bez titulu

1
ENDOCRINE SYSTEM
Do not write !!!!!! Everything is available _at_
http//www.lfhk.cuni.cz/patanat/endocrine
2
ENDOCRINE SYSTEM
secretion of hormones (steroids,
peptides) feedback inhibition
blood regulation of
activity of various organs
3
PITUITARY GLAND 0.5 g sella turcica
(sphenoidal bone) diaphragma sellae (dura
mater) stalk - neural and vascular connection
with hypothalamus adeno- neuro- (so called
neurohemal organ)
4
Adenohyphysis ventral lobe
embryologically derived from mouth cavity
(Rathke's cleft)
5 hormones ACTH TSH FSHLH prolactin GH
eosinophils (A cells) basophils (B
cells) chromophobes
5
Hyperpituitarism and adenomas of
pituitary prolactinoma 30 from A and
chromophobes FSH LH 15 from B ACTH
15 from A and chromophobes GH
5 TSH 1
6
Pituitary adenomas
majority of adenomas produce only 1 hormone up to
30 adenomas non-functional only local pressure
effect balloon expansion of sella
usuration rupture of diaphragm suprasellar
growth pressure to chiasma n. opticus,
impression of brain paranasal sinuses
disturbances of vision, headache X-ray
changes carcinoma very rare
7
Hormonal syndromes prolactin
oligo-, amenorrhea,
galaktorrhea, impotence GH
gigantism up to 240 cm
acromegaly, macroglossy ACTH
Cushing's d. obesity,
moon-face, hirsutism,
hypertension etc. (see adrenal)
8
Hypopituitarism
loss of at least 75 of parenchyma due to 1.
nonfunctional adenoma (pressure atrophy) 2.
ischemic necrosis (Sheehan's sy post-partum
necrosis of enlarged hypophysis by bleeding
or haemorr. shock lactation arrest, no
restoration of menstrual cycle) 3. empty sella sy
following inflammation, operation,
irradiation herniation of arachnoid CSF
into the sella
9
Hypopituitarism - clinical symptoms
pituitary nanism decrease
of GH substitution hypogonadism
(Fröhlich's sy dystrophia
adiposogenitalis) accomp. by mental retardation
namely in males hypothyroidism disorders
of adrenal cortex
10
Posterior lobe syndrome the cause is
usually in hypothalamus, very rare decreased ADH
diabetes insipidus (polyuria, polydypsia
, dehydratation)
11
Craniopharyngioma benign tumor
from canalis craniopharyngicus remnants
(residual structure from Rathke's cleft source
of adenohypophysis) suprasellar expansion
often cystic, similar structure as adamantinoma
of the jaws
12
THYROID GLAND regulated by
adenohypophysis (TSH) and blood levels of
iodine thyroglobulin in follicular colloid
transformation to thyroxine (T4) a
triiodothyronine (T3) parafollicular C cells
calcitonin facilitates binding of Ca2 to
bones and inhibits bone resorption derived from
pharyngeal epithelium thyroglossal duct
persistence thyroglossal duct cyst
(median neck cyst) lingual thyroid
13

• Thyroid gland - pathology
• more frequent in females (MF 110!)
• namely enlargement - goiter
• increased secretion - hyperthyroidism,
• thyreotoxicosis
• decreased secretion - hypothyroidism
• hyperplasia, inflammations, tumors

14

• Hyperthyroidism
• diffuse hyperplasia of TG (M. Graves-Basedow)
• toxic nodular goiter
• toxic adenoma
• thyroiditis
• pituitary adenoma, hypothalamic disorders

15

• Hyperthyroidism - clinical symptoms
• increase of basal metabolism, O2 consumption
• restlessness, emotional lability
• tremor, sweating, loss of weight,
• intolerance of warmth
• SOB, increased heart rate and output,
  palpitations
• congestive heart failure due to thyrotoxic
• cardiomyopathy (dilated type)
• exophtalmus

16

• Hypothyroidism
• loss of parenchyma (resection, irradiation,
• medication)
• Hashimoto's thyroiditis
• idiopathic (autoimmune?) hypothyroidism

