PITUITARY DISORDERS 5.1 Pituitary Adenoma A 37-year-old woman presented with headaches and blurry vision. She was found to have a bitemporal hemianopsia on examination. Images 5.1A–5.1C: Postcontrast axial, sagittal, and coronal T1-weighted images demonstrate a large complex multilobulated mass in the sellar/suprasellar area. The sella turcica is massively expanded. The tumor shows the characteristic “snowman” appearance. Image 5.1D: Postcontrast sagittal T1-weighted image of a normal MRI. The pituitary gland (yellow arrow) and stalk normally enhance and are seen below the optic chiasm (red arrow). Table 5.1.1 Characteristics of Hormonally Active Tumors Images 5.1E–5.1H: Non-contrast axial, coronal, and sagittal CT images demonstrate a large complex multilobulated mass in the sellar/suprasellar area. The sella turcica is massively expanded. Images 5.1I–5.1L: Axial fluid-attenuated inversion recovery, coronal T2-weighted, and postcontrast axial and coronal T1-weighted images demonstrate a large pituitary adenoma. It is hyperintense on T2-weighted imaging and can be seen encasing the carotid arteries (red arrows). Table 5.1.2 Differential Diagnosis of a Sellar Mass Pituitary adenoma Rathke’s cleft cyst Craniopharyngioma Meningioma Germinoma Chordoma Carcinoma Epidermoid, dermoid cyst, and teratomas Pituitary sarcoid Aneurysm Abscess Hypothalamic hamartoma, glioma, and gangliocytoma Metastases Histiocytosis X Infiltrative lesions (hereditary hemochromatosis) Lymphocytic hypophysitis Image 5.1M: Gross specimen demonstrates a pituitary adenoma (image credit WikiDocs, www.wikidoc.org/index.php/File:Gross_pituitary_adenoma_A..jpg). Image 5.1N: Hematoxylin and eosin stain: Left image shows normal pituitary gland. Note the heterogeneity of the cells, arranged in acinar clusters interspersed with sinusoids (black arrowheads). There is a mixture of acidophils, basophils, and chromophobe cells. The right image shows pituitary adenoma with sheets of monomorphous cells and loss of acinar pattern (image credit Dr. Seema Shroff, Fellow, Neuropathology, NYULMC). Image 5.1O: Pituitary glandular as well as adenoma cells are positive for chromogranin and synaptophysin (neuronal markers). Image 5.1P: Normal pituitary acini are outlined by reticulin; however, the acinar pattern is lost in adenomas, and they show sheet like growth. Images 5.1Q and 5.1R: Pituitary adenomas may be silent or secrete hormones. Markers for growth hormone and follicle stimulating hormone are shown in two separate patients. 1. Syro LV, Rotondo F, Ramirez A, et al. Progress in the diagnosis and classification of pituitary adenomas. Front Endocrinol (Lausanne). June 2015;6:97. 2. Oldfield EH, Merrill MJ. Apoplexy of pituitary adenomas: the perfect storm. J Neurosurg. June 2015;122(6):1444–1449. 3. Melmed S. Pituitary tumors. Endocrinol Metab Clin North Am. March 2015;44(1):1–9. 4. Melmed S. Pathogenesis of pituitary tumors. Nat Rev Endocrinol. May 2011;7(5):257–266. 5.2 Craniopharyngioma A 20-year-old man developed gradual, but severe visual loss and also failed to develop secondary sexual characteristics. Images 5.2A–5.2C: Postcontrast sagittal T1-weighted, axial T2-weighted, and non-contrast axial T1-weighted images demonstrate an enormous, hyperintense cystic pituitary mass, which has expanded the sella turcica, with mass effect on the brainstem and both medial temporal lobes. Image 5.2D: Gross pathology of a craniopharyngioma (image credit The Armed Forces Institute of Pathology). Table 5.2.1 Characteristics of Common Subtypes of Craniopharyngiomas Adamantinomatous Papillary Frequency More common Less common Age of onset Occurs at a younger age but also seen in adults Occurs typically in adults MRI brain Complex multilobular, and commonly calcified and cystic Calcification is less