Environmental chemicals have been indicated to cause disruption of thyroid homeostasis in human populations. However, previous studies mostly focused on single group of chemicals. Herein, we investigate the independent and combined effects of multiple pollutants on thyroid homeostasis, including thyroid-stimulating hormone (TSH), total and free thyroxine (tT4 and fT4) and total and free triiodothyronine (tT3 and fT3) in elderly people. These environmental pollutants (n = 144) are from ten categories, including phenols, parabens, perfluoroalkyl substances (PFASs), polychlorinated biphenyls (PCBs), phthalate esters (PAEs), polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), organophosphate pesticides (OPPs), synthetic pyrethroids (SPs), herbicides, and metals. Few studies have evaluated the health risks of these 144 chemicals, especially their joint effects. In single-pollutant evaluations, multiple linear regression (MLR) models were used to estimate the independent associations between multiple exposures and thyroid biomarkers. In multi-pollutant evaluations, elastic net regression and Bayesian kernel machine regression (BKMR) models were used to estimate the combined associations. The MLR models showed that 41 chemicals were significantly related to THs levels. BKMR models revealed the most important chemical groups: metals for TSH, PAHs, SPs and PCBs for tT4, herbicides and SPs for tT3. This study will contribute to the understanding of multipollutant exposure and help prioritize specific chemical groups related to thyroid hormone disruption.

2024-02-20·The Journal of clinical endocrinology and metabolism

Association of Gestational Free and Total Triiodothyronine With Gestational Hypertension, Preeclampsia, Preterm Birth, and Birth Weight: An Individual Participant Data Meta-analysis

Article

作者: Korevaar, Tim I M ; Chen, Liangmiao ; Walsh, John P ; Chaker, Layal ; Brown, Suzanne J ; Pearce, Elizabeth N ; Suvanto, Eila ; Bassols, Judit ; Aminorroaya, Ashraf ; Auvinen, Juha ; Guxens, Mònica ; Lu, Xuemian ; Vaidya, Bijay ; Hattersley, Andrew T ; Huang, Kun ; Kishi, Reiko ; Feldt-Rasmussen, Ulla ; Fernández-Somoano, Ana ; Chatzi, Leda ; Carrasco, Paula ; Kianpour, Maryam ; Osinga, Joris A J ; Grineva, Elena N ; Lertxundi, Aitana ; Itoh, Sachiko ; Vasukova, Elena A ; Nicolaides, Kypros H ; Bramer, Wichor M ; López-Bermejo, Abel ; Männistö, Tuija ; Peeters, Robin P ; Oken, Emily ; Alexander, Erik K ; Bliddal, Sofie ; Derakhshan, Arash ; Tao, Fang-Biao ; Ashoor, Ghalia ; Popova, Polina V ; Vafeiadi, Marina

Abstract:

Context:

Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to thyroid-stimulating hormone and free thyroxine, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes.

Objective:

To investigate the associaiton of gestational free or total T3 (FT3 or TT3) with adverse obstetric outcomes.

Methods:

We collected individual participant data from prospective cohort studies on gestational FT3 or TT3, adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age [SGA], and large for gestational age [LGA]), and potential confounders. We used mixed-effects regression models adjusting for potential confounders.

Results:

The final study population comprised 33 118 mother–child pairs of which 27 331 had data on FT3 and 16 164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = .0069) and a J-shaped association with the risk of gestational hypertension (P = .029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 1.20, 95% CI 1.08 to 1.33; P = .0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR 0.72, 95% CI 0.55 to 0.94; P = .018). TT3 but not FT3 was positively associated with birth weight (mean difference per 1 SD increase in TT3 12.8, 95% CI 6.5 to 19.1 g, P < .0001) but there was no association with SGA or LGA.

Conclusion:

This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes that form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.

2023-07-14·The Journal of clinical endocrinology and metabolism

The Use of Levothyroxine Absorption Tests in Clinical Practice.

Article

作者: Caron, Philippe ; Declèves, Xavier

Although levothyroxine (LT4) is a widely prescribed drug, more than 30% of LT4-treated patients fail to achieve the recommended serum level of thyrotropin with a body weight-based dose of LT4. An LT4 absorption test (LT4AT) is part of the workup for confirming normal LT4 absorption or diagnosing malabsorption. We searched PubMed with the terms levothyrox*, L-T4, LT4, TT4, FT4, FT3, TT3, test, loading, uptake, absorp*, "absorb*, bioavailab*, bioequiv* malabsorb*, and pseudomalabsorb*. A total of 43 full-text publications were analyzed. The published procedures for LT4AT differ markedly in the test dose, formulation, test duration, frequency of blood collection, analyte (total thyroxine [TT4] or free thyroxine [FT4]), metric (absolute or relative peak or increment, or area under the curve) and the threshold for normal absorption. In a standardized LT4AT for routine use, the physician could advise the patient to not consume food, beverages, or medications the morning of the test; administer 1000 µg of LT4 in the patient's usual formulation as the test dose; ensure that the patient is supervised throughout the LT4AT; perform a 4-hour test, with hourly blood samples; assay FT4; and consider that normal LT4 absorption corresponds to an FT4 increment of more than 0.40 ng/dL (5.14 pmol/L) or a TT4 increment of more than 6 μg/dL (77.23 nmol/L) for a test dose of at least 300 µg, or a percentage TT4 absorption of more than 60%. If the test indicates abnormal LT4 absorption, the physician can increase the LT4 dose, change the formulation or administration route, and/or refer the patient to a gastroenterologist.

项与 TT-3 相关的新闻（医药）

2024-04-12

·FierceBiotech

Portage Biotech hints at potential closure as it halts programs, hunts for strategic options

Portage Biotech said in January that it was halting development of its iNKT programs. Portage Biotech is putting the clamps on existing work to save cash as it prioritizes a hunt for strategic alternatives. The company said Friday that after a review of the financing market and the amount of spending necessary to advance its pipeline, the search for strategic alternatives would commence. In the meantime, Portage is halting enrollment in a clinical trial testing both its adenosine 2A inhibitor PORT-6 and its adenosine 2B inhibitor PORT-7. Portage bought both assets from Tarus Therapeutics less than two years ago. Portage is considering anything from securing partners for its assets to a merger, sale or a full wind-down of the company. The biotech has no timetable for finding a path forward. About three months ago, Portage said it was all in on prioritizing development of its adenosine inhibitors, electing to pause further development of an iNKT program. The biotech had been expecting to provide interim data from a phase 1a trial testing PORT-6 in patients with solid tumors at this year’s American Society of Clinical Oncology annual meeting in June, with final data teased for November. But the company had little money to work with, entering 2024 with just $5.3 million in cash on hand, according to a full-year earnings report from February. Still, Portage affirmed at the time that it intended to press ahead with its adenosine work. Those assets were acquired from Tarus back in July 2022, with Portage handing over 2.4 million shares and taking on $3 million in liabilities. In addition to PORT-6 and PORT-7, Portage took hold of a dual adenosine inhibitor, PORT-8, and a preclinical candidate to treat gastrointestinal tumors, dubbed PORT-9. But neither PORT-8 or PORT-9 are still in development, according to Portage’s pipeline.