Pathology of the Endocrine System Zhang Wenyan Department of Pathology Sichuan University 2003

Endocrine System Endocrine glands （ pituitary, thyroid, parathyroid, adrenal gland, pineal body, and islet ） Dispersed neuroendocrine cells （ thyroid C cells, gastrointestinal and bronchopulmary neuroendocrine cells ）

Purpose of Endocrine System To maintain a state of homeostasis among the various organs of the body Endocrine cells secrete hormones to regulate the activity of target organs

T 3, T 4 TRH TSH

Abnormal activity of Endocrine System Impaired synthesis or release of hormones Abnormal interactions between hormones and their target tissues Abnormal responses of target organs to their hormones

hyperplasia neoplasm inflammation disturbance of blood supply genitics factors over-/underproduction of hormones biochemical consequences hyperplasia, hypertrophy or atrophy of target organs/tissue clinic consequences

A proper understanding of endocrine diseases requires a careful integration of morphologic findings with biochemical measurements of the levels of hormones, their regulators, and other metabolites.

contents Pituitary Adenomas Diseases of Thyroid Diseases of Adrenal Gland Diabetes Mellitus

Posterior pituitary Antidiuretic hormone, ADH Oxytocin, OT

Anterior pituitary Acidophile cell Growth hormone, GH Prolactin, PRL Basophile cell Thyroid stimulating hormone, TSH Follicle stimulating hormone, FSH Luteinizing hormone, LH Adrenocoticotrophin hormone, ACTH Lipotrophic hormone, LPH Chromophobe cell

Pituitary 1.5×0.9×0.6cm 0.5~0.9g

Anterior pituitary

Prolactin, PRL

Pituitary Adenoma Benign neoplasm arising from anterior pituitary cells 25% of all intracranial tumors 20% of the general population Their prevalence increases with advancing age Both sexes are equally affected They are usually invasive in children

Pituitary adenoma

Microadenoma diameter ＜ 1cm 5%~10% of the adults rare functional

Clinical Features Hyperpituitarism Hypopituitarism Local mass effects

Gigantism Growth hormone adenoma occurs before puberty Generalized increase in body size

Acromegaly Growth hormone adenoma occurs after puberty Protruding jaw Broaden lower face Enlarged hands

acromegaly

Pituitary Adenomas Diseases of Thyroid Diseases of Adrenal Gland Diabetes Mellitus

normal thyroid gland

Diseases of Thyroid hyperthyroidism hypothyroidism goiter thyroiditis neoplasms of thyroid

Hyperthyroidism Excessive secretion of thyroid hormones A consequence of an increase in body’s metabolism

Clinical Features of Hyperthyroidism feeling hot increased sweating weight loss, with proximal muscle weakness rapid heart rate, palpitations atrial fibrillation (occasionally) diarrhoea anxiety and restless hyperactivity

Diseases of Thyroid hyperthyroidism hypothyroidism goiter thyroiditis neoplasms of thyroid

Hypothyroidism Decreased production of thyroid hormone Hypothyroidism present at birth: cretinism Hypothyroidism present in adults: myxoedema

cretinism mental retardation short stature coarse facial features protruding tongue umbilical hernia

myxoedema

Diseases of Thyroid hyperthyroidism hypothyroidism goiter thyroiditis neoplasms of thyroid

Goiter Simple enlargement of the thyroid diffuse toxic goiter/Grave’s disease diffuse nontoxic goiter

Diffuse Toxic Goiter/Graves Disease Excessive secretion of thyroid hormones in the bloodstream Organ-specific autoimmune disorder Occurs primarily in younger adults F ︰ M ＝ 8 ︰ 1

Graves disease

Histological changes Hyperplasia of follicular epithelium Reduction of stored colloid Local accumulation of lymphocytes

Clinical features Diffuse enlargement of the thyroid Exophthalmos (protruding eyes) Hyperthyroidism Pretibial myxedema

exophthalmic goiter

Diffuse Nontoxic Goiter / Multinodular Goiter Most common thyroid disease Most common cause for an enlarged thyroid

