ECE2007 Oral Communications Neuroendocrinology clinical (7 abstracts)
Idiopathic central hypothyroidism: report of a human natural model of congenital TRH receptor (TRHR) absence
Marco Bonomi 1 , Marta Busnelli 1 , Alba Pilotta 2 , Elena Prandi 2 , Mario Maggi 3 , Fabio Buzi 2 , Paolo Beck-Peccoz 1 & Luca Persani 1
1Dept. of Medical Sciences, University of Milan; Istituto Auxologico Italiano IRCCS and Fondazione Ospedale Policlinico IRCCS, Milan, Italy; 2Growth and Development Unit, Children’s Hospital, Brescia, Italy; 3Dept. of Physiopathology, University of Florence, Florence, Italy.
Central Hypothyroidism (CeH) is a rare thyroid hormone production defect due to an insufficient stimulation of a normal thyroid gland. Candidate genes for isolated CeH include TSHβ (several cases reported) and TRHR (only one case reported so far). Here, we report the clinical and genetic studies in 2 males and 3 females affected with isolated CeH with normal/low TSH levels (0.05–0.95 mU/L) and low FT4 levels (3.6–4.6 pM). None of the patients was detected at neonatal screening, but came to medical attention during childhood or even adulthood (3–42 years). MRI alterations were detected only in one case (empty sella). Ultrasound showed hypoplastic/normal thyroids. None of the patients presented thyroid autoimmunity. In 3 subjects, TRH test showed absent TSH but normal PRL responses but TSHβ gene analysis was negative. The fourth patient presented CeH associated with severe obesity and type 2 diabetes mellitus and a normal TSH response to TRH. No mutations were identified in TRH as well as in Leptin and LeptinR genes. The last case presented with growth delay at 11 years. Absent TSH/PRL responses after TRH stimulation suggested TRH resistance. We identified a C to T homozygous nonsense mutation in TRHR gene resulting in a premature stop codon (R17X) and the production of a truncated receptor lacking the 7 transmembrane domains. This is the 2nd patient with TRHR mutations and represents a natural model of TRHR congenital absence associated with CeH and absent/poor neonatal manifestations. Since TRH is considered to play an essential role in postnatal adaptation to extrauterine life and maturation of thyroid axis, our findings may challenge this view or uncover the possible existence of other TRHR isoforms also in humans. The lack of mutations in 4/5 cases suggests the existence of still unknown candidate genes for CeH.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more