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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