CUTANEOUS MANIFESTATIONS IN THYROID DISORDERS
Dissertation Submitted in
Partial fulfillment of the University regulations for
MD DEGREE IN
DERMATOLOGY, VENEREOLOGY AND LEPROSY
(BRANCH XX)
MADRAS MEDICAL COLLEGE
THE TAMILNADU DR. M.G.R. MEDICALUNIVERSITY CHENNAI, INDIA.
APRIL 2017
CERTIFICATE
Certified that this dissertation titled “CUTANEOUS MANIFESTATIONS IN THYROID DISORDERS” is a bonafide work done by Dr UMA MAHESWARI S, Post graduate student of the Department of Dermatology, Venereology and Leprosy, Madras Medical College, Chennai-3, during the academic year 2014 – 2017. This work has not previously formed the basis for the award of any degree.
Prof. U.R.DHANALAKSHMI MD.,D.D.,DNB Professor and Head,
Department of Dermatology,
Madras Medical College& Rajiv Gandhi Govt.General Hospital,
Chennai-3
Prof Dr.M.K. MURALITHARAN.,M.S.,Mch Dean
Madras Medical College & RGGGH, Chennai-03.
DECLARATION
The dissertation entitled “CUTANEOUS MANIFESTATIONS IN THYROID DISORDERS” is a bonafide work done by Dr. UMA MAHESWARI S at Department of Dermatology, Venereology and Leprosy, Madras Medical College, Chennai – 3, during the academic year 2014– 2017 under the guidance of Prof.Dr.A.RAMESH M.D.,DD.,DNB(DVL) Professor, Department of Dermatology, Madras Medical College, Chennai -3.
This dissertation is submitted to The Tamil Nadu Dr. M.G.R. Medical University, Chennai towards partial fulfillment of the rules and regulations for the award of M.D Degree in Dermatology, Venereology and Leprosy (BRANCH – XX)
Prof. Dr.A.RAMESH, M.D.,DD.,DNB (DVL) Professor,
Department of Dermatology, Madras Medical College, Chennai-03
DECLARATION
I, Dr. UMA MAHESWARI. S solemnly declare that this dissertation titled “CUTANEOUS MANIFESTATIONS IN THYROID DISORDERS” is a bonafide work done by me at Madras Medical College during 2014-2017 under the guidance and supervision of Dr. U.R.DHANALAKSHMI.,M.D., D.D.,DNB, Professor and head department of Dermatology, Madras Medical College,Chennai-600003.
This dissertation is submitted to The Tamil Nadu Dr. M.G.R. Medical University, Chennai towards partial fulfilment of the rules and regulations for the award of M.D Degree in Dermatology, Venereology and Leprology (BRANCH – XX)
PLACE :
DATE : (Dr. UMA MAHESWARI S)
SPECIAL ACKNOWLEDGEMENT
My sincere thanks to Prof Dr.M.K. MURALITHARAN, M.S.,Mch., Dean, Madras Medical College for allowing me to do this dissertation and utilize the Institutional facilities.
ACKNOWLEDGEMENT
I am gratefully indebted to Professor and Head of the Department of Dermatology, Prof. Dr U.R.DHANALAKSHMI, M.D., D.D.,DNB for her invaluable advice, guidance and encouragement throughout the study.
I would like to express my sincere and heartfelt gratitude to Prof.Dr.S KALAIVANI M.D., D.V., Director(i/c) and Professor, Institute of Venereology, for her kindness and support throughout the study.
I sincerely thank Prof. Dr. A.RAMESH, M.D., D.D., DNB (DVL) Professor of Dermatology for his priceless support. He has been a source of constant motivation and encouragement throughout the study. I am extremely grateful to him for guiding me throughout the study.
I thank Prof Dr. S. KUMARAVEL M.D.,DD Professor of Dermatology for his support and encouragement.
I thank my Professor and Head of the department of Occupational and Contact Dermatitis, Prof. Dr. S. NIRMALA M.D., for her help and support.
I sincerely thank Prof. Dr .R. PRIYAVATHANI M.D., D.D., DNB., MNAMS., Professor of Dermatology for her precious advice and encouragement.
I express my sincere gratitude to Prof. Dr. V. SAMPATH M.D. ,Professor of Dermatology for his guidance and support.
I am grateful to Prof. Dr. J.MANJULA M.D., DNB., Associate Professor, Department of Dermatology for her invaluable guidance and help.
I wish to thank Prof. Dr.. K. MANOHARAN.M.D.,D.D., former Professor and Head of department,,Dermatology for his support and motivation.
I also wish to thank Prof. Dr. V.SUDHA M.D., D.V., D.D., former Professor and Director, institute of venereology for her support and motivation.
I humbly thank my Co-Guide, Dr. K. UMA MAHESHWARI M.D.D.V.L assistant prof. of dermatology for her valuable guidance throughout my work.
I would like to express my sincere and heartfelt gratitude for the time which she has devoted for my research project.
I extend my gratitude to Dr.R.MADHU M.D., D.C.H., Dr.V.N.S.AHAMED SHARIFF M.D.D.V.L., Dr.SAMUEL JEYARAJ DANIEL M.D. D.V.L., Dr. V VIJAYALAKHSMI, M.D. (D.V.L.) DR.R.MANIPRIYA MD (DVL).,DCH., DR K DEEPA MD (DVL). ,DR.
C.L.CHITHRA MD (DVL), Assistant professors, Department of Dermatology for their kind support and encouragement.
I also thank my Assistant Professors Dr. P. PRABHAKAR M.D.D.V.L., Dr. C. VIDHYA, M.D.DVL., Dr. R HEMAMALINI M.D.D.V.L.,Dr H.DHANASELVI M.D(DVL).,DLO., Dr. K GAYATHRI M.D.D.V.L.,Dr.E .
BALASUBRAMANIAN M.D.D.V.L.,Dr .S SNEHAVALLI M.D.D.V.L., of Institute of Venereology for their able guidance.
I express my thanks to Dr. G.K. THARINI M.D.,Dr. N. SARAVANAN M.D. D.V.L., Dr. NITHYA GAYATHRI DEVI, M.D.D.V.L.my former assistant professors,Department of Dermatology, for their support and help.
I wish to thank to Dr.P.MOHAN M.D., D.V.,Dr. S. VENKATESAN D.V., DNB (D.V.L.), Dr.V. GOMATHY M.D. D.V.L former Assistant Professors, Institute of Venereology for their constant guidance.
I am thankful to my colleagues for their support throughout the study.
I am also grateful to all paramedical staffs for rendering timely help to complete my study.
I am also extremely thankful to my family for their motivation and encouragement.