Pathogenesis dietary iodine deficiency impairment of thyroid hormone synthesis compensatory rise in the serum TSH level hypertrophy & hyperplasia of thyroid follicular cells gross enlargement of the thyroid gland

diffuse nontoxic goiter

multinodular goiter

Clinical features Neck mass Compression symptoms airway obstruction dysphagia compression of large vessels compression of upper thorax normal thyroid function

Diseases of Thyroid hyperthyroidism hypothyroidism goiter thyroiditis neoplasms of thyroid

Hashimoto’s thyroiditis/ chronic lymphocytic thyroiditis

anti-thyroglobulin antibody

thyroid gland (atrophy)

subacute granulomatous thyroiditis (DeQuervain's disease)

Clinical features of subacute granulomatous thyroiditis Painful enlarged thyroid Self-limited clinical course

Diseases of Thyroid hyperthyroidism hypothyroidism goiter thyroiditis neoplasms of thyroid

Neoplasms of thyroid gland Range from adenoma to carcinoma Present with thyroid nodules Carcinomas of thyroid are uncommon, accounting for under 1% of thyroid nodules

Clinical criteria to the nature of a thyroid nodule ( Ⅰ ) Solitary nodules are more likely to be neoplastic than are multiple nodules Solid nodules are more likely to be neoplastic than are cystic nodules Nodules in younger patients are more likely to be neoplastic than are those in older patients

Clinical criteria to the nature of a thyroid nodule ( Ⅱ ) Nodules in males are more likely to be neoplastic than are those in females Nodules that do not take up radioactive iodine in imaging studies ( “cold” nodules ) are more likely to be neoplastic, “hot” nodules are almost benign

follicular adenoma. Thyroid Adenoma

Thyroid Carcinoma Papillary carcinoma ( 75%~85% of cases) Follicular carcinoma ( 10%~20% of cases) Anaplastic carcinoma ( 5% of cases) Medullary carcinoma ( 5% of cases)

Papillary Carcinoma

Follicular Carcinoma F

Medullary Carcinoma Neoroendocrine neoplasm derived from parafollicular cells Secrete carcitonin, the measurement of which play an important role in the diagnosis and postoperation follow-up of patients

Medullary carcinoma

Congo red staining

anaplastic carcinoma

Pituitary Adenomas Diseases of Thyroid Diseases of Adrenal Gland Diabetes Mellitus

Hormones of the adrenal gland Cortex Medulla Mineralocorticoid Glucocorticoid Androgen / Estrogen Catecholamines (Adrenaline, Noradrenaline)

Disorders of Adrenal Gland Hypercortisolism (Cushing Syndrome) Adrenocortical Insufficiency Adrenocortical Neoplasms Pheochromocytoma

Cushing Syndrome The symptoms and signs are associated with prolonged inappropriate elevation of glucocorticoid levels.

Forms of Cushing syndrome Endogenous Cushing syndrome Exogenous Cushing syndrome

Primary hypothalamic- pituitary diseases associated with hypersecretion of ACTH Primary adrenocortical hyperplasia or neoplasia

The section of ectopic ACTH by nonendocrine neoplasms Administration of exogenous glucocorticoids

Clinic features Central obesity and moon face Plethora and acne Menstrual irregularity Hirsutism and hair thinning Hypertension Diabetes Osteoporosis Muscle wasting and weakness Atrophy of skin and dermis: paper thin skin with bruising tendency, purple stride

Cushing syndrome

NormalCushing syndrome

Disorders of Adrenal Gland Hypercortisolism (Cushing Syndrome) Adrenocortical Insufficiency Adrenocortical Neoplasms Pheochromocytoma

Primary adrenocortical insufficiency Chronic adrenocortical insufficiency (Addison disease) Acute adrenocortical insufficiency

Clinical features of Addison disease gastrointestinal disturbances hyperpigmentation hyperkalemia hyponatremia volume depletion hypotension

Waterhouse-Friderichsen syndrome Primary acute adrenal insufficiency Caused by G- (usually meningococcal) septicaemia Bilateral adrenal hemorrhage

Waterhouse-Friderichsen syndrome

Disorders of Adrenal Gland Hypercortisolism (Cushing Syndrome) Adrenocortical Insufficiency Adrenocortical Neoplasms Pheochromocytoma

