PITUITARY TUMORS

1. PITUITARY TUMORS

5. PITUITARY TUMORS • Account for 10-25 % of brain tumors • Medium age at debut: between 20-50 years • Children rarely have pituitary adenomas. Most tumor in children are craniphariogiomas and are associated with growth failure and diabetes insipidus. • Most pituitary adenomas in children are prolactinomas • Prolactinomas, Gh secreting adenomas and ACTH-secreting adenomas are more frequent in women. GH secreting adenomas are more frequent in men.

7. PITUITARY TUMORS - CLASSIFICATION According to their size: • Microadenomas:have less than 1 cm, do not modify the shape of sella turcica and do not produce pituitary tumor syndrome • Macroadenomas:have nore tahn 1 cm. and according to the direction they develop produce “the syndrome of pituitary tumors” According to their degree of aggression • Benign adenomas • Invasive adenomas • Carcinamas: less then 1 % of pituitary tumors

8. HISTOGENESISOF PITUITARY TUMORS Two hit hypothesis: Pituitary adenomas are monoclonal tumors Polyclonal adenomas may result from excessive stimulation of pituitary by specific releasing hormones Pituitary cells have a genetic protective factor against tumor proliferation. Lost of one protective allelle - first hit is not associated with tumor transformation, a point mutation of the second allelle – second hit results in tumor proliferation . Tumor occurs only if both protective factors are lost

9. HISTOGENESISOF PITUITARY TUMORS Anotherpathogenic hypothesis is an activating mutation of alpha subunit of GTP-binding protein which activates cAMP and stimulates cell proliferation În MEN 1– Multiple Endocrine Neoplasia type 1 there is an autosomal dominant deletion of a protective gene MENINE encoded on chromosome 11 (11q13)and multiple tumors simultaneous or successive occur: - multiple parathyroid adenoams with primary hyperparathyroidism - gastro-entero-pancreatic tumors: gastrinoma, insulinoma, glucagonoma - carcinoid tumors - adrenal adenomas - lipomas - facial angiofibromas

10. Pituitary macroadenoma

11. Microadenoma

12. PITUITARY TUMOR SYNDROME • NEUROLOGIC SYMPTOMS: • Headache • Nerves III, IV and VI which cross the cavernous sinus • Temporal seizures • Other seizures • Meningeal signs • OPHTALMOLOGICSIGNS • Decreased visual acuity • Reduction of visual field according to tumor extension • Exophtalmos : rare • RADIOLOGICAL SYGNS • Enlarged surface of sella turcica • Radiologic signs specific for some pituitary adenomas: acromegaly

13. Effects of pituitary enlargement on optic chiasma and visual field

15. Loss of lateral visual field due to optic chiasm compression

16. Nerve IV palsy

17. Radiological signs in pituitary macroadenoma: enlarged sella turcica, destroyed sellar walls

18. CT

19. MRI – Pituitary adenoma T1 imaging

20. DIAGNOSIS OF PITUITARY ADENOMAS • Clinical suspicion • Assessment of pituitary hormones to determine hormonal secretion of adenomas and level of other pituitary hormones in case if pituitary is partially dystroyed. • Radiograph of sella turcica: useful in case of macroadenomas • CT orMRI of hypothalamic-pituitary area • Inhibitory tests, biochemical markers for some adenomas

21. MRI Imaging – invasive macroadenoma

22. Invasive macroadenoma with temporal extension

24. TREATMENT of PITUITARY ADENOMAS • SURGERY • RADIOTHERAPY • PHARMACOTHERAPY

25. SURGICAL TREATMENT OF PITUITARY ADENOMAS • First intention therapy for all adenomas with exception of those which have a proven beneficial pharmacological treatment • Immediately indicated in tumors which exert compression over structures from the proximity and involve a risk for sight loss or have intracranial hypertension. • Is an emergency treatment for pituitary apoplexy – pituitary infarct. • May be delayed until pharmacological treatment may reduce tumor volume and make the tumor more accessible to surgery in some responsive cases

26. SURGICAL TREATMENT OF PITUITARY ADENOMAS Aim of surgery: • To reduce mass effect produced by large tumors over adiacent structures • To inhibit hormone secretion in pituitary secreting adenomas • To preserve morphologic and functional integrity of the pituitary

27. SURGICAL TREATMENT OF PITUITARY ADENOMAS Approach of the pituitary during surgery: • Transcranial approach: in large tumors with extra selar extension. The aim is to reduce tumor volume and has greater number of complications • Transphenoidal approach – is used in most adenomas with medium and small size. This treatment have no complications in a skillful hand and preserves the pituitary function if it was not previously affected. • Complete cured: 90 % of microadenomas • Tumor reduction without complete cure in larger tumors

28. SURGICAL TREATMENT OF PITUITARY ADENOMAS Complication of pituitary surgery depend of the size of the tumor and quality of surgery: • Death by carotid injury • Severe complication due to injury of cavernosal sinus and nerves III,IV and VI • Brain injuries • Chiasma injury with complete sight loss • Infections: meningitis, enchephalitis • Cerebro-spinal flud fistula • Diabetes insipidus: permanent 5 % of (frequently transitory condition – some weeks) • Syndrome of inapropriate vasopressine secretion 10 % • Hypopituitarism 5-10 % in large tumors