Last but not the least I am profoundly grateful to all patients for their co-operation and participation in this study. They have been the principal source of knowledge which I have gained during the course of my clinical research.
CONTENTS
S.
NO. TITLE PAGE
NO.
1. INTRODUCTION 1
2. REVIEW OF LITERATURE 2
3. AIMS AND OBJECTIVES 36
4. MATERIALS AND METHODS 37
5. OBSERVATION AND RESULTS 41
6. DISCUSSION 70
7. CONCLUSION 79
8. BIBLIOGRAPHY 81
9. ANNEXURES
PATIENT INFORMATION SHEET & CONSENT FORM
PROFORMA
MASTER CHART
ABBREVIATIONS
ETHICS COMMITTEE APPROVAL
PLAGIARISM APPROVAL
Introduction
1
INTRODUCTION
Thyroid disorders influence almost every organ system of human body and the largest organ of our body, skin is no exception to this. Skin depicts numerable external markers which are associated with underlying abnormality of thyroid function and diseases. These cutaneous changes can appear as the first presenting signs, or may occur subsequently to the development of thyroid diseases or in some cases may precede the diagnosis of thyroid disorders even by many years.
Hence it is important for a dermatologist to be well equipped with knowledge of various cutaneous manifestations of thyroid disorders which in turn aids in early diagnosis and prompt treatment of thyroid diseases.
This study has been done to evaluate the prevalence and pattern of various cutaneous manifestations in patients with thyroid disorders.
Review of Literature
2
REVIEW OF LITERATURE
Anatomy and physiology of thyroid gland
The thyroid gland along with thymus and parathyroid gland start forming in the fifth week of intrauterine life. The thyroid gland develops mainly from the thyroglossal duct, which in turn is derived from the endoderm of the fourth and fifth pharyngeal arches. [1]
The gland is present in anterior aspect of neck at the vertebral level of C5 - T1. It weighs about 15-20 grams in a healthy adult and has two lateral lobes connected by a median isthmus. Blood supply to the gland is by superior and inferior thyroid arteries. It drains into external jugular vein and is richly innervated by autonomic nerves. [2]
Histologically the gland consists of aggregates of follicles which are formed by single layer of cuboidal epithelial cells, surrounding a central thick colloid substance. The gland begins to function at the end of third month of intra uterine life. [3]
The principal hormones synthesized and secreted by thyroid gland are 1) Thyroxine (T4)
2) Triiodothyroxine (T3)
3) Calcitonin (secreted from parafollicular C cells of thyroid)
4) RT3 (reverse triiodothyronine), which is secreted in small quantity.
3
T3 is more active form than T4. But it is the T4 secreted in more quantity than T3 by the thyroid gland. However majority of T4 is being converted to T3 in peripheral blood and tissues. Thus T4 is mainly a prohormone.
Thyroid hormones secreted from thyroid gland, activates the cytoplasmic receptors of target tissues, and then subsequently translocate into their nucleus and activate the thyroid specific response genes thus exhibiting their principle action on target cells. [4]
Steps involved in thyroid hormone synthesis are:
1. Iodide trapping
2. Iodide to iodine conversion 3. Synthesis of thyroglobulin 4. The coupling reaction 5. Proteolysis of thyroglobulin 6. Thyroid hormones secretion.
Regulation of thyroid hormone synthesis:
The hypothalamus secretes “thyrotropin releasing hormone” (TRH). The thyrotropes of anterior pituitary gland is stimulated by “thyrotropin releasing hormones” to secrete “thyroid stimulating hormone” (TSH). This TSH stimulates thyroid gland to secrete T3 and T4. The synthesis and release ofthyroid hormones is executed by the G-protein coupled receptor binding action of TSH on thyroid gland.
4
The rate of secretion of thyroid hormones is as follows; [5]
1) Thyroxine : 80 -90 microgram / day 2) Tri iodothyroxine : 4-5 microgram / day
The normal plasma levels of total T3 is 0.12 microgram/dL and that of T4 is 8 microgram /dL. These secreted T3 and T4 are present in major as protein bound form in the peripheral blood to the following plasma proteins;
1) Thyroid binding globulin (TBG) - major plasma binding protein.
2) Albumin
3) Pre albumin (Transthyretin)
The protein binding acts as a reservoir, protects the hormones against metabolic de gradation thus increasing the half-life of T3 and T4. The unbound form of T3 and T4 provides feedback signal for regulated release of TRH and TSH. A better indicator of thyroid function is the activity of T3.
5
Figure 1: Regulation of thyroid hormone synthesis
The following is the action of thyroid hormone in various organ system of our body:
Hypothalamus
Anterior pituitary
thyroid
TRH
TSH
T3 T4 Negative feed back
6
Table 1: Action of thyroid hormone in various organ systems TARGET
SYSTEM FUNCTIONS
1) Metabolism ↑ in oxygen consumption there by increase in BMR
2) CVS
Tachycardia, ↑ cardiac output, ↓peripheral resistance,↑ myocardial contractility 3) Bone Skeletal development and increased growth
4) Muscle
Increased expression of MHC genes, protein catabolism
5) Adipose tissue Increased lipolysis
6) CNS Brain development
7) GIT
↑appetite, stimulates GI motility, ↑carbohydrate metabolism
8) Skin
Stimulates fibroblasts & increases proteoglycan synthesis,
Regulates epidermal differentiation, essential in hair and sebum formation.
9) Reproduction Maturation of follicles and ovulation
7
Etiopathogenesis and manifestations of thyroid disorders:
Several factors including medical conditions [6] and medications [7] have a profound influence on thyroid functional status. They are as follows;
\
Table 2: Medical conditions affecting thyroid hormone levels
Abnormality causes
Conditions in which thyroid-binding globulin levels are decreased
Severe systemic illness
Acromegaly
Chronic liver disease
Nephrosis
Conditions increasing thyroid binding globulin levels
Chronic active hepatitis
Pregnancy
Acute intermittent porphyria peripheral conversion of T4 to T3 is
decreased
Systemic illness
Malnutrition
Trauma
8
Table3: The effect of various drugs on thyroid gland:
Drugs Effect on thyroid gland
Iodide
Amiodarone
Lithium
↑ or ↓ thyroid hormone secretion
↑ or ↓ thyroid hormone secretion TH secretion is decreased
Anabolic steroids
Androgens
Glucocorticoids
Nicotinic acid
Decreases serum thyroid binding globulin levels.
Estrogens
5 fluorouracil
Methadone
Increases serum TBG levels
Bexarotene thyrotropin levels is decreased
Amiodarone
Propylthiouracil
Beta blockers
Decreases the de iodisation of T4 to T3
Phenytoin
Phenobarbital
Rifampin
Metabolism of thyroid hormones in the liver is increased
Genetic predisposition along with environmental factors including infection predisposes to the pathogenesis of autoimmune thyroid disorders.
