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