1.Cutaneous features of endocrine diseases

2. DIABETES MELLITUS SKIN SYMPTOMS DUE TO DIABETICVASCULAR ABNORMALITIES Diabetic microangiopathy Both small and large blood vessels are affected in diabetesmellitus. In diabetic microangiopathy, there is proliferation of endothelial cells and deposits of PAS-positive material in the basement membrane of arterioles, capillaries and venules with resulting decreased luminal area . Basement membrane thickening is a characteristic finding in diabetic and prediabetic patients 3. Microangiopathy is responsible for the retinopathy,nephropathy and possibly also neuropathy and dermopathy associated with diabetes. Erysipelas-like erythema This condition is seen mostly in elderly diabetic patients with an average duration of diabetes mellitus of 5 years. Well-demarcated, red areas occur on the legs or feet, and there may be underlying destructive bone disease caused by a small vessel insufficiency. 4. Wet gangrene of thefoot This is a late manifestation of diabetic microangiopathy. Non-diabetic atherosclerotic subjects tend to develop a dry form as a result of large vessel insufficiency. 5. Diabetic rubeosis A peculiar rosy reddeningof the face, and sometimes of the hands and feet, may be seen in long-standing diabetes. The changes have been attributed to decreased vascular tone or diabetic microangiopathy 6. Diabetic dermopathy (diabetic shin spots) This is the most common dermatosis associated with diabetes mellitus. Microangiopathy and neuropathy are involved . Lesions are predominantly situated on the shins, forearms, thighs and over bony prominences. The initial lesion is an oval, dull-red papule 0.51 cm in diameter. It evolves slowly, producing a superficial scale, leaving an atrophic brownish scar. The colour is due to haemosiderin in histiocytes near the vessels. 7. Large vessel disease Atherosclerosis is the second form of vascular diseasefrequently associated with diabetes mellitus. The patient shows intermittent claudication with pallid and cool skin distally on the extremities. Common clinical sequelae are myocardial infarction, cerebral thrombosis, nephrosclerosis and ischaemic gangrenous lesions of the legs and feet. 8. Diabetic neuropathy There is a distal symmetrical polyneuropathy with mixedmotor and sensory nerve involvement. The motor neuropathy of the foot is characterized by dorsally subluxed digits, distally displaced plantar fat pads, depressed metatarsal heads, hammer toes and pes cavus . A painless and slowly penetrating ulcer of the sole and of other pressure sites is suggestive of diabetic neuropathy. The ulcer is circular and punched out in shape, occurring in the middle of a callosity . 9. An initial subepidermal haemorrhagic bulla may give rise to discoloration of the surrounding skin. Loss of temperature and pain sensation and absence of the ankle reflex (an early sign of diabetic neuropathy) indicate a neuropathic origin. Sensory abnormalities of the lower extremities include numbness, tingling, aching and burning. Burning feet and restless legs are common complaints. 10. Damage to autonomic nerves of the skin in chronicadvanced cases is manifested by oedema, erythema and atrophy. Complex nature of diabetic foot requires special attention. There is a multifactorial aetiology. Predisposing factors include abnormal plantar pressure points, foot deformities and minor trauma 11. Cutaneous infections in diabetesmellitus Skin infections due to Staphylococcus aureus and group AStreptococcus haemolyticus are common in diabetic patients . infections causing severe furuncles, carbuncles and styes were frequent among diabetic individuals. Invasive Pseudomonas infection of the ear can progress through cellulitis and osteitis to cranial nerve damage and meningitis with a high mortality rate, so-called malignant otitis externa. 12. Non-clostridial gas gangrene This complication develops in the soft tissues near agangrenous focus. It was diagnosed in 17% of diabetics who were admitted to hospital because of gangrene or ulceration. The commonest pathogens are Escherichia coli, Klebsiella, Pseudomonas and Bacteroides spp. in various combinations. 13. Candida albicans Candida albicans infections of mouth, nail folds, genitals and intertriginous skin areas are frequent in diabetics. Candidiasis may be the presenting feature of diabetes, and is frequently seen in diabetic patients whose disease is not well controlled. A high glucose level of the saliva seems to account for the oral infection . Phimosis is a common complaint of diabetic men, and recurring candidal infection is usually the cause. 14. Insulin resistance and acanthosisnigricans Acanthosis nigricans is characterized by symmetric, velvetyto verrucous, hyperkeratotic and hyperpigmented plaques that have a predilection for the axillae, the nape, and other flexural areas. High plasma levels of insulin are thought to contribute to the development of acanthosis nigricans. 15. Various skin disorders associatedwith diabetes mellitus Necrobiosis lipoidica Frequencies of diabetes between 42% and 62% have beenreported in patients with necrobiosis lipoidica. whereas necrobiosis lipoidica is uncommon (0.3%) among diabetic patients. Nonscaling plaques with a yellow atrophic center, surface telangiectases, and an erythematous or violaceous border that may be raised. 