9
Iodine is the principle source of thyroid hormone synthesis. So any abnormality in iodine levels can lead to both hypothyroidism and hyperthyroidism.
Hypothyroidism: Hypothyroidism (also known as myxedema) results from reduced levels of thyroid hormones with resultant hypo metabolic state. It can be broadly classified as primary and secondary hypothyroidism.[8]
1) Primary hypothyroidism: It occurs due to conditions that primarily affects thyroid gland itself. The common causes are
a) Iodine deficiency
b) Autoimmune hypothyroidism ( Hashimoto’s disease)
c) Iatrogenic causes: excess use of radioiodine I131, post thyroidectomy status.
d) Drugs like lithium, anti-thyroid drugs etc.
e) Congenital hypothyroidism: It is the hypothyroidism occurring in children. Also called cretinism. Congenital hypothyroidism occurs in the frequency of 1 case per 4000 live births. It can occur as both genetically and sporadically. Genetic etiology constitutes 5% of cases while majority of cretinism cases (almost 95%) occur sporadically. [9]
The major etiological factors being thyroid dysgenesis, maternal iodine deficiency in pregnancy, inborn errors of thyroid hormone synthesis etc.
10
2) Secondary hypothyroidism: Here defect is primarily outside thyroid gland that is either in the pituitary or in the hypothalamus.
a) Pituitary hypothyroidism: Hypothyroidism occurs due to decreased TSH secretion as in case of pituitary resection, tumors of thyrotrophs, post- partum pituitary necrosis (Sheehan syndrome).
b) Hypothalamic hypothyroidism: It occurs due to decreased secretion of TRH, which is caused by any injury or tumor of hypothalamus.
c) Thyroid hormone resistance: It is a hypo metabolic state similar to hypothyroidism which occur due to resistance of peripheral tissues to thyroid hormones.
Clinical features of hypothyroidism: [10]
Symptoms:
Weakness, fatigue
Increase in weight
dry skin
swelling of face
hoarseness of voice
intolerance to cold
loss of hair
constipation
carpal tunnel syndrome
menorrhagia (in females)
11
psychosis
poor memory
Signs and complications:
goiter
cold, xerotic skin
loss of lateral third of eyebrows
dry hair
decreased BMR
bradycardia
hypertension
anemia
facial and hands/feet edema
slowing of deep tendon reflexes
pericardial effusion
Hyperthyroidism
Hyperthyroidism (or thyrotoxicosis) is characterized by hyper metabolism secondary to excess levels of thyroid hormones. It can be broadly classified as primary and secondary hyperthyroidism respectively.
Primary hyperthyroidism: occurs due to primary pathology of thyroid gland as in the following condition
a) Multinodular goiter b) Adenoma of thyroid
12
c) Grave’s disease: (long acting thyroid stimulating auto antibodies - LATS causes aberrant activation of TSH receptors and leads to resultant hyperthyroid state.)
d) Metastatic carcinoma from functioning thyroid gland e) TSH receptor mutation
f) Jod -Basedow phenomenon due to iodine excess
Secondary hyperthyroidism: Here the pathology is outside the thyroid gland like pituitary or extra thyroid tissue.
a) Pituitary causes: tumor of anterior pituitary secreting excess TSH b) Extra thyroidal cause: tumor of ectopic thyroid (lingual thyroid), hCG
secreting tumor (choriocarcinoma), iatrogenic.
Manifestations of hyperthyroidism:[11]
Symptoms:
heat intolerance
sweating
palpitation
weight loss
pruritus
hyper defecation
irritability
oligo menorrhea
13
Signs and complications:
goiter
warm moist extremities
tremors
tachycardia
atrial fibrillation
high output cardiac failure
gynecomastia
ophthalmopathy
increased BMR
proximal muscle weakness
thyroid storm.
14
SKIN AS A NEURO-ENDOCRINE ORGAN:
The primary endocrine signaling pathways which are being controlled by brain are: [12]
1) The hypothalamus pituitary–adrenal (HPA) axes 2) hypothalamopituitary–thyroid (HPT) axes;
3) catecholamines, prolactin, and acetylcholine predominated signaling axes, controlled by central nervous system.(CNS)
Any hormonal imbalance within these central axis will affect the serum levels of key hormones and subsequently affect the peripheral tissues including skin. This is because the CNS, peripheral nervous system, endocrine organs and peripheral tissues such as skin generate and share a spectrum of neuro mediators and hormonal ligands .they also express similar type of cognate receptors thus perpetuating a better intersystem communication between them.[13 -17]
Our skin is particularly known to contain certain functional equivalents of the HPA axis {CRH → ACTH → cortisol}, and key elements of HPT axis {TRH
→ TSH [18, 19]. It also plays an important role in epidermal immunity [20], skin cancer [21], wound healing, [22-24] metabolism of several neuro mediators and hormones. The keratinocytes of epidermis, hair follicle, sebocytes and subcutaneous adipocytes are a potent source of peptide and steroid hormones and neuro mediators. Among these the scalp hair follicles have gained paramount importance in neuroendocrine biology of human skin as it produces or is sensitive to wide range of neuro mediators. [25]
15
THE SKIN AND THE THYROID:
The cutaneous manifestations of thyroid diseases may be categorized clinically as follows: [26]
1) Specific skin lesions
2) Nonspecific lesions due to hypothyroidism and hyper thyroid state (includes general hyperthyroidism and graves diseases).
3) Other auto immune systemic or dermatological diseases associated thyroid disorders. These includes
[A] “Immune mediated disorders" like
vitiligo
utricaria /angioedema
alopecia areata
, pernicious anemia
“Connective tissue diseases” like a) Lupus erythematosus
b) Scleroderma c). Dermatomyositis
Endocrinopathies
a). Multiple endocrine neoplasia b). Acanthosis nigricans
“Bullous disorders” which includes a). Pemphigus vulgaris
b). Dermatitis herpetiformis
16
c). Herpes gestationalis d). Bullous pemphigoid
“Pustulosis palmoplantaris”
“Sweet's syndrome”
[B] Miscellaneous conditions like “Cowden syndrome, Carney complex and McCune-Albright syndrome”
[C] Those complications which results from treatment of underlying disorders.
SPECIFIC SKIN LESIONS:
It includes,
1) Thyroglossal duct cysts.
2) Cutaneous metastasis from thyroid malignancies.
