pathology of the endocrine organs - i pituitary jaroslava dušková inst. pathol. 1st med. fac....

Pathology of the Endocrine Organs - I

Pituitary

Jaroslava Dušková

Inst. Pathol. 1st Med. Fac. Charles Univ. Prague http://www1.lf1.cuni.cz/~jdusk/

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

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

1. formation of the Rathke´s pouch & proc. infundibularis

2. splitting of the Rathke´s pouch

3. mature formation

Neuroimmunoendocrine Regulation Messengers

Neurotransmitters

Interleukins

Hormons

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

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)

Pituitary - architecture

adenohypophysis pars infundibularis (tuberalis) pars intermedia neurohypophysis

hypophysis pharyngea (+ hidden islets of pit. cells in the os sphenoides)

Pituitary - cell inclusions

squamous epithelium Rathke´s pouch between AH and NH

salivary glands - NH, often with

oncocytes

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

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)

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

Pituitary - cell population & hormonal production

Hormonal production mostly mixed

(e.g. ACTH+FSH,LH,TSH,PRL)

Pituitary - cell population &hormonal production

Individual producents

able of interconversion

following stimulation

(e.g. PRL-GH)

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

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

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

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

Necrosis hypophysis intra partum

sy. Sheehani

• hyperplasia • shock• ischaemia• necrosis• panhypo- pituitarismus

Pituitary - inflammation

non specific (peri)hypophysitis

purulenta

non purulenta

septicpyemic

microabscesses

lymphocytic– autoimmune

specific tbc

hematogenous dissemination

solitary tuberculoma

lues inbornacquired

Pituitary syndromes

Hypofunctional–panhypopituitarismus–selective hypofunction

Hyperfunctional–monohormonal–combined

Hypopituitarismus

Total >90% AH destroyed

Syndromes:

Simmonds Sheehan Falta Lorain

Partialmonohormonalcombined

Regulatory hypofunction

peripheral glands ectopic

production iatrogenous

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.

Pituitary Adenomas

no galactorea-amenorea acromegaly hypercortisolism chiasma opticum compression

hypopituitarism

Clin. symptomes 9%9%

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%

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%

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

Pituitary Adenomas

acidophillic basophillic chromophobe mixed

Acidophillic adenomas

somatotroph lactotroph mixed somatotroph and lactotroph somatolactotroph densely granulated

onkocytic

Basophillic adenomas

corticotrophic thyreotrophic gonadotrophic densely granulated

m. Cushing paraneopl. pituitary ad.

m. Cushing periph. hypothalamic

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%

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

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

Chromophobe adenomas

all types of hormonal productions

scarcely granulated

null cell

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

Plurihormonal and PlurifunctionalPituitary Adenoma with Acromegaly Syndroma

doc. MUDr Jaroslava Dušková, CSc*,

prof. MUDr Josef Marek, DrSc**,

prof. MUDr Ctibor Povýšil,DrSc*

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

Plurihormonal and PlurifunctionalPituitary Adenoma

with Acromegaly

STH +++

Prl ++

ACTH ++

TSH +++

FSH (beta)+

LH (beta)+

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

Other Pituitary Tumours

craniopharyngeoma metastases

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

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

Other Pituitary Tumours

craniopharyngeoma metastases