Publications by authors named "Kristiina Makkonen"
The clinical spectrum of thyrotropin receptor-mediated (TSHR-mediated) diseases varies from loss-of-function mutations causing congenital hypothyroidism to constitutively active mutations (CAMs) leading to nonautoimmune hyperthyroidism (NAH). Variation at the TSHR locus has also been associated with altered lipid and bone metabolism and autoimmune thyroid diseases. However, the extrathyroidal roles of TSHR and the mechanisms underlying phenotypic variability among TSHR-mediated diseases remain unclear.
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- Central hypothyroidism (CeH) is a rare disorder that can impact normal development, often going undetected in newborn screenings as they focus on more common forms of hypothyroidism.
- A study identified a novel genetic mutation in two brothers diagnosed with CeH, utilizing targeted next-generation sequencing (NGS) and extensive diagnostic tests.
- The research highlights a strong genetic association with thyroid disorders in a Finnish population, indicating potential links between the identified mutation and broader thyroid disease risk.
Background: Constitutively active thyrotropin receptor (TSHR) mutations are the most common etiology of non-autoimmune hyperthyroidism (NAH). Thus far, the functionality of these mutations has been tested in vitro, but the in vivo models are lacking.
Methods: To understand the pathophysiology of NAH, the patient-derived constitutively active TSHR D633H mutation was introduced into the murine Tshr by homologous recombination.