for weight loss or diabetes may be at increased risk of aspiration during anesthesia due to delayed gastric emptying. In 2023, the American Society of Anesthesiologists suggested holding the day-of-surgery or weekly dose of GLP-1 agonists prior to elective surgery because of case reports of aspiration [4]. For patients who have not held their GLP-1 (ie, no drug on day of procedure/surgery for daily dosing, no drug in the week prior to procedure/surgery for weekly dosing), gastric ultrasound can be used to assess for gastric contents or a rapid sequence induction and intubation should be considered. (See "Rapid sequence induction and intubation (RSII) for anesthesia", section on 'Patients taking GLP-1 receptor agonists'.) Investigational triple agonist therapy (retatrutide) for the treatment of type 2 diabetes (July 2023) Retatrutide is a triple glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptor agonist in development for the treatment of type 2 diabetes. In a trial in 281 adults with type 2 diabetes (mean A1C 8.3 percent), participants were randomly assigned to once-weekly injections of retatrutide, placebo, or dulaglutide (a GLP-1 receptor agonist) [5]. After 24 weeks, retatrutide led to greater mean reduction in A1C than placebo or dulaglutide (-2.02 percentage points with 12 mg retatrutide versus -0.01 and -1.41 percentage points with placebo and dulaglutide, respectively). After 36 weeks, mean body weight loss with 12 mg retatrutide was 17.2 kg. Triple agonist therapy is a promising strategy for the treatment of type 2 diabetes. (See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Glycemic efficacy'.) Investigational small molecule oral GLP-1 receptor agonist (orforglipron) for the treatment of type 2 diabetes (July 2023) https://www.uptodate.com/contents/whats-new-in-endocrinology-and-diabetes-mellitus/print?search=endocrinology&source=search_result&select… 2/8 10/10/23, 8:56 PM What's new in endocrinology and diabetes mellitus - UpToDate Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are highly effective for the treatment of type 2 diabetes, but the inconvenience of administration limits use for some patients. Nonpeptide GLP-1 RAs are in development and can be taken orally in a nonfasting state. In a trial in 383 adults with type 2 diabetes (mean A1C 8.1 percent), participants were randomly assigned to daily oral orforglipron, placebo, or once-weekly dulaglutide (an injectable GLP-1 RA) [6]. After 26 weeks, orforglipron doses ≥12 mg daily led to greater mean reduction in A1C than placebo or dulaglutide (-1.79 to -2.1 percentage points with orforglipron versus -0.43 and -1.1 percentage points with placebo and dulaglutide, respectively). Orforglipron 45 mg daily led to mean body weight loss of 10 kg. Nonpeptide oral GLP-1 RAs may allow expanded access to GLP-1-based therapies. (See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Glycemic efficacy'.) Verapamil treatment in newly diagnosed type 1 diabetes (June 2023) The calcium channel blocker verapamil reduces the expression of thioredoxin-interacting protein, which is toxic to beta cells. It may help preserve beta cell function and endogenous insulin secretion in early type 1 diabetes. In a trial in 88 children and adolescents aged 7 to 17 years with newly diagnosed type 1 diabetes (mean time from diagnosis 24 days), participants were randomly assigned to treatment with verapamil or placebo [7]. After 52 weeks, the C-peptide area under the curve was 30 percent higher in the verapamil group (mean adjusted difference 0.14 pmol/L). Three participants developed abnormal electrocardiogram findings, including first- and second-degree heart block, and hypotension occurred in one participant. Off-label use in type 1 diabetes should be avoided until additional studies further evaluate the safety and efficacy of verapamil treatment in this population. (See "Type 1 diabetes mellitus: Prevention and disease-modifying therapy".) More fully automated insulin delivery system for type 1 diabetes (June 2023) For patients with type 1 diabetes (T1D), more fully automated insulin delivery (AID) 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 (aged 6 to 79 years, A1C 5.5 to 13.1 percent) were randomly assigned to more fully AID or standard care (any mode of insulin delivery coupled with continuous glucose monitoring), the AID system led to a greater reduction in A1C (mean adjusted difference in A1C -0.5 percent) [8]. Participants assigned to AID also had a higher percentage of time spent in the target glucose range without increased frequency of hypoglycemia. In the United States, this more automated system has regulatory approval for individuals with TID aged ≥6 years and may expand use of continuous insulin therapy [9]. (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Insulin only, fully automated system'.) https://www.uptodate.com/contents/whats-new-in-endocrinology-and-diabetes-mellitus/print?search=endocrinology&source=search_result&select… 3/8 10/10/23, 8:56 PM What's new in endocrinology and diabetes mellitus - UpToDate 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 [10]. 