Hypothyroidism has multiple etiologies and manifestations. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions. This paper describes evidence-based ...clinical guidelines for the clinical management of hypothyroidism in ambulatory patients.
The development of these guidelines was commissioned by the American Association of Clinical Endocrinologists (AACE) in association with American Thyroid Association (ATA). AACE and the ATA assembled a task force of expert clinicians who authored this article. The authors examined relevant literature and took an evidence-based medicine approach that incorporated their knowledge and experience to develop a series of specific recommendations and the rationale for these recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach outlined in the American Association of Clinical Endocrinologists Protocol for Standardized Production of Clinical Guidelines-2010 update.
Topics addressed include the etiology, epidemiology, clinical and laboratory evaluation, management, and consequences of hypothyroidism. Screening, treatment of subclinical hypothyroidism, pregnancy, and areas for future research are also covered.
Fifty-two evidence-based recommendations and subrecommendations were developed to aid in the care of patients with hypothyroidism and to share what the authors believe is current, rational, and optimal medical practice for the diagnosis and care of hypothyroidism. A serum thyrotropin is the single best screening test for primary thyroid dysfunction for the vast majority of outpatient clinical situations. The standard treatment is replacement with L-thyroxine. The decision to treat subclinical hypothyroidism when the serum thyrotropin is less than 10 mIU/L should be tailored to the individual patient.
Hypothyroidism has multiple etiologies and manifestations. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions. This paper describes evidence-based ...clinical guidelines for the clinical management of hypothyroidism in ambulatory patients.
The development of these guidelines was commissioned by the American Association of Clinical Endocrinologists (AACE) in association with American Thyroid Association (ATA). AACE and the ATA assembled a task force of expert clinicians who authored this article. The authors examined relevant literature and took an evidence-based medicine approach that incorporated their knowledge and experience to develop a series of specific recommendations and the rationale for these recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach outlined in the American Association of Clinical Endocrinologists Protocol for Standardized Production of Clinical Guidelines-2010 update.
Topics addressed include the etiology, epidemiology, clinical and laboratory evaluation, management, and consequences of hypothyroidism. Screening, treatment of subclinical hypothyroidism, pregnancy, and areas for future research are also covered.
Fifty-two evidence-based recommendations and subrecommendations were developed to aid in the care of patients with hypothyroidism and to share what the authors believe is current, rational, and optimal medical practice for the diagnosis and care of hypothyroidism. A serum thyrotropin is the single best screening test for primary thyroid dysfunction for the vast majority of outpatient clinical situations. The standard treatment is replacement with L-thyroxine. The decision to treat subclinical hypothyroidism when the serum thyrotropin is less than 10 mIU/L should be tailored to the individual patient.
In response to infection, naïve CD4
T cells differentiate into two subpopulations: T follicular helper (T
) cells, which support B cell antibody production, and non-T
cells, which enhance innate ...immune cell functions. Interleukin-2 (IL-2), the major cytokine produced by naïve T cells, plays an important role in the developmental divergence of these populations. However, the relationship between IL-2 production and fate determination remains unclear. Using reporter mice, we found that differential production of IL-2 by naïve CD4
T cells defined precursors fated for different immune functions. IL-2 producers, which were fated to become T
cells, delivered IL-2 to nonproducers destined to become non-T
cells. Because IL-2 production was limited to cells receiving the strongest T cell receptor (TCR) signals, a direct link between TCR-signal strength, IL-2 production, and T cell fate determination has been established.
Late-onset sepsis (LOS) is thought to result from systemic spread of commensal microbes from the intestines of premature infants. Clinical use of probiotics for LOS prophylaxis has varied owing to ...limited efficacy, reflecting an incomplete understanding of relationships between development of the intestinal microbiome, neonatal dysbiosis and LOS. Using a model of LOS, we found that components of the developing microbiome were both necessary and sufficient to prevent LOS. Maternal antibiotic exposure that eradicated or enriched transmission of Lactobacillus murinus exacerbated and prevented disease, respectively. Prophylactic administration of some, but not all Lactobacillus spp. was protective, as was administration of Escherichia coli. Intestinal oxygen level was a major driver of colonization dynamics, albeit via mechanisms distinct from those in adults. These results establish a link between neonatal dysbiosis and LOS, and provide a basis for rational selection of probiotics that modulate primary succession of the microbiome to prevent disease.
