The Acyl-Proteome of Syntrophus aciditrophicus Reveals Metabolic Relationships in Benzoate Degradation

Syntrophus aciditrophicus is a model syntrophic bacterium that degrades fatty and aromatic acids into acetate, CO₂, formate, and H₂ that are utilized by methanogens and other hydrogen-consuming microbes. S. aciditrophicus benzoate degradation proceeds by a multistep pathway with many intermediate reactive acyl-coenzyme A species (RACS) that can potentially N^ε-acylate lysine residues. Herein, we describe the identification and characterization of acyl-lysine modifications that correspond to RACS in the benzoate degradation pathway. The amounts of modified peptides are sufficient to analyze the post-translational modifications without antibody enrichment, enabling a range of acylations located, presumably, on the most extensively acylated proteins throughout the proteome to be studied. Seven types of acyl modifications were identified, six of which correspond directly to RACS that are intermediates in the benzoate degradation pathway including 3-hydroxypimeloylation, a modification first identified in this system. Indeed, benzoate-degrading enzymes are heavily represented among the acylated proteins. A total of 125 sites were identified in 60 proteins. Functional deacylase enzymes are present in the proteome, indicating a potential regulatory system/mechanism by which S. aciditrophicus modulates acylation. Uniquely, N^ε-acyl-lysine RACS are highly abundant in these syntrophic bacteria, raising the compelling possibility that post-translational modifications modulate benzoate degradation in this and potentially other, syntrophic bacteria. Our results outline candidates for further study of how acylations impact syntrophic consortia.     

Endocrine Follow-up During Post-Acute COVID-19: Practical Recommendations Based on Available Clinical Evidence

ObjectiveCOVID-19 affects multiple endocrine organ systems during the disease course. However, follow-up data post-COVID-19 is scarce; hitherto available limited data suggest that most of the biochemical endocrine dysfunctions observed during acute phase of COVID-19 tend to improve after recovery. Hence, we aim to provide a rational approach toward endocrine follow-up of patients during post-acute COVID-19.MethodsWe performed a literature review across PubMed/MEDLINE database looking into the effects of COVID-19 on endocrine system and subsequent long-term endocrine sequelae. Accordingly, we have presented a practical set of recommendations regarding endocrine follow-up post-acute COVID-19.ResultsCOVID-19 can lead to new-onset hyperglycemia/diabetes mellitus or worsening of dysglycemia in patients with preexisting diabetes mellitus. Hence, those with preexisting diabetes mellitus should ensure optimum glycemic control in the post-COVID-19 period. New-onset diabetes mellitus has been described post-acute COVID-19; hence, a selected group of patients (aged <70 years and those requiring intensive care unit admission) may be screened for the same at 3 months. Thyroid dysfunction (euthyroid sick syndrome and atypical thyroiditis) and adrenal insufficiency have been described in COVID-19; however, thyroid/adrenal functions usually normalize on follow-up; hence, widespread screening post-acute COVID-19 should not be recommended. Pituitary apoplexy and male hypogonadism have rarely been documented in COVID-19; therefore, appropriate follow-up may be undertaken as per clinical context. Hypocalcemia during COVID-19 is not uncommon; however, routine estimation of serum calcium post-COVID-19 is not warranted.ConclusionThe recommendations herein provide a rational approach that would be expected to guide physicians to better delineate and manage the endocrine sequelae during post-acute COVID-19.     

Hereditary Endocrine Tumors and Associated Syndromes: A Narrative Review for Endocrinologists and Endocrine Surgeons

ObjectiveHereditary endocrine tumors (HET) were among the first group of tumors where predisposition syndromes were recognized. The utility of genetic awareness is having the capacity to treat at an earlier stage, screen for other manifestations and initiate family cascade testing. The aim of this narrative review is to describe the most common hereditary syndromes associated with frequently encountered endocrine tumors, with an emphasis on screening and surveillance.MethodsA MEDLINE search of articles for relevance to endocrine tumors and hereditary syndromes was performed.ResultsThe most common hereditary syndromes associated with frequently encountered endocrine tumors are described in terms of prevalence, genotype, phenotype, penetrance of malignancy, surgical management, screening, and surveillance.ConclusionMedical practitioners involved in the care of patients with endocrine tumors should have an index of suspicion for an underlying hereditary syndrome. Interdisciplinary care is integral to successful, long-term management of such patients and affected family members.     

