Full text of DOI:10.1007/BF03343905

J. Endocrinol. Invest. 24: 628-638, 2001
REVIEW ARTICLE
Skin disorders and thyroid diseases
H. Niepomniszcze* and R. Huaier Amad**
*
Thyroid Section, Division of Endocrinology, Hospital de Clínicas “José de San Martín”,
University of Buenos Aires, Buenos Aires; **Section of Medical Physiology, Department of Medicine,
Austral University, Derqui, Partido de Pilar, Pcia. de Buenos Aires, Argentina
ABSTRACT. Thyroid disorders have a high preva-
lence in medical practice; they are associated with
a wide range of diseases with which they may or
may not share etiological factors. One of the or-
gans which best show this wide range of clinical
signs is the skin. This review is an attempt to ap-
proach most of the dermopathies reflecting sev-
eral degrees of harmfulness, coming directly or in-
directly from thyroid abnormalities, as well as to
update current knowledge on the relationship be-
tween the thyroid and skin. We have proposed a
primary classification of skin disorders, regarding
thyroid involvement, into two main groups: 1) der-
mopathies associated with thyroid abnormalities,
mainly with autoimmune thyroid diseases, like
melasma, vitiligo, Sjögren’s syndrome, alopecia,
idiopathic hirsutism, pre-menstrual acne, bullous
diseases, connective tissue diseases, hamartoma
syndrome, atopy, leprosy and DiGeorge anoma-
ly; and 2) dermopathies depending on the nature
of the thyroid disorder, in which the evolution and
outcome of the skin disorder depend on the thy-
roidal treatment in most cases, such as trophism
and skin blood flow, myxedema, alopecia, ony-
chodystrophy, hypo- and hyperhidrosis, xanthomas,
intraepidermal bullae, carotenodermia, pruritus,
flushing, pyodermitis, palmoplantar keratoderma,
ecchymosis, etc. In some other cases, the skin dis-
ease which developed as a consequence of the thy-
roid abnormality can remain unaltered despite
functional treatment of the thyroid problem, such
as pretibial myxedema, thyroid acropachy and
some cutaneous manifestations of multiple en-
docrine neoplasia types 2A and 2B.
(J. Endocrinol. Invest. 24: 628-638, 2001)
©
2001, Editrice Kurtis
INTRODUCTION
ly or not) but in which no cause-effect relationship
has been demonstrated, and those dependent on
the thyroid disease itself (hyper- and hypothy-
roidism). The evolution and outcome of the der-
mopathy will depend, in most cases, on the thyroid
function (1).
Thyroid disorders have a high prevalence in medi-
cal practice; they are associated with a wide range
of diseases with which they may or may not share
etiological factors. Since manifestations are so var-
ied, their knowledge is interesting not only for en-
docrinologists but also for internists and other spe-
cialists. One of the organs which best show this
wide range of clinical signs is the skin, i.e. the three
layers (epidermis, dermis and hypodermis) and the
cutaneous phaneras (hair and nails).
DERMOPATHIES ASSOCIATED
WITH THYROID DISORDERS
These cutaneous disorders are seen with greater
incidence in patients affected by thyroid dysfunc-
tion than in the general population, though many of
the symptoms may overlap with the thyroid disease
itself (Fig. 1 and 2).
In an attempt to classify these cutaneous manifesta-
tions, we have divided them into two main groups:
those associated with thyroid diseases (temporari-
The most common classical association is dyschro-
mia or pigmentation spots, which may be classified
into hyper- and hypochromias that generally share
an autoimmune etiology.
The most frequent hyperchromia is melasma, a café-
au-lait pigmentation, without prurite or scaling, gen-
erally with centrofacial location, and which presents
Key-words: Skin, thyroid, hyperthyroidism, hypothyroidism, thyroid neo-
plasia, dermopathies, thyroid diseases.
Correspondence: Dr. Hugo Niepomniszcze, Av. Forest 335, Apt. 3-B,
1427 Buenos Aires, Argentina.
E-mail: hniepom@elsitio.net
Accepted February 19, 2001.
