Hindawi Publishing Corporation
Journal of Thyroid Research
Volume 2013, Article ID 124538, 5 pages
Thyroid Hormone and Wound Healing
Joshua D. Safer
Section of Endocrinology, Boston University School of Medicine, Room M-1016, 715 Albany Street, Boston, MA 02118, USA
Correspondence should be addressed to Joshua D. Safer; firstname.lastname@example.org
Received 29 January 2013; Accepted 9 February 2013
Academic Editor: Constantinos Pantos
Copyright © 2013 Joshua D. Safer. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
to treat cutaneous pathology has never been subject to rigorous investigation. A number of investigators have demonstrated
be of large consequence and merits further study. This is a review of the literature regarding thyroid hormone action on skin along
action on cutaneous cells in vitro and in vivo which may portend the use of thyroid hormone to promote wound healing.
Topical T4has been used to treat xerosis in humans. It is clear that the use of thyroid hormone to treat cutaneous pathology may
Despite early observation of cutaneous pathology associated
with thyroid disease [1, 2], research on the topic remains
sparse. Direct thyroid hormone action has been demon-
strated on cutaneous biology including on the epidermis,
dermis, and hair. In addition, autoimmune diseases with
cutaneous manifestations may be associated with thyroid
dysfunction (which may be autoimmune in etiology itself).
roid hormone might be attributed to the fact that mostcases
of thyroid disease are controlled with existing medication.
However, there is a slowly evolving literature that suggests
that the thyroid hormone pathway is integral to cutaneous
physiology and that manipulation of the thyroid hormone
pathway in skin could be used to treat cutaneous disease.
The skin manifestations of hypothyroidism have been
tion associating hypothyroidism with the thyroid .
tations . Although autoimmune-associated manifestations
may be specific to Graves’ disease, thyrotoxicosis in general
may result in skin sequelae. Starting in the 1950s, there were
attempts to use parenteral and topical tri-iodothyronine (T3)
to treat pretibial myxedema in Graves’ patients [4–7]. In all
cases, lesions improved with topical or intralesional steroids
time, it was noted that topical thyroxine (T4) stimulated hair
growth and pigmentation in cows .
2. Direct Thyroid Hormone Action on
Thyroid hormone action on skin is mediated through the
thyroid hormone receptor (TR). The three most recognized
thyroid hormone binding isoforms of TR have been found
in cutaneous tissues [9–12] although methods used do not
specifically distinguish which of the three isoforms predomi-
hormone, T4. T4is converted to the active thyroid hormone,
third enzyme, D3, converts T4to inactive reverse T3(rT3).
in cutaneous cultures, demonstrating indirectly the presence
of thyroid hormone deiodinases in skin [15–17]. D3 is not
expressed significantly in most peripheral tissues. However,
assays of enzyme activity suggest that D3 is active in goat
epidermis , mouse epidermis , and human skin in
of the enzymes (D1, D2) primarily activate T4to T3. The
2 Journal of Thyroid Research
vivo [20, 21]. D2 activity has been demonstrated in cultured
human fibroblasts . Neither D1 nor D3 has been found
to be active in the dermal fibroblasts, suggesting that D3
expression may be limited to epidermis.
In addition, investigators have identified elements of the
mediate skin proliferation and inflammation along with skin
response to retinoids [26, 27].
formation by increasing the activity of enzymes in the
cholesterol sulfate cycle, and hypothyroidism may hinder
the epidermal barrier function [28, 29]. Hypothyroidism
also may affect the development of the lamellar granules
(Odland bodies), which are vital in the establishment of a
normal stratum corneum . In vitro keratinocyte studies
have shown that depletion of T3results in elevated levels of
depleted keratinocytes have diminished levels of plasmino-
gen activator .
In tissue culture studies, T3has been shown to directly
dermal fibroblasts [32–34]. However, in vivo, skin prolifera-
tion directly stimulated by T3may be offset by inhibiting fac-
of skin in thyrotoxic patients are complicated by the fact that
most cases of thyrotoxicosis are the result of Graves’ disease
which has an associated finding of autoimmune-mediated
glycosaminoglycan deposition in the dermis .
transglutaminase (involved in the formation of the cornified
envelope). Further in vitro analysis has suggested that T3
stimulate proliferation of both epidermal keratinocytes and
2.2. Dermal Changes. The skin tends to be pale in hypothy-
roidism both because of the dermal mucopolysaccharides
and the dermal water content. Changes in hypothyroid
dermis can be seen in weeks and reversed in weeks [36,
37]. Hyaluronic acid is the major glycosaminoglycan that
drainage may explain the formation of exudates that are
apparent in the myxedematous state . Increased dermal
carotene may appear as a yellow hue on the palms, soles,
and nasolabial folds. In vitro, thyroid hormone actions
on cultured skin fibroblasts include inhibiting synthesis of
hyaluronic acid, fibronectin, and collagen [40–42].
