1. PRESENTED BY :Dr SANDIP KUMAR BARIK DEPT OF RADIOTHERAPYMODERATOR: Dr RAJENDRA KUMAR

2. INTRODUCTION Pituitary or hypophysis cerebri is an endocrine gland situated in relation to the base of the brain It is called the Master of endocrine orchestra It produces a number of hormones which control the secretions of many other endocrine gland of the body

3. ANATOMY The pituitary gland or hypophysis is an endocrinabout 15 mm in ant-post and 12 mm in supero inferior axis It weighs about 0.5 gm. The pituitary gland occupies a cavity of the sphenoid bone called sella turcica Roof is formed by diaphragm sellae The stalk of pituitary is attached above to the floor of third ventricle

4. Anatomy(cont..) Relations Superiorly:Diaphragma sellae,optic chiasma,infundibular recess of 3rd ventricle Inferiorly:Hypophyseal fossa and its venous channels On each side :The cavernous sinus with its contentModified from Lechan RM. Neuroendocrinology of Pituitary Hormone Regulation. Endocrinology and Metabolism Clinics 16:475-501, 1987

5. The anterior and intermediate lobe arises from the Rathkes pouch The posterior lobe or neurohypophysis arises from the downward pocketing of third ventricle. Posterior lobe releases hormones the Oxytocin and Vasopressin which are synthesised in the supraoptic and paraventricular nuclei in hypothalamus Anterior lobe releases hormones ACTH,TSH,GH,FSH,LH,Prolactin

6. EPIDEMIOLOGY Pituitary neoplasm account for 10% to 15% of diagnosed primary intracranial neoplasm 3% -25% pituitary glands are identified by autopsy 10% of healthy population has pituitary abnormality detected by MRI Approximately 70% are endocrinologically active Incidence of macroadenomas is similar between males and females However clinical manifestations of microadenomas are more in women

7. EPIDEMIOLOGY (Cont) 70% of adenomas present between the ages 30 -50 yrs Women have high incidence of pituitary adenomas(15-44 yrs) Annual incidence ranges from 0.5 to 0.7/100,000 Etiology of most adenomas is unknown A genetic predisposition to develop adenomas has been described in MEN I syndrome Carney complex Isolated familial somatotropinomas(IFS)

8. NATURAL HISTORY Usually has a long natural history with an insidious onset of symptoms Symptoms are usually present for years prior to diagnosis When small pituitary tumour tends to be smooth round tumours Macroadenomas are known for their local invasive properties Malignant behaviour with distant metastases is rare

9. CLINICAL PRESENTATIONS The presenting symptoms may be due to Hormonal malfunction Due to local tumour growth and pressure effect Endocrine abnormalities may be a consequence of hyper or hypo secretion of pituitary hormones. Hypopituitarism Hyperpituitarism Cushings syndrome Hyperprolactinomas Hyperthyroidism Acromegaly

10. HYPOPITUITARISM Growth hormone deficiency:Short stature(Dwarfism) Gonadotrophins deficiency:Infertility,decreased sexual functions,loss of secondary sexual characters,menstrual irregularities TSH deficiency :Hypothyroidism ACTH deficiency :Hypocortisolism Prolactin deficiency :Lactation failure Vasopressin deficiency :Diabetes insipidus

11. HYPERPITUITARISM HYPERPROLACTINEMIA Most common cause of pituitary hormone hypersecretion Amennorhoea Galactorrhoea Infertility INCREASED GH Acromegaly in adults Frontal bossing Increased hand foot size Mandibular enlargement,Prognathism Large fleshy nose Proximal muscle wasting,carpal tunnel syndrome,macroglossia Gigantism in children

12. INCREASED ACTH Causes cushing syndrome Central obesity Plethoric moon facies Purple striae,increased bruisability Glucose intolerence Acne,hirsuitism Proximal muscle weakness Hypertension Amennorhoea,infertility

13. FEATURES OF SELLAR MASS LESION PITUITARY Hypopituitarism OPTIC CHIASMA Bitemporal Hemianopia Superior temporal defect CAVERNOUS SINUS Ophthalmoplegia Ptosis Diplopia OTHERS Head ache Hydrocephalus Dementia

14. DIAGNOSTIC WORKUP Detailed History and complete physical examination Confirmation of diagnosis Radiological Examination MRI-preferred modality better visualisation of soft tissue and vascular structure CT Scan Biopsy In a case of non secreting lesion

15. STAGING WORKUP: Chest x ray USG Whole abdomen General condition: Complete blood count Kidney function tests liver function test Urine analysis

16. HORMONAL ANALYSIS Serum Prolactin level Growth hormone:basal growth hormone level IGF-I Glucose suppression,insulin tolerence ACTH Hypersecretion: Serum ACTH,Dexamethasone supression test 24 hrs urine for 17-hydroxy corticosteroids and free cortisol Gonadal function:FSH,LH,Esradiol,Testosterone Thyroid function test Adrenal function:basal plasma,urinary steroids cortisol response to insulin induced hypoglycaemia

17. CLASSIFICATION OF PITUITARY TUMOURS ANATOMICAL SIZE Microadenoma(10 mm) PHYSIOLOGICAL Ant pituitary1. Prolactin2. Growth hormone3. Adrenocorticotrophic hormone4. Leutinizing hormone5. Follicle stimulating hormone6. Thyroid stimulating hormone Post pituitary1. Oxytocin2. Vasopressin