628

H. Niepomniszce and R. Huaier Amad
Connective tissue diseases:
•
Systemic
lupus erythematosus
Scleroderma
CREST syndrome
Sjögren’s syndrome
•
•
•
Epidermis
Dermis
Bullous diseases:
•
•
Pemphigus
Dermatitis herpetiformis
Miscellaneous associations:
•
•
Pre-menstrual acne
Leprosy
Oil
gland
• Psoriasis
• ANOTHER syndrome
•
Candida endocrinopathy
syndrome
Hamartoma syndrome:
Cowden’s disease
•
Fatty tissue
• Bannayan-Riley-Ruvalcaba
Dyschromia:
•
•
•
Melasma
Vitiligo
Leukomelanoderma
Atopy:
•
•
•
Atopic eczema
Urticaria
Dermographism
Fig. 1 - List of dermopathies associated
with thyroid diseases independently of
thyroid function.
Nerve
Follicle
Sweat gland
mainly in dark-skinned women who live in areas of
intense sunlight. In previous studies, we established
two etiologic groups with positive thyroid autoanti-
bodies: one idiopathic and another related to es-
trogen - progesterone. In the latter group, about
protein pmel 17 (6), which enable us to allocate it to
the category of autoimmune diseases. In our stud-
ies in this field, we also showed that this dyschromia
occurs with increased frequency and severity in fe-
males. Thus, we saw that 42% of males with vitiligo
had an alteration in their thyroidal parameters vs
62.5% of females, who had a clearly higher incidence
of thyroiditis (7, 8). Hegedus et al. found one or more
signs of thyroid disease in 43% of patients with vi-
tiligo (9). More recently, Beherens-Williams et al. (10)
applied an in vivo testing of cell-mediated immuni-
ty to define the cutaneous delayed-type hypersensi-
tivity (DTH) in the presence or absence of serum thy-
roid autoantibodies. DTH was evaluated both in nor-
mal and depigmented skin of vitiligo patients using
the dermal application of seven common recall anti-
gens, together with a negative control. Their in vivo
studies revealed, however, no clinically significant
aberrant cellular immunity in those patients.
7
0% of melasma patients had some thyroidal ab-
normalities vs 40% of patients in the idiopathic
group (2). We suggested that sexual steroidal hor-
mones (endogenous as in pregnancy or exogenous,
such as oral contraceptives) trigger the development
of melasma in women who have a particular genet-
ic predisposition to thyroidal autoimmune diseases.
Among hypochromias, the main expression is vitiligo,
which is characterized by achromic areas with hy-
perpigmented margins. These lesions have an in-
sidious onset, without pruritus or anesthesia, and are
not coupled with scaling, atrophy or sclerosis. Ge-
nerally, they are symmetrically located, mainly in the
back of the hands, face, neck, folds and genitals. Its
prevalence in the general population is 1-2%, where-
as in subjects with Graves’ disease it rises to 6-7%. It
has been demonstrated that in vitiligo there are an-
tibodies against melanine (3), tyrosinase (4), tyrosi-
nase-related protein-1 (5) and melanocyte-specific
The two lesions described above may combine in-
to leukomelanoderma, and may occasionally be as-
sociated with Sjögren’s syndrome (11, 12).
The Vogt-Koyanagi-Harada’s syndrome, which af-
fects the melanocyte-containing tissues, has also
629

Thyroid and skin disorders
Lesion of phaneras
Plate
Bed
Matrix
Bone
Medulla
Cortex
Cuticle
Shaft
Sebaceous
gland
Associated
Alopecia areata
Alopecia totalis
Diffuse alopecia
Idiopathic hirsutism
Hypoplasia of nails
Arrector pili
keratinization
zone
Dependent
Diffuse alopecia
Alopecia universalis
Fetal hypertrichosis
Onycholysis
Follicle
Hair bulb
Papilla
Root
Koilonychias
Blood vessel
Plummer’s nails
Beau’s ridge
Fig. 2 - Lesions of phaneras associated
with and dependent on thyroid abnor-
malities.
Thyroid acropachy
been associated with Hashimoto’s thyroiditis (13).
