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

Germinoma

2) pituitary lesions:

Nonsecretory adenomas

Sheehan’s syndrome

Empty sella syndrome

Clinically – 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 (papillary, folicular, anaplastic, medullary)

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 psychosis

Pseudohypoparathyroidism

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