Version August 2025
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
Pheochromocytoma and paraganglioma in von Hippel-Lindau syndrome (March 2025)
Pheochromocytomas and paragangliomas (PPGLs) are rare, catecholamine-secreting tumors that can be associated with genetic disorders including von Hippel-Lindau (VHL) syndrome. In a study that compared the clinical and biochemical features of PPGLs in 59 patients with VHL (mean age 25 years) and 145 patients with sporadic disease (mean age 44 years), the prevalence of hypertension and tumor-related symptoms was high (≥75 percent) in both groups [1]. Patients with VHL exhibited higher rates of postoperative recurrence (45 versus 15 percent with sporadic disease), multiple lesions, and predominant norepinephrine secretion. These findings indicate that the natural history of sporadic and VHL-associated PPGLs may differ, and patients with VHL merit close monitoring even after apparent surgical cure of PPGL. (See "Pheochromocytoma and paraganglioma in genetic disorders", section on 'Phenotype of MEN2 versus VHL syndrome' and "Treatment of pheochromocytoma in adults", section on 'Prognosis and monitoring'.)
DIABETES MELLITUS
Automated insulin delivery in adults with type 2 diabetes (March 2025)
Automated insulin delivery (AID) systems are often used to treat type 1 diabetes, but few studies have evaluated their use in type 2 diabetes. In a 13-week trial, 319 adults with type 2 diabetes (mean age 58 years, mean A1C 8.2 percent) were randomly assigned to treatment with AID (n = 215) or their usual insulin delivery strategy (predominantly multiple daily injections [MDI]; n = 104) [2]. AID use led to a greater reduction in mean A1C (-0.9 versus -0.3 percentage points with usual care) and a greater increase in time spent in the target glucose range (70 to 180 mg/dL [3.9 to 10 mmol/L]). The rate of hypoglycemia was low in both groups. These findings support the utility of AID in adults with type 2 diabetes who are not meeting glycemic goals with MDI insulin regimens. (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Patient selection'.)
Oral antihyperglycemics are less effective than insulin in pregnancy (February 2025)
Insulin is the preferred antihyperglycemic medication for pharmacotherapy of gestational diabetes mellitus (GDM) because of its well-established safety and efficacy. In a recent randomized trial comparing a sequential strategy of beginning metformin therapy and adding glyburide if glucose targets were not met versus a strategy of insulin alone, the oral antihyperglycemic strategy resulted in higher rates of large-for-gestational-age infants and maternal hypoglycemia [3]. We continue to recommend insulin therapy for management of persistent hyperglycemia in pregnancy. (See "Gestational diabetes mellitus: Glucose management, maternal prognosis, and follow-up", section on 'Choice of pharmacotherapy'.)
Diabetic neuroarthropathy risk factors (January 2025)
Risk factors for diabetic neuroarthropathy (ie, Charcot foot) include repeated trauma, foot ulceration, and infection or surgery of the affected foot. A retrospective study of 3400 patients with diabetic neuroarthropathy (and 27,000 patients with diabetes alone) identified additional risk factors for diabetic neuroarthropathy, including atherosclerosis, macroalbuminuria, microalbuminuria, and retinopathy, both in patients with type 1 and type 2 diabetes [4]. These data suggest that patients with atherosclerosis and/or microvascular complications of diabetes mellitus may benefit from screening for diabetic neuroarthropathy. (See "Diabetic neuroarthropathy", section on 'Epidemiology and risk factors'.)
Intensive blood pressure lowering in patients with type 2 diabetes mellitus (January 2025)
We suggest intensive blood pressure (BP) lowering (eg, systolic blood pressure [SBP] <125 mmHg using standardized methods) for patients with type 2 diabetes based on goal BP trials that included diabetic patients and indirect data from the SPRINT trial, although one trial found no significant benefit to this approach. In a randomized trial in over 12,800 patients with type 2 diabetes, hypertension, and other cardiovascular risk factors, patients assigned to a target SBP of <120 mmHg had a lower incidence of a cardiovascular composite of nonfatal stroke, nonfatal myocardial infarction, heart failure, and cardiovascular death at a median of 4.2 years, compared with patients assigned to a target SBP of <140 mmHg [5]. The algorithm for follow-up and antihypertensive therapy was similar to that used in the SPRINT trial. These data, combined with previous studies, support a strong recommendation for intensive BP lowering in patients with diabetes mellitus. (See "Goal blood pressure in adults with hypertension", section on 'Patients with diabetes mellitus'.)
