Kaplan Adam I, Luxford Catherine, Clifton-Bligh Roderick J
Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia.
Endocrinol Diabetes Metab Case Rep. 2022 Aug 1;2022. doi: 10.1530/EDM-22-0230.
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.
Pathogenic variants in the TSH subunit β gene (TSHB) are rare causes of central congenital hypothyroidism (CCH). c.217A>C, p.(Thr73Pro), is a novel TSHB variant, presented in association with CCH in this case report. Thyroxine replacement is critical to prevent clinical hypothyroidism and pituitary hyperplasia. Pituitary hyperplasia can recur post-surgery if adherence to thyroxine replacement is not maintained. Pituitary hyperplasia can dramatically reverse if compliance with thyroxine replacement is improved to maintain free thyroxine (FT4) levels in the middle-to-upper normal range, without the need for additional medications or surgeries.
促甲状腺激素（TSH）β亚基基因（TSHB）的双等位基因病理性变异导致孤立性TSH缺乏和继发性甲状腺功能减退，这是一种罕见的中枢性先天性甲状腺功能减退症（CCH），估计发病率为每65000例出生中有1例。其特征是游离甲状腺素水平低且血清TSH水平不适当降低，因此可能在依赖TSH升高的常规新生儿甲状腺功能减退筛查中被漏诊。我们描述了一名CCH患者，由于甲状腺素替代治疗依从性差，出现垂体增生复发和症状性甲状腺功能减退。她在新生儿期被诊断为CCH，此前因甲状腺素替代治疗依从性不一，在17岁时因垂体增生伴视交叉受压风险而接受经蝶窦垂体切除术。对TSHB进行基因检测发现复合杂合性突变，包括新变异c.217A>C，p.（Thr73Pro），以及先前报道的变异c.373delT，p.（Cys125Valfs*10）。成年后持续的治疗依从性不一导致显著的垂体增生复发，随后通过改善依从性得到缓解，无需额外药物治疗或再次手术。本病例描述了一种与CCH相关的新型TSHB变异，并证明了持续依从甲状腺素替代治疗对于治疗甲状腺功能减退和预防中枢性甲状腺功能减退症患者垂体增生的重要性。
促甲状腺激素β亚基基因（TSHB）中的致病变异是中枢性先天性甲状腺功能减退症（CCH）的罕见病因。c.217A>C，p.（Thr73Pro）是一种新型TSHB变异，在本病例报告中与CCH相关。甲状腺素替代治疗对于预防临床甲状腺功能减退和垂体增生至关重要。如果不维持甲状腺素替代治疗的依从性，垂体增生可能在手术后复发。如果改善甲状腺素替代治疗的依从性以将游离甲状腺素（FT4）水平维持在中高正常范围内，垂体增生可显著逆转，无需额外药物或手术。
