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.     

Arterial Stiffness,Carotid Intima-Media Thickness,Endocan, and A Disintegrin and Metalloproteinase With Thrombospondin Type I Motif 9 Levels and Their Relationship With Disease Activity in Patients With Acromegaly With and Without Cardiovascular Risk Factors

ObjectiveCardiovascular complications such as cardiomyopathy and endothelial dysfunction, which are frequently seen in patients with acromegaly, are among the most important causes of morbidity and mortality. In this study, we aimed to investigate arterial stiffness, carotid intima-media thickness, endocan level, and A disintegrin and metalloproteinase with thrombospondin type I motif 9 level and their relationship with disease activity in patients with acromegaly with and without cardiovascular risk factors.MethodsA total of 60 patients with acromegaly—25 with active disease, 26 with well-controlled disease, and 9 with newly diagnosed disease—and 60 age-, sex-, and body mass index (BMI)-matched healthy control subjects were enrolled in this study. All the subjects’ height, weight, BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG) level, insulin, hemoglobin A1C (HbA1C), C-reactive protein , lipid, endocan, A disintegrin and metalloproteinase with thrombospondin type I motif 9 levels, pulse wave velocity (PWV), and carotid intima-media thickness were measured.ResultsThe SBP, DBP, FPG level, HbA1C level, and PWV of the acromegaly group were higher than those of the control group. In patients with acromegaly with cardiovascular disease (CVD) risk factors, the PWV was higher than that in the control group, and in patients with acromegaly without CVD risk factors, the PWV was similar to that in the control group. In a correlation analysis, a positive correlation was found between PWV and age, BMI, SBP, DBP, FPG level, and HbA1C level in the acromegaly group.ConclusionIn our study, we found that arterial stiffness increased in patients with acromegaly with CVD risk factors and that increased arterial stiffness was associated with hemodynamic (SBP and DBP) and metabolic (BMI, FPG level, and HbA1C level) parameters.     

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.     

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.     

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.     

Cost-Effectiveness of Empagliflozin and Metformin Combination Versus Standard Care as First-Line Therapy in Patients With Type 2 Diabetes Mellitus

ObjectiveSodium-glucose cotransporter 2 inhibitors have been shown to reduce cardiovascular events but are currently not used as the first-line therapy. This study was conducted to evaluate the cost-effectiveness of first-line empagliflozin plus metformin versus metformin monotherapy among Australians with type 2 diabetes mellitus (T2DM) and existing cardiovascular disease (CVD).MethodsA Markov model with 1-year cycles and a 5-year time horizon was constructed to simulate the occurrence of recurrent cardiovascular events among Australians aged 50 to 84 years with T2DM and CVD. Efficacy results were derived from the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose trial. Costs and utilities were drawn from published sources. The evaluation adopted both health care and societal perspectives, with the latter ascribing the Australian government’s “value of statistical life year” (A$213 000) to each year lived by a person. Future outcomes were discounted at 5% annually. Sensitivity analyses were conducted to enhance the robustness of conclusions.ResultsCompared with metformin monotherapy, first-line empagliflozin plus metformin reduced overall cardiovascular events by 0.82% and overall deaths by 7.72% over 5 years. There were 0.2 years of life saved per person and 0.16 quality-adjusted life years gained, at a net health care cost of A$4408. These equated to incremental cost-effectiveness ratios of A$22 076 per year of life saved and A$28 244 per quality-adjusted life year gained. The gains in the value of statistical life year equated to A$42 530 per person, meaning that from a societal perspective, the intervention was cost-saving.ConclusionFirst-line empagliflozin plus metformin may represent a cost-effective strategy for the management of T2DM and CVD in Australia.     