16. yellow aspect in central areaof the lesions is most likely due to thinning of the dermis, making subcutaneous fat more visible. Ulceration occurs in up to 35% of cases. 17. Disseminated granuloma annulare This is rarely seen in diabetic patients Pruritus. Pruritus was once considered a typical symptom ofdiabetes mellitus. The frequency of generalized pruritus in diabetic patients is unknown. Anogenital pruritus may be due to secondary infection with candidiasis or haemolytic streptococci. Stiff joints and waxy skin Waxy tight skin on the backs of the hands and limited joint mobility may be seen in patients with insulindependent diabetes 18. Scleredema diabeticorum The most common sites ofinvolvement are the neck and upper back . The condition is mainly seen in overweight adults with non-insulindependent diabetes, is essentially permanent, painless and causes no morbidity. 19. Finger pebbles Thickening of the skin onthe dorsum of the hand due to many causes, diabetes among them, is often manifest by a pebbling of the skin on the knuckle area. 20. Skin tags Skin tags are small, soft,pedunculated lesions occurring on eyelids, neck and axillae, often associated with obesity. 21. Eruptive xanthomas of the skin Eruptive xanthomas maydevelop in diabetic patients with hyperlipidaemia. The lesions slowly resolve when the diabetes is properly managed. 22. Vitiligo Vitiligo occurs more frequently in diabetic individuals. In late-onset diabetes, a 4.5% frequency has been reported . Lichen planus An increased incidence of abnormal glucose tolerance tests in patients with lichen planus, especially oral lichen planus, has been reported . The overall support for a true association seems limited . Haemochromatosis - The main symptoms are liver disease, hyperpigmentation, joint disease, hypogonadism and eventually, diabetes. 23. Diabetic bullae Diabetic bullae are uncommon,but believed to be a distinct marker for diabetes . The location is the lower legs and feet, occasionally hands and fi ngers. They range in size from less than one centimetre to several centimetres. A typical blister arises on a noninflamed base, and heals without scarring in 25 weeks. 24. Reactive perforating collagenosis There have been reports ofperforating collagenosis in patients with diabetes with and without renal insuffi ciency. The cause is attributed to diabetic microangiopathy and lesions are due to minor injury such as pressure or scratching 25. Insulin lipodystrophy Insulin lipodystrophy israre. Patients present with atrophic plaques at the sites of insulin injection. There is atrophy of the subcutaneous fat. 26. Local insulin reactions Insulin may cause immediate local reactions, starting as erythema, which turn urticarial within 30 min and subside within an hour; these are probably IgE mediated. Serious generalized immediate reactions are rare. The most common reactions are delayed, starting about 2 weeks after onset of insulin therapy. An itchy nodule develops at the site of injection. It lasts for days and heals with hyperpigmentation and perhaps a scar. Delayed hypersensitivity is involved. 27. Addisons disease This condition is due to insufficient secretion or supply ofadrenocortical hormones or hormonal compounds mainly cortisol and mineralocorticoids. General symptoms include wasting, fatigue, orthostatic hypotension, dizziness, anorexia, abdominal pain and amenorrhoea. Self-mutilation, presenting as gouges in the skin, has been reported as a result of psychiatric symptoms hyperpigmentation of the skin, due to increased secretion of pituitary MSH and ACTH as a response to low adrenal corticosteroid levels, is the cardinal dermatological feature. 28. In women, in whom the adrenal gland is the mainsource of androgens, there may be loss of axillary and pubic hair and improvement in acne. Features of associated autoimmune disease may be present, notably vitiligo in 15% of patients with autoimmune causation. 29. Cushings disease and syndrome Chronic glucocorticoid excess may occur due toIncreased secretion of adrenocorticotrophic hormone (ACTH, corticotrophin), usually from the pituitary . 2. Glucocorticoid hypersecretion of adrenal origin . 3. Exogenous administration of glucocorticoids. 1. 