How do thyroid hormones control hair growth?

How Thyroid Hormones Control Hair Growth

Direct Cellular Mechanisms

Thyroid hormones (T3 and T4) directly control hair growth by modulating hair follicle cell proliferation, extending the anagen (growth) phase, regulating apoptosis, and stimulating melanin production in hair follicles. 1

Hair Matrix Keratinocyte Proliferation

• T4 directly upregulates proliferation of hair matrix keratinocytes, the rapidly dividing cells responsible for hair shaft production 1
• T3 and T4 both downregulate apoptosis (programmed cell death) in hair matrix cells, allowing follicles to remain in active growth longer 1
• In hyperthyroid patients, S and G2+M phase cell percentages increase by 30%, indicating accelerated cell division in hair bulbs 2
• Conversely, hypothyroid patients show a 15% decrease in S and G2+M phase percentages, reflecting slowed cellular proliferation 2

Hair Cycle Regulation

• T4 prolongs the anagen (growth) phase duration by downregulating TGF-beta2, the key growth factor that terminates anagen and pushes follicles into catagen (regression phase) 1
• Topical T3 application induces telogen (resting) phase follicles to enter anagen phase within 5 days in murine models, compared to 9-15 days in untreated controls 3
• Hair follicles express thyroid hormone receptors (TRα1 and TRβ), making them direct targets for thyroid hormone action 1, 4

Intrafollicular Hormone Conversion

• Human hair follicles transcribe deiodinase genes (D2 and D3), enabling them to convert T4 to the more active T3 locally 1
• This local conversion allows follicles to regulate their own thyroid hormone exposure independent of systemic levels 1

Effects on Hair Structure and Pigmentation

Keratin Expression

• T3 and T4 modulate expression of thyroid hormone-responsive keratins: T4 enhances cytokeratin 6 (CK6) while downregulating cytokeratin 14 (CK14) 1
• These keratin changes alter hair shaft structure and may explain the characteristic fine, brittle hair seen in thyroid disorders 1

Melanogenesis

• Both T3 and T4 significantly stimulate intrafollicular melanin synthesis, affecting hair pigmentation 1
• Excess T3 from treatment can reverse gray hair by reactivating follicular melanocytes 3
• This explains why thyroid dysfunction can cause changes in hair color as well as hair loss 3

Clinical Manifestations of Thyroid Dysfunction

Hypothyroidism and Hair Loss

• Hypothyroidism causes diffuse hair shedding (telogen effluvium) through decreased follicular cell proliferation and shortened anagen phase 5, 2
• Hair loss is a recognized symptom requiring evaluation with TSH and free T4 levels 6, 7
• Iron deficiency commonly coexists with hypothyroidism and directly impairs thyroid metabolism, creating a synergistic effect on hair loss that requires addressing both deficiencies 7

Hyperthyroidism and Hair Changes

• Hyperthyroidism accelerates hair cycling, potentially leading to increased shedding despite enhanced proliferation 5, 2
• The accelerated turnover can manifest as fine, fragile hair that breaks easily 5

Receptor-Mediated Mechanisms

• Mice lacking both TRα1 and TRβ receptors display impaired hair cycling with decreased follicular cell proliferation, demonstrating that thyroid hormone effects are receptor-mediated 4
• Individual deletion of either TRα1 or TRβ alone does not impair hair cycling, indicating overlapping or compensatory receptor functions 4
• TRα1/TRβ-deficient mice develop alopecia after serial depilation, confirming the critical role of thyroid hormone receptors in maintaining hair growth capacity 4

Clinical Approach to Thyroid-Related Hair Loss

Initial Evaluation

• Screen TSH and free T4 in all patients with unexplained hair loss, fatigue, weight changes, or cold intolerance 6, 7
• If TSH is elevated with low free T4, check thyroid peroxidase (TPO) antibodies to identify autoimmune thyroiditis 6, 8

Comprehensive Nutritional Assessment

• Check serum ferritin, as iron deficiency directly impairs thyroid peroxidase activity and thyroid hormone synthesis 7, 8
• Measure 25-OH vitamin D levels (target ≥30 ng/mL), as 70% of alopecia areata patients are deficient versus 25% of controls 7, 8
• Consider selenium and zinc levels, as selenium is required for T4 to T3 conversion and zinc serves as a cofactor for hair follicle enzymes 7, 8

Treatment Priorities

• When both adrenal insufficiency and hypothyroidism are present, always start steroids before thyroid hormone replacement to avoid precipitating adrenal crisis 6
• Ensure thyroid medication is taken on an empty stomach, 30-60 minutes before eating, to optimize absorption 7
• Address coexisting iron deficiency, as it directly impairs thyroid metabolism independent of thyroid hormone replacement 7

Important Caveats

• Avoid excessive iodine intake (>300 μg daily), as it can paradoxically worsen thyroid function in some individuals, particularly those with autoimmune thyroiditis 7
• Multiple nutrient deficiencies often coexist in hypothyroid patients, requiring comprehensive assessment rather than isolated thyroid hormone replacement 7
• Hair regrowth typically lags behind biochemical correction by 3-6 months due to the hair cycle timeline, so patients require counseling about delayed response 1, 5