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4/1/2014 Pathology of the Endocrine System นายแพทย ดร.ณตพล ศุภณัฐเศรษฐกุล ภาควิชาพยาธิวิทยา คณะแพทยศาสตร มหาวิทยาลัยนเรศวร 4 เมษายน พ.ศ. 2557 Topics • Introduction • Diseases of the Endocrine glands – Pituitary gland – Thyroid gland – Parathyroid glands – Endocrine pancreas – Adrenal cortex – Adrenal medulla 1 4/1/2014 Introduction • Endocrine = (Gr.) endo + krinein (inside) (to secrete) • Primary function of the endocrine glands is to produce hormone to regulate the functions of other cells or organs • “Ductless glands” (ตางจาก Exocrine gland) • “Autocrine, Paracrine, Endocrine effects” • “Endocrinologist” Endocrine Glands • • • • • Pituitary gland Thyroid gland Parathyroid glands Endocrine pancreas (Islets of Langerhans) Adrenal gland – Adrenal cortex – Adrenal medulla 2 4/1/2014 Pituitary Diseases • Pituitary Gland • Pituitary hyperfunction – Pituitary adenomas • Pituitary hypofunction – Pituitary insufficiency 3 4/1/2014 Pituitary Gland • Located intracranially at “sella turcica” at base of the cranium • Anterior pituitary – Posterior pituitary • Connected to the hypothalamus via a stalk Pituitary Gland • Anterior pituitary (Adenohypophysis) : Growth hormone (GH) Prolactin (PRL) Adrenocorticotropic hormone (ACTH) Gonadotropins (Follicle stimulating hormone (FSH) and Luteinizing hormone (LH) – Thyroid‐stimulating hormone (TSH) – – – – • Posterior pituitary (Neurohypophysis) : – Oxytocin – Antidiuretic hormone (ADH) 4 4/1/2014 Pituitary Hyperfunction • Pituitary adenomas • Prolactinomas (lactotropic adenomas) is most common • Cause Hyperprolactinemia – Amenorrhea (lack of menstruation) – Galactorrhea (milk secretion unrelated to pregnancy) – Infertility (inhibit normal ovulation) • Somatotropic adenomas : Growth hormone (GH) – Before closure of the epiphyseal plate : Gigantism – After closure of the epiphyseal plate : Acromegaly 5 4/1/2014 Pituitary Adenoma Acromegaly 6 4/1/2014 Gigantism Pituitary Hypofunction • Panhypopituitarism (pituitary insufficiency) – General weakness, cold intolerance, weight loss, hypotension, amenorrhea, impotence, dwarfism • Selective pituitary hypofunction • Diabetes insipidus – A lack of antidiuretic hormone (ADH) secondary to destructive lesions of the hypothalamus or pituitary stalk or tumors of the posterior pituitary – Secrete large amounts (5‐6 L/day) of hypotonic urine 7 4/1/2014 Thyroid Diseases • • • • Thyroid gland Hyperthyroidism Hypothyroidism Thyroid Neoplasms Thyroid Gland • An endocrine gland located in the neck • Two types of cells : Follicular cells and C cells • Follicular cells – Thyroxine or tetraiodothyronine (T4) – Triiodothyronine (T3) • C cells – Calcitonin involved in maintenance of calcium homeostasis 8 4/1/2014 Hypofunction & Hyperfunction 9 4/1/2014 Hyperthyroidism • Hyperthyroidism or thyrotoxicosis is a hypermetabolic state that results from an excess of free thyroid hormone (T3 and T4) in blood • Graves’ disease (autoimmune disease) – Antibodies to the TSH receptor on the surface of thyroid follicular cells – Diffusely enlarged gland with lymphoid follicles – Tachycardia, restlessness, sweating, palpitation, tremor, increased appetite, weight loss – Exophthalmos (bulging eyes) and pretibial myxedema