REVIEW ARTICLE: CARDIOVASCULAR DISORDERS ASSOCIATED WITH ACROMEGALY: An Update.

The most common causes of increased cardiovascular mortality in acromegaly are due to cardiac arrhythmias and sudden cardiac death. Acromegalic cardiomyopathy, is defined as concentric biventricular hypertrophy and diastolic dysfunction when other cardiac diseases like hypertension, diabetes mellitus, and arrhythmias related cardiac disorders have been excluded. This also contributes to significant morbidity and mortality in these patients. The main risk factors contributing to the development of cardiomyopathy include advancing age, disease duration and body mass index (BMI). The duration of GH excess rather than the degree of hormone elevation is more closely associated with the development of biventricular enlargement, diastolic dysfunction, heart failure, and valvular disease. Additionally, other cardiovascular disorders such as coronary artery disease, arrhythmias, valvular heart diseases, systemic hypertension, atherosclerosis, and rarely congestive cardiac failure are also involved in the shortened life span of these patients especially if poorly controlled. Biochemical control of acromegaly with the recently available multimodal treatment along with better management of cardiovascular co-morbidities has improved the morbidity and mortality rates of patients with acromegaly. However, with the recent advances in the treatment of acromegaly neoplastic causes presently remain as the main leading cause of death in these patients.

Effects of Teprotumumab and Role of Human Leukocyte Antigens Markers in Patients With Thyroid Eye Disease.

OBJECTIVE: To evaluate the effects of teprotumumab on ophthalmologic and biochemical findings and assess potential genetic markers for response to treatment. METHODS: This is a retrospective study. Participants were 18-76 year old. All subjects were treated with teprotumumab. The primary outcome was the change in proptosis before and after teprotumumab treatment. Secondary outcomes include change in other ophthalmic measures and thyroid laboratory tests. Human leukocyte antigens (HLA) markers were analyzed for response to teprotumumab. RESULTS: Twenty-six patients were included in the final analysis. There was a significant decrease in thyroid stimulating immunoglobulin and thyrotropin receptor antibody levels and significant increases in glycated hemoglobin A1c, fasting glucose, and total T3 levels. There was also significant reduction in proptosis, clinical activity score, retinal nerve fiber layer thickness, ganglion cell analysis, and intraocular pressure. HLA haplotypes were distinct between responders and nonresponders, with HLA-DRB3 02:02:01G, HLA-DRB4 neg, and HLA-DQB1 02:01:01G demonstrating better response to teprotumumab and HLA-A 23:01:01G strongly correlating to nonresponse. CONCLUSIONS: Patients with both acute and chronic thyroid eye disease treated with teprotumumab had a significant reduction in thyroid stimulating immunoglobulin and thyrotropin receptor antibody levels and improvement in proptosis, clinical activity score, retinal nerve fiber layer and ganglion cell analysis thickness, and intraocular pressure. HLA may predict responders vs nonresponders. Further studies with longer duration and larger population comparing teprotumumab with steroids or other immunomodulatory agents (tocilizumab, rituximab, etc) may be helpful.

Use of corticosteroids for adult chronic pain interventions: sympathetic and peripheral nerve blocks, trigger point injections - guidelines from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, the American Society of Interventional Pain Physicians, the International Pain and Spine Intervention Society, and the North American Spine Society.