Like dyschromias, alopecia areata (14) is classically
associated with thyroid diseases. Its main features
are circumscribed bald patches in the scalp or
beard. The lesions have a clean appearance and the
hair follicles can be observed within them. Genetic
factors are undoubtedly important in its etiology,
since a direct relation with DQ7, DR4 and DR5 has
been demonstrated. As regards alopecia totalis/uni-
versalis (14), it was HLA-DR11 that showed a more
direct relation (30.2 increase in relative risk). Also,
polymorphisms were detected in intron 2 of the in-
terleukin 1 receptor antagonist gene, which is as-
sociated with severity in other chronic inflammato-
ry autoimmune disorders. Clinical studies revealed
that the strongest association is with vitiligo and
thyroid diseases. Thyroid disorders (mainly thy-
roiditis) were reported in 8% of alopecia cases in
comparison with 2% of controls. Several studies re-
ported an increased frequency of thyroid autoanti-
bodies in this entity and the presence of antibodies
that react with the endothelia of perifollicular cap-
illaries. Furthermore, both pathologies share cellu-
lar immunity abnormalities, such as reduced num-
bers of circulating T suppressor/cytotoxic cells
(CD8+ve), with a clear prevalence of CD4+ve cells.
Lymphocytic infiltration results in an increased ex-
pression of class I and class II HLA antigens. Hair
bulb melanocytes are damaged in this process as
well, and melanogenesis may cease. There is also a
630

H. Niepomniszce and R. Huaier Amad
rise in the expression of intercellular adhesion
molecule 1 (ICAM-1) in both dermal papilla and hair
matrix and hair bulb keratinocytes. It was suggest-
ed that increased antigen HLA and ICAM-1 ex-
pression might result from cytokine release by in-
filtrating inflammatory cells, though this remains to
be confirmed. The investigation of Sterzl et al.
about the frequency of extrathyroid organ specific
and non-specific autoantibodies in patients with au-
toimmune thyroiditis is interesting. The authors re-
fer 45% of mutual positivity of antibodies against
thyroid peroxidase and antibodies against the hair
follicles (15). Asanuma et al. (16) reported the first
documented case of alopecia universalis during
pregnancy with remission on prednisolone thera-
py. Autoantibody measurements were positive for
the antithyroid and antinuclear antibodies. Ho-
wever, thyroid function and glucose tolerance were
normal, and other clinical evidence of collagen vas-
cular disorders were not found.
rophic variant of Hashimoto’s thyroiditis (19).
However, the goitrous variant of Hashimoto’s thy-
roiditis was not seen in any of those patients.
Chronic mucocutaneous candidosis is a complex
disorder characterized by chronic and recurrent can-
dida infections of the skin, nails and oropharynx. In
over 50% of cases there is an associated endocrine
disease to follow an autosomal recessive pattern:
Candida endocrinopathy syndrome. Coleman et al.
reported a new syndrome in which there is vertical
transmission of chronic mucocutaneous candidosis
within families associated with primary hypothy-
roidism (20).
Connective tissue diseases, such as systemic lupus
erythematosus (21) (mainly seronegative types),
Scleroderma and the CREST syndrome (calcinosis,
Raynaud’s phenomenon, esophageal dysfunction,
scleroderma, telangiectasias) (11, 22) show the
strongest association with thyroid diseases. We find
a great variety of associated cutaneous manifesta-
tions, ranging from xeroderma and sclerosis to pur-
pura and ecchymosis, from butterfly shaped ery-
thema and Raynaud’s phenomenon to telangiec-
tasias and calcinosis. A remarkable high prevalence
of autoimmune thyroiditis in systemic sclerosis has
already been described (23).
Psoriasis (12, 24) is one of the entities most fre-
quently associated with Sjögren’s syndrome (11,
12), which is, in turn, related to autoimmune thy-
roiditis. Few cases of association between these
three entities have been described. A gene in-
volved in psoriasis susceptibility was mapped to hu-
man chromosome 17q (25) and Torma et al. (26)
found that the retinoid and thyroid hormone sig-
nalling is abnormal in lesional psoriatic skin. The ex-
pression of three housekeeping genes (cyclophilin,
GAPDH and β-actin) was consistently higher in le-
sional than in non-lesional skin, and the expression
of the nuclear receptor for retinoic acid, vitamin D3
and thyroid hormone plus the common hetero-
dimer partners, the 9-cis-retinoic acid receptors,
were found to be lower in lesional than in non-le-
sional skin.
Researches conducted by our group showed an as-
sociation between diffuse alopecia (17) and thyroid
diseases in 60% of the cases, mainly of autoimmune
origin, with normal T and T circulating levels but
3
4
with subclinical abnormalities, such as small goiters
and/or hyperresponses of TSH to TRH, as well as
the presence of circulating autoantibodies to thy-
roid peroxidase. In the same study (17), we report-
ed the association of thyroid diseases with idiopathic
hirsutism (55.5%) and pre-menstrual acne (50%) in
female patients with normal androgenic levels. Only
1
2.5% of control patients, however, presented thy-
roid disturbances. In addition to these associations,
it is interesting to mention the case report of a 13-
year-old girl who presented remission of acantho-
sis nigricans, hypertrichosis, and Hashimoto’s thy-
roiditis with T replacement (18).
