Diverse presentations of Cushing's syndrome during pregnancy - A case series.

BACKGROUND: Cushing's syndrome (CS) encompasses various causes of hypercortisolism including adrenocorticotropic hormone (ACTH) secreting pituitary adenoma with or without bilateral adrenal hyperplasia, an adrenal adenoma or carcinoma, ectopic ACTH or corticotrophin-releasing hormone (CRH) secretion by a neoplasm or exogenous corticosteroid therapy. The diagnosis of CS in pregnancy presents a challenge due to overlapping clinical features of pregnancy (weight gain, striae, acne). If untreated, CS in pregnancy is associated with increased risk of maternal and fetal complications. AIMS: With fewer than 250 cases currently published, we aim to review the clinical presentations, diagnostic methods, management, and outcomes of patients with CS in pregnancy to help optimise our clinical practice. MATERIALS AND METHODS: This is a single-centre, retrospective review of woman with documented hypercortisolism receiving antenatal care at a tertiary maternity hospital in Perth between 2006 to 2022. Data were collated from electronic and chart reviews. OMNI calculator was used for birthweight calculations. Local ethics and patient consent were obtained. RESULTS: Five women and seven pregnancies were identified. Four women had a pituitary source of ACTH-dependent CS as confirmed by brain magnetic resonance imaging. One woman had an ectopic source of ACTH. Two women were diagnosed during pregnancy. All pregnancies occurring prior to treatment of the Cushing's disease were complicated by secondary hypertension and diabetes. CONCLUSION: CS represents a rare and difficult to diagnose condition in pregnancy. When untreated, maternal and fetal outcomes are compromised. Close monitoring of the associated complications with involvement of a multidisciplinary team are recommended.

Serum 21-Deoxycortisol for Diagnosis of Nonclassic Congenital Adrenal Hyperplasia in Women With Androgen Excess.

CONTEXT: Nonclassic congenital adrenal hyperplasia (NCCAH) requires exclusion before diagnosing polycystic ovary syndrome (PCOS). Increasing use of liquid chromatography and tandem mass spectrometry (LC-MS/MS) necessitates revision of immunoassay-based criteria for NCCAH. Measurement of 21-deoxycortisol (21DF) may simplify the diagnosis of heterozygosity (HTZ), the presence of 1 affected CYP21A2 allele, which currently relies on complex molecular studies. OBJECTIVE: We aimed to determine LC-MS/MS-specific criteria for NCCAH and HTZ and compare the diagnostic accuracy of 21DF and 17-hydroxyprogesterone (17OHP). METHODS: A cross-sectional study involving 99 hyperandrogenic females was performed. We identified females who had undergone both a synacthen stimulation test (SST) and CYP21A2 genotyping from 2010 to 2017, and prospectively recruited females referred for an SST to investigate hyperandrogenic symptoms from 2017 to 2021. Steroids were compared between genetically confirmed NCCAH, HTZ, and PCOS. Optimal 17OHP and 21DF thresholds for HTZ and NCCAH were determined by receiver operating characteristic analysis. RESULTS: Basal 17OHP, stimulated 17OHP, and 21DF were measured in 99, 85, and 42 participants, respectively. Optimal thresholds for NCCAH were 3.0 nmol/L and 20.7 nmol/L for basal and stimulated 17OHP, respectively. Basal and stimulated 21DF thresholds of 0.31 nmol/L and 13.3 nmol/L provided 100% sensitivity with specificities of 96.8% and 100% for NCCAH, respectively. Diagnostic thresholds for HTZ of 8.0 nmol/L, 1.0 nmol/L, and 13.6 for stimulated 17OHP, 21DF, and the ratio (21DF + 17OHP)/cortisol each provided 100% sensitivity with specificities of 80.4%, 90.5%, and 85.0%, respectively. CONCLUSION: LC-MS/MS-specific 17OHP thresholds for NCCAH are lower than those based on immunoassay. LC-MS/MS-quantified 17OHP and 21DF accurately discriminate HTZ and NCCAH from PCOS.

