Pituitary Adenoma

Aka: Pituitary Adenoma, Pituitary Neoplasm, Functionless Pituitary Adenoma, Non-Functioning Pituitary Adenoma, Secretory Pituitary Adenoma, Pituitary Macroadenoma, Pituitary Microadenoma, Pituitary Incidentaloma, Prolactinoma, Prolactin-Secreting Pituitary Adenoma, Growth Hormone-Secreting Pituitary Adenoma, ACTH-Secreting Pituitary Adenoma, Thyrotroph Adenoma, TSH-Secreting Adenoma, Pituiatry Apoplexy, Pituitary Lesion

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II. Pathophysiology

  1. See Pituitary Gland

III. Definition: Pituitary Adenoma

  1. Benign Pituitary Neoplasm

IV. Epidemiology

  1. Pituitary Adenomas account for 10-15% of all Intracranial Masses
  2. Prevalence: 77 per 100,000 persons
    1. Prevalence suspected to be much higher (May incidentally occur in as many as 20% of all patients)

V. Types: Based on Hormone Secretion

  1. Prolactinoma (32 to 66% of Pituitary Adenomas)
    1. Lactotroph cell adenoma with Hyperprolactinemia
    2. Presents with Galactorrhea and Gynecomastia
    3. Most (90%) Prolactinomas are microadenomas
    4. Also suppresses LH secretion resulting in Erectile Dysfunction in men and Amenorrhea and Infertility in women
    5. More common in women 20 to 50 years old compared with men by 10:1 ratio
      1. After age 50 years, Prevalence is equal for men and women
  2. Non-functioning Adenoma (>28% of adenomas)
    1. Findings are related to mass effect (Headache, Vision change) or Hypopituitarism
  3. Growth Hormone Secreting adenomas (11-13% of adenomas)
    1. Somatotroph cell adenoma with Gigantism (prior to Growth Plate closure) or Acromegaly (adults)
    2. Presents with hand/foot/Mandible hypertrophy, Fatigue, proximal Muscle Weakness, Hypertension, Cardiomegaly or LVH
  4. ACTH Secreting adenomas (1-2%)
    1. Corticotroph cell adenoma with increased ACTH and Cushing Disease
    2. Presents with proximal Muscle Weakness, striae, central Obesity, moon facies, Hypertension, Acne Vulgaris, Hyperglycemia
  5. TSH-Secreting Adenoma (rare)
    1. Thyrotroph cell adenoma with increased TSH and Hyperthyroidism
  6. LH or FSH Secreting tumor (rare)
    1. Gonadotroph cell adenoma typically results in no symptoms unless mass effect (Headache, Vision change) or Hypopituitarism
    2. However Prolactinomas do suppress LH secretion resulting in Hypogonadism

VI. Types: Based on size

  1. Microadenoma (<10 mm)
    1. Symptomatic Prevalence 40 per 100,000 in U.S.
    2. More common in premenopausal women
  2. Macroadenoma (10 mm or larger)
    1. Symptomatic Prevalence 10 per 100,000 in U.S.
    2. More common in men and older, postmenopausal women
    3. Most likely to grow and manifest clinically

VII. Findings: Presentations

  1. Incidental finding on imaging (asymptomatic Pituitary Incidentaloma)
    1. Found in >10% of patients and Clinically Significant in 0.1% of patients
  2. Hormone increased secretion - typically only one of the following affected (see above)
    1. Galactorrhea in Prolactinoma (Hyperprolactinemia)
    2. Gigantism in children prior to Growth Plate fusion or Acromegaly in adults (increased Growth Hormone)
    3. Cushing Disease (increased ACTH)
    4. Central Hyperthyroidism (increased TSH, rare)
  3. Mass effect (delayed presentation, especially in non-functioning adenomas)
    1. Hypopituitarism (30% of Pituitary Adenomas)
    2. Headache
      1. Related to dural sheath Stretching
      2. Not correlated with Pituitary Adenoma size
    3. Vision change
      1. Initial compression
        1. Optic Chiasm compression from superior aspect
        2. Results in bitemporal Hemianopsia
      2. Later may expand into the Cavernous Sinus laterally with additional Cranial Nerve Involvement (as adenoma grows)
        1. Cranial Nerve III (Oculomotor Nerve)
        2. Cranial Nerve IV (Trochlear Nerve)
        3. Cranial Nerve VI (Abducens Nerve)
      3. Later expansion
        1. Cranial Nerve II (Optic Nerve)

