Rare thyroid non-neoplastic diseases

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.

Conservative in utero treatment of fetal dyshormonogenetic goiter with levothyroxine, a systematic literature review

“…Fetal dyshormonogenetic goiter is a rare disease characterized by increased fetal thyroid gland size due to inherited defects in genes that control thyroid hormone synthesis and transportation. The incidence varies between 1:30,000 and 1:50,000 live births in the European and North American regions, and it accounts for up to 15% of congenital hypothyroidism cases (1,2). It affects predominantly female fetuses (male:female ratio, 1:2) and has no racial or ethnic predilection, but it is encountered more often in consanguineous couples (3).…”

Rare case of multisystem sarcoidosis

“…With fewer than 70 cases reported in the medical literature, thyroid sarcoidosis is most commonly identified during postmortem, with a prevalence of only 1%–4% of those with systemic disease 14 15. Thyroid sarcoidosis has been associated with solitary hypoechoic nodules, Hashimoto’s, Graves’ disease with resistance to radioiodine, hypothalamic–pituitary involvement with secondary hypothyroidism or diffuse infiltration, with or without deranged hormonal status, as in this case 16–20…”

Causal relationship between particulate matter 2.5 and hypothyroidism: A two-sample Mendelian randomization study

“…Hypothyroidism is associated with disturbed cytokine concentrations, an abundance of reactive oxygen species (ROS), and altered signal transduction in most parts of the brain (53). In addition, chronic inflammation plays an important role in the pathogenesis of many diseases, including hypothyroidism (54). A recent experimental study in female rats found that PM 2.5 exposure reduces circulating thyroid hormone levels by interrupting thyroid hormone biosynthesis, biotransformation, and transport; by inducing oxidative stress and inflammatory responses; and ultimately by activating the hypothalamicpituitary-thyroid axis and inducing the production of hepatic transthyretin (55).…”