Autoimmune Lymphocytic Hypophysitis Research Articles

Diabetes Insipidus caused by autoimmune lymphocytic hypophysitis resulting in diagnosis and cure of Diffuse Large B-Cell Lymphoma

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

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

Primary Hypoparathyroidism and Non-functioning Pituitary Adenoma: An Incidental Coexistence?

Primary hypoparathyroidism is caused by a group of heterogeneous conditions in which hypocalcemia and hyperphosphatemia occur as a result of deficient parathyroid hormone (PTH) secretion. The most common cause is surgical excision and damage to the parathyroid gland(s). Nonetheless, autoimmune endocrine disorder of primary hypothyroidism has been well-described in polyglandular autoimmune syndromes (PAS). 1 Its association with pituitary lesion may be autoimmune lymphocytic hypophysitis as the cause for pituitary disorder. In this report, we encountered a patient with primary hypoparathyroidism who had a non-functioning pituitary tumour. It was confirmed as pituitary adenoma rather than lymphocytic hypophysitis from the histopathological examination. To our knowledge, this is the first reported case of non-functioning pituitary macroadenoma and primary hypoparathyroidism.

A rare case of hypopituitarism with psychosis

SummaryA 46-year-old woman presented multiple times in a 4-month period with hypotension, sepsis, hypoglycaemia and psychosis. A low random cortisol in combination with her presenting complaint made adrenal insufficiency the likely diagnosis. Fluid resuscitation and i.v. steroid therapy led to clinical improvement; however, a short synacthen test (SST) demonstrated an apparently satisfactory cortisol response. The test was repeated on a later admission and revealed a peak cortisol level of 25 nmol/l (>550 nmol/l). Concurrent treatment with i.v. hydrocortisone had led to a false-negative SST. ACTH was <5 ng/l (>10 ng/l), indicating secondary adrenal failure. We discuss the challenges surrounding the diagnosis of adrenal insufficiency and hypopituitarism, the rare complication of psychosis and a presumptive diagnosis of autoimmune lymphocytic hypophysitis (ALH).Learning points Adrenocortical insufficiency must be considered in the shocked, hypovolaemic and hypoglycaemic patient with electrolyte imbalance. Rapid treatment with fluid resuscitation and i.v. corticosteroids is vital.Polymorphic presentations to multiple specialities are common. Generalised myalgia, abdominal pain and delirium are well recognised, psychosis is rare.A random cortisol can be taken with baseline bloods. Once the patient is stable, meticulous dynamic testing must follow to confirm the clinical diagnosis.The chronic disease progression of ALH is hypothesised to be expansion then atrophy of the pituitary gland resulting in empty sella turcica and hypopituitarism.If hypopituitarism is suspected, an ACTH deficiency should be treated prior to commencing thyroxine (T4) therapy as unopposed T4 may worsen features of cortisol deficiency.

MECHANISMS IN ENDOCRINOLOGY: Ipilimumab: a novel immunomodulating therapy causing autoimmune hypophysitis: a case report and review

Ipilimumab (Yervoy; Medarex and Bristol-Myers Squibb) is a human MAB against cytotoxic T-lymphocyte antigen 4, which enhances co-stimulation of cytotoxic T-lymphocytes, resulting in their proliferation and an anti-tumour response. It is licensed for the treatment of unresectable or metastatic malignant melanoma, while multiple clinical trials using this medication in the treatment of other malignancies are ongoing. As a clinical response to ipilimumab results from immunostimulation, predictably it generates autoimmunity as well, causing immune-related adverse events in the majority of patients. Of those, endocrinopathies are frequently seen, and in particular, autoimmune lymphocytic hypophysitis with anterior panhypopituitarism has been reported a number of times in North America. We present a case of a male referred to our department with manifestations of anterior panhypopituitarism after his third dose of ipilimumab for metastatic malignant melanoma, and we discuss the management of his case in the light of previous reports. We also review the published literature on the presenting symptoms, time to presentation, investigations, imaging, treatment and follow-up of ipilimumab-induced autoimmune lymphocytic hypophysitis.

Pituitary apoplexy in pregnancy: a case report

IntroductionPituitary apoplexy is a clinical syndrome of selective or multi-hormonal pituitary failure, classically described as a result of infarction of a pre-existing pituitary adenoma associated with pituitary or peri-pituitary haemorrhage....