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.     

The Prevalence of Euthyroid Hypertriiodothyroninemia in Newly Diagnosed Multiple Myeloma and its Clinical Characteristics

ObjectiveTo evaluate the prevalence of euthyroid hypertriiodothyroninemia and/or hyperthyroxinemia and its clinical characteristics in multiple myeloma (MM) patients.MethodsPreviously untreated, newly diagnosed patients with MM were enrolled at the Beijing Chao-yang Hospital between January 2016 and December 2019. Thyroid function and clinical characteristics were analyzed.ResultsA total of 105 patients were enrolled in this study. Thirteen (12.38%) patients exhibited euthyroid hypertriiodothyroninemia with strikingly elevated total triiodothyronine (TT3) levels (>8 ng/mL). Among these 13 patients, 12 patients were immunoglobulin (Ig) G type (92.31%), and 1 patient was light-chain κ type (7.69%). Compared with other patients with MM, patients with hypertriiodothyroninemia were more likely to be IgG type and had higher serum globulin and lower albumin levels and more advanced International Staging System stage (all P < .05). Among the 13 euthyroid hypertriiodothyroninemia patients, 8 patients have been followed up and checked for thyroid function. The TT3 levels in all 8 patients were normalized to the reference range after antimyeloma chemotherapy.ConclusionAbout 12% of patients with MM had euthyroid hypertriiodothyroninemia. Their strikingly elevated TT3 was normalized after chemotherapy. Clinicians should be aware of the possibility of high TT3 levels in euthyroid patients with MM and the potential risk of MM in patients with strikingly elevated TT3.     

Long-Term Prognosis of Acute Myocardial Infarction Associated With Metabolic Health and Obesity Status

ObjectiveEmerging evidence supports the favorable cardiovascular health in nonobese subjects with healthy metabolism. However, little is known regarding the prognosis across the range of metabolic phenotypes once cardiovascular disease is established. We examined the prognosis of patients with acute myocardial infarction (AMI) stratified according to metabolic health and obesity status.MethodsThis is a retrospective study on consecutive patients with AMI admitted to a tertiary hospital between 2014 and 2021. Patients were allocated into the following 4 groups based on metabolic and obesity profile: (1) metabolically healthy obese (MHO), (2) metabolically healthy nonobese (MHNO), (3) metabolically unhealthy obese (MUO), and (4) metabolically unhealthy nonobese (MUNO). Metabolic health was defined in accordance to the Biobank Standardisation and Harmonisation for Research Excellence in the European Union Healthy Obese Project. The primary outcome was all-cause mortality. The Cox regression analysis examined the independent association between mortality and metabolic phenotypes, adjusting for age, sex, AMI type, chronic kidney disease, smoking status, and left ventricular ejection fraction.ResultsOf 9958 patients, the majority (68.5%) were MUNO, followed by MUO (25.1%), MHNO (5.6%), and MHO (0.8%). MHO had the lowest mortality (7.4%), followed by MHNO (9.7%), MUO (19.2%), and MUNO (22.6%) (P < .001). Compared with MHNO, MUO (hazard ratio [HR], 1.737; 95% confidence interval [CI], 1.282-2.355; P < .001) and MUNO (HR, 1.482; 95% CI, 1.108-1.981; P = .008) had a significantly higher mortality risk but not MHO (HR, 1.390; 95% CI, 0.594-3.251; P = .447), after adjusting for confounders. The Kaplan-Meier curves showed favorable survival in the metabolically healthy and obesity groups, with the highest overall survival in the MHO, followed by MHNO, MUO, and MUNO (P < .001).ConclusionMetabolically healthy and obese patients with AMI have favorable prognosis compared with metabolically unhealthy and nonobese patients. It is equally important to prioritize intensive metabolic risk factor management to weight reduction in the early phase after AMI.     

