Pituitary Adenomas, Prolactinomas, & Sheehan Syndrome PDF

Pituitary Adenoma, Prolactinoma, Sheehan Syndrome and More EMILY BODFISH, MPAS, PA-C PA 511- CLINICAL MEDICINE I EMORY & HENRY UNIVERSITY  Pituitary Function Pituitary Tumors including Pituitary Adenoma Other pituitary conditions Pituitary Apoplex...

Pituitary Adenoma, Prolactinoma, Sheehan Syndrome and More EMILY BODFISH, MPAS, PA-C PA 511- CLINICAL MEDICINE I EMORY & HENRY UNIVERSITY  Pituitary Function Pituitary Tumors including Pituitary Adenoma Other pituitary conditions Pituitary Apoplexy Empty Sella Outline Sheehan Syndrome Acromegaly Dwarfism Diabetes Insipidus Physiology Review Function of the Pituitary Gland  Anterior Pituitary Gland produces  Luteinizing Hormone (LH) & Follicle- Stimulating Hormone (FSH)  Prolactin  Thyroid Stimulating Hormone (TSH)  Adrenocorticotropic Hormone (ACTH)  Growth Hormone (GH) Physiology of the Posterior Pituitary Gland  Posterior Pituitary Gland produces:  Oxytocin  Important in childbirth & lactation by moving milk into the breast  ADH  Important for maintaining water balance  Central Diabetes Insipidus  SIADH (Syndrome of inappropriate ADH) Pituitary Tumors  Pituitary Tumors Pituitary Tumors make of 10% of all intracranial tumors Most are benign Tumor growth in the confined sellar & suprasellar regions can cause serious neurologic damage Local Anatomic Structures Affected by Mass of the Sella  Pituitary Tumors  22% population has a pituitary mass  By imaging + autopsy  Usually clinically silent  16% population has a pituitary adenoma  By imaging + autopsy  Almost all are clinically silent  Most common pituitary mass  Adenoma Benign tumor of glandular tissue Hyperplasia Enlargement of tissue or organ Non-adenoma Benign Tumor Pituitary Mass Craniopharyngioma – derived from pituitary embryonic tissue Differential Malignant Tumor Lymphoma, germ cell tumors, carcinoma, metastatic Inflammatory/Infection Abscess, lymphocytic hypophysitis Vascular Pituitary apoplexy (compromised blood flow), aneurysm   Pituitary Adenoma: A benign tumor of the anterior pituitary  Most common mass of the pituitary  Can cause pituitary hypersecretion or hyposecretion  Epidemiology: 15% of all intracranial neoplasms Pituitary Adenoma  Prevalence: 80/100,000 Epidemiology  At autopsy, up to 1/4th of all pituitary glands harbor an unsuspected microadenoma ( men  Pituitary Mass/Adenoma: Clinical Features  Asymptomatic→ “Incidentaloma”- incidental finding on MRI or CT  Neurologic Manifestations (Mass Effect)  Headache (common)  Visual Disturbance (Optic chiasm compression)  Mental status changes Bitemporal Hemianopsia  CN abnormalities (dural sinus)  Vomiting  Papilledema  Pituitary apoplexy  Prolactinoma: Hypogonadism Oligo/amenorrhea, galactorrhea, infertility, decreased libido Males: Decreased libido and impotence Post-menopausal females & males – Sx usually related to mass effect of tumor Pituitary GH secreting: Adenoma: Acromegaly, gigantism Hypersecretion ACTH secreting: of Hormones Adrenal hyperplasia→ Cushingoid features Wt. gain, hirsutism, amenorrhea, decreased libido, Clinical Features unexplained osteopenia TSH secreting: Goiter, palpitations, tremor etc. Lymphocytic hypophysitis: Mass effect & adrenal insufficiency  When to Evaluate for Pituitary Mass Consider evaluation for pituitary mass when there is: Hypersecretion of Vision changes & Complex - Hypopituitarism 1 or more anterior headache(mass hormonal excess (slow onset) pituitary hormones effect) &/or deficiencies  Choose labs based on Sx of hormonal excess or insufficiency: IGF-1 Prolactin TSH & Free T4 AM Cortisol (8 am) Pituitary Mass ACTH LH & FSH, estradiol (females) & testosterone (males) Laboratory Consider: Evaluation CBC & UA ESR & CRP Serum Na Alpha-fetoprotein & HCG (suspected germ-cell tumor) Auto-antibodies Surgical Bx  MRI – T1 weighted with & without gadolinium = Gold Standard Allows precise visualization of the pituitary gland with clear delineation of the surrounding tissue Pituitary Mass Determines size: Imaging < 1 cm = Microadenoma ≥ 1 cm = Macroadenoma Differentiates: Adenoma vs. hyperplasia Mass vs. inflammation vs abscess Hemorrhage vs aneurysm  Skull radiograph May see enlargement or Pituitary Mass distortion of the sella if tumors > 10 mm in diameter Imaging Suprasellar calcification suggests a craniopharyngioma CT may show some macroadenomas Pituitary Adenoma Pituitary Adenoma Pituitary Adenoma Treatment  Three primary goals in treatment of pituitary adenomas:  Reducing hormone hypersecretion & its clinical manifestations  Decreasing tumor size to improve symptoms of mass effect  Correcting hormone deficiencies   Prolactinoma  Diagnosis: Basal prolactin level of > 200 ng/mL; brain MRI  Medical Treatment Prolactinoma Dopamine agonists Dx & Treatment (bromocriptine & cabergoline) decrease prolactin levels Can reduce tumor size & stop the galactorrhea, return menses to normal Large invasive prolactinoma successfully treated with cabergoline. A–B. Prolactin-secreting macroadenoma in a 32 y/o male measuring 5.6×6.9 cm invading the skull base. PRL level was 122,260 μg/L. 4 days after cabergoline was started, PRL was 10,823 μg/L & dropped to 772 μg/L after 3 weeks. C–D. Substantial tumor regression after 40 months of treatment, with PRL levels stable at 25 μg/L.  