The effect of thyroid disorders on the cutaneous manifestations in patients with chronic kidney disease

Abstract

For several decades, the cutaneous manifestations related to chronic kidney disease (CKD) have presented substantial clinical challenges. However, the underlying etiology and pathophysiology of these manifestations remain incompletely understood. Thyroid disorders represent a highly prevalent but often under-recognized endocrine dysfunction in patients with CKD. Recently, several studies have suggested that thyroid disorders play critical roles in modulating the cutaneous manifestations related to CKD and serve as a key factor in effectively addressing these issues. However, there is a notable lack of systematic reviews that comprehensively summarize the effect of thyroid disorders on CKD-related cutaneous manifestations, thereby impeding the advancement of research in this domain. In this review, we summarized the current knowledge on the effect of thyroid disorders on cutaneous manifestations related to CKD. Then, the underlying mechanisms through which thyroid disorders may induce or aggravate these cutaneous manifestations were further discussed. This comprehensive analysis can enhance our understanding on the roles of thyroid disorders in dermatological complications related to CKD, and help to identify novel targets and strategies for the effective management toward these refractory cutaneous manifestations.

Keywords: Cutaneous manifestation; chronic kidney disease; endocrine dysfunction; pathophysiology; thyroid disorder.

Figure 1.

Overview of the associations between chronic kidney disease (CKD), thyroid disorders, and cutaneous manifestations. HPT-axis, hypothalamic-pituitary-thyroid axis; T3, triiodothyronine; T4, thyroxine. Original figure (made with figdraw).

Figure 2.

Pathophysiological mechanisms of TH affecting the skin barrier. TH can bind to TH receptor in keratinocytes and modulate the keratin to regulate the skin’s ordered keratinization. TH can regulate keratinocytes to synthesize lipids, such as ceramides, cholesterol and cholesterol esters, and stimulate the sebaceous gland to secrete sebum, thereby replenishing the skin lipid bilayer. TH can facilitate keratinocytes to produce filaggrin, which degrades into natural moisturizing factors, such as pyrrolidine carboxylic acid and trans-urocanic acid. TH, thyroid hormone. Original figure (made with figdraw).

Figure 3.

Mechanisms of the effect of thyroid autoantibodies and TH on pruritus. Thyroid autoantibodies and elevated levels of TH can stimulate mast cells to release histamine, and mediate the sensation of skin itch. TH, thyroid hormone; H1R, histamine H(1) receptor; H4R, histamine H(4) receptor. Original figure (made with figdraw).

Figure 4.

Pathophysiology of TH on hair follicle. TH can down-regulate the intrafollicular protein expression of TGF-β to stimulate the proliferation of human hair matrix keratinocytes while inhibiting their apoptosis. Meanwhile, TH can help prolong the anagen and decrease the catagen and telogen in the hair cycle, and induce the hair growth. T3, triiodothyronine; T4, thyroxine; rT3, reverse triiodothyronine; D2, deiodinase 2; D3, deiodinase 3; TRs, thyroid hormone receptors; TRE, tet-responsive element; TGF-β, transforming growth factor beta. Original figure (made with figdraw).