17
Hypothyroidism - clinical symptoms IN
CHILDHOOD - cretinism endemic iodine deficiency
in mountain regions ( addition of iodine
to salt) short stature, big tongue, defective
teeth, rough facial features IN ADULTHOOD -
myxedema accumulation of mucopolysacharides in
corium pale thick (doughlike) skin, namely
in periorbital areas bradycardia, apathy,
intolerance of cold, big lips and tongue enlarged
and failing heart with pericardial fluid coronary
arteriosclerosis due to hypercholesterolemia
18
THYROIDITIS Hashimoto's
thyroiditis ( H. goiter) most frequent
inflammation, autoimmune immune
reaction against TG - up to 20 more frequent in
females histology replacement of parenchyma by
lymphoid tissue with formation of lymph.
follicles with germinal centers follicular
cells eosinophillic, finely granular
oncocytes (Hürthle cells), goiter Dx.
clinical symptoms, autoAb., US, ( FNACytology)
risk of MALT - lymphoma !
19
Focal lymphocytic t. very frequent, in
females usually only subclinical manifestation
(increase of TSH, normal T3, T4) often
incidental morphological finding Subacute
granulomatous t. (De Quervain's) viral etiol.?
- fever, palp. tenderness, pain, transitory
hyperfunction granulomas with multinucleated
giant cells heals spontaneously, not
operated Fibrous goiter (Riedel's) firm
idiopathic fibrosis of the gland, merging into
surrounding structures, extremely rare
20

• GRAVES - BASEDOW DISEASE
• toxic goiter (pulsans, vibrans et fremens)
• most frequent cause of hyperthyroidism
  (diffuse hyperplasia)
• triad hyperthyroidism
• exophthalmia (in 2/3) - edema of retrobulbar
• connective tissue
• ("malignant" e. not possible to close eyelids
  corneal
• ulcers - blindness)
• pretibial edema - (in 1/6) - mucin,
  lymphocytes
• up to 7 more frequent in females
• autoimmune mechanism (thyroid stimulating Ab.,
• thyroid growth stimulating Ab.) against
  TSH-receptors

21
GB goiter - histology "too much
epithelium, too few colloid" epithelial cells
tall, colloid pale, "watery", vacuolated (marginal
usurations), stromal lymphoid infiltrates rich
vascularization
22
GOITER this term doesn't say
neither anything about etiology nor about the
character of the process most often of
hyperplastic origin first diffuse, later on
nodular often accompanied by regressive changes
23
Endemic goiter by iodine deficiency decreased
synthesis of hormone compensatory increase of
TSH enlargement (hyperplasia) of the
gland Sporadic goiter multifactorial, i.e.
iodine and goitrogenes in diet cabbage,
cauliflower, turnip, kale females, frequently
onset in puberty or pregnancy
24
Nodular colloidal goiter weight 300g up to
1kg, sometimes retrosternal growth histologically
- nodules, sometimes with bleeding and/or
calcifications micro- normo- a macrofollicular
(majority) - large follicles with colloid
(colloidal goiter) eufunctional g., toxic g.,
hypofunctional g. cytology of cold nodes (diff.
from carcinoma) (suspicious goiters and g. with
clin. symptoms are operated)
25
TUMORS 80 of solitary nodules
are adenomas benign, mainly solitary, spheric,
encapsulated follicular adenoma normofollicular,
macrofollicular (colloidal), microfollicular
(fetal), trabecular (embryonic) nonfunctional a.
(scintigrafic) - cold nodule functional a. hot
nodule ( toxic) oncocytic adenoma large
eosinophillic cells
26

• CARCINOMAS
• not frequent, up to 3 more often in females
• post-irradiation- Hiroshima 7 survivors,
  Tschernobyl,
• therapeutic irradiation (lymphomas in
• childhood)
• from follicular cells
• well differentiated - papillary, follicular,
  oncocytic
• poorly differentiated - insular
• undifferentiated - anaplastic
• from C cells
• medullary

27
Papillary carcinoma approx. 70 of all
carcinomas diagnostic feature is not presence
of papillae, but so called ground glass
nuclei" sometimes only minute (mm) -
microcarcinoma invasion into capsule, fibrosis
psammoma bodies (concentric calcifications)
meta to LN, good prognosis - 80 10y. survival
28
Follicular carcinoma about 20 of
malignancies difficult diff. dg. vs. adenoma -
invasion through the capsule and/or vascular
invasion! meta to bones, lungs, brain
Anaplastic carcinoma 10 of malignancies,
highly agressive histologically small cell,
large cell, spindle cell type death within 2
years Medullary carcinoma from C cells
(calcitonin!), sometimes familial occurrence
solid foci of small cells, production of amyloid
(APUD amyloid")
29
PARATHYROID GLANDS derived from 3rd and
4th branchial pouches (together w. thymus) !
ectopy frequent supernumerary gland production
of parathormone (PTH) releases Ca2 from
bones increases Ca2 level in
serum Hyperparathyroidism primary - cause
within the gland secondary - causes outside the
gland (e.g. kidneys) hypercalcaemia
30