Lipoprotein(a), family history of cardiovascular disease,and incidence of heart failure

Lipoprotein(a) (Lp(a)) is a largely genetically determined biomarker for cardiovascular disease (CVD), while its potential interplay with family history (FHx) of CVD, a measure of both genetic and environmental exposures, remains unclear. We examined the associations of Lp(a) in terms of circulating concentration or polygenetic risk score (PRS), and FHx of CVD with risk of incident heart failure (HF). Included were 299,158 adults from the UK Biobank without known HF and CVD at baseline. Hazards ratios (HRs) and 95% Cls were estimated by Cox regression models adjusted for traditional risk factors defined by the Atherosclerosis Risk in Communities study HF risk score. During the 11.8-year follow-up, 5,502 incidents of HF occurred. Higher levels of circulating Lp(a), Lp(a) PRS, and positive FHx of CVD were associated with higher risks of HF. Compared with individuals who had lower circulating Lp(a) and no FHx, HRs (95% CIs) of HF were 1.36 (1.25, 1.49), 1.31 (1.19, 1.43), and 1.42 (1.22, 1.67) for those with higher Lp(a) and a positive history of CVD for all family members, parents, and siblings, respectively; similar results were observed by using Lp(a) PRS. The risk estimates for HF associated with elevated Lp(a) and positive FHx were attenuated after excluding those with incident myocardial infarction (MI) during follow-up. Lp(a) and FHx of CVD were independent risk factors for incident HF, and the highest risk of HF was observed among individuals with both risk factors. The association may be partly mediated by myocardial infarction.     

Association of Early Pregnancy Free and Total Triiodothyronine With the Subsequent Risk of Gestational Diabetes Mellitus

ObjectiveTo estimate the association of free triiodothyronine (FT3) and total triiodothyronine (TT3) in early pregnancy and subsequent gestational diabetes mellitus (GDM) risk and define appropriate TT3 thresholds for GDM screening.MethodsThis investigation is a hospital-based cohort study of pregnant women submitted to a universal thyroid function test before 24 weeks of gestation. GDM was diagnosed according to a 75-g oral glucose tolerance test. The association of maternal high FT3 and TT3 levels in early pregnancy with the risk of GDM was estimated using logistic regression. The potential nonlinear association was probed by the restricted cubic spline curve method.ResultsA total of 27 184 pregnant women and 3073 GDM cases were included in the analysis. FT3 and TT3 were associated with an increased subsequent risk of GDM in a nonlinear fashion. The adjusted odds ratios were 1.59 (95% confidence interval, 1.50-1.68) and 2.80 (95% confidence interval, 2.46-3.18) for FT3 and TT3 continuous levels, respectively. Associations were strong in euthyroid women, showed heterogeneity in women with mild thyroid dysfunction, and lacked in patients with overt hypothyroidism and hyperthyroidism. The TT3 thresholds of 1.5 and 2.0 ng/mL between 7 and 12 weeks of gestation and 1.6 and 2.1 ng/mL for 13 to 23 weeks of gestation effectively distinguished the subsequent risk of GDM.ConclusionThe increased FT3 and TT3 levels in early pregnancy were associated with a subsequent higher risk of GDM. These findings provide measures for early detection and potential prevention of GDM.     

The Prevalence of Dysglycemia-Based Chronic Disease in a European Population – a New Paradigm to Address Diabetes Burden: A Kardiovize Study

ObjectiveTo determine the prevalence rate and associated risk factors for each stage of the Dysglycemia-Based Chronic Disease (DBCD) model, which 4 distinct stages and prompts early prevention to avert Diabetes and cardiometabolic complications.MethodsSubjects between 25 and 64 years old from a random population-based sample were evaluated in Czechia from 2013 to 2014 using a cross-sectional design. DBCD stages were: stage 1 “insulin resistance” (inferred risk from abdominal obesity or a family history of diabetes); stage 2 “prediabetes”(fasting glucose between 5.6 and 6.9 mmol/L); stage 3 “type 2 diabetes (T2D)” (self-report of T2D or fasting glucose ≥7 mmol/L); and stage 4 “vascular complications” (T2D with cardiovascular disease).ResultsA total of 2147 subjects were included (57.8% women) with a median age of 48 years. The prevalence of each DBCD stage were as follows: 54.2% (stage 1); 10.3% (stage 2), 3.7% (stage 3); and 1.2% (stage 4). Stages 2 to 4 were more frequent in men and stage 1 in women (P < .001). Using binary logistic regression analysis adjusting by age/sex, all DBCD stages were strongly associated with abnormal adiposity, hypertension, dyslipidemia, and smoking status. Subjects with lower educational levels and lower income were more likely to present DBCD.ConclusionUsing the new DBCD framework and available metrics, 69.4% of the population had DBCD, identifying far more people at risk than a simple prevalence rate for T2D (9.2% in Czechia, 2013-2014). All stages were associated with traditional cardiometabolic risk factors, implicating common pathophysiologic mechanisms and a potential for early preventive care. The social determinants of health were related with all DBCD stages in alarming proportions and will need to be further studied.     