common Commonly solid, well circumscribed Genetic Mutation in β-catenin present in 70% of cases of this subtype Lack of β-catenin mutation Histology Complex epithelial pattern with peripherally palisading cells and wet keratin, calcification, foreign body giant cells, and cholesterol clefts, keratinized “ghost cells” Composed of simple squamous epithelium and fibrovascular islands of connective tissue; keratin nodules are not seen Prognosis High rates of recurrence are seen within the first five years and usually after subtotal or partial resection Readily resected surgically and recurs less often Image 5.2E: Adamantinomatous craniopharyngioma showing sheets of keratinized cells of stratified squamous epithelium with a palisading basal layer with “piano key” appearance. The epithelium may be more flattened in cystic cavities with loose matrix (stellate reticulum) (image credit Dr. Seema Shroff, Fellow, Neuropathology, NYULMC). 1. Fernandez-Miranda JC, Gardner PA, Snyderman CH, et al. Craniopharyngioma: a pathologic, clinical, and surgical review. Head Neck. July 2012;34(7):1036–1044. 2. Kuratsu J, Usio Y. Epidemiological study of primary intracranial tumor in childhood. A population based survey in Kumamoto Prefecture, Japan. Pediatr Neurosurg. 1996;25:946–50. 3. Izuora GI, Ikerionwu S, Saddeqi N, IIoeje SO. Childhood intracranial neoplasms Enugu, Nigeria. West Africa Journal of Med. 1989;8:171–174. 4. Zada G, Lin N, Ojerholm E, Ramkissoon S, Laws ER. Craniopharyngioma and other cystic epithelial lesions of the sellar region: a review of clinical, imaging, and histopathological relationships. Neurosurg Focus. April 2010;28(4):E4. 5. Hoffman HJ, De Silva M, Humphreys RP, et al. Aggressive surgical management of craniopharyngiomas in children. J Neurosurg. 1992;76:47–52. 6. Samii M, Tatagiba M. Surgical management of craniopharyngiomas: a review. Neurol Med Chir. (Tokyo). 1997;37:141–149. 7. Samii M, Samii A. Surgical management of craniopharyngiomas. In: Schmidek HH, ed. Schmidek and Sweet Operative Neurological Techniques: Indications, Methods, and Results. 4th ed. Philadelphia, PA: WB Saunders; 2000:489–502. 8. Lin A, Bluml S, Mamelak AN. Efficacy of proton magnetic resonance spectroscopy in clinical decision making for patients with suspected malignant brain tumors. J Neurooncol. 1999;45:69. 9. Thiel A, Pietrzyk U, Sturm V, et al. Enhanced accuracy in differential diagnosis of radiation necrosis by positron emission tomography-magnetic resonance imaging coregistration: technical case report. Neurosurgery. 2000;46:232. 5.3 Rathke’s Cleft Cyst A 34-year-old woman developed headaches and “blurry vision.” She was found to have bitemporal hemianopsia on exam. Images 5.3A–5.3D: Axial T2-weighted and postcontrast axial, coronal, and sagittal T1-weighted images demonstrate a large well-defined sellar/suprasellar T1-bright mass. The bulk of the lesion demonstrates T2-hypointense signal and T1-hyperintense suprasellar mass consistent with a giant Rathke’s cleft cyst. Images 5.3E and 5.3F: Axial T2-weighted and postcontrast sagittal T1-weighted images demonstrate a sellar mass with a nodule that is hyperintense on T1-weighted images and hypointense on T2-weighted images (red arrows). 1. Larkin S, Karavitaki N, Ansorge O. Rathke’s cleft cyst. Handb Clin Neurol. 2014;124:255–269. 2. Trifanescu R, Ansorge O, Wass JA, Grossman AB, Karavitaki N. Rathke’s cleft cysts. Clin Endocrinol (Oxf). February 2012;76(2):151–160. 3. Han SJ, Rolston JD, Jahangiri A, Aghi MK. Rathke’s cleft cysts: review of natural history and surgical outcomes. J Neurooncol. April 2014;117(2):197–203. 