Clinical presentation and magnetic resonance imaging characteristics of lymphocytic hypophysitis: a systematic review with meta-analysis

This meta-analysis was to analyze the clinical presentation, magnetic resonance imaging (MRI) characteristics, and the management of Lymphocytic hypophysitis (LYH). Meta-analysis showed that the percentage of women in LYH patients was 78%. LYH was associated with pregnancy in 15% of the female patients, with headache (49%) and symptoms of central diabetes insipidus (CDI) (45%) being the most frequent presentation. In 24 % of the LYH patients, there was an association with another autoimmune disease. The incidence of secondary hypogonadism, secondary hypoadrenalism, secondary hypothyroidism, and growth hormone deficit was 54%, 49%, 43%, and 22%, respectively. Pituitary contrast enhancement (63%), symmetrical pituitary enlargement (60%), thickening of the pituitary stalk (58%), sella mass or suprasellar extension (58%), and loss of posterior pituitary hyperintensity (50%) were typical MRI findings. Regarding LYH treatment, the percentage of patients who had observation or hormone replacement, steroid therapy, and surgery was 43%, 36%, and 34%, respectively.

A case report of lymphocytic hypophysitis

Background: Lymphocytic hypophysitis (LH) is a rare condition that mostly affects women of the reproductive age. Because it is infrequently encountered, it is not often considered as a differential diagnosis of sellar masses. The diagnosis is made clinically with the aid of magnetic resonance imaging (MRI) and should be considered if the patient has endocrine derangements in addition to a sellar mass. Case Description: A 37-year-old female presents with a complaint of headaches and CT imaging showed a sellar mass. She was also being investigated simultaneously by the endocrine department and was diagnosed with panhypopituitarism. She proceeded to surgery for a presumed pituitary adenoma but histopathology returned as LH. Conclusion: It is important to have a wide differential diagnosis when managing pituitary masses. Clinical correlation with atypical MRI findings is useful to determine the diagnosis of LH.

A Rare Case of Recurrent Lymphocytic Hypophysitis Spanning 8 Years

Background: Lymphocytic Hypophysitis (LH) is predominantly a self-limiting condition. Reports of recurrent LH have been limited to case series, predominantly within first two years of initial presentation (1). There is paucity of data on long term follow up of these cases and late recurrence of LH is considered very rare (2). Clinical Case: We describe the clinical course of a 47-year female, who first presented to us, 8 years back, with headache, visual disturbance and secondary amenorrhea. Her MRI pituitary was suggestive of a pituitary mass, which was removed by trans-sphenoidal surgery. Histopathology of the mass was suggestive of LH. Patient had symptomatic improvement, and remained well on out-patient follow-up, on hormone replacement therapy. She took replacement dose of glucocorticoid for 4 years after the initial surgery and then it was discontinued. However, she re-presented to us with headache and visual disturbance this time associated with xerostomia and xerophthalmia. In this presentation, due to presence of sicca symptoms a suspicion of autoimmune aetiology was kept. Her lab parameters were consistent with pan hypopituitarism along with new appearance of anti-TPO antibodies. She underwent two consecutive trans-sphenoidal surgeries for relief of pressure symptoms, and has been started immunosuppressive doses of glucocorticoids along with methotrexate. Other causes of recurrent hyophysitis, as IgG4 related Hypophysitis, were excluded by immunohistochemistry and normal serum IgG4 level (0.72g/l). She has since been discharged, and remains well on outpatient follow-up with no mass effect. MRI pituitary done at 2 months follow up is not suggestive of residual regrowth or mass effect. Conclusion: This case highlights the importance of long term follow up of LH patients. Other autoimmune aetiology maybe considered in cases unresponsive to standard treatment, necessitating titration of additional immunosuppressive therapy. References: 1.M.N. Joshi et al, Hypophysitis: diagnosis and treatment, European Journal of Endocrinology 2018, 179, R151-R1632.Honegger et al, Treatment of Primary Hypophysitis in Germany: Journal Clinical Endocrinology and Metabolism, September 2015, 100(9):3460 –3469

A Case of Relapse of Lymphocytic Hypophysitis Triggered by the Pregnancy of the Second Child

Lymphocytic hypophysitis is a rare immune-mediated inflammatory disorder that causes pituitary dysfunction. It has been reported that lymphocytic hypophysitis onset during pregnancy rarely relapses or exacerbates in subsequent pregnancies. We herein report a patient with relapse of lymphocytic hypophysitis triggered by the pregnancy of the second child. Case Presentation: At the age of 34, at 28 weeks of gestation of the first child, she became aware of left visual field disorder and was diagnosed as an upper left visual field defect. An MRI scan revealed an enlargement of the pituitary gland and the thickening of the stalk. She was referred to our hospital for diagnosis and treatment. Laboratory data showed central adrenocortical dysfunction and central hypothyroidism. Based on the course of the disease, MRI findings and laboratory data, we diagnosed her as lymphocytic hypophysitis occurred during pregnancy. With a replacement dose of hydrocortisone and levothyroxine, she gave birth by cesarean section at 38 weeks of gestation. We performed detailed assessment of anterior pituitary functions with hypothalamic hormone challenges after giving birth. It showed panhypopituitarism without diabetes insipidus. An MRI scan found the compression of the optic chiasm remained after childbirth, the patient underwent steroid pulse therapy. After that, visual field defect improved rapidly, and the patient continued to receive oral prednisolone with gradually reduced amount. An MRI scan performed over time and found the pituitary swelling gradually improved. The pituitary was completely intact 3 years after the onset of disease. At the age of 38, the patient became pregnant with her second child, showed no signs of hypopituitarism at the time of pregnancy. She still had been administrated with 3.5mg/day prednisolone. At the 21 weeks of pregnancy, she became aware of blurred vision and was diagnosed as a left paracenter scotoma. Laboratory data showed a decrease in blood glucose and neutrophil count, suggesting the occurrence of central adrenocortical insufficiency. Therefore, we suspected the relapse of hypophysitis due to second pregnancy. We started hydrocortisone supplementation in addition to prednisolone. No MRI scan was performed during pregnancy, since no progression of visual impairment was observed. She gave birth at 37 weeks of gestation, and postpartum MRI scan showed mild thickening of the stalk. Steroid pulse therapy was not performed because the visual field abnormality was spontaneously improved. Lymphocytic hypophysitis has a diverse course, and there is currently no confirmed risk factor for recurrence. In this case, hypophysitis recurred due to pregnancy despite the continuation of prednisolone administration, and the pathogenic mechanism may be different from the previously reported cases of recurrence of hypophysitis.

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