4
Another association described in patients with au-
toimmune thyroid diseases is pemphigus (3), in its
vulgaris variety as well as in its erythematous and
foliaceous manifestations. It may or may not simul-
taneously appear with the thyroid disease. Among
bullous diseases, dermatitis herpetiformis (3) also
has a strong association with thyroid diseases. It
was found that 34% of these patients had clinical
or functional thyroidal abnormalities, including hy-
pothyroidism, Graves’ disease, toxic multinodular
goiter and follicular carcinoma. Antimicrosomal an-
tibodies were significantly present: 38% vs 12% in
control patients. There was also a preponderance of
HLA-B8 and HLA-Dw3 antigens, which are related
to Graves’ disease and Hashimoto’s thyroiditis, re-
spectively. A recent study investigated a cohort of
Cox et al. proposed to replace the acronym TASS
syndrome (thyroiditis, Addison’s disease, Sjögren’s
syndrome and sarcoidosis) by another acronym,
TOASSUC (thyroiditis, other autoimmunity, Sjögren’s
syndrome, sarcoidosis and ulcerative colitis), because
it includes a wider range of disorders (27).
Cowden’s disease (3) or multiple hamartoma syn-
drome is an autosomal dominant disorder which is
characterized by warty skin lesions (trichilemmo-
mas) affecting the face, mucous membranes and
distal extremities, in association with benign or ma-
lignant tumors of the thyroid and breasts. About
4
1 patients, vs a control group, demonstrating that
dermatitis herpetiformis is associated with the at-
631

Thyroid and skin disorders
two-thirds of patients present with thyroid disease,
early multinodular goiter being the most frequent,
though there is also a high frequency of solitary
nodules, thyroiditis and carcinoma. Perriard et al.
describe a family with the unusual association of
Cowden’s disease and Bannayan-Riley-Ruvalcaba’s
though the thyroid is neither the only gland affected
nor the most frequently affected one, and there is
no strong evidence for this relationship in the litera-
ture. Some studies have reported decreased thyroid
hormone levels with a statistically significant corre-
lation between the T decrease and lepromatose re-
3
(BRR) syndrome (28). The later is an hamartoma syn-
action, and between the T decrease and lepro-
4
drome characterized by early-onset macrocephaly,
lipomatosis, hemangiomas, hamartomatous polyps
of the gastrointestinal tract, vascular malformations,
pigmented maculas of the glans penis (speckled
penis) in males, Hashimoto’s thyroiditis, and mild
intellectual delay. Germline mutations in PTEN, a
tumor suppressor gene mapping to 10q23.3, have
been found in 13-81% of Cowden’s syndrome pa-
tients and 57-60% of BRR cases (29). Two cases of
matose leprosy and borderline states. Lepromatose
reactions coupled with Type 2 diabetes mellitus and
hypothyroidism have also been described.
Sweet’s syndrome (acute febrile neutrophilic der-
matosis) can be associated with subacute thyroidi-
tis. The role of cytokines might be the link between
these two conditions (37).
About phaneras, hypoplasia of all nails was de-
scribed in DiGeorge anomaly, with absent thyroid
isthmus, congenital heart defects and multiple mal-
formations in infants (38).
10q deletion encompassing PTEN have also been
reported in BRR (30). Gorlin et al. proposed to ex-
pand the phenotypic spectrum of BRR to include
Hashimoto’s thyroiditis (31).
There is also an entity termed either hypohydrotic
ectodermal dysplasia or ANOTHER syndrome,
which associates alopecia, nail dystrophy, ophtalmic
complications, thyroid dysfunction, hypohidrosis,
ephelides/enteropathy and respiratory tract infec-
tion. Only three cases of this syndrome have been
described (3).
Another association established in the literature is
atopy in its different expressions. We might say that
the most studied entity is atopic eczema. High his-
tamine levels (in dermic tissue samples of affected
patients) were shown to have a relation, still unex-
plained, to increased circulating histaminase activ-
ity in patients with medullar thyroid carcinoma.
