Pituitary Adenoma: A Two Part Approach I. A General Overview II. Hypersecretion/Incidentaloma Jose Manuel Calero, MD
Outline I. General Overview 1) Definition 2) Classification Cell origin Hormone Secreted Size 3) Anatomy/Physiology 4) Pathophysiology 5) Clinical Presentation Hormonal Neurological Incidental 6) General Diagnostic and Treatment Approach
Outline II. Hypersecretion/Incidentaloma 1) Hypersecretion/Pituitary Adenoma Hyperprolactinemia Acromegaly Cushing Disease 2) Incidentaloma III. Summary IV. Clinical Vignettes V. Question/Answer
Definition Pituitary Adenomas are the most common type of noncancerous tumors that occur in the pituitary gland These benign adenomas account for 10%- 15% of all intracranial masses
Classification 1) Cell Origin 2) Hormone Secreted 3) Size Microadenoma Macroadenoma
Pituitary Anatomy
Pituitary Physiology
Pathophysiology 1) Mass Effect 2) Hypersecretion or Diminished Inhibition
Clinical Presentation Pituitary Adenomas clinically present in three different ways: 1) Hormone Hypersecretion or Deficiency 2) Neurological: Mass Effect 3) Incidentally on Imaging
1a) Hormone Hypersecretion The most common types of hypersecretion are: Prolactin/Hyperprolactinemia GH/Acromegaly ACTH/Cushing Disease
1b) Hormone Deficiency Interference of normal hormone secretion Direct Compression Inhibition of pulsatile secretion of LH
2) Neurological: Mass Effect Headaches No Correlation to Tumor Size Dural Sheath Visual Field Deficits (Superior Expansion) Correlation to Tumor Size Bitemporal hemianopsia Cranial Nerves (Lateral Expansion) Optic Nerve Compression
3) Incidentally on Imaging Increased use of CT and MRI have identified many pituitary lesions that otherwise might not have been detected
Diagnostic Approach The diagnostic approach to a suspected pituitary adenoma depends on the presenting symptoms
Diagnostic Approach Hormonal Symptoms Patient who presents with symptoms of hormone excess likely has a functioning adenoma These patients should have an endocrine evaluation
Diagnostic Approach Neurologic Symptoms If a pituitary mass is suspected, MRI is the best initial imaging study 61% to 72% sensitive and 88% to 90% specific for sellar masses Visual field testing and ophthalmologic exam
Treatment Approach The three primary treatment goals for Pituitary Adenomas: 1. Reducing Hypersecretion and its clinical manifestations 2. Decreasing Tumor Size/Mass Effect 3. Correcting Hormone Deficiencies
IIa. Hormone Hypersecretion: Clinical Syndrome 1. Hyperprolactinemia/prolactin 2. Acromegaly/GH 3. Cushing Disease/ACTH
1) Hyperprolactinemia (lactotroph) Definition: The presence of abnormally high levels of prolactin in the blood
Hyperprolactinemia Symptoms: General: galactorrhea, decrease in libido, infertility Men: gynecomastia, impotence Premenopausal women: oligomenorrhea/ amenorrhea
Hyperprolactinemia Signs: Gynecomastia Hypogonadism (testicular atrophy/breast shrinkage/hair loss) Morbidity: Osteoporosis
Hyperprolactinemia Diagnostic Test: Serum prolactin levels Treatment: The majority of prolactinomas can be managed with a dopamine agonist, bromocriptine, or cabergoline
Underwriting Pearls Microprolactinoma Diameter <10mm and prolactin <200 Macroprolactinoma Diameter > or = 10mm and prolactin 200-500 Extrasellar Prolactinoma Extends outside the pituitary and prolactin >500
2) Acromegaly (Somatotroph) Definition: A chronic disease of adults marked by enlargement of the bones of the extremities, face, and jaw that is caused by over-activity from a GH secreting pituitary adenoma
Acromegaly Symptoms Increase in hand and foot size Change in facial features (large mandible) Voice deepening Carpal tunnel symptoms Hyperhidrosis Fatigue Proximal muscle weakness Decrease in libido Menstrual changes
Acromegaly Signs: Hypertension Coarse facial features Visual field changes Visceromegaly Hypercalciuria Goiter Left ventricular hypertrophy Cardiomyopathy