The Iodine Status and Prevalence of Thyroid Disorders Among Women of Childbearing Age in China: National Cross-sectional Study

ObjectiveMandatory universal salt iodization in China was implemented 20 years ago. However, the current iodine status and prevalence of thyroid disorders among childbearing-age women are unknown.MethodsA nationally representative cross-sectional study with 26 166 enrolled participants aged 18 to 49 years from all 31 provincial regions of mainland China was performed. The participants were given a questionnaire and underwent B-mode ultrasonography of the thyroid. The serum concentrations of thyroid hormones and thyroid antibodies and the urinary iodine concentration (UIC) were measured.ResultsThe median UIC was 178.7 μg/L, indicative of adequate iodine status. pHowever, 19.04% and 19.87% of the participants were classified as having iodine deficiency and excessive iodine, respectively. The weighted prevalence of thyroid disorders was as follows: 1.08% had overt hyperthyroidism, 0.58% had subclinical hyperthyroidism, 0.76% had Graves disease, 1.28% had overt hypothyroidism, 14.28% had subclinical hypothyroidism, 13.53% were positive for thyroid peroxidase antibodies, and 14.55% were positive for thyroglobulin antibodies. Excessive iodine and overweight were associated with higher odds of subclinical hypothyroidism. A family history of thyroid disorders and an age between 40 and 49 years were significantly associated with higher odds of positivity for thyroid peroxidase antibodies and thyroglobulin antibodies.ConclusionIodine deficiency, excessive iodine, subclinical hypothyroidism, and positivity for thyroid autoantibodies remain prevalent among women of childbearing age in China. Women of childbearing age who are relatively older, are overweight, or have a family history of thyroid disorders are encouraged to undergo active screening of their UIC and thyroid function when planning a pregnancy.     

The Prevalence of Probable Familial Chylomicronemia Syndrome in a Southern California Population

ObjectiveTo estimate the prevalence of probable familial chylomicronemia syndrome (FCS) in a major Southern California Academic Center as well as to provide a systematic review of past FCS studies and management recommendations.MethodsElectronic medical records were queried based on single fasting plasma triglyceride (TG) levels of ≥880 mg/dL and at least 1 episode of acute pancreatitis. After the exclusion of secondary causes (diabetes, alcohol misuse, gallbladder disease, chronic kidney disease, uncontrolled hypothyroidism, estrogen, and drug use) and responses to lipid-lowering treatment, probable patients with FCS were identified. A systematic review of all published literature on the prevalence and management guidelines for FCS was then presented and discussed.ResultsOut of 7 699 288 charts queried, 138 patients with TG levels of ≥880 mg/dL and documented evidence of at least 1 episode of acute pancreatitis were identified. Nine patients did not have any documented secondary causes of chylomicronemia. Four of the 9 patients had >20% decrease in TG levels after lipid-lowering treatment, 2 patients were not responsive to lipid-lowering medication, and data on lipid-lowering medications were missing in 3 patients.ConclusionOur study estimates the prevalence of probable FCS at a range of 0.26 to 0.66 per million. Using the recommended criteria, probable FCS cases can be identified to allow early diagnosis and management.     

Efficacy of Control-IQ Technology in a General Endocrine Clinic

ObjectiveRecent advances in technology have allowed for the expanded use of hybrid closed-loop insulin pump therapy and automated insulin delivery systems for the management of diabetes mellitus. We assessed the outcomes of introducing Tandem t:slim X2 with the Control-IQ technology in a general endocrine clinic.MethodsData from 66 adults with type 1 (n = 61) and type 2 (n = 5) diabetes mellitus were aggregated for analysis. Patients were either transitioned from traditional insulin pump therapy or multiple daily injection therapy to Tandem t:slim X2 with the Control-IQ technology from January 2020 to June 2021. The assessed clinical end points included changes in time below range, time above range, and time in target range. Changes in hemoglobin A1C before and after Control-IQ technology implementation were noted. The primary outcome was a change in time in target range with the Control-IQ technology.ResultsThere was a significant increase in time in target range when comparing pre- and post–Control-IQ technology (49.5% vs 63.3%, P < .0003) values. There was a reduction in time above range (46.8% vs 34.9%, P < .0013), a decrease in time below range (4.0% vs 1.7%, P = .017), and a decrease in hemoglobin A1C after transitioning to the Control-IQ technology (7.7% [61 mmol/mol] vs 7.1% [54 mmol/mol], P < .017). The patient dropout rate was low (7%).ConclusionThe Control-IQ technology system was effective in reducing hyperglycemia while increasing time in target range and decreasing hypoglycemia. This technology is a useful and effective addition to the growing number of automated insulin delivery systems. The clinical outcomes mirror the results found in the key adult pivotal trials.     