These findings led to the proposal that the intra-
dermal histamine test should be used to determine
the extent of disease dissemination or metastases
DERMOPATHIES DEPENDING
ON THYROID DISORDERS (FIG. 2 AND 3)
Hypothyroid state
In hypothyroidism, the skin is characteristically dry,
rough and cool to the touch. This is the result of the
direct influence of thyroid hormones on trophism
and skin blood flow. Thus, measurements of skin
perfusion by Laser-Doppler flowmetry (39) demon-
strated that in hypothyroid patients, not undergo-
ing treatment, mean capillary flow velocity, capil-
lary pulse wave amplitude and capillary flow oscil-
lation amplitude were decreased in comparison to
euthyroid patients. This decrease was even higher
in comparison to hyperthyroid patients. In this case,
thyroid opotherapy proved to be effective. Electro-
dermal abnormalities in the absence of measurable
psychiatric symptoms were also observed in hy-
pothyroid subjects. Lower skin conductance levels,
lower fluctation rates and prolonged onset latencies,
but normal amplitudes, were related to changes of
the hypothalamic-pituitary-thyroid axis function (40).
Pazos-Moura et al. (41) also found that the skin mi-
crovascular autoregulatory mechanism is disturbed.
They used direct intravital microscopic examination
of nailfold capillaries.
Acquired variants of palmoplantar keratoderma (42),
seen in hypothyroid patients among others, show an
impressive response to specific treatment. The dis-
ease may be due to the longer mitotic duration and
decrease in epidermal steroidogenesis. Additionally,
there is an increased keratin production and a re-
duction of intercellular lipids, both contributing to
changes in transepidermal water loss. The kerato-
derma can become generalized; in this case it is
known as xeroderma or ichthyosiform conditions,
(
32). It is thought that endocrine disorders act as
triggering factors in the development of the ecze-
ma. A recent finding showed that IgE responsive-
ness is linked to a locus on chromosome 11q13,
close to a gene encoding the β-subunit of the high-
affinity IgE receptor. Such locus is also involved in
the development of type I MEN. Other manifesta-
tions of atopy related to both hyper- and hypothy-
roidism are urticaria and dermographism, though
a direct cause-effect relation has not been estab-
lished. Recently, the association of chronic urticaria
and angioedema (CUA) with autoimmune thyroidi-
tis was observed in both patients with thyroid dys-
function and euthyroid subjects (33), and resolution
of chronic urticaria was achieved under T treatment
(
4
34).
There are entities, such as leprosy (35, 36), which are
less habitually associated with thyroid diseases,
632

H. Niepomniszce and R. Huaier Amad
Hyperthyroidism
Hyperhidrosis
Hyperpigmentation
Erythema
Pretibial myxedema
Pruritus
Flushing
Peau d’orange
Epidermis
Hypothyroidism
Xeroderma
Pilose keratosis
Palmoplantar keratoderma
Skin microvascular autoregulatory mechanism disturbed
Hypohidrosis
Generalized myxedema
Intraepidermal bullae
Purpura
Dermis
Oil
gland
Ecchymosis
Carotenodermia
Xanthomas
Generalized pruritus
Granuloma annulare
Pyodermitis
Fatty tissue
Fig. 3 - Skin disorders due to alterations of the thyroid func-
tion, both in hyper- and hypothyroidism, and also due to
Graves’ disease itself.
Nerve
Follicle
Sweat gland
more frequently found in severe cases of hypothy-
roidism. A mild expression of ichthyosis is pilose ker-
atosis, a keratosis in hair follicles with permanent
alopecia, frequently associated with hypothyroidism,
with which it shares an autoimmune etiology. It is
more commonly found in teenagers and is mainly lo-
cated in the back of arms and thighs.
A consequence of thyroid dysfunction that con-
tributes to skin dryness is the decrease in sweating
and in sebum secretion, known as hypohidrosis (3).
Generalized myxedema or cutaneous mucinosis is
a characteristic sign of the hypothyroid state. Pa-
tients present with diffuse edema, without fovea,
most prominent in periorbital and acral locations.
This disorder is the result of a generalized increase
in dermal acid mucopolysaccharides, particularly
hyaluronic acid and chondroitin sulfate. Occasio-
nally, generalized myxedema may simulate the
musculoskeletal symptoms of polymyositis (43).
