Neuroimaging of hypophysitis: etiologies and imaging mimics

Abstract

Hypophysitis is an inflammatory disease affecting the pituitary gland. Hypophysitis can be classified into multiple types depending on the mechanisms (primary or secondary), histology (lymphocytic, granulomatous, xanthomatous, plasmacytic/IgG4 related, necrotizing, or mixed), and anatomy (adenohypophysitis, infundibulo-neurohypophysitis, or panhypophysitis). An appropriate diagnosis is vital for managing these potentially life-threatening conditions. However, physiological morphological alterations, remnants, and neoplastic and non-neoplastic lesions may masquerade as hypophysitis, both clinically and radiologically. Neuroimaging, as well as imaging findings of other sites of the body, plays a pivotal role in diagnosis. In this article, we will review the types of hypophysitis and summarize clinical and imaging features of both hypophysitis and its mimickers.

Keywords: Hypophysitis; Magnetic resonance imaging; PitNET.

Fig. 1

A 38-year-old woman with lymphocytic hypophysitis. An enlarged pituitary gland shows heterogeneous hyperintensity on T2-weighted sagittal image (a, white arrow), isointensity on T1-weighted sagittal image (b, white arrow), and homogeneous contrast enhancement (c, white arrow). A dark signal intensity area is observed on the sellar floor (“parasellar T2 dark sign”; a, black arrow). The posterior pituitary T1-weighted bright spot is absent (b, arrowhead). The different images of this case were evaluated in the previous study [9]

Fig. 2

A 37-year-old woman with lymphocytic hypophysitis. A “snowman-like” shaped enlarged pituitary gland is observed (a–c, arrows). The pituitary gland shows homogeneous hyperintensity on fluid-attenuated inversion recovery (FLAIR) coronal and sagittal images (a, b) and homogeneous isointensity on T1-weighted sagittal image (c). The posterior pituitary T1-weighted bright spot is preserved in this case

Fig. 3

A 29-year-old man with primary granulomatous hypophysitis. Artifacts due to the patient’s body motion are observed. An enlarged pituitary gland shows heterogeneous hyperintensity on T2-weighted coronal image (a, white arrow), isointensity on T1-weighted coronal image (b, white arrow), and homogeneous contrast enhancement on post-contrast T1-weighted coronal and sagittal images (c, d, white arrows). Extension into bilateral cavernous sinus is observed (e, arrowheads). T2-weighted hypointensity areas around the enlarged pituitary gland are found, suggestive of granulomatous/fibrous inflammation (a, black arrow)

Fig. 4

A 45-year-old woman with secondary granulomatous hypophysitis associated with Crohn’s disease. Both pituitary gland and stalk are enlarged (a–e, white arrows; e, white arrowhead), abutting the optic chiasm superiorly (a, black arrow). The pituitary gland shows heterogeneous hyperintensity on T2-weighted coronal image (a), hypointensity on T1-weighted coronal image (b), and heterogeneous vivid enhancement (c, e). The posterior pituitary T1-weighted bright spot is absent (d, black arrowhead)

Fig. 5

A 67-year-old man with plasmacytic/IgG4-related hypophysitis. An enlarged pituitary gland shows heterogeneous hyperintensity on T2-weighted coronal image (a, arrow) and hypointensity on T1-weighted coronal image (b, arrow) with peripheral enhancement and loss of central enhancement (c, arrow). The posterior pituitary T1-weighted bright spot is absent (d, black arrowhead)

Fig. 6

A 76-year-old woman with plasmacytic/IgG4-related hypophysitis. An enlarged strongly enhanced pituitary gland and stalk are observed (a–c, white arrows). The lesion shows heterogeneous hypointensity on T2-weighted coronal image a and hypo- to isointensity on T1-weighted coronal image b with involvement of the right cavernous sinus and compression of the optic chiasm (c, black arrow). Inflammatory extension along the dorsal surface of the clivus is observed (d, arrowhead)

Fig. 7

A 31-year-old woman with xanthomatous hypophysitis. Post-contrast T1-weighted images show an enlarged pituitary gland with central non-enhancing components and peripheral contrast enhancement (a–c, arrows). Pathology shows fragments of intact, normal pituitary gland infiltrated by foamy histiocytes (d). The images were cited and modified from [19]

Fig. 8

A 20-year-old woman with necrotizing hypophysitis. The enlarged pituitary gland and stalk showing homogeneous hyperintensity on T2- and T1-weighted coronal images a, b with an absence of central contrast enhancement and strong peripheral enhancement c, e are observed. The posterior pituitary T1-weighted bright spot is absent (d). The images were cited from [21]

Fig. 9

Schematic illustrations of mechanisms of immune checkpoint inhibitors (ICIs), ICI-related isolated adrenocorticotropic hormone deficiency (ICI-IAD), and ICI-related hypophysitis (a). ICIs inhibit interactions between antigen-presenting cells (APC)/tumor cells and T cells. ICIs include PD-1 inhibitors, PD-L1 inhibitors, and CTLA-4 inhibitors. ICIs reactivate the immune response of the host, resulting in T-cell activation and proliferation. ICI-IAD is mainly caused by the cytotoxic effect of activated T cells due to PD-1 inhibitors, whereas ICI-related hypophysitis is typically caused by antigen (Ag)-antibody (Ab) reaction due to CTLA-4 inhibitors. b, c A 68-year-old man with ICI-IAD. Both T2-weighted coronal image b and post-contrast T1-weighted coronal image c show a normal-appearing pituitary gland. d, e A 62-year-old woman with ICI-related hypophysitis. A heterogeneously enhanced, enlarged pituitary gland with longitudinal T2-weighted hypointensity areas with poor enhancement (d, e, arrows) is observed. The different images of the same patient were evaluated in a previous study [24]