• Primary hyperparathyroidism
• adenoma or hyperplasia
• carcinoma (extremely rare)
• adenoma mostly solitary, up to 2 cm,
  encapsulated,
• embedded within thyroid, thymus, soft tissue of
  the neck
• histologically chief cells or oxyphillic cells
  (oncocytes)
• treatment surgery (rarely alcohol injection)
• hyperplasia (all 4 glands) CAVE MEN!
• clinically metastatic calcification, urolithiasis
• osteomalacia, ostitis fibrosa cystica (brown
  tumor of bones)

31
Secondary hyperparathyroidism compensatory
hyperfunction most frequent in chronic renal
insuf. (hyperphosphataemia, hypocalcaemia)
hypovitaminosis D (reduced supply of Ca2
increase of PTH hyperplasia of
parathyr. g. - reversible paraneoplastic
sy Hypoparathyroidism complication of surgery
(thyroidectomy) hypocalcaemia neuromuscular
cramps (tetany)
32
ADRENAL GLANDS 2 organs in 1 cortex vs.
medulla different embryogenesis different
structure function
33
ADRENAL CORTEX spongiocytes producing
steroid hormones glucocorticoids,
mineralocorticoids, sex steroids hyperfunction,
hypofunction, tumors Hyperfunction
(hypercorticism) steroids glucocorticoids
(mainly cortisol)
Cushing's sy mineralocorticoids (mainly
aldosterone)
hyperaldosteronism (Conn's sy) androgens
virilism (adrenogenital sy)
34

• Cushing's sy - clinical symptoms
• obesity (so called arachnoid type)
• moon-face, neck hump, striae
• hypertension, muscle weakness
• osteoporosis, hirsutism and amenorrhea
• impaired metabolism of glucose (steroid
  diabetes)
• psychotic disorders

35

• Cushing's sy - causes
• pituitary adenoma increase of ACTH
• hyperplasia of the cortex
• functioning cortical adenoma
• paraneoplastic sy - (in 10-15) increased ACTH
  
• produced by tumor cells (most often small cell
  lung cancer)
• hyperplasia of the cortex
• iatrogenic Cushing's sy caused by treatment
• (glucocorticoids - immunosupression
  atrophy of
• the cortex)

36
Cushing's sy - morphology cortical
adenoma - high level of cortisol causes
hyaline degeneration of B cells in
hypophysis Crooke's cells - atrophy
of the cortex pituitary adenoma -
hyperplasia of adrenal cortex - diffuse or
nodular - bilateral
37
Hyperaldosteronism mineralocorticoid
aldosterone regulation through renin-angiotensin
system increased excretion of K and retention
of Na hypokalemia, hypernatremia
increased volume of extracellular fluid, blood
hypertension muscle weakness (including
myocardium) primary aldosteronism in cortical
adenoma - Conn's sy
38
Adrenogenital sy adenoma, hyperplasia
or carcinoma of the cortex in young females
masculinisation in young males pubertas praecox
39
Hypofunction primary
insufficiency due to damage of cortex
(Addison's disease) secondary
insufficiency due to pituitary lesion
( decrease of ACTH)
40
Addison's disease decrease of
gluco-, mineralocorticoids and androgens damage
of at least 90 of parenchyma (bilaterally) in
the past majority of cases - TBC
epinephritis today usually idiopathic -
autoimmune?, amyloidosis, meta, sudden
termination of steroid treatment (cortex is
atrophic!)
41

• Addison's disease
• Morphology
• leaf-like adrenals (very thin cortex)
• Clinical symptoms
• weakness, fatigue, skin and mucosa pigmentation -
  melanin
• hypoglycemia, hypotension
• diarrhea, loss of weight
• stress may lead to acute crisis with coma (acute
• cortical insufficiency)
• massive bleeding into cortex (labor trauma,
  venous
• thrombosis, meningoc. sepsis w. DIC
• Waterhause-Friderichsen sy)

42

• Tumors
• adenoma majority non-functional, 1-2 cm
• incidental finding in US, CT or at autopsy
• histology zona fasciculata
• carcinoma very rare, usually non-functional
• myelolipoma - benign mesenchymal tumor
• histology similar to bone marrow

43

• ADRENAL MEDULLA
• chromaffine cells producing epinephrine
  (adrenalin)
• and norepinephrine (noradrenalin)
• pathology of medulla virtually only 2 neoplasms
• Pheochromocytoma
• Neuroblastoma

