Pathology of the endocrine system. Markéta Hermanová Masaryk University, Medical Faculty Posterior lobe of pituitary gland Pathological basis of endocrine signs and symptoms Sign or symptom Pathological basis Hormone excess (hyperfunction) Endocrine gland hyperplasia cause by increased trophic stimulus to secretion Functioning neoplasm of endocrine gland Hormone deficiency (hypofunction) Endocrine gland atrophy due to loss of trophic stimulus to secretion Destruction of endocrine gland by inflammation, ischamia or non-functioing tumor Diffuse enlargement of gland Inflammatory cell infiltration Hyperplasia Pituitary nAdenohypophysis nHypofunction -Due to destruction by tumor or compression; due to hypothalamic reasons -Due to inflammation (autoimmune); due to genetic abnormalities of hormone synthesis -Due to ischaemic necrosis, radiation damage or surgical ablation -Leads to secondary hypofunction of adenohypophyseal dependent endocrine glands n (atrophy of gonads, hypothyreosis, hypocorticalism,…) n nHyperfunction -in adenomas, hyperplasias, due to hypothalamic reasons n n Adenoma type Clinical picture Prolactinoma Commonest type, produces galactorrhoea and menstrual disturbances GH-secreting Produces gigantism in children and acromegaly in adults ACTH-secreting Produces Cushing syndrome Others Exceptionally rare Cushing syndrome Neurohypophysis nAntidiuretic hormone (ADH) nADH deficiency – diabetes insipidus (DI) -Due to hypothalamus damage (trauma, tumor,..) -Polyuria, polydipsia -In peripheral forms of DI the renal tubules insensitive to adh - nExcess ADH -Usually due to ectopic production by tumors (neuroendocrine carcinomas of the lung) n nOxytocin n Adrenals nMedulla nProduction of catecholamins (adrenalin, noradrenalin) nTumors: -Pheochromocytoma n(symptoms due to excess catecholamine secretion (secondary hypertension with ↑risk of cerebral bleeding), sweating) -Neuroblastoma n(tumor of children, malignant) n n n Adrenals nCortex nProduction of glucocorticoids,mineralocorticoids, sex steroids nHyperfunction: nCushing syndrome n(excess secretion of ACTH, tumors of adrenals, treatment by steroids nConn´s syndrome n(overproduction of mineralocorticoids: retention of water, hypertension, muscular weakness, arrhythmias) n nHypofunction nCaused by autoimmune adrenalitis, tbc, necrosis of adrenals in sepsis, destruction by tumors,… nWeight loss, lethargy, hypotension, pigmentation, hyponatraemia n n n n n n n n n n n Thyroid nHyperthyroidism nSyndrome due to excess T3 and T4 nVery rarely due to excess TSH nCaused by Grave´disease/thyreoiditis, in which the thyroid stimulating autoantibodies are produced nRarely due to functioning adenoma or toxic nodular goiter n nHypothyroidism (myxoedema) nSyndrome due to insufficient circulating T3 and T4 nIf congenital , causes cretenism nCommonest cause is Hashimoto´s thyreoiditis (=autoimmune thyreoiditis) n Goitre (enlargement of the whole gland) nParenchymatous goitre vs colloid goitre nDiffuse vs nodular goitre n nAetiology nIodine deficiency, due to endemic goitre or food faddism nRare inherited enzyme defects in T3 and T4 synthesis nDrugs that induce hypothyroidism Thyroid tumors nBenign -Follicular adenoma - nMalignant -Carcinoma -Lymphoma n (lymphoma (usually non-Hodgkin´s lymphomas of B-cell type, variable prognosis) n n Carcinoma of the thyroid Type Proportion of all cases (%) Typical age range Mode of spread Prognosis Papillary 60-70 Children, young adults Lymphatic, to lymph nodes Excellent Follicular 20-25 Young-middle age Haematogenous, to bones Good Anaplastic 10-15 Elderly Aggressive local extension Very poor Medullary 5-10 Usually elderly, also familial case (MEN sy) Local, lymphatic, haematogenous Variable, more aggressive in familial cases Parathyroid Secondary hyperparathyreoidsm: a