VIII. Labs: Initial

  1. Serum Prolactin
    1. Serum Prolactin 100-200 mcg/L is typical for most Prolactin-Secreting Pituitary Microadenomas
    2. Serum Prolactin >250 mcg/L is highly suggestive of Prolactinoma
    3. Serum Prolactin >500 mcg/L is highly suggestive of macroprolactinoma (Test Specificity 98%, but poorly sensitive)
    4. Very large macroadenomas (>3 cm) may give false negative Serum Prolactin (Hook effect)
      1. False Negatives (Hook effect) result if Prolactin detecting Antibody is saturated by very high Prolactin levels
  2. Insulin-like growth factor 1 (IGF-1)
  3. Leutenizing Hormone (LH)
  4. Follicle Stiulating Hormone (FSH)
  5. Thyroid Stimulating Hormone (TSH)
  6. Thyroxine Level (T4 Free)
  7. 24 hour Urine Cortisol (or Late Night Salivary Cortisol or low dose Dexamethasone suppression)

IX. Imaging

  1. Brain MRI (with and without gadolinium, cone-down sella turcica) - preferred
    1. Test Sensitivity: 61-72% (for sella turcica mass)
    2. Test Specificity: 88-90% (for sella turcica mass)
    3. Also obtain if MRI not contraindicated and Pituitary Adenoma inicidentally found on CT Head
    4. Repeat Brain MRI in 6-12 months depending on lesion size
  2. CT Head
    1. Indicated if MRI contraindicated or not available
    2. Coronal sections of 1.5 mm or less

X. Differential Diagnosis: Incidentaloma

  1. Pituitary Adenoma
  2. Rathke Cleft Cyst
  3. Craniopharyngioma
  4. Pituitary Hyperplasia

XI. Evaluation: Approach

  1. Obtain all initial labs as above
    1. Even if asymptomatic and pituitary mass incidentally found on brain imaging
  2. Obtain Brain imaging (MRI preferred)
    1. If Pituitary Adenoma is suspected
  3. Ophthalmology and Endocrine referrals as below
    1. Suspected Pituitary Adenoma
    2. Consult ophthalmology for macroadenoma even if no visual changes are readily evident
      1. Detailed Visual Field testing (evaluate for bitemporal Hemianopsia)
      2. Detailed Eye Examination (Visual Acuity, fundus, ocular movement)

