Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia
Biallelic pathological variants in the thyroid stimulating hormone (TSH) subunit β gene (TSHB) result in isolated TSH deficiency and secondary hypothyroidism, a rare form of central congenital hypothyroidism (CCH), with an estimated incidence of 1 in 65 000 births. It is characterised by low levels...
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| Format: | Article |
| Language: | English |
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Bioscientifica
2022-08-01
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| Series: | Endocrinology, Diabetes & Metabolism Case Reports |
| Online Access: | https://edm.bioscientifica.com/view/journals/edm/2022/1/EDM22-0230.xml |
| _version_ | 1798041626907508736 |
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| author | Adam I Kaplan Catherine Luxford Roderick J Clifton-Bligh |
| author_facet | Adam I Kaplan Catherine Luxford Roderick J Clifton-Bligh |
| author_sort | Adam I Kaplan |
| collection | DOAJ |
| description | Biallelic pathological variants in the thyroid stimulating hormone (TSH) subunit β gene (TSHB) result in isolated TSH deficiency and secondary hypothyroidism, a rare form of central congenital hypothyroidism (CCH), with an estimated incidence of 1 in 65 000 births. It is characterised by low levels of free thyroxine and inappropriately low serum TSH and may therefore be missed on routine neonatal screening for hypothyroidism, which relies on elevated TSH. We describe a patient with CCH who developed recurrence of pituitary hyperplasia and symptomatic hypothyroidism due to poor compliance with thyroxine replacement. She was diagnosed with CCH as a neonate and had previously required trans-sphenoidal hypophysectomy surgery for pituitary hyperplasia associated with threatened chiasmal compression at 17 years of age due to variable adherence to thyroxine replacement. Genetic testing of TSHB identified compound heterozygosity with novel variant c.217A>C, p.(Thr73Pro), and a previously reported variant c.373delT, p.(Cys125Valfs*10). Continued variable adherence to treatment as an adult resulted in recurrence of significant pituitary hyperplasia, which subsequently resolved with improved compliance without the need for additional medications or repeat surgery. This case describes a novel TSHB variant associated with CCH and demonstrates the importance of consistent compliance with thyroxine replacement to treat hypothyroidism and prevent pituitary hyperplasia in central hypothyroidism. |
| first_indexed | 2024-04-11T22:24:17Z |
| format | Article |
| id | doaj.art-dacbc6b897e242f2b01a969f33f1021a |
| institution | Directory Open Access Journal |
| issn | 2052-0573 |
| language | English |
| last_indexed | 2024-04-11T22:24:17Z |
| publishDate | 2022-08-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrinology, Diabetes & Metabolism Case Reports |
| spelling | doaj.art-dacbc6b897e242f2b01a969f33f1021a2022-12-22T03:59:53ZengBioscientificaEndocrinology, Diabetes & Metabolism Case Reports2052-05732022-08-01111710.1530/EDM-22-0230Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasiaAdam I Kaplan0Catherine Luxford1Roderick J Clifton-Bligh2Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Cancer Genetics Laboratory, Kolling Institute, Royal North Shore Hospital, Sydney, Australia Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia; Cancer Genetics Laboratory, Kolling Institute, Royal North Shore Hospital, Sydney, Australia Biallelic pathological variants in the thyroid stimulating hormone (TSH) subunit β gene (TSHB) result in isolated TSH deficiency and secondary hypothyroidism, a rare form of central congenital hypothyroidism (CCH), with an estimated incidence of 1 in 65 000 births. It is characterised by low levels of free thyroxine and inappropriately low serum TSH and may therefore be missed on routine neonatal screening for hypothyroidism, which relies on elevated TSH. We describe a patient with CCH who developed recurrence of pituitary hyperplasia and symptomatic hypothyroidism due to poor compliance with thyroxine replacement. She was diagnosed with CCH as a neonate and had previously required trans-sphenoidal hypophysectomy surgery for pituitary hyperplasia associated with threatened chiasmal compression at 17 years of age due to variable adherence to thyroxine replacement. Genetic testing of TSHB identified compound heterozygosity with novel variant c.217A>C, p.(Thr73Pro), and a previously reported variant c.373delT, p.(Cys125Valfs*10). Continued variable adherence to treatment as an adult resulted in recurrence of significant pituitary hyperplasia, which subsequently resolved with improved compliance without the need for additional medications or repeat surgery. This case describes a novel TSHB variant associated with CCH and demonstrates the importance of consistent compliance with thyroxine replacement to treat hypothyroidism and prevent pituitary hyperplasia in central hypothyroidism.https://edm.bioscientifica.com/view/journals/edm/2022/1/EDM22-0230.xml |
| spellingShingle | Adam I Kaplan Catherine Luxford Roderick J Clifton-Bligh Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia Endocrinology, Diabetes & Metabolism Case Reports |
| title | Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia |
| title_full | Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia |
| title_fullStr | Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia |
| title_full_unstemmed | Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia |
| title_short | Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia |
| title_sort | novel tshb variant c 217a c causing severe central hypothyroidism and pituitary hyperplasia |
| url | https://edm.bioscientifica.com/view/journals/edm/2022/1/EDM22-0230.xml |
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