Osilodrostat: A Review of Recent Clinical Studies and Practical Recommendations for its Use in the Treatment of Cushing Disease

ObjectiveCushing disease (CD) is characterized by chronic hypercortisolism caused by an adrenocorticotropic hormone-secreting pituitary adenoma. Surgery remains the first-line treatment option; however, medical therapy is essential if surgery is contraindicated or fails to achieve remission or when recurrence occurs after surgical remission. Osilodrostat (Isturisa), a novel steroidogenic inhibitor, is now approved for the treatment of CD in the United States and Cushing syndrome in Europe. Herein, we review pharmacology and data on the efficacy, safety, and clinical use of osilodrostat and provide guidance on its use in treating patients with CD.MethodsWe reviewed the literature and published clinical trial data of osilodrostat use in patients with Cushing syndrome. Detailed information related to the clinical assessment of osilodrostat use, potential drug-to-drug interactions, drug initiation, dose titration, and the monitoring of drug tolerability were discussed.ResultsClinical trial data demonstrated that osilodrostat, by virtue of inhibiting 11-β hydroxylase, potently and rapidly decreased the 24-hour urinary free cortisol levels and sustained these reductions, with improved glycemia, blood pressure, body weight, and quality of life as well as lessened depression. Osilodrostat may interact with certain drugs, resulting in QT prolongation, which requires careful assessment of concomitant medications and periodic monitoring using electrocardiogram, respectively. The common adverse effects include adrenal insufficiency, hypokalemia, edema, and hyperandrogenic symptoms, which can be minimized using a slower up-titration dosing regimen.ConclusionOsilodrostat is an effective, new treatment option for CD, with positive effects on cardiovascular and quality of life parameters as well as tolerable adverse effects. This article provides a review of the pharmacology of osilodrostat and offers practical recommendations on the use of osilodrostat to treat CD.     

Management of Mild-to-Moderate Hypertriglyceridemia

ObjectiveHypertriglyceridemia (HTG) is highly prevalent globally, and its prevalence is rising, with a worldwide increase in the incidence of obesity and diabetes. This review examines its current management and future therapies.MethodsFor this review, HTG is defined as mild-to-moderate elevation in the levels of triglyceride (TG): a fasting or nonfasting TG level of ≥150 mg/dL and <500 mg/dL. We reviewed scientific studies published over the last 30 years and current professional society recommendations regarding the evaluation and treatment of HTG.ResultsGenetics, lifestyle, and other environmental factors impact TG levels. In adults with mild-to-moderate HTG, clinicians should routinely assess and treat secondary treatable causes (diet, physical activity, obesity, metabolic syndrome, and reduction or cessation of medications that elevate TG levels). Because atherosclerotic cardiovascular disease risk is the primary clinical concern, statins are usually the first-line treatment. Patients with TG levels between ≥150 mg/dL and <500 mg/dL whose low-density lipoprotein cholesterol is treated adequately with statins (at “maximally tolerated“ doses, per some statements) and have either prior cardiovascular disease or diabetes mellitus along with at least 2 additional cardiovascular disease risk factors should be considered for added icosapent ethyl treatment to further reduce their cardiovascular disease risk. Fibrates, niacin, and other approved agents or agents under development are also reviewed in detail.ConclusionThe treatment paradigm for mild-to-moderate HTG is changing on the basis of data from recent clinical trials. Recent trials suggest that the addition of icosapent ethyl to background statin therapy may further reduce atherosclerotic cardiovascular disease risk in patients with moderate HTG, although a particular TG goal has not been identified.     

Cardiovascular Health Maintenance in Aging Individuals: The Implications for Transgender Men and Women on Hormone Therapy

ObjectiveTo review screening guidelines for cardiometabolic disease in aging patients and review literature describing the effect of hormone therapy (HT) on several key cardiometabolic processes to inform providers caring for older transgender individuals.MethodsA traditional literature review was performed using PubMed and Google Scholar databases.ResultsThe risk of cardiovascular disease increases with age. Exogenous sex hormones may interact with hormone-dependent metabolic pathways and affect some biochemical assays, but they do not necessarily impact clinical outcomes. While long-term HT is associated with an increased risk of some adverse cardiovascular outcomes, modern treatment regimens minimize this risk.ConclusionScreening for cardiometabolic derangements and risk reduction are important for all aging individuals. Currently, there is insufficient evidence to propose separate screening recommendations for transgender individuals on long-term HT. Aging transgender men and women should be monitored for cardiovascular disease in much the same way as their cisgender counterparts.     

