Effect of Thyroid Status Modulation on Pituitary and Peripheral Hormone Concentrations in Healthy Older Subjects.

Introduction: Depending on age, sex, and familial longevity, alterations in thyroid status occur frequently and often co-occur with differences in other hormonal axes. However, studies that explore the effects of thyroid status modulation on other hormonal axes remain scarce. We aimed to determine the effects of thyroid status modulation on prolactin, IGF-1, cortisol, LH, testosterone, and SHBG levels.

External quality assessment-based tumor marker harmonization simulation; insights in achievable harmonization for CA 15-3 and CEA.

Objectives: CA 15-3 and CEA are tumor markers used in routine clinical care for breast cancer and colorectal cancer, among others. Current measurement procedures (MP) for these tumor markers are considered to be insufficiently harmonized. This study investigated the achievable harmonization for CA 15-3 and CEA by using an simulation of external quality assessment (EQA) data from multiple EQA programs using patient-pool based samples.

Impact of a Public Health Emergency on Behavior, Stress, Anxiety and Glycemic Control in Patients With Pancreas or Islet Transplantation for Type 1 Diabetes.

A public health emergency such as the COVID-19 pandemic has behavioral, mental and physical implications in patients with type 1 diabetes (T1D). To what extent the presence of a transplant further increases this burden is not known. Therefore, we compared T1D patients with an islet or pancreas transplant (β-cell Tx; = 51) to control T1D patients ( = 272).

The addition of the sFlt-1/PlGF ratio to the protein/creatinine ratio in multiple pregnancy: Post-hoc analysis of the PREPARE cohort study.

Objective: To assess the predictive accuracy of the sFlt-1/PlGF ratio cut-off 38 in addition to the standard-of-care spot urine protein/creatinine ratio (PCr) for multiple pregnancies in women with suspected pre-eclampsia.

Study Design: Post-hoc analysis of a prospective cohort study.

Main Outcome Measures: Primary outcome was the occurrence of pre-eclampsia in one and four weeks after presentation with suspected pre-eclampsia.

Investigating the Current Harmonization Status of Tumor Markers Using Global External Quality Assessment Programs: A Feasibility Study.

Background: The harmonization status of most tumor markers (TMs) is unknown. We report a feasibility study performed to determine whether external quality assessment (EQA) programs can be used to obtain insights into the current harmonization status of the tumor markers α-fetoprotein (AFP), prostate specific antigen (PSA), carcinoembryonic antigen (CEA), cancer antigen (CA)125, CA15-3 and CA19-9.

Methods: EQA sample results provided by 6 EQA providers (INSTAND [Germany], Korean Association of External Quality Assessment Service [KEQAS, South Korea], National Center for Clinical Laboratories [NCCL, China], United Kingdom National External Quality Assessment Service [UK NEQAS, United Kingdom], Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek [SKML, the Netherlands], and the Royal College of Pathologists of Australasia Quality Assurance Programs [RCPAQAP, Australia]) between 2020 and 2021 were used.

Incidence and Determinants of Spontaneous Normalization of Subclinical Hypothyroidism in Older Adults.

Context: With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown.

Objective: To investigate incidence and determinants of spontaneous normalization of TSH levels in older adults with subclinical hypothyroidism.

Clinical value and cost analysis of the sFlt-1/PlGF ratio in addition to the spot urine protein/creatinine ratio in women with suspected pre-eclampsia: PREPARE cohort study.

Background: This study investigated the clinical value of adding the sFlt-1/PlGF ratio to the spot urine protein/creatinine ratio (PCr) in women with suspected pre-eclampsia.

Methods: This was a prospective cohort study performed in a tertiary referral centre. Based on the combination of PCr (< 30) and sFlt-1/PlGF (≤38) results, four groups were described: a double negative result, group A-/-; a negative PCr and positive sFlt-1/PlGF, group B-/+; a positive PCr and negative sFlt-1/PlGF, group C+/-; and a double positive result, group D+/+.

Screening for thyroid dysfunction with free T4 instead of thyroid stimulating hormone (TSH) improves efficiency in older adults in primary care.

Subclinical hypothyroidism (SCHT) is defined as a consistently elevated thyroid stimulating hormone (TSH) with a free T4 (fT4) within the reference range. This diagnosis may lead to additional monitoring, levothyroxine therapy and increased patient concerns, despite lack of evidence of treatment benefit in older adults. In order to avoid this diagnosis, we evaluated the efficiency of fT4-based screening for thyroid dysfunction, in older adults in primary care and compared it with TSH-based screening.

Familial longevity is associated with lower baseline bone turnover but not differences in bone turnover in response to rhTSH.

Context: Offspring from long-lived families have a different thyroid status than controls, characterised by higher circulating levels of thyroid stimulating hormone (TSH) and similar levels of thyroid hormone. Expression of the TSH receptor has previously been observed on various extrathyroidal tissues, including bone. However, potential physiological consequences of differences in circulating TSH as observed in familial longevity on bone tissue remain unclear.

Adrenal Vein Sampling in a Patient With Primary Hyperaldosteronism and Severe Contrast Allergy.

We report on a case of a 50-year-old female patient with primary hyperaldosteronism, in whom adrenal venous sampling was required to differentiate between unilateral and bilateral disease. Because of a history of severe allergy to iodinated contrast media, premedication with glucocorticoids was indicated. Exogenous glucocorticoids, however, can affect measurements of serum cortisol.

Increased stress, weight gain and less exercise in relation to glycemic control in people with type 1 and type 2 diabetes during the COVID-19 pandemic.

Introduction: Lockdown measures have a profound effect on many aspects of daily life relevant for diabetes self-management. We assessed whether lockdown measures, in the context of the COVID-19 pandemic, differentially affect perceived stress, body weight, exercise and related this to glycemic control in people with type 1 and type 2 diabetes.