Transcapillary escape of albumin into the dermis
contributes to edema formation. Finally, the der-
mal concentration of elastic fibers is reduced in the
skin from patients with generalized myxedema.
Recently, an association between Hashimoto’s thy-
roiditis and mid-dermal elastolysis (loss of elastic
fibers in the mid-dermis due to elastophagocyto-
sis, with giant cells and granuloma formation) has
also been described (44) as well as reticular ery-
thematous mucinosis and acral papulokeratotic le-
sions, showing a rapid regression after levothyrox-
ine treatment (45). All these disorders determine
the development of friction-induced intraepidermal
bullae as well as purpura and ecchymosis. Actually,
Le Brun et al. (46) recommended thyroid hormone
assays in any patient presenting pretibial bullae.
They report a case of hypothyroidism and pretibial
epidermolysis bullosa, which rapidly regressed after
hormone therapy. Pathology reported blisters with
subepidermal cleavage and a substance which is
dense at the electron microscopy.
A reflex cutaneous vasoconstriction as a mechanism
to maintain body temperature is induced by hy-
633

Thyroid and skin disorders
Hyperthyroid state
pothermia in hypothyroid patients, resulting in pal-
lor and skin that is cool to the touch (39).
Hyperthyroid patients present an hypermetabolic
and hyperdynamic state in cutaneous perfusion
(49). Their skin is often warm and moist to the
touch, resulting in hyperhidrosis. They also present
with erythema, particularly facial and palmar. Flu-
shing occurs as a mechanism for body temperature
regulation by dermal vasodilatation. The sebum ex-
cretion rate was found to be normal and uninflu-
enced by therapy. Hyperpigmentation in a local-
ized and/or diffuse distribution (not caused by as-
sociated melasma) may occur in hyperthyroid states
due to an increased release of pituitary adreno-
corticotropic hormone compensating for acceler-
ated cortisol degradation.
Unlike hypothyroid patients, in hyperthyroid cases
myxedema appears mainly in pretibial locations
and is characterized by sharply circumscribed
plaques, though diffuse or elephantiasic presenta-
tions may also occur, the latter consisting of ede-
ma and superimposed plaques. Pretibial myxede-
ma is most commonly associated with Graves’ dis-
ease (53). Three to five percent of patients with this
disease develop myxedema, and 70-90% of cases
are associated with exophthalmous. When the
pretibial myxedema is combined with bilateral ex-
ophtalmous and acropachyderma of fingers and
toes, it is called Diamond syndrome (54). The pla-
ques may have a peau d’orange appearance and
overlying hypertrichosis is sometimes noted (3).
Histologically, pretibial myxedema is caused by ac-
cumulation of mucin in the lower two thirds of the
dermis that produces wide separation of collagen
fibers. Fibroblasts in tissue culture from patients
with Graves’ disease demonstrated increased hya-
luronic acid production as compared with sera
from euthyroid patients (55). A heat-stable, pro-
tease sensitive, and dialyzable stimulating sub-
stance, which differs from thyroid-stimulating im-
munoglobulins, has been identified. This substance
is thought to be involved in the development of
myxedema in Graves’ disease. It has been sug-
gested that fibroblasts have an intrinsic defect in
local degradation of cutaneous proteoglycans, and
we have observed, by means of in vitro studies,
that radiolabeled human serum albumin is selec-
tively accumulated in the skin of pretibial myxede-
ma (56).
The lack of hepatic metabolization of carotene pro-
duces its accumulation in the stratum corneum. Caro-
tene then is excreted in sweat and reabsorbed by the
skin, with deposition occurring mainly in areas rich in
sebaceous glands. This is another factor that may
change skin color, giving it a characteristic yellowish
tint or carotenodermia. Hypercholesterolemia is al-
so manifested in the skin of hypothyroid patients;
both tuberous and eruptive xanthomas (3) are fre-
quently seen. The skin of these patients, as we have
seen, is a dermis with delayed cicatrisation and a ten-
dency to develop pyodermitis. Generalized pruritus
(
47) is not rare, though there are discrepancies in
the literature as regards this symptom, since in
some cases it is reported as associated to and not
dependent on thyroid dysfunction.
There were evidences that granuloma annulare and
autoimmune thyroiditis may be associated (48, 49).
Treatment with T resulted in the restoration of a
4
euthyroid state and a progressive decrease in the
number of the skin lesions in patients with gener-
alized granuloma annulare associated with mild hy-
pothyroidism, which was due to an atrophic au-
toimmune thyroiditis (50).