Thyroglossal duct cyst:
Thyroglossal cyst is reported to be the most common congenital cystic abnormality of neck. It accounts for seventy percentage of such lesions and it is usually observed in first decade of life. It is a remnant of thyroglossal duct, occurring anywhere along the course of the duct during embryonic development but the most common site is infra hyoid position.[27] It appears as soft to firm cystic swelling which moves during deglutition and on protrusion of tongue because of its underlying attachment to hyoid cartilage. On histopathology, cyst with pseudostratified columnar to squamous epithelium containing thyroid follicles in its walls ,without any adjacent smooth muscle, mucous glands, or
17
cartilage is seen.[28] The undifferentiated cells of the ductal epithelium can transform itself into salivary, squamous, columnar, sebaceous, or thyroid lineage in the later part of life [29]. This may sometimes develop into a retro sternal goiter and subsequent superior vena cava syndrome may manifest clinically as vertical, palpable, dilated, and tortuous cutaneous vessels on the trunk above the lower margin of the rib cage. Erythema, facial edema, cyanosis, neck vein distension, proptosis, conjunctival injection, and swelling of the nasal mucosa are seen later
[30]. Thyroglossal duct cyst may also break open in to a sinus tract or carcinoma
[31] can occur in it as a complication. So complete removal of the thyroglossal duct remnants is essential during surgery. Thyroglossal duct cyst could be easily confused with other conditions which causes localised swelling of neck such as cystic hygroma, anomalies of branchial arch, desmoid tumor, pyramidal lobe of the thyroid gland, lymph nodes, pharyngocele or laryngocele with an external component and lipoma [27]
Cutaneous manifestations from thyroid malignancies: The thyroid carcinoma is the most common endocrine malignancy. However cutaneous metastasis is very rare occurring in less than one percent of thyroid tumors, and they tend to occur only in the setting of disseminated neoplastic disease of thyroid gland. [32] The most common subtype to metastasize to the skin is papillary thyroid carcinoma, followed by follicular carcinoma subtype, next comes the anaplastic carcinoma and medullary carcinoma. [33] The most common site is head and neck, particularly the scalp. Clinically they may appear ranging from solitary or multiple, flesh colored, violaceous or bluish papules and nodules. They may
18
manifest either as a recurrence after a previous surgery for thyroid cancers, or as an initial manifestation of an occult thyroid carcinoma. [34]
The metastatic skin lesions can be mistaken for a primary adnexal skin tumor. However it can be distinguished by biopsy, in which medullary, follicular and papillary thyroid carcinoma retain their histologic pattern.
Immunohistochemical studies also aids in diagnosis. [35] Cutaneous metastasis of thyroid carcinoma has a poor prognosis with a mean survival rate of nineteen months. [36]
A characteristic cutaneous symptom in case of Multiple Endocrine Neoplasia (MEN) type 2a or familial medullary thyroid carcinoma (MTC) is pruritus, which is localised to scapular region, in the form of either notalgia parasthetica or macular /lichen/biphasic amyloidosis. Therefore a vigilant probing of family history of MEN2a syndrome in such patients is warranted. [37]
NON SPECIFIC LESIONS DUE TO HYPO OR HYPER THYROID STATE:
Various thyroid disorders that causes increased or decreased serum levels of thyroid hormone are associated with altered human skin and hair structure as well as function [38] .Cutaneous manifestations of hypothyroidism and hyperthyroidism is imparted in the following ways
19
1. Those manifestations because of direct action of thyroid hormone on skin 2. Those skin manifestations of increased or decreased thyroid hormone
action on non-skin tissues
3. Thyroid dysfunction of autoimmune etiology (clinically manifesting as hyper or hypothyroidism) associated with autoimmune skin diseases.
Thyroid Hormone Action on Skin Tissues by direct mechanism:
The cutaneous thyroid receptors (TR) is known to mediate the effects of thyroid hormones on the skin. [39] Skin is known to contain all three types of thyroid hormone binding isoforms of TR’s. These receptors are located in epidermal keratinocytes, skin fibroblasts, sebaceous gland cells, smooth muscle cells, arrector pili muscle cells, in numerous other hair follicle cells, vascular endothelial cells and Schwann cells. [40] Recently various thyroid hormone responsive genes and certain important constituents of the hypothalamic pituitary- thyroid hormone axis have been discovered in skin. [41]
The following are features of hypothyroidism and hyperthyroidism due to direct hormone action: [42]
20
Table 4: Direct action of thyroid hormone on skin
Hypothyroidism Hyperthyroidism Changes in Epidermis Coarse, thin, scaly skin. Smooth, thin skin
Changes in dermis
Non-pitting edema (myxedema)
Edema of hands, face, and eyelids
macroglossia
Carotenemia
Pallor −
Hair and Nail Changes
Dry, brittle, coarse hair
Alopecia
Loss of lateral third of eyebrows
Coarse, dull, thin, brittle nails
Fine hair (“loses wave”)
Alopecia
Premature greying of hair
Shiny, soft, friable nails onycholysis, Plummer’s nails
Sweat gland changes
Dry skin (xerosis) Decreased sweating
−
21
THYROID HORMONES AND EPIDERMIS:
The epidermal homeostasis is principally regulated by thyroid hormone.
Xerosis is one of the most common skin manifestation in hypothyroidism and reported to be present in approximately 60% of these patients. The pathophysiology of Xerosis is attributed due to an alteration of skin texture accompanied by deficient hydration of stratum corneum. Hypothyroidism is characterised by scaly, rough skin seen preferentially on the extensor aspect of the extremities. Xerosis resembling acquired ichthyosis, dry palms and soles are other features. Thinning and hyperkeratosis noticed on biopsy can be explained by the decreased T3 levels resulting in elevated levels of transglutaminase. This in turn leads to the excessive formation of the cornified skin layers. The decreased circulating T3 levels leads to depletion of plasminogen activator, an enzyme involved in shedding of cells of stratum corneum. [42]
Hypothyroidism also may affect the activity of enzymes involved in the cholesterol sulfate cycle. This is known to affect the epidermal barrier function
[43]. Hypothyroidism can hamper the formation of the lamellar granules (Odland bodies). These bodies are important in the structural integrity of a normal stratum corneum. [44]
However, in hyperthyroidism epidermis appears to be thin but not atrophic.
22
CHANGES IN DERMIS:
In hyperthyroid patients, the dermal changes are attributed to autoimmune mechanisms rather than due to direct effect of thyroid hormones. In hypothyroid patients, the mechanism behind the development of pale skin is due to the deposition of the dermal mucopolysaccharides and increased dermal water content. [45]
Increased accumulation of dermal carotene over the sites like nasolabial folds, palms and soles gives the clinical appearance of “yellowish hue” termed as Carotenemia. This is alternatively termed as “pseudojaundice “as well in literature. The possible etiology for this is a reduction in carotene metabolism leading to the above clinical profile. Scleral sparing helps to differentiate this condition from true jaundice.