Diabetic ketoacidosis in pregnancy and severe maternal morbidity (December 2024)
Diabetic ketoacidosis (DKA) is a serious complication of pregnancy. Among nearly 400,000 pregnancies affected by pre-existing diabetes mellitus in a nationally representative United States database (2010-2020), the prevalence of DKA antepartum and at delivery hospitalization was approximately 3 and 1 percent, respectively [6]. Patients who had DKA during the delivery hospitalization had a much higher risk of nontransfusion severe maternal morbidity compared with patients with diabetes without DKA (21 versus 2 percent). Our approach to managing DKA in pregnancy is shown in the algorithm (algorithm 1). (See "Diabetic ketoacidosis in pregnancy", section on 'Epidemiology' and "Diabetic ketoacidosis in pregnancy", section on 'Outcome'.)
OBESITY
Intermittent fasting for weight loss (April 2025)
Traditional daily calorie restriction is effective in the treatment of obesity, but long-term adherence can be challenging; intermittent fasting has gained attention as a possible alternative strategy. In a randomized trial of 165 patients with overweight or obesity, intermittent fasting (4:3 fasting; with 80 percent calorie restriction on 3 nonconsecutive days per week and ad-libitum intake on non-fasting days) achieved slightly greater weight loss after 12 months compared with traditional daily caloric restriction [7]. Caloric restriction was greater over the 12-month period with intermittent fasting, suggesting the benefit was due to reduced calorie consumption. We personalize dietary counseling and promote interventions that are most likely to be sustainable for individual patients. (See "Obesity in adults: Dietary therapy", section on 'Intermittent fasting'.)
New classifications for patients with obesity (February 2025)
Body mass index (BMI) is increasingly recognized as an inadequate tool to fully capture an individual’s obesity-related health status. A global commission of obesity experts has proposed new strategies to better identify those with increased adiposity and further classify patients based on obesity-related health consequences [8]. One important change is the proposal of new diagnostic categories for "preclinical" and "clinical" obesity. Those with clinical obesity have objectively altered organ function or symptoms related to obesity, whereas those with preclinical obesity have no identifiable health effects from extra weight. These new classifications may help identify those who would benefit most from intensive treatment. We continue to individualize obesity interventions based on overall health status and risk factors for obesity-related morbidity. (See "Obesity in adults: Prevalence, screening, and evaluation", section on 'Preclinical versus clinical obesity'.)
OSTEOPOROSIS
Accelerated bone loss in older men with type 2 diabetes (February 2025)
In people with type 2 diabetes, fracture risk is elevated despite normal or increased bone mineral density (BMD). In an analysis of 4095 older men (mean age approximately 73 years) in whom BMD at the total hip was measured at baseline and after a mean of 4.6 years, those with type 2 diabetes (n = 578) exhibited a greater decline in BMD than those with normoglycemia (n = 1993; mean decrease -2.23 versus -1.57 percent, respectively) [9]. Accelerated bone loss was evident despite higher mean baseline BMD at the hip among men with diabetes. These findings suggest that accelerated bone loss may contribute to fracture risk in people with type 2 diabetes. (See "Bone disease in diabetes mellitus", section on 'Bone quantity and quality'.)
Extended-interval dosing for zoledronic acid in postmenopausal women with low bone mass (February 2025)
In postmenopausal women with low bone mass, zoledronic acid administered every one to two years increases bone mineral density. The clinical efficacy of a longer dosing interval was evaluated in a 10-year trial of zoledronic acid (5 mg IV once at baseline only or once at baseline and again at five years) versus placebo in 1054 early postmenopausal women (mean age 56 years) with T-scores >-2.5 and <0.0 [10]. Participants who received one or two doses of zoledronic acid had a lower incidence of morphometric vertebral fracture compared with those who received placebo. Both zoledronic acid regimens also reduced risk of major osteoporotic fracture. Extended dosing intervals for zoledronic acid may help reduce treatment burden for postmenopausal women who opt for pharmacotherapy to prevent osteoporosis. (See "Overview of the management of low bone mass and osteoporosis in postmenopausal women", section on 'Options for pharmacotherapy'.)