Low concentrations of medium-sized HDL particles predict incident CVD in chronic kidney disease patients

Patients with chronic kidney disease (CKD) are at high risk for CVD. However, traditional CVD risk factors cannot completely explain the increased risk. Altered HDL proteome is linked with incident CVD in CKD patients, but it is unclear whether other HDL metrics are associated with incident CVD in this population. In the current study, we analyzed samples from two independent prospective case-control cohorts of CKD patients, the Clinical Phenotyping and Resource Biobank Core (CPROBE) and the Chronic Renal Insufficiency Cohort (CRIC). We measured HDL particle sizes and concentrations (HDL-P) by calibrated ion mobility analysis and HDL cholesterol efflux capacity (CEC) by cAMP-stimulated J774 macrophages in 92 subjects from the CPROBE cohort (46 CVD and 46 controls) and in 91 subjects from the CRIC cohort (34 CVD and 57 controls). We tested associations of HDL metrics with incident CVD using logistic regression analysis. No significant associations were found for HDL-C or HDL-CEC in either cohort. Total HDL-P was only negatively associated with incident CVD in the CRIC cohort in unadjusted analysis. Among the six sized HDL subspecies, only medium-sized HDL-P was significantly and negatively associated with incident CVD in both cohorts after adjusting for clinical confounders and lipid risk factors with odds ratios (per 1-SD) of 0.45 (0.22–0.93, P = 0.032) and 0.42 (0.20–0.87, P = 0.019) for CPROBE and CRIC cohorts, respectively. Our observations indicate that medium-sized HDL-P—but not other-sized HDL-P or total HDL-P, HDL-C, or HDL-CEC—may be a prognostic cardiovascular risk marker in CKD.     

Metabolic Associated Fatty Liver Disease Increases the Risk of Systemic Complications and Mortality. A Meta-Analysis and Systematic Review of 12 620 736 Individuals

ObjectiveThe recent introduction of the term metabolic associated fatty liver disease (MAFLD) sought to reclassify nonalcoholic fatty liver disease (NAFLD). MAFLD is thought to improve the encapsulation of metabolic dysregulation. However, recent evidence has found significant differences between MAFLD and NAFLD, and prevailing knowledge has largely arisen from studies on NAFLD. Hence, we conducted a meta-analysis and systematic review of the outcomes associated with MAFLD.MethodsMEDLINE and Embase databases were searched for articles relating to outcomes in MAFLD. Analysis was conducted in random effects with hazard ratios (HRs) to account for longitudinal risk assessment of mortality and systemic complications.ResultsA total of 554 articles were identified, of which 17 articles were included. MAFLD resulted in an increase in the overall mortality (HR, 1.24; confidence interval [CI], 1.13-1.34), cancer-related mortality (HR, 1.27; CI, 1.01-1.54), and cardiovascular disease mortality (HR, 1.28, 1.03-1.53; P = .04) compared with non-MAFLD. MAFLD also increases the risk of cardiovascular events (HR, 1.49; CI, 1.34-1.64; P < .01), stroke (HR, 1.55; CI, 1.37-1.73; P < .01), and chronic kidney disease (HR, 1.53; CI, 1.38-1.68). The presence of MAFLD was also associated with an increased risk of heart failure, obstructive sleep apnea, and malignancy.ConclusionMAFLD can significantly elevate the risk of systemic diseases and mortality. The care of MAFLD thus requires interdisciplinary collaboration, and future clinical trials conducted on MAFLD should aim to reduce the incidence of end-organ damage aside from improving liver histology.     