5.4 Lymphocytic Hypophysitis A 19-year-old woman developed a severe headache and vision loss postpartum. Images 5.4A–5.4C: Postcontrast axial, coronal, and sagittal T1-weighted images demonstrate enlargement and enhancement of the pituitary gland (red arrows) and stalk (blue arrows). This creates a “pear-shaped” lesion. Image 5.4D: Postcontrast sagittal T1-weighted image demonstrates enlargement and enhancement of the anterior pituitary gland and stalk (red arrow) with sparing of the posterior pituitary (yellow arrow). 1. Molitch ME, Gillam MP. Lymphocytic hypophysitis. Horm Res. 2007;68(Suppl. 5):145–150. 2. Rivera JA. Lymphocytic hypophysitis: disease spectrum and approach to diagnosis and therapy. Pituitary. 2006;9(1):35–45. 5.5 Pituitary Apoplexy A 63-year-old woman presented with the sudden onset of a severe headache along with confusion and blurry vision. On exam she was lethargic but able to answer simple questions. She had bilateral abducens nerve palsies. Images 5.5A–5.5D: Axial CT image and axial, sagittal, and coronal T1-weighted images demonstrate acute blood products (red arrow) in the pituitary gland in a patient with pituitary apoplexy. 1. Briet C, Salenave S, Bonneville JF, Laws ER, Chanson P. Pituitary apoplexy. Endocr Rev. September 2015;36(6):622–645. doi:10.1210/er.2015-1042. 2. Briet C, Salenave S, Chanson P. Pituitary apoplexy. Endocrinol Metab Clin North Am. March 2015;44(1):199–209. 3. Piantanida E, Gallo D, Lombardi V, et al. Pituitary apoplexy during pregnancy: a rare, but dangerous headache. J Endocrinol Invest. September 2014;37(9):789–797.
Case History
Diagnosis: Pituitary Adenoma
Introduction
Pituitary adenomas are slow-growing, benign tumors that arise from one of the cell types in the anterior lobe of the pituitary gland. They are the most common tumor in the sellar region, and comprise about 10% of primary intracranial tumors.
Macroadenomas are larger than 10 mm, while microadenomas are smaller than this. They are often incidental findings.
Clinical Presentation
Though the majority of pituitary tumors do not secrete hormones, most patients nonetheless present due to endocrine dysfunction. There is no relationship between the size of a tumor and the probability of it being hormonally active. The three most common hormonally active tumors are presented in Table 5.1.1.
In addition to causing endocrine dysfunction via the oversecretion of pituitary hormones, any sellar or suprasellar mass may present with panhypopituitarism if there is compression of the pituitary gland or stalk. Symptoms of panhypopituitarism include lethargy, growth failure, diabetes insipidus, hypogonadism, and hypoadrenalism.
Tumors that are not hormonally active present due to mass effect on adjacent brain structures. Such tumors present with headaches, cranial neuropathies if there is involvement of the cavernous sinus, or a bitemporal hemianopsia if there is compression of the optic chiasm. Less commonly, there may be monocular visual loss if there is involvement of the optic nerve or a homonymous hemianopsia if the optic tract is affected distal to the optic chiasm. Very large tumors may cause personality changes if there is involvement of the frontal lobe, or seizures if there is involvement of the medial temporal lobe. In rare cases, patients may suffer pituitary apoplexy with potentially devastating consequences.
Radiographic Appearance and Diagnosis
The evaluation of a patient with a suspected pituitary disorder should include:
Neuroimaging: On CT, adenomas appear as hyperdense masses emerging from the sella turcica with upward deviation of the optic chiasm. Computed tomography angiography is extremely useful in preoperative planning for macroadenomas. The relationship of the tumor to the anterior cerebral arteries and optic nerve is critical to the surgeon. MRI brain sagittal, coronal, and axial images with and without contrast with attention to sella turcica can help differentiate a sellar mass (Table 5.1.2).