Adrenocortical Neoplasms Adrenocortical adenoma Adrenocortical carcinoma

1.3 cm adrenal adenoma

adrenocortical adenoma

Adrenocortical carcinoma

Disorders of Adrenal Gland Hypercortisolism (Cushing Syndrome) Adrenocortical Insufficiency Adrenocortical Neoplasms Pheochromocytoma

Neoplasm composed of chromaffin cells, which synthesize and release catecholamines

Rule of 10s 10% of pheochromocytomas arise in association with one of several familial syndromes 10% of pheochromocytomas are extra-adrenal 10% of adrenal pheochromocytomas are bilateral 10% of adrenal pheochromocytomas are biologically malignant

Bilateral pheochromocytoma

Clinic features Hypertension an abrupt, precipitous elevation in blood pressure, associated with tachycardia, palpitation, headache, sweating, tremor,and a sense of apprehension

Pituitary Adenomas Diseases of Thyroid Diseases of Adrenal Gland Diabetes Mellitus

normal pancreatic islet

Pancreatic islet 10%~15% of the pancreatic substance Each islet contains 1000 cells beta cells alpha cells delta cells PP (pancreatic polypeptide) cells

insulin glucagon

Diabetes Mellitus, DM Definition A chronic disorder of carbohydrate, fat, and protein metabolism, which is characterized by hyperglycemia due to inadequate insulin action/production

Incidence Affects 13million people in U.S.A. Annual mortality rate of 35,000 The seventh leading cause of death in U.S.A.

Classification Type 1 diabetes (insulin-dependent DM, IDDM) immune mediated (type 1A) idiopathic Type 2 diabetes (non-insulin-dependent DM, NIDDM) Other specific types of diabetes Gestational diabetes mellitus

Type 1 Type 2 childhood/adolescent middle-aged/elderly 1/3 2/3 F=M F>M(by4:1) acute/subacute gradual thin obese ketoacidosis common ketoacidosis rare plasma insulin absent/low normal/raised insulin sensitive insulin insensitive autoimmune mechanism non-autoimmune genetic predisposition polygenic inheritance associated with HLA-DR

Diagnosis Diagnosis Venous whole blood glucose fasting sample 2hs after 75g glucose load Normal ＜ 5.6mmol/l ＜ 6.7mmol/l Impaired ＜ 6.7mmol/l 6.7~10mmol/l glucose tolerance Diabetic mellitus ＞ 6.7mmol/l ＞ 10mmol/l

Morphology & Late Complication Pancreas Vascular system Diabetic microangiopathy Diabetic nephropathy Diabetic ocular complications Diabetic neuropathy

Insulitis (type 1 diabetes mellitus)

Amyloidosis (type 2 diabetes mellitus)

Morphology & Late Complication Pancreas Vascular system Diabetic microangiopathy Diabetic nephropathy Diabetic ocular complications Diabetic neuropathy

Late Complication of Vascular System Accelerated severe atherosclerosis in aorta, large- and medium-sized arteries Myocardial infarction Gangrene of the lower extremities Hyaline arteriolosclerosis

in afferent arteriole of the kidney

Morphology & Late Complication Pancreas Vascular system Diabetic microangiopathy Diabetic nephropathy Diabetic ocular complications Diabetic neuropathy

Morphology & Late Complication Pancreas Vascular system Diabetic microangiopathy Diabetic nephropathy Diabetic ocular complications Diabetic neuropathy

Diabetic nephropathy Glomerular lesions thickening of glomerular capillary basement membranes diffuse glomerulosclerosis nodular glomerulosclerosis Renal vascular lesions arteriolosclerosis Pyelonephritis

diffuse glomerulosclerosis

nodular glomerulosclerosis

nephrosclerosis

Morphology & Late Complication Pancreas Vascular system Diabetic microangiopathy Diabetic nephropathy Diabetic ocular complications Diabetic neuropathy

Morphology & Late Complication Pancreas Vascular system Diabetic microangiopathy Diabetic nephropathy Diabetic ocular complications Diabetic neuropathy