The interpretation of immunometric, chromatographic and mass spectrometric data for steroids in diagnosis of endocrine disorders.

The analysis of steroids for endocrine disorders is in transition from immunoassay of individual steroids to more specific chromatographic and mass spectrometric methods with simultaneous determination of several steroids. Gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry (MS) offer unrivalled analytical capability for steroid analysis. These specialist techniques were often judged to be valuable only in a research laboratory but this is no longer the case. In a urinary steroid profile up to 30 steroids are identified with concentrations and excretion rates reported in a number of ways. The assays must accommodate the wide range in steroid concentrations in biological fluids from micromolar for dehydroepiandrosterone sulphate (DHEAS) to picomolar for oestradiol and aldosterone. For plasma concentrations, panels of 5-20 steroids are reported. The profile results are complex and interpretation is a real challenge in order to inform clinicians of likely implications. Although artificial intelligence and machine learning will in time generate reports from the analysis this is a way off being adopted into clinical practice. This review offers guidance on current interpretation of the data from steroid determinations in clinical practice. Using this approach more laboratories can use the techniques to answer clinical questions and offer broader interpretation of the results so that the clinician can understand the conclusion for the steroid defect, and can be advised to program further tests if necessary and instigate treatment. The biochemistry is part of the patient workup and a clinician led multidisciplinary team discussion of the results will be required for challenging patients. The laboratory will have to consider cost implications, bearing in mind that staff costs are the highest component. GC-MS and LC-MS/MS analysis of steroids are the choices. Steroid profiling has enormous potential to improve diagnosis of adrenal disorders and should be adopted in more laboratories in favour of the cheap, non-specific immunological methods.

Endocrine immune-related adverse events by immune checkpoint inhibitors and potential predictive markers: a prospective study from a single tertiary center.

Immune checkpoint inhibitors (ICIs) can trigger immune-related adverse events (irAEs). The appearance pattern of irAEs, who is prone to them, and their mechanisms are still uncertain. In this study, we aimed to monitor patients initiated on ICIs for endocrinological aspects and to investigate the potential predictive markers in the development of endocrine-irAEs. The study prospectively included 43 patients with metastatic disease scheduled for anti-PD-1/L1 therapy. Endocrinological follow-up was conducted at specified intervals as well as in response to any additional reported complaints. Serum concentrations of CXCL10, IL-1beta, and IL-17A were measured prior to ICI and during the endocrine-irAEs. A total of 39.5% of the patients experienced endocrine-irAEs, with a median onset time of 3 months. Among patients, 34.9% developed thyroid-related adverse events, and 4.6% experienced hypophysitis. Thyroid autoantibodies were associated with a higher incidence of thyroid-related irAEs (P = 0.004). In the irAE group, median pre-ICI CXCL10 and baseline thyroid stimulating hormone (TSH) levels were significantly higher, baseline total testosterone level in men was lower than in the non-irAE group (P < 0.05), whereas IL-1beta and IL-17A levels did not differ (P > 0.05). Serum CXCL10, IL-1beta, and IL-17A concentrations did not differ significantly pre-ICI and during adverse events (P > 0.05). Pre-ICI CXCL10 concentration was correlated positively with anti-TPO levels in patients with at least one thyroid autoantibody positivity (r = 0.706, P = 0.01) and negatively with baseline total testosterone level of men (r = 0.509, P = 0.002). Our results suggest that higher pre-ICI serum CXCL10 and TSH levels might have a predictive role in the development of endocrinopathies. Besides, baseline thyroid antibody measurements could be beneficial in predicting thyroid dysfunction.

Trace element status in canine endocrine diseases.