Longitudinal Stability of Vitamin D Status and Its Association With Bone Mineral Density in Middle-aged Australians.

Context: The skeletal effects of vitamin D remain controversial and it is uncertain whether variation in serum 25-hydroxyvitamin D (25OHD) levels over time influences bone mineral density (BMD). Objective: We evaluated longitudinal stability of serum 25OHD and associations with changes in BMD in participants aged 46-70 years at baseline. Methods: We studied 3698 Busselton Healthy Ageing Study participants (2040 female) with serum 25OHD and dual-energy x-ray absorptiometry (DXA) BMD assessments at baseline and at ∼6 years follow-up. Restricted cubic splines were used to evaluate associations between changes in 25OHD and BMD. Results: Mean season-corrected serum 25OHD was 81.3 ± 22.7 and 78.8 ± 23.1 nmol/L at baseline and 6 years, respectively, and showed moderate correlation (intraclass correlation coefficient: 0.724). Significant predictors of change in 25OHD concentration (Δ25OHD) included baseline 25OHD, change in body mass index and vitamin D supplementation at follow-up. Greater decline in serum 25OHD over time was associated with significantly greater reduction in BMD at total hip and femoral neck, but the magnitude of the differences was small (estimated differences 0.004 g/cm2 and 0.005-0.007 g/cm2, respectively, for lowest quartile of Δ25OHD compared with higher quartiles, adjusted for sex, baseline BMD, 25OHD, and demographics). No significant associations between Δ25OHD and lumbar spine BMD were observed. Increase in 25OHD levels was not associated with change in BMD. Conclusions: In this predominantly vitamin D-replete middle-aged cohort, serum 25OHD showed moderate longitudinal stability. Declining serum 25OHD over time was associated with greater reduction in BMD at the total hip and femoral neck.

Immunoregulatory effects of testosterone supplementation combined with exercise training in men with Inclusion Body Myositis: a double-blind, placebo-controlled, cross-over trial.

Objectives: Sporadic Inclusion Body Myositis (IBM) is an inflammatory muscle disease affecting individuals over the age of 45, leading to progressive muscle wasting, disability and loss of independence. Histologically, IBM is characterised by immune changes including myofibres expressing major histocompatibility complex molecules and invaded by CD8+ T cells and macrophages, and by degenerative changes including protein aggregates organised in inclusion bodies, rimmed vacuoles and mitochondrial abnormalities. There is currently no cure, and regular exercise is currently the only recognised treatment effective at limiting muscle weakening, atrophy and loss of function. Testosterone exerts anti-inflammatory effects, inhibiting effector T-cell differentiation and pro-inflammatory cytokine production. Methods: We conducted a double-blind, placebo-controlled, cross-over trial in men with IBM, to assess whether a personalised progressive exercise training combined with application of testosterone, reduced the inflammatory immune response associated with this disease over and above exercise alone. To assess intervention efficacy, we immunophenotyped blood immune cells by flow cytometry, and measured serum cytokines and chemokines by Luminex immunoassay. Results: Testosterone supplementation resulted in modest yet significant count reduction in the classical monocyte subset as well as eosinophils. Testosterone-independent immunoregulatory effects attributed to exercise included altered proportions of some monocyte, T- and B-cell subsets, and reduced IL-12, IL-17, TNF-α, MIP-1ß and sICAM-1 in spite of interindividual variability. Conclusion: Overall, our findings indicate anti-inflammatory effects of exercise training in IBM patients, whilst concomitant testosterone supplementation provides some additional changes. Further studies combining testosterone and exercise would be worthwhile in larger cohorts and longer testosterone administration periods.

Anti-Müllerian hormone concentration is associated with central adiposity and reproductive hormones in expectant fathers.

