Case Of Granulomatous Hypophysitis Research Articles

Rituximab as an Alternative Treatment for Refractory Granulomatous Hypophysitis

Background: Although glucocorticoids have been adopted as the main stay treatment for granulomatous hypophysitis, refractory cases have been treated by infliximab with success in multiple reported case.[1,2,3] Given the low prevalence, incidence of granulomatous hypophysitis[4] and the advent of biologics, evidence of rituximab’s efficacy are largely based on a handful of case reports[1,2,3] and needs more evidence to label its utility. We describe a case of recurrent primary granulomatous hypophysitis in a 48-year-old female who had significant treatment challenge until there was good response after initiation of rituximab. Clinical Case: Patient was a known case of granulomatous hypophysitis and had undergone total hypophysectomy. Despite this approximately a year after her surgery she had become symptomatic and had MRI changes. She was started on a succession of immunosuppressive agents and high dose steroids to control recurrent symptoms. Due to treatment failure and very high steroid dose, patient was eventually started on Rituximab and patient had significant improvement of her symptoms as well as resolution of the MRI changes. Conclusion: Although there is a lack of prospective, double blind and controlled studies this case study highlights the utility of Rituximab as a potent alternative treatment for refractory given the adverse effect associated with the steroids and other immunosuppressive agents. Reference statement: 1. Schreckinger M, Francis T, Rajah G, Jagannathan J, Guthikonda M, Mittal S. Novel strategy to treat a case of recurrent lymphocytic hypophysitis using rituximab. J Neurosurg. 2012 Jun;116(6):1318-23. doi: 10.3171/2012.2.JNS111456. Epub 2012 Mar 23. PMID: 22443503. 2. Xu C, Ricciuti A, Caturegli P, Keene CD, Kargi AY. Autoimmune lymphocytic hypophysitis in association with autoimmune eye disease and sequential treatment with infliximab and rituximab. Pituitary. 2015 Aug;18(4):441-7. doi: 10.1007/s11102-014-0592-7. PMID: 25224140. 3. Gu WJ, Zhang Q, Zhu J, Li J, Wei SH, Mu YM. Rituximab was used to treat recurrent IgG4-related hypophysitis with ophthalmopathy as the initial presentation: A case report and literature review. Medicine (Baltimore). 2017 Jun;96(24):e6934. doi: 10.1097/MD.0000000000006934. PMID: 28614220; PMCID: PMC5478305. 4. Angelousi A, Alexandraki K, Tsoli M, Kaltsas G, Kassi E. Hypophysitis (Including IgG4 and Immunotherapy). Neuroendocrinology. 2020;110(9-10):822-835. doi: 10.1159/000506903. Epub 2020 Mar 4. PMID: 32126548

Granulomatous hypophysitis: experience with eight surgical cases of a single center

Although primary hypophysitis is not uncommon, a granulomatous etiology of hypophysitis is relatively rare. Radiological and diagnostic characteristics of several isolated cases have been described to date. However, to the best of our knowledge, surgical treatment of eight cases of granulomatous hypophysitis confirmed by histopathology has not yet been reported. A retrospective study was performed to review cases of granulomatous hypophysitis from November 2003 to November 2013 in our neurosurgical department. Only eight out of 1345 operations were diagnosed with granulomatous hypophysitis. The cohort included two men and six women. The most common manifestations reported were headache, fatigue and polyuria. All six female patients presented with either menstrual disorders or amenorrhea. Seven of eight patients suffered polyuria. Two patients suffered bitemporal hemianopsia. One was accompanied with eosinophilic granuloma of the skull. Prolactin levels were increased in six patients, four of them were noted to have thyroid axis imbalances, one was noted to be deficient in the gonadotropin axis and two were deficient in the adrenal axis. The lesion demonstrated homogenous enhancement and an abnormally thickened pituitary stalk. A histological diagnosis of granulomatous hypophysitis was established in all eight patients, who were treated surgically. Characteristic granulomas formed by epithelioid histiocytes and multinucleated giant cells were observed. Pure glucocorticoid therapy is less effective than surgical intervention and has not been recommended for the treatment of granulomatous hypophysitis. Although replacement therapy can relieve associated symptoms, we conclude surgical intervention, particularly minimally invasive surgery via a transsphenoidal approach, to be mandatory in establishing a diagnosis and reducing the size of the inflammatory mass. Adjuvant corticosteroids therapy is recommended.