Phaneras are also affected by this systemic disor-
der. The decrease in sebaceous gland output caus-
es hair to be opaque; its growth rate is retarded
owing to the delayed initiation of the anagen
phase. Hair loss resulting in diffuse alopecia is also
possible.
The presence of fetal hypertrichosis in hypothyroid
newborn babies and the retention or apparition of
lanugo hair in children with severe hypothyroidism
are well known (3). To investigate the cellular basis
of the action of thyroid hormone on hair follicles,
Ahsan et al. (51) studied the immunohistochemical
localization of thyroid hormone receptors in human
scalp skin; they were found in the nuclei of the out-
er root sheath cells, dermal papilla cells, fibrous
sheath cells of hair follicles, hair arrector pili mus-
cle cells and sebaceous gland cells. L-T stimulated
3
the in vitro proliferation and/or metabolism of all
these types of cells significantly, although there
were variations on the rate of stimulation. Likewise,
there was a correlation between selenium concen-
tration in hair and nails and thyroid morphology,
serum concentrations of thyroid hormones and pe-
ripheral parameters of hormone actions (Achilles
tendon reflex, pulse rate or antrophometric vari-
ables) (52). In hypothyroidism, the nails are thin and
brittle. They grow slowly and with longitudinal ridg-
ing. In addition, onycholysis and koilonychias (flat
or concave nails) may develop.
An acral ichthyosiform mucinosis in association with
Sjögren’s syndrome, in the absence of Graves’ dis-
ease, has been described as a peculiar form of
pretibial myxedema (57).
As regards phaneras, hyperthyroid patients may al-
so present with diffuse alopecia due to reduction
of the anagen phase of the hair cycle, which alters
634

H. Niepomniszce and R. Huaier Amad
CONCLUSIONS
the anagen/telogen ratio. Exceptionally, we have
seen alopecia universalis after radioiodide treat-
ment of thyrotoxicosis in psychiatric patients with
Graves’ disease. Nails are usually shiny and grow
more rapidly, though they may also be friable, and
the lifting of the distal nail plate gives the hypony-
chium a ragged and dirty appearance (Plummer’s
nails). Beau’s ridge, a thick transversal ridge, is com-
monly found (3).
An effect that is rarely seen is thyroid acropachy,
which is characterized by a triad of findings: 1) club-
bing of the fingers/toes; 2) thickening and fibrosis
of the subcutaneous tissue; 3) diaphyseal periosteal
proliferation with occasional new bone formation
in the distal extremities.
There is a wide range of skin disorders which reflects
several degrees of harmfulness coming directly or in-
directly from thyroid abnormalities. Their manifesta-
tions are so varied that they become amazing for
both endocrinologists and dermatologists as well as
for general clinicians. This review is an attempt to ap-
proach most of these dermopathies and to update
the current knowledge on the relationship between
the thyroid and the skin. We have proposed a pri-
mary classification of the skin disorders, regarding the
thyroid involvement, in two main groups: 1) der-
mopathies associated with thyroid abnormalities,
mainly to autoimmune thyroid diseases, like dyschro-
mias, Sjögren’s syndrome, alopecia, idiopathic hir-
sutism, pre-menstrual acne, bullous or connective tis-
sue diseases, hamartoma syndrome, atopy, leprosy
and DiGeorge anomaly; and 2) dermopathies de-
pending on the nature of the thyroid disorder, in
which the endocrinological treatment leads to the
cure or amelioration of the dermatological symptoms
in most of the patients. The skin alterations, seen in
hyper and hypothyroidism, are good examples of the
strong influence of the circulating levels of thyroid
hormones on the dermic tissue.
Pruritus is usually part of the constellation of symp-
toms in hyperthyroidism (41). Thus, assessment of
thyroid status is a common practice in laboratory
evaluation for this symptom, which is undoubtedly
associated with hyperthyroidism.
Thyroid neoplasia
Multiple endocrine neoplasia (MEN), especially
type 2B, which is associated with medullary thy-
roid carcinoma, is characterized by café-au-lait
spots, diffuse lentigos, neuromas and neurofibro-
mas (3). In the Carney complex, which combines
multiple neoplasia and lentiginosis syndrome, thy-
roid abnormalities ranging from follicular hyperpla-
sia and/or cystic changes to carcinoma have been
described (58).
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