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Journal of Clinical Lipidology May 2024Cardiovascular disease (CVD) is the leading cause of death among women and its incidence has been increasing recently, particularly among younger women. Across major...
Cardiovascular disease (CVD) is the leading cause of death among women and its incidence has been increasing recently, particularly among younger women. Across major professional society guidelines, dyslipidemia management remains a central tenet for atherosclerotic CVD prevention for both women and men. Despite this, women, particularly young women, who are candidates for statin therapy are less likely to be treated and less likely to achieve their recommended therapeutic objectives for low-density lipoprotein cholesterol (LDL-C) levels. Elevated LDL-C and triglycerides are the two most common dyslipidemias that should be addressed during pregnancy due to the increased risk for adverse pregnancy outcomes, such as preeclampsia, gestational diabetes mellitus, and pre-term delivery, as well as pancreatitis in the presence of severe hypertriglyceridemia. In this National Lipid Association Expert Clinical Consensus, we review the roles of nutrition, physical activity, and pharmacotherapy as strategies to address elevated levels of LDL-C and/or triglycerides among women of reproductive age. We include a special focus on points to consider during the shared decision-making discussion regarding pharmacotherapy for dyslipidemia during preconception planning, pregnancy, and lactation.
PubMed: 38824114
DOI: 10.1016/j.jacl.2024.05.005 -
Lancet (London, England) Jun 2024
Topics: Humans; Male; Lymphomatoid Granulomatosis; Adult; Addison Disease
PubMed: 38823995
DOI: 10.1016/S0140-6736(24)00974-7 -
Clinical Case Reports Jun 2024Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disorder defined by the presence of at least two of the following conditions: chronic mucocutaneous...
KEY CLINICAL MESSAGE
Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disorder defined by the presence of at least two of the following conditions: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism, and Addison's syndrome. Despite the lack of CMC and autoimmune history, APS-1 can be diagnosed using genetic testing.
UNLABELLED
We present the case of a 28-year-old female patient with a history of hypocalcemia due to hypoparathyroidism since the age of 2 years. She presented to the endocrine clinic with hypogonadism, primary amenorrhea, and primary ovarian insufficiency. Addison's disease was eventually diagnosed, despite a negative Synacthen test. The adrenal crisis required intravenous hydrocortisone therapy. No CMC was documented, and there was no family history of such conditions. The diagnosis of APS-1 was confirmed by genetic testing, revealing homozygous pathogenic variants of the autoimmune regulator gene. Management included oral calcium and calcitriol and oral hydrocortisone and fludrocortisone for Addison's disease. Hormonal induction of secondary sexual characteristics was initiated. The patient received combined oral estrogen and progesterone pills. This case highlights the critical significance of early recognition, thorough evaluation, and tailored treatment for patients with APS-1 to enhance their quality of life and mitigate potentially life-threatening complications. This underscores the importance of screening for associated minor autoimmune diseases as part of a holistic approach to care.
PubMed: 38808199
DOI: 10.1002/ccr3.9015 -
The American Journal of the Medical... May 2024Autoimmune polyglandular syndrome (APS) is a rare group of immune-mediated disorders, which are typically, but not exclusively, related to the presence of endocrine... (Review)
Review
Autoimmune polyglandular syndrome (APS) is a rare group of immune-mediated disorders, which are typically, but not exclusively, related to the presence of endocrine abnormalities. APS type 2 is the most common subtype of the syndrome, more often observed in adulthood, with a characteristic clinical triad, which includes adrenal insufficiency, autoimmune thyroiditis and diabetes mellitus type 1. Adrenal insufficiency is an essential and necessary clinical manifestation of the syndrome, as it is observed in 100 % of the cases, while it can be accompanied by hyperchloremic metabolic acidosis. Herein, we present a 23 years-old patient with adrenal insufficiency in the context of autoimmune polyglandular syndrome type 2 with coexisting autoimmune thyroiditis and metabolic acidosis with an increased anion gap attributed to prolonged malnutrition. Additionally, we analyze the main clinical features of adrenal insufficiency, which is a central component of autoimmune polyglandular syndrome; highlight characteristics that differentiate the major APS subtypes.
PubMed: 38801948
DOI: 10.1016/j.amjms.2024.05.019 -
Endocrine Reviews May 2024Glucocorticoid hormones (GC) are secreted in a circadian and ultradian rhythm and play a critical role in maintaining physiological homeostasis, with both excess and...
