Cutaneous Manifestations in Patients with Endocrine Diseases

INTRODUCTION

Skin and its appendages frequently reflect the changes and disorders involving the internal milieu, and thus, examination of these important structures may provide vital clues to diagnosis and guide patient’s work up in the proper direction. Clinicians can observe, diagnose and track endocrine illness through the skin. The health and quality of life of an individual are profoundly impacted by the dermatologic signs and symptoms of endocrinopathies.^[1] Hormones are known to be essential in regulating physiologic processes in each system of the body, including the skin. Endocrine diseases, through excess or deficiencies of hormones, can result in changes in cutaneous function and morphology and lead to complex symptomatology.^[2] Patients with endocrine diseases may present with different cutaneous manifestations, some of which are specific to these disorders, while others are non-specific or secondary to metabolic changes [Table 1].^[3]

Diabetes mellitus is a clinical syndrome characterised by hyperglycaemia due to either deficiency or decreased effect of insulin. This insulin deficiency whether actual or relative affects the metabolism of carbohydrate, protein, fat, water and electrolytes. Such long-term metabolic derangement is frequently associated with permanent and irreversible functional and structural damage to the cells in various tissues and organs.^[4]

The clinical syndrome of excessive thyroid activity is known as ‘thyrotoxicosis’. It presents commonly as ‘Grave’s disease’ with a triad of enlarged toxic goitre, exophthalmos and dermopathy. Less common causes include thyroiditis, toxic multinodular goitre, toxic adenoma and exogenous thyroid hormone use. Cutaneous findings seen are warm, moist, smooth skin and flushing due to increased cutaneous blood flow and peripheral vasodilatation, palmar erythema, hyperhidrosis, diffuse scalp hair thinning, fine thin hair, increased incidence of alopecia areata, onycholysis, koilonychia, clubbing, pretibial myxedema, thyroid acropachy, generalised pruritus, chronic urticaria, vitiligo (increased incidence) and hyperpigmentation (localised/generalised).

In the hypothyroid state, there is slowdown of the metabolism of all tissues.

It may result from congenital hypothyroidism (cretinism), primary hypothyroidism in adults (autoimmune), Sheehan’s syndrome, pituitary tumour, goitrous hypothyroidism, lack of TSH/TRH production and Hashimoto’s thyroiditis.

Cutaneous changes seen are pale cold; scaly wrinkled skin absence of sweating; ivory yellow skin colour (carotenaemia); puffy oedema of hands, face and eyelids; eczema craquele; xanthomatosis (tuboeruptive xanthoma secondary to hyperlipidaemia); coarse sparse scalp hair; loss of pubic, axillary and facial hair; loss of lateral third of eyebrows, brittle and striated nails; purpura and ecchymoses; punctate telangiectasis on arms and fingertips and delayed wound healing. The most prominent feature is a dermal accumulation of mucopolysaccharides (hyaluronic acid and chondroitin sulphate) that lead to puffiness of the skin.^[5]

MATERIALS AND METHODS

The study was conducted in Outpatient Department of Dermatology, Venereology and Leprosy of a tertiary care hospital over a period of 2 years. 150 patients were enrolled based on inclusion and exclusion criteria and study duration. Patients with previously diagnosed endocrine disorders who presented to the dermatology outpatient departments, having cutaneous manifestations and consented to participate were included in the study. Study was initiated after permission from Institutional Review Board. Written informed consent of patients was taken. Pro forma containing detailed history including demographic data was taken and a detailed clinical examination was carried out. Routine investigations and specific investigations were reviewed and noted. A biopsy report if suggested by the consultant was reviewed.

RESULTS

The study included 150 patients in total, of whom 90 (60%) were female and 60 (40%) were male. Out of a total of 150 patients, 88 patients (58.66%) had diabetes mellitus. Forty four (50%) of the 88 patients were men. The most common non-infectious manifestations were generalised pruritus (28.41%), followed by, acanthosis nigricans (10.2%), acquired reactive perforating collagenosis (6.84%), dry coarse skin (6.82%), acrochordons with acanthosis nigricans (5.69%), lipodystrophy (4.55%), xanthelasma palpebrarum (2.28%), acquired icthyosis (1.1%) and granuloma annulare (1.1%) [Table 2]. The most common infectious manifestations were tinea cruris/corporis (11.36%), followed by candidal balanoposthitis (5.69%) and vaginal candidiasis (4.55%).

Out of 150 patients, 39 had hypothyroidism out of which eight were males (20.51%) and 12 had hyperthyroidism out of which four were males (33.33%). The most common non-infectious manifestations in hypothyroidism were generalised pruritus (38.46%) followed by dry coarse skin (33.33%), Melasma (12.83%), diffuse hair fall (12.83%), acrochordons (7.69%), vitiligo (5.13%), chronic spontaneous urticaria (5.13%), oral/cutaneous lichen planus (5.13%), alopecia areata (5.13%) and pretibial myxedema (5.13%). Infectious manifestation seen was tinea cruris/corporis (7.68%).