Sequential therapy with zoledronic acid after denosumab discontinuation (January 2025)
If denosumab treatment is discontinued, bone mineral density (BMD) is rapidly lost, and there is an increased risk of vertebral fractures. Bisphosphonate therapy can attenuate this bone loss, but optimal use of zoledronic acid in this setting remains uncertain. In a trial comparing a single dose of zoledronic acid (administered six months after the last denosumab injection) versus continuation of denosumab in 101 older adults who had received denosumab for ≥2 years, lumbar spine BMD decreased in the zoledronic acid group (n = 76) compared with the denosumab group (n = 25) after one year (median change -0.68 versus +1.3 percent, respectively) [11]. Greater BMD loss was evident in participants with ≥3 years of prior denosumab treatment. Prior to denosumab initiation, there must be a clear treatment plan to address duration of denosumab therapy and mitigation of bone loss and fracture risk if denosumab is discontinued or delayed. (See "Denosumab for osteoporosis", section on 'Bisphosphonates (preferred)'.)
THYROID DISORDERS
Age-related increase in upper reference limit for TSH (January 2025)
Although a growing number of studies have reported an age-related increase in the upper reference limit for thyroid stimulating hormone (TSH), few laboratories provide age-specific reference ranges for adults. In a recent multicenter, retrospective study (7.6 million TSH samples), the upper reference limit for TSH increased starting at age 50 years in females and 60 years in males [12]. The upper reference limit for an individual 70 to 80 years old ranged from 5.0 to 6.2 mU/L, depending on assay, with the reported upper limit ranging from 4.1 to 4.8 mU/L. If age-adjusted normal ranges for TSH were employed, there would be a decrease in the diagnosis of subclinical hypothyroidism in adults >50 to 60 years of age; we favor using age-based normal ranges for TSH. (See "Laboratory assessment of thyroid function", section on 'Serum TSH'.)
OTHER ENDOCRINOLOGY
Estimation of free calcium using albumin-adjusted calcium formulas (March 2025)
Albumin-adjusted calcium formulas are often used to estimate free calcium when albumin is abnormal, but none appears to be universally acceptable when compared with ionized calcium. In a new cross-sectional study that included 17,500 patients who had simultaneous testing of albumin, total calcium, and ionized calcium, very few (≤0.3 percent) patients with an albumin <3 g/dL and hypercalcemia by ionized calcium were misclassified as normocalcemic by a commonly used calcium correction formula [13]. However, the formula misclassified 44 percent with hypocalcemia by ionized calcium as normocalcemic, and 6.8 percent with normocalcemia by ionized calcium were misclassified as hypercalcemic. If reliable measurement of ionized calcium is not available, the total calcium may be corrected for any abnormalities in albumin, but the accuracy of the estimate may be poor in a variety of populations. (See "Diagnostic approach to hypercalcemia", section on 'Verify elevated calcium' and "Relation between total and ionized serum calcium concentrations".)
Prostate-specific antigen values in transgender women receiving estrogen (November 2024)
Gender-affirming hormone therapy for transgender women reduces prostate-specific antigen (PSA) levels; however, the magnitude of this effect is unknown. In a retrospective study of 210 transgender women receiving estrogen, the median PSA was 0.02 ng/mL [14]. Thirty-six percent of patients had undetectable PSA values. By comparison, the median PSA in similar-age cisgender male patients without known prostate cancer has historically been reported as 1.0 ng/mL. These findings suggest PSA may be falsely low in transgender women receiving estrogen. The role of PSA for prostate cancer screening in this population is an area requiring further study. (See "Measurement of prostate-specific antigen", section on 'Medications'.)
