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.

Eyes on the Prize: Decoding the Ophthalmic Product Regulations and Intricacies of the U.S. Food and Drug Administration Approval.

The dynamic and continuously evolving field of ophthalmology necessitates rigorous regulatory oversight in the United States. This review outlines the multifaceted Food and Drug Administration's (FDA) approval process for ophthalmic products, detailing the classifications, pathways, and regulatory compliance for devices, drugs, biologics, and combination products. Particular emphasis is placed on distinct frameworks for Class I, II, and III devices, as well as regulations for drugs, biologics, and combination products.

Combined Use of RT-qPCR and NGS for Identification and Surveillance of SARS-CoV-2 Variants of Concern in Residual Clinical Laboratory Samples in Miami-Dade County, Florida.

Over the course of the COVID-19 pandemic, SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and immune escape capabilities, such as Delta and Omicron, have triggered waves of new COVID-19 infections worldwide, and Omicron subvariants continue to represent a global health concern. Tracking the prevalence and dynamics of VOCs has clinical and epidemiological significance and is essential for modeling the progression and evolution of the COVID-19 pandemic. Next generation sequencing (NGS) is recognized as the gold standard for genomic characterization of SARS-CoV-2 variants, but it is labor and cost intensive and not amenable to rapid lineage identification.

Congenital Hypothyroidism in Two Sudanese Families Harboring a Novel Iodotyrosine Deiodinase Mutation (IYD R279C).

Congenital hypothyroidism due to defects in iodotyrosine deiodinase has variable phenotypes and can present as hypothyroid or with normal thyroid testing. Whole exome sequencing was performed in individuals from two families originating from different regions of Sudan. Mass spectrometry of urine and serum iodotyrosines was performed on subjects from both families.

Automation of mass vaccination against COVID-19 at an academic health center.

As vaccines against COVID-19 became available for distribution, the University of Miami addressed several challenges to facilitate vaccine allocation to the highest risk employees, patients, and students. Advanced use of technology allowed for the automation of key processes in the mass vaccination effort, which expedited vaccine outreach and scheduling, while maintaining routine delivery of healthcare services. The University's employees were initially prioritized for vaccination; employees who opted in were stratified into 5 vaccine administration phases.

Rivalry between human ideation and virus mutation: two competing means of sustainability.

For the first time in human history, obtaining a COVID-19 vaccine has become essential for the sustainability of our species. As an amazing product of collective ideation, remarkably safe and efficient vaccines have been invented, tested, distributed, and administered to the population on a voluntary basis. The fast-mutating individual behavior of the virus is probably guided by a similar goal of the sustainability of the species.

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 ().

Measurement of Reverse Triiodothyronine Level and the Triiodothyronine to Reverse Triiodothyronine Ratio in Dried Blood Spot Samples at Birth May Facilitate Early Detection of Monocarboxylate Transporter 8 Deficiency.

Monocarboxylate transporter 8 (MCT8) deficiency is an X-chromosome-linked neurodevelopmental disorder resulting from impaired thyroid hormone transport across the cell membrane. The diagnosis of MCT8 deficiency is typically delayed owing to the late appearance of signs and symptoms as well as the inability of standard biomarkers of neonatal screening to provide early detection. In this study, we report, for the first time, the ability to detect MCT8 deficiency at birth using dried blood spot (DBS) samples.

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.

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.

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.

Insertion of an Alu Element in Thyroglobulin Gene as a Novel Cause of Congenital Hypothyroidism.

The () gene encodes a protein required for thyroid hormone synthesis and iodine storage. Deleterious mutations produce congenital hypothyroidism (CH) often presenting with undetectable serum TG. Alu elements, common throughout the human genome, have a poly(dA) region in the 3' end of the strand.

Increased Prevalence of TG and TPO Mutations in Sudanese Children With Congenital Hypothyroidism.

Context: Congenital hypothyroidism (CH) is due to dyshormonogenesis in 10% to 15% of subjects worldwide but accounts for 60% of CH cases in the Sudan.

Objective: To investigate the molecular basis of CH in Sudanese families.

Design: Clinical phenotype reporting and serum thyroid hormone measurements.

Sorting Variants of Unknown Significance Identified by Whole Exome Sequencing: Genetic and Laboratory Investigations of Two Novel Variants.

Mutations in the cell membrane thyroid hormone (TH) transporter monocarboxylate transporter (MCT) 8 produce severe neuropsychomotor defects and characteristic thyroid function test (TFT) abnormalities. Two children with mild neurological phenotypes and normal TFTs were found to harbor gene variants of unknown significance (VUS), MCT8-R388Q that occurred and MCT8-Q212E. Normal TH transport and action in fibroblasts of MCT8-R388Q was demonstrated in a novel nonradioactive functional assay measuring the intracellular TH availability after L-T3 treatment.

Congenital Hypothyroidism due to Oligogenic Mutations in Two Sudanese Families.

Dyshormonogenic congenital hypothyroidism (CH) generally results from biallelic defects in thyroid hormone synthesis genes. Whole exome sequencing allows easier identification of multiple gene defects. Two Sudanese families with CH resulting from oligogenic defects identified by whole exome sequencing are presented.

A Novel Missense Mutation in the SLC5A5 Gene in a Sudanese Family with Congenital Hypothyroidism.

Thyroid hormone synthesis requires the presence of iodide. The sodium-iodide symporter (NIS) is a glycoprotein that mediates the active uptake of iodide from the blood stream into the thyroid grand. NIS defects due to SLC5A5 gene mutations are known to cause congenital hypothyroidism (CH).

Prenatal Diagnosis of Resistance to Thyroid Hormone and Its Clinical Implications.

Context: Resistance to thyroid hormone-β (RTH-β) is an autosomal dominant disorder characterized by reduced sensitivity of target tissues to thyroid hormones (THs). Individuals with RTH-β have high TH levels usually due to mutations in the TH receptor-β (THRB) gene. The management of RTH-β during pregnancy is challenging, as wild-type (WT) fetuses born to RTH-β mothers have low birth weight and suppressed postnatal thyroid-stimulating hormone (TSH), due to intrauterine exposure to excess TH.

An Essential Physiological Role for MCT8 in Bone in Male Mice.

T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter (MCT) 8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone.

Fetal Exposure to High Maternal Thyroid Hormone Levels Causes Central Resistance to Thyroid Hormone in Adult Humans and Mice.

Context: Fetuses exposed to the high thyroid hormone (TH) levels of mothers with resistance to thyroid hormone beta (RTH-β), due to mutations in the THRB gene, have low birth weight and suppressed TSH.

Objective: Determine if such exposure to high TH levels in embryonic life has a long-term effect into adulthood.

Design: Observations in humans with a parallel design on animals to obtain a preliminary information regarding mechanism.

A NOVEL MUTATION CAUSING COMPLETE THYROID BINDING GLOBULIN DEFICIENCY (TBG-CD MIA) IN A MALE WITH COEXISTING GRAVES DISEASE.

Objective: An asymptomatic male was found on screening to have a low serum TSH and total T. The diagnosis of Graves' disease was made with positive thyroid stimulating immunoglobulin (TSI) and elevated free T in the presence of complete TBG deficiency (TBG-CD). Genetic testing of the patient and family members revealed a novel frameshift mutation in the () gene resulting in a complete deficiency of the protein.