Among the glycosaminoglycan’s, hyaluronic acid is the major component that gets accumulated in hypothyroid dermis. These mucopolysaccharides have hygroscopic characteristics causing it to undergo massive swelling which can reach more than one thousand times of its dry weight on hydration. [46]
Mucin deposition occurs in skin, tongue resulting in macroglossia, myocardium and kidney. These deposition together with increased trans capillary escape of albumin, inadequate lymphatic drainage [47] contributes to edema and virtually the characteristic myxedematous features in hypothyroidism.
23
The clinical appearance of facial coarseness and an expressionless face is due to changes like a broad nose, edema around the periorbital region, swollen lips and macroglossia.
Thyroid hormones improves the rate and quality of wound healing [48] that is why poor wound healing occurs in hypothyroidism.
CHANGES IN HAIR AND NAIL:
In hyperthyroidism, the hair appears soft and fine with increased hair growth rate, however diffuse non scaring alopecia can also occur. L- Triiodothyronine has stimulant properties on outer root sheath keratinocytes and dermal papilla cells leading to their overgrowth. [49]
Hypertrichosis occurring in thyroid dermopathy is attributed to the proteoglycan changes observed in the dermal papilla [50]. Sometimes loss of pigment and early gray hair development can occur as an early system.
Typical nail changes includes concave contour and distal onycholysis which is referred by the term “Plummer’s nails”. These changes are observed in 5% of individuals.
In hypothyroidism, hair can be dry, coarse, and brittle and slow growing.
[51] Diffuse or partial alopecia may be observed along with characteristic loss of the lateral third of the eyebrow (madarosis) can also occur. Diminished body hair, sparse pubic and axillary hair is seen. The long, lanugo-type hair is
24
characteristically seen in pediatric patients especially over the extremities and back. [52]
The thyroid hormones exert its effect on the development and sustenance of hair growth. Moreover, in hypothyroid states, higher percentage of the scalp hairs enter into a telogen phase. Hence the occurrence of alopecia is attributable to the above etiology. At times, the patient may presents only with the complaints of hair loss to the dermatologist, which may lead to the diagnosis of the underlying hypothyroid disorder.
Hypothyroid patients have decreased sebum secretion leading to the development of coarse hair. Moreover, the lower sebum levels leads to overgrowth of Candida albicans replacing the normal lipophilic hair flora. This leads to the frequent occurrence of Candida folliculitis in such patients. [53]
There is a slow growth rate of the nails in these patients. They tend to appear brittle, striated and thick. Sometimes, onycholysis can occur in hypothyroidism.
Sweat gland changes:
There is decreased eccrine gland secretion in hypothyroidism, which is one of the reason for dryness of skin seen in this condition [54]. Hypohidrosis and decreased epidermal sterol biosynthesis can contribute to acquired palmoplantar keratoderma.
25
Table 5: Skin features of hormonal action on other tissues
HYPOTHYROIDISM: HYPERTHYROIDISM:
Cold intolerance
Pallor
Purpura
Drooping of upper eyelids
“Nerve entrapment syndromes”(facial nerve palsy and carpel tunnel syndrome)
Heat intolerance
Warm skin
Increased sweating (“hyperhidrosis”)
Erythema
Telangiectasia
Hyperpigmentation
There are numerous skin manifestations of hypothyroidism, which is attributable to the actions of thyroid hormones in non-skin tissues. In hypothyroidism, there is a reduced activity of the basal metabolic, vascular and sympathetic nervous systems owing to the low levels of circulating thyroid hormones. This results in decreased skin perfusion due to reflex vasoconstriction compensatory to diminished core temperature. The reduced thermogenesis leads to decreased core temperature. [55] This clinically manifests as cold pale skin. The decreased skin perfusion has been documented with nail fold capillaroscopy. [56]
Diminished levels of clotting factors leads to purpuric features occasionally. The decreased vascular support due to the increased dermal mucin contributes to the same. [57]The drooping of the upper lids is due to the lowered sympathetic stimulation of the superior palpebral muscle. Entrapment syndromes
26
manifests clinically in the form of facial nerve palsy and carpal tunnel syndrome in these patients. [58]
Hyperthyroidism is characterised by smooth, warm and moist skin resembling an infant’s skin. The increased cutaneous vascular circulation and metabolic activity leads to warmth and moist skin respectively. The characteristic facial flushing and palmar erythema in these patients is due to peripheral vasodilatation and increased cutaneous blood flow.
The generalized hyperhidrosis is seen in hyperthyroidism and typically evident on the palms and soles. [59] The thyroid hormones and catecholamines act synergistically to increase the sympatho-adrenal activity. This along with hypermetabolic state leads to increased sweating. However, localized hyperhidrosis has also been reported pretibial myxedema. [60]
Hyperpigmentation occurs in both localized and generalized distribution.
The localized form is seen predominantly over buccal mucosa, gingiva and creases of the palms and soles. The pituitary adrenocorticotropic hormone which is released in excess to compensate the degeneration of cortisol is responsible for the hyperpigmentation seen in these patients. [61]Hyperthyroid patients complain of pruritus irrespective of presence or absence of utricaria. [62][63]
27
ASSOCIATED AUTOIMMUNE PHENOMENA
Apart from classical signs and symptoms of hypo or hyperthyroidism, additional skin findings and diseases pertaining to autoimmune etiology do occur.
Patients with autoimmune thyroid disease are at increased risk for developing other autoimmune diseases with can be either tissue-specific or generalized. [63] In these patients, the thyroid specific auto antibodies in addition to the thyroid hormones per se, can affect the structure and function of skin tissues. [64] The relationship between autoimmune diseases and thyroid specific auto-antibodies can be due to following etiology:
1. Immunomodulatory actions of anti-thyroid antibodies,
2. Thyroid and disease-specific epitopes sharing a molecular mimicry between them
3. A genetic association between anti-thyroid autoimmunity and a vulnerability to develop autoimmune disease[65]
The major potential antigenic targets that mediate auto immune thyroid diseases (AITD) are
1) Tg (thyroglobulin) 2) TPO (thyroid peroxidase)
3) TSH-R (thyroid stimulating hormone receptor) and 4) Sodium iodide symporter (NIS).
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Autoantibodies to other antigens whose clinical significance are yet to be proven are as follows: [66- 74]
Autoantibodies to p53
Anticardiolipin antibodies
Antinuclear antibodies
Anti–connective tissue antibodies
Antiphospholipid antibodies
Anti–double-stranded DNA antibodies
Anti–glomerular basement membrane antibody-mediated disease
Anti–heat shock protein autoantibodies
Antipituitary antibodies
Anti–smooth muscle antibodies
Anti–striated muscle antibodies
Natural autoantibodies (including actin, tubulin, myosin, and human albumin.)
