Transcript Laura Knecht, MD - Barrow Pituitary Blog

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
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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
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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
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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
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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
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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
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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)
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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
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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
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Degree
Duration
Presence/absence androgen excess
Cause
Tumor related symptoms
Age
Clinical Manifestations
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Obesity
Moon facies
Dorsal cervical fat pad
Exophthalmos
Periorbital edema
Conjunctival injection
Chest/facial plethora
Growth retardation
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Skin atrophy
Easy bruisability
Striae
Hyperpigmentation
Hirsutism
Acne
Complications
• Fungal infections
• Cardiovascular complications
– Stroke, heart attack
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Proximal myopathy
Psychiatric disturbances
Menstrual abnormalities
Osteoporosis
PCOS (Polycystic Ovarian Syndrome)
Diabetes/impaired glucose tolerance
Screening Tests
• 1 mg overnight dexamethasone
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Take at 11pm
Draw cortisol at 8am
Cortisol < 1.8mg/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 <1.8mg/dL
– Cortisol <50% of baseline
Inferior Petrosal Sinus Sampling/IPSS
Surgery
• Goal is for cure
– Immediate post-op cortisol <2-3mg/dl within 2472hours
• If not cured, consider
– Repeat surgery
– Radiation treatment
Ketoconazole
• Dosing 200-400mg BID-TID
• Side effects
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HA
Sedation
Nausea/vomiting
Gynecomastia
Decreased libido
Impotence
• Life threatening-reversible hepatotoxicity
Mifepristone (Korlym)
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Dosing 300mg daily
Maximum dose 1200mg daily
Maximum dose in hyperglycemia 600mg daily
Side effects
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Adrenal insufficiency
Peripheral edema
Hypertension
Headache
Hypokalemia
Endometrial hypertrophy
• Cannot follow cortisol levels
Pasireotide
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Dosing 600-900 mcg subcutaneously twice daily
Decrease in cortisol, ACTH, salivary cortisol
Signs and symptoms improved
Side effects
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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
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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
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Enlargement of hands/feet
Excessive sweating
Dental malocclusions
Sleep apnea
Signs/Symptoms
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Diabetes
Hypertension
Colon polyps
Arthralgias
Skin tags
Carpal tunnel
Co-morbidities
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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 AgonistsBromocriptine/Cabergoline
• Improvement in symptoms - 90%
• Normalize IGF-1<20%
• Likely more effective in co-secreting tumors
GH receptor Antagonist –
Pegvisomant (Somavert)
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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
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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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