Views on Short Stature of Female vs Male Endocrine Pediatric Patients Undergoing Provocative Growth Hormone Testing and Their Parents

ObjectiveBoys outnumber girls in short stature evaluations and growth hormone treatment despite absence of gender differences in short stature prevalence. Family views on short stature influence medical management, but gender-based analysis of these views is lacking. This study explored endocrine patients’ and their parents’ perceptions of short stature and its impact on quality of life by patient gender.MethodsPatients aged 8 to 14 years undergoing provocative growth hormone testing and 1 parent each completed semistructured interviews. Clinical data were extracted by chart review.ResultsTwenty-four patient-parent dyads (6 female patients, 22 mothers; predominantly non-Hispanic White) participated. Six major themes emerged: (1) patients’ perceptions of their short stature were similar by gender, (2) physical experiences of short stature were similar by gender, (3) social experiences of short stature were both similar and different by gender, (4) parental perceptions of short stature as a factor limiting their child’s functionality were similar by gender, (5) concern about societal stigma related to short stature arose for both genders, and (6) patients’ perceptions of parental messaging about the import of their short stature were similar by gender.ConclusionOur data reveal more similarities than differences between genders in patient perceptions and patient and parent-reported experiences of short stature. Worry about stature-related stigma was noted for patients of both genders. Parental messaging about short stature emerged as an important area to explore further by patient gender. Our findings suggest that clinicians should be wary of making gender or stigma-based assumptions when evaluating children with short stature.     

Albumin-Corrected Calcium and the Prevalence and Categories of Hypercalcemia in Hospitalized Patients With 1-Year Follow-Up of Undiagnosed Cases

ObjectiveTo assess the impact of using corrected calcium versus total calcium on hypercalcemia case detection in hospitalized patients.MethodsPatients hospitalized from June 2012 to June 2017 with a corrected calcium level of ≥10.5 mg/dL were identified by medical record review. One-year follow-up data through June 2018 were acquired. Albumin-corrected calcium level was calculated: (4 − albumin concentration in g/dL) × 0.8 + total serum calcium in mg/dL.ResultsA group of 1067 patients had a corrected calcium level of ≥10.5 mg/dL. The prevalence of hypercalcemia was 0.73% with total calcium and 1.09% with corrected calcium, respectively, with a 49% relative increase. Most patients (62%) had mild hypercalcemia (10.5-11.9 mg/dL); 3.7% had severe hypercalcemia (>14 mg/dL). With corrected calcium, the most common categories of hypercalcemia were malignancy (35.4%), hypercalcemia that was not further evaluated (31.1%), and hyperparathyroidism (22.4%). All patients in the unidentified category had albumin levels <2.8 g/dL. At the 1-year follow–up, 63% of the unidentified cases had normal calcium levels, and 26.8% had mild persistent hypercalcemia. Of those with persisting hypercalcemia at 1 year, 16.8% were diagnosed with hyperparathyroidism.ConclusionUsing albumin-corrected calcium resulted in an ∼50% increase in the detection of hypercalcemia cases. Although hypercalcemia resolved in majority of the undiagnosed cases at 1 year, a number of these remained abnormal. Detecting hypercalcemic disorders by correcting for low albumin level can help identify conditions such as hyperparathyroidism. Adding auto-calculated albumin-corrected calcium to routine laboratory tests could be a cost-effective intervention to improve the detection of hypercalcemic disorders.     

Comparative Proteomic Analysis Identifies Key Metabolic Regulators of Gemcitabine Resistance in Pancreatic Cancer