OBJECTIVE: The role of the anti-Müllerian hormone (AMH) as an indicator of physical and reproductive health in men is unclear. We assessed the relationships between AMH and follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and metabolic parameters, in a cohort of expectant fathers. DESIGN: ORIGINS Project prospective cohort study. SETTING: Community-dwelling men. PARTICIPANTS: Partners of pregnant women attending antenatal appointments. MAIN OUTCOME MEASURES: Serum AMH, FSH, LH, testosterone, and metabolic parameters. RESULTS: In 485 expectant fathers, median age 33 years, median AMH was 40 pmol/L (quartiles 29, 56). AMH was inversely correlated with FSH, age, and body mass index (BMI) (correlation coefficients: -.32, -.24, and -.17 respectively). The age association was nonlinear, with peak AMH between 20 and 30 years, a decline thereafter, and somewhat steady levels after 45 years. The inverse association of AMH with FSH was log-linear and independent of age and BMI (ß: -.07, SE: 0.01, p < .001). AMH was inversely correlated with waist circumference and directly associated with sex hormone-binding globulin. Testosterone was moderately correlated with AMH (correlation coefficient: .09, ß: .011, SE: 0.004, p = .014): this association was mediated by an inverse relationship with BMI (mediated proportion 0.49, p < .001). CONCLUSIONS: In reproductively active men, lower AMH is a biomarker for advancing age, and for poorer metabolic and reproductive health. The inverse association between AMH and FSH is independent of age and BMI, whereas the association of AMH and testosterone is mediated via BMI. The utility of AMH to predict reproductive and cardiometabolic outcomes in men warrants further investigation.

Genome-wide analysis of thyroid function in Australian adolescents highlights SERPINA7 and NCOA3.

OBJECTIVE: Genetic factors underpin the narrow intraindividual variability of thyroid function, although precise contributions of environmental vs genetic factors remain uncertain. We sought to clarify the heritability of thyroid function traits and thyroid peroxidase antibody (TPOAb) positivity and identify single nucleotide polymorphisms (SNPs) contributing to the trait variance. METHODS: Heritability of thyroid-stimulating hormone (TSH), free T4 (fT4), free T3 (fT3) and TPOAb in a cohort of 2854 euthyroid, dizygous and monozygous twins (age range 11.9-16.9 years) from the Brisbane Longitudinal Twin Study (BLTS) was assessed using structural equation modelling. A genome-wide analysis was conducted on 2832 of these individuals across 7 522 526 SNPs as well as gene-based association analyses. Replication analysis of the association results was performed in the Raine Study (n = 1115) followed by meta-analysis to maximise power for discovery. RESULTS: Heritability of thyroid function parameters in the BLTS was 70.8% (95% CI: 66.7-74.9%) for TSH, 67.5% (59.8-75.3%) for fT4, 59.7% (54.4-65.0%) for fT3 and 48.8% (40.6-56.9%) for TPOAb. The genome-wide association study (GWAS) in the discovery cohort identified a novel association between rs2026401 upstream of NCOA3 and TPOAb. GWAS meta-analysis found associations between TPOAb and rs445219, also near NCOA3, and fT3 and rs12687280 near SERPINA7. Gene-based association analysis highlighted SERPINA7 for fT3 and NPAS3 for fT4. CONCLUSION: Our findings resolve former contention regarding heritability estimates of thyroid function traits and TPOAb positivity. GWAS and gene-based association analysis identified variants accounting for a component of this heritability.

Familial Dysalbuminemic Hyperthyroxinemia as a Cause for Discordant Thyroid Function Tests.