A balanced trace element status is essential for the optimal functioning of all organisms. However, their concentrations are often altered in diverse medical conditions. This study investigated the trace element profiles in plasma samples of dogs with endocrine diseases and used chemometric techniques to explore their associations with biochemical data. Thirteen elements (As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Se and Zn) were measured in 40 dogs with hyperadrenocorticism (HAC), 29 dogs with diabetes mellitus (DM), 11 dogs with hypothyroidism (HT) and 30 control dogs using inductively coupled plasma mass spectrometry (ICP-MS). Statistically significant differences were observed for As, Cu, Mo, Se and Zn. In comparison with the control group, the HT patients had higher As and lower Se levels, while the HAC group had higher concentrations of Mo. All three disease groups had higher Cu and Zn concentrations than the control group, with the DM group having higher Cu concentrations and the HAC group higher Zn concentrations than the other endocrinopathy groups. The chemometric analysis revealed distinctive association patterns for discriminating each pathology group and the control group. Moreover, the analysis revealed the following associations: Mo with glucose levels and Cu with fructosamine levels in the DM group, As with cortisol levels in the HAC group, and Se with TT4 levels and As with TSH levels in the HT group. The study findings provide valuable insights into the complex relationships between trace elements and endocrinopathies, elucidating the associations with biochemical markers in these diseases. Larger-scale studies are necessary to fully understand the observed relationships and explore the potential clinical applications.

The prevalence of elevated biotin in patient cohorts presenting for routine endocrinology, sepsis, and infectious disease testing.

Elevated blood biotin levels may interfere with some biotin-streptavidin immunoassays, used in clinical laboratories to aid diagnosis. The objective of this study was to determine the prevalence of elevated blood biotin levels in three at risk patient cohorts, where misclassification of disease status would have a high clinical impact. This retrospective, single-center study screened residual, de-identified plasma samples (N = 700) from adult patients undergoing routine thyroid stimulating hormone (TSH) (n = 500), procalcitonin (PCT) (n = 100), or human immunodeficiency virus (HIV) (n = 100) testing using the Elecsys® BRAHMS PCT (Roche Diagnostics), Access TSH (3rd IS) (Beckman Coulter Inc), and ARCHITECT HIV Ag/Ab Combo (Abbott Laboratories) immunoassays, respectively, for elevated levels of biotin (quantified by gas chromatography-time of flight mass spectrometry). Patients taking biotin supplements were included and dosages recorded from medical records. In the overall study cohort, blood biotin levels ranged 0.1-21.3 ng/mL; 44.3% (310/700) of samples were < 1 ng/mL, 54.7% (383/700) were 1-<10 ng/mL, and 1% (7/700) were ≥ 10 ng/mL. The sub-cohorts had similar ranges of biotin levels: 0.5-21.3 ng/mL (TSH), 0.1-12.1 ng/mL (PCT), and 0.3-7.3 ng/mL (HIV). In the 44 patients (6.3% of overall study cohort) who were documented as taking biotin supplements (range of doses, 2.5-10 mg/day), blood biotin levels ranged 0.9-21.3 ng/mL; 2.3% (1/44) of samples were < 1 ng/mL, 86.4% (38/44) were 1-<10 ng/mL, and 11.4% (5/44) were ≥ 10 ng/mL. Most patients who reported taking biotin supplements had blood biotin levels ≥ 1 ng/mL and the highest blood biotin level detected was 21.3 ng/mL.

Endocrine Disorders and Genital Infections Impair Gynecological Health in APECED (APS-1).

Objective: In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) defects in the autoimmune regulator gene lead to impaired immunotolerance. We explored the effects of immunodeficiency and endocrinopathies on gynecologic health in patients with APECED. Design: Cross-sectional cohort study combined with longitudinal follow-up data. Methods: We carried out a gynecologic evaluation, pelvic ultrasound, and laboratory and microbiologic assessment in 19 women with APECED. Retrospective data were collected from previous study visits and hospital records. Results: The study subjects' median age was 42.6 years (range, 16.7-65.5). Sixteen patients (84%) had premature ovarian insufficiency, diagnosed at the median age of 16.5 years; 75% of them used currently either combined contraception or hormonal replacement therapy. In 76% of women, the morphology and size of the uterus were determined normal for age, menopausal status, and current hormonal therapy. Fifteen patients (79%) had primary adrenal insufficiency; three of them used dehydroepiandrosterone substitution. All androgen concentrations were under the detection limit in 11 patients (58%). Genital infections were detected in nine patients (47%); most of them were asymptomatic. Gynecologic C. albicans infection was detected in four patients (21%); one of the strains was resistant to azoles. Five patients (26%) had human papillomavirus infection, three of which were high-risk subtypes. Cervical cell atypia was detected in one patient. No correlation between genital infections and anti-cytokine autoantibodies was found. Conclusions: Ovarian and adrenal insufficiencies manifested with very low androgen levels in over half of the patients. Asymptomatic genital infections, but not cervical cell atypia, were common in female patients with APECED.

