Hypophysitis, the Growing Spectrum of a Rare Pituitary Disease

Abstract

Hypophysitis is defined as inflammation of the pituitary gland that is primary or secondary to a local or systemic process. Differential diagnosis is broad (including primary tumors, metastases, and lympho-proliferative diseases) and multifaceted. Patients with hypophysitis typically present with headaches, some degree of anterior and/or posterior pituitary dysfunction, and enlargement of pituitary gland and/or stalk, as determined by imaging. Most hypophysitis causes are autoimmune, but other etiologies include inflammation secondary to cellar tumors or cysts, systemic diseases, and infection or drug-induced causes. Novel pathologies such as IgG4-related hypophysitis, immunotherapy-induced hypophysitis and paraneoplastic pituitary-directed autoimmunity are also included in a growing spectrum of this rare pituitary disease. Typical magnetic resonance imaging reveals stalk thickening and homogenous enlargement of the pituitary gland, however, imaging is not always specific. Diagnosis can be challenging and ultimately, only a pituitary biopsy can confirm hypophysitis type and rule out other etiologies. A presumptive diagnosis can be made often without biopsy. Detailed history and clinical examination are essential, notably for signs of underlying etiology with systemic manifestations. Hormone replacement and in selected cases careful observation is advised with imaging follow-up. High-dose glucocorticoids are initiated mainly to help reduce mass effect. A response may be observed in all auto-immune etiologies, but also in lymphoproliferative diseases, and as such should not be used for differential diagnosis. Surgery may be necessary in some cases to relieve mass effect and allow a definite diagnosis. Immunosuppressive therapy and radiation are sometimes also necessary in resistant cases.

Response to Letter to the Editor From Asa and Mete: “Hypophysitis, the Growing Spectrum of a Rare Pituitary Disease”

“…Interestingly, Goyal et al ( 8 ) and Gulati et al ( 3 ), as cited by the authors ( 2 ), although focusing on a new proposed ECD/LCH nomenclature, also describe hypothalamic/pituitary involvement as infiltrative. As highlighted ( 1 ), we concur that it is important to raise awareness of the origin of ECD and LCH as both diagnosis and treatment are complex and require specific imaging, tissue biopsy, chemotherapy, targeted therapy (eg, BRAF and MEK inhibitors), glucocorticoids, radiation, or a combination of all. Furthermore, management pathways for ECD and LCH vs those for malignancy with mass effect are different, as shown in Figure 5 ( 1 ).…”

“…However, we detail that xanthomatous Hy is often linked to rupture of a Rathke cleft cyst or other cystic pituitary masses and could be an important unrecognized clinical problem. This is highlighted in case 2 ( 1 ) (a patient with xanthomatous Hy and craniopharyngioma) and in Figure 1 ( 1 ). Furthermore, additional literature on this topic is referenced in the article ( 1 ).…”

“…This is highlighted in case 2 ( 1 ) (a patient with xanthomatous Hy and craniopharyngioma) and in Figure 1 ( 1 ). Furthermore, additional literature on this topic is referenced in the article ( 1 ).…”

“…We thank Asa and Mete for their interest in our article “Mini-review: Hypophysitis, the Growing Spectrum of a Rare Pituitary Disease” ( 1 ), in which we discuss diagnosis and management of hypophysitis (Hy), address common clinical questions, and describe a variety of underlying etiologies and conditions associated with Hy. The authors ( 2 ) point to an omission of xanthomatous Hy often associated with rupture of a Rathke cleft cyst.…”

“…Recent discovery of activating mutations in proto-oncogene B rapidly accelerated fibrosarcoma (BRAF) V600E and other genes involved in MAPK pathways in many patients with LCH and ECD, have shed new light on these entities, pointing to a neoplastic process and new treatment options for some, but not all, patients. In the article ( 1 ), we referenced several recent reports ( 3-6 ) that describe these genetic pathways and note available treatments in the text and figures, including use of targeted BRAF and MEK inhibitor therapies ( 1 ).…”