Lipoprotein(a) and Atherosclerotic Cardiovascular Disease,the Impact of Available Lipid-Lowering Medications on Lipoprotein(a): An Update on New Therapies

ObjectiveTo review evidence of existing and new pharmacological therapies for lowering lipoprotein(a) (Lp[a]) concentrations and their impact on clinically relevant outcomes.MethodsWe searched for literature pertaining to Lp(a) and pharmacological treatments in PubMed. We reviewed articles published between 1963 and 2020.ResultsWe found that statins significantly increased Lp(a) concentrations. Therapies that demonstrated varying degrees of Lp(a) reduction included ezetimibe, niacin, proprotein convertase subtilisin/kexin type 9 inhibitors, lipoprotein apheresis, fibrates, aspirin, hormone replacement therapy, antisense oligonucleotide therapy, and small interfering RNA therapy. There was limited data from large observational studies and post hoc analyses showing the potential benefits of these therapies in improving cardiovascular outcomes.ConclusionThere are multiple lipid-lowering agents currently being used to treat hyperlipidemia that also have a Lp(a)-lowering effect. Two RNA therapies specifically targeted to lower Lp(a) are being investigated in phase 3 clinical trials and, thus far, have shown promising results. However, evidence is lacking to determine the clinical relevance of reducing Lp(a). At present, there is a need for large-scale, randomized, controlled trials to evaluate cardiovascular outcomes associated with lowering Lp(a).     

Oral Octreotide: A Review of Recent Clinical Trials and Practical Recommendations for Its Use in the Treatment of Patients With Acromegaly

ObjectiveAcromegaly is characterized by chronic growth hormone (GH) and insulin-like growth factor 1 (IGF-1) hypersecretion, often caused by a GH-secreting pituitary adenoma. Even though surgery remains the first line of treatment, medical therapy is essential if surgery is contraindicated, does not achieve remission, or does not prevent recurrence despite apparent surgical remission. Oral octreotide capsules (OOCs) that combine octreotide with a transient permeability enhancer technology are the first oral somatostatin receptor ligands (SRLs) approved in the United States for acromegaly.MethodsWe review the literature and clinical trial data on OOC therapy in patients with acromegaly and discuss the clinical assessment of OOC use, potential drug–drug interactions, drug initiation, dose titration, and monitoring of drug efficacy and tolerability.ResultsIn 4 pivotal clinical trials involving 238 patients with acromegaly treated with OOC, effective suppression of serum GH and IGF-1 levels, maintenance of disease control, decreased breakthrough symptoms and symptomatic improvement with non-inferiority of OOCs to injectable SRLs in maintaining biochemical response was seen. Additionally, the safety profile of OOC therapy is comparable to that of injectable SRLs. Most patients who completed the clinical trials of OOCs have also expressed preference for oral compared with injectable SRL administration.ConclusionOOCs are an effective treatment option for patients with acromegaly who previously responded to injectable SRLs, with the benefits of avoiding injection-related side effects. This article provides a review of the pharmacology, safety, and efficacy and offers practical recommendations on the use of OOCs to treat injectable SRL-responsive patients with acromegaly.     

