THYROID AND PARATHYROID DISEASES: DIAGNOSIS, TREATMENT AND SURGERY WITH CURRENT APPROACHES

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GENETIC AND MOLECULAR INDICATORS IN PARATHYROID DISEASES

Emine Berrin Yüksel

Karamanoğlu Mehmetbey University, Faculty of Medicine, Department of Medical Genetics, Karaman, Türkiye

Yüksel EB. Genetic and Molecular Indicators in Parathyroid Diseases. Kesici U, ed. Thyroid and Parathyroid Diseases: Diagnosis, Treatment and Surgery with Current Approaches. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.175-185.

ABSTRACT

This book chapter delves into the genetic and molecular foundations of parathyroid diseases, high- lighting advancements in diagnostic and therapeutic approaches. Parathyroid disorders, such as hyper- parathyroidism, hypoparathyroidism, and parathyroid carcinoma, disrupt calcium balance, leading to systemic effects like osteoporosis, nephrolithiasis, and cardiovascular complications. Genetic muta- tions, notably in MEN1, CDC73, and CASR, play pivotal roles in the pathogenesis of these conditions. Furthermore, epigenetic changes, including DNA methylation and histone modifications, contribute to tumor development, emphasizing the complexity of these disorders.

Advances in next-generation sequencing (NGS) have significantly improved the diagnosis and man- agement of parathyroid diseases. NGS enables comprehensive genetic profiling, distinguishing hered- itary syndromes from sporadic cases. This differentiation is critical for clinical decisions, particularly in surgical interventions. For example, identifying MEN1 mutations informs strategies for managing multi-glandular disease, while distinguishing familial hypocalciuric hypercalcemia (FHH) through CASR mutations avoids unnecessary surgeries.

The molecular pathways underlying parathyroid diseases provide insights into therapeutic targets. The calcium-sensing receptor (CaSR) pathway regulates PTH secretion, and its dysfunction is implicated in conditions like FHH and autosomal dominant hypocalcemia. Aberrant Wnt/b-catenin signaling and PI3K/Akt pathway activation drive tumor progression, highlighting potential targets for novel ther- apies. Additionally, the interplay of genetics and epigenetics, such as CDC73 hypermethylation and miRNA dysregulation, underscores the need for advanced molecular diagnostics.

Emerging biomarkers, including miRNAs and noncoding RNAs, enhance diagnostic precision and prognostication. For instance, miR-126 differentiates parathyroid carcinomas from adenomas. Genetic testing for key mutations, such as those in CDC73 and RET, not only facilitates early detection but also guides personalized management strategies. These approaches ensure targeted therapies for hereditary and sporadic cases, improving patient outcomes.

The integration of genetic findings into clinical practice has transformed the management of parathy- roid disorders. Multidisciplinary collaboration among endocrinologists, geneticists, and surgeons en- ables personalized care. The chapter emphasizes the potential of precision medicine, driven by AI and multi-omics approaches, to advance diagnostics and therapies. Despite these advancements, challenges remain, including accessibility to genetic testing, cost barriers, and ethical concerns. Overcoming these obstacles requires global collaboration and investment in research.

In conclusion, this chapter underscores the importance of genetic and molecular research in improving the understanding and management of parathyroid diseases. Ongoing advancements promise to refine diagnostics, optimize therapies, and pave the way for precision medicine in endocrine disorders.

Keywords: Parathyroid diseases; Mutation; Epigenetic; Precision medicine; Next generation sequencing

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