Adenomas are typically isodense to gray matter on both T1-weighted images and T2-weighted images, though larger lesions may have a more heterogeneous appearance due to hemorrhage, cystic changes, or necrosis. They enhance homogenously with the addition of contrast. The sella turcica is expanded, and large tumors expand after emerging from its confines, creating the “snowman sign.” There is often invasion of the cavernous sinus, and the tumor encases the internal carotid artery.
Visual field testing: Formal visual testing is important even on patients with grossly intact visual fields.
Endocrinological evaluation: Patients should be screened carefully for endocrine dysfunction and electrolyte disturbances. Specific tests include prolactin level, thyroid function tests, 24-hour urine cortisol, follicle-stimulating hormone (FSH), and lymphocytic hypophysitis (LH) levels, growth hormone (GH) assays, and insulin-like growth factor (IGF) to screen for GH irregularities.
Ultimately, pathological examination is needed to confirm the diagnosis.
Treatment
Symptomatic tumors are treated primarily with surgery, which is curative in most cases. The transsphenoidal approach using endoscopic techniques is preferred, though larger and more invasive adenomas may require a transfrontal resection. Risks of transsphenoidal surgery include postoperative infarction and hemorrhage, diabetes insipidus, fluid and electrolyte disturbances, cerebrospinal fluid (CSF) rhinorrhea, meningitis, and cranial nerves III, IV, VI palsies.
Medically, therapy is an option in hormonally active tumors. Dopamine agonists such as bromocriptine are used in tumors that secrete prolactin. In tumors that secrete GH or TSH, somatostatin analogues are used.
Small tumors can be effectively targeted by a focused beam of radiation therapy (RT) referred to as “stereotactic radiosurgery.” There should be at least 5 mm separation between the tumor and chiasma/optic nerve before considering radiosurgery as an option. In certain cases, adjunctive, stereotactic radiotherapy is used, especially in the case of nonfunctioning tumors that are unable to be completely resected.
Patients with panhypopituitarism are treated with hormone replacement therapy.
References
Case History
Diagnosis: Craniopharyngioma
Introduction
Craniopharyngiomas are slow-growing, WHO grade I tumors, which account for 2% of all intracranial neoplasms and 5% to 10% of childhood intracranial neoplasms. They arise from the cells along the pituitary stalk that are derived from remnants of Rathke’s pouch and the craniopharyngeal duct.
The peak incidence is in children aged 5 to 15 years. A second peak occurs later in life, between ages 50 and 60 years. There is no sexual predilection, but these tumors are more common in Africa, the Far East, and Japan.
Clinical Presentation
The common presenting symptoms of these tumors are:
Visual disturbances due to compression of the optic chiasm; more common in adults than children
Endocrine dysfunction due to compression of the pituitary or hypothalamus; these presentations include short stature, delayed puberty in children, amenorrhea, sleep disturbances, changes in appetite and weight, and diabetes insipidus
Cranial nerve dysfunction
Symptoms of increased intracranial pressure
Cognitive and personality changes due to extension in the frontal or temporal lobes
Chemical meningitis if there is rupture of the cyst
Radiographic Appearance and Diagnosis
The appearance of craniopharyngiomas varies on MRI; these are typically multilobular, multicystic lesions in the suprasellar/intrasellar region, which are hypointense on T1-weighted images and hyperintense on T2-weighted images. The appearance depends on the exact components of the fluid in the cyst. The cyst is typically hyperintense on T2-weighted images but has a highly variable signal on T1-weighted images. With the administration of contrast, there is often enhancement around the edge of the cyst as well as enhancement of any solid components.
Calcifications are common in the cyst wall and/or solid component. They are best seen on CT scans. Fine flaky calcification suggests fast-growing tumors, whereas dense calcification is seen in slowly growing craniopharyngiomas.