Immunohistochemical Study for IgG4-positive Plasmacytes in Pituitary Inflammatory Lesions

On histology, IgG4-related hypophysitis is essentially similar to lymphocytic hypophysitis besides massive IgG4-positive plasmacyte infiltration. This immunohistochemical study was performed to investigate the presence of IgG4-positive plasmacytes in 14 various inflammatory lesions. Five cases of lymphocytic hypophysitis and a case of granulomatous hypophysitis were either negative or showed only a few IgG4-postive cells. A case of hypophysitis associated with pachymeningitis and a case of pituitary invasion of lymphoma were IgG4 negative. On the other hand, some IgG4-positive cells that tended to accumulate were observed in every six cases of secondary inflammation. In conclusion, immunohistochemistry for IgG4 can be a clue for differentiating IgG4-related hypophysitis from lymphocytic hypophysitis. However, clusters of IgG4-positive plasmacytes could be observed in secondary inflammation. Diagnosing hypophysitis with small biopsy specimen still remains troublesome.

Inflammatory hypophysitis - the spectrum of disease.

Inflammatory conditions of the pituitary are rare and consequently there are a number of single case reports of this condition but few reports of series. The condition is often divided into lymphocytic and granulomatous hypophysitis and it has been suggested that these two conditions represent the ends of a spectrum of disease. We present our experience with 14 cases of this condition, correlating the presenting symptoms with the neuroradiology, surgical findings and subsequent histology. The subjects (11 female 3 male) ranged in age from 13 to 64 years. Final histopathological diagnoses included 5 cases of lymphocytic hypophysitis, 4 cases of Rathke's pouch cyst with granulomatous response, 2 cases of granulomatous hypophysitis and 1 case with an inflammatory process that did not fit the current classification. Two subjects did not undergo surgery. Headache was a presenting feature in 11 of 14 cases and fever in 3 of 14 cases. Length of symptoms prior to presentation varied from acute onset to 9 years. One case of lymphocytic hypophysitis was associated with pregnancy. Evidence of hypopituitarism was present in 9 of 10 subjects assessed preoperatively. Preoperative radiology showed three patterns of disease: A cystic appearance was common with low signal content on MRI T1 weighting with an enhancing ring and a thickened enhancing stalk (5 patients). 4 patients showed a solid enhancing mass. A third group (2 patients) showed cysts with high signal content on T1 weighting - both of these were Rathke's cysts on histology. Overall there were no striking features in the clinical presentation to distinguish pituitary inflammation from pituitary adenoma. The prognosis was generally good.

Lymphocytic and Granulomatous Hypophysitis

Objective Lymphocytic hypophysitis and granulomatous hypophysitis are rarely encountered. The aim of this study was to demonstrate their clinical peculiarities among pituitary disorders and to provide an approach for their clinical management. Methods In a retrospective study, we reviewed our surgical experience with nine patients harboring hypophysitis. The series included six cases of lymphocytic hypophysitis, two cases of granulomatous hypophysitis, and one case with evidence of coexisting lymphocytic and granulomatous hypophysitis. Results A striking similarity of clinical signs was found for our nine patients. Headache or aseptic meningitis, thickening of the sphenoid sinus mucosa, pituitary stalk enlargement, and tongue-shaped extension of the lesion along the basal hypothalamus were characteristic signs. Lymphocytic hypophysitis was not associated with pregnancy in any of the seven cases. No recurrence has been observed in six cases with total removal of the inflammatory tissue. Conclusion Lymphocytic hypophysitis and granulomatous hypophysitis represent related inflammatory disorders. Their conspicuous clinical features frequently allow preoperative diagnosis of hypophysitis. In view of their sometimes insidious clinical course, early surgical exploration is justified.