In both Graves’ disease and Hashimoto’s thyroiditis, the cutaneous involvement may be linked to the thyroid hormone levels or to the associated T and/or B cell abnormalities [74].
HASHIMOTO’S THYROIDITIS:
Hashimoto’s thyroiditis (HT) is an autoimmune disorder which clinically manifests as hypothyroidism. It is the most common cause of hypothyroidism in developed countries where occurrence of iodine deficiency induced goiter is very
29
rare. It is predominantly a disease of middle age. Females have a high predilection for acquiring this condition with a male-to-female ratio being 1:7. The probable risk factors for this condition includes genetic susceptibility, environmental triggers, CTLA-4 (“Cytotoxic T-Lymphocyte Antigen 4”) genes and Human Leucocyte antigen (HLA). [63] Furthermore, there is an alteration in the natural immune system of the body owing to expression of certain HLA antigens which are of thyroid- specific in nature. In 95% of patients, antibodies to thyroid peroxidase occurs whereas the prevalence of antibodies to thyroglobulin (Tg) in noticed only in 50% to 60% of the patients.
The two variants of Hashimoto’s are;
goitorous type and
atrophic type.
Goitorous or hypertrophic form is associated with HLA-DR5 and characterized by enlarged, nodular and rubbery thyroid gland. The expression of HLA B8 and HLA DRw3 has been implicated in the occurrence of atrophic form of HT. Moreover, the circulating cytotoxic antibodies leads to the development of thyroid atrophy.
Among the cutaneous manifestations of HT, dermatitis herpetiformis is specifically linked to its atrophic variant. [75]
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The goitorous variant is associated with the following cutaneous conditions:
Vitiligo
Dermal mucinosis
Lichen sclerosis et atrophicus
Alopecia areata
Alopecia totalis
Diffuse alopecia
Morphea
Granuloma annulare
Acanthosis nigricans
Palmoplantar pustulosis
Reticular erythematous mucinosis
Primary localized cutaneous amyloidosis
Epidermolysis bullosa
Leprosy
Melasma
Middermal elastolysis
Keratosis pilaris
Onycholysis
Vogt-Koyanagi-Harada syndrome
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GRAVES DISEASE:
Graves’ disease (GD) the autoimmune thyroid disease, is the most common cause of noniatrogenic hyperthyroidism. It occurs most commonly in young women. The pathophysiology of this disease is due to infiltration of thyroid gland with lymphocytes. These lymphocytes in turn produces autoantibodies directed against TSH receptors leading to thyroid gland over activity. Clinically it is featured by classic hyperthyroid signs and symptoms in addition to the specific findings listed below:
diffuse goitorous enlargement
Thyroid dermopathy (“pretibial myxedema”)
Thyroid acropachy.
ophthalmopathy
The thyroid gland enlargement is clinically evident as a smooth, symmetric, and non-tender goiter. Sometimes, a non-palpable goiter may be seen as an exception especially in the elderly patients.
Graves’s ophthalmopathy:
The incidence of Graves’s ophthalmopathy is reported to be approximately 25% which is evident at the time of initial presentation. [76] The etiology of this phenomenon is due to the accumulation of hyaluronic acid which is a mucopolysaccharidase. This is deposition is specifically seen in the fibrous and fatty tissues of retro-orbital region and in extraocular muscles. This leads to the clinical presentation of periorbital edema and proptosis. The patients frequently
32
complain of ocular symptoms like excessive lacrimation, pain in ocular or infraorbital region, xerophthalmia, blurred vision, diplopia, and rarely even complete blindness. These symptoms gets worsened when the patients is exposed to bright lights, cold air and wind. Various management options include use of topical instillation like artificial tears, head elevation at sleep, eye shields, oral prednisone, pain killers, external orbital radiation, and finally orbital decompression surgery. But correction of underlying hyperthyroidism stays the main form of treatment.
Thyroid dermopathy:
The incidence of thyroid dermopathy is estimated to be 0.5% to 4% of patients with GD [77]. Generally, as a dictum,thyroid ophthalmopathy precedes the occurrence of dermopathy. This pattern of indurated and non-pitting edematous skin involvement can occur in any part of the body and not exclusive to the pretibial area alone. Hence, this condition is a misnomer. The other sites include predominantly the entire upper limb involvement, neck, shoulder and upper back.
It can also involve donor skin graft areas, scars and areas of previous trauma. [78,
79] The clinical presentation may be in the form of firm nodules and plaques which can be erythematous or yellowish brown. This pattern of skin involvement is usually asymmetrical and bilateral in distribution. These lesions are mostly painless in character. The histopathology is characterized by the accumulation of hyaluronic acid in the entire dermis. Theses deposits can also infiltrate the subcutis. The various types of clinical presentations of Graves’s dermopathy are as follows:
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1) Non pitting type - most common type 2) Plaque type
3) Nodular type
4) Rare forms like elephantiastic or polypoid type ( clinically it appears as edematous or verrucous nodules with underlying skin fibrosis)
Even with treatment of the underlying hyperthyroidism, the features of thyroid dermopathy is known to persist, in contrast to thyroid ophthalmopathy.
Thus, the management of Graves’s dermopathy is challenge to the treating physician. Furthermore, it has a high rate of recurrence. Glucocorticoids, surgical excision have limited rate of success. The newer strategies include the use of intravenous immunoglobulins, pentoxifylline, somatostatin analogues and plasmapheresis.
Thyroid acropachy:
Thyroid acropachy is an uncommon, benign condition affecting less than 1
% of the Graves population. This disease is characterized by the occurrence of clubbing of digits, swelling of soft tissues of hands and feet and long bones showing features of periosteal reaction in skiagram. [80] The bony involvement predominantly involves the small bones of the hands and feet. This includes the first two and last metacarpals with the involvement of their corresponding phalanges. Similar manifestations are observed in the first metatarsal bone as well. These changes are transient and resolves completely after correction of the co-existent thyroid pathology.
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There are certain other skin conditions which are commonly associated with Graves’ disease. They can be categorized as follows:
Table 6: Skin diseases associated with Graves disease
Bullous disorders
Pemphigus vulgaris
Pemphigoid gestationalis
Dermatitis herpetiformis
Disorders of connective tissue
Mid dermal elastolysis
Anetoderma Pigmentary disorders vitiligo
Neutrophilic disorders
Acute febrile neutrophilic dermatosis (“ Sweets syndrome”)
Nail Onycholysis
In general, following are the most common autoimmune conditions associated with thyroid disorders: [81-86]
Vitiligo
Alopecia areata
Chronic utricaria
Bullous disorders
Connective tissue diseases.