Medical GH & ACTH management of GH Secreting & ACTH secreting Tumor tumors is less effective Treatment than prolactinomas Surgery for these tumors is preferred treatment Treatment  Requires accurate diagnosis of lesion type  Most are benign & slow growing  If resection required  Transsphenoidal is desired approach  Transfrontal Resection may be necessary:  For tumors with optic chiasm compression or those that extend far outside the sella turcica  Radiation Therapy – Used alone or in conjunction with surgery may decrease the size of pituitary tumors & decrease hormone production Management of Incidental Pituitary Adenoma  When a pituitary mass is found incidentally, investigation must determine Is it causing mass effect? Is it secreting excess hormone? If it grows, will it cause problems in the future?  Management of Incidental Pituitary Adenoma  If there is no mass effect on MRI, & the tumor is not secreting excess hormone, repeat MRI in 6 months for macroadenoma & 12 months for microadenoma to assess for further growth  If no growth noted at the 6-12 month follow up, repeat MRI every 1-2 years for 3 years total (then intermittently)  Biochemical testing not recommended unless tumor enlarges, or the patient develops symptoms Hypopituitarism  Null Cell pituitary adenoma Growth of the nonsecreting tumor can cause destruction of the adjacent normal gland Sheehan Syndrome Empty Sella Syndrome Hypopituitarism Condition due to an incompetent diaphragm sella that allows herniation of arachnoid into the sella turcica The herniated arachnoid presses on the pituitary gland & it will atrophy Pituitary Apoplexy Other: Surgery, radiation, inflammatory reactions, DIC, sickle cell, necrosis from increased ICP  Sheehan’s Syndrome  Infarction of the anterior pituitary gland during childbirth → Pituitary gland necrosis → hypopituitarism  This is due to maternal hemorrhage & hypotension resulting in hypoperfusion  Incidence: Improved in the past 50 years due to better delivery & postpartum care  Globally about 1/100,000 live births  Rare in industrialized nations due to better care  Sheehan Syndrome Pathophysiology  Pregnancy causes the pituitary gland to increase in size & the number of prolactin secreting cells  Despite the increase in size of the anterior pituitary, the blood supply of the pituitary is derived from the low pressure hypothalamic-hypophyseal portal- venous system & does not increase → vulnerable to ischemic injury  If hypotension occurs & blood flow to the anterior pituitary is compromised (obstetrical hemorrhage) → pituitary infarction → hypopituitarism  Necrosis of the gland can occur  Loss of all pituitary hormones = 56% Sheehan 44% selective loss of Syndrome pituitary hormones GH def. most common GH secreting cells located on periphery of pituitary gland  Hypopituitarism: Severe Development of lethargy, anorexia, weight loss CLUE: These patients will not lactate due to prolactin deficiency Patients who may have Sheehan syndrome should be emergently tested & treated for secondary cortisol deficiency Sheehan Other hormone deficiencies can be evaluated 6 weeks after delivery Syndrome Long term symptoms may develop slowly over months-years & mild hypopituitarism can go unrecognized for years Eventual development of a small pituitary within a sella of normal size, sometimes read as an "empty sella" on MRI Treatment Lifelong hormonal replacement No treatment available to induce lactation  Diagnosed when normal pituitary gland is not seen or is excessively small with MRI It is a radiologic finding, not a distinct clinical condition Causes: Empty Sella Increased CSF entering & enlarging sella Secondary to tumor Syndrome Previous pituitary surgery, radiation, or infarction Congenital Can be a long-term consequence of Sheehan Syndrome Evaluation: To determine if there is a cause or if patient has S/S of pituitary hormone deficiency Repeat imaging is usually not necessary  Pituitary Apoplexy  Acute hemorrhage into the pituitary gland often at site of preexisting adenoma  Can cause acute pituitary hormone deficiency or mass effect (from rapid expansion of the sellar contents due to bleeding)  Symptoms: Severe headache, visual loss, diplopia, hypopituitarism.  Imaging reveals pituitary macroadenoma  Endocrine & neurosurgical emergency  Acute ACTH deficiency is common & can be life-threatening  If suspected - stress dose glucocorticoid emergently  Surgical decompression of the pituitary is often performed in cases with severe or progressive impairment of vision or neurologic symptoms  Other tx that can be used = high doses of & administration of a dopamine agonist to reduce adenoma size Infiltrative & Inflammatory Pituitary Disorders  Inflammatory & infiltrative disorders can also affect pituitary gland:  Lymphocytic hypophysitis  Sarcoidosis  Hemochromatosis  Amyloidosis  Lymphoma  TB  Pituitary gland is also enlarged diffusely in untreated primary hypothyroidism & during pregnancy