Rare thyroid non-neoplastic diseases.

Katarzyna Lacka,Adam Maciejewski

doi:10.1186/s13044-015-0017-3

Abstract

Rare diseases are usually defined as entities affecting less than 1 person per 2,000. About 7,000 different rare entities are distinguished and, among them, rare diseases of the thyroid gland. Although not frequent, they can be found in the everyday practice of endocrinologists and should be considered in differential diagnosis. Rare non-neoplastic thyroid diseases will be discussed. Congenital hypothyroidism’s frequency is relatively high and its early treatment is of vital importance for neonatal psychomotor development; CH is caused primarily by thyroid dysgenesis (85%) or dyshormonogenesis (10-15%), although secondary defects - hypothalamic and pituitary - can also be found; up to 40% of cases diagnosed on neonatal screening are transient. Inherited abnormalities of thyroid hormone binding proteins (TBG, TBP and albumin) include alterations in their concentration or affinity for iodothyronines, this leads to laboratory test abnormalities, although usually with normal free hormones and clinical euthyroidism. Thyroid hormone resistance is most commonly found in THRB gene mutations and more rarely in THRA mutations; in some cases both genes are unchanged (non-TR RTH). Recently the term ‘reduced sensitivity to thyroid hormones’ was introduced, which encompass not only iodothyronine receptor defects but also their defective transmembrane transport or metabolism. Rare causes of hyperthyroidism are: activating mutations in TSHR or GNAS genes, pituitary adenomas, differentiated thyroid cancer or gestational trophoblastic disease; congenital hyperthyroidism cases are also seen, although less frequently than CH. Like other organs and tissues, the thyroid can be affected by different inflammatory and infectious processes, including tuberculosis and sarcoidosis. In most of the rare thyroid diseases genetic factors play a key role, many of them can be classified as monogenic disorders. Although there are still some limitations, progress has been made in our understanding of rare thyroid diseases etiopathogenesis, and, thanks to these studies, also in our understanding of how normal thyroid gland functions.

Highlights

Rare diseases are usually defined as entities affecting 5 or fewer per 10,000 (1 person per 2,000), different thresholds can be found, e.g. in Japan - fewer than 4 cases per 10,000 or in the United States - fewer than 200,000 patients affected across the country
Some cases of congenital thyroid hormones deficiency are transient and euthyroidism is achieved within the first months or years of life [3]
Most of the rare thyroid diseases presented in this paper have a genetic origin, among them monogenic disorders can be found

Summary

Introduction

Rare diseases are usually defined as entities affecting 5 or fewer per 10,000 (1 person per 2,000), different thresholds can be found, e.g. in Japan - fewer than 4 cases per 10,000 or in the United States - fewer than 200,000 patients affected across the country. Cases of thyroid dysgenesis are usually sporadic, inherited genetic defects are only recognized in about 2% of all cases and result from transcription factor genes mutations (PAX8, NKX2-1/TITF1, NXK2-5, FOXE1/ TITF-2) [9]. As these transcription factors are involved in extrathyroid development, different organs’ congenital anomalies may coexist (Table 1). As G protein is responsible for signal transduction of other peptide

Locus Type of inheritance Expression

Findings

Conclusions