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Vitiligo and alopecia areata often precede thyroid dysfunction by many years thus serving as a useful clinical tool to evaluate for thyroid hormone levels and for thyroid antibodies levels even in euthyoid patients. Thereby patients at risk for thyroid diseases can be identified far ahead their actual clinical appearance.
Aims and Objectives
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AIMS AND OBJECTIVES
To evaluate the prevalence of cutaneous manifestations various thyroid disorders
To analyze the pattern and prevalence of thyroid disorders and their cutaneous manifestations in this tertiary care center in south India
Materials &Methods
37
MATERIALS AND METHODS
Study Centre
Department of Dermatology, Madras Medical College &
Rajiv Gandhi Government General Hospital, Chennai – 600003.
Duration of the Study
October 2015 – September 2016
Study Design Prospective observational study
Inclusion Criteria
All patients who present to dermatology op with skin findings suggestive of thyroid disorders.
All patients with known thyroid dysfunction and skin manifestations referred from endocrinology (medical & surgical) op.
Exclusion Criteria
Patients not willing for study
Thyroid patients undergoing radiation therapy
Those having other associated endocrine disorders
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Sample Size:
The sample size (N) was calculated using the below formula:
N =Z
1 −ἁ
2pq ∕ d
2 Z1 - ἁ is standard normal deviation at 95% confidence level (1.96)
p is the prevalence of cutaneous manifestations of thyroid disorders taken from previous studies.{here 65.22%}
q is (1-p )
d is the relative precision (20%)
The rounded off sample size using the above formula was 105.
Thus 105 consecutive patients with thyroid disorders and cutaneous findings (includes those attending dermatology op and those who are referred from endocrinology op.) were considered as study subjects.
METHODOLOGY:
With the help of proforma, an elaborative medical history pertaining to various thyroid disorders were elicited in each patient. The history mainly comprised of both general and cutaneous complaints of thyroid diseases including duration, history of evolution and progression of symptoms in them.
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A general physical examination, systemic examination and a detailed dermatological examination were carried out in each patient after taking an informed consent from each of them. The relevant details recorded and were tabulated.
Apart from routine laboratory investigations, thyroid function tests (TSH, T3 and T4) was done by electro-chemiluminescence assay (ECLIA) for all cases and thyroid auto antibodies in selected cases were done.
Normal ranges for thyroid hormones and autoantibodies were accepted as follows:
o Free T3: 1.71–3.71 pg/mL, o Free T4: 0.70–1.48 ng/mL, o Total T3: 60-181 ng/dl o Total T4: 4.5-12.6 μg/dl o TSH: 0.35–4.94 IU/mL ,
o Anti g thyroglobulin autoantibody: 0–34 IU/mL and o Anti thyroid peroxidase: 0–115 IU/mL
o Anti thyroid stimulating hormone receptor binding inhibitor Ig: < 1.75 IU/L
Skin biopsy and ultrasound thyroid was done in selected cases if needed.
Based on above, categorization of patients with congenital defects, hypothyroid, hyperthyroid, autoimmune, malignant features was done
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Specific and nonspecific skin findings pertaining to above thyroid disorders and/or any other associated dermatosis was documented.
Statistical analysis of various cutaneous findings were performed by appropriate statistical methods (SPSS 20) and inferences were drawn.
Observation &Results
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OBSERVATIONS AND RESULTS
Out of total 105 patients, 95 patients were females and 10 patients were males with a male female ratio of 1:9. Female preponderance was seen in our study. The age of the participants ranged from 13 years to 70 years with a mean of 38.22 (+/-13.8) years. 76 patients (72.6%) were having hypothyroidism.
Hyperthyroidism was seen in 29 (27.3%) patients. Autoimmune antibodies were positive in 12(11.3%) patients.
Figure 2: Distribution of thyroid disorders:
27%
68%
5%
hyperthyroidism clinical hypothyroidism subclinical hypothyroidism
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HYPOTHYROIDISM:
A total of 76 patients were having hypothyroidism.one had congenital hypothyroidism.75 had adult onset hypothyroidism. Among them five (6.57%) patients had subclinical hypothyroidism. Sixty nine patients were females (90.78%) and ten (13.15%) were males. The average age of presentation was thirty eight years (range 13 years to 70 years).One (1.31%) had thyroglossal duct cyst. One (1.31%) patient had congenital hypothyroidism and the rest (98.68%) had adult onset disease. Forty out of seventy six patients were already on treatment still their thyroid parameters fell within the range of hypothyroidism when we examined them. The main medical complaints in the history of hypothyroid patients are as follows;
Tiredness
Cold intolerance
Weight gain
Constipation
Sleepiness
Decreased appetite
Depression
Oligo menorrhea
Among these the most common history given by the hypothyroid patients is tiredness, seen in about 53 (69.73%) patients. 31 (40.78%) patients complained of weight gain which was the next common history. This was followed by history
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of oligo menorrhea, 31.57% (in case of females) and history of constipation.
(25%).
Table 7: Distribution of hypothyroid patients based on clinical history
CLINICAL HISTORY NO. OF PATIENTS PERCENTAGE
Tiredness 53 69.73%
Weight gain 31 40.78%
Oligo menorrhea 24 31.57%
Sleepiness 11 14.47%
Decreased appetite 12 15.78%
Constipation 19 25.0%
Depression 9 11.84%
Hoarseness of voice 6 7.89%
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Twelve patients (15.78%) had decreased appetite; eleven (14.47%) of them complained of sleepiness throughout the day .Depression was seen in nine (11.84%) of the patients. Six patients (7.89%) typically had hoarseness of voice.
However some patients had more than one symptom in clinical history. On haemogram analysis, 14 patients were found to be anemic (iron deficiency anemia).
Figure 3: Distribution of hypothyroid patients as per clinical history(N=76) The common cutaneous findings observed in hypothyroid patients were thin scaly xerotic skin, myxedema, and coarse dry hair, diffuse or partial loss of hair, hypohydrosis, and coarse, dry brittle nails.
0 10 20 30 40 50 60
number of patients
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Figure 4: Distribution of clinical features in hypothyroid patients
Figure 5: Prevalence of clinical features in hypothyroidism
Xerosis was seen in a total of 69 (90.8%) patients. This was followed by puffiness of face in about 40 (52.6%) patients.diffuse visible and palpable swelling in neck region (goiter) was seen in 2(2.63%) of hypothyroid patients.
