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.

Effects of teprotumumab and role of HLA markers in patients with thyroid eye disease.

OBJECTIVE: To evaluate the effects of teprotumumab on ophthalmological and biochemical findings and assess potential genetic markers for TED responses. METHODS: This is a retrospective study. Participants were 18-76 years 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) were also analyzed as markers for response to teprotumumab. RESULTS: Twenty-six patients were included in the final analysis. There was a significant decrease in TSI and TRAb levels and significant increases in HbA1c, fasting glucose, and total T3 levels. There was also significant reduction in proptosis, clinical activity score (CAS), retinal nerve fiber layer (RNFL) thickness, ganglion cell thickness (GCA), and intraocular pressure (IOP). HLA haplotypes were distinct between responders and non-responders, 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 non-response. CONCLUSIONS: Patients with both acute and chronic TED treated with teprotumumab had a significant reduction in TSI and TRAb levels and improvement in proptosis, CAS, RNFL and GCA thickness, and IOP. HLA may predict responders vs. non-responders. Further studies with longer duration and larger population comparing teprotumumab with steroids or other immunomodulatory agents (tocilizumab, rituximab, etc) may be helpful.

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.

Diagnostic Challenges of Medullary Thyroid Carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) comprises 1-2% of all thyroid cancers, yet 15% of all thyroid cancer-related deaths. While up to 20% of cases may be predicted due to autosomal dominant germline mutations, 80% of cases are sporadic. However, due to non-specific presenting symptoms and diagnostic imaging, prompt diagnosis and treatment has remained elusive. This article will further investigate the limitations of MTC diagnosis and look into future areas for diagnostic improvement. METHODS: Relevant articles were identified using a systematic PubMed and Google Scholar search. RESULTS: Prophylactic total thyroidectomy for the 20% of MTC cases that are present in autosomal dominant disorder provides definitive treatment. Serum calcitonin (Ctn) screening has several technical limitations due to population variability and laboratory assay interference, but advances in laboratory technology and combined use with fine needle aspiration increase its sensitivity. Other serum assays such as carcinoembryonic antigen and procalcitonin have limited applicability. Thyroid ultrasound remains the gold standard for the initial diagnostic planning, with limited application for CT, MRI, and PET imaging. CONCLUSION: With complete surgical resection the only definitive treatment, early MTC diagnosis has presented an elusive challenge, mainly due to its relative rarity and difficulty in finding an economic screening strategy. Careful family history combined with fine needle aspiration with serum Ctn analysis can improve diagnostic sensitivity and specificity to greater than 95%.

Recognition and Treatment of Adrenal Insufficiency Secondary to Abiraterone: A Case Report and Literature Review.

OBJECTIVE: Abiraterone is a relatively noncytotoxic drug approved by the US Food and Drug Administration in 2011 for the treatment of metastatic prostate cancer (MPC). As an inhibitor of 17α-hydroxylase and C17,20-lyase (CYP17), abiraterone blocks androgen synthesis and glucocorticoid production. Decreased cortisol levels result in an increased ACTH release, which can lead to increased mineralocorticoid levels. While coadministration of abiraterone and glucocorticoids has been effective in reducing an apparent mineralocorticoid excess, adequate replacement of physiologic glucocorticoids, especially in times of acute stress, remains less well-defined. METHODS: A literature search was conducted using the PubMed and Google Scholar databases for abiraterone and adrenal insufficiency. Publications were selected based on the quality of the data and clinical relevance. We reviewed the landmark trials leading to FDA approval and establishment of the standard glucocorticoid replacement dosing. RESULTS: We present 2 patients with MPC on abiraterone therapy. These 2 patients required modification of the glucocorticoid therapy because of adverse effects. CONCLUSIONS: We found that a standard dose of prednisone of 5 mg/day as recommended previously may be inadequate to achieve physiologic glucocorticoid replacement in some patients with prostate cancer while on abiraterone treatment and as a result adrenal insufficiency due to inadequate dosing might be more common than initially thought. Additionally 10 mg of prednisone daily may cause adverse effects in some patients. Thus clinicians should be aware of the potential for development of adrenal insufficiency or symptoms of glucocorticoid excess in these patients receiving prednisone so that appropriate modifications in glucocorticoid dosing can be instituted without any delay. Prednisone dosing may need to be individualized in each patient receiving abiraterone therapy.

ASSOCIATIONS OF SERUM IONIZED CALCIUM, PHOSPHATE, AND PTH LEVELS WITH PARATHYROID SCAN IN PRIMARY HYPERPARATHYROIDISM.

OBJECTIVE: To evaluate the relationship between various biochemical parameters in patients with primary hyperparathyroidism (PHPT) with positive and negative technetium-99 sestamibi (Tc) parathyroid scans performed with single-photon emission computed tomography/computed tomography (SPECT/CT). METHODS: This retrospective analysis was used to develop a logistic probability model. It included 218 patients with PHPT. The main outcome measures were serum total calcium, ionized calcium, intact parathyroid hormone (PTH), albumin, alkaline phosphatase, phosphate, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, 24-h urinary calcium levels, and parathyroid adenoma weight. RESULTS: Individually, using cut-off levels of 6.0 mg/dL for ionized calcium, 3.0 mg/dL for phosphate, and 90 pg/mL for intact PTH, we found that 91.3% ( P = .005), 70.7% ( P = .004) and 87.90% ( P = .023) of the patients had a positive Tc scan with their corresponding strengths of associations in the parentheses. Similar significant associations were sustained in multivariate setting for serum ionized calcium ( P = .015), phosphate ( P = .016), and intact PTH ( P = .028). A logistic probability model was designed to predict the probability of being positive for Tc scan given a set of covariates. CONCLUSION: There are significant associations between the levels of serum ionized calcium, phosphate, intact PTH, and Tc scan positivity. Further studies with larger patient populations are needed. ABBREVIATIONS: BMI = body mass index; CT = computed tomography; CV = coefficient variation; DXA = dual-energy x-ray absorptiometry; MRI = magnetic resonance imaging; PHPT = primary hyperparathyroidism; PPV = positive predictive value; PTH = parathyroid hormone; SPECT = single-photon emission computed tomography; Tc = technetium-99 sestamibi.

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.

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.

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.

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.

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.