Biology of thyroid hormones and their effects on the appendages
The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), play a crucial role in maintaining the general health of the body, including tissues such as nails and hair. These hormones regulate numerous metabolic processes, influencing cell growth, metabolism and tissue regeneration. Alterations in the production of these hormones can have significant effects on nails and hair, which are rapidly growing tissues and highly sensitive to metabolic changes. Iodine deficiency, which is essential for the synthesis of thyroid hormones, can exacerbate problems related to nail and hair health, highlighting the importance of an adequate intake of this element in the diet. In addition, changes in thyroid hormone concentrations can be modulated by other factors, such as stress, diet and autoimmune conditions.
Among these, the most common are Hashimoto’s thyroiditis or Graves’ disease, which frequently accompany noticeable aesthetic changes in nails and hair. Hypothyroidism (insufficient production of thyroid hormones) is often associated with dry, brittle hair that is prone to falling out. This is due to a reduction in the rate of metabolism and cell turnover in the hair follicles, which leads to a prolongation of the telogen (resting) phase of the hair growth cycle. Nails can also be affected: they tend to become brittle, with slow growth, and may present transverse lines (Beau’s lines). A common sign of advanced hypothyroidism is the loss of hair on the sides of the eyebrows, known as Hertoghe’s sign.
On the other hand, hyperthyroidism, due to excessive production of thyroid hormones, can speed up metabolism and increase cell turnover, with consequent deleterious effects on hair and nails. In hair, this often results in increased shedding (telogen effluvium) due to the rapid transition from the growth phase (anagen) to the resting phase (telogen). Nails, on the other hand, may become thin and brittle, with a tendency to flake. A characteristic manifestation of hyperthyroidism is onycholysis, or the detachment of the nail plate from the nail bed, which occurs particularly in the thumb and fourth finger. Thyroid hormones are essential for regulating cellular metabolism and the growth cycle of tissues, including hair follicles.
These hormones exert their effects through specific nuclear receptors present in almost all cells of the body, modulating gene expression and influencing processes such as cell proliferation, differentiation and survival. In the context of hair follicles, thyroid hormones play a key role in maintaining the anagen phase (active growth phase) and regulating the hair cycle. Under normal conditions, T3 and T4 promote hair growth and vitality by stimulating the activity of keratinocytes and matrix cells of the hair follicle. Their action is mediated by increased protein synthesis, increased mitochondrial activity and improved local blood flow, which ensures an optimal supply of nutrients and oxygen to the follicle.
Alterations in thyroid function, however, disrupt this balance, leading to visible effects on the health and appearance of hair and nails, similar to what happens in the case of martial anemia (iron deficiency). That is why timely diagnosis and drug treatment of thyroid disorders can significantly improve the health of nails and hair, although full recovery may take months, as these tissues need time to regenerate. Therefore, it is essential to monitor thyroid function in patients with persistent hair and nail problems, as these signs may be an early indicator of underlying systemic disorders.
Mechanisms of thyroid hormones and their effects on hair
Thyroid hormones act directly on the cells of the follicular matrix through specific receptors, activating intracellular signaling pathways that influence the production of structural proteins such as keratin. The nuclear thyroid receptors TR-alpha and TR-beta are the main mediators of these effects as they are nuclear transcription factors that can be activated by hormones. They work in concert with other chromatin proteins to induce the right gene battery based on the homeostatic conditions in which the cells are located. It is not yet known whether cytoplasmic receptors for T3 are involved, since it has been discovered that a variant of TR-alpha synthesized by cells is not able to act as a transcription factor, but rather remains in the cytoplasm and leads to the activation of protein kinase signaling pathways (PKG-II, ERK, PI3K, c-Akt).
These signaling pathways are positively associated with cell proliferation and survival. In addition, thyroid hormones regulate the activity of fibroblasts in the dermal papilla, which are crucial for the production of growth factors necessary for the hair follicle cycle. In fact, the cells of the hair bulb do not differ from all the others in terms of their dependence on the nutritional (trophic) effect of proteins circulating in the bloodstream, growth factors, which have a powerful inductive action on cell replication and possibly on differentiation. Ultimately, these are the ones that cooperate with the thyroid hormone receptors, controlling the phases of growth, maintenance or decline of the bulb (anagen, catagen, etc.).
In hyperthyroidism, excessive levels of T3 and T4 accelerate cellular metabolism and follicular turnover. This leads to a rapid transition from the anagen phase to the telogen phase, causing telogen effluvium, or diffuse hair loss. The hair appears thin, soft and more prone to falling out, although the growth rate may initially appear increased. Fragility is often accentuated by disorganization of the keratin structure and increased sensitivity of the hair follicles to oxidative stress. Chronic hyperthyroidism can also contribute to progressive atrophy of the hair follicles, exacerbating thinning.
Hypothyroidism, on the other hand, slows down cellular metabolism and reduces mitotic activity in the hair follicles. This leads to a prolongation of the telogen phase (resting phase) and a reduction in the anagen phase, causing general thinning and slow hair growth. The hair becomes thin, dry, brittle and tends to break easily, reflecting the decrease in keratin synthesis and reduced sebum production by the sebaceous glands. In addition, atrophy of the hair follicles can lead to diffuse hair loss, with non-scarring patterns. A specific symptom of advanced hypothyroidism is the loss of the lateral part of the eyebrows, which is a distinctive diagnostic sign.
Thyroid autoimmunity and hair health
Autoimmune thyroid diseases, such as Hashimoto’s thyroiditis and Graves’ disease, can further worsen hair health. Autoimmune processes can directly involve the hair follicle, damaging the matrix cells or interfering with the molecular signals that regulate the hair cycle. In some cases, these conditions can coexist with other forms of autoimmune alopecia, such as alopecia areata, amplifying hair loss. Early diagnosis and appropriate treatment of thyroid disorders, often with levothyroxine for hypothyroidism or antithyroid drugs for hyperthyroidism, can lead to improved hair health. Autoimmune disease, however, requires targeted treatment to keep the underlying cause at bay.
In this case, biological drugs may be an option, since traditional immunosuppressive drugs (especially methotrexate, corticosteroids and mycophenolate mofetil) interfere with the replicative processes of continuously renewing cells (bone marrow, mucous membranes, skin and also hair follicles and nail roots). However, the response of the hair follicle to hormonal changes takes time, and the benefits on hair growth and appearance may be visible only after several months. Integrated management that includes nutritional support, such as supplementation with sulfur-containing amino acids (cysteine, methionine), vitamins (folic acid, biotin) and minerals (especially iron, copper and zinc), may be useful to speed up recovery.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific referenes
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