Acromegaly Morbidity and Mortality: Cardiac disease Diabetes Sleep apnea Increased risk of colon cancer Goiter
Acromegaly Diagnostic test: Serum Insulin-like growth factor 1 levels (Somatomedin C) Oral glucose suppression test followed by GH measurement after 2 hours MRI
Acromegaly Treatment: Transsphenoid resection is the preferred treatment Somatostatin analogues: Octreotide and Lanreotide Growth hormone receptor antagonist: Somavert
Underwriting Pearls Favorable outcome with: Surgical removal with no residual tumor Normal BP Normal ECG/ECHO GH level <2ng/ml IGF-1 level is normal for age and sex
3) Cushing Disease (Corticotroph) Definition: A rare condition caused by excess corticosteriod hormones in the body, characterized by obesity of the trunk and face, HTN, striated skin, and loss of calcium from the bones
Cushing Disease Symptoms: Weight gain Labile mood Proximal muscle weakness Skin and facial feature changes Depression Hirsutism Decrease in libido Menstrual changes
Cushing Disease Signs: Thin skin Striae/bruising Central obesity Moon facies Plethora Hypertension Acne Glucose intolerance Neutropenia Lymphocytopenia Eosinophilia
Cushing Disease Morbidity and Mortality: Diabetes mellitus Cardiac disease Osteoporosis
Cushing Disease
Cushing Disease Diagnostic tests: 24- hour urine free cortisol Late-night salivary cortisol Dexamethasone suppression
Cushing Disease Treatment: Surgical resection of pituitary tumor Adrenostatic medications Ketoconazole Metyrapone Mifepristone (Mifeprex) Mitotane (Lysodren) Radiation Therapy Bilateral Adrenalectomy
Underwriting Pearls Cushing Disease is due an adenoma or hyperplasia of the pituitary gland Prognosis is favorable with treatment and resolution of high cortisol levels
IIb. Incidentaloma Definition: A tumor found by coincidence without clinical symptoms or suspicion Symptoms: None Signs: None
Incidentaloma Diagnostic: Discovered incidentally on CT or MRI of head Diagnostics should be geared toward determining if the mass is functioning or nonfunctioning Treatment: Biochemical monitoring Repeat imaging
Summary Pituitary Adenomas are the most common type of pituitary disorder Prolactinomas and Incidentalomas comprise the majority Underwriters should be aware of some general clinical features of adenomas (both hormonal and neurological) Pituitary Adenomas should be underwritten by evaluating: Which hormones are compromised How complete the treatment is, and If there are any permanent consequences after surgery
Clinical Vignette #1 42 yr old male presents with decreased libido, ED, and headaches He reports no weight change, gynecomastia, or other symptoms He takes no meds and his testicular size is decreased Prolactin levels are 647ug per liter (nl <15) MRI shows a 2.5 by 1.5 by 2.0 cm sellar mass that is 5mm below the optic chiasm
Clinical Vignette #2 A 25 year old woman with history of chronic non-specific headaches MRI was performed and showed a 5-mm lesion in the pituitary gland consistent with a microadenoma Except for headaches, the patient is asymptomatic She has normal menses, no galactorrhea, and normal physical exam and labs
Clinical Vignette #3 47 yr old male with history of arthritis of knees, hips, and soft-tissue swelling, and excessive swelling He noticed progressive enlargement of hands and feet He has been taking antihypertensive medication for the past 3 years On physical examination, he has coarse facial features with bulging lower jaw and prominent supraorbital ridges The tongue is enlarged and the fingers are thickened His wife complains that he frequently snores
Clinical Vignette #3
Clinical Vignette #3 (IGF-1) concentration of 560 micrograms/l (nl for age 120-235 micrograms/l) Plasma growth hormone level of 15 micrograms/l (nl 1-9 ng/ml for males) MRI showed a 14mm pituitary mass in the sella turcica region
Question & Answer