Cardiovascular and Renal Outcomes With Sodium-Glucose Cotransporter-2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors Combination Therapy: A Meta-Analysis of Randomized Cardiovascular Outcome Trials

ObjectiveThe cardiovascular (CV) and renal benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in people with type 2 diabetes are well known. However, similar beneficial effects of SGLT2i in combination with dipeptidyl peptidase-4 inhibitors (DPP4i) are unknown. It is of interest to explore a trial-level meta-analysis to fill this knowledge gap.MethodsA literature search was conducted in the PubMed and Embase databases until January 31, 2023. All CV outcome trials (CVOTs) reporting the CV and renal outcomes of SGLT2i with or without background DPP4i therapy against the placebo were retrieved. A meta-analysis was subsequently conducted by applying the inverse variance-weighted averages of pooled logarithmic hazard ratio using primarily random-effects analysis.ResultsThis meta-analysis showed that the beneficial 3-point major adverse cardiovascular events composite (3 CVOTs; N = 32 418), the composite of CV death or heart failure hospitalization (hHF) (4 CVOTs; N = 37 687), hHF (3 CVOTs; N = 27 545), CV death (4 CVOTs; N = 34 565), and renal outcomes (2 CVOTs; N = 25 406) with SGLT2i were similar with or without background DPP4i therapy against the placebo (P_{heterogeneity} = .71, .07, .87, .72, and .25; respectively). However, against the placebo, the summary estimates for the 3-point major adverse cardiovascular events composite, hHF, and renal outcomes were stronger with SGLT2i alone, whereas the summary estimates for CV death or hHF composite were larger with SGLT2i with background DPP4i therapy.ConclusionBeneficial CV and renal effects of SGLT2i are similar against the placebo regardless of background DPP4i therapy.     

Are We Restoring Thyroid Hormone Signaling in Levothyroxine-Treated Patients With Residual Symptoms of Hypothyroidism?

IntroductionLevothyroxine (LT4) at doses that maintain the serum thyroid-stimulating hormone levels within the normal range constitutes the standard of care for the treatment of hypothyroidism. After a few months, this eliminates the signs and symptoms of overt hypothyroidism in the majority of patients, owing to the endogenous activation of thyroxine to triiodothyronine, the biologically active thyroid hormone. Still, a small percentage of the patients (10%-20%) exhibit residual symptoms, despite having normal serum thyroid-stimulating hormone levels. These symptoms include cognitive, mood, and metabolic deficits, with a significant impairment in psychological well-being and quality of life.ObjectiveTo provide a summary of progress in the approach of patients with hypothyroidism that exhibit residual symptoms despite treatment.MethodsWe reviewed the current literature and here we focused on the mechanisms leading to a deficiency of T3 in some LT4-treated patients, the role of residual thyroid tissue and the rationale for combination therapy with LT4 + liothyronine (LT3).ResultsA score of clinical trials comparing therapy with LT4 versus LT4 + LT3 concluded that both are safe and equally effective (neither is superior); however, these trials failed to recruit a sufficiently large number of patients with residual symptoms. New clinical trials that considered LT4-treated symptomatic patients revealed that such patients benefit from and prefer therapy containing LT4 + LT3; desiccated thyroid extract has also been used with similar results. A practical approach to patients with residual symptoms and on initiation of combination therapy with LT4 + LT3 is provided.ConclusionA recent joint statement of the American, British, and European Thyroid Associations recommends that a trial with combination therapy be offered to patients with hypothyroidism that do not fully benefit from therapy with LT4.     

Optimizing Diagnostic Accuracy and Treatment Decisions in Men With Testosterone Deficiency

ObjectiveThis narrative review offers a guideline-based approach for optimizing diagnostic evaluation and treatment decision making in men being evaluated for testosterone deficiency.MethodsA narrative review.ResultsTestosterone deficiency is a clinical syndrome that results from the inability of the testes to produce normal amounts of testosterone and is characterized by a constellation of symptoms and signs associated with consistently low testosterone concentrations. The diagnosis of testosterone deficiency is made by the ascertainment of symptoms and signs; the measurement of total and, if indicated, free testosterone levels in early-morning fasting samples on ≥2 days; the measurement of luteinizing hormone and follicular-stimulating hormone levels to distinguish primary from secondary hypogonadism; and an additional evaluation to ascertain the cause of testosterone deficiency. Nonspecificity of symptoms and signs, variations in testosterone levels over time, inaccuracy in the measurement of total and free testosterone levels, variations in binding protein concentrations, and suboptimal reference ranges contribute to diagnostic inaccuracy. Testosterone treatment is indicated for men with symptomatic testosterone deficiency. Testosterone treatment should be avoided in men with prostate or breast cancer, erythrocytosis, thrombophilia, increased risk of prostate cancer or severe lower urinary tract symptoms without prior urologic evaluation, a recent major adverse cardiovascular event, uncontrolled heart failure, or severe untreated sleep apnea. Testosterone replacement therapy should be accompanied by a standardized monitoring plan.ConclusionA shared decision of the patient and physician to treat should be guided by the consideration of the burden of symptoms, potential benefits and risks, patient’s values, and the cost and burden of long-term treatment and monitoring.     