Common manifestations of hyperthyroidism were generalised pruritus (33.33%) followed by warm moist skin (25%), chronic spontaneous urticaria (16.67%) and pretibial myxedema (16.67%) [Table 3].

Three patients had polycystic ovarian syndrome, all had hirsutism and one patient additionally had lower face acne. One patient with hypopituitarism and macroadenoma presented with hirsutism. The patient having hypogonadotropic hypogonadism had acanthosis nigricans and sparseness of hair over androgen-dependent sites. Cushing’s syndrome was seen in six patients [Table 4].

Two of these patients (one male and one female) with Cushingoid habits, such as moon face and weight gain (>5% bodyweight after 1 month of therapy), who were receiving glucocorticoid therapy (iatrogenic) were included in the study [Figures 1a-h and 2a-c].

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Figure 1:

(a) Xanthelasma palpebrarum, (b) Moon facies, (c) Acanthosis nigricans, (d) Acquired ichthyosis, (e) Acquired reactive perforating collagenosis, (f) Granuloma annulare, (g) Hirsutism, (h) Striae in Cushing’s syndrome.

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Figure 2:

(a) Pretibial myxedema. (b) Dermoscopy of pretibial myxedema showing yellowish-white structureless areas with irregular pigmentation (black arrow) and telangiectasias (red arrow). (c) Histopathology of pretibial myxedema showing separation of collagen bundles by large amount of mucin in the dermis (black arrow) (Hematoxylin and eosin stain, 40× magnification).

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DISCUSSION

The skin serves as a window for clinicians to understand, diagnose and monitor endocrine disease. Dermatologic manifestations of endocrinopathies contribute significantly to an individual’s health and quality of life.^[1] The endocrine and integumentary systems interact through a cohort of complex mechanisms. Dysregulation of endocrine hormones, as seen in many endocrinopathies, often results in clinically significant dermatologic disease.^[1] Cutaneous manifestations in our study were divided according to the endocrine diseases into diabetes mellitus, hypothyroidism, hyperthyroidism, Cushing’s syndrome, polycystic ovarian syndrome, hypogonadotropic hypogonadism and hypopituitarism with microadenoma. Poorly controlled or undiagnosed diabetics have a greater susceptibility to bacterial and fungal infections of the skin. Following factors are contributory to infections in diabetics:

• Impaired microcirculation

• Hypohidrosis

• Suppression of cell-mediated immunity.

Candidal infections, especially vulvovaginitis and balanoposthitis, are more prevalent in diabetics than in the general population. Paronychia, oral thrush and disseminated candidiasis may occur in uncontrolled diabetics.^[6,7] Recurrent infections are more common in diabetics.

Investigations including histopathological evaluation were reviewed as and when required. The youngest patient in our study was 18 years old while the oldest patient was 81.

In our study, the incidence of generalised pruritus was maximum (28.41%) in diabetes mellitus which was consistent with the study done by Goyal et al.,^[8] i.e. 30%. In infective aetiologies, the incidence of fungal infections was maximum (23.88%) in the present study which was found closer to Goyal et al. study^[8] (16%) and Chatterjee et al. study^[9] (16.3%) than in comparison with Greenwood study^[10] where incidence was higher (40%). The incidence of erythrasma in the present study was 4.55% which was more compared to the study done by Chatterjee et al.^[9] (1.76%). The incidence of herpes zoster in the present study was 2.28% which was also more compared to the study done by Roslind et al.^[11] (1%). Incidence of furunculosis was 6% in study done by Goyal et al.^[8] and 3.82% in study done by Chatterjee et al.^[9] which was more as compared to 1.13% in the present study.