10.0%0.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
80.0%
90.0%
100.0% 90.8%
35.5%
52.6%
38.2%
26.3%
51.3%
32.9% 34.2% 31.6%
Percentage of Individuals
HYPOTHYROIDISM
46
Figure 6: Prevalence of xerosis in hypothyroidism
Figure 7: Myxedema in hypothyroidism
39 (51.3%) patients had diffuse hair loss, telogen effluvium, whereas 20 (26.3%) participants had coarse dry hair.
91%
9%
XEROSIS
YES NO
47% 53%
MYXEDEMA
YES NO
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Figure 8: Hair changes in hypothyroidism
Thus diffuse hair loss was the predominant finding on examination of hair in our patients followed by coarse dry scalp hair. The other hair changes were loss of lateral eyebrows (madarosis) seen in 1(1.31%) patient and sparse pubic and axillary hair seen in one (1.31%) patient No hair changes were detected in sixteen (20.05%) patients.
Pallor was observed in 29 (38.2%) patients. Altered skin texture, in the form of thin, scaly skin was seen in 27 (35.5%) patients.
no hair changes
madarosis
diffuse hair loss coarse hair
sparse axillary and pubic hair
hair changes
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Figure 9: Frequency of pallor in hypothyroidism
Figure 10: Distribution of scaly skin in hypothyroidism
Decreased sweating was noticed in 26 (34.2%) subjects. 24 (31.5%) patients had intolerance to cold.
Nail changes were detected in 25 (32.9%) of participants.
YES 38%
NO 62%
PALLOR
YES NO
36%
64%
THIN SCALY SKIN
YES NO
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Figure 11: prevalence of nail changes in hypothyroidism
The commonest nail change observed in hypothyroid patients was brittle dry nails seen in about 20 (26.3%) cases. This was followed by slow nail growth in 5 (6.5%) patients. No nail changes was detected in 51(67%) patients.
Other cutaneous features pertaining to hypothyroidism seen in our patients were puffiness of only hands, drooping of eyelid (ptosis), macroglossia, poor wound healing, purpura, palmoplantar keratoderma, Xanthelasma palpebrarum.
33%
67%
NAIL CHANGES
YES NO
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Table 8: Least common features seen in hypothyroid patients Skin features Number of patients percentage
Puffiness of only hands 2 2.63%
Drooping of eyelid 4 5.26%
Macroglossia 2 2.63%
Poor wound healing 3 3.94%
purpura 2 2.63%
keratoderma 12 15.7%
Xanthelasma
palpebrarum 1 1.31%
Interestingly diffuse hyperpigmentation involving face, arms trunks was also found in 3(3.94%) of our patients. Hirsutism was seen in 2(2.63%) patients.
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Table 9: Distribution of associated cutaneous diseases in hypothyroid patients.
Associated cutaneous disease No. of patients (N=76) Vitiligo
Utricaria AA SLE PPK Eczema Psoriasis Leprosy Melasma LSA
Acanthosis nigricans Erythrasma
Lichen planus Keloid
Seborrheic dermatitis Granuloma annularae Rheumatoid arthritis Papular mucinosis Dermatophyte infection
6 6 4 6 4 4 3 1 1 1 7 1 1 1 1 1 1 1 1
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The patient with papular mucinosis presented with multiple asymptomatic lichenoid papules some coalescing to form plaques seen over acral regions, upper trunk, thighs etc. On histopathology, Eosin and Hematoxylin staining showed widely spaced collagen in the middle and deep dermis. There was also increased fibroblasts due to mucin deposition was evident. Based on clinico pathological evidence a diagnosis of papular mucinosis was made.
Figure 12: Distribution of various cutaneous conditions in hypothyroidism
7.9 7.9
5.3
7.9
5.3 5.3
3.9
1.3 1.3
0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0
Percentage of individuals
ASSOCIATED CUTANEOUS CONDITIONS
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Figure 13: prevalence of autoantibodies in hypothyroid patients
Auto antibodies to thyroid peroxidase and thyroglobulin was seen in 6(7.8%) patients. Among them all six patients were positive for TPO autoantibodies whereas only 2 of them showed additional Tg autoantibodies.
POSITIVE 8%
NEGATIVE 92%
AUTO ANTIBODIES
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HYPERTHYROIDISM
Hyperthyroidism was seen in a total of 29(27.61%) out of 105 patients in our study. The most common cause of hyperthyroidism in our study was toxic multinodular goiter seen in about 19 (65.51%) patients. Next came autoimmune thyroiditis detected in six (20.68%) patients, lymphocytic thyroiditis noticed in two (6.89%) patients, iatrogenic seen in one (3.44%) patient. one patient (3.44%)had papillary carcinoma of thyroid with lymph node metastasis . Twenty seven (93.10%) patients were females and two (6.89%) were males. The average age of presentation was thirty six years (range 13 years to 57 years). Fourteen out of twenty nine patients were already on treatment. However their thyroid parameters were within hyperthyroid range during examination. The main medical complaints in the history of hyperthyroid patients are as follows
Weight loss
Palpitation
Increased appetite
Nervousness/ anxiety
Dyspnea
Hyper defecation
Menstrual disturbances
Irritability
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The most common history given by hyperthyroid patients is weight loss, seen in about 18 (62.06%) patients. Next common complaint was palpitation told by 16 (55.17%) patients. 15 (51.72%) patients had increased appetite. This was followed by history of nervousness (48.27%), and history of dyspnea. (31.03%).
Six (20.66%) females complained of menstrual disturbances mainly in the form of polymenorrhea. Some patients had more than one complaint.
Table 10: Distribution of hyperthyroid patients based on clinical history
Clinical history No. of patients percentage
palpitation 16 55.17%
Weight loss 18 62.06%
Increased appetite 15 51.72%
Nervousness 14 48.27%
Dyspnea 9 31.03%
Hyper defecation 8 27.58%
Menstrual disturbance 6 20.68%
Irritability 4 13.79%
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Figure 14: Distribution of hyperthyroid patients as per clinical history
The common cutaneous findings observed in hyperthyroid patients were soft, smooth and warm skin, erythema, hyperpigmentation, fine hair, pruritus, heat intolerance, hyperhidrosis etc. Their frequency of occurrence in our study is as follows;
Table 11: Frequency of clinical features in hyperthyroid patients:
Count Column N %
SOFT SMOOTH SKIN 18 64.30%
WARM SKIN 23 82.10%
HYPERPIGMENTATION 15 53.60%
ERYTHEMA 11 39.30%
FINE HAIR 11 39.30%
NAIL CHANGES 2 7.10%
PRURITIS 17 60.70%
HYPERHIDROSIS 18 64.30%
HEAT INTOLERANCE 10 35.70%
0 2 4 6 8 10 12 14 16 18 20
no. of patients
history in hyperthyroid patients