Factors Associated With Insulin Pump Discontinuation in Adults With Diabetes: A Time-to-Invent Analysis and Prediction Model

ObjectiveInsulin pump discontinuation has mostly been studied in children and adolescents living with diabetes. We aimed to assess the rate of insulin pump continuation in a population of adult patients with diabetes, at 18 months after initiation; determine the factors associated with pump discontinuation; and develop a simple prediction model.MethodsThis single-center, retrospective study included all adult patients with type 1 diabetes or type 2 diabetes who started insulin pump treatment between January 2015 and June 2018. The exclusion criteria were pregnancy, short-term pregnancy plans, and insulin pump discontinuation within the previous 6 months. The probability of insulin pump continuation after 18 months was estimated using the Kaplan-Meier method. Factors associated with insulin pump discontinuation were studied using a Cox regression model, and an exponential model was built for prediction purposes.ResultsThe study included 315 patients. The mean age was 41 years, the mean duration of diabetes was 16 years, 50% were men, 74% had type 1 diabetes, and the mean hemoglobin A1c level was 9.1% (76 mmol/mol). After 18 months, the rate of insulin pump continuation was 0.80 (95% Confidence Interval (CI), 0.76-0.85). By multivariate analysis, the occurrence of severe hypoglycemia in the previous year was associated with insulin pump discontinuation (hazard ratio, 2.42; 95% CI, 1.30-4.51), while other factors did not reach statistical significance.ConclusionInsulin pump discontinuation occurred in 20% of patients at 18 months after initiation and was mainly associated with a recent history of severe hypoglycemia. The type of diabetes and glycemic control at baseline were not associated with treatment discontinuation.     

Desensitization to Methimazole

ObjectiveThionamides (methimazole and propylthiouracil) have been associated with common side effects, such as rash and pruritus, and rare but serious adverse effects, such as agranulocytosis and hepatotoxicity. Methimazole is usually the preferred thionamide for the treatment of hyperthyroidism if the patient is not planning to conceive or not in the first trimester of pregnancy, given the less frequent dosing and lower risk of hepatotoxicity. In patients who experience rash or itching when treated with methimazole, switching them to propylthiouracil is one treatment option. Here we report our experience regarding desensitization to methimazole to allow continued treatment with methimazole as an alternative management option.MethodsWe conducted a retrospective chart review of patients at a single institution who had side effects to methimazole and who were desensitized to methimazole under the supervision of an allergist. A total of 7 patients were included who experienced side effects to methimazole that did not include agranulocytosis or hepatotoxicity.ResultsAll 7 patients were able to take methimazole for treatment of their hyperthyroidism, either for continued medical therapy or as a bridge to definitive therapy, with either surgery or radioactive iodine treatment.ConclusionUnder the supervision of an allergist, desensitization to methimazole is an option for treating patients who experience side effects to methimazole (excluding agranulocytosis and hepatotoxicity).     