It is rare to find craniopharyngiomas completely confined to the intrasellar compartment. About 70% are combined suprasellar and intrasellar. They can extend anteriorly to the prechiasmatic cistern and subfrontal spaces, posteriorly into the prepontine and interpeduncular cisterns, cerebellopontine angle, third ventricle, posterior fossa, and foramen magnum, and laterally toward the subtemporal spaces.
Classification: These tumors have been classified based on their location, vertical extension, or subtypes. Hoffman et al classified these tumors as intrasellar, prechiasmatic, and retrochiasmatic. Samii and Samii et al divided these tumors into five grades based on their vertical projection as follows:
Grade I: intrasellar or infradiaphragmatic
Grade II: localized to the cistern with or without an intrasellar component
Grade III: reaches the lower half of the third ventricle
Grade IV: reaches the upper half of the third ventricle
Grade V: tumor dome reaches the septum pellucidum or lateral ventricles
Craniopharyngioma comprises three clinically, histologically, and genetically distinct subtypes as follows (Table 5.2.1):
Adamantinomatous (most common)
Papillary
Mixed (15%)
Complete endocrinological evaluation is necessary to uncover hypopituitarism, particularly GH, cortisol, and thyroid hormone.
Treatment
Radical surgery is the treatment of choice in most cases, as craniopharyngiomas are benign tumors and many affected patients are young. The surgical approach is influenced by the tumor location with respect to sella, chiasm, and third ventricle. Anterior midline (transsphenoidal, subfrontal), anterolateral (pterional, orbitozygomatic), transpetrosal, subtemporal, intraventricular (transcallosal–transventricular, transcortical–transventricular translamina terminalis), or a combination of these approaches is used to tackle such tumors. There have been anecdotal case reports of craniopharyngioma seeding along the surgical access route and through the CSF pathways. Cystic lesion aspiration with implantation of an Ommaya reservoir or intracavitary instillation of a radioisotope (brachytherapy) may be employed in treating cystic craniopharyngiomas.
Radiation therapy (RT) can be used to treat patients with residual disease who have undergone a partial surgical resection or to treat disease that has recurred following what was initially thought to be a gross total resection. Fractionated stereotactic radiosurgery (FSRT), stereotactic radiation therapy (SRT), proton beam RT, and intensity modulated RT (IMRT) are various currently employed RT techniques. In a retrospective series, the recurrence rate was significantly higher in patients receiving ≤54 Gy compared with higher doses (50% versus 15%). The rates of radiation-induced endocrine, neurological, and vascular sequelae are low with doses less than 61 Gy.
Hormonal replacement therapy is needed for patients with endocrinological dysfunction; thyroid supplements for hypothyroidism, intranasal and intravenous supplementation with desmopressin in patients with diabetes insipidus. High doses of hydrocortisone may be required to treat symptoms of hypoadrenalism postoperatively.
Tumor recurrence is a very common phenomenon even after complete resection and postoperative radiotherapy. To avoid adhesions from the previous surgery, a different surgical approach can be selected.
References
Case History
Diagnosis: Rathke’s Cleft Cyst
Introduction
A Rathke’s cleft cyst (also known as a pars intermedia cyst) is a benign, fluid-filled cyst typically located in the center of the pituitary gland. They are congenital malformations due to incomplete development of Rathke’s pouch.
Unlike craniopharyngiomas, which are more common in men, Rathke’s cleft cysts are twice as common in women.
Clinical Presentation
Most often, they are incidental findings. Large cysts may extend into the suprasellar cistern where they can present with visual disturbances, endocrine dysfunction, and headaches. The most common endocrine disturbances are diabetes insipidus and increased prolactin levels due to compression of the pituitary stalk.
Radiographic Appearance and Diagnosis
The cyst arises in the sella turcica with slightly more than half extending into the suprasellar region. The MRI signal depends on the protein contents of the cyst. On T1-weighted images, half are hyperintense and half are hypointense. On T2-weighted images, most are hyperintense, but about 25% are hypointense. They do not enhance with the administration of contrast, other than a thin rim on the periphery.