Research Design And Methods: We performed a short-term observational cohort study at the Leiden University Medical Center.

Circulating Thyroid Hormone Profile in Response to a Triiodothyronine Challenge in Familial Longevity.

Context: Familial longevity is associated with higher circulating levels of thyrotropin (TSH), in the absence of differences in circulating thyroid hormones, and a lower thyroid responsivity to TSH, as previously observed in the Leiden Longevity Study (LLS). Further mechanisms underlying these observations remain unknown.

Objective: We hypothesized that members from long-lived families (offspring) have higher thyroid hormone turnover or less negative feedback effect on TSH secretion compared to controls.

Familial Longevity is Associated with an Attenuated Thyroidal Response to Recombinant Human Thyroid Stimulating Hormone.

Context: Longevity is associated with higher circulating levels of TSH in the absence of differences in circulating thyroid hormones (TH), as previously observed in F2 members of long-lived families (F2-LLS) and their partners (F2-Con). The mechanism underlying this observed difference remains unknown.

Objective: We hypothesized that the thyroid gland of members from long-lived families are less responsive to TSH stimulation, thereby requiring higher circulating TSH levels to maintain adequate TH levels.

Associations of Elevated Antithyroperoxidase Antibodies with Thyroid Function, Survival, Functioning, and Depressive Symptoms in the Oldest Old: The Leiden 85-plus Study.

Elevated levels of antithyroperoxidase antibodies (TPOAbs) have been associated with progression of subclinical thyroid dysfunction, extrathyroidal diseases, and decrease in functional status. However, TPOAb as determinant of future thyroid dysfunction and other clinical outcomes has not been studied well for adults aged 85 years and over. This study aimed to assess associations of TPOAb levels with thyroid function, survival, physical function, disability in activities of daily living (ADL), cognitive function, and depressive symptoms in the oldest old.

Men Have a Stronger Monocyte-Derived Cytokine Production Response upon Stimulation with the Gram-Negative Stimulus Lipopolysaccharide than Women: A Pooled Analysis Including 15 Study Populations.

The incidence of bacterial infections and sepsis, as well as the mortality risk from sepsis, is sex specific. These clinical findings have been attributed to sex differences in immune responsiveness. The aim of the present study was to investigate sex differences in monocyte-derived cytokine production response upon stimulation with the gram-negative stimulus lipopolysaccharide (LPS) using cytokine data from 15 study populations.

Endogenous sex hormones and risk of venous thromboembolism in young women.

Background: The risk of venous thromboembolism (VTE) in young women can predominantly be attributed to exogenous hormone use. The influence of (abnormalities in) endogenous sex hormones, as in polycystic ovary syndrome (PCOS) or primary ovarian insufficiency (POI), on VTE risk is uncertain.

Objectives: Th assess the association between endogenous sex hormone levels and VTE risk.

Validation of the blood gas analyzer for pH measurements in IVF culture medium: Prevent suboptimal culture conditions.

Measurement of pH in IVF-media using the blood gas analyzer (BGA) requires validation, because IVF-media is outside the intended scope of the BGA. To determine whether the Siemens Rapidpoint 500 BGA is suitable for pH measurements in IVF-media this study will validate the BGA and assess its accuracy. In this method comparison study, the pH of over three hundred IVF-media samples was measured with the BGA and a pH electrode (Hanna pH checker).

Increased cardiovascular disease risk in women with a history of recurrent miscarriage.

Introduction: Cardiovascular disease is the leading cause of death in women. Observational studies suggest that women with a history of recurrent miscarriage have an increased risk of cardiovascular disease.

Material And Methods: Women who visited the recurrent miscarriage clinic at Leiden University Medical Center between 2000 and 2010 and who had their third consecutive miscarriage before the age of 31 years, were invited to participate in this follow-up study (between 2012 and 2014).

Determinants of Advanced Bone Age in Childhood Obesity .

Background: Childhood obesity is associated with advanced bone age (BA). Previous studies suggest that androgens, oestrogens, sex hormone-binding globulin, and insulin are responsible for this phenomenon, but results are contradictory and might be biased by confounders. We aim to elucidate this matter by applying a multivariate approach.

Familial Longevity Is Not Associated with Major Differences in the Hypothalamic-Pituitary-Gonadal Axis in Healthy Middle-Aged Men.

Context: A trade-off between fertility and longevity possibly exists. The association of the male hypothalamic-pituitary-gonadal (HPG) axis with familial longevity has not yet been investigated.

Objective: To study 24-h hormone concentration profiles of the HPG axis in men enriched for familial longevity and controls.

Growth hormone secretion is diminished and tightly controlled in humans enriched for familial longevity.

Reduced growth hormone (GH) signaling has been consistently associated with increased health and lifespan in various mouse models. Here, we assessed GH secretion and its control in relation with human familial longevity. We frequently sampled blood over 24 h in 19 middle-aged offspring of long-living families from the Leiden Longevity Study together with 18 of their partners as controls.

IGSF1 Deficiency: Lessons From an Extensive Case Series and Recommendations for Clinical Management.

Context: Mutations in the immunoglobulin superfamily, member 1 (IGSF1) gene cause the X-linked IGSF1 deficiency syndrome consisting of central hypothyroidism, delayed pubertal testosterone rise, adult macroorchidism, variable prolactin deficiency, and occasionally transient partial GH deficiency. Since our first reports, we discovered 20 new families with 18 new pathogenic IGSF1 mutations.

Objective: We aimed to share data on the largest cohort of patients with IGSF1 deficiency to date and formulate recommendations for clinical management.