Age-Related Factors Associated With The Risk of Hip Fracture

ObjectiveAdvancing age is a powerful risk factor for hip fractures. The biological mechanisms through which aging impacts the risk of hip fractures have not been well studied.MethodsBiological factors associated with “advancing age” that help to explain how aging is associated with the risk of hip fractures are reviewed. The findings are based on analyses of the Cardiovascular Health Study, an ongoing observational study of adults aged ≥65 years with 25 years of follow-up.ResultsThe following 5 age-related factors were found to be significantly associated with the risk of hip fractures: (1) microvascular disease of the kidneys (albuminuria and/or elevated urine-albumin-to-creatinine ratio) and brain (abnormal white matter disease on brain magnetic resonance imaging); (2) increased serum levels of carboxymethyl-lysine, an advanced glycation end product that reflects glycation and oxidative stress; (3) reduced parasympathetic tone, as derived from 24-hour Holter monitoring; (4) carotid artery atherosclerosis in the absence of clinical cardiovascular disease; and (5) increased transfatty acid levels in the blood. Each of these factors was associated with a 10% to 25% increased risk of fractures. These associations were independent of traditional risk factors for hip fractures.ConclusionSeveral factors associated with older age help to explain how “aging” may be associated with the risk of hip fractures. These same factors may also explain the high risk of mortality following hip fractures.     

Echocardiographic Findings in Patients With Normocalcemic Primary Hyperparathyroidism Compared With Findings in Hypercalcemic Primary Hyperparathyroid Patients and Control Subjects

ObjectiveThere are no data regarding echocardiographic parameters in patients with normocalcemic primary hyperparathyroidism (NCPHPT). We compared the echocardiographic findings in postmenopausal women with NCPHPT with those in patients with hypercalcemic primary hyperparathyroidism (PHPT) and controls.MethodsSeventeen consecutive Caucasian postmenopausal women with NCPHPT were compared with 20 women with hypercalcemic PHPT and 20 controls. Obesity, diabetes, kidney failure, and previous cardiovascular diseases were considered exclusion criteria. Each patient underwent biochemical evaluation, bone mineral density scan, and echocardiographic measurements. Patients with parathyroid disorders underwent kidney ultrasound evaluation.ResultsPatients with PHPT had significantly higher mean total serum calcium, ionized calcium, 24-hour urinary calcium, and parathyroid hormone and lower mean phosphorus levels compared with those in the controls (all P < .05). The only differences between patients with NCPHPT and PHPT were significantly lower mean total serum calcium, ionized calcium, and 24-hour urinary calcium and higher phosphorus levels in patients with NCPHPT (all P < .05). The only biochemical difference between patients with NCPHPT and the controls was a higher level of mean parathyroid hormone in patients with NCPHPT. There were no differences in cardiovascular risk factors between patients with NCPHPT and PHPT and the controls. Hypertension was the most frequent cardiovascular risk factor, diagnosed in 65% of patients with PHPT. This high prevalence was not statistically significant compared with that observed in patients with NCPHPT (59%) and in the controls (30%). Echocardiography parameters were not different between patients with NCPHPT and PHPT and the controls when subdivided according to the presence of hypertension (ANOVA followed by Bonferroni correction).ConclusionIn a population with a low cardiovascular risk, we found no differences in cardiovascular risk factors and echocardiographic parameters between patients with NCPHPT and PHPT and the controls.     

Posthemithyroidectomy Pregnancy Thyroid Function Surveillance: Frequency,Adherence, and Guideline Impact

ObjectivePosthemithyroidectomy women are at an increased risk for gestational subclinical hypothyroidism. Therefore, the American Thyroid Association (ATA) recommends increased thyroid function surveillance for this subgroup of pregnant women. The purpose of this study was to evaluate the frequency of thyroid function surveillance during pregnancy in posthemithyroidectomy women and to evaluate the adherence to the 2017 ATA guidelines and its possible impact since being published on thyroid function surveillance rates.MethodsA retrospective study of pregnant posthemithyroidectomy women operated at our institution between 1997 and 2020 was performed. The study cohort was subdivided by pregnancy dates before 2018 and 2018 onward to evaluate the impact of the 2017 ATA guidelines. Adherence to the guidelines was defined as at least 1 thyroid-stimulating hormone test in each trimester.ResultsAfter exclusions, a total of 120 pregnancies conceived by 66 women who underwent hemithyroidectomy surgeries were included in this study. Overall, serum thyroid-stimulating hormone examinations were performed during the first, second, and third pregnancy trimesters in 86.6%, 40%, and 16.6% of pregnancies, respectively (P <.005). The examination rate since 2018 was 88%, 40%, and 8% for the first, second, and third trimesters, respectively (P <.005).ConclusionAdherence to the latest ATA guidelines is low, and its publication in 2017 did not increase the thyroid function surveillance rate in posthemithyroidectomy women. Better patient education regarding the risks of gestational hypothyroidism following hemithyroidectomy and improved communications among treating surgeons, obstetricians, and endocrinologists may improve these rates.     