http://www.immuneweb.com/images/20/figure20‐04.jpg 10 4/1/2014 Exophthalmos http://www.beltina.org/pics/exophthalmos.jpg Hypothyroidism • Congenital developmental defects – Thyroid dwarfism – Cretinism (mental retardation) • Autoimmune Hashimoto’s thyroiditis (most common cause of hypothyroidism) • Thyroidectomy • Iodine deficiency : nodular goiter • Sleepy, lacks of mental alertness, bradycardia, cold intolerance, constipation, muscle weakness • Myxedema : increased connective tissue deposition (glycoaminoglycans, hyaluronic acid, and other mucopolyscaccharides) 11 4/1/2014 Dwarfism http://healthtalk.info/wp‐content/uploads/Fig‐2‐cretinism.jpg http://howshealth.com/wp‐content/uploads/2010/11/cretinism.jpg Clinical Features Myxedema http://healthtalk.info/wp‐content/uploads/Fig‐3‐ myxedema‐thyroid‐hormone‐deficiency‐ hypothyroidism.jpg Graves’ dis. http://www.checkbook.org/sitemap/health/Gr aves_Disease/..%5CGraphics%5CGraves_eyes.j pg 12 4/1/2014 Goiter http://s1.hubimg.com/u/2822516_f520.jpg Thyroid Neoplasms • Follicular adenoma : most common benign tumor – Small, well encapsulated with fibrous tissue, composed of thyroid follicles • Papillary carcinoma : 80% of all malignant thyroid tumors – Four times more common in women than in men – Tends to metastasize to the local lymph nodes 13 4/1/2014 Follicular Adenoma 1 Follicular Adenoma Fibrous capsule Follicular cells 2 14 4/1/2014 Papillary carcinoma of thyroid 1 Papillary carcinoma of thyroid 2 15 4/1/2014 Diseases of the Parathyroid Glands • Parathyroid Glands • Hyperparathyroidism • Hypoparathyroidism Parathyroid Glands • Usually, 4 glands behind the thyroid • Secrete parathormone (PTH) in response to a decrease in plasma calcium level • PTH stimulates the release of calcium from bone and also resorption of calcium from urine in the kidney Æ to elevate calcium concentration in blood 16 4/1/2014 Hyperparathyroidism • Primary : parathyroid hyperplasia, neoplasia • Secondary : compensatory mechanism triggered by hypocalcemia caused by chronic renal failure, hypovitaminosis D • Excess of PTH in the circulation • Hypercalcemia : muscle weakness, cardiac arrhythmia, nephrocalcinosis, urolithiasis • Bone weakness and prone to fracture 17 4/1/2014 Parathyroid Hyperplasia & Neoplasia 18 4/1/2014 Hypoparathyroidism • Most commonly occurs after all 4 glands are totally removed during cancer surgery of the neck • Hypocalcemia : hypocalcemic tetany (muscular spasm), irregular heart beat, cardiac arrest Endocrine pancreas • The endocrine cells are arranged into islets of Langerhans, scattered through the entire organ but are most prominent in the tail of pancreas • The islets of Langerhans contain several endocrine cell types – Alpha cells (20%) secrete glucagon – Beta cells (70%) secrete insulin – Delta cells (10%) secrete somatostatin or pancreatic polypeptide (PP) 19 4/1/2014 http://www.gopetsamerica.com/anatomy/illustrations/pancreas.jpg http://embryology.med.unsw.edu.au/histology/endocrine/pan20he.jpg http://wikis.lib.ncsu.edu/images/8/80/Endoexoc.gif 20 4/1/2014 Diabetes mellitus (DM) • (Gr) = diabetes + mellitus (sweet) • diabetes = “Pass through” to denote polyuria (large amount of urine) • DM caused by – Absolute or relative deficiency of insulin – Target tissue resistance to insulin • Type 1 DM (5‐10%) children and adolescents • Type 2 DM (90‐95%) overweight adults Clinical features of DM • • • • • • Hyperglycemia Glycosuria Æ Osmotic diuresis Æ Polyuria Polydipsia Polyphagia Muscle wasting and weight loss Increase lipolysis Æ ketone body formation Æ ketoacidosis 21 4/1/2014 Complications of DM • Cardiovascular system – Atherosclerosis, coronary heart disease, stroke – Artery occlusion : DM foot gangrene • Kidneys – Glomerulosclerosis, pyelonephritis – Renal ischemia, renal failure • Eyes – Retinal microaneurysm, hemorrhage – Cataract • Nervous system – Peripheral neuropathy (sensory and motor deficits) • Immune system – Prone to infection (immunocompromised) Atherosclerosis http://upload.wikimedia.org/wikipedia/commons/thumb/f/f1/Atherosclerosis,_aorta,_gross_pathology_ PHIL_846_lores.jpg/230px‐Atherosclerosis,_aorta,_gross_pathology_PHIL_846_lores.jpg 22 4/1/2014 DM Foot gangrene Diabetic nephropathy http://1.bp.blogspot.com/_8HtJsALJ3Q4/TNK37lr9wLI/AAAAAAAAADc/TvtyKgaDodo /s1600/Diabetic+Nephropathy+photo.JPG 23 4/1/2014 http://whatisdiabetesmellitus.org/wp‐ content/uploads/2011/11/Diabetic_Retinopathy_Symptoms.jpg Adrenal Gland • Attached to the upper pole of each kidney • Adrenal cortex • Adrenal medulla http://www.georgiahealth.edu/medicine/phy/raineylab/images/webfigure1.jpg 24 4/1/2014 Diseases of the Adrenal Cortex • • • • Adrenal Gland Adrenal Cortex Adrenocortical Hyperfunction Adrenocortical Hypofunction Adrenal Cortex • • • • Consists of 3 zones Zona glomerulosa – mineralocorticoids (e.g. aldosterone) Zona fasciculata – glucocorticoids (e.g. cortisone) Zona reticularis – sex steroids (e.g. estrogens and androgens) 25 4/1/2014 http://humanphysiology2011.wikispaces.com/file/view/structure_of_adrenal_gland s.jpg/198568168/structure_of_adrenal_glands.jpg Adrenocortical Hyperfunction • Hyperaldosteronism (Conn’s syndrome) – Hypersecretion of mineralocorticoids (aldosterone) • Hypercorticolism (Cushing’s syndrome) – Hypersecretion of glucocorticoids (cortisol) – Most common of these three syndromes • Adrenogenital syndrome – Hypersecretion of adrenal sex steroids (androgens) 26 4/1/2014 Cushing’s syndrome • Excessive production of cortisol caused by – Adrenocortical tumors : adenoma, carcinoma – Exogenous corticosteroids • Cushing’s disease : hypercortisolism caused by hypersecretion of the ACTH either from – pituitary adenoma or – small‐cell lung cancer (paraneoplastic) • Clinical features : Central obesity, moon face, buffalo hump, hypertension, thinning of the skin and striae 27 4/1/2014 Adrenocortical Adenoma 28 4/1/2014 Adrenocortical Hypofunction • Adrenal insufficiency or Addison’s disease • Caused by autoimmune adrenalitis, infection (tuberculosis, histoplasmosis), metastatic tumors (breast, lung) • Clinical features: fatigue, weight loss, hypotension, syncope, cannot tolerate stress, metabolic disturbance, personality change 29 4/1/2014 Disease of the Adrenal Medulla • Adrenal Medulla – Epinephrine, Norepinephrine in ANS • Neuroblastoma – malignant tumor in children • Pheochromocytoma – benign tumor causing secondary hypertension in the young 30 4/1/2014 References • Damjanov I., “Pathology for the Health Professions, 4th edition.”, Elsevier Saunders, Missouri, 2012, page 377 – 393. 31