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)'.) FEMALE REPRODUCTION Obstetric outcomes of transgender men (May 2023) Transgender men are capable of pregnancy, but their obstetric outcomes have not been well studied. A United States database study comparing birth outcomes of nearly 2000 transgender men with 2.7 million cisgender people reported similar rates of severe morbidity and preterm birth for both groups [11]. Transgender men experienced lower rates of cesarean birth despite an overall increased prevalence of chronic medical conditions, anxiety, and depression. While study limitations included potential gender misclassification and a low frequency of severe morbidity, we discuss these reassuring findings with transgender men desiring or experiencing pregnancy. (See "Sexual and gender minority women (lesbian, gay, bisexual, transgender, plus): Medical and reproductive care", section on 'Transgender individuals'.) MENOPAUSE Fezolinetant, a neurokinin 3 receptor antagonist for hot flashes (August 2023) Hormone therapy remains the most effective treatment for hot flashes. However, a new class of nonhormonal drugs, neurokinin 3 receptor (NK3R) antagonists, appears to be a https://www.uptodate.com/contents/whats-new-in-endocrinology-and-diabetes-mellitus/print?search=endocrinology&source=search_result&select… 4/8 10/10/23, 8:56 PM What's new in endocrinology and diabetes mellitus - UpToDate reasonable alternative for those who cannot take hormone therapy. The first NK3R antagonist to be approved and available for clinical use is fezolinetant. In one trial of over 500 postmenopausal women with moderate-to-severe hot flashes, fezolinetant significantly reduced hot flash frequency and severity when compared with placebo [12,13]. After 12 weeks of therapy, the mean reductions in hot flash frequency for fezolinetant 45 mg, 30 mg, or placebo were 64, 59, and 45 percent, respectively. Women receiving fezolinetant 45 mg also had significant improvements in sleep disturbances when compared with placebo. (See "Menopausal hot flashes", section on 'Neurokinin 3 receptor antagonist'.) Nonhormonal therapies for menopausal hot flashes (August 2023) The 2023 nonhormonal therapy position statement from the North American Menopause Society (NAMS) suggests a number of treatment options for hot flashes in women who cannot take hormone therapy [14]. These include cognitive behavioral therapy, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, oxybutynin, gabapentin, and fezolinetant. Nonhormonal therapies that NAMS does not recommend for vasomotor symptoms include paced respiration, supplements/herbal remedies, cooling techniques, avoiding triggers, exercise, yoga, mindfulness-based intervention, relaxation, soy, cannabinoids, acupuncture, and clonidine. (See "Menopausal hot flashes", section on 'NAMS 2023 recommendations'.) Menopausal symptoms and adverse work outcomes (June 2023) Hot flashes and other menopausal symptoms are associated with adverse work outcomes (absences, decreased hours, layoffs, firings, and job changes specifically due to menopause symptoms). In a survey study of 4440 menopausal women with moderate symptom scores based upon the Menopause Rating Scale (MRS), 480 (11 percent) reported missing work in the preceding year (average of three days missed) [15]. Women with more severe symptoms (in the highest quartile of MRS scores) were approximately 15 times more likely to have an adverse work outcome than those in the lowest quartile. Based on workdays missed due to menopause symptoms, the authors of the survey study estimated an annual $1.8 billion direct loss to the United States' economy. (See "Clinical manifestations and diagnosis of menopause", section on 'Hot flashes'.) 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 https://www.uptodate.com/contents/whats-new-in-endocrinology-and-diabetes-mellitus/print?search=endocrinology&source=search_result&select… 5/8 10/10/23, 8:56 PM What's new in endocrinology and diabetes mellitus - UpToDate percent of patients experienced no change or a decrease in size of their microadenomas [16]. 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 if the first follow-up MRI after initial diagnosis shows no change in size. (See "Pituitary incidentalomas", section on 'Natural history'.) THYROID DISORDERS Preoperative treatment of hyperthyroidism (September 2023) In patients with untreated or poorly controlled hyperthyroidism, an acute event such as surgery can precipitate thyroid storm, a potentially life-threatening condition. Preoperative treatment with a thionamide until the free T4 and T3 are normal reduces this risk. A recent retrospective study suggests thyroid surgery in patients with uncontrolled hyperthyroidism may be performed safely [17]. However, the study used a more stringent definition for the diagnosis of thyroid storm, potentially underestimating its occurrence. We continue to suggest preoperative thionamide and beta blocker treatment for patients with hyperthyroidism. There may be some patients in whom euthyroidism cannot be achieved prior to thyroidectomy (eg, poor compliance, severe hyperthyroidism), and the risk of thyroid storm may be higher if thyroidectomy is deferred. In this setting, surgery in a thyrotoxic patient ideally should be performed at a center with experienced anesthesiologists. (See "Surgical management of hyperthyroidism", section on 'Management of hyperthyroidism'.) Treatment of symptomatic benign thyroid nodules (September 2023) In a systematic review and network meta-analysis of 16 studies (3 randomized trials and 13 comparative case series) using thermal ablation techniques (eg, radiofrequency ablation, laser ablation, microwave ablation, high-intensity focused ultrasound) or conventional surgery to treat benign thyroid nodules, thyroidectomy was associated with the largest reduction in thyroid volume compared with thermal ablation techniques but a higher risk of postoperative complications (eg, laryngeal nerve damage) and