Statin Intolerance: A Review and Update

ObjectiveTo review the evidence of existing literature on the management of statin intolerance.MethodsWe searched for literature pertaining to statin intolerance and treatments in PubMed. We reviewed articles published between 2005 and 2022.ResultsStatin-associated myalgia is the most common adverse effect of statin therapy and the most common reason for statin discontinuation. The risk factors for statin intolerance include unexplained muscle pain with other lipid-lowering therapy, unexplained cramps, a history of increased creatine kinase levels, a family history of muscle symptoms, and a family history of muscle symptoms with lipid therapy. Vitamin D repletion and coenzyme Q supplementation may help alleviate the musculoskeletal effects of statins. Trials of different types of statins and different dosing regimens are recommended to improve tolerability. The use of statins in individuals who perform regular exercise requires closer attention to muscular symptoms and creatine kinase levels; however, it does not preclude the use of statins.ConclusionManagement of the adverse effects of statin therapy and improving statin tolerability are key to achieving optimum cardiovascular benefits. Identifying statin-associated adverse effects and managing them appropriately can reduce unnecessary statin discontinuation and subsequently provide longer cardiovascular protection.     

Postpartum Levothyroxine Adjustment and Its Impact Factors in Women With Hypothyroidism in Pregnancy

ObjectiveWomen with hypothyroidism need to increase exogenous thyroid hormone levels during pregnancy to reduce adverse outcomes. Few studies have reported the effect of gestational levothyroxine (LT4) variations on postpartum LT4 treatment.MethodsWomen were classified as having subclinical hypothyroidism (SCH) (n = 101), overt hypothyroidism (OH) caused by autoimmune thyroiditis (AIT-OH), OH following thyroidectomy for benign thyroid disease (BA-OH) (n = 66), and OH after surgery for papillary thyroid cancer (PTC-OH) (n = 46). Thyroid function was monitored, and LT4 therapy was adjusted accordingly.ResultsAfter delivery, all women with SCH stopped LT4 treatment, and 57.4% of them restarted LT4 treatment in the following 1 year, independently of the gestational LT4 variations. Among patients with OH, after adjusted by gestational body weight, 49.1% of them had LT4 doses less than the prepregnancy dose (baseline) in late pregnancy, leading to LT4 reduction in postpartum. The LT4 dose was reduced to approximately 50% baseline for women with AIT-OH and BA-OH and reduced by 27% for women with PTC-OH. The reduction reasons for AIT-OH and BA-OH were thyroid-stimulating hormone levels of <2.5 mU/L during pregnancy and postpartum thyrotoxicosis occurrence (39.4%), and for PTC-OH, the reason was thyroid-stimulating hormone overinhibition (<1.0 mU/L) before delivery.ConclusionFor patients with SCH, postpartum LT4 treatment could initially be suspended. For women with OH, if the LT4 dose in late pregnancy was less than baseline, a prepregnancy dose reduced by 50%, 50%, and 27% should be applied after delivery for women with AIT-OH, BA-OH, and PTC-OH, respectively.     