physiological response to hypocalcaemia (e.g. in malabsorption, renal failure) Primary Hypoparathyreoidism nCauses hypocalcaemia nTetany (spasm of the skeletal muscle) nConvulsions nParaesthesiae nPsychiatric disturbances nRarely cataracts and brittle nails n nCaused by: nRemoval of or damage of the glands during thyreoidectomy nIdiopathic nCongenital deficiency Other causes of hypocalcaemia: chronic renal failure, vitamin D deficiency, excess loss during lactation Endocrine pancreas: tumors – islet cell tumors nLess common than pancreatic adenocarcinoma nPresent with endocrine effects and may be malignant: -Insulinoma: hypoglycaemia due to hypersecretion of insulin -Glucagonoma: secondary diabetes and skin rash -Gastrinoma: hypersecretion of gastric acid due to gastrin action resulting in severe peptic ulcerations -….others n n n Islet cell tumor and gastrionams may occur as a part of inherited MEN (multiple endocrine neoplasia) syndrome. Multiple endocrine neoplasia (MEN) syndromes Differences between types of diabetes mellitus (DM: abnormal metabolic state characterised by glucose intolerance due to inadequate insulin action) Features Type 1 (ketosis-prone, juvenile onset, insulin-dependent) Type 2 (not ketosis-prone, maturity onset, non-insulin-dependent) Age of onset Usually ˂20y Usually ˂40y Proportion of all cases ˂10 % ˃90% Type of onset Abrupt (acute or subacute) Gradual Etiological factors Possible viral/autoimmune, resulting in destruction of islet cells Obesity associated insulin resistence HLA asocciation Yes (=genetic predisposition in DM) No Insulin antibodies Yes No Body weight at onset Normal or thin, obesity uncommon Majority are obese (80%) Endogenous insulin production Decreased (little or none) Variable (above or below normal) Ketoacidosis May occur Rare Treatment Insulin, diet, exercise Diet, oral hypoglycemic agents, exercise, insulin, and weight control Risk factors for type 1 and type 2 diabetes mellitus Type 1 DM risk factors Type 1 DM in a first-degree relative (sibling or parents) Type 2 DM risk factors Positive family history Ethnic origin (black, native americans, hispanic, asian american, pacific islanders) Obesity Increasing age Habitual physical inactivity, sedentary lifestyle History of gestational DM Other clinical conditions assoc. with insulin resistence (e.g. polycystic ovary syndrome) History of vasular diseases Previously identified impaired fasting glucose or impaired glucose tolerance Hypertension HDL cholesterol level ˂35mg/dL and/or triglyceride level ≥250mg/dL Cigarette smoking Cardinal clinical signs of DM at diagnosis nPolyuria nPolydipsia nPolyphagia, excessive hunger (in type 1) nWeight loss (in type 1) nRecurrent blured vision nKetonuria (in type 1) nWeakness, fatigue, dizziness nOften asymptomatic (type 2) n Complications of diabetes Situation Complication Large blood vessels Accelerated arteriosclerosis leading to: -Myocardial infarction -Cerebrovascular diseases -Ischaemic limbs -Responsible for 80 % of adult diabetic death Small blood vessels Endothelial cells and basal lamina damage. Retinopathy (major cause of blindness), nephropathy Peripheral nerve Diabetic neuropathy (v.s. due to disease of small vessels supplying the nerves) Neutrophils Susceptibility to infection Pregnancy Pre-eclamptic toxaemia Large babies Neonatal hypoglycamia Skin Gangrene of extremities Soft tissue lesions (Granuloma annulare, necrobiosis lipoidica) Complications of diabetes. komplikace diabetu Pathology of the skin Pathological basis of dermatological signs Clinical signs Pathological basis Scaling Parakeratosis Erythema Dilatation of skin vessels Blisters Separation of layers of the epidermis or epidermis from dermis Bruising Leakage of blood into dermis Pigmentation Increased aktivity of melanocytes Increased