Recurrent autoimmune hypophysitis successfully treated with glucocorticoids plus azathioprine: a report of three cases

Recurrent autoimmune hypophysitis is a rare autoimmune endocrine disease involving lymphocytic infiltration and chronic pituitary inflammation. It is even more rare than primary hypophysitis. The objective of the study was to evaluate the efficacy of glucocorticoid treatment combined with azathioprine for treating three cases of recurrent autoimmune lymphocytic hypophysitis encountered within a two-year period. The clinical features and follow-up data of these cases were analyzed, including results of treatment with glucocorticoids combined with azathioprine. All three patients were female and presented with the following clinical characteristics: case 1 was a 22-year-old with headache and diplopia; case 2 was a 70-year-old with dry mouth, polydipsia, and polyuria; case 3, a 32-year-old, with polydipsia, polyuria and menstrual disorders with headache and dizziness. Regarding recurrence, case 1 recurred 4 months after surgery and again 14 months after discontinuing prednisone; case 2 relapsed 16 months after receiving high-dose methylprednisolone pulse therapy; and case 3 recurred during the period of prednisone dose reduction. The patients were treated with glucocorticoids plus azathioprine, and positive responses were seen in all three cases. Symptoms were relieved, and MRI revealed significant reduction of lesions during follow-up. Pituitary function resumed in cases 1 and 3; permanent hypopituitarism was present in case 2. At last follow-up, MRI showed no further recurrence of disease in any patient. Treatment and responses of these patients with autoimmune hypophysitis suggest that glucocorticoid therapy combined with azothioprine is effective treatment for recurrent autoimmune hypophysitis. Endocrine and radiologic studies are an essential part of follow-up.

Induction of an organ-specific autoimmune disease, lymphocytic hypophysitis, in hamsters by recombinant rubella virus glycoprotein and prevention of disease by neonatal thymectomy

Glycosylated, membrane-associated E1 (58-kDa) and E2 (47- to 49-kDa) rubella virus proteins and unglycosylated nucleoprotein C (33 kDa), from separately expressed vaccinia virus recombinants, were injected into golden Syrian hamsters. Rubella virus E1 and E2 glycoproteins consistently induced an organ-specific autoimmune disease, autoimmune lymphocytic hypophysitis, which was evidenced by the induction of autoantibodies against pituitary cells and by lymphocytic infiltration of the pituitary. Neonatal thymectomy prevented the disease. In contrast, rubella virus nucleoprotein C did not induce either autoantibodies against pituitary cells or lymphocytic infiltration of the pituitary. This finding raises the possibility that virus-specific protein itself can induce an organ-specific autoimmune disease in certain circumstances.

AUTOIMMUNITY TO ANTERIOR PITUITARY CELLS AND THE PATHOGENESIS OF INSULIN-DEPENDENT DIABETES MELLITUS

An immunofluorescence study using unfixed cryostat sections of human pituitary glands was carried out on sera from patients with type-Ia (juvenile-onset) diabetes (61 recent onset, 48 longstanding). 63 of their selected high-risk first-degree relatives and 117 patients with type-Ib ("polyendocrine") diabetes were tested for comparison. Healthy controls included 48 sera from laboratory staff and students. Pituitary-cell antibodies were found in none of the controls, in 2% of patients with longstanding diabetes, in 16·6% of patients with diabetes of recent onset, and in 36·6% of genetically predisposed relatives with islet-cell antibodies in their sera (of whom 7 became diabetic during a 3-year follow-up period, 4 of them reacting with pituitary cells for 1-3 years before the onset of diabetes). Thus pituitary antibodies tended to disappear after onset of symptoms. Many of the sera reacted with multiple anterior-pituitary cell types. These findings suggest a wider involvement of the endocrine-organ system in the pathogenesis of insulin-dependent diabetes and are in accordance with clinical observations showing excess growth in prepubertal boys at onset of diabetic symptoms and with the results of experiments on virus-induced diabetes in mice. The connection of these pituitary antibodies with autoimmune lymphocytic hypophysitis is at present unknown.

Humoral autoimmunity to gut-related endocrine cells

An immunofluorescence study using unfixed cryostat sections of human pituitary glands was carried out on sera from patients with type-Ia (juvenile-onset) diabetes (61 recent onset, 48 longstanding). 63 of their selected high-risk first-degree relatives and 117 patients with type-Ib ("polyendocrine") diabetes were tested for comparison. Healthy controls included 48 sera from laboratory staff and students. Pituitary-cell antibodies were found in none of the controls, in 2% of patients with longstanding diabetes, in 16·6% of patients with diabetes of recent onset, and in 36·6% of genetically predisposed relatives with islet-cell antibodies in their sera (of whom 7 became diabetic during a 3-year follow-up period, 4 of them reacting with pituitary cells for 1-3 years before the onset of diabetes). Thus pituitary antibodies tended to disappear after onset of symptoms. Many of the sera reacted with multiple anterior-pituitary cell types. These findings suggest a wider involvement of the endocrine-organ system in the pathogenesis of insulin-dependent diabetes and are in accordance with clinical observations showing excess growth in prepubertal boys at onset of diabetic symptoms and with the results of experiments on virus-induced diabetes in mice. The connection of these pituitary antibodies with autoimmune lymphocytic hypophysitis is at present unknown.