Pathology of the Endocrine System

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Pathology of the Endocrine System นายแพทย ดร.ณตพล ศ ภณ ฐเศรษฐก ล ภาคว ชาพยาธ ว ทยา คณะแพทยศาสตร มหาว ทยาล ยนเรศวร 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

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 (ต างจาก 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

Pituitary Diseases Pituitary Gland Pituitary hyperfunction Pituitary adenomas Pituitary hypofunction Pituitary insufficiency 3

Located intracranially at sella turcica at base of the cranium Anterior pituitary Posterior pituitary Connected to the hypothalamus via a stalk Pituitary Gland 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

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

Pituitary Adenoma Acromegaly 6

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

Thyroid gland Hyperthyroidism Hypothyroidism Thyroid Neoplasms Thyroid Diseases 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

Hypofunction & Hyperfunction 9

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

Dwarfism http://healthtalk.info/wp content/uploads/fig 2 cretinism.jpg http://howshealth.com/wp content/uploads/2010/11/cretinism.jpg Clinical Features Myxedema Graves dis. http://healthtalk.info/wp content/uploads/fig 3 myxedema thyroid hormone deficiencyhypothyroidism.jpg http://www.checkbook.org/sitemap/health/gr aves_disease/..%5cgraphics%5cgraves_eyes.j pg 12

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

Follicular Adenoma 1 Follicular Adenoma Fibrous capsule Follicular cells 2 14

Papillary carcinoma of thyroid 1 Papillary carcinoma of thyroid 2 15

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 to elevate calcium concentration in blood 16

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

Parathyroid Hyperplasia & Neoplasia 18

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

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

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 Osmotic diuresis Polyuria Polydipsia Polyphagia Muscle wasting and weight loss Increase lipolysis ketone body formation 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

DM Foot gangrene Diabetic nephropathy http://1.bp.blogspot.com/_8htjsalj3q4/tnk37lr9wli/aaaaaaaaadc/tvtykgadodo /s1600/diabetic+nephropathy+photo.jpg 23

http://whatisdiabetesmellitus.org/wpcontent/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

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

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

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

Adrenocortical Adenoma 28

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

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

References Damjanov I., Pathology for the Health Professions, 4 th edition., Elsevier Saunders, Missouri, 2012, page 377 393. 31