Pancreatic adenocarcinoma (PDAC) is highly refractory to treatment. Standard-of-care gemcitabine (Gem) provides only modest survival benefits, and development of Gem resistance (GemR) compromises its efficacy. Highly GemR clones of Gem-sensitive MIAPaCa-2 cells were developed to investigate the molecular mechanisms of GemR and implemented global quantitative differential proteomics analysis with a comprehensive, reproducible ion-current–based MS1 workflow to quantify ～6000 proteins in all samples. In GemR clone MIA-GR8, cellular metabolism, proliferation, migration, and ‘drug response’ mechanisms were the predominant biological processes altered, consistent with cell phenotypic alterations in cell cycle and motility. S100 calcium binding protein A4 was the most downregulated protein, as were proteins associated with glycolytic and oxidative energy production. Both responses would reduce tumor proliferation. Upregulation of mesenchymal markers was prominent, and cellular invasiveness increased. Key enzymes in Gem metabolism pathways were altered such that intracellular utilization of Gem would decrease. Ribonucleoside-diphosphate reductase large subunit was the most elevated Gem metabolizing protein, supporting its critical role in GemR. Lower Ribonucleoside-diphosphate reductase large subunit expression is associated with better clinical outcomes in PDAC, and its downregulation paralleled reduced MIAPaCa-2 proliferation and migration and increased Gem sensitivity. Temporal protein-level Gem responses of MIAPaCa-2 versus GemR cell lines (intrinsically GemR PANC-1 and acquired GemR MIA-GR8) implicate adaptive changes in cellular response systems for cell proliferation and drug transport and metabolism, which reduce cytotoxic Gem metabolites, in DNA repair, and additional responses, as key contributors to the complexity of GemR in PDAC. These findings additionally suggest targetable therapeutic vulnerabilities for GemR PDAC patients.     

PD-L1 Expression in Normal Endocrine Tissues Is Not Increased Despite High Incidence of PD-1 Inhibitor-Associated Endocrinopathies

ObjectiveTreatment with immune-checkpoint inhibitors often results in endocrine immune-related adverse events (irAEs), affecting the pituitary, thyroid, adrenal, and parathyroid glands and pancreas. The mechanism underlying the endocrine irAEs has not been fully elucidated, and it remains unclear why endocrine organs are so commonly affected. In the present study, we evaluated immunostaining patterns of programmed death-ligand 1 (PD-L1) in normal endocrine tissues to determine whether increased expression may explain the predilection of endocrinopathies in patients treated with programmed cell death-1 inhibitors.MethodsNormal formalin-fixed paraffin-embedded endocrine tissues (pituitary, thyroid, adrenal, pancreas, and parathyroid) were collected from our hospital’s pathology tissue archive. The tissues were assessed for membranous and cytoplasmic PD-L1 immunostaining using the Dako 22C3 pharmDx assay on an automated staining platform.ResultsWe examined 49 endocrine tissues, including 12 thyroid, 5 pancreatic, 17 adrenal, 5 parathyroid, and 10 pituitary samples. Samples with less than 1% membranous PD-L1–positive cells were considered negative, while those with more than 1% of PD-L1 membranous staining were considered positive. Immunostaining result of immune-related cells was also evaluated, considering the cytoplasmic PD-L1–positive cells with the same cutoff of 1%. None of the endocrine tissues demonstrated PD-L1 positivity higher than 1% in the relevant cells.ConclusionWhile our results do not suggest a role of PD-L1 expression in the pathogenesis of endocrine irAEs, they may serve as a basis for future studies further investigating the mechanisms of autoimmune, inflammatory, or malignant endocrine conditions.     

Predictive Role of Child-To-Adult Blood Pressure Trajectories for Incident Metabolic Syndrome: 30-Year Hanzhong Adolescent Hypertension Study

ObjectiveThe relationship between child-to-adult blood pressure (BP) trajectories and metabolic syndrome (MetS) is unknown. We aimed to determine the predictive role of BP trajectories for incident MetS and its components.MethodsThe prospective Hanzhong Adolescent Hypertension study began in 1987 and included 2692 participants free of MetS at baseline with at least 3 BP measurements available from 1987 to 2017.ResultsThe systolic BP (SBP) trajectory patterns were grouped as normal (class 1, 18.7%), high normal (class 2, 60.3%), prehypertensive (class 3, 13.1%), stage 1 hypertensive (class 4, 5.7%), and stage 2 hypertensive (class 5, 2.2%). Compared with those in the normal group, individuals in classes 2 to 5 had significantly higher risks of MetS (all Ps < .05), and those with hypertension had more than an 8-fold higher risk of MetS (both P < .05). The fully adjusted risk ratios (RRs) of central obesity increased significantly in a stepwise manner as the SBP trajectory group increased from class 1 to class 5 (P < .05). Compared with those with a normal SBP trajectory, participants in the prehypertensive group and stage 1 and stage 2 hypertensive groups had significantly higher RRs for high-risk triglycerides after full adjustment (RR = 1.89 [1.22-2.94]; RR = 3.61 [2.16-6.02]; and RR = 3.22 [1.52-6.84], respectively).ConclusionOur study suggests that BP trajectories are predictive of incident MetS outcomes. Early detection of hypertension or modest elevations in BP is crucial. The stage of hypertension based on SBP level showed a greater association with central obesity.     