Management of Hypothyroidism and Hypothyroxinemia During Pregnancy

ObjectiveTo review the diagnosis and management of hypothyroidism during pregnancy, in the preconception period, and in the postpartum period.MethodsA literature review of English-language papers published between 1982 and 2022, focusing on the most recent literature.ResultsDuring pregnancy, thyroid function laboratory tests need to be interpreted with regard to gestational age. Overt hypothyroidism, regardless of the thyroid-stimulating hormone (TSH) level, should always be promptly treated when it is diagnosed before conception or during pregnancy or lactation. Most women with pre-existing treated hypothyroidism require an increase in levothyroxine (LT4) dosing to maintain euthyroidism during gestation. LT4-treated pregnant patients need close monitoring of their serum TSH levels to avoid overtreatment or undertreatment. There is no consensus about whether to initiate LT4 in women with mild forms of gestational thyroid hypofunction. However, in light of current evidence, it is reasonable to treat women with subclinical hypothyroidism with LT4, particularly if the TSH level is >10 mIU/L or thyroperoxidase antibodies are present. Women who are not treated need to be followed up to ensure that treatment is initiated promptly if thyroid failure progresses. Additional studies are needed to better understand the effects of the initiation of LT4 in early gestation in women with subclinical hypothyroidism and hypothyroxinemia and determine optimal strategies for thyroid function screening in the preconception period and during pregnancy.ConclusionThe diagnosis and management of hypothyroidism in the peripregnancy period present specific challenges. While making management decisions, it is essential to weigh the risks and benefits of treatments for not just the mother but also the fetus.     

COVID-19 Outcomes of Patients With Differentiated Thyroid Cancer: A Multicenter Los Angeles Cohort Study

ObjectiveCancer may be a risk factor for worse outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections. However, there is a significant variability across cancer types in the extent of disease burden and modalities of cancer treatment that may impact morbidity and mortality from coronavirus disease-19 (COVID-19). Therefore, we evaluated COVID-19 outcomes in patients with a differentiated thyroid cancer (DTC) history.MethodsThis is a retrospective cohort study of patients with a history of DTC and SARS-CoV2 infection from 2 academic Los Angeles healthcare systems. Demographic, thyroid cancer, and treatment data were analyzed for associations with COVID-19 outcomes.ResultsOf 21 patients with DTC and COVID-19, 8 (38.1%) were hospitalized and 2 (9.5%) died from COVID-19. Thyroid cancer initial disease burden and extent, treatment, or current response to therapy (eg, excellent vs incomplete) were not associated with COVID-19 severity in DTC patients. However, older age and the presence of a comorbidity other than DTC were significantly associated with COVID-19 hospitalization (P = .047 and P = .024, respectively). COVID-19–attributed hospitalization and mortality in DTC patients was lower than that previously reported in cancer patients, although similar to patients with nonthyroid malignancies in these centers.ConclusionThese data suggest that among patients with DTC, advanced age and comorbid conditions are significant contributors to the risk of hospitalization from SARS-CoV2 infection, rather than factors associated with thyroid cancer diagnosis, treatment, or disease burden. This multicenter report of clinical outcomes provides additional data to providers to inform DTC patients regarding their risk of COVID-19.     

Risk Factors of Thyroid Eye Disease

ObjectiveTo examine risk factors that might be associated with thyroid eye disease (TED) in patients with Graves’ disease (GD), which may guide physicians in the prevention and management of TED.MethodsMedline and Embase were searched for articles discussing risk factors of TED. Comparisons were made between GD patients with and without TED, and between active and inactive TED GD patients. Weighted mean differences (WMDs) and odds ratios (ORs) were determined for continuous and dichotomous outcomes, respectively. Results were pooled with random effects using the DerSimonian and Laird model.ResultsFifty-six articles were included in the analysis. Smoking, inclusive of current and previous smoking status, was a significant risk factor for TED (OR: 2.401; CI: 1.958-2.945; P < .001). Statistical significance was found upon meta-regression between male sex and the odds of smoking and TED (β = 1.195; SE = 0.436; P = .013). Other risk factors were also examined, and patients with TED were significantly older than those without TED (WMD: 1.350; CI: 0.328-2.372; P = .010). While both age (WMD: 5.546; CI: 3.075-8.017; P < .001) and male sex (OR: 1.819; CI: 1.178-2.808; P = .007) were found to be significant risk factors for active TED patients compared to inactive TED patients, no statistical significance was found for family history, thyroid status, cholesterol levels, or body mass index.ConclusionFactors such as smoking, sex, and age predispose GD patients to TED, and TED patients to active TED. A targeted approach in the management of GD and TED is required to reduce the modifiable risk factor of smoking.