XII. Management

  1. Management directed by endocrinology
    1. Consult prior to starting management and in completing evaluation once Pituitary Adenoma is identified
  2. Prolactinoma
    1. Refer to endocrinology
    2. Refer to opthalmology (see above) for comprehensive Eye Exam including Visual Field exam
      1. Periodic Visual Field examinations are typically scheduled
    3. Pharmacotherapy (normalizes Prolactin in 75 to 90% of Prolactinomas)
      1. Titrate dosing to decrease tumor size, Prolactin level and improve gonadal function
        1. Consider no treatment in asymptomatic microadenomas (e.g. normal Menses)
      2. Dopamine Agonists (adult dosing)
        1. Cabergoline
          1. Preferred agent with more rapid improvement and better tolerated by patients
          2. Start 0.25 orally twice weekly
            1. Increase in 0.25 mg increments/month to a maximum of 1 mg twice weekly
        2. Bromocriptine (Parlodel)
          1. Preferred in pregnancy or desired fertility (due to longer established safety record)
          2. Start: 1.25 to 2.5 mg at bedtime
          3. Increase by 2.5 mg every 2-7 days typically to 2.5 to 15 mg daily (absolute max 40 mg)
      3. Miscellaneous medications
        1. Oral Contraceptives may be considered for Amenorrhea management
    4. Monitoring
      1. Follow Serum Prolactin levels every 3 months
      2. Periodic recheck of TSH and FSH levels
      3. Repeat MRI pituitary at one year (or earlier for significantly rising Serum Prolactin)
      4. Medications are continued for at least 2 years, and then tapered off if Prolactin levels normal and tumor size reduced
      5. Discontinue Medications in Pregnancy (although Bromocriptine may be used if needed)
        1. Microadenoma growth risk in pregnancy is very low (<3%)
        2. However, macroadenomas, esp with Optic Chiasm impingement, often require medication continuation
      6. Recurrence off medications occurs in two thirds of patients (esp. larger tumors)
        1. Monitor Prolactin every 3 months for first year off medication, then yearly
    5. Other measures in select refractory macroadenoma patients (see non-functioning adenoma below)
      1. Transphenoidal Surgery
        1. Patients disease free after surgery: 76%
        2. Risk of Hypopituitarism, Diabetes Insipidus, CSF Leak, local infection
      2. Radiation Therapy
  3. ACTH-Secreting Pituitary Adenoma
    1. Refer to endocrinology and neurosurgery
    2. Surgical management options
      1. Surgical Resection
      2. Radiation Therapy
      3. Bilateral adrenalectomy
    3. Adrenostatic Medications (decrease adrenal steroidogenesis)
      1. Titrate medication dosing to decrease tumor size, Cortisol level and improve pituitary function
      2. Metyrapone (Metopirone) 250 mg four times daily (up to 6000 mg/day maximum)
      3. Mefepristone (Mifeprex) 300 mg once daily (up to 1200 mg/day maximum)
      4. Mitotane (Lysodren) 500 mg three times daily (up to 9000 mg/day maximum)
      5. Ketoconazole
        1. No longer recommended due to Ketoconazole hepatotoxicity
  4. GH-Secreting Pituitary Adenoma
    1. Refer to endocrinology and neurosurgery
    2. Surgical management options
      1. Surgical Resection
      2. Radiation Therapy
    3. Somatostatin Analogues
      1. Titrate medication dosing to decrease tumor size, Growth Hormone and IGF-1 level and improve pituitary function
      2. Octreotide (Sandostatin) 50 mcg SQ three times daily (or depot 20 mg every 4 weeks)
      3. Lanreotide (Somatuline) 90 mg SQ every 4 weeks
    4. Growth HormoneAntagonists (reduce IGF-1 and associated Acromegaly symptoms)
      1. Pegvisomant (Somavert) 15-20 mg daily
  5. Non-Functioning Pituitary Adenoma
    1. Obtain ophthalmology Consultation for Visual Field testing and complete Eye Examination
      1. Indicated for Non-functioning Pituitary Macroadenoma (>1 cm)
    2. Neurosurgery Consultation indications
      1. Abnormal ophthalmology examination (especially Visual Field Deficit)
      2. Neurologic symptoms (e.g. Headache)
      3. Lesion increasing in size to abut the Optic Chiasm or growth to >1 cm (macroadenoma)
    3. Repeat MRI Brain in one year, then in 2-3 years
      1. Neurosurgery Consultation if meets criteroa
    4. Repeat labs (see above), then in 1-3 years (or as directed by endocrinology)
      1. If abnormal, treat as functioning adenoma as above

XIII. Complications: Pituitary Apoplexy

  1. Bleeding and swelling at Pituitary Adenoma
  2. Presents with Thunderclap Headache, Visual Field cut (bitemporal Hemianopsia) and cranial Neuropathy
  3. Lumbar Puncture with high opening pressure and CSF Red Blood Cells
  4. CT Head is often normal

XIV. References

  1. Bruehlman (2022) Am Fam Physician 106(6): 695-700 [PubMed]
  2. Freda (2011) J Clin Endocrinol Metab 96(4): 894-904 [PubMed]
  3. Hitzeman (2014) Am Fam Physician 90(11): 784-9 [PubMed]
  4. Lake (2013) Am Fam Physician 88(5): 319-27 [PubMed]
  5. Molitch (2001) Endocrinol Metab Clin North Am 30:585 [PubMed]
  6. Schlechte (2003) N Engl J Med 349:2035-41 [PubMed]

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