Risk Assessment and Coronary Artery Calcium Scoring in Transgender and Gender-Diverse Individuals Receiving Gender-Affirming Hormone Therapy

ObjectiveTo evaluate cardiovascular risk factors and prevalent coronary artery disease (CAD) using Coronary Artery Calcium (CAC) scoring in transgender and gender-diverse (TGD) individuals receiving gender-affirming hormone therapy (GAHT) and compare the CAC scores of TGD individuals with those of the general population.MethodsTGD individuals aged ≥30 years, without known risk factors for cardiovascular disease (CVD), other than tobacco use and family history of CVD, on GAHT were recruited, and baseline information, including metabolic parameters, was collected. CAC scores were obtained and compared with those of a cisgender age-matched population.ResultsOf 25 transwomen recruited, 24 underwent CAC scans. Of them, 2 (8.3%) had a CAC score of >0 to 99 and 1 (4.1%) had a CAC score of ≥100. Of 22 transmen recruited, 16 underwent CAC scans. Of them, 26 (12.5%) had a CAC score of >0 to 99 and none had a CAC score of ≥100. Framingham Risk Scores were not correlated with the presence of CAC.ConclusionThe presence of CAC in this small cohort of TGD individuals on GAHT was similar to that in the cisgender age-matched population. CAC scoring is a means to assess the prevalence of CAD in TGD individuals and identify those in whom aggressive risk reduction is indicated.     

Denosumab Use in Adults With Fibrous Dysplasia: Case Reports and Review of the Literature

ObjectiveIn fibrous dysplasia (FD) of the bone, a gain-of-function mutation in the G-nucleotide binding protein alpha subunit results in constitutively active cyclic adenosine monophosphate. Downstream effects include formation of disorganized cortex and bone marrow fibrosis. Patients with FD experience bone pain and are at risk of fracture. Bisphosphonates are traditionally used to manage pain with mixed results. We sought to report denosumab use in patients with FD at our institution and summarized the existing literature on denosumab use in FD.MethodsWe retrospectively identified patients with FD who were treated with denosumab at our institution, describing patient characteristics and outcomes. We reviewed the existing literature on denosumab use in patients with FD.ResultsPatient 1 was diagnosed with FD at the age of 17 years and took bisphosphonates with initial improvement in pain. Pain eventually worsened; therefore, she received 4 doses of denosumab. Patient 2 was diagnosed with FD after a fall and was treated with bisphosphonates, reporting some initial improvement in bone pain. A few years later, the pain recurred, and he received 3 doses of denosumab. Both patients tolerated denosumab well but experienced no improvement in pain. On literature review, although some serious side effects were noted, patients experienced a decline in bone turnover markers, and most reported improvement in bone pain with denosumab.ConclusionDenosumab is a promising therapy for managing symptoms of FD. Further studies are needed to determine the optimal dose and duration of treatment. Its long-term effect on FD lesions remains unclear.     

New Insights on Effects of Glucocorticoids in Patients With SARS-CoV-2 Infection

ObjectiveSince January 2020, the highly contagious novel coronavirus SARS-CoV-2 has caused a global pandemic. Severe COVID-19 leads to a massive release of proinflammatory mediators, leading to diffuse damage to the lung parenchyma, and the development of acute respiratory distress syndrome. Treatment with the highly potent glucocorticoid (GC) dexamethasone was found to be effective in reducing mortality in severely affected patients.MethodsTo review the effects of glucocorticoids in the context of COVID-19 we performed a literature search in the PubMed database using the terms COVID-19 and glucocorticoid treatment. We identified 1429 article publications related to COVID-19 and glucocorticoid published from 1.1.2020 to the present including 238 review articles and 36 Randomized Controlled Trials. From these studies, we retrieved 13 Randomized Controlled Trials and 86 review articles that were relevant to our review topics. We focused on the recent literature dealing with glucocorticoid metabolism in critically ill patients and investigating the effects of glucocorticoid therapy on the immune system in COVID-19 patients with severe lung injury.ResultsIn our review, we have discussed the regulation of the hypothalamic-pituitary-adrenal axis in patients with critical illness, selection of a specific GC for critical illness-related GC insufficiency, and recent studies that investigated hypothalamic-pituitary-adrenal dysfunction in patients with COVID-19. We have also addressed the specific activation of the immune system with chronic endogenous glucocorticoid excess, as seen in patients with Cushing syndrome, and, finally, we have discussed immune activation due to coronavirus infection and the possible mechanisms leading to improved outcomes in patients with COVID-19 treated with GCs.ConclusionFor clinical endocrinologists prescribing GCs for their patients, a precise understanding of both the molecular- and cellular-level mechanisms of endogenous and exogenous GCs is imperative, including timing of administration, dosage, duration of treatment, and specific formulations of GCs.     