Orthostatic intolerance (OI), having difficulty tolerating an upright posture because of symptoms or signs that abate when returned to supine, is common in pediatrics. For example, ∼40% of people ...faint during their lives, half of whom faint during adolescence, and the peak age for first faint is 15 years. Because of this, we describe the most common forms of OI in pediatrics and distinguish between chronic and acute OI. These common forms of OI include initial orthostatic hypotension (which is a frequently seen benign condition in youngsters), true orthostatic hypotension (both neurogenic and nonneurogenic), vasovagal syncope, and postural tachycardia syndrome. We also describe the influences of chronic bed rest and rapid weight loss as aggravating factors and causes of OI. Presenting signs and symptoms are discussed as well as patient evaluation and testing modalities. Putative causes of OI, such as gravitational and exercise deconditioning, immune-mediated disease, mast cell activation, and central hypovolemia, are described as well as frequent comorbidities, such as joint hypermobility, anxiety, and gastrointestinal issues. The medical management of OI is considered, which includes both nonpharmacologic and pharmacologic approaches. Finally, we discuss the prognosis and long-term implications of OI and indicate future directions for research and patient management.
To estimate the incidence of herpes zoster (HZ) in patients with rheumatoid arthritis (RA) compared with the general population in the USA.
This retrospective, longitudinal cohort study used data ...from an administrative claims database containing both commercial and Medicare Advantage Part D data, with a data period from October 2015 to February 2020. Patients were aged ≥ 18 years and divided into 2 cohorts: patients with RA and patients without RA. Diagnosis and procedure codes were used to identify HZ cases and calculate incidence rates (IRs) of HZ in the 2 cohorts. Data were stratified by age group (ie, 18-49, 18-29, 30-39, 40-49, 50-64, and ≥ 65 yrs) and RA therapy type. IR ratios (IRRs), adjusted by cohort baseline characteristics, were estimated using generalized linear models to compare the incidence of HZ between cohorts.
The overall IR of HZ was higher in the RA cohort (21.5 per 1000 person-years PY; N = 67,650) than in the non-RA cohort (7.6 per 1000 PY; N = 11,401,743). The highest IRs in both cohorts were observed in the age group of ≥ 65 yrs (23.4 and 11.4 per 1000 PY in the RA cohort and non-RA cohort, respectively). The overall adjusted IRR of HZ was 1.93 (95% CI 1.87-1.99,
< 0.001) for the RA cohort compared with the non-RA cohort. In the RA cohort, the highest IRs by medication class were observed in patients using corticosteroids and those using Janus kinase inhibitors.
These results highlight the increased incidence of HZ in patients with RA.
Interleukin (IL)-22 is central to immune defense at barrier sites. We examined the contributions of innate lymphoid cell (ILC) and T cell-derived IL-22 during Citrobacter rodentium (C.r) infection ...using mice that both report Il22 expression and allow lineage-specific deletion. ILC-derived IL-22 activated STAT3 in C.r-colonized surface intestinal epithelial cells (IECs) but only temporally restrained bacterial growth. T cell-derived IL-22 induced a more robust and extensive activation of STAT3 in IECs, including IECs lining colonic crypts, and T cell-specific deficiency of IL-22 led to pathogen invasion of the crypts and increased mortality. This reflected a requirement for T cell-derived IL-22 for the expression of a host-protective transcriptomic program that included AMPs, neutrophil-recruiting chemokines, and mucin-related molecules, and it restricted IFNγ-induced proinflammatory genes. Our findings demonstrate spatiotemporal differences in the production and action of IL-22 by ILCs and T cells during infection and reveal an indispensable role for IL-22-producing T cells in the protection of the intestinal crypts.
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•ILCs and T cells localize to distinct microanatomic niches during C.r infection•IL-22+ innate cells target surface IECs to limit early bacterial colonization•IL-22+ T cells target crypt IECs to prevent C.r dissemination into colonic crypts•IL-22+ T cells amplify IEC-derived host defense genes and repress IFN-induced genes
Interleukin (IL)-22-producing innate and adaptive immune cells contribute to host protection at barrier sites. Zindl et al. reveal that IL-22+ ILCs and T cells are specialized for early versus late protection of the intestinal mucosa via distinct patterns of activation of intestinal epithelial cells: actions of ILCs are limited to the superficial IECs to limit early bacterial colonization, whereas IL-22+ CD4 T cells recruited to the LP uniquely target crypt IECs to restrain bacterial spread into the colonic crypts.
Mendelian genetics presumes inheritance of fitness through DNA. Kinder et al. find that maternal microchimerism induces stable immune tolerance to non-inherited maternal antigens in offspring. Female ...offspring that share these antigens with their mate experience reduced fetal wasting, establishing a role for vertical transmission of non-genetic information in reproductive fitness.
Mendelian genetics presumes inheritance of fitness through DNA. Kinder et al. find that maternal microchimerism induces stable immune tolerance to non-inherited maternal antigens in offspring. Female offspring that share these antigens with their mate experience reduced fetal wasting, establishing a role for vertical transmission of non-genetic information in reproductive fitness.
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