Meta-Analysis of Clinical Fracture Risk Reduction of Antiosteoporosis Drugs: Direct and Indirect Comparisons and Meta-Regressions

ObjectiveAntiosteoporotic drug (AOD) trials have variabilities in duration and fracture risks. This study evaluated AOD’s versus controls regarding reduction in relative rates and rate differences in vertebral and hip fractures and comparative costs.MethodsPrimary randomized controlled trials of antiosteoporotic drugs in postmenopausal women with documentation of vertebral fracture rates or hip fracture rates were extracted from meta-analyses and PubMed through February 2021. Direct and indirect meta-analyses and meta-regressions analyzed the fracture reductions.ResultsThere were 24 randomized controlled trials of drug versus placebo (73 862 women) and 10 randomized controlled trials of drug versus drug. The reductions in the relative rates of vertebral fractures were significant for antiresorptive (alendronate, risedronate, zoledronate, denosumab, and raloxifene) and anabolic (teriparatide, abaloparatide, and romosozumab) drugs. Denosumab, teriparatide, and abaloparatide were more effective in reducing vertebral fracture rates than oral bisphosphates (all P < .05) but were not more effective in reducing vertebral fracture rates than zoledronate. The reductions in hip fracture rates were significant for alendronate, denosumab, and zoledronate (all P < .05), without significant differences among drugs. Anabolic drugs did not show significant hip fracture rate reduction. Meta-regression of rate differences enabled the calculation of costs per vertebral fracture prevented, which were estimated at >$100 000 for anabolic drugs and between $2289 and $28 947 for antiresorptive drugs. Many direct drug versus drug trials were underpowered to demonstrate benefits of one drug over another.ConclusionThis study suggests goal-directed, cost-effective therapies relative to patient risk for vertebral and hip fractures. Anabolic drugs are better at preventing vertebral fractures than oral bisphosphonates. Anabolic drugs are not superior to zoledronate or denosumab and are substantially more expensive. When comparing drugs that prevented hip fractures, there was no statistical benefit of any drug.     

The Prevalence of Cancer and Its Relation to Disease Activity in Patients With Acromegaly: Two Centers' Experience

ObjectiveAcromegaly is characterized by increased serum concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Although animal studies have demonstrated a relationship between these hormones and cancer risk, the results of human studies evaluating cancer prevalence in acromegaly are inconsistent. We aimed to investigate the prevalence of malignant neoplasms in patients with acromegaly.MethodsCancer risk was evaluated in a cohort of 280 patients (male/female: 120/160; mean age: 50.93 ± 12.07 years) with acromegaly. Patients were categorized into 2 groups according to the presence or absence of cancer. Standard incidence ratios were calculated as compared to the general population.ResultsFrom 280 patients, cancer was diagnosed in 19 (6.8%) patients; 9 (47%) of them had thyroid cancer, which was the most common cancer type. Standard incidence ratios of all cancers were 0.8 (95% CI, 0.5-1.1) and 1.0 (95% CI, 0.8-1.3) in men and women, respectively. Compared to patients without cancer, the current age was higher in patients with cancer (59 [49-65] to 51 [42-59], P = .027). In contrast, the age at diagnosis was similar in both groups. Not only was the time to diagnosis and disease duration similar in both groups but also the basal and current GH and IGF-1 levels. The prevalence of active disease was also similar between the groups (32% to 23%, P = .394).ConclusionOur findings were not consistent with the studies suggesting that patients with acromegaly encounter an increased cancer risk. Furthermore, there were similar basal and current GH and IGF-1 levels in patients with acromegaly, both with and without cancer.     