Cardiovascular Disease in Women Update: Ischemia,Diagnostic Testing,and Menopause Hormone Therapy

ObjectiveThis update will address 3 areas specifically that are essential to improving cardiovascular outcomes for women.MethodsThe current literature has been reviewed and three important areas of cardiovascular care in women are highlighted. First is that even though women and men share many traditional risk factors for ischemic heart disease, several of these risk factors affect women disproportionately when it comes to CVD risk and events. There are also unique sex-specific risk factors for women and risk factors that are more common in women than in men. Adverse outcomes of pregnancy and hypertensive disorders of pregnancy are associated with an increased long-term risk of CVD and events. At menopause, cardiovascular risks increase, and lipids become unfavorable. Second is that diagnostic testing for ischemic heart disease presents different specificities and sensitivities between men and women and testing should be determined according to what is best and safest for women. Third is that currently, menopause hormone therapy is approved by the U.S. Food and Drug Administration for the treatment of vasomotor and genitourinary symptoms, prevention of osteoporosis, and estrogen replacement in the setting of surgical menopause, hypogonadism, or premature ovarian insufficiency. It is not recommended for the primary or secondary prevention of CVD and not recommended for women with high atherosclerotic CVD risk.ResultsCardiovascular disease (CVD) remains the most common cause of death in women in the United States despite tremendous improvements in cardiovascular care for men and women. The prevention of CVD in women with early detection and implementation of preventive therapies before atherosclerotic CVD develops is critical to improving outcomes for women.     

American Association of Clinical Endocrinology Disease State Clinical Review: The Clinical Utility of Minimally Invasive Interventional Procedures in the Management of Benign and Malignant Thyroid Lesions

ObjectiveThe objective of this disease state clinical review is to provide clinicians with a summary of the nonsurgical, minimally invasive approaches to managing thyroid nodules/malignancy, including their indications, efficacy, side effects, and outcomes.MethodsA literature search was conducted using PubMed and appropriate key words. Relevant publications on minimally invasive thyroid techniques were used to create this clinical review.ResultsMinimally invasive thyroid techniques are effective and safe when performed by experienced centers. To date, percutaneous ethanol injection therapy is recommended for recurrent benign thyroid cysts. Both ultrasound-guided laser and radiofrequency ablation can be safely used for symptomatic solid nodules, both toxic and nontoxic. Microwave ablation and high-intensity focused ultrasound are newer approaches that need further clinical evaluation. Despite limited data, encouraging results suggest that minimally invasive techniques can also be used in small-size primary and locally recurrent thyroid cancer.ConclusionSurgery and radioiodine treatment remain the conventional and established treatments for nodular goiters. However, the new image-guided minimally invasive approaches appear safe and effective alternatives when used appropriately and by trained professionals to treat symptomatic or enlarging thyroid masses.     

Thionamide-induced Agranulocytosis: A Retrospective Analysis of 36 Patients With Hyperthyroidism

ObjectiveAgranulocytosis is a rare but serious adverse drug reaction (ADR) of thionamide antithyroid drugs (ATDs). We explored the characteristics of ADRs in patients with hyperthyroidism.MethodsThis retrospective study included 3558 inpatients with Graves disease treated in a Class A Grade 3 hospital between 2015 and 2019. The clinical presentation and laboratory workup of patients with antithyroid drug (ATD)-induced agranulocytosis was analyzed.ResultsAgranulocytosis was thought to be caused by ATDs in 36 patients. The hospital length of stay was 12 (10-16) days, and hospitalization costs were approximately $2810.89 ($2156.50-$4164.67). The median duration of ATD therapy prior to agranulocytosis development was 30 (20-40) days. Fever (83.33%) and sore throat (75%) were the most common symptoms as early signs of agranulocytosis. The lowest neutrophil counts were 0.01 (0.00-0.03) × 10⁹/L and 0.14 (0.02-0.29) × 10⁹/L in the methimazole and propylthiouracil groups, respectively (P = .037). The recovery times of agranulocytosis were 9.32 ± 2.89 days and 5.60 ± 4.10 days in the methimazole and propylthiouracil groups, respectively (P = .016). Patients with severe agranulocytosis required a longer time to recover (P < .001) and had closer to normal serum thyroxine and triiodothyronine levels. The interval between the first symptom of agranulocytosis and ATD withdrawal was 1 (0-3) day.ConclusionsPatients with agranulocytosis needed a long hospital length of stay and incurred high costs. Methimazole was prone to causing a more serious agranulocytosis than propylthiouracil. High thyroid hormone was unlikely to play a role in adverse drug reactions. Patient education is important.     