INTRODUCTION: Discordant thyroid function tests are routinely encountered in clinical practice. Differential diagnoses include acute thyroxine (T4) ingestion, laboratory interference from heterophilic antibodies, thyroid hormone resistance, thyroid-stimulating hormone (TSH)-secreting pituitary adenomas, and T4 protein binding abnormalities. The impact of abnormal binding proteins may be less recognized since widespread use of free T4 (FT4) assays compared to older total T4 assays. CASE REPORT: A 69-year-old female was referred for assessment of discordant thyroid function tests. Biochemistry since July 2015 showed persistently elevated FT4 levels by immunoassay ranging between 25 to 34 pmol/L with normal or slightly decreased TSH ranging between 0.05 to 2.74 mU/L. The patient was clinically euthyroid on 100 mcg daily of levothyroxine for Hashimoto's thyroiditis. FT4 measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was 19.5 pmol/L. Exome sequencing (confirmed by Sanger sequencing) detected a guanine to adenine substitution at residue 725 of the ALB gene previously associated with dysalbuminemic hyperthyroxinemia. The patient's daughter had similar thyroid function tests and the same genetic variant. FT4 results from 3 different automated immunoassays showed the Roche Cobas and Siemens Centaur platforms to be most affected by the variant, and Abbott Architect had the best agreement with LC-MS/MS. CONCLUSION: Familial dysalbuminemic hyperthyroxinemia is a potential cause of discordant thyroid function tests. Clinicians suspecting protein-binding abnormalities may further investigate using reference methods such as LC-MS/MS and equilibrium dialysis if available. The increasing accessibility of exome sequencing offers a cost-effective method of diagnosing genetic variants that cause discordant thyroid function tests.

Higher Undercarboxylated to Total Osteocalcin Ratio Is Associated With Reduced Physical Function and Increased 15-Year Falls-Related Hospitalizations: The Perth Longitudinal Study of Aging Women.

Evidence from animal models suggests that undercarboxylated osteocalcin (ucOC) is involved in muscle mass maintenance and strength. In humans, the ucOC to total (t)OC ratio may be related to muscle strength and perhaps physical function and falls risk, but data are limited. We tested the hypothesis that ucOC and ucOC/tOC ratio are associated with muscle function (muscle strength and physical function) in older women and 15-year falls-related hospitalizations. Serum tOC and ucOC were assessed in 1261 older women (mean age 75.2 ± 2.7 years) forming the Perth Longitudinal Study of Aging Women (1998 to 2013). Timed-up-and-go (TUG) and grip strength were assessed at baseline and at 5 years. Falls-related hospitalizations (14.5-year follow-up) were captured by the Hospital Morbidity Data Collection, via the Western Australian Data Linkage System. At baseline, women with higher ucOC/tOC ratio (quartile 4) had slower TUG performance compared with quartile 1 (~0.68 seconds, p < .01). Grip strength and 5-year change of TUG and grip were not different (p > .05) between quartiles. Fear of falling limiting house, outdoor, and combined activities was significantly different across quartiles (p < .05). Higher ucOC/tOC was significantly associated with poorer TUG performance at baseline and 5-year change in performance, increased walking aid use, and fear of falling (all p < .05). Higher ucOC was related to lower grip strength at baseline (p < .05) but not 5-year change in strength. Those with the highest ucOC/tOC had greater falls-related hospitalizations (unadjusted log rank, p = .004) remaining significant after adjusting for key variables (hazard ratio [HR] = 1.31, 95% confidence interval [CI] 1.09-1.57, p = .004). We identified a large proportion of older women with high ucOC/tOC ratio who had reduced physical function, including its long-term decline and increased risk of falls-related hospitalizations. Early identification of women at higher risk can enable prevention and intervention strategies to occur, reducing risk for injurious falls. © 2020 American Society for Bone and Mineral Research (ASBMR)..

Calculated globulin as a screening tool for hypogammaglobulinaemia or paraproteins in hospitalized patients.