The net effect of thyroid hormone on dermal thickness
remains the subject of debate. In the past, investigators
have reported skin thinning in rats made thyrotoxic with
intraperitoneal(IP) T4. Therehave been demonstrations
animals and increased collagen catabolism in thyrotoxic
dermal thickness in mice treated topically with TRIAC (a
thyroid hormone analog ).
both of decreased collagen production in the thyrotoxic
intraperitoneally [32, 33]. There is also a report of increased
2.3. Hair and Nail Changes. Hale and Ebling demonstrated
that intraperitoneal T4decreased both the resting phase
of the hair growth cycle (telogen) and the growth phase
of the hair growth cycle (anagen). Although there was an
enhanced turnover, the net hair length at any given time
was not changed from that of untreated animals . The
time to regrowth of hair following epilation was shortened
by approximately 10%.
In hypothyroidism, hair can be dry, coarse, brittle, and
slow growing. Nails may be thickened, brittle, and slow
growing . Diffuse or partial alopecia may be observed
The alopecia connected to hypothyroidism may be mediated
by hormoneeffects on the initiationas well as the durationof
backs and extremities of hypothyroid children . The hair
disappeared following thyroid hormone replacement, but no
mechanism was determined.
Clinically, the hair in thyrotoxicosis may be fine and soft.
Nail changes may also occur, characterized by a concave
contour and distal onycholysis (Plummer’s nails). Diffuse,
nonscarring alopecia may also be observed.
Like with epidermal proliferation, hair changes with
ically administered thyroid hormone. Mice and rats treated
daily for 1-2 weeks with topical T3had increased hair counts,
2 weeks had decreased hair counts [33, 44]. Thyrotoxic goats
had increased mohair length but decreased fiber diameter
. A topical mixture including thyroxine, insulin, and
growth hormone increased hair counts over a 6-month
treatment period in men with androgenic alopecia .
The dryness of hypothyroid skin results from decreased
ing is not clear although the glands are atrophic on histologic
examination . Hypothyroidism has been reported to be a
from cystic fibrosis .
Hypothyroid patients may sometimes suffer Candida
folliculitis. It has been theorized that this may result from
decrease sebum production relative to euthyroid persons.
The hair follicles may develop a flora with fewer lipophilic
organisms, which are replaced by Candida albicans .
but mice made thyrotoxic with daily intraperitoneal T3for 1-
3. Potential Use of Thyroid Hormone in the
Treatment of Cutaneous Pathology
Knowledge of cutaneous manifestations of thyrotoxicosis
does not predict the direct effects of T3on skin in vivo. T3
expresses the inactivating type 3 deiodinase , thyroid
hormone action on epidermis in systemic thyrotoxicosis is
less than might be predicted. In contrast to the findings with
systemic thyrotoxicosis, topical T3bypasses the inactivating
mal thickening, and hair growth [32, 33]. Topical application
of TRIAC (tri-iodothyroacetic acid), the thyroid hormone
analog, thickens skin by stimulating production of collagen
. Further, topical TRIAC has been shown to reverse the
dermal atrophy associated with corticosteroids.
Journal of Thyroid Research3
The importance of thyroid hormone in wound healing
had been debated historically. In 1973 and 1974, Mehregan
and Zamick reported that oral T3accelerated the rate of
treated animals. Lennox and Johnston reported accelerated
wound healing and increased tensile strength when rats
were given supraphysiologic doses of T4. Pirk et al.
rate of fracture repair . Ashton and Dekel also reported
body weight subcutaneous T4. In small series, there are
Conversely, Cannon  reported that hypothyroidism did
In contrast, most recent data suggest that topical thyroid
hormone may accelerate wound healing rate. Topical appli-
cation of supraphysiological doses of T3accelerated wound
addition to growth hormone and insulin .
While direct thyroid hormone action has been demon-
strated on cutaneous cell biology, much more study remains
to be done. There is a slowly evolving literature to suggest
an important role for thyroid hormone in cutaneous wound
repair that could be harnessed as a pharmaceutical.
wound healing in euthyroid rats and improved the qual-
ity of the wounds [54, 55]. Scars were smoother in T3-
reported no change in wound healing with 1.3휇g/100mg
body weight intraperitoneal T4in hamsters but increased
increased fracture repair rate in mice given 20휇g/100mg
reports that hypothyroid patients required thyroid hormone
healing in normal mice and rats [63–65]. A human wound
healing formulation has been described that requires T4in
Conflict of Interests
The author has no conflict of interests relating to this paper.
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