Understanding Worry About Risks Associated With Thyroid Hormone Therapy: A National Survey of Endocrinologists,Family Physicians,and Geriatricians

ObjectiveThyroid hormone use is widespread, and prior studies have shown that over- and undertreatment with thyroid hormone are common. Our objective was to understand physician worry regarding risks associated with thyroid hormone therapy, specifically overtreatment or undertreatment.MethodsA nationwide survey was administered to physician members of the Endocrine Society, the American Academy of Family Practice, and the American Geriatrics Society. Participants were asked how often they were worried about various risks that may be associated with thyroid hormone over- or undertreatment, that is, cardiovascular complications, bone complications, and poor quality of life due to overtreatment or undertreatment with thyroid hormone. Multivariable regression analyses were conducted to determine physician characteristics associated with each worry.ResultsThe response rate was 63% (359 of 566); of those who responded, 128 (36%) were primary care physicians, 114 (32%) were endocrinologists, and 113 (32%) were geriatricians. Overall, 74 (21%) physicians reported that they frequently or always worried about cardiovascular complications, 74 (21%) about bone complications, 111 (31%) about the poor quality of life due to symptoms from undertreatment with thyroid hormone, and 87 (24%) about the poor quality of life due to symptoms from overtreatment with thyroid hormone. Endocrinologists were more likely to frequently or always worry about the patients' poor quality of life due to symptoms from overtreatment (odds ratio, 2.05; 95% confidence interval, 1.09-3.93) compared with primary care physicians.ConclusionUp to one third of the physicians frequently or always worried about risks resulting from the thyroid hormone overtreatment or undertreatment. More research is needed across specialties to understand physician perceptions of how thyroid hormone therapy impacts the patients' quality of life.     

The Effect of Gender-Affirming Hormone Therapy on the Risk of Subclinical Atherosclerosis in the Transgender Population: A Systematic Review

ObjectiveThe impact of gender-affirming hormone therapy (GAHT) on cardiovascular (CV) health is still not entirely established. A systematic review was conducted to summarize the evidence on the risk of subclinical atherosclerosis in transgender people receiving GAHT.MethodsA systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and data were searched in PubMed, LILACS, EMBASE, and Scopus databases for cohort, case-control, and cross-sectional studies or randomized clinical trials, including transgender people receiving GAHT. Transgender men and women before and during/after GAHT for at least 2 months, compared with cisgender men and women or hormonally untreated transgender persons. Studies reporting changes in variables related to endothelial function, arterial stiffness, autonomic function, and blood markers of inflammation/coagulation associated with CV risk were included.ResultsFrom 159 potentially eligible studies initially identified, 12 were included in the systematic review (8 cross-sectional and 4 cohort studies). Studies of trans men receiving GAHT reported increased carotid thickness, brachial-ankle pulse wave velocity, and decreased vasodilation. Studies of trans women receiving GAHT reported decreased interleukin 6, plasminogen activator inhibitor-1, and tissue plasminogen activator levels and brachial-ankle pulse wave velocity, with variations in flow-mediated dilation and arterial stiffness depending on the type of treatment and route of administration.ConclusionsThe results suggest that GAHT is associated with an increased risk of subclinical atherosclerosis in transgender men but may have either neutral or beneficial effects in transgender women. The evidence produced is not entirely conclusive, suggesting that additional studies are warranted in the context of primary prevention of CV disease in the transgender population receiving GAHT.Systematic Review RegistrationPROSPERO, identifier CRD42022323757.