The endocrine system

Pituitary gland

Anterior lobe Posterior lobe Endocrine abnormalities Local mass effect

Hyperpituarism

Caused by adenomas: Growth hormone Adrenocorticotropic hormone Prolactin Rare – thyroid stimulating hormone, gonadortropin 25% adenomas – non-functional (causes HYPOpituarism

by compression) Microadenomas, macroadenomas (10mm) Nuclear atypia is NOT sign of malignancy Ultrastructurally – secretory granules

Somatotropic adenomas

Acromegaly – in adults Gigantism – prior to closure of epiphyses Granulated, eosinophilic cells – eosinophilic adenoma

Prolactinomas

Hypogonadism Galactorrhea Granulated acidophilic or chromophobic cells –

chromophobic adenoma

Corticotroph tumors

Cushing’s syndrome Basophilic cells – basophilic adenoma

Hypopituarism

Caused by 1) hypothalamic lesions: Craniopharyngioma Glioma Germinoma2) pituitary lesions: Nonsecretory adenomas Sheehan’s syndrome Empty sella syndromeClinically – variable Hypogonadotropism Hypothyroidism, etc.

Hypothalamic lesions – craniopharyngioma

Benign cystic tumor Calcifications Squamous epithelial cells and reticular stroma

Nonsecretory chromophobe pituitary adenoma

Mass effect (visual problems, headache) Chromophobic or oncocytic forms exists

Sheehan’s syndrome

Associated with obstetric haemorrhage or shock Caused by infarction of anterior pituitary Gonadal failure – inability to lactate ACTH, TSH deficiency Healing of necrosis – fibrous tissue

Posterior pituitary syndrome

Excess or deficiency of antidiuretic hormone – ADH Caused by suprasellar/hypothalamic lesions

Posterior pituitary syndrome

Excess of ADH Abnormal resorption of water, hyponatremia and inability

to excrete diluted urine

Caused by ectopic ADH secretion: Non-endocrine neoplasms (small cell carcinoma of the

lung) Non-neoplastic pulmonary diseases (TBC,

pneumonia) Primary CNS lesions (infarcts, meningitis,

haemorrhage)

Posterior pituitary syndrome

ADH deficiency (Diabetes insipidus)

Inability to concentrate urine: Polyuria Polydipsia Hypernatremia

Thyroid gland

Hyperthyroidism Hypothyroidism Goitre – focal, diffuse

Hyperthyroidism (thyrotoxicosis)

Increased levels of triodothyronine (T3), thyroxine (T4) Clinically: wide-eyed gaze, tachycardia, palpitations,

nervouseness, weight loss (increased appetite), moist hand, tremor, peripheral vasodilatation

Associated with diffuse hyperplasia (Graves’ disease) or with toxic multinodular goitre or toxic adenoma

May be associated with struma ovarii (teratoma)!!

Graves’ disease

Autoimmune process Presence of thyroid stimulating antibody (TSAb) and

thyrotropin binding inhibitor immunoglobulin (TBII) Associated with other autoimmune diseases Presence of hyperplasia of foIlicular epithelium ,

depletion of colloid and lymphoid aggregates

Hypothyroidism

Cretinism (during infancy) Endemic form Sporadic form Physical an mental retardation

Myxoedema (in adults)

Slowing of physical and mental activity, fatigue and apathy

Signs - periorbital oedema, coarsening of skin,

cardiomegaly, accumulation of mucopolysaccharides in

dermis

Various causes - idiopathic primary, inflammation –

Hashimoto thyroiditis, etc.

Thyroiditis

Hashimoto’s thyroiditis De Quervain’s thyroiditis Riedel’s fibrosing thyroiditis Lymphocytic thyroiditis Infectious thyroiditis

Hashimoto’s thyroiditis

Autoimmune disorder Female predominance Defect in suppressor T cells, production of

autoantibodies Associated with other autoimmune disease (SLE,

Sjögren sy, rheumatoid arthritis…) Microscopically – dense lymphocytic infiltrate,

germinal centers, abundant eosinophilic oncocytes (Hürtle cells)

De Quervain’s subacute granulomatous thyroiditis

Also known as giant cell thyroiditis Probably viral etiology Destruction of follicles, neutrophil infiltrate,

multinucleate giant cells Recovery in 6-8 weeks

Subacute lymphocytic thyroiditis

Nonspecific lymphoid infiltration Without germinal centre In women in postpartum period