BACKGROUND: There is potential for adverse events from corticosteroid injections, including increase in blood glucose, decrease in bone mineral density and suppression of the hypothalamic-pituitary axis. Published studies note that doses lower than those commonly injected provide similar benefit. METHODS: Development of the practice guideline was approved by the Board of Directors of American Society of Regional Anesthesia and Pain Medicine with several other societies agreeing to participate. The scope of guidelines was agreed on to include safety of the injection technique (landmark-guided, ultrasound or radiology-aided injections); effect of the addition of the corticosteroid on the efficacy of the injectate (local anesthetic or saline); and adverse events related to the injection. Based on preliminary discussions, it was decided to structure the topics into three separate guidelines as follows: (1) sympathetic, peripheral nerve blocks and trigger point injections; (2) joints; and (3) neuraxial, facet, sacroiliac joints and related topics (vaccine and anticoagulants). Experts were assigned topics to perform a comprehensive review of the literature and to draft statements and recommendations, which were refined and voted for consensus (≥75% agreement) using a modified Delphi process. The United States Preventive Services Task Force grading of evidence and strength of recommendation was followed. RESULTS: This guideline deals with the use and safety of corticosteroid injections for sympathetic, peripheral nerve blocks and trigger point injections for adult chronic pain conditions. All the statements and recommendations were approved by all participants after four rounds of discussion. The Practice Guidelines Committees and Board of Directors of the participating societies also approved all the statements and recommendations. The safety of some procedures, including stellate blocks, lower extremity peripheral nerve blocks and some sites of trigger point injections, is improved by imaging guidance. The addition of non-particulate corticosteroid to the local anesthetic is beneficial in cluster headaches but not in other types of headaches. Corticosteroid may provide additional benefit in transverse abdominal plane blocks and ilioinguinal/iliohypogastric nerve blocks in postherniorrhaphy pain but there is no evidence for pudendal nerve blocks. There is minimal benefit for the use of corticosteroids in trigger point injections. CONCLUSIONS: In this practice guideline, we provided recommendations on the use of corticosteroids in sympathetic blocks, peripheral nerve blocks, and trigger point injections to assist clinicians in making informed decisions.

The Effects of Medium-Chain Triglyceride Oil and Butter on Lipid Profiles.

Background and objective Butter coffee drinks, mainly a form of a saturated fat diet, are widely accepted as a "healthy energy-boosting drink", especially in the young and healthy military population. The objective of our study was to determine the effects of medium-chain triglyceride (MCT) oil and butter on lipid profile, especially apolipoprotein B (ApoB), low-density lipoprotein (LDL)-cholesterol (LDL-C), high-density lipoprotein (HDL)-cholesterol (HDL-C), and other risk factors for coronary heart disease, such as BMI, BP, fasting blood glucose, HbA1c, and high-sensitivity C-reactive protein (hs-CRP) levels in healthy adults. Materials and methods We conducted a prospective study of 60 subjects who were randomized to one of the two following regimens: (1) coffee or (2) coffee with butter plus MCT oil combination. The primary outcome was the effect on ApoB. Secondary outcomes were as follows: non-HDL-C, LDL-C, triglycerides, BP, waist circumference, fasting blood glucose, and HbA1c. These parameters were evaluated at the baseline and after 12 weeks. The Mann-Whitney U test was utilized for analysis of the results. Results While 60 subjects were recruited for the study, only 41 completed it, meeting the minimum required sample size (17 per group) necessary to achieve the desired effect size: 21 males (nine in the control group and 12 in the experimental group) and 20 females (10 in each group). Anthropometric measures were similar between the two groups at baseline, and so were age and BMI (average age: 33.00 ± 5.84 years among controls and 30.86 ± 6.14 years in the experimental group; BMI: 27.35 ± 4.63 kg/m2 vs. 25.74 ± 2.70 kg/m2). The pulse rate was 69.35 ± 10.98 in the control vs. 70.68 ± 10.32 bpm in the experimental group. The waist size was also similar in both groups. Baseline lab findings were as follows: ApoB: 89.85 ± 17.52 (control), 81.60 ± 12.84 mg/dL (experimental); hs-CRP: 0.18 ± 0.27 (control), 0.17 ± 0.27 mg/L (experimental); LDL-C 113.65 ±23.71 (control), 106.50 ± 18.99 mg/dL (experimental); HDL-C 57.35 ± 14.63 (control), 62.41 ± 16.15 mg/dL (experimental); and triglycerides: 76.00 ± 31.30 (control), 56.77 ± 14.77 mg/dL (experimental), and these values were similar. The values after 12 weeks of intervention were as follows: BMI: 27.37 ± 5.24 (control), 26.36 ± 3.55 (experimental); pulse rate: 78.88 ± 14.00 (control), 74.20 ± 11.90 bpm (experimental); ApoB 87.1 ± 17.38 (control), 85.7 ±20.59 mg/dL (experimental); hs-CRP 0.26 ± 0.22 (control), 0.15 ± 0.14 mg/L (experimental); LDL-C 111.59 ± 20.35 (control), 114.10 ± 26.99 mg/dL (experimental); HDL-C 57.71 ± 12.93 (control), 64.85 ± 13.32 mg/dL (experimental); and triglycerides: 74.71 ± 25.39 (control), 60.80 ± 15.77 mg/dL (experimental). Conclusion At a significance level of 5%, there was no difference between the two groups, either at the baseline or at 12 weeks of intervention. Based on our findings, adding MCT oil and butter to coffee may be safe. However, further studies with larger sample sizes and longer duration are needed to validate our findings.

