pathology of the endocrine organs - i pituitary jaroslava dušková inst. pathol. 1st med. fac....
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Pathology of the Endocrine Organs - I
Pituitary
Jaroslava Dušková
Inst. Pathol. 1st Med. Fac. Charles Univ. Prague http://www1.lf1.cuni.cz/~jdusk/
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Pituitary - history - I
Galenos (2nd cent.)
lat. pituita = gr. phlegm = moisture, mucus
A. Vesalius (16th cent.)
glandula pituitam cerebri excepiens
R. Lower (17th cent.)
Dissertatio de origine catarrhi – incretion
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Pituitary - history - II
H. Rathke (1838)
Über die Entstehung der glandula pituitaria Arch Anat. Physiol. u. Wiss. Med. , 5, 482-5
W. Haberfeld (1909) Die Rachendachhypophyse, andere Hypophysengangreste und deren Bedeutung für die Pathologie Beiträge zur path. Anat. u. allg. Pathol. , 46, 133-
232
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1. formation of the Rathke´s pouch & proc. infundibularis
2. splitting of the Rathke´s pouch
3. mature formation
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Neuroimmunoendocrine Regulation Messengers
Neurotransmitters
Interleukins
Hormons
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Pituitary - regulation
Higher neural centra
limbic system reticular system
hypothalamus
peripheral endocrine glands
adenohypophysis
tissues
liberins & statins
trophic hormons of the adenohypophysis
hormons of periph. glands
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Pituitary – weight
Rasmussen, ATAm.J. Anat. 1928 a 1934
Females
505 - 1002 mg
(average 660 mg)
pregnant women
560 - 1220 mg
(average 762 mg)
Males
400 - 855 mg
(average 570 mg)
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Pituitary - architecture
adenohypophysis pars infundibularis (tuberalis) pars intermedia neurohypophysis
hypophysis pharyngea (+ hidden islets of pit. cells in the os sphenoides)
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Pituitary - cell inclusions
squamous epithelium Rathke´s pouch between AH and NH
salivary glands - NH, often with
oncocytes
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Pituitary - parts - function
Adenohypophysis secretion of tropins
Pars infundibularis (tuberalis)
modulation of AH secretion
Pars intermedia Neurohypophysis secretion of neuropeptides hypophysis pharyngea possible secretion
of tropins
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Pituitary – cell populations acidophil somatotrophs, lactotrophs basophil corticotrophs, gonadotrophs,
thyreotrophs chromofobe (transitional. +
folliculostellate) oncocytes (or preoncocytes) mesenchymal pituicytes (macroglia) secretion neurons (tractus supraoptico-
et tuberohypophyseus)
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Hypophysis - cell population & hormonal production
acidophil PRL , STH basophil ACTH, FSH, LH, TSH chromophobe 0, PRL , STH , ACTH, FSH, LH, TSH
oncocytes 0, PRL , STH , ACTH, FSH, LH, TSH
mesenchymal pituicytes secretion neurons oxytocin, vasopresin
acidophil PRL , STH basophil ACTH, FSH, LH, TSH chromophobe 0, PRL , STH , ACTH, FSH, LH, TSH
oncocytes 0, PRL , STH , ACTH, FSH, LH, TSH
mesenchymal pituicytes secretion neurons oxytocin, vasopresin
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Pituitary - cell population & hormonal production
Hormonal production mostly mixed
(e.g. ACTH+FSH,LH,TSH,PRL)
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Pituitary - cell population &hormonal production
Individual producents
able of interconversion
following stimulation
(e.g. PRL-GH)
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L e p t i n 7th chromosome
adipocytes - blood - CSF - hypothalamus (ncl. arcuatus )
regulation of energetic homeostasis correlation with the body fat content in most obese individuals high levels -
resistence?Friedman et al., Nature 1994
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Pituitary - regressive changes
Dystrophy (Crooke´s hyaline change) Atrophy - in aging increased fibrosis, no
functional influence
NECROSIS – traumatic
(mostly due to the stalk lesion)– ischemic
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Pituitary - vascularisation
a. hypophysea sup. (from ACI)– a. trabecularis directly to AH– long portal veins in the stalk
a. hypophysea inf. (from ACI in sinus c.)– short portal veins
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Pituitary - necrosis
incidence 1- 8 % large autopt.