Riedel’s fibrosing thyroiditis

Thyroid replaced by fibrous tissue Fibrous tissue extends and penetrate into the

surrounding neck structures May be mistaken for infiltrating neoplasm

Tumors

Benign – adenomas Well demarcated Fibrosis Haemorrhage Calcifications Hürtle cell adenoma - oncocytic Usually „cold“Malignant - carcinomas See transparency

Parathyroid gland

Primary hyperparathyroidism Hypersecretion of parathormone Caused by adenoma (80%), hyperplasia (15%),

carcinoma (5%) Bone resorption, hypercalcemia – osteoporosis,

muscle weaknes, nephrolithiasis, ulcers, pancreatitis, headache, depression

Secondary hyperparathyroidism In patients with renal failure Compensatory hypersecretion of parathormone (reaction

to phosphate retention and hypocalcemia)

Parathyroid gland - tumors

Adenoma Solitary, encapsulated – compression of adjacent gland No stromal fat Composed predominatly of chief cells Part of MEN I, MEN II

Carcinoma Rare Invasion, metastases

Hyperplasia All glands Fat cells interspersed

Hypoparathyroidism, pseudohypoparathyroidism

Hypoparathyroidism Multiple etiology (surgical removal, autoimunne

destruction, congenital…) Tetany, neuromuscular excitability, paraesthesiae

psychosisPseudohypoparathyroidism Rare Abnormality PTH receptors, loss of responsiveness,

hypocalcemia Compensatory parathyroid hyperfunction

Adrenal cortex - hyperfunction

Three syndromes: Cushing’s syndrome Hyperaldosteronism Adrenogenital syndromes

Cushing’s syndrome

Causes: Administration of exogenous glucocorticoids – most

common Pituitary hypersecretion of ACTH (Cushing’s disease) –

adenoma Ectopic ACTH secretion – small cell carcinoma !!

Histology: Crooke’s hyaline changes within pituitary basophils

Clinically: Central obesity, moon facies, fatigability, hirsutism,

hypertension, osteoporosis, cutaneous striae

Hyperaldosteronism

Conn’s syndrome: Adenoma/hyperplasia Excessive production of aldosterone – low plasma renin,

sodium retention, hypertension, loss of potassium, muscular weakness, cardiac arrhytmias, metabolic alkalosis, tetany

Secondary: Reduced glomerular perfusion (fail in blood volume) –

activation of renin angiotensin system – stimulation of aldosterone secretion

Most common

Adrenogenital syndromes

Variable manifestation (virilization, pubertax praecox, hermaphroditism, pseudohermaphroditism)

Autosomal recessive trait Most often – deficiency of 21-hydroxylase - virilization

Hypofunction of adrenal cortex

Adrenal crisis Addison’s disease Secondary insufficiency

Primary acute adrenocortical insufficiency

Rapid withdrawal of steroids Massive destruction of steroids – Waterhouse-

Friderichsen syndrome:• During septic meningococcal infection• Massive hemorrhage• Hypotension• Shock• DIC

Addison’s disease (chronic adrenocortical insufficiency)

Autoimunne Infection (TBC, fungi, etc.) Metastatic cancer (lung, stomach, etc.) Clinically:• Anorexia• Weakness• Cutaneous hyperpigmentation• ACTH elevation (in primary insufficiency)

Secondary insufficiency decreased production of ACTH, absence of

hyperpigmentation, normal aldosterone levels

Adrenal medulla

Phaeochromocytoma Catecholamine production – hypertension 85% in medulla (extra-adrenal tumors designated

paragangliomas) Sporadic (90%) or associated with familial syndromes

(MEN, von Hippel-Lindau, von Recklinghausen) Histologically – pleomorphism, mitotic activity - however

there are no reliable histological predictors of malignancy!! Only criterion of malignancy – metastasis

Other tumors – neuroblastoma, ganglioneuroma

Multiple Endocrine Neoplasia MEN

MEN I (Wermer’s syndrome) Parathyroid (hyperplasia, adenoma) Pancreas (islet cell tumors) Pituitary (adenoma)

MEN II (Sipple’s syndrome) Medullary thyroid carcinoma Phaeochromocytoma Parathyroid adenoma/hyperplasia

MEN III MEN II and neuroma/ganglioneuroma

All MENs – autosomal dominant trait