Post on 22-Dec-2015
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.
PITUITARY TUMORS
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
HISTOGENESIS OF 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
HISTOGENESIS OF PITUITARY TUMORS
Another pathogenic 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
Pituitary macroadenoma
Microadenoma
PITUITARY TUMOR SYNDROME• NEUROLOGIC SYMPTOMS:
– Headache – Nerves III, IV and VI which cross the cavernous sinus– Temporal seizures– Other seizures– Meningeal signs
• OPHTALMOLOGIC SIGNS– 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
Effects of pituitary enlargement on optic chiasma and visual field
Loss of lateral visual field due to optic chiasm compression
Nerve IV palsy
Radiological signs in pituitary macroadenoma: enlarged sella turcica, destroyed sellar walls
CT
MRI – Pituitary adenoma T1 imaging
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 or MRI of hypothalamic-pituitary area• Inhibitory tests, biochemical markers for some
adenomas
MRI Imaging – invasive macroadenoma
Invasive macroadenoma with temporal extension
TREATMENT of PITUITARY ADENOMAS
• SURGERY
• RADIOTHERAPY
• PHARMACOTHERAPY
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
SURGICAL TREATMENT OF PITUITARY ADENOMAS
Aim of surgery:
a. To reduce mass effect produced by large tumors over adiacent structures
b. To inhibit hormone secretion in pituitary secreting adenomas
c. To preserve morphologic and functional integrity of the pituitary
SURGICAL TREATMENT OF PITUITARY ADENOMAS
Approach of the pituitary during surgery:
a. Transcranial approach: in large tumors with extra selar extension. The aim is to reduce tumor volume and has greater number of complications
b. 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
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
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
IRRADIATION IN PITUITARY ADENOMASComplications 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 yearsOnly 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
Gamma knife irradiation
Effect of gamma knife irradiation in a pituitary adenoma
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.
Prolactinomas and hyperprolactinemiaIn 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”
Microprolactinoma Macroprolactinoma
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
ASSESSEMENT OH HYPERPROLACTINEMIA
A. 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 bromocriptine must reduce prolactin levels
• Assessement of lesions: CT, IRM
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
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
Large prolactinoma cured by dopamine agonists
ACROMEGALY
PREVALENCE:• 40 – 60 cases / 1 milion /year
• 3-2 new cases per year
• 1 / 15.000 person
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,
Histology of a acidophilic GH secreting adenoma
Development of the disease is insidious and graduated during years, the disease being recognized 10 years after real debut
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
ACROMEGALY SIGNS AND SYMPTOMS
SIGNS AND SYMPTOMS AT THE DEBUT:• Headache• Joint and bone pain• Dental problems• Amenorhea, galactorhea, loss of libido• Diabetes mellitus• Hyperhydrosis• Carpal tunell syndrome• Sleep apnea• HTA, cardiomyopathy• Colonic poliposis
ACROMEGALY signs and symptoms
• Pituitary tumor syndrome: • Narrowing of the visual field, • Decreased visual acuity
• Facial abnormalities: – Prominent frontal boses– Prominent occipital bone– Enlargement of low jaw – Dental : spaces between tees– Large tongue
ACROMEGALIA signs and symtpoms
• Abnormalities of hands and feet: – Thicknening of the fingers– Carpal tunell syndrome
• Joints and spine: – Spondilosis– Osteoarthritis– skin: hyperhidrosis– Cutis giratta– Moluscum pendulum– Skin spots
Hand of an acromegalic patient.
Enlarge feet.
Anchor-like shape of the diastal phalange in acromegaly
Normal
Increased thickness of heel soft tissue
ACROMEGALY – metabolic problems
• Lypolisis• Insulinoresistence• Diabetes mellitus• Hypercalciuria, hypercalciuria• Sodium and water retention
ACROMEGALy – Complication
• Hearth :– Increased cardiac volume and systolic volume– Interstitial fibrosis– Systolic and dyastolic dysfunction– Ventricular dillatation– Hearth failure
• Lung:– Laringeal hypertrophy– Respiratory dysfunction – Sleep apnea
• Digestive : colonic polyposis• Other tumors
ACROMEGALIA – diagnosticGH increased in multiple
determinations. IGF-1 increased
GH during OTTG
GH below < 1 ng/ml GH not inhibited during OTTG
Imagery CT, IRM
Fundus of the eye VF
Nu este acromegalie
OCTREOSCAN – Indium labeled Somatostatin scintigraphy allows to detect somatostatin
receptors and predicts the response of tumors to somatostatin analoques
Pancreatic tumor producing GH-RH with pituitary hyprplasia , excessive GH secretion and
acromegaly
ACROMEGALY TREATMENT
• Surgery: transphenoidal, transcranial• Radioterapy• Long-acting somatostain analoques• Inhibitors of GH receptor
ACROMEGALY SURGICAL TREATMENT
• In emergency if there are symptoms of pituitary apoplexy• Guided by MRI and computer-assisted navigation• Transphenoidal approach is most frequent
• Criteria for cure: GH during OTTG < 0.30 ng/ ml, Partial response medium GH per 24 h les than 2.5 ng/mL
• Normal IGF
ACROMEGALY pharmacotherapy
ACROMEGALIA TRATAMENT MEDICALDrugs Debut dosage
Maximal dosage
Side effects Monitoring
Cabergoline 1mg/7days 4mg/7 days nausea GH, IGF1
Octreotide LAR Long acting
somatostatin analoque
20 mg/ month
30mg/ month nausdea
colethiasisGH, IGF1
US
LanreotidLong acting somatostatin analoque
30 mg/ x2 4week
30 mg/x4/ week
The same Same+ MRI anually
Lanreotid autogel
60 mg/ 4 week
120 mg/ 4 week
The same Same+ MRI anually
Pegvisomant 10 mg/ zi s.c.
40 mg/zi s.c. Headache, lethargy, increased of tumor volume if not associated with somatostatin analoques
MRI anualyLiver enzymes
ACROMEGALY: pharmacotherapy
Treatment of complications
• Osteoarthritis• Osteoporosis• Hypercalciuria• Hyperparatiroidism in MEN1• Treatment of sleep apnea• Monitorig Hb A1c, triglycerides• Treatment of hearth complications• Monitoring for colonic polyposis and colonic cancer
ACTH- SECRETING ADENOMA
• Small or very small size• Clinically manifested by Cushing’s disease• Diagnosis: cortisol, Dexametasone inhibition test, • Tretament: surgery and /or gamma knife
Prolactinoma