hypothyroidism [18]. There was no difference among the thermal ablation techniques in volume reduction, symptom score, or cosmetic score. There were no trials comparing thyroid lobectomy with any thermal ablation technique. Surgical complications are generally lower when the extent of resection is limited (lobectomy versus total thyroidectomy). We continue to suggest surgery (typically lobectomy) for the treatment of symptomatic benign thyroid nodules. Ultrasound-directed thermal ablation techniques are alternatives when clinical expertise is available. (See "Diagnostic approach to and treatment of thyroid nodules", section on 'Symptomatic benign nodules'.) https://www.uptodate.com/contents/whats-new-in-endocrinology-and-diabetes-mellitus/print?search=endocrinology&source=search_result&select… 6/8 10/10/23, 8:56 PM What's new in endocrinology and diabetes mellitus - UpToDate Levothyroxine dosing in young, healthy adults with primary hypothyroidism (May 2023) The initial dose of levothyroxine in young, healthy adults with primary hypothyroidism is typically the average full replacement dose, approximately 1.6 mcg/kg body weight per day. However, the range of required doses is broad, depending on the etiology of hypothyroidism and individual patient characteristics. In a retrospective study of post thyroidectomy patients, only 285 of 951 (30 percent) who received initial weight-based dosing of levothyroxine met their thyroid-stimulating hormone (TSH) goal at the first postoperative assessment [19]. A levothyroxine dose calculator based on weight, height, age, sex, and calcium supplementation was able to modestly increase the number of patients meeting their TSH goals (43 percent). Serum TSH should be reevaluated four to six weeks after initiation of levothyroxine and after any dose adjustment; most patients will need one or more dose adjustments before the optimal maintenance dose is identified. (See "Treatment of primary hypothyroidism in adults", section on 'Initial dose'.) Clinical characteristics of myxedema coma (April 2023) Myxedema coma is a rare manifestation of hypothyroidism. In a recent multicenter cohort study including 82 cases over 18 years, common clinical findings included hypothermia, hemodynamic instability, and central nervous system involvement (somnolence, coma) [20]. While thyroiditis and thyroidectomy were common causes of preexisting hypothyroidism, 54 percent of patients did not have a prior known diagnosis of hypothyroidism. Precipitating events included discontinuing thyroid hormone (28 percent), sepsis (15 percent), and amiodarone (11 percent). The mortality rate in the intensive care unit (ICU) was 26 percent. This study emphasizes the importance of early diagnosis and prompt initiation of thyroid hormone and supportive measures (eg, hemodynamic monitoring in ICU, mechanical ventilation if needed, treatment of any underlying cause). (See "Myxedema coma", section on 'Epidemiology and risk factors'.) OTHER ENDOCRINOLOGY Parathyroidectomy and kidney function in patients with primary hyperparathyroidism (April 2023) In primary hyperparathyroidism (PHPT), an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 is an indication for parathyroidectomy, but the benefit of surgery for preserving kidney function remains uncertain. In an observational study in 43,697 predominantly asymptomatic individuals with PHPT (approximately 88 percent male, mean age 66.8 years), the rate of a sustained decline (≥50 percent) in eGFR over 10 years of followup did not differ between individuals who underwent initial treatment with https://www.uptodate.com/contents/whats-new-in-endocrinology-and-diabetes-mellitus/print?search=endocrinology&source=search_result&select… 7/8 10/10/23, 8:56 PM What's new in endocrinology and diabetes mellitus - UpToDate parathyroidectomy and those who received nonsurgical management (cumulative incidence 10.8 versus 12 percent) [21]. Baseline eGFR and delayed performance of parathyroidectomy did not affect the findings. However, in individuals aged <60 years, a benefit of surgery was evident. These findings are observational and primarily confined to males and therefore do not change our suggestion for surgical intervention in patients with PHPT and low eGFR. (See "Primary hyperparathyroidism: Management", section on 'Subclinical kidney disease'.) This generalized information is a limited summary of diagnosis, treatment, and/or medication information. It is not meant to be comprehensive and should be used as a tool to help the user understand and/or assess potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a health care provider based on the health care provider's examination and assessment of a patient's specific and unique circumstances. Patients must speak with a health care provider for complete information about their health, medical questions, and treatment options, including any risks or benefits regarding use of medications. This information does not endorse any treatments or medications as safe, effective, or approved for treating a specific patient. UpToDate, Inc. and its affiliates disclaim any warranty or liability relating to this information or the use thereof. The use of this information is governed by the Terms of Use, available at https://www.wolterskluwer.com/en/know/clinical-effectiveness-terms ©2023 UpToDate, Inc. and its affiliates and/or licensors. All rights reserved. Topic 8354 Version 12239.0  https://www.uptodate.com/contents/whats-new-in-endocrinology-and-diabetes-mellitus/print?search=endocrinology&source=search_result&select… 8/8