Glucocorticoid hormones (GC) are secreted in a circadian and ultradian rhythm and play a critical role in maintaining physiological homeostasis, with both excess and insufficient GC associated with adverse effects on health. Current assessment of GC status is primarily clinical, often in conjunction with serum cortisol values, which may be stimulated or suppressed depending on the GC disturbance being assessed. In the setting of extreme perturbations in cortisol levels i.e. markedly low or high levels, symptoms and signs of GC dysfunction may be overt. However, when disturbances in cortisol GC status values are less extreme, such as when assessing optimization of a GC replacement regimen, signs and symptoms can be more subtle or non-specific. Current tools for assessing GC status, are best suited to identifying profound disturbances but may lack sensitivity for confirming optimal GC status. Moreover, single cortisol values do not necessarily reflect an individual's GC status, as they are subject to inter- and intra-individual variation, do not take into account the pulsatile nature of cortisol secretion, variation in binding proteins, or local tissue concentrations as dictated by 11βeta-hydroxysteroid dehydrogenase (11β-HSD) activity, as well as GC receptor sensitivity. In the present review, we evaluate possible alternative methods for the assessment of GC status that do not solely rely on measurement of circulating cortisol levels. We discuss the potential of changes in metabolomic profiles, miRNA, gene expression, epigenetic, and other novel biomarkers such as GDF-15 and osteocalcin, that could in future aid in the objective classification of GC status.
PubMed: 38795365
DOI: 10.1210/endrev/bnae016 -
Endocrinologia, Diabetes Y Nutricion Oct 2023Little is known about the quality of adherence to glucocorticoid replacement therapy in patients with Addison disease (AD). The aim of this study was to evaluate the...
UNLABELLED
Little is known about the quality of adherence to glucocorticoid replacement therapy in patients with Addison disease (AD). The aim of this study was to evaluate the quality of glucocorticoid treatment adherence in patients with AD and to assess its association with patients' disease knowledge and quality of life.
METHODS
This is a cross-sectional study including 58 patients with AD. The Girerd questionnaire was used to assess the quality of adherence to glucocorticoid replacement therapy. A questionnaire was specially designed to assess patients' disease knowledge. The AddiQol questionnaire, specific to AD, was used to assess the patients' quality of life. Patients were considered non-adherent if they gave three or fewer than three negative answers to the Girerd questionnaire (score≤3/6).
RESULTS
The mean age of the patients was 48.4±13.3 years (39 women and 19 men). Twenty-seven patients (46%) were non-adherent to glucocorticoid replacement therapy. An age below 48 years, poor adherence to comorbidity treatments, baseline cortisolemia at diagnosis>5μg/dl, history of adrenal crisis, poor knowledge about the disease, BMI<26.7kg/m, waist circumference<90cm, low systolic blood pressure, fasting blood glucose<0.9g/l, and triglyceride<1g/l were the factors independently associated with non-adherence (respectively ORa [CI 95%]=4.8 [2.8-10.7], 5.0 [3.0-12.2], 2.3 [1.2-6.2], 4.1 [2.0-8.3], 3.9 [1.2-7.2], 3.9 [1.1-6.9], 1.8 [1.1-2.9], 4.8 [2.6-8.2], 2.5 [1.1-5.3], and 2.2 [1.1-5.1]). There was a positive correlation between the disease knowledge questionnaire score and the Girerd score (p=0.02, r=0.31). There was a positive correlation between the AddiQoL score and the Girerd score (p=0.01, r=0.32).
CONCLUSION
Non-adherence to glucocorticoid replacement therapy was common in patients with AD and was associated with more frequent adrenal crisis and poorer quality of life. The quality of treatment adherence was correlated with patients' disease knowledge. Therapeutic education is essential to reduce the frequency of non-adherence, especially among young patients.
Topics: Humans; Addison Disease; Male; Female; Quality of Life; Glucocorticoids; Cross-Sectional Studies; Middle Aged; Medication Adherence; Hormone Replacement Therapy; Adult; Surveys and Questionnaires; Health Knowledge, Attitudes, Practice
PubMed: 38783727
DOI: 10.1016/j.endien.2023.10.004 -
BMJ Case Reports May 2024A woman in her 40s presented with a history of fatigue, symptoms of light-headedness on getting up from a sitting position and hyperpigmentation of the skin and mucous...