18. Classification(Cont) ACCORDING TO CLINICAL SYMPTOMS Functional Non functionaL ACCORDING TO EXTENT OF EXPANSION OR EROSION OF SELLA Grade 0: Intrapituitary microadenoma with normal sellar appearance Grade I: Nml-sized sella with asymmetric floor Grade II: Enlarged sella with an intact floor Grade III: Localized erosion of sellar floor Grade IV: Diffuse destruction of floor

19. Classification(Cont) ACCORDING TO SUPRASELLAR EXTENSION Type A: Tumor bulges into the chiasmatic cistern Type B: Tumor reaches the floor of the 3rd ventricle Type C: Tumor is more voluminous with extension into the 3rd ventricle up to the foramen of Monro Type D: Tumor extends into temporal or frontal fossa

20. PATHOLOGICAL CLASSIFICATIONS Ant Pituitary has 5 specific cell types Somatotrophs:produces growth hormone,acidophilic Lactotrophs:produces prolactin,acidophilic Corticotrophs:produces ACTH,MSH,basophilic Thyrotrophs:produces TSH,basophilic Gonadotrophs:FSH,LH,basophilic Post pituitary:pituicytes and non myelinated fibres

21. MANAGEMENT Observation Surgery Radiotherapy

22. OBSERVATION In asymptomatic non secreting microadenomas Small asymptomatic prolactinomas 2 -4 mm no testing required 5-9 mm MRI can be done once yearly Indications for intervention Tumour growth on imaging symptoms of hypersecretion development of visual field defects

23. < 10 mm > 10 mm Evaluate for: Evaluate for Hormonal Hypersecretion Hormonal Hormonal Hyposecretion Hypersecretion Visual Changes/defects Hormonal or VisualNormal Abnormalities No AbnormalitiesObserve Observe Treatment

24. SURGERYINDICATIONS It is the first line treatment for most symptomatic pituitary tumours Useful when medical or radiotherapy fails When prompt relief from mass effect and hormone secretion is required Pituitary apoplexy

25. TYPES MICROSCOPIC TRANSSEPTAL TRANSSPHENOIDAL Current standard surgical procedure Safe procedure with mortality rate 0.5% Contraindications are sphenoid sinusitis,ectatic midline carotid arteries,lateral surpasellar extent

26. ENDOSCOPIC TRANSNASAL TRANSSPHENOIDAL Allows better visualisation of pituitary gland,ghyophyseal stalk,cavernous sinuses,optic nerve and suprasallar areas .TRANSCRANIAL Requires craniotomy and retraction of frontal lobes Used for large invasive tumours with significant suprasellar extension When transsphenoidal approach is contraindicated

27. COMPLICATIONS OF SURGERY CSF rhinorrhoea Meningitis Haemorrhage Stroke Damage to pituitary Visual loss

28. RADIOTHERAPY INDICATIONS1. Hypersecretion and mass effect due to large tumours2. Incomplete resection of tumour3. Progressive disease after surgery4. Recurrent tumours

29. RADIOTHERAPY TECHNIQUES Conventional External Beam Radiotherapy Manual planning 2D Planning 3D CRT Fractionated Stereotactic Radiation Therapy Gammaknief Radiosurgery

30. MANUAL AND 2D PLANNING Positioning Supine with neck flexed and head at 45 degrees Pituitary board can be used to achieve this Immobilisation done with thermoplastic mask VOLUME The entire pituitary gland with extensions and a margin of 1-1.5 cm

31. PORTALS Two parallel and opp lat fields and one anterior or vertex beam that enters above the eyes The centre of the pituitary is located at a point 2-2.5 anteriorly to tragus and 2-2.5 cm superiorly to that point Taking this point as centre a field of( 4*4)cm-(6*6) cm is marked ENERGY 4-10 Mev or Co 60 DOSE Nonfunctioning tumours 45-50.4 Gy@1.8 Gy/# Functional tumours 50.4-54 Gy

32. 3D PLANNING Image based treatment planning using a 3D technique is the standard of care Defining the tumour volume MRI,CT as well as clinical and surgical findings should be used to define the tumour volume CT simulation assists in defining treatment volume GTV is the pituitary adenomas including any extention into adjacent anatomic regions CTV :GTV+5 mm in a clear defined tumour or entire sella and cavernous sinus with invasive tumours PTV:CTV+5mm

33. FRACTIONATED STEREOTACTIC RADIOTHERAPY(FSRT) FSRT is characterised by improved patient localisation,tighter volume definition more conformal isodose distributions It has better safety profile and efficacy IMMOBILISATION Aim is to achieve a patient positioning error of less than 3mm by various means like Invasive halo ring Radiocamera bite block Non invasive Head frames

34. Stereotactic(cont) TARGET VOLUME DELINEATION GTV is designed with help of MRI and extent of cavernous sinus invasion should be included No additional margins is required for CTV PTV:CTV +2-3 mm margin TREATMENT PLANNING Depends on the delivery systems available Options include Multiple spherical shots Dynamic conformal arches Nonisocentric robotic delivery DOSE 50.4 Gy in 28#@1.8Gy/#

35. STEREOTACTIC RADIOSURGERY Accepted treatment for smaller,radiologically well defined tumours located at a distance (3-5 mm) from optic apparatus Contraindicated if optic chiasma is closer than (3 -5)mmto the tumour Delivery systems include linear accelerator and gamma knife Head is fixed with an appropriate stereotactic head frame and a high resolution imaging study is obtained MRI used for gamma knief while ct scan for linear accelerator Gamma knife uses smallest collimators and maximum number of isocentres . The dose to optic chiasma is limited to