Severe neurodevelopmental phenotype, diagnostic, and treatment challenges in patients with SECISBP2 deficiency.

Purpose: Defects in the gene encoding selenocysteine insertion sequence binding protein 2, SECISBP2, result in global impaired selenoprotein synthesis manifesting a complex syndrome with characteristic serum thyroid function tests due to impaired thyroid hormone metabolism. Knowledge about this multisystemic defect remains limited.

Methods: Genetic and laboratory investigations were performed in affected members from 6 families presenting with short stature and failure to thrive.

Combined Levothyroxine and Propylthiouracil Treatment in Children with Monocarboxylate Transporter 8 Deficiency: A Multicenter Case Series of 12 Patients.

To evaluate the combined administration of propylthiouracil (PTU) and levothyroxine (LT4) in managing monocarboxylate transporter 8 (MCT8) deficiency and identify optimal therapeutic dosages. This multicenter case series involved 12 male patients with MCT8 deficiency whose parents/guardians consented to PTU and LT4 treatment. Data were collected from January 2008 to June 24, 2024.

STR mutations on chromosome 15q cause thyrotropin resistance by activating a primate-specific enhancer of MIR7-2/MIR1179.

Thyrotropin (TSH) is the master regulator of thyroid gland growth and function. Resistance to TSH (RTSH) describes conditions with reduced sensitivity to TSH. Dominantly inherited RTSH has been linked to a locus on chromosome 15q, but its genetic basis has remained elusive.

Impaired T3 uptake and action in MCT8-deficient cerebral organoids underlie Allan-Herndon-Dudley syndrome.

Patients with mutations in the thyroid hormone (TH) cell transporter monocarboxylate transporter 8 (MCT8) gene develop severe neuropsychomotor retardation known as Allan-Herndon-Dudley syndrome (AHDS). It is assumed that this is caused by a reduction in TH signaling in the developing brain during both intrauterine and postnatal developmental stages, and treatment remains understandably challenging. Given species differences in brain TH transporters and the limitations of studies in mice, we generated cerebral organoids (COs) using human induced pluripotent stem cells (iPSCs) from MCT8-deficient patients.

Effect of the Fetal THRB Genotype on the Placenta.

Context: Pregnant women with mutations in the thyroid hormone receptor beta (THRB) gene expose their fetuses to high thyroid hormone (TH) levels shown to be detrimental to a normal fetus (NlFe) but not to an affected fetus (AfFe). However, no information is available about differences in placental TH regulators.

Objective: To investigate whether there are differences in placentas associated with a NlFe compared with an AfFe, we had the unique opportunity to study placentas from 2 pregnancies of the same woman with THRB mutation G307D.

Evaluation of independent risk factors associated with surgical site infections from caesarean section.

Background: The present study assessed factors associated with the risk of surgical site infections (SSI) after a caesarean section (C-section).

Methods: Data were collected in 1682 women undergoing elective (53.9%) and emergency (46.

Reduction of adverse outcomes from cesarean section by surgical-site infection prevention care bundles in maternity.

Objective: To reduce average surgical-site infection (SSI) rates to less than 7.5%, as well as other complications by incrementally implementing an SSI prevention care bundle in maternity: (1) ChloraPrep; (2) PICO dressings, performing elective cesarean sections in a main theater rather than a labor ward and warming blankets; (3) vaginal cleansing; and (4) Hibiscrub.

Methods: In this prospective cohort study, the association between categorical variables was assessed by χ tests, temporal trends in the monthly percentage change of SSI were measured using the Joinpoint Regression Program v4.

Graves' disease and papillary thyroid carcinoma: case report and literature review of a single academic center.

Background: Graves' disease (GD) and papillary thyroid cancer (PTC) can be concomitant. The existence of a link between these entities has long been investigated, but a clear correlation hasn't been established. We report a case of GD resistant to medical treatment in which surgery revealed unsuspected PTC and we aim to study the prevalence of PTC in Graves' disease, its clinical characteristics and review of the literature.

A Novel Pathogenic Variant in Leads to Familial Congenital Hypothyroidism.

We report a 10-month-old girl with familial congenital hypothyroidism harboring a novel heterozygous pathogenic variant in the paired DNA-binding domain of (NM_003466:c.110T>C:p.Leu37Pro).

AAV9-MCT8 Delivery at Juvenile Stage Ameliorates Neurological and Behavioral Deficits in a Mouse Model of MCT8-Deficiency.

Allan-Herndon-Dudley syndrome (AHDS) is a severe psychomotor disability disorder that also manifests characteristic abnormal thyroid hormone (TH) levels. AHDS is caused by inactivating mutations in monocarboxylate transporter 8 (MCT8), a specific TH plasma membrane transporter widely expressed in the central nervous system (CNS). mutations cause impaired transport of TH across brain barriers, leading to insufficient neural TH supply.

Severe Resistance to Thyroid Hormone Beta in a Patient with Athyreosis.

We report a patient with congenital hypothyroidism due to athyreosis complicated by a heterozygous thyroid hormone receptor beta ( gene mutation (R320L), resulting in a severe resistance to thyroid hormone beta phenotype. The proband inherited the mutant allele from his father, presenting a very mild phenotype. While the precise reason for this discrepancy remains unknown, we postulate the possibility of mutation and mosaicism in the father.

Extended Absorption of Liothyronine from Poly-Zinc-Liothyronine: Results from a Phase 1, Double-Blind, Randomized, and Controlled Study in Humans.