series pathogenesis
intracranial hypertensionischemiavasospasmusatherosclerosisthrombistalk lesion
healing scar focal regenerates possible
meaning – hypofunction only in
case of more than 3/4 of volume destruction
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Necrosis hypophysis intra partum
sy. Sheehani
• hyperplasia • shock• ischaemia• necrosis• panhypo- pituitarismus
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Pituitary - inflammation
non specific (peri)hypophysitis
purulenta
non purulenta
septicpyemic
microabscesses
lymphocytic– autoimmune
specific tbc
hematogenous dissemination
solitary tuberculoma
lues inbornacquired
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Pituitary syndromes
Hypofunctional–panhypopituitarismus–selective hypofunction
Hyperfunctional–monohormonal–combined
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Hypopituitarismus
Total >90% AH destroyed
Syndromes:
Simmonds Sheehan Falta Lorain
Partialmonohormonalcombined
Regulatory hypofunction
peripheral glands ectopic
production iatrogenous
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Petzold S, Keller A, Keller E, Meigen C, Hirsch W, Kratzsch JK, Kiess W, Pfäffle R.
A prismatic case: A 31-year old man who did not miss his pituitary. lab. panhypopituitarismus – dg. at the age of 13 MRI- empty sella growth retardation correction, cryptorchidism, hypoglycemie, He felt better without hormonal therapy, hypogenitalism, normal
professional life & mental status
Hormones (Athens). 2008 Jul-Sep;7(3):203-4.
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Pituitary Adenomas
no galactorea-amenorea acromegaly hypercortisolism chiasma opticum compression
hypopituitarism
Clin. symptomes 9%9%
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Pituitary Adenomas
1. chiasma opticum compression 432. acromegaly 233. galactorea-amenorea 74. hypopituitarism 7
Clin. symptomes in surgically treated (n=80)
54%28%
9%9%
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Pituitary Adenomas
Guanine nucleotide- binding protein (G protein) mutations - signal transduction- uncontrolled proliferation (40% GH adenomas and som ACTH have GNAS I gene mutations)
Familiar pituitary adenomas: MEN I, CDKN I B, PRKAR I A, AIP
TP 53 mutations – aggressive behaviour
pathogenesis 9%9%
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The WHO Classificationof Adenohypophysial Neoplasms .
A proposed five-tier scheme
1. endocrine activity2. imaging/ surgery3. histology4. immunohistochemistry5. ultrastructure
Kovacs, K., Scheithauer, B., Horvath Eva, Lloyd, R Cancer 1996, 78,502-10
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Pituitary Adenomas
acidophillic basophillic chromophobe mixed
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Acidophillic adenomas
somatotroph lactotroph mixed somatotroph and lactotroph somatolactotroph densely granulated
onkocytic
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Basophillic adenomas
corticotrophic thyreotrophic gonadotrophic densely granulated
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m. Cushing paraneopl. pituitary ad.
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m. Cushing periph. hypothalamic
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Sharma ST et al:
Cushing´s syndrome: epidemiology and developments in disease management.
Clinical Epidemiology, 2015, 7, 281-93
Classification - adultsexogenous - iatrogenousendogenous
ACTH – dependent ~ 80% Cushing disease - pituitary adenoma ~ 85% ectopic production of ACTH (small cell lung ca, NETs, thymic
NETs, gastrinomas, medullary thyroid ca, phaechromocytoma…)
ACTH – independent ~15% unilateral adrenal adenoma ~ 80% adrenocortical carcinoma ~ 20%
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Sharma ST et al:
Cushing´s syndrome: epidemiology and developments in disease management.