Obesity Is Strongly Associated With Low Testosterone and Reduced Penis Growth During Development.

CONTEXT: Growth of male genitalia represents an important marker of sexual development. Testicle size is the primary measure and little is known regards penile length changes during puberty. OBJECTIVE: This work aims to assess penis growth and testosterone levels in obese vs normal-weight children and adolescents, to evaluate a possible influence of obesity on genital development in boys, and to establish a new method for measuring penis length that allows comparison of normal-weight and overweight boys. METHODS: We assessed anthropometric and genital development in 1130 boys from birth to age 20 years. Testosterone levels were also measured. A new method for penile length measurement was employed to minimize errors when comparing obese and nonobese children. Penis length was measured with a gentle, painless, straight positioning on a centimetric ruler without stretching, which is doable from the first years of life until the end of adolescence. RESULTS: Penis length and testosterone are strongly related in children during puberty. Penile length growth is significantly decreased (by about 10%) in obese boys when compared to normal-weight boys, with concomitantly reduced testosterone levels, across puberal phases. CONCLUSION: Childhood obesity represents an important determinant of lower testosterone level and reduced penis development. A new method should be employed to improve penis measurement in normal-weight and overweight/obese boys. The possible significance of these observations for adult genital development and reproductive potential will require large longitudinal studies.

Definition, Prevalence, and Risk Factors of Low Sex Hormone-Binding Globulin in US Adults.

CONTEXT: Lower sex hormone-binding globulin (SHBG) is associated with many diseases including cardiovascular disease, cancer, polycystic ovarian syndrome, arthritis, and liver disease. However, the definition of low SHBG and its prevalence in US adults are unknown. OBJECTIVE: To define low SHBG and to determine its prevalence and risk factors in US adults. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included adults ≥20 years from the US National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016 who had fasting serum SHBG. EXPOSURES: NHANES coverage during 2013-2016. MAIN OUTCOMES MEASURES: Definition, prevalence, and risk factors of low SHBG. RESULTS: This study included 4093 adults (weighted sample size of 204 789 616) with a mean (SD) age of 47.5 (17.0) years. In a "healthy" reference sub-cohort of 1477 adults, low SHBG was defined as SHBG < 12.3 nmol/L in men < 50 years, <23.5 nmol/L in men ≥ 50 years, <14.5 nmol/L in women < 30 years, and <21.9 nmol/L in women ≥ 30 years. The estimated US national prevalence of low SHBG was 3.3% in men, 2.7% in women, and 3.0% overall. Risk factors for this condition in both men and women included higher body mass index, diabetes, ethnicity (being other than Hispanic, non-Hispanic black, or non-Hispanic white), chronic obstructive pulmonary disease, coronary heart disease, and smoking. CONCLUSIONS: This study established the criteria for low SHBG among US adults. The estimated US national prevalence of low SHBG was 3.3% in men and 2.7% in women.

Multiplex Autoantibody Detection in Patients with Autoimmune Polyglandular Syndromes.

The diagnosis of autoimmune polyglandular syndrome (APS) types 1/2 is difficult due to their rarity and nonspecific clinical manifestations. APS-1 development can be identified with assays for autoantibodies against cytokines, and APS-2 development with organ-specific antibodies. In this study, a microarray-based multiplex assay was proposed for simultaneous detection of both organ-specific (anti-21-OH, anti-GAD-65, anti-IA2, anti-ICA, anti-TG, and anti-TPO) and APS-1-specific (anti-IFN-ω, anti-IFN-α-2a, and anti-IL-22) autoantibodies. Herein, 206 serum samples from adult patients with APS-1, APS-2, isolated autoimmune endocrine pathologies or non-autoimmune endocrine pathologies and from healthy donors were analyzed. The prevalence of autoantibodies differed among the groups of healthy donors and patients with non-, mono- and multi-endocrine diseases. APS-1 patients were characterized by the presence of at least two specific autoantibodies (specificity 99.5%, sensitivity 100%). Furthermore, in 16 of the 18 patients, the APS-1 assay revealed triple positivity for autoantibodies against IFN-ω, IFN-α-2a and IL-22 (specificity 100%, sensitivity 88.9%). No anti-cytokine autoantibodies were found in the group of patients with non-APS-1 polyendocrine autoimmunity. The accuracy of the microarray-based assay compared to ELISA for organ-specific autoantibodies was 88.8-97.6%. This multiplex assay can be part of the strategy for diagnosing and predicting the development of APS.

