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Common Types of Pituitary Tumors. Laura Knecht MD. Medical Director of the Barrow Pituitary Center. Introduction. Pituitary tumors comprise 10-15% of all intracranial tumors Gliomas – Meningiomas - Pituitary adenomas 10% of all surgically resected tumors - PowerPoint PPT Presentation
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Common Types of Pituitary Tumors
Laura Knecht MD
Medical Director of the Barrow Pituitary Center
Introduction
• Pituitary tumors comprise 10-15% of all intracranial tumors– Gliomas – Meningiomas - Pituitary adenomas
• 10% of all surgically resected tumors• Affects up to 20% population (1 in 5)• Majority arise from anterior pituitary gland
Pituitary Adenomas
• Classified based on size, secretory abilities, histology
• <10mm-microadenomas• >10mm-macroadenomas• Beyond sella-giant adenomas
• M:F• Females
– Present with micoadenomas– Age 20-30– Hormone dysfunction
• Menstral irregularities• Infertility
• Males– Present with macroadenomas– Age 40-50– Mass effect
• HA• Visual compromise
• FSH/LH-Gonadotroph adenomas– Nonfunctioning, rarely functions
• Prolactin-Prolactinomas– Most common
• TSH-TSHomas– Rare cause of hyperthyroidism, <1% pituitary
adenomas
• GH-Acromegaly– Can be cosecretors with GH/prolactin
• ACTH-Cushing’s Disease– 2/3 of causes of Cushing’s Syndrome
Nonfunctioning Pituitary Tumors
Nonfunctioning Pituitary Tumors
• 30% of all pituitary tumors• No evidence of hormonal hypersecretion• Large at presentation• Mass effects
– HA– Visual field deficits– Hypopituitarism
Mass Effects
• Hypopituitarism– GHRH – FSH/LH/prolactin – TSH - ACTH
• Elevated prolactin from stalk effect• Compression of optic chiasm
– Bilateral superior temporal hemianopsia
• Lateral growth into cavernous sinus– Cranial nerve palsies
Mass Effects
• Headache– Pressure on dura– Blood products– Cystic components
• Pressure on frontal/temporal lobes– Hydrocephalus– Memory issues
Hormonal Testing
• ACTH, 8am cortisol• TSH, free T4, free T3• Prolactin
– With 1:100 dilution if macroadenoma
• GH, IGF-1• FSH, LH, total testosterone/estradiol• Alpha subunit
MRI
• Pituitary protocol• Gadolinium• 3T• Dynamic protocol• Experience of center
Neuro-ophthalmology Testing
• Formal visual fields
• Visual acuity
• Health of optic nerves
Prolactinomas
Prolactinomas
• Most common hormonally active tumor• F>>M• Microadenomas
– Benign, regress spontaneously, can have no growth
• Macroadenomas– Present w/ pressure symptoms, increase in size, rarely
disappear
Prolactinomas
• Clinical features dependent on prolactin level, mass effects, hypopituitarism
• Gender, age, tumor size• Prolactin stimulates milk in Estrogen-primed
breast• High prolactin inhibits GnRH which decreases
FSH/LH which decreases testosterone/estrogen
When to Treat
• Infertility• Menstral disturbances• Bothersome galactorrhea• Enlarging tumor• Apoplexy w/ headache
Treatment
• Medications– 1st line treatment regardless of size
• Surgery– In resistant prolactinomas– Intolerance to both dopamine agonists
• Radiation– For residual/recurrent tumor
• Cabergoline– Better tolerated– Fewer side effects– More likely to normalize level– No increased risks in pregnancy– ½ life-2-3days– Effective dose 1-1.5mg twice a week, resistant
prolactinomas 7-12mg/week
• Cabergoline– May be fast metabolizers
• Change to every day or every other day– Valvulopathy
• Mitral valve stenosis• May be reversible• ? role of echocardiogram
• Bromocriptine– Cheaper– ½ life-8hrs– Should be 2-3 times daily– Common dose up to10mg every night or 5mg twice a
day– Doses >20-40mg not more efficacious– Preferred agent in pregnancy– No risk of valvulopathy
Side Effects of Dopamine Agonists
• Nausea• Lightheadedness• Mental fog• Worsening of depression• Psychotic reaction• Minimize if take at night, start low, go slow, take
w/ snack
Use of Hormone Replacement in Prolactinomas (Estrogen)
• Possible growth of tumor• In combo w/ dopamine agonists-safe• No prospective studies when used alone• Would not use if chiasmopathy• Monitor prolactin regularly
Pregnancy
• Risk of micro growing-1-3%• Risk of macro growing-<15%• Stop medication once pregnant• Go thru pregnancy, breastfeeding, restart if
amenorrhea, future fertility• Monitor for headache, vision changes• Can get MRI not Gadolinium• May have issues w/ lactation• Role of debulking if macroadenoma, chiasmopathy
Cushing’s Disease
Clinical Manifestations
• Degree• Duration• Presence/absence androgen excess• Cause• Tumor related symptoms• Age
Clinical Manifestations
Complications
• Fungal infections• Cardiovascular complications
– Stroke, heart attack
• Proximal myopathy• Psychiatric disturbances• Menstrual abnormalities• Osteoporosis• PCOS (Polycystic Ovarian Syndrome)• Diabetes/impaired glucose tolerance