Candidal balanoposthitis was seen in 5.69% of patients in our study while a study done by Goyal et al.^[8] showed 9% of patients and study done by Chatterjee et al.^[9] showed 11.91% of patients with candidal balanoposthitis. Onychomycosis was noted in 2.28% of patients. Incidence of acanthosis nigricans in diabetes mellitus was found to be 15.91% which was very close to Roslind et al.^[11] study where acanthosis nigricans was seen in 13% of diabetic patients. Lipodystrophy was seen in 4.55% of patients at the sites of insulin injection in our study, which was consistent with the study done by Goyal et al.^[8] (4%). 3.41% of patients had trophic ulcers in diabetes mellitus in the present study, which was found closer to Roslind et al.^[11] study (2%). The incidence of acquired reactive perforating collagenosis in the present study was 6.84% which was higher as compared to Roslind et al.^[11] study (2%). Incidence of dry skin in diabetic patients was 6.82% in our study because of autonomic diabetic neuropathy which was low as compared to Goyal et al.^[8] study (44%), Chatterjee et al.^[9] study (25.58%) and Roslind et al.^[11] study (21%) where higher percentage of patients presented with dry skin. The incidence of acquired ichthyosis in the present study was only 1.13%, which was not consistent with the study done by Goyal et al.^[8] (10%). Psoriasis and eczema were found in 1.13% of patients with diabetes each, which were comparable with the study done by Goyal et al.,^[8] where 2% of patients had similar findings. The incidence of vitiligo in diabetes mellitus in the present study was 3.41% and that of cutaneous/oral lichen planus was 2.28% which was higher than the study done by Chatterjee et al.^[9] (1.76% and 0.44%, respectively). Incidence of scleredema diabeticorum (1.13%), granuloma annulare (1.13%) and gangrene (1.13%) was found very close to Roslind et al.^[11] study (1%, 1% and 2%, respectively). Macular amyloidosis was seen in 1.13% of patients in our study which was higher as compared to Chatterjee et al.^[9] study (0.58%) and lower as compared to Goyal et al.^[8] study (4%) whereas other cutaneous manifestations which we encountered were lipodermatosclerosis (3.41%), pyoderma gangrenosum (1.13%), erythema nodosum (1.13%), cellulitis (1.13%), pretibial pigmented patch (1.13%) and stasis dermatitis (1.13%).

In our study, the second most common (26%) endocrinological disorder was hypothyroidism. The incidence of generalised pruritus was maximum, i.e. 38.46% which was higher in comparison with study done by Bains et al.^[12] (16.81%), Keen et al.^[13] (17.17%) and Paswett et al.^[14] (10%). Incidence of dry coarse skin was 33.33% in our study which was lower than the study done by Bains et al.^[12] (67.25%) and Keen et al.^[13] (51.17%) but was higher than the study done by Paswett et al.^[14] (15%). Diffuse hair falls in hypothyroidism was present in 12.83% and alopecia areata was present in 5.13% of patients which was consistent with the study done by Paswett et al.^[14] (13%) and Bains et al.^[12] (5.3%), respectively. Chronic spontaneous urticaria, vitiligo and oral/cutaneous lichen planus were seen in 5.13% of patients which were consistent with the study done by Paswett et al.^[14] (8%, 6% and 2%, respectively). Autoimmunity is the reason behind the association. The incidence of melasma in hypothyroidism in the present study was higher (12.83%) as compared to Bains et al.^[12] study (9.73%). Pretibial myxedema in hypothyroidism in the present study was seen in 5.13% of patients whereas it was 2% in study done by Paswett et al.^[14] Incidence of other cutaneous manifestations was as follows: Pyoderma gangrenosum (2.56%), hirsutism (2.56%), lipodermatosclerosis (2.56%) and onychomycosis (2.56%).

Hyperthyroidism was seen in 8% of the patients in our study. Generalised pruritus was the most common (33.33 %) symptom which was in line with Bains et al.^[12] study (30.76%) followed by warm moist skin (25%) which was less common than the Bains et al.^[12] study (53.84%) but was considerably more in line with Puri study^[15] (23.98%). The incidence of pretibial myxedema was 16.67% in our study which was found surprisingly equal to the study done by Puri, i.e. 16.67%.^[15] Chronic spontaneous urticaria in hyperthyroidism was seen in 16.67% of patients which was closer to Bains et al.^[12] study (15.38%). The incidence of onycholysis was 8.33% which was discordant with the study done by Puri^[15] (28.6%). On the other hand, lipodermatosclerosis and acanthosis nigricans were the other most common cutaneous symptoms observed in hyperthyroidism (8.33%).

Other patients had polycystic ovarian syndrome (PCOS) (2%), hypogonadotropic hypogonadism (0.67%) and hypopituitarism with microadenoma (0.67%). Hirsutism alone was present in 66.67% patients of PCOS which was consistent with the study done by Spritzer et al.^[16] where 70–80% of patients with PCOS had hirsutism. Hirsutism was predominantly of lateral type. The sparseness of hairs over androgenic sites was found in patients with hypogonadotropic hypogonadism due to decreased androgen levels while acanthosis nigricans were noted in the patients which could be attributed to ongoing hormonal therapy. In patients with hypopituitarism with macroadenoma, predominantly central-type hirsutism was noted.

CONCLUSION

Overall, generalised pruritus was the most common manifestation observed in the majority of patients with endocrinal disorders. This study highlights the importance of an integrated approach between dermatology and endocrinology. By systematically documenting various cutaneous changes in endocrinal disorders, diagnostic accuracy is enhanced, promoting earlier intervention and improved patient outcomes. Hence, this study supports the inclusion of cutaneous evaluation in the routine assessment of patients with suspected or confirmed endocrinal diseases.