Histology and Pathology of the Endocrine System 06 01 23.pptx

Histology and Pathology of the Endocrine System Catherine Chinyama Consultant Pathologist Guernsey Honorary Clinical Professor [email protected] 6th January 2023 1 Learning Objectives • To understand the relationship of the endocrine glands and target organs • To learn the types of hormones se...

Histology and Pathology of the Endocrine System Catherine Chinyama Consultant Pathologist Guernsey Honorary Clinical Professor [email protected] 6th January 2023 1 Learning Objectives • To understand the relationship of the endocrine glands and target organs • To learn the types of hormones secreted by the major endocrine glands • To learn the histological features of the major endocrine glands • To learn the basic pathology of the major endocrine glands 2 Endocrine Glands • No duct system as in exocrine glands • Hormones are organic chemicals released at specific times in small amounts into the tissue fluids or blood vessels • Hormone Gk - hormaein meaning ‘to arouse’ ‘to excite’ • Pancreas both exocrine and endocrine gland 3 Some definitions : Action of hormones • Endocrine - Action of the hormone on a target organ away from the secreting cell • Autocrine - Action of the hormone on the secreting cell • Paracrine - Action of the hormone on the adjacent cell • Neuroendocrine - Neural stimulation of endocrine cells to secrete hormones e.g. the medulla of adrenal gland 4 Overall Structure of Endocrine Glands • Functional unit consist of cuboidal secretory cells with a lumen at the centre • Secretory cells supported by myoepithelial cells which contract to facilitate the secretion • Not all endocrine functional units have lumen e.g. pituitary and parathyroid glands have no lumina 5 What are the clinical manifestations of endocrine diseases? • Hormone overproduction • Hormone underproduction • Tumour/mass lesion which can be: – Non-functional → pressure effect – Associated over production of hormones • Understanding clinical features requires knowledge of the pathology and related biochemical abnormalities 6 Pituitary Gland (hypophysis) Divided into: • Adenohypophysis/anterior lobe • Neurohypophysis/posterior lobe 7 From Basic Histology: Junqueira et al; 1977; 2nd Ed 8 Cells of the Anterior Pituitary Gland • • • • Acidophils – take up the acidic dyes Basophils – take up the basic dyes Chromophobe – no specific staining features Staining pattern not related to specific hormone secretion e.g. ACTH is secreted by both chromophobes & basophils • Antibody staining against specific hormone termed immunocytochemistry assists in identifying specific cells of the pituitary gland e.g. antibodies to growth hormone will identify cells which secrete GH if there is tumour secreting this hormone 9 Histology of Anterior Pituitary Acidophils Capillary Basophils 10 Hormones From Anterior Pituitary Gland Cell Hormone Target Organ Somatotroph Lactotroph Corticotroph Growth Hormone Bones Prolactin Breasts Adrenocorticotrophic Adrenal glands hormone (ACTH) Gonadotroph Follicle stimulating Ovary & testis hormone (FSH) Luteinising hormone Ovary & testis (LH) Thyrotroph Thyroid stimulating Thyroid gland hormone (TSH) NB: The pituitary hormones are under the influence of the hypothalamic releasing or inhibitory hormones. 11 Hormones from Posterior Pituitary Gland • Two hormones • Antidiuretic hormone (ADH) facilitates the absorption of water in the kidneys which concentrates the urine • Lack of ADH leads to diabetes insipidus • Oxytocin promotes contractions of the smooth muscle in the uterus during childbirth and myoepithelial cells in the breast during breast feeding 12 Pathology of the Pituitary Gland • Pituitary adenomas ( benign tumours) – Arise from anterior lobe – Can be functional or non-functional – Constitute 10% of intra-cranial neoplasms – Productive adenomas cause hyperpituitarism e.g. acromegaly – Pressure effect causing hypopituitarism • Space occupying effect of functional or nonfunctioning adenomas causes: Headaches, vomiting, nausea, diplopia, impaired vision 13 Post Mortem Pituitary Adenoma From 7th Ed Robin & Cotran, Pathologic Basis of Disease 2005 14 The adenoma has been removed to illustrate the optic chiasma which was compressed by the tumour. Patients present with bitemporal hemianopia. From 7th Ed Robins & Cotran Pathologic Basis of Disease 2005 15 Thyroid Gland • Synthesises two hormones: Thyroxine (T4) and Triiodothyronine (T3) which stimulate metabolic rate • Synthesis of T4 and T3 requires iodine • Sea salt is rich in iodine • Lack of iodine leads to an enlarged thyroid gland, termed goitre • The gland enlarges to absorb the maximum concentration of iodine 16 ‘Normal Thyroid Gland' • Wt. = 35-45grams • 2 lobes and isthmus • Thyroid tissue is composed of follicles with variable-sized lumina • Follicles contain colloid with eosinophilic or pink appearance 17 The follicles are lined by cuboidal cells 18 Other Features of the Thyroid Gland • Increased vascularity • The endothelial cells lining the capillaries are fenestrated (i.e. have gaps between them) →a common feature in endocrine glands • Fenestration allows passage of hormones into the circulation 19 Increased vascularity in a thyroid gland 20 Pathology of the Thyroid Gland • • • • • Goitre - Euthyroid Grave’s Disease - Hyperthyroid Hashimoto’s disease - Hypothyroid Adenoma - Euthyroid Cancer - Euthyroid 21 Multi-nodular Goitre • Lack of iodine leads to an enlarged thyroid gland termed goitre due to hyperplasia and hypertrophy of the thyroid cells • The gland enlarges to maximise the