Organochlorine pesticides and risk of papillary thyroid cancer in U.S. military personnel: a nested case-control study.

BACKGROUND: The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk. METHODS: This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined. RESULTS: There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs.

Endocrine disrupting chemical mixture exposure and risk of papillary thyroid cancer in U.S. military personnel: A nested case-control study.

Single-pollutant methods to evaluate associations between endocrine disrupting chemicals (EDCs) and thyroid cancer risk may not reflect realistic human exposures. Therefore, we evaluated associations between exposure to a mixture of 18 EDCs, including polychlorinated biphenyls (PCBs), brominated flame retardants, and organochlorine pesticides, and risk of papillary thyroid cancer (PTC), the most common thyroid cancer histological subtype. We conducted a nested case-control study among U.S. military servicemembers of 652 histologically-confirmed PTC cases diagnosed between 2000 and 2013 and 652 controls, matched on birth year, sex, race/ethnicity, military component (active duty/reserve), and serum sample timing. We estimated mixture odds ratios (OR), 95% confidence intervals (95% CI), and standard errors (SE) for associations between pre-diagnostic serum EDC mixture concentrations, overall PTC risk, and risk of histological subtypes of PTC (classical, follicular), adjusted for body mass index and military branch, using quantile g-computation. Additionally, we identified relative contributions of individual mixture components to PTC risk, represented by positive and negative weights (w). A one-quartile increase in the serum mixture concentration was associated with a non-statistically significant increase in overall PTC risk (OR = 1.19; 95% CI = 0.91, 1.56; SE = 0.14). Stratified by histological subtype and race (White, Black), a one-quartile increase in the mixture was associated with increased classical PTC risk among those of White race (OR = 1.59; 95% CI = 1.06, 2.40; SE = 0.21), but not of Black race (OR = 0.95; 95% CI = 0.34, 2.68; SE = 0.53). PCBs 180, 199, and 118 had the greatest positive weights driving this association among those of White race (w = 0.312, 0.255, and 0.119, respectively). Findings suggest that exposure to an EDC mixture may be associated with increased classical PTC risk. These findings warrant further investigation in other study populations to better understand PTC risk by histological subtype and race.

Three cases highlighting possible discrepancies in the interpretation of transgender DXA scores.

For diagnosis of osteoporosis, a T-score of ≤-2.5 is recommended for all transgender and gender-diverse patients aged 50 years or older, regardless of hormonal status. This case series presents 3 transgender individuals younger than 50 years undergoing gender-affirming hormone therapy (GAHT) who had DXA scores suggestive of osteoporosis. We highlight possible discrepancies in DXA scan interpretations, especially in forearm bone mineral density measurements. We present the baseline (prior to beginning GAHT), 6-month, and 1-year follow-up DXA data along with pertinent labs to include 25-OH vitamin D, calcium, and alkaline phosphatase, for 2 transgender males (assigned female at birth) and 1 transgender female (assigned male at birth) undergoing GAHT who had low Z-scores and T-scores suggestive of osteoporosis. Multiple studies have analyzed the BMD data of individuals taking GAHT over time, which identify possible causes for low baseline Z-scores for transgender females, but less so for transgender males. Other than positional statements, guidelines remain unclear regarding diagnostic approaches to osteoporosis and low Z-scores in transgender individuals who are premenopausal or under 50 years of age. This case series addresses discrepancies in interpretation that may be encountered by clinicians with baseline and follow-up DXAs, especially involving the forearm, during the course of GAHT. This highlights the importance of establishing clearer guidelines for the diagnosis and treatment of osteoporosis and low BMD for chronological age in the transgender population.

Simultaneous diagnosis of papillary thyroid cancer and systemic mastocytosis.