Fig. 10

A 64-year-old woman status post-oophorectomy with pituitary hyperplasia. The pituitary gland is symmetrically enlarged with normal signal intensity on T2- and T1-weighted images a, b and homogeneous contrast enhancement (c). The posterior pituitary T1-weighted bright spot is preserved (b, arrow)

Fig. 11

A 24-year-old woman with Rathke’s cleft cyst. There is a sellar/suprasellar mass (a–d, arrows) between the anterior and posterior lobes of the pituitary gland with hypointensity on T2-weighted coronal image (a) and hyperintensity on T1-weighted images b, c without contrast enhancement (d)

Fig. 12

A 33-year-old woman with PitNET causing pituitary apoplexy. MRI shows a snowball-shaped mass extending from within the sella turcica to the suprasellar region (a–f, arrows). The mass has non-enhancing T1-weighted hyperintense components (a, arrowhead), suggestive of hemorrhagic changes, and enhancing peripheral components with T2-weighted isointensity c and restricted diffusion (e, f)

Fig. 13

a–c, arrows A 14-year-old boy with adamantinomatous craniopharyngioma. MRI shows a mass with heterogeneous cystic signal intensity with contrast-enhanced components (a, T1-weighted coronal image; b post-contrast T1-weighted coronal image). Calcifications are observed on contrast-enhanced CT (c arrowheads). (d–f, arrows) A 21-year-old man with papillary craniopharyngioma. There is a suprasellar mass with heterogeneous high-to isointense solid components on T2-weighted coronal image d with strong contrast enhancement e, f and peripheral multicystic components

Fig. 14

(a–c, arrows) A 76-year-old woman with pituitary metastasis of breast cancer. Post-contrast T1-weighted sagittal image shows heterogeneously enhanced mass in the pituitary gland and stalk (a). Contrast-enhanced CT shows the mass extending posteriorly through the clivus with evidence of bone destruction (b, c, arrowhead). (d, arrow) A 60-year-old woman with pituitary metastasis of small cell lung cancer. There are multiple other metastatic lesions involving the pineal region, cerebellum, and clivus (d, black arrows)

Fig. 15

A 17-year-old woman with germinoma involving the pituitary gland and pineal gland. MRI shows enlarged pituitary gland and stalk with T2-weighted hyperintensity (a, arrow) and heterogeneous enhancement (b, c, arrows). A pineal gland lesion is also demonstrated (c, arrowhead)

Fig. 16

a, b A 49-year-old man with meningioma. Post-contrast fat-suppressed T1-weighted image shows homogeneously enhanced suprasellar mass (a, arrow). Dural-tail sign (a, white arrowhead) and hyperostosis (b, black arrowhead) are observed. c, d A 60-year-old woman with lymphoma. Non-enhanced CT shows an infiltrative hyperdense suprasellar mass (c, arrowheads), which shows restricted diffusion with low apparent diffusion coefficient (d, arrow). e, f A 51-year-old man with pituicytoma. T2-weighted coronal image shows a suprasellar well-defined mass with homogeneous hypointensity and small cystic areas (e, arrow). Contrast-enhanced CT shows homogeneous enhancement (f, arrow). g, h A 14-year-old girl with Rosai–Dorfman disease. FLAIR image shows an infiltrative suprasellar mass with an ill-defined margin, involving the midbrain and bilateral thalami (g, arrow). Post-contrast T1-weighted image shows heterogeneous and strong enhancement (h, arrow)

Fig. 17

A 53-year-old woman with sarcoidosis. Enlarged pituitary gland and stalk with homogeneous and strong contrast enhancement are observed (a–c, white arrows). The posterior pituitary T1-weighted bright spot is absent (a, black arrow). The lesion is extending into the bilateral cavernous sinus (c, white arrowheads). Chest CT shows mediastinal lymphadenopathy, highly suggestive of sarcoidosis (d, black arrowheads)

Fig. 18

A 20-year-old man with proteinase 3-antineutrophil cytoplasmic antibody-positive GPA. The pituitary gland is enlarged and shows heterogeneously hypointensity on T2-weighted coronal image (a, white arrow) with heterogeneous enhancement (b, white arrow), extending posteriorly along the surface of the clivus (b, white arrowhead). The sphenoid sinus (b, black arrow), bilateral lacrimal glands (c, black arrows), right mastoiditis (d, black arrow), and left lung (e, black arrow) are also involved

Fig. 19

A 33-year-old woman with Sheehan’s syndrome after a cesarean section with massive blood loss. The size of the pituitary gland is within normal limits. The anterior pituitary lobe shows hyperintensity on T2-weighted coronal image (a, arrow), isointensity on T1-weighted coronal image (b, arrow) without contrast enhancement (c, arrow)

Fig. 20

A 62-year-old woman with spontaneous intracranial hypotension. An enlarged pituitary gland is observed on post-contrast T1-weighted sagittal image (a, arrow). Diffuse dural thickening and linear enhancement in both supra- and infratentorial regions are observed (b, c, white arrowheads). A slight downward displacement of the structures appears near the base of the brain, including the hypothalamus, midbrain, pons, and cerebellum