BACKGROUND: Calculated globulin fraction is derived from the liver function tests by subtracting albumin from the total protein. Since immunoglobulins comprise the largest component of the serum globulin concentration, increased or decreased calculated globulins and may identify patients with hypogammaglobulinaemia or hypergammaglobulinaemia, respectively. METHODS: A retrospective study of laboratory data over 2.5 years from inpatients at three tertiary hospitals was performed. Patients with paired calculated globulins and immunoglobulin results were identified and clinical details reviewed. The results of serum electrophoresis testing were also assessed where available. RESULTS: A total of 4035 patients had paired laboratory data available. A calculated globulin ≤20 g/L (<2nd percentile) had a low sensitivity (5.8%) but good positive predictive value (82.5%) for hypogammaglobulinaemia (IgG ≤5.7 g/L), with a positive predictive value of 37.5% for severe hypogammaglobulinaemia (IgG ≤3 g/L). Paraproteins were identified in 123/291 (42.3%) of patients with increased calculated globulins (≥42 g/L) who also had a serum electrophoresis performed. Significantly elevated calculated globulin ≥50 g/L (>4th percentile) were seen in patients with either liver disease (37%), haematological malignancy (36%), autoimmune disease (13%) or infections (9%). CONCLUSIONS: Calculated globulin is an inexpensive and easily available test that assists in the identification of hypogammaglobulinaemia or hypergammaglobulinaemia which may prompt further investigation and reduce diagnostic delays.

Epigenome-Wide Association Study of Thyroid Function Traits Identifies Novel Associations of fT3 With KLF9 and DOT1L.

CONTEXT: Circulating concentrations of free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) are partly heritable traits. Recent studies have advanced knowledge of their genetic architecture. Epigenetic modifications, such as DNA methylation (DNAm), may be important in pituitary-thyroid axis regulation and action, but data are limited. OBJECTIVE: To identify novel associations between fT3, fT4, and TSH and differentially methylated positions (DMPs) in the genome in subjects from 2 Australian cohorts. METHOD: We performed an epigenome-wide association study (EWAS) of thyroid function parameters and DNAm using participants from: Brisbane Systems Genetics Study (median age 14.2 years, n = 563) and the Raine Study (median age 17.0 years, n = 863). Plasma fT3, fT4, and TSH were measured by immunoassay. DNAm levels in blood were assessed using Illumina HumanMethylation450 BeadChip arrays. Analyses employed generalized linear mixed models to test association between DNAm and thyroid function parameters. Data from the 2 cohorts were meta-analyzed. RESULTS: We identified 2 DMPs with epigenome-wide significant (P < 2.4E-7) associations with TSH and 6 with fT3, including cg00049440 in KLF9 (P = 2.88E-10) and cg04173586 in DOT1L (P = 2.09E-16), both genes known to be induced by fT3. All DMPs had a positive association between DNAm and TSH and a negative association between DNAm and fT3. There were no DMPs significantly associated with fT4. We identified 23 differentially methylated regions associated with fT3, fT4, or TSH. CONCLUSIONS: This study has demonstrated associations between blood-based DNAm and both fT3 and TSH. This may provide insight into mechanisms underlying thyroid hormone action and/or pituitary-thyroid axis function.

Investigating Potential Dose-Response Relationships between Vitamin D Status and Cognitive Performance: A Cross-Sectional Analysis in Middle- to Older-Aged Adults in the Busselton Healthy Ageing Study.

Low vitamin D status has been linked to adverse cognitive outcomes in older adults. However, relationships at higher levels remain uncertain. We aimed to clarify patterns of association between vitamin D status and cognitive performance, using flexible regression methods, in 4872 middle- to older-aged adults (2678 females) from the Busselton Healthy Ageing Study. Cross-sectional associations of serum levels of 25-hydroxyvitamin D (25OHD) and performance in cognitive domains were modelled using linear regression and restricted cubic splines, controlling for demographic, lifestyle, and health factors. Mean ± SD serum 25OHD levels were 78 ± 24 nM/L for women and 85 ± 25 nM/L for men. Increasing levels in women were associated with better global cognition (linear trend, p = 0.023) and attention accuracy (continuity of attention), with improvement in the latter plateauing around levels of 80 nM/L (nonlinear trend, p = 0.035). In men, increasing levels of serum 25OHD were associated with better attention accuracy (linear trend, p = 0.022), but poorer semantic verbal fluency (linear trend, p = 0.025) and global cognition (nonlinear trend, p = 0.015). We identified patterns of association between serum 25OHD levels and cognitive performance that may reflect early dose-response relationships, particularly in women. Longitudinal analyses extending through to older ages may help to clarify the nature, strength, and temporality of these relationships.

