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Pathology of the Endocrine Organs - I

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

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Pathology of the Endocrine Organs - I

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  1. Pathology of the Endocrine Organs - I Pituitary Jaroslava Dušková Inst. Pathol. 1st Med. Fac. Charles Univ. Prague http://www1.lf1.cuni.cz/~jdusk/

  2. 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

  3. 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

  4. 1. formation of the Rathke´s pouch & proc. infundibularis 2. splitting of the Rathke´s pouch 3. mature formation

  5. Neuroimmunoendocrine Regulation Messengers • Neurotransmitters • Interleukins • Hormons

  6. Pituitary - regulation Higher neural centra limbic system reticular system hypothalamus liberins & statins adenohypophysis trophic hormons of the adenohypophysis peripheral endocrine glands hormons of periph. glands tissues

  7. Pituitary – weight Females 505 - 1002 mg (average 660 mg) pregnant women 560 - 1220 mg (average 762 mg) Males 400 - 855 mg (average 570 mg) Rasmussen, AT Am.J. Anat. 1928 a 1934

  8. Pituitary- architecture • adenohypophysis • pars infundibularis (tuberalis) • pars intermedia • neurohypophysis • hypophysis pharyngea (+ hidden islets of pit. cells in the os sphenoides)

  9. Pituitary- cell inclusions • squamous epithelium • Rathke´s pouch between AH and NH • salivary glands- NH, often with oncocytes

  10. Pituitary- parts - function • Adenohypophysis secretion of tropins • Pars infundibularis (tuberalis) modulation of AH secretion • Pars intermedia • Neurohypophysissecretion of neuropeptides • hypophysis pharyngea possible secretion of tropins

  11. Pituitary– cell populations • acidophilsomatotrophs, lactotrophs • basophilcorticotrophs, gonadotrophs, thyreotrophs • chromofobe(transitional. + folliculostellate) • oncocytes(or preoncocytes) • mesenchymal • pituicytes (macroglia) • secretion neurons(tractus supraoptico- et tuberohypophyseus)

  12. 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

  13. Pituitary- cell population & hormonal production Hormonal production mostly mixed (e.g. ACTH+FSH,LH,TSH,PRL)

  14. Pituitary - cell population &hormonal production Individual producents able of interconversion following stimulation (e.g. PRL-GH)

  15. 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

  16. 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

  17. 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

  18. incidence 1- 8 % large autopt. series pathogenesis intracranial hypertension ischemia vasospasmus atherosclerosis thrombi stalk lesion healingscar focal regenerates possible meaning hypofunction only in case of more than 3/4 of volume destruction Pituitary- necrosis

  19. Necrosis hypophysis intra partum sy. Sheehani • hyperplasia • shock • ischaemia • necrosis • panhypo- pituitarismus

  20. non specific (peri)hypophysitis purulenta non purulenta septic pyemic microabscesses lymphocytic autoimmune specific tbc hematogenous dissemination solitary tuberculoma lues inborn acquired Pituitary- inflammation

  21. Pituitary syndromes • Hypofunctional • panhypopituitarismus • selective hypofunction • Hyperfunctional • monohormonal • combined

  22. Total >90% AH destroyed Syndromes: Simmonds Sheehan Falta Lorain Partial monohormonal combined Regulatory hypofunction peripheral glands ectopic production iatrogenous Hypopituitarismus

  23. 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.

  24. Pituitary Adenomas 9% Clin. symptomes • no • galactorea-amenorea • acromegaly • hypercortisolism • chiasma opticum compression • hypopituitarism 9%

  25. Pituitary Adenomas 9% • chiasma opticum compression 43 • acromegaly 23 • galactorea-amenorea 7 • hypopituitarism 7 Clin. symptomesin surgically treated (n=80) 9% 54% 28%

  26. Pituitary Adenomas 9% pathogenesis • 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 9%

  27. The WHO Classificationof Adenohypophysial Neoplasms . A proposed five-tier scheme 1. endocrine activity 2. imaging/ surgery 3. histology 4. immunohistochemistry 5. ultrastructure Kovacs, K., Scheithauer, B., Horvath Eva, Lloyd, R Cancer 1996, 78,502-10

  28. Pituitary Adenomas • acidophillic • basophillic • chromophobe • mixed

  29. Acidophillic adenomas • somatotroph • lactotroph • mixed somatotroph and lactotroph • somatolactotroph densely granulated • onkocytic

  30. Basophillic adenomas • corticotrophic • thyreotrophic • gonadotrophic densely granulated

  31. m. Cushing paraneopl. pituitary ad.

  32. m. Cushing periph. hypothalamic

  33. Chromophobe adenomas • all types of hormonal productions scarcely granulated • null cell

  34. Monohormonal Syndromes: 1. gigantismus/acromegaly 2. hyperprolactinemia (galaktorea, amenorea) 3. Cushing 4. hyperthyreosis 5. (hypergonadotropinismus) Combined 1+2, 1+3, 1+4, 2+3, 3+4 Regulatory hyperfunction periph. glands ectopic production iatrogenous Hyperpituitarismus

  35. Plurihormonal and PlurifunctionalPituitary Adenoma with Acromegaly Syndroma doc. MUDr Jaroslava Dušková, CSc*, prof. MUDr Josef Marek, DrSc**, prof. MUDr Ctibor Povýšil,DrSc*

  36. 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

  37. STH +++ Prl ++ ACTH ++ TSH +++ FSH (beta)+ LH (beta)+ Plurihormonal and PlurifunctionalPituitary Adenoma with Acromegaly

  38. Pituitary INCIDENTALOMA- algorithm of Investigation and treatment Pituitary function repeat NMR in1,2,5 yrs other visual field, excl. hypopituit. repeat NMR in 0.5,1,2,5 yrs no change operation end check- ups neoplasm growth, visual field def., hypopituitarism operation

  39. Other Pituitary Tumours • craniopharyngeoma • metastases

  40. 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

  41. 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

  42. Other Pituitary Tumours • craniopharyngeoma • metastases

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