An intracystic nodule that is hyperintense on T1-weighted images and hypointense on T2-weighted images is highly specific and can be found in up to 80% of cases.
Treatment
Symptomatic cysts can be drained surgically.
References
Case History
Diagnosis: Lymphocytic Hypophysitis
Introduction
Lymphocytic hypophysitis (LH) is an autoimmune disease that is characterized by lymphocytic infiltration of the hypophysis or infundibulum. It is pathologically related to orbital pseudotumor and Tolosa–Hunt syndrome. It is a rare cause of pituitary hypofunction.
It classically affects pregnant young women in third trimester or the postpartum period, but can be seen in both men and women at any age.
Clinical Presentation
Patients present with headache, the most common symptom, and hypopituitarism (fatigue, decreased libido, amenorrhea). Large lesions may cause visual disturbances due to mass effect on the optic chiasm or cranial neuropathies due to involvement of the cavernous sinus.
Involvement of the posterior pituitary presents with diabetes insipidus.
Radiographic Appearance and Diagnosis
MRI is the imaging modality of choice to evaluate pituitary lesions. The lesion is isointense on T1-weighted images, and there is enhancement of the pituitary gland and stalk. The pituitary gland and stalk are “pear-shaped.” The pituitary stalk enhances normally, but is markedly enlarged in LH.
Most commonly, the anterior pituitary gland is affected, termed lymphocytic adenohypophysitis.
When the entire pituitary gland is affected, the condition is termed lymphocytic infundibulo-panhypophysitis. In rare cases, the posterior pituitary alone is affected. This is called lymphocytic infundibular neurohypophysitis.
All patients with suspected LH should have a thorough endocrine evaluation and visual field testing.
A variety of other lesions can have a similar appearance, including adenomas, germinomas, tuberculosis, IgG4-related hypophysitis, CTL4-blockade-related hypophysitis, sarcoidosis, metastatic disease, lymphomas, or hypothalamic gliomas. In children, the most common etiology is eosinophilic granulomatous disease of the pituitary stalk (also known as Langerhans cell histiocytosis). The most common presentation is diabetes insipidus.
Treatment
LH is treated with glucocorticoids and hormone replacement if needed. Recognition is important as it is usually self-limited, and patients can be spared surgery if the lesion is not confused with a pituitary adenoma. Chronic immunosuppression might be needed in refractory patients and surgery is indicated for patients with refractory headaches or potential visual loss.
References
Case History
Diagnosis: Pituitary Apoplexy
Introduction
Pituitary apoplexy occurs when there is an acute hemorrhage within or a necrotic infarction of the pituitary gland. It most often occurs in a preexisting adenoma and can be the presenting feature of the tumor. It may also occur in patients with a variety of systemic diseases such as hypertension, diabetes, or sickle cell disease. It is known as Sheehan’s syndrome when it occurs in postpartum women, as normal enlargement of the pituitary gland during pregnancy is a predisposing factor to hemorrhage.
Clinical Presentation
Patients present with the sudden onset of a severe headache, visual loss, ophthalmoplegia, and altered mental status. Other common symptoms include nausea/vomiting and photophobia.
Radiographic Appearance and Diagnosis
CT scans will reveal the hemorrhage only if there is gross intracranial blood.
MRI will show a pituitary lesion with variable signal on both T1-weighted and T2-weighted images depending on the age of the blood products and whether there is an underlying adenoma. A fluid level is often seen. Enhancement on postcontrast images may occur.
Treatment
For most patients, pituitary apoplexy is a neurosurgical emergency as a subarachnoid hemorrhage can be fatal. Any patient with visual changes or loss of consciousness should undergo emergent surgical decompression. Patients with no visual disturbances or mental status changes can be monitored with serial imaging and treated with glucocorticoids. Hypopituitarism is common even in treated patients.
References
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