44
Pheochromocytoma production of
adrenalin a noradrenalin 90 from medulla, 10
from sympatic ganglia (paraganglioma) tumor of
3 10" 10 bilateral 10
extraadrenal 10 malignant grams to
kg! histology polygonal cells, EM a
immunocytoch. neuroendocrine
granules clinically permanent or paroxysmal
hypertension (tachycardia, sweating, headache)
45
Neuroblastoma highly
malignant tumor of children aged 5 - 15
years from adrenal medulla and sympat. ganglia
(cervical, thoracic and abdominal) related to
retinoblastoma frequent necroses, bleeding and
intratumoral calcifications (X-ray!), sometimes
production of catecholamins histology small
cells, Homer-Wright rosettes metastases to bones
and liver according to degree of
differentiation neuroblastoma
ganglioneuroblastoma
ganglioneuroma
46
LANGERHANS ISLETS part of APUD
system A-cells (glucagon - hyperglycemia) B-
cells (insulin) D- cells (somatostatin -
inhibits both above mentioned) PP- cells
(pancr. polypeptide - activates secretion of
various GI enzymes) gastrin where???
47
DIABETES MELLITUS !! 5 of population in Czech
Republic !! chronic defect of carbohydrates
metabolism affects also metabolism of lipids and
proteins insufficient production of insulin by
B-cells hyperglycemia glycosuria,
polyuria (osmotic) causes idiopathic (genetic)
secondary (destruction of L.i. by
inflammation, surgery, tumor,
hemochromatosis)
48
Idiopathic DM type I
insulin-dependent, juvenile 10 type II
insulin-non-dependent, adult 90 genetic
disposition obesity (80 DM-II pts. are obese,
60 of obese pts. have disorders of
metabolism of carbohydrates) pregnancy, stress,
viral infections 7th most frequent cause of
death increasing tendency!
49
Pathogenesis of DM insulin
regulates utilisation of glucosis in cells
synthesis of glycogen (liver and muscles)
synthesis of triglycerides from glucose
synthesis of proteins lack of insulin
hyperglycemia glycosuria ketosis acidosis
intoxication by ketones diabetic coma DM
I - insulin is missing B cells destroyed by
autoimmunity, viral infection, ??? survival -
exogenous insulin (insulin-dependent DM) DM II
mildly impaired secretion resistance of
peripheral cells to insulin
50

• Morphology
• Pancreas changes of L. islets
• often none
• sometimes reduction of size and/or number
• sometimes increase of size and/or number
• - babies of diabetic mothers
• less frequently APUD amyloid in L.i.
• degranulation of B cells (EM)
• lymphocytic infiltration of L.i. (insulitis")

51

• Vessels
• from capillary vessels to aorta
• after 10-15 years since onset of DM are vascular
  lesions prominent!
• diabetic microangiopathy
• thickening of BM and narrowing of capillaries
• skin, retina, nerves, muscles, glomerules
• arteriolosclerosis
• hyaline change in arterioles, identical with
  hypertonic
• sometimes combination
• arteriosclerosis
• most prominent in large arteries
• MI (most freq. cause of d. in diabetics)
  silent !
• diabetic gangrene of lower extr. (10
  amputations)

52

• Kidneys
• 2nd most freq. cause of death in diabetics is
  renal failure
• Diabetic nephropathy
• four lesion - glomerular, vascular, tubular,
  pyelonephritic
• glomerulosclerosis
• diffuse or nodular (Kimmelstiel - Wilson)
• thickened BM and hyalinization within glomeruli
• arterio- and arteriolosclerosis
  necrosis of papillae
• nephrosclerosis (arteriosclerotic,
  arteriolosclerotic)
• storage of glycogen in tubular cells (Armani
  cells)
• and steatosis
• pyelonephritis more frequent than in
  non-diabetics

53
Eyes diabetic retinopathy diagnostic of DM
(ophthalmoscopy) based on vascular changes
exudation, edema, bleeding, microaneurysms,
fibrosis cataract of lens (turbidity) glaucoma
(even blindness) changes in retina
correlate with changes in kidneys non-invasive
monitoring!
54
Nerves diabetic neuropathy lower
extremities vascular changes damage of both
motoric and sensoric functions Other liver
steatosis, glycogen nuclei" necrobiosis
lipoidica of the skin immunosupression
infections
55

• Clinical symptoms - "3 poly"
• polyuria (excessive urination)
• polydypsia (excessive thirst)
• polyfagia (excessive appetite)
• laboratory - hyperglycemia, glycosuria
• type I symptoms since onset (usually childhood)
• type II symptoms at circa 40's
• average age of diabetics for 7 - 9 y. shorter,
  namely in type I

56
Syndrome of multiple endocrine neoplasia (MEN)
(polyendocrine sy, polyadenomatosis) familial
- autosomaly dominant inheritance hyperplasia,
adenoma or carcinoma MEN I (Wermer's sy)
pituitary, parathyroid, L.i. (hypercalcaemia,
hypoglycemia, hypergastrinemia) persisting
gastric peptic ulcer (Zollinger - Ellison's
sy) MEN II (MEN IIa Sipple's sy)
medullary ca of thyroid, pheochromocytoma MEN
III (MEN IIb) MEN II skin mucosal neuromas