Screening Tests
• 1 mg overnight dexamethasone– Take at 11pm– Draw cortisol at 8am– Cortisol < 1.8g/dL – r/o hypercortisolism– Cortisol > 5mg/dL = hypercortisolism
• 24 hour urinary free cortisol– If >3x normal, diagnostic of true Cushing’s– Lesser elevations require confirmation– False elevations of UFC
• Physical stress• Exercise• Large volume intake• Medications
Late Night Salivary Cortisol
• Bedtime/11pm salivary cortisol (series of 2-3)
Overnight High Dose Dexamethasone Suppression
• Dexamethasone 8mg by mouth at 11pm
• Serum cortisol at 8am
• Will suppress in pituitary source– Cortisol <1.8g/dL– Cortisol <50% of baseline
Inferior Petrosal Sinus Sampling/IPSS
Surgery
• Goal is for cure– Immediate post-op cortisol <2-3g/dl within 24-
72hours
• If not cured, consider– Repeat surgery– Radiation treatment
Ketoconazole
• Dosing 200-400mg BID-TID• Side effects
– HA– Sedation– Nausea/vomiting– Gynecomastia– Decreased libido– Impotence
• Life threatening-reversible hepatotoxicity
Mifepristone (Korlym)
• Dosing 300mg daily• Maximum dose 1200mg daily• Maximum dose in hyperglycemia 600mg daily• Side effects
– Adrenal insufficiency– Peripheral edema– Hypertension– Headache– Hypokalemia– Endometrial hypertrophy
• Cannot follow cortisol levels
Pasireotide
• Dosing 600-900 mcg subcutaneously twice daily• Decrease in cortisol, ACTH, salivary cortisol• Signs and symptoms improved• Side effects
– Hyperglycemia– Diarrhea– Abdominal discomfort– Gallstones
Bilateral Adrenalectomy
• Immediate cure
• Complication-Nelson’s Syndrome– Vision loss– Progression of pituitary tumor– Dependent on glucocorticoids and mineralicorticoids
Post-op Management
• Adrenal insufficiency results
• Treat w/ decreasing doses of steroids– Initial dosing – hydrocortisone 40-80mg daily– Wean over 6-24months– Cosyntropin stimulation testing once off to confirm
normal axis
Monitoring
• Lifelong• Patients usually feel symptoms prior to
abnormalities in testing• Yearly cortisol, ACTH• Scheduled MRIs• Consider hypercortisolemia testing
– Late night salivary testing– 24 hour urine free cortisol– 1mg overnight dexamethasone suppression
Acromegaly
Acromegaly
• M=F• Mean age 42-44• Usually have diagnosis 7-10 years prior• Premature mortality from cardiovascular disease
with risk decreasing when normalize IGF-1, GH
Symptoms
• Change in facial features– Enlargement in forehead, mandible, tongue, gap in teeth
• Enlargement of hands/feet• Excessive sweating• Dental malocclusions• Sleep apnea
Signs/Symptoms
• Diabetes• Hypertension• Colon polyps• Arthralgias• Skin tags• Carpal tunnel
Co-morbidities
• Cardiomyopathy/Congestive Heart Failure• Diabetes/Insulin resistance• Hypertension• Obstructive sleep apnea• Precancerous colon polyps• Thyroid nodules
Lab Values
• Elevated GH
• Elevated IGF-1
• Lack of GH suppression to glucose load
Treatment
• Surgery– 1st line treatment by experienced surgeon
• Medications– Has been used as adjunctive vs primary medical
therapy
• Radiation
Surgery
• Post op day 1 GH<5 highly predictive of remission
• Remission if GH<1 after OGTT
• IGF-1 takes weeks to months to decrease because of delayed clearance
Medical Treatment
• Somatostatin analogs
• Dopamine agonists
• GH receptor antagonist
Somatostatin analogs-Octreotide LAR(Sandostatin)/Lanreotide
(Somatuline)
• Improvement in symptoms - 90%
• Lower GH - 90%
• Normalize IGF-1 - 50-60%
• Reduce tumor size by 25%
Somatostatin Analogs-Octreotide LAR(Sandostatin)/Lanreotide
(Somatuline)
• Side effects– Transient abdominal discomfort– Diarrhea– Gallstones – 18%
Dopamine Agonists-Bromocriptine/Cabergoline
• Improvement in symptoms - 90%
• Normalize IGF-1<20%
• Likely more effective in co-secreting tumors
GH receptor Antagonist – Pegvisomant (Somavert)
• Elevates GH• Normalize IGF-1 - 89-97% at 1 year• Shot subcutaneously daily• Can be combined w/ somatostatin analog once or
twice weekly– Decrease dose of somatostatin analog– Improvement in cost savings
GH receptor Antagonist – Pegvisomant (Somavert)
• Side effects
– Hepatitis picture• Resolves w/ stopping med
– Enlargement of tumor• Likely from termination of somatostatin analog
Radiation Treatment
• Adjunctive therapy after surgery for residual/recurrent disease
• Starts working in 3-6mo, continues working 3-10 years
• GH falls 50% every 2-3years• Normalization of IGF-1 rare prior to 5 years• Normalize IGF-1 - 60-80%
Screening Tests w/ Diagnosis
• Baseline echo, repeat 1 year, prn• Colonoscopy every 5years• Thyroid u/s, fine needle aspirate all nodules >1cm• A1c, Fasting lipid panel• Hypertension• Obstructive sleep apnea• Carpal tunnel• Joint pain/hip x-rays• Bone density/DXA if hypogonadism,
hyperprolactinemia
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