In "High-Risk" Infants with Sufficient Vitamin D Status at Birth, Infant Vitamin D Supplementation Had No Effect on Allergy Outcomes: A Randomized Controlled Trial.

Lower vitamin D status at birth and during infancy has been associated with increased incidence of eczema and food allergies. The aim of this study was to investigate the effect of early infancy vitamin D supplementation on allergic disease outcomes in infants at "hereditary risk" of allergic disease, but who had sufficient vitamin D levels at birth. Here, we report the early childhood follow-up to 2.5 years of age of "high-risk" infants who participated in a double-blinded, randomized controlled trial. For inclusion in this trial, late gestation (36-40 weeks) maternal 25-hydroxyvitamin D levels needed to be ≥50 nmol/L. Infants were randomized to either oral vitamin D supplementation of 400 IU/day (n = 97) or a placebo (n = 98) for the first six months of life. Vitamin D levels and allergic disease outcomes were followed up. There were no statistically significant differences in incidence of any medically diagnosed allergic disease outcomes or allergen sensitization rates between the vitamin D-supplemented and placebo groups at either 1 year or at 2.5 years of age. In conclusion, for "allergy high-risk" infants who had sufficient vitamin D status at birth, early infancy oral vitamin D supplementation does not appear to reduce the development of early childhood allergic disease.

In infants with sufficient vitamin D status at birth, vitamin D supplementation does not impact immune development.

BACKGROUND: Low vitamin D levels have been associated with allergic diseases. Vitamin D has potent immunomodulatory properties, but the mechanisms remain unclear. We have investigated the effect of oral vitamin D supplementation on circulating immune cell phenotypes in infants. METHOD: A double-blinded randomised controlled trial was conducted to investigate the effect of oral vitamin D supplementation (400 IU/d) on eczema and immune development. A subset of 78 infants was included in this analysis. Phenotypic analysis of immune cell subsets was performed using flow cytometry. RESULTS: Vitamin D supplementation resulted in median 25(OH)D levels of 80.5 vs 59.5 nmol/L in the placebo group at 3 months of age (P = .002) and 87.5 vs 77 nmol/L at 6 months of age (P = .08). We observed significant changes in immune cell composition from birth (cord blood) to 6 months of age. Vitamin D supplementation did not impact these changes, nor did immune cell composition correlate with plasma 25(OH)D levels. Through exploratory analysis, we identified possible associations with eczema development and increased abundance of naïve CD4- T cells at birth, as well as associations with basophils, iNKT and central memory CD4+ T cells, and altered expression patterns of IgE receptor (FcεR1) on monocytes and dendritic cells with eczema at 6 months. CONCLUSIONS: Vitamin D supplementation in infants who were vitamin D sufficient at birth did not affect developmental changes in immune cells during the first 6 months of life. However, immune cell profiles at birth and at 6 months of age were associated with early life eczema.

Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases.