Clinical Epidemiology, 2015, 7, 281-93
Classification - childrenexogenous - iatrogenousendogenous
Mc Cune Albright syndrome – less than 5-7 years of age
7+ years - pituitary adenoma ectopic extremely rare
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McCune-Albright syndrome
is caused by mutations in the GNAS1 gene. May be diagnosed at birth - café au lait spots, early childhood - polyostotic
fibrous dysplasia or by adolescence - precocious puberty. The clinical presentation is highly variable
Marked polyostotic fibrous dysplasia May involve a single or multiple skeletal sites with osteoarthrosis, pathological fractures, rickets, scoliosis
Endocrine abnormalities precocious puberty (vaginal bleeding or spotting and development of breast tissue in
girls, testicular and penile enlargement and precocious sexual behaviour in boys) hyperthyroidism, growth hormone excess, Cushing's syndrome. goitre (with or without hyperthyroidism), diabetes mellitus
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Chromophobe adenomas
all types of hormonal productions
scarcely granulated
null cell
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Hyperpituitarismus
Monohormonal
Syndromes:1. gigantismus/acromegaly
2. hyperprolactinemia
(galaktorea, amenorea)
3. Cushing
4. hyperthyreosis5. (hypergonadotropinismus)
Combined1+2, 1+3, 1+4, 2+3, 3+4
Regulatory hyperfunctionperiph. glands
ectopic production
iatrogenous
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Plurihormonal and PlurifunctionalPituitary Adenoma with Acromegaly Syndroma
doc. MUDr Jaroslava Dušková, CSc*,
prof. MUDr Josef Marek, DrSc**,
prof. MUDr Ctibor Povýšil,DrSc*
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F 75 yrs
30 yrs lasting acromegaly refused surgery Symptomatic therapy
– hyperfunction thyr . – Carbimazol– cardiomegaly - cardiotonica– 5 yrs prior tu death ca coli – surg. removed– 6 yrs prior tu death corticoid substitution– death cardial failure
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Plurihormonal and PlurifunctionalPituitary Adenoma
with Acromegaly
STH +++
Prl ++
ACTH ++
TSH +++
FSH (beta)+
LH (beta)+
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Pituitary INCIDENTALOMA- algorithm of Investigation and treatment
m e d ik a m e n t . th .b r o m o c r ip t in
p r o la k t in o m
o p e r a c e
j in ý
h y p e r f .
k o n e c s le d .
b e z e z m ě n y
o p a k o v a t N M R z a 1 ,2 ,5 ,le t
< 1 c m
o p e r a c e
r ů st tu m o r up o r u c h a z o r . p o le
h y p o p itu ita r ism u s)
o p a k o v at N M R z a 0 ,5 1 ,2 ,5 ,le t
z o r n é p o lev y l . h y p o p itu ita r ism u s
> 1 c m
F u n k c e h y p o fý z yPituitary function
other
operation
repeat NMR in1,2,5 yrs
no change
visual field, excl. hypopituit.
repeat NMR in 0.5,1,2,5 yrs
end check- ups
operation
neoplasm growth, visual field def., hypopituitarism
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Other Pituitary Tumours
craniopharyngeoma metastases
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WHO Histological Typing of Tumours of the CNS
TUMOURS OF THE SELLA REGION
& TUMOUR LIKE LESIONS
– craniopharyngeoma– Rathke´s cyst– epidermoid cyst– dermoid cyst– colloid cyst of 3rd ventricle– enterogenous cyst, pituicytoma, nasal glioma
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WHO Histological Typing of Tumours of the CNS
TUMOUR LIKE LESIONS OF THE SELLA REGION – diff. dg.!!!
– Rathke´s cyst
– epidermoid cyst
– dermoid cyst
– colloid cyst of 3rd ventricle
– enterogenous cyst
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Other Pituitary Tumours
craniopharyngeoma metastases