L-triiodothyronine (LT3) has been increasingly used in combination with levothyroxine in the treatment of hypothyroidism. A metal coordinated form of LT3, known as poly-zinc-liothyronine (PZL), avoided in rats the typical triiodothyronine (T3) peak seen after oral administration of LT3. To evaluate in healthy volunteers (i) the pharmacokinetics (PK) of PZL-derived T3 after a single dose, (ii) the pharmacodynamics of PZL-derived T3, (iii) incidence of adverse events, and (iv) exploratory analysis of the sleep patterns after LT3, PZL, or placebo (PB) administration.

Dietary Selenium Deficiency Partially Mimics the Metabolic Effects of Arsenic.

Chronic arsenic exposure via drinking water is associated with diabetes in human pop-ulations throughout the world. Arsenic is believed to exert its diabetogenic effects via multiple mechanisms, including alterations to insulin secretion and insulin sensitivity. In the past, acute arsenicosis has been thought to be partially treatable with selenium supplementation, though a potential interaction between selenium and arsenic had not been evaluated under longer-term exposure models.

Novel Gene Mutation Acting as Phenotype Modifier for Novel Compound Heterozygous Gene Mutations Causing Congenital Hypothyroidism.

A family with congenital hypothyroidism was identified with two novel deleterious compound heterozygous thyroid peroxidase () mutations (, and ). Serum thyroid tests showed higher-than-expected serum-free thyroxine (T4) relative to TT3, while reverse triiodothyronine (rT3) was also elevated. Two siblings manifested a more severe phenotype of developmental delay compared with another sibling and were found to harbor an additional novel heterozygous deleterious iodothyronine deiodinase 1 () mutation ().

Early Diagnosis and Treatment of an Infant with a Novel Thyroid Hormone Receptor α Gene (pC380SfsX9) Mutation.

Resistance to thyroid hormone alpha (RTHα) is caused by mutations in thyroid hormone receptor α (). Little is known about the natural history and treatment of RTHα, and diagnosis before the age of 1 year has not been previously reported. A heterozygous mutation (pC380SfsX9) was identified in a 10-month-old female investigated for developmental delay, hypotonia, macrocephaly, and severe constipation.

Prenatal Treatment of Thyroid Hormone Cell Membrane Transport Defect Caused by Gene Mutation.

Mutations of the thyroid hormone (TH)-specific cell membrane transporter, (), produce an X-chromosome-linked syndrome of TH deficiency in the brain and excess in peripheral tissues. The clinical consequences include brain hypothyroidism causing severe psychoneuromotor abnormalities (no speech, truncal hypotonia, and spastic quadriplegia) and hypermetabolism (poor weight gain, tachycardia, and increased metabolism, associated with high serum levels of the active TH, T3). Treatment in infancy and childhood with TH analogues that reduce serum triiodothyronine (T3) corrects hypermetabolism, but has no effect on the psychoneuromotor deficits.

Human Type 1 Iodothyronine Deiodinase () Mutations Cause Abnormal Thyroid Hormone Metabolism.

Iodothyronine deiodinase-1 (D1) selenoenzyme regulates the systemic supply of active thyroid hormone (TH). Transient decrease in D1 enzymatic activity is clinically relevant and adaptive in nonthyroidal illness such as fasting or acute illness. However, gene defects have not been reported in humans.

Clinical and Molecular Analysis in 2 Families With Novel Compound Heterozygous SBP2 (SECISBP2) Mutations.

Context: Selenocysteine insertion sequence binding protein 2 (SECISBP2, SBP2) is an essential factor for selenoprotein synthesis. Individuals with SBP2 defects have characteristic thyroid function test (TFT) abnormalities resulting from deficiencies in the selenoenzymes deiodinases. Eight families with recessive SBP2 gene mutations have been reported to date.

A Novel G385E Variant in the Cold Region of the T3-Binding Domain of Thyroid Hormone Receptor Beta Gene and Investigations to Assess Its Clinical Significance.

Background: Resistance to thyroid hormone beta (RTHβ) is characterized by elevated thyroid hormone and unsuppressed thyroid-stimulating hormone (TSH), caused by thyroid hormone receptor beta gene () defects. Most mutations producing RTHβ phenotype are located in CG-rich regions of , encoding the T3-binding and hinge domains of the receptor. However, a region encompassing codons 384-425 is virtually devoid of RTHβ-causing mutations, termed "cold region.

Central Congenital Hypothyroidism Caused by a Novel Mutation, C47W, in the Cysteine Knot Region of TSHβ.

Background: Isolated central congenital hypothyroidism (ICCH) is a rare form (1:50,000 newborns) of congenital hypothyroidism, which can present with growth and neuropsychological retardation. Unlike the more common primary CH (1:1,500-1:4,000), which presents on newborn screening with elevated serum thyroid-stimulating hormone (TSH) and low thyroxine (T4) and triiodothyronine (T3), ICCH presents with low TSH and low thyroid hormone levels. ICCH, therefore, may be missed in most newborn screens that are based only on elevated TSH.

Nonautoimmune Hyperthyroidism Caused by a Somatic Mosaic Mutation Involving Part of the Thyroid Gland.

Nonautoimmune hyperthyroidism caused by activating mutations in the gene is a rare condition. In this study, we report a five-year-old girl diagnosed with nonautoimmune hyperthyroidism and tall stature harboring a somatic mosaic gain-of-function mutation in the gene (NM_080425.3: c.