Should Pediatric Endocrinologists Consider More Carefully When to Perform a Stimulation Test?

Introduction: Pediatric endocrinology rely greatly on hormone stimulation tests which demand time, money and effort. The knowledge of the pattern of pediatric endocrinology stimulation tests is therefore crucial to optimize resources and guide public health interventions. Aim of the study was to investigate the distribution of endocrine stimulation tests and the prevalence of pathological findings over a year and to explore whether single basal hormone concentrations could have saved unnecessary stimulation tests. Methods: Retrospective study with data collection for pediatric endocrine stimulation tests performed in 2019 in a tertiary center. Results: Overall, 278 tests were performed on 206 patients. The most performed test was arginine tolerance test (34%), followed by LHRH test (24%) and standard dose Synachthen test (19%), while the higher rate of pathological response was found in insulin tolerance test to detect growth hormone deficiency (81%), LHRH test to detect central precocious puberty (50%) and arginine tolerance test (41%). No cases of non-classical-congenital adrenal hyperplasia were diagnosed. While 29% of growth hormone deficient children who performed an insulin tolerance test had a pathological peak cortisol, none of them had central adrenal insufficiency confirmed at low dose Synacthen test. The use of basal hormone determinations could save up to 88% of standard dose Synachthen tests, 82% of arginine tolerance + GHRH test, 61% of LHRH test, 12% of tests for adrenal secretion. Conclusion: The use of single basal hormone concentrations could spare up to half of the tests, saving from 32,000 to 79,000 euros in 1 year. Apart from basal cortisol level <108 nmol/L to detect adrenal insufficiency and IGF-1 <-1.5 SDS to detect growth hormone deficiency, all the other cut-off for basal hormone determinations were found valid in order to spare unnecessary stimulation tests.

Inflammatory markers in autoimmunity induced by checkpoint inhibitors.

PURPOSE: Immune checkpoint inhibitors (ICI) are highly effective in several cancer entities, but also invoke a variety of immune-related adverse events (irAE). These are mostly reversible, but can be life-threatening or even fatal. Currently, the pathogenesis is not fully understood, but crucial for effective treatment. Prediction and early detection of irAE could be facilitated and treatment optimized if relevant biomarkers and effector mechanisms were better characterized. METHODS: This study included a total of 45 irAE in patients with metastatic melanoma who were treated with ICI. All patients underwent a complete work-up with exclusion of other causes. Longitudinal blood samples were analyzed for a panel of soluble markers and compared to baseline and to patients who did not experience any irAE. Measurements included LDH, interleukin (IL)-6, IL-1ß, IL-17, C-reactive protein (CRP) and tumor necrosis factor (TNF)-alpha as well as tumor markers S100 and melanoma inhibitory activity (MIA). RESULTS: During the early onset of irAE increases in serum IL-6 (from mean 24.4 pg/ml at baseline to 51.0 pg/ml; p = 0.003) and CRP (from mean 7.0 mg/l at baseline to 17.7 mg/l; p = 0.001) and a decrease in MIA (from mean 5.4 pg/ml at baseline to 4.8 pg/ml; p = 0.035) were detected. No changes in IL-17 were noted. These effects were observed for irAE of different organ systems. CONCLUSION: Increases of a combination of IL-6 and CRP serum levels can be used for the early detection of irAE and tailored management. Interestingly, changes in MIA serum levels also correlate with irAE onset.

Clinical characteristics of endocrinopathies in Chinese patients with hereditary haemochromatosis.

