Abstract
Central, secondary or low TSH hypothyroidism can be congenital or acquired. Congenital Central hypothyroidism (CH-C), either isolated or (unlike primary hypothyroidism) combined with deficiency of other pituitary hormones, is usually caused by mutations in genes related either to TSH synthesis or pituitary ontogenesis. The prevalence of CH-C is higher than previously considered, ranging from 1:16000 to 1:20000 live births. Isolated CH-C is most frequently caused by mutations in the TSΗβ-subunit and in rare cases by TRHR gene mutations. Either one of these mutations are inherited as a recessive trait. In patients with multiple pituitary hormone deficiency, molecular defects have been detected in the following genes: IGSF1, PROP1, POU1F1, LHX3, LHX4, HESX1, SHH, TGIF, GLI2. The resulting phenotype varies and the mode of inheritance could be autosomal dominant, autosomal recessive or X-linked, depending on the specific gene involved. In patients with CH-C, the timely identification of the underlying genetic defect is crucial because it leads to early and appropriate management that improves prognosis and determines genetic counseling.
Highlights
Central hypothyroidism (CH) refers to hypothyroidism that is not caused by anatomical or functional defects of the thyroid gland per se but by inefficient synthesis of TSH [1,2]
A distinction between primary and secondary hypothyroidism is important because in many Central hypothyroidism might be congenital (CH-C) cases TSH deficiency is accompanied by deficiency of other pituitary hormones
In a more recent study from The Netherlands, a CH-C prevalence of 1:20263 was reported [9]; 78% of these subjects had MPHD, 53% had a pituitary malformation on magnetic resonance imaging (MRI)
Summary
Central hypothyroidism (CH) refers to hypothyroidism that is not caused by anatomical or functional defects of the thyroid gland per se (primary hypothyroidism) but by inefficient synthesis of TSH (secondary hypothyroidism) [1,2]. That is usually the case, normal or mildly elevated TSH values can be detected in certain cases, leading to an erroneous diagnosis of primary hypothyroidism. A distinction between primary and secondary hypothyroidism is important because in many CH-C cases TSH deficiency is accompanied by deficiency of other pituitary hormones (multiple pituitary hormone deficiency – MPHD) In such cases the concomitant deficiency of growth hormone (GH) and/or cortisol may cause hypoglycemia with adverse effects on brain function. In a more recent study from The Netherlands, a CH-C prevalence of 1:20263 was reported [9]; 78% of these subjects had MPHD, 53% had a pituitary malformation on magnetic resonance imaging (MRI) In this particular report, it was mentioned that delay in the detection of MPHD resulted in significant morbidity, and a mortality rate of 14%, possibly accounted for by the co-existence of GH and/or cortisol deficiency. J Genet Syndr Gene Ther 4: 172. doi:10.4172/2157-7412.1000172
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