31. IRRADIATION IN PITUITARY ADENOMAS Convenţional irradiation: The tumor is irradiated based on a computerized program which includes CT and MRI in order to spare the proximal regions with CT/IRM 4000 – 5000 cGy, in fractionated doses of 180 – 200 cGy per day, 5 days per week Succes: • 80 % in acromegaly, but full effect appear variably in time until 8 years and even more • 55 – 60 % in ACTH-secreting tumors , in a shorter time • In prolactinomas the response rate is less important because tumor secretion may be successfully controlled with dopamine agonists

32. IRRADIATION IN PITUITARY ADENOMAS Complications of conventional irradiation: • Hypopituitarism in 50-60 % of cases in 8-10 years • Optic nerve injury • Brain radio necrosis • Occurrence of other neoplasia of the brain favor by previous irradiation Gamma knife delivers in one MRI –guided the entire dose of irradiation on a very small field The effects of irradiation are more rapid – until 4 years Only in tumors which are more distant of the optic chiasm: at least 4 mm. Until the cure obtained by irradiation the tumor secretion and growth must be controlled by pharmacotherapy

33. Gamma knife irradiation

34. Effect of gamma knife irradiation in a pituitary adenoma

35. Prolactinomas and hyperprolactinemia Prolactin excess inhibits gonadotropins secretion In women: • Secondary amenorrhea, oligomenorrhea, infertility • Galactorhea • Hirsutism • Signs of estrogen deficiency with genital atrophy • Osteoporosis • Pituitary failure in large prolactinomas Most prolactinomas in women are microadenomas.

36. Prolactinomas and hyperprolactinemia In men: decreased testosterone secretion with: • Decreased libido • Erectile dysfunction • Infertility • rare: gynecomastia şi galactorhea • Pituitary failure In men most prolactinomas are macroprolactinomas and are associated with “pituitary tumor syndrome”

37. Microprolactinoma Macroprolactinoma

38. OTHER CAUSES OF HYPERPROLACTINEMIA • Physiological: breast feeding, sexual activity, sleep, stimulation of mamary gland • Interruption of conection between hypothalamus and pituitary and inhibitory control of the hypothalamus over pituitary, stalk section, stalk compression by other tumors, hypothalamic tumors • Empty sella syndrome • Drugs which inhibit dopamine: psychotropes, antidepressives, l-DOPA, 5HT2 inhibitors, estrogeni, oral contraceptives • Hypothalamic diseases: sarcoidosis, hysticytosis • Polycystic ovarian disease, acromegaly, hipothyroidism, kidney failure, liver cirrhosis • Torax unjuries

39. ASSESSEMENT OH HYPERPROLACTINEMIA • Prolactin values • Prolactin levels correlates with tumor size • Normal prolactin levels: 9-25 ng/ ml • 50 ng/ ml functional hyperprolactinemia • between 50-100 ng/ ml microprolactinomas • over 100 ng/ ml macroprolactinomas • Bromocriptine test: • 2,5 mg bromocriptinemust reduce prolactin levels • Assessement of lesions: CT, IRM

40. TREATMENT OF PROLACTINOMAS Pharmacotherapy – dopamine agonists • First choice treatment in microprolactinomas and pre treatment in macroprolactinomas in order to reduce tumor size and facilitate surgery • Bromocriptine: 2,5 – 20 mg /day • Cabergolină: 0,5 – 3,5 mg /week • quinagolid • Effects of pharmacotherapy: - menses occur again - fertility is restored - during pregnancy the treatment may be stoped - during pregnancy the tumor is followed by assessing the visual field

41. TREATMENT OF PROLACTINOMAS SSurgery • For large tumors with compressive symptoms • May be done after previous pharmacotherapy • Effects of surgery: - in best cases gonadotropin secretion occurs again - risks and complications are similar to other pituitary tumors submited to surgery - residual disease may be controlled with dopamine agonists C. External irradiation is rarely needed

42. Large prolactinoma cured by dopamine agonists

43. ACROMEGALY PREVALENCE: • 40 – 60 cases / 1 milion /year • 3-2 new cases per year • 1 / 15.000 person

44. ACROMEGALY Causes : • sporadic: • Adenoama pure high granulated, sparse granulate • Mixed GH and prolactin secreting adenomas • Acidofilic adenoams with stem cells • Ectopic adenomas • GH secreting carcinoma • Mc Cune-Albright syndrome • Familial forms: izolated, MEN 1, Carney complex, FIPA - • Hypothalamic GH.RH excess: harmartoms, gangliocytoma, glyoma, • Extrahypothalamic GH-RH secretion • Pancreatic carcinoids, bronchial carcinoma MTC,

45. Histology of a acidophilic GH secreting adenoma

47. Development of the disease is insidious and graduated during years, the disease being recognized 10 years after real debut

50. Acromegaly – signs and symptoms • Signs and symptoms of the disease are determined by the effects of GH and IGF1 over target tissues after the epiphyseal growth plates are closed. In case of a precocious debut gigantism occurs • Short and flat bones are more affected, • GH and IGF1 excess produce • Hypertrophy of all structures containig connective tissue and bone • Metabolic abnormalities