AIMS: Hereditary haemochromatosis (HH) is a genetic disorder characterised by systemic iron overload and can lead to end-organ failure. However, very few data on this disorder, especially those on endocrine gland involvement in Chinese populations, are currently available. This study aimed to analyse the clinical features of endocrinopathies in patients with HH to generate concern among endocrinologists and improve the management of this disorder. MATERIALS AND METHODS: Chinese patients with HH-related endocrine dysfunction were enrolled at Peking Union Medical College Hospital from January 2010 to December 2018. All clinical data were analysed and summarised. RESULTS: A total of six patients were enrolled in this study, comprising five men and one woman; the average age was 36.5 ± 13.3 years. Mean serum ferritin concentration was 4508.8 ± 1074.3 ng/ml, and median transferrin saturation was 97.9% (96.6%-110.0%). Endocrine gland involvement associated with HH included the pancreas (5/6 patients), the adenohypophysis (5/6 patients) and the bones (1/6 patients); secondary endocrinopathies consisted of diabetes mellitus, hypogonadism, adrenal insufficiency and osteoporosis. Based on phlebotomy and iron chelation therapy, five patients were treated with exogenous insulin preparations, and three patients were treated with exogenous sex hormone replacement therapy. The clinical symptoms of five patients improved, although one patient died of hepatic encephalopathy and multiple organ failure. CONCLUSIONS: HH can cause multiple endocrinopathies. The possibility of HH should be carefully considered in patients with endocrine gland dysfunctions and concomitant elevated serum ferritin levels. Endocrine gland function should also be assessed and followed up in patients with a clear diagnosis of HH.

Clinical Heterogeneity of Acquired Idiopathic Isolated Adrenocorticotropic Hormone Deficiency.

Objective: Heterogeneous clinical characteristics are observed in acquired isolated adrenocorticotropic hormone (ACTH) deficiency (IAD); however, its classification remains to be established because of its largely unknown pathophysiology. In IAD, anti-pituitary antibodies have been detected in some patients, although their significance remains unclear. Therefore, this study aimed to classify patients with IAD and to clarify the significance of anti-pituitary antibodies. Design and Methods: We analyzed 46 consecutive patients with IAD. Serum anti-pituitary antibodies were analyzed via immunofluorescence staining using a mouse pituitary tissue. Principal component and cluster analyses were performed to classify IAD patients based on clinical characteristics and autoantibodies. Results: Immunofluorescence analysis using the sera revealed that 58% of patients showed anti-corticotroph antibodies and 6% of patients showed anti-follicular stellate cell (FSC) antibodies. Principal component analysis demonstrated that three parameters could explain 70% of the patients. Hierarchical cluster analysis showed three clusters: Groups A and B comprised patients who were positive for anti-corticotroph antibodies, and plasma ACTH levels were extremely low. Groups A and B comprised middle-aged or elderly men and middle-aged women, respectively. Group C comprised patients who were positive for the anti-FSC antibody and elderly men; plasma ACTH levels were relatively high. Conclusions: Patients with IAD were classified into three groups based on clinical characteristics and autoantibodies. The presence of anti-corticotroph antibody suggested severe injury to corticotrophs. This new classification clearly demonstrated the heterogeneity in the pathogenesis of IAD.

Functions, pathophysiology and current insights of exosomal endocrinology (Review).

Studies on extracellular vesicles have increased in recent years. The multi­dimensional nature of their roles in cellular homeostasis, cell­to­cell and tissue­to­tissue communication at the level of the organism, as well as their actions on the holobiome (intra­/interspecies interaction), have garnered the interest of a large number of researchers. Exosomes are one of the most researched classes of extracellular vesicles because they are carriers of targeted protein and DNA/RNA loads. Their multi­functional cargo have been indicated to regulate a vast number of biological pathways in target cells. However, the mechanisms governing these interactions have not yet been fully determined. Endocrinology, by definition, focuses on homeostatic, and cell­to­cell and tissue­to­tissue communication mechanisms. Therefore exosomes should be included in this research topic. Exosomes have previously been associated with a number of endocrine disorders, including obesity, type 2 diabetes mellitus, disorders of the reproductive system and cancer. Furthermore, their biogenesis, composition and function have been associated with viruses, an entirely different domain of life. The profound roles of exosomes in homeostasis, stress and several pathological conditions, in conjunction with their selective and cell­specific composition/function, allude to their use as promising circulating clinical biomarkers of systemic stress and specific pathologic states, and as biocompatible vehicles of therapeutic cargo. The current review provides information on exosomes and discusses their endocrine implications.