Key Clinical Message: When managing patients with differentiated thyroid cancers (DTC) and lytic bone lesions, physicians should consider etiologies other than DTC bony metastases when there is no biochemical and functional radiographic evidence of extensive DTC burden. Abstract: Systemic mastocytosis (SM) is a clonal expansion of mast cells associated with an increased risk of solid malignancies. There is no known association between systemic mastocytosis and thyroid cancer. We report a young woman who presented with cervical lymphadenopathy, palpable thyroid nodule, and lytic bone lesions who was diagnosed with papillary thyroid cancer (PTC). The patient's post-surgical thyroglobulin was lower than expected for metastatic thyroid cancer, and the lytic bone lesions did not demonstrate uptake of I123. Upon further evaluation, the patient was found to have SM. We report a case of co-occurrence of PTC and SM.

64-year-old woman • hot flashes, facial flushing, excessive sweating, and palpitations • daily headaches • history of hypertension • Dx?

► hot flashes, facial flushing, excessive sweating, and palpitations ► daily headaches ► history of hypertension.

Persistent level 1 hypoglycemia due to hypothyroidism and underlying Neurofibromatosis type 1.

Key Clinical Message: Hypoglycemia in non-diabetic patients is rare and may be due to various etiologies. It is important to recognize hypoglycemia early and appropriately manage hypoglycemia in patients with neurofibromatosis 1 and hypothyroidism. Abstract: Non-diabetic hypoglycemia is not common and can be seen in certain conditions like Neurofibromatosis type 1 (NF1). We report a rare case of 66-year-old man with hypothyroidism and NF1 who developed a persistent level 1 hypoglycemia.

Protocol for Development of American Association of Clinical Endocrinology Clinical Practice Guidelines and Consensus Statements: Summary of Methodology, Process, and Policy - 2023 Update.

OBJECTIVE: This 2023 updated protocol summarizes the American Association of Clinical Endocrinology's (AACE's) new framework for the development of clinical practice guidelines and other guidance documents that includes changes to methodology, processes, and policies. METHODS: AACE has critically reviewed its development processes for guidance documents over the last several years against the National Academy of Medicine Standards for Developing Trustworthy Clinical Practice Guidelines and the Council of Medical Specialty Societies Principles for Development of Specialty Society Clinical Guidelines to determine areas for improvement. RESULTS: The new AACE framework for development of guidance documents incorporates many changes, including a revised conflicts of interest (COI) policy; strengthened commitment to collection of disclosures and management of relevant COI during development; open calls to membership for authors; new requirements for authors; new diversity, equity, and inclusion (DEI) policy; new empanelment process that incorporates consideration of DEI; and adoption of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to increase the quality of evidence assessment and standardize recommendation grades and statements, among other improvements. CONCLUSIONS: AACE has revised its policies and adopted a completely new methodology for guideline development in support of the mission to elevate the practice of clinical endocrinology to improve patient care. With the use of an evidence-based medicine framework and by continually assessing and improving its processes for development of guidance, AACE strives to deliver trustworthy, unbiased, and up-to-date information that ensures clinician and patient confidence in AACE content. Further, AACE hopes that these enhancements foster a more collaborative approach to development and increase engagement with the worldwide medical community to improve global health.

Dental loss, stress fractures, and musculoskeletal pain in a 48-year-old woman.

We report a 48-year-old female patient with various stress fractures of extremities, musculoskeletal pain, and tooth loss. Hypophosphatasia was diagnosed based on clinical and laboratory findings and ALPL genetic results. This case highlights the importance of early diagnosis of hypophosphatasia in adults and appropriate treatment to prevent further complications.

A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings.

BACKGROUND: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data. METHODS: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation. RESULTS: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals. CONCLUSION: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

Dilemmas in the diagnosis and management of osteoporosis in a patient with alkaptonuria: Successful treatment with teriparatide.

Management of osteoporosis in patients with alkaptonuria can be challenging. This is the first case report confirming the effectiveness of teriparatide following zoledronic acid therapy in treating osteoporosis and preventing fragility fractures in a patient with alkaptonuria.

Graves' disease complicated by concurrent thyroid eye disease and pretibial myxedema successfully treated with teprotumumab.

We report a 51-year-old woman with thyroid eye disease and biopsy-proven pretibial myxedema that was subsequently treated with teprotumumab with improvement.