A woman in her 40s presented with a history of fatigue, symptoms of light-headedness on getting up from a sitting position and hyperpigmentation of the skin and mucous membranes. During the evaluation, she was diagnosed with primary adrenal insufficiency. Radiological imaging and microbiological evidence revealed features of disseminated tuberculosis involving the lungs and the adrenals. She was found to have an HIV infection. This patient was prescribed glucocorticoid and mineralocorticoid replacement therapy and was administered antituberculous and antiretroviral treatment.
Topics: Humans; Female; Adult; HIV Infections; Antitubercular Agents; Addison Disease; Glucocorticoids; Diagnosis, Differential; Tuberculosis, Pulmonary; Adrenal Insufficiency; Tuberculosis, Miliary
PubMed: 38782434
DOI: 10.1136/bcr-2023-256844 -
Lancet (London, England) Jun 2024Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial.
BACKGROUND
Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear.
METHODS
RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
FINDINGS
Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths.
INTERPRETATION
Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population.
FUNDING
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
Topics: Humans; Male; Prostatic Neoplasms; Androgen Antagonists; Prostatectomy; Aged; Tosyl Compounds; Anilides; Middle Aged; Nitriles; Oligopeptides; Gonadotropin-Releasing Hormone; Combined Modality Therapy; Prostate-Specific Antigen
PubMed: 38763154
DOI: 10.1016/S0140-6736(24)00548-8 -
Lancet (London, England) Jun 2024Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial.
BACKGROUND
Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain.
METHODS
RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
FINDINGS
Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths.
INTERPRETATION
Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.
FUNDING
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
Topics: Humans; Male; Prostatic Neoplasms; Androgen Antagonists; Prostatectomy; Aged; Tosyl Compounds; Middle Aged; Anilides; Nitriles; Oligopeptides; Gonadotropin-Releasing Hormone; Prostate-Specific Antigen; Combined Modality Therapy; Drug Administration Schedule
PubMed: 38763153
DOI: 10.1016/S0140-6736(24)00549-X -
Child Abuse & Neglect Jul 2024Empirical studies have demonstrated associations between ten original adverse childhood experiences (ACEs) and multiple health outcomes. Identifying expanded ACEs can...
BACKGROUND
Empirical studies have demonstrated associations between ten original adverse childhood experiences (ACEs) and multiple health outcomes. Identifying expanded ACEs can capture the burden of other childhood adversities that may have important health implications.
OBJECTIVE
We sought to identify childhood adversities that warrant consideration as expanded ACEs. We hypothesized that experiencing expanded and original ACEs would be associated with poorer adult health outcomes compared to experiencing original ACEs alone.
PARTICIPANTS
The 11,545 respondents of the National Longitudinal Surveys (NLS) and Child and Young Adult Survey were 48.9 % female, 22.7 % Black, 15.8 % Hispanic, 36.1 % White, 1.7 % Asian/Native Hawaiian/Pacific Islander/Native American/Native Alaskan, and 7.5 % Other.
METHODS
This study used regression trees and generalized linear models to identify if/which expanded ACEs interacted with original ACEs in association with six health outcomes.
RESULTS
Four expanded ACEs-basic needs instability, lack of parental love and affection, community stressors, and mother's experience with physical abuse during childhood -significantly interacted with general health, depressive symptom severity, anxiety symptom severity, and violent crime victimization in adulthood (all p-values <0.005). Basic needs instability and/or lack of parental love and affection emerged as correlates across multiple outcomes. Experiencing lack of parental love and affection and original ACEs was associated with greater anxiety symptoms (p = 0.022).
CONCLUSIONS
This is the first study to use supervised machine learning to investigate interaction effects among original ACEs and expanded ACEs. Two expanded ACEs emerged as predictors for three adult health outcomes and warrant further consideration in ACEs assessments.
Topics: Humans; Female; Male; Adverse Childhood Experiences; Adult; Longitudinal Studies; Child; Young Adult; Adolescent; Health Status; Regression Analysis; Depression; Crime Victims; Anxiety; United States; Adult Survivors of Child Abuse
PubMed: 38761717
DOI: 10.1016/j.chiabu.2024.106844