From a single steroid to the steroidome: Trends and analytical challenges.

For several decades now, the analysis of steroids has been a key tool in the diagnosis and monitoring of numerous endocrine pathologies. Thus, the available methods used to analyze steroids in biological samples have dramatically evolved over time following the rapid pace of technology and scientific knowledge. This review aims to synthetize the advances in steroids' analysis, from classical approaches considering only a few steroids or a limited number of steroid ratios, up to the new steroid profiling strategies (steroidomics) monitoring large sets of steroids in biological matrices. In this context, the use of liquid chromatography coupled to mass spectrometry has emerged as the technique of choice for the simultaneous determination of a high number of steroids, including phase II metabolites, due to its sensitivity and robustness. However, the large dynamic range to be covered, the low natural abundance of some key steroids, the selectivity of the analytical methods, the extraction protocols, and the steroid ionization remain some of the current challenges in steroid analysis. This review provides an overview of the different analytical workflows available depending on the number of steroids under study. Special emphasis is given to sample treatment, acquisition strategy, data processing, steroid identification and quantification using LC-MS approaches. This work also outlines how the availability of steroid standards, the need for complementary analytical strategies and the improvement of calibration approaches are crucial for achieving complete steroidome quantification.

Neurological and endocrinological manifestations of 49 children with intracranial pure germinoma at initial diagnosis in Taiwan.

BACKGROUND: Intracranial pure germinoma is a rare extragonadal neoplasm. Affected patients may have motor impairment, visual disturbance, neurological signs, and endocrine disorder, depending on the size and location of the tumor. This study investigated and analyzed patients' demographic data and neuroimaging, clinical, laboratory, and endocrinological findings. METHODS: We performed a retrospective chart review of 49 children diagnosed with pure germinoma in Taiwan from 1990 to 2018. The initial clinical presentation, tumor markers (beta-hCG, alpha fetoprotein, and carcinoembryonic antigen), pituitary function, and brain images were reviewed and analyzed. RESULTS: This study included 49 patients (37 boys and 12 girls). Their ages ranged from 7.5 to 17.9 years, and the mean age at diagnosis was 13.6 years. Initial symptoms included visual disturbance (n = 23, 47.9%), motor impairment (n = 20, 40.8%), polyuria (n = 20, 40.8%), headache (n = 17, 34.7%), dizziness or vertigo (n = 14, 28.6%), nausea/vomiting (n = 13, 26.5%), and short stature (n = 8, 18.2%). Laboratory data indicated growth hormone deficiency or low IGF-1 levels (n = 18, 85.7%), adrenal insufficiency (n = 21, 77.8%), central diabetes insipidus (n = 27, 55.1%), central hypothyroidism (n = 15, 48.4%), and hypogonadotropic hypogonadism (n = 4, 44.4%). CONCLUSION: Intracranial pure germinomas may initially manifest as neurological symptoms or endocrinological findings at diagnosis. As endocrinologic presentation is related to delayed diagnosis, clinicians should be aware of patients with such complaints. Laboratory data should be surveyed carefully, and neuroimaging must be considered if the result is abnormal.

MANAGEMENT OF ENDOCRINE DISEASE: The role of surgical adrenalectomy in primary aldosteronism.

Primary aldosteronism is common and contributes to adverse cardiovascular, kidney, and metabolic outcomes. When instituted early and effectively, targeted therapies can mitigate these adverse outcomes. Surgical adrenalectomy is among the most effective treatments because it has the potential to cure, or attenuate the severity of, pathologic aldosterone excess, resulting in a host of biochemical and clinical changes that improve health outcomes. Herein, we review the role of surgical adrenalectomy in primary aldosteronism while emphasizing the physiologic ramifications of surgical intervention, and compare these to other targeted medical therapies for primary aldosteronism. We specifically review the role of curative adrenalectomy for unilateral primary aldosteronism, the role of non-curative adrenalectomy for bilateral primary aldosteronism, and how these interventions influence biochemical and clinical outcomes in relation to medical therapies for primary aldosteronism.