30. Thyroid diseases Skin manifestations of thyroid dysfunction may bedivided into three categories: (1) Direct action of thyroid hormone on skin tissues (2) Skin manifestations of direct thyroid hormone action on non-skin tissues (3) Autoimmune skin disease associated with thyroid dysfunction of autoimmune etiology 31. Direct thyroid hormone action on skin tissues (1) HYPOTHYROIDISM Epidermal Changes -Coarsened, thin, scaly skin Dermal Changes -Non-pitting edema (myxedema) -Edema (hands, face, eyelids) -Carotenemia -Pallor Hair and Nail Changes -Dry, brittle, coarse hair -Alopecia -Loss of lateral third of eyebrows -Coarse, dull, thin, brittle nails 32. Sweat Gland Changes-Dry skin (xerosis) -Decreased sweating (2) THYROTOXICOSIS Epidermal Changes -Smooth, thin skin Hair and Nail Changes -Fine hair -Alopecia -Shiny, soft, friable nails (onycholysis, Plummer's nails) 33. Skin manifestation of thyroid hormoneaction on other tissues HYPOTHYROIDISM-Cold intolerance -Pallor -Purpura -Drooping of upper eyelids -Nerve entrapment syndromes 34. THYROTOXICOSIS-Warm skin -Heat intolerance -Increased sweating(hyperhydrosis) -Hyperpigmentation -Erythema -Telangiectasia 35. Associated autoimmune phenomena Dermopathy (pretibial myxedema) Acropachy Urticaria, pruritis Vitiligo Pernicious anemia Bullous disorders Eczema Connective tissue diseases 36. Thyroid acropachy Clubbing of the fingers and toes in Graves disease,associated with soft-tissue swelling of hands and feet and with periosteal new bone formation, is termed thyroid acropachy. It occurs in less than 1% of thyrotoxic patients, and is usually associated with exophthalmos and pretibial myxoedema (Diamonds triad). The proximal phalanges and first or second metacarpals are most commonly affected. Most patients have minimal or no symptoms, but in those with symptoms, stiffness is the most frequent. 37. Pretibial myxoedema Localized oedematous and thickened pretibial plaqueformation occurs in 110% of patients with hyperthyroidism. It is usually a late feature, occurring after ophthalmopathy and diagnosis of hyperthyroidism. Also occurs on the dorsum of the hallux, and may affect other sites, including the lower abdomen, arms, shoulders, neck and pinnae. 38. Clinical features The lesions first appear on the anterolateral aspect ofthe lower limbs and only later extend to the back of the legs, and feet . The nodules are pink or skin-coloured, sometimes yellow-brown and waxy, with prominent hair follicles giving a peau dorange appearance. 39. They may occur in old or recent scars localized pruritus or hypertrichosis over the lesions may bea feature localized hyperhidrosis has also been reported . Three clinical types are recognized: (1) Sharply circumscribed, in which both nodular and tuberous lesions appear on the shins and toes (2) Diffuse, producing solid non-pitting oedema of the shins and feet (3) Elephantiasic, in which there is both oedema and nodule formation 40. Elephantiasic pretibial myxoedema 41. Pituitary syndromes HYPERPITUITARISM Excessive secretion of growth hormone (GH, somatotrophin)causes an increase in plasma insulin-like growth factor-1 (IGF-1). These hormones stimulate synthesis of collagen and glycosaminoglycan in the skin and skeleton, leading to insidious hypertrophy of skin, subcutaneous tissues and viscera, and to periosteal bone growth. This causes acromegaly in the adult Gigantism in children whose bony epiphyses have not yet closed. 42. Acromegaly and gigantism Periosteal new bone formation of the facial bones and skincauses the characteristic facies. Features are prognathism, frontal bossing, widely spaced teeth and acral hypertrophy, which causes elongated, blunt and thickened fingers. Dermatological features include a protruding, thickened lower lip, oedematous thick eyelids, a large and furrowed tongue, triangular large ears, numerous skin tags (fibroma molluscum). widened skin pores, wet and oily skin due to hyperhidrosis and increased sebum production, acne and cutis gyrata of the scalp in more extreme cases. 43. Eruptive seborrhoeic keratoses mimicking the sign ofLeserTrlat have been reported in acromegaly . Hyperpigmentation develops in about half of the affected individuals due to increased levels of melanocytestimulating hormone (MSH), and acanthosis nigricans may occur. The scalp hair is initially coarse and there may be hirsutism, but later in the disease there is a decrease in gonadotrophin production, which causes the hair to become finer, with loss of secondary sexual hair. The nails are flat and wide and grow fast. 44. Non-cutaneous features include macroglossia, visualfield defect and headache due to the neoplasm, arthropathy, carpal tunnel syndrome and proximal myopathy. Cardiovascular morbidity and mortality is markedly increased. 45. PITUITARY INSUFFICIENCY Insufficiency of the adenohypophysis (anterior pituitary) may involve individual or multiple hormones. In classical hypopituitarism, all endocrine cell functions of thepituitary gland are involved to a varying degree. Pallor of the skin due to decreased MSH secretion results in generalized hypopigmentation, most apparent in the skin of the nipple areola and genitalia; in contrast with anaemia, the mucous membranes retain their normal colour. There is an increased sunburn tendency and lack of tanning, and there may be a degree of carotenaemia due to hypothyroidism. 46. Loss of terminal hair due to decreased gonadotrophin secretion is observed in all patients, fi rst in the axillae and later, but not invariably, in the pubic area. Fine wrinkling and dryness of the skin simulates advanced age. The face appears expressionless due to diminution of the facial skinfolds. The activity of sebaceous and sweat glands is reduced. Pituitary dwarfism is characterized by proportionate retardation of somatic growth in conjunction with normal mental development. 47. THANKS