The Effect and Potential Mechanism Analysis of Growth Hormone–Secreting Pituitary Adenomas on Thyroid Function

ObjectiveCurrent studies on the effect of high growth hormone (GH)/insulin-like growth factor (IGF)-1 on thyroid function are inconsistent. The aim was to explore the effect and potential mechanism of high GH/IGF-1 on thyroid function by analyzing the changes of thyroid function in patients with growth hormone–secreting pituitary adenoma (GHPA).MethodsThis was a retrospective cross-sectional study. Demographic and clinical data of 351 patients with GHPA who were first admitted to Beijing Tiantan Hospital, Capital Medical University, from 2015 to 2022 were collected to analyze the relationship between high GH/IGF-1 levels and thyroid function.ResultsGH was negatively correlated with total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH). IGF-1 was positively correlated with total triiodothyronine (TT3), free triiodothyronine (FT3), and FT4 and negatively correlated with TSH. Insulin-like growth factor–binding protein (IGFBP)-3 was positively correlated with TT3, FT3, and FT3:FT4 ratio. The FT3, TT3, TSH, and FT3:FT4 ratio of patients with GHPA and diabetes mellitus (DM) were significantly lower than those with GHPA but without DM. With the increase of tumor volume, thyroid function gradually decreased. GH and IGF-1 were correlated negatively with age in patients with GHPA.ConclusionThe study emphasized the complex interaction between the GH and the thyroid axes in patients with GHPA and highlighted the potential effect of glycemic status and tumor volume on thyroid function.     

Consensus Statement by the American Association of Clinical Endocrinology (AACE) and the American Head and Neck Society Endocrine Surgery Section (AHNS) on Pediatric Benign and Malignant Thyroid Surgery

ObjectivesTo provide a clinical disease state review of recent relevant literature and to generate expert consensus statements regarding the breadth of pediatric thyroid cancer diagnosis and care, with an emphasis on thyroid surgery. To generate expert statements to educate pediatric practitioners on the state-of-the-art practices and the value of surgical experience in the management of this unusual and challenging disease in children.MethodsA literature search was conducted and statements were constructed and subjected to a modified Delphi process to measure the consensus of the expert author panel. The wording of statements, voting tabulation, and statistical analysis were overseen by a Delphi expert (J.J.S.).ResultsTwenty-five consensus statements were created and subjected to a modified Delphi analysis to measure the strength of consensus of the expert author panel. All statements reached a level of consensus, and the majority of statements reached the highest level of consensus.ConclusionPediatric thyroid cancer has many unique nuances, such as bulky cervical adenopathy on presentation, an increased incidence of diffuse sclerosing variant, and a longer potential lifespan to endure potential complications from treatment. Complications can be a burden to parents and patients alike. We suggest that optimal outcomes and decreased morbidity will come from the use of advanced imaging, diagnostic testing, and neural monitoring of patients treated at high-volume centers by high-volume surgeons.     

Anemia in Patients With Diabetes and Prediabetes With Normal Kidney Function: Prevalence and Clinical Outcomes

ObjectiveAnemia is a known complication of diabetes mellitus (DM); however, its prevalence and prognostic relevance in patients with DM and pre-DM with normal kidney function have not been well defined. This study assessed the prevalence of anemia in patients with DM and pre-DM and evaluated its association with clinical outcomes during a 4-year follow-up period.MethodsThis retrospective analysis included patients with DM and pre-DM referred to the Meir Medical Center Endocrine Institute in 2015. Patients with an estimated glomerular filtration rate (eGFR) of <60 mL/min or any other recognized cause of anemia were excluded. The risk of developing microvascular or macrovascular complications or of death during the 4-year follow-up period was determined.ResultsA total of 622 patients (408 with DM and 214 with pre-DM) were included. The mean age of the patients was 64 ± 10.6 years, and 70% were women. The baseline hemoglobin A1C level was 7.1% ± 1.7% (54 mmol/mol), and the eGFR was 86.1 ± 15.3 mL/min. At the time of inclusion, 77 patients (19%) with DM and 23 (11%) with pre-DM had anemia (hemoglobin level 11.9 ± 0.8 and 11.8 ± 0.8 g/dL, respectively), compared with normal hemoglobin levels of 13.8 ± 0.9 and 13.7± 0.9 g/dL, respectively, in the others. A multivariable analysis demonstrated an inverse correlation between baseline hemoglobin (as a continuous variable) and mortality (P = .035), microvascular complications (P = .003), and eGFR decline (P < .001) but not between baseline hemoglobin and macrovascular complications (P = .567).ConclusionThis study found a significant prevalence of anemia unrelated to renal failure, both in patients with DM and pre-DM. Anemia in these patients is associated with the development of microvascular complications, eGFR decline, and mortality. These results underscore the need for intensive lifestyle and pharmacologic interventions in these patients.