Lipid Management in Patients with Endocrine Disorders: An Endocrine Society Clinical Practice Guideline.

OBJECTIVE: This guideline will provide the practicing endocrinologist with an approach to the assessment and treatment of dyslipidemia in patients with endocrine diseases, with the objective of preventing cardiovascular (CV) events and triglyceride-induced pancreatitis. The guideline reviews data on dyslipidemia and atherosclerotic cardiovascular disease (ASCVD) risk in patients with endocrine disorders and discusses the evidence for the correction of dyslipidemia by treatment of the endocrine disease. The guideline also addresses whether treatment of the endocrine disease reduces ASCVD risk. CONCLUSION: This guideline focuses on lipid and lipoprotein abnormalities associated with endocrine diseases, including diabetes mellitus, and whether treatment of the endocrine disorder improves not only the lipid abnormalities, but also CV outcomes. Based on the available evidence, recommendations are made for the assessment and management of dyslipidemia in patients with endocrine diseases.

Carbohydrate antigen 19-9 elevation without evidence of malignant or pancreatobiliary diseases.

Although carbohydrate antigen 19-9 (CA 19-9) may be elevated in benign diseases, elevated CA 19-9 may cause a fear of cancer and unnecessary follow-up studies. Research on how to approach systematically in this case is very limited. The purpose of this study was to analyze the clinical features and the causes of CA 19-9 elevation without evidence of malignant or pancreatobiliary diseases. We retrospectively reviewed the medical records of patients who had CA 19-9 elevation (≥80 U/mL) and were found to be unrelated to cancer after follow-up. After exclusion, 192 patients were included in this study. The median level of CA 19-9 was 136.5 U/mL. The causes of CA 19-9 elevation were determined in 147 (76.6%) patients, and that was unknown in 45 (23.4%). The estimated causative diseases were hepatic diseases in 63 patients, pulmonary diseases in 32, gynecologic diseases in 38, endocrine diseases in 13, and spleen disease in 1. Of 45 patients with unknown cause, 35 had normalization of CA 19-9 and 10 had persistently elevated CA 19-9. In conclusion, CA 19-9 elevation without malignancies or pancreatobiliary diseases should be systematically evaluated and followed up. We suggest an algorithm to investigate the causes and follow up these patients.

Optimal Endocrine Evaluation and Treatment of Male Infertility.

This article aims to define the optimal endocrine workup of male factor infertility, including evaluation and treatment of men who have previously been on exogenous testosterone or anabolic steroids. Future directions include the expansion of genetic testing for infertility to include endocrine gene products.

Biochemical bone turnover markers in hormonal disorders in adults: a narrative review.

BACKGROUND: Hormonal disorders are often associated with abnormal levels of bone turnover markers (BTMs). N-terminal propeptide of type I procollagen (PINP) and serum C-terminal cross-linking telopeptide of type I collagen (CTX-I) are the reference markers of bone formation and bone resorption, respectively. METHODS: A comprehensive literature search within the MEDLINE and Web of Science databases was performed. RESULTS: Acromegaly is associated with higher BTM levels, which decrease during the remission after treatment. Adult-onset growth hormone deficiency is often associated with decreased BTM levels. Growth hormone replacement therapy stimulates bone turnover and increases BTM levels. Hypothyroidism is characterized by general slowing of bone metabolism which is reflected by lower BTM levels. The replacement thyroid hormone therapy increases the bone turnover rate and BTM levels increase. Patients with thyroid cancer receive a suppressive dose of thyroid hormones and may have slightly elevated BTM levels. Patients with overt hyperthyroidism had higher BTM levels and anti-thyroid therapy induces a rapid decrease in the BTM levels. Patients with overt primary hyperparathyroidism have higher BTM levels, whereas those with asymptomatic and normocalcemic hyperparathyroidism usually have normal BTM levels. Hypoparathyroidism is characterized by slightly decreased BTM levels. Cushing's syndrome is characterized consistently by markedly decreased osteocalcin concentration, whereas data on other BTMs are discordant. CONCLUSIONS: BTMs help us to better understand mechanisms of the impact of hormonal disorders and their treatment on bone metabolism. However, it is unknown whether BTMs may be used to monitor the effect of their treatments on bone in the clinical practice.