A novel variant of THRβ and its 4-year clinical course in a Korean boy with resistance to thyroid hormone
Thyroid hormone resistance (RTH) is characterized by a decreased sensitivity of target tissues to thyroid hormones due to a defect in the THRα- and THRβ-encoded thyroid hormone receptors (THRs). The clinical manifestations range from no symptoms to simple goiter and hypo- or hyperthyroidism, dependi...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Korean Society of Pediatric Endocrinology
2023-09-01
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| Series: | Annals of Pediatric Endocrinology & Metabolism |
| Subjects: | |
| Online Access: | http://e-apem.org/upload/pdf/apem-2142246-123.pdf |
| _version_ | 1797672799214501888 |
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| author | Sejin Kim Soyun Park Jungeun Moon Heungsik Kim Seokjin Kang |
| author_facet | Sejin Kim Soyun Park Jungeun Moon Heungsik Kim Seokjin Kang |
| author_sort | Sejin Kim |
| collection | DOAJ |
| description | Thyroid hormone resistance (RTH) is characterized by a decreased sensitivity of target tissues to thyroid hormones due to a defect in the THRα- and THRβ-encoded thyroid hormone receptors (THRs). The clinical manifestations range from no symptoms to simple goiter and hypo- or hyperthyroidism, depending on the receptor subtype distribution in the tissues. Here, we report the case of a thyroid hormone-resistant 12-month-old boy carrying a novel THRβ variant who was initially diagnosed with congenital hypothyroidism. An extensive evaluation revealed increased free T4 level and inappropriately increased thyroid-stimulating hormone (TSH) level; a normal lipid profile, sex hormone-binding globulin, and free alpha subunit of TSH; exaggerated TSH response to THR; and no radiological evidence of pituitary adenoma. A targeted next-generation sequencing panel identified a heterozygote c.993T>G (p.Asn331Lys) mutation in the THRβ gene. During the first year of life, a higher dose of levothyroxine was administered to the patient due to uncompensated RTH. Levothyroxine treatment was continued after 3 years to maintain TSH level <5 mIU/mL, but the observed weight gain was poor, height increase was insufficient, and bone development was delayed. However, neither hyperactivity nor developmental delay was observed. Patients with RTH exhibit various clinical features. Due to its heterogeneous nature, genetic test for accurate diagnosis is important to provide proper management. |
| first_indexed | 2024-03-11T21:35:28Z |
| format | Article |
| id | doaj.art-13f770ed43f448bba7d661f1dafff44e |
| institution | Directory Open Access Journal |
| issn | 2287-1012 2287-1292 |
| language | English |
| last_indexed | 2024-03-11T21:35:28Z |
| publishDate | 2023-09-01 |
| publisher | Korean Society of Pediatric Endocrinology |
| record_format | Article |
| series | Annals of Pediatric Endocrinology & Metabolism |
| spelling | doaj.art-13f770ed43f448bba7d661f1dafff44e2023-09-27T00:10:03ZengKorean Society of Pediatric EndocrinologyAnnals of Pediatric Endocrinology & Metabolism2287-10122287-12922023-09-0128321922410.6065/apem.2142246.123998A novel variant of THRβ and its 4-year clinical course in a Korean boy with resistance to thyroid hormoneSejin Kim0Soyun Park1Jungeun Moon2Heungsik Kim3Seokjin Kang4 Department of Pediatrics, Keimyung University Dongsan Hospital, Keimyung University school of Medicine, Daegu, Korea Department of Pediatrics, Keimyung University Dongsan Hospital, Keimyung University school of Medicine, Daegu, Korea Department of Pediatrics, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea Deparment of Pediatrics, Keimyung University Daegu Dongsan Hospital, Daegu, Korea Department of Pediatrics, Keimyung University Dongsan Hospital, Keimyung University school of Medicine, Daegu, KoreaThyroid hormone resistance (RTH) is characterized by a decreased sensitivity of target tissues to thyroid hormones due to a defect in the THRα- and THRβ-encoded thyroid hormone receptors (THRs). The clinical manifestations range from no symptoms to simple goiter and hypo- or hyperthyroidism, depending on the receptor subtype distribution in the tissues. Here, we report the case of a thyroid hormone-resistant 12-month-old boy carrying a novel THRβ variant who was initially diagnosed with congenital hypothyroidism. An extensive evaluation revealed increased free T4 level and inappropriately increased thyroid-stimulating hormone (TSH) level; a normal lipid profile, sex hormone-binding globulin, and free alpha subunit of TSH; exaggerated TSH response to THR; and no radiological evidence of pituitary adenoma. A targeted next-generation sequencing panel identified a heterozygote c.993T>G (p.Asn331Lys) mutation in the THRβ gene. During the first year of life, a higher dose of levothyroxine was administered to the patient due to uncompensated RTH. Levothyroxine treatment was continued after 3 years to maintain TSH level <5 mIU/mL, but the observed weight gain was poor, height increase was insufficient, and bone development was delayed. However, neither hyperactivity nor developmental delay was observed. Patients with RTH exhibit various clinical features. Due to its heterogeneous nature, genetic test for accurate diagnosis is important to provide proper management.http://e-apem.org/upload/pdf/apem-2142246-123.pdf thyroid hormone resistancethyroid hormone receptorlevothyroxineheterozygous mutationthyroid-stimulating hormone |
| spellingShingle | Sejin Kim Soyun Park Jungeun Moon Heungsik Kim Seokjin Kang A novel variant of THRβ and its 4-year clinical course in a Korean boy with resistance to thyroid hormone Annals of Pediatric Endocrinology & Metabolism thyroid hormone resistance thyroid hormone receptor levothyroxine heterozygous mutation thyroid-stimulating hormone |
| title | A novel variant of THRβ and its 4-year clinical course in a Korean boy with resistance to thyroid hormone |
| title_full | A novel variant of THRβ and its 4-year clinical course in a Korean boy with resistance to thyroid hormone |
| title_fullStr | A novel variant of THRβ and its 4-year clinical course in a Korean boy with resistance to thyroid hormone |
| title_full_unstemmed | A novel variant of THRβ and its 4-year clinical course in a Korean boy with resistance to thyroid hormone |
| title_short | A novel variant of THRβ and its 4-year clinical course in a Korean boy with resistance to thyroid hormone |
| title_sort | novel variant of thrβ and its 4 year clinical course in a korean boy with resistance to thyroid hormone |
| topic | thyroid hormone resistance thyroid hormone receptor levothyroxine heterozygous mutation thyroid-stimulating hormone |
| url | http://e-apem.org/upload/pdf/apem-2142246-123.pdf |
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