numbers of melanocytes Endogenous pigment, e.g. Ochronosis Exogenous pigment, e.g. tattoo Plaques Increase in epidermal and dermal thickness with cells Macules Dilated blood vessels Inflammatory cells Altered pigmentation Papules Inflammatory cells Oedema Tumor Nodules Epidermal, adnexal and dermal tumors Cysts Rashes restricted to exposed areas Photosensitivity Contact eczema Nail abnormalities Trauma to nail bed Psoriasis Fungi Eczema - a reaction pattern, not a single disease - several causes - varied clinical patterns - histologically: early inflammation and spongiosis, later hyperkeratosis, parakeratosis Spongiosis: intercellular oedema + genetic factors Inflammatory disorders: infections nViral -human papillomavirus (verruca vulgaris, genital condyloma accuminatum) -Pox virus (molluscum contagiosum) -Herpes virus (herpes zoster: chickenpox, shingles; cold sores (HSV1) and genital herpes (HSV2) -HIV (Kaposi´s sarcoma) - nBacterial -Staphylococcal impetigo -Streptococcal celullitis -tbc of the skin -leprosy - nFungal -Tines capitis, pedis, cruris… -Candida albicans, Trychophyton species,…. - nProtozoal -leishmaniasis, amoebiasis, trypanosomiasis n HSV infection 00756+ 00100+ Non-infectious inflammatory diseases nUrticaria (hives, wheals) nReaction pattern, oedema =basic lesion nClinically itching, swelling nCaused by plants and animal toxins, physical stimuli, various drugs n nLupus erythematosus nAutoimmune disease affecting connective tissue nSystemic form involves kidneys nSkin lesions involve epidermis and adnexa n nLichen planus nPolygonal itchy papules nBand-like chronic inflammatory infiltrace nCentred on dermo-epidermal junction n nPsoriasis nGenetically determined disease nSilvery-grey scales of parakeratosis nPolymorphs enter epidermis but abscesses are sterile n n Clinicopathological features of bullous disorders Disease Location of bullae Immune reaction Clinical feature Pemphigus Intra-epidermal IgG on intercellular junctions High mortality Pemphigoid Subepidermal IgG on basement membranes Elderly patiens Dermatitis herpetiformis Subepidermal IgG on papillary dermis Associated with coeliac disease Pemphigus vulgaris 00010+ IgG immunopositivita among keratinocytes 00075+ Suprabasal acantolysis, acantolytic bulla Pemphigoid n n A – subepidermal bulla B - linear, continuous deposition of IgG at the dermoepidermal basement membrane zone in perilesional skin Skin: Epidermal antibodies 2 Epidermolysis bullosa nInherited disease, 30 types n nMutations in genes coding specific keratins in the basal epithelial layer (intraepithelial bullae), collagens and other attachement proteins (subepithelial bullae) n nExtreme fragility of the skin n nMucosae also affected nBenign epidermal neoplasms nFibroepithelial polyp nSeborrhoic warts/keratosis (basal cell papiloma) nSquamous cell papilloma (often HPV related) nCysts (epidermal and sebaceous) n nMalignant epidermal neoplasms nBasal cell carcinoma -Very common skin malignancy -Related to chronic sun exposure, most commonly on face -Locally very invasive, metastasis exteremely rare nSquamous cell carcinoma -Malignant skin neoplasms -Related to chronic sun exposure -Locally invasive, metastasis late nActinic keratosis and Bowen´s disease (=, in situ carcinomapremalignant lesion) Benign melanocytic naevi Lentigo Junctional naevus Compound naevus Intradermal naevus Blue naevus Malignant melanoma Malignant melanoma nTumor composed of malignant melanocytes nUsually pigmented, but may be amelanotic nPrognosis depends on stage of the disease nAetiologically associated with fair skin and sunburn nDysplastic naevus syndrome: familial tendency to melanomas, high risk developing melanomas nClinicopathological types: -Lentigo maligna -Acral lentiginous melanoma -Superficial spreading melanoma -Nodular melanom