The pathogenesis of autoimmune thyroid diseases (AITD) is poorly understood and the association between different immune features and the germline variants involved in AITD are yet unclear. We previously observed systemic depletion of IgG core fucosylation and antennary α1,2 fucosylation in peripheral blood mononuclear cells in AITD, correlated with anti-thyroid peroxidase antibody (TPOAb) levels. Fucose depletion is known to potentiate strong antibody-mediated NK cell activation and enhanced target antigen-expressing cell killing. In autoimmunity, this may translate to autoantibody-mediated immune cell recruitment and attack of self-antigen expressing normal tissues. Hence, we investigated the crosstalk between immune cell traits, secreted proteins, genetic variants and the glycosylation patterns of serum IgG, in a multi-omic and cross-sectional study of 622 individuals from the TwinsUK cohort, 172 of whom were diagnosed with AITD. We observed associations between two genetic variants (rs505922 and rs687621), AITD status, the secretion of Desmoglein-2 protein, and the profile of two IgG N-glycan traits in AITD, but further studies need to be performed to better understand their crosstalk in AITD. On the other side, enhanced afucosylated IgG was positively associated with activatory CD335- CD314+ CD158b+ NK cell subsets. Increased levels of the apoptosis and inflammation markers Caspase-2 and Interleukin-1α positively associated with AITD. Two genetic variants associated with AITD, rs1521 and rs3094228, were also associated with altered expression of the thyrocyte-expressed ligands known to recognize the NK cell immunoreceptors CD314 and CD158b. Our analyses reveal a combination of heightened Fc-active IgG antibodies, effector cells, cytokines and apoptotic signals in AITD, and AITD genetic variants associated with altered expression of thyrocyte-expressed ligands to NK cell immunoreceptors. Together, TPOAb responses, dysregulated immune features, germline variants associated with immunoactivity profiles, are consistent with a positive autoreactive antibody-dependent NK cell-mediated immune response likely drawn to the thyroid gland in AITD.

Decreased Immunoglobulin G Core Fucosylation, A Player in Antibody-dependent Cell-mediated Cytotoxicity, is Associated with Autoimmune Thyroid Diseases.

Autoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. Immunoglobulins and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. We investigated associations of total circulating IgG and peripheral blood mononuclear cells glycosylation with AITD and the influence of genetic background in a case-control study with several independent cohorts and over 3,000 individuals in total. The study revealed an inverse association of IgG core fucosylation with TPOAb and AITD, as well as decreased peripheral blood mononuclear cells antennary α1,2 fucosylation in AITD, but no shared genetic variance between AITD and glycosylation. These data suggest that the decreased level of IgG core fucosylation is a risk factor for AITD that promotes antibody-dependent cell-mediated cytotoxicity previously associated with TPOAb levels.

Changes in Thyroid Function Across Adolescence: A Longitudinal Study.

OBJECTIVE: There are no large, longitudinal studies of thyroid function across adolescence. The aims of this study were to examine longitudinal trends in thyrotropin (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) and determine age-specific reference ranges. METHODS: Thyroid function was assessed in 3415 participants in the Brisbane Longitudinal Twin Study at ages 12, 14, and 16, using the Abbott ARCHITECT immunoassay. Longitudinal analyses were adjusted for body mass index and puberty. RESULTS: In girls, mean fT4 (± SE) increased between age 12 and 14 (by 0.30 ±â€…0.08 pmol/L; P < 0.001), while remaining unchanged in boys; from age 14 to 16, fT4 increased in both girls (by 0.42 ±â€…0.07 pmol/L; P < 0.001) and boys (0.64 ±â€…0.07 pmol/L, P < 0.001). There was a slight increase in fT3 from age 12 to 14 years in girls (by 0.07 ±â€…0.03 pmol/L; P = 0.042), with a more marked increase in boys (0.29 ±â€…0.03 pmol/L; P < 0.001), followed by a decrease from age 14 to 16 in both sexes (girls, by 0.53 ±â€…0.02 pmol/L; P < 0.001; boys, by 0.62 ±â€…0.03 pmol/L; P < 0.001). From age 12 to 14, TSH showed no significant change in girls or boys, then levels increased from age 14 to 16 in both sexes (in girls, by 4.9%, 95% CI: 2.4%-10.3%, P = 0.020; in boys, by 7.2%, 95% CI: 3.0%-11.6%, P = 0.001). Reference ranges differed substantially from adults, particularly for fT4 and fT3. CONCLUSIONS: Thyroid function tests in adolescents display complex, sexually dimorphic patterns. Implementation of adolescence-specific reference ranges may be appropriate.