amount of iodine absorbed • The increase in size overcomes the hormone deficiency and the patients are therefore euthyroid 22 Clinical: Multi-nodular Goitre 23 Surgery: Multi-nodular Goitre 488.2 g 24 Pathology: Multi-nodular Goitre 25 • Multi-nodular goitre PM: compressing the trachea • Important to assess the radiology before surgery as the patient may arrest after successful thyroidectomy due to tracheomalacia • softening of the trachea which collapses and obstruct the airways Multi-nodular Goitre 26 A retrosternal goitre caused post-op respiratory distress necessitating ICU admission due to tracheomalacia 27 Grave’s Disease • Auto-antibodies stimulate TSH receptors • Diffuse enlargement of the thyroid gland due to hyperplasia of thyroid cells • Infiltrative ophthalmopathy - accumulation of soft tissue and inflammatory cells behind the eye leading to proptosis • Infiltrative dermopathy – thickening and induration of the skin on the anterior shin→ pre-tibial myxoedema; ↓TSH↑T3/T4 28 Thyroidectomy for Grave’s Disease Note vascular surface 29 Grave’s disease: the colloid has ‘soap bubble’ appearance due to hyperactivity 30 Hashimoto’s Thyroiditis • Most common cause of hypothyroidism in areas where iodine is readily available • An autoimmune disease – immune system destroys its own thyroid tissue • Progressive depletion of thyroid cells by inflammation & replaced by fibrosis • ↑TSH↓T3/T4 31 Hashimoto Thyroiditis The gland is irregular with a solid cut surface On histology there is a prominent lymphocytic infiltrate 32 Hashimoto thyroiditis with prominent lymphocytic infiltrate/inflammation 33 Thyroid Tumours • Follicular adenoma - benign tumour of the thyroid follicular cells • Carcinoma – Four main types – Papillary ( 75-85%); ↑ risk of lymph node metastasis – Follicular (10-20%); ↑ Mets to bone, lung & liver – Medullary (5%); arises from C cells ; 20% associated with MEN 2 syndrome (multiple endocrine neoplasm) – Anaplastic (<5%); older patients; poor prognosis 34 Benign adenoma vs Cancer 35 Para-follicular Cells • C cells secrete calcitonin which promotes reduction of calcium concentration in the blood • Para-follicular cells or clear cells (C cells) are found between the follicles • C cells are the origin of medullary carcinoma of the thyroid 36 Parathyroid Glands • Secrete parathyroid hormone (PTH) • Controls the levels of calcium in the blood • Decrease in blood calcium stimulates PTH secretion • Chief cells have no lumen and are separated by prominent vascularity 37 Pathology of Parathyroid Glands • Adenoma - involves one gland • Hyperplasia - involves all four glands • Both cause hypercalcaemia 38 Normal PTH gland; 6mm; ~2g PTH gland adenoma; 19mm; 9g; 39 Adrenal Glands • Paired glands • Upper poles of the kidneys • Consist of adrenal cortex and adrenal medulla which are embryologically, morphologically and functionally distinct • Adrenal cortex derived from the mesoderm • Adrenal medulla derived from the neural crest 40 Normal Adrenal Gland • Characteristically orange/yellow in colour because the cells are rich in lipids 41 Adrenal Cortex • Divided into three distinct zones: - Zona glomerulosa - Zona fasciculata - Zona reticularis • The cells appear pale on histology because the lipids are cleared by chemicals during processing 42 Whole mount histological slide of adrenal gland to illustrate the zones of the cortex + medulla Available on virtual microscope on the server 43 Functional Zonation of the Adrenal Cortex: Salt, Sugar & Sex ! • Zona glomerulosa - Mineralocorticoid - Aldosterone - For absorption of sodium • Zona fasciculata - Glucocorticoids - Cortisol & corticosterone - Sex hormones • Zona reticularis - 17 Ketosteroids - Sex hormones 44 ZG = Zona Glomerulosa – closely packed round cells ZF = Zona Fasciculata – clear cells arranged in cords ZR = Zona Reticularis – smaller darker staining cells ZG ZF ZR Medulla 45 Pathology of the Adrenal Glands • Adrenocortical hyperactivity • Due to hyperplasia, adenoma or cancer (rare) • Cushing’s Syndrome ( excess cortisol) • Conn’s Syndrome ( excess aldosterone) • Adrenogenital syndrome ( excess androgens) • Adrenocortical insufficiency • Addison’s disease 46 Adrenal Cortex Adenoma • Non-functional cortical adenoma • Incidental finding on abdominal imaging • Functional adenomas can cause Cushing’s Syndrome or Conn’s Syndrome 47 Adrenal Medulla • Compact cells which secrete adrenaline and noradrenaline in response to intense emotional reaction (such as exams!) • Flight or fight hormones • Secretion results in vasoconstriction, ↑heart rate, blood sugar levels → Part of the organism’s response to stress 48 Adrenal Cortex Adrenal medulla cells are neuroendocrine – darker staining than the adrenal cortex cells Adrenal medulla 49 Pheochromocytoma • Tumour of the adrenal medulla • 0.1-0.3% cause of treatable hypertension • 10% Tumour • 10% are familial as part of the MEN2 • 10% are extra-adrenal • 10% bilateral • 10% are malignant • 10% arise in childhood 50 Pheochromocytoma • Due to high levels of catecholamines • Paroxysmal↑ BP + tachycardia, palpitations, headache, sweating, tremor & sense of apprehension • Complications of ↑ BP • CCF, IHD, cardiac arrhythmias, CVA 51 Take Home Message • Endocrine diseases are due to: – Hormone overproduction – Hormone underproduction – Tumour/mass lesion which can be: • Non-functional → pressure effect • Associated with overproduction of hormones • Associated with underproduction of hormones • Understanding clinical features requires knowledge of the pathology and related biochemical abnormalities 52 THE END 53