Lymphocytic panhypophysitis (LPH) is a rare inflammatory disorder that primarily affects the pituitary gland. Extension into the cavernous sinus has been described, but clival involvement is exceedingly rare. To date, no cases of isolated clival extension have been documented. Anti-rabphilin-3A antibodies have been identified as diagnostic markers that may facilitate the diagnosis of this challenging condition. An 81-year-old man presented with headache, anorexia, and fatigue. Evaluation demonstrated panhypopituitarism followed by central diabetes insipidus. MRI revealed homogeneous pituitary enlargement with isolated clival extension. Endoscopic evaluation during transsphenoidal biopsy demonstrated thickened dura mater extending from the pituitary gland to the clivus. Histopathological analysis revealed lymphoplasmacytic infiltration with a predominance of CD20-positive B cells over CD3-positive T cells and inflammatory infiltration between the clival bone trabeculae, confirming direct invasion. The serum anti-rabphilin-3A antibody test was positive. Hormone replacement therapy resulted in clinical improvement, and follow-up MRI at 3 and 6 months showed marked resolution. This appears to be the first reported case of LPH with isolated clival extension. Intraoperative dural thickening and histological evidence of trabecular bone infiltration suggest a potential pathway for extrapituitary extension. Anti-rabphilin-3A antibody testing can support diagnosis, particularly in such atypical presentations. https://thejns.org/doi/10.3171/CASE25737.

A 39-year-old woman presented with a 5-year history of severe intermittent headaches, rhinitis, hemoptysis, unintentional weight loss of 40 kg over a year, and unilateral vision loss. Then, she noticed polyuria, amenorrhea, muscle weakness, and cold intolerance. Diagnosis of granulomatosis with polyangiitis (GPA) was confirmed with elevated c-ANCA levels and PR3-positive antibodies. Physical examination revealed hypotension, absence of pubic and axillary hair, and classical signs of hypothyroidism. The patient reported multiple previous hospitalizations due to episodes of hypernatremia, hypotension, and hypoglycemia. The biochemical evaluation showed early signs of chronic kidney disease and central adrenal, thyroid, and gonadotropin deficiencies. Pituitary MRI revealed a heterogeneous pituitary gland with peripheral enhancement, central necrosis, and extension to adjacent structures, as well as the absence of posterior pituitary bright spot on T1-weighted imaging. A diagnosis of GPA with pituitary involvement was established. Remission therapy with corticosteroids and rituximab was started. After disease control, pituitary hormonal deficiencies persisted, requiring long-term hormone replacement therapy. Pituitary involvement in cases with GPA is a rare manifestation frequently misdiagnosed. It is important to be aware of hypophysitis as a GPA activity complication that warrants a prompt diagnostic approach and treatment. The pathophysiology of hypophysitis may be mediated by a granulomatous lesion or due to vascular damage. Pituitary dysfunction in GPA may occur at any moment, as an initial manifestation or as a concomitant syndrome together with other organ compromise. Deficiency of arginine vasopressin and central hypogonadism are the most frequent pituitary hormonal alterations. Pituitary dysfunction usually persists despite remission of systemic activity, requiring long-term hormone replacement therapy and surveillance.

A 3 yr old intact male Doberman pinscher was referred with chronic diarrhea, severe polyuria-polydipsia, and behavioral changes for 2 wk. Biochemical abnormalities were consistent with central diabetes insipidus, hypothyroidism, and hypoadrenocorticism. Brain MRI and cerebrospinal fluid analysis raised suspicion for lymphocytic hypophysitis and meningitis, later confirmed histologically. Immunosuppressive steroid therapy and hormonal supplementation were implemented, resulting in a marked clinical improvement. Brain MRI at a 3 mo follow-up showed a resolution of inflammatory lesions along with pituitary atrophy. The patient was euthanized 4.5 mo following diagnosis because of uncontrolled aggressiveness. Lymphocytic hypophysitis (LHP) is a rare autoimmune condition in people and dogs, often accompanied by total or partial pituitary hormonal deficiency. This is the first case of histologically confirmed canine LHP with documented clinical and biochemical response to medical management. As described in people, LHP should be considered as a differential diagnosis for pituitary lesions. Although the overall prognosis of this disease remains guarded to poor, early diagnosis and adequate immunosuppressive treatment might improve the outcome.

This systematic review aims to collect and examine recent research findings regarding hypophysitis in COVID-19 patients. We conducted a comprehensive literature review in English on the topic "Hypophysitis in COVID-19," using the MEDLINE (PubMed) database in July 2024. The selected articles were systematically tabulated and we have assessed in this review patient demographics, symptom presentation, imaging results, diagnosis, clinical management, and outcomes. Seven reported cases of post-COVID-19 hypophysitis were identified, comprising 4 (57%) females and 3 (43%) males, with a median age of 37 years. The interval between COVID-19 infection symptoms and the onset of hypophysitis ranged from 2 to 3 weeks. Initial symptoms included frontal headache in 4 (57%) cases and polyuria and polydipsia in 3 (43%) cases. Anterior or posterior hypopituitarism was observed in 6 (85%) patients. Radiological findings varied: 2 (28.5%) cases showed panhypophysitis, 3 (43%) cases exhibited gland enlargement with homogeneous contrast enhancement on magnetic resonance imaging (MRI), 1 case involved the loss of the posterior pituitary bright spot, and 1 case involved pituitary apoplexy/enlargement of the gland and infundibulum. No pituitary biopsies were performed. Four (57%) patients received glucocorticoid (GC) treatment. Long-term follow-up was documented in only one case, a 16-year-old female followed for 2 years reporting complete clinical and radiological resolution. Although rare, hypophysitis related to COVID-19 is documented in the literature exhibiting distinct characteristics such as a homogeneous gender prevalence, an average age of onset around 35 years, and primary symptoms of headache, polyuria, and polydipsia which are indicative of angiotensin-vasopressin deficiency. This is in contrast with primary autoimmune hypophysitis characterized by a female prevalence and typical symptoms with headache and visual impairment. Longer-term follow-up of these patients is needed to better understand the potential lasting impact on pituitary function and radiological improvement. Future research should also explore the presence of anti-pituitary antibodies and the other possible pathophysiological mechanisms potentially involved in these cases.

To investigate the autoimmune and genetic relationship between primary hypophysitis (PH) and celiac disease (CD). The study was retrospective and patients with PH followed in our clinic between 2007 and 2022 were evaluated. Clinical, endocrinologic, pathologic, and radiologic findings and treatment modalities were assessed. Patients diagnosed with CD in the Gastroenterology outpatient clinic in 2020-2022 were included in the study as a control group. Information such as sociodemographic data, year of diagnosis, human leukocyte antigen (HLA) DQ2/8 information, CD-specific antibody levels, pathologic results of duodenal biopsy, treatment received, follow-up status, additional diseases, hormone use, and surgical history was obtained from patient records at PH.In patients diagnosed with PH, a duodenal biopsy was obtained, and the tissue was examined for CD by experienced pathologists. Anti-pituitary antibody (APA) and anti-arginine-vasopressin (AAVP) antibody levels of individuals with PH and CD were measured. The study included 19 patients with lymphocytic hypophysitis, 30 celiac patients, and 30 healthy controls. When patients diagnosed with lymphocytic hypophysitis were examined by duodenal biopsy, no evidence of CD was found in the pathologic findings. The detection rate of HLA-DQ2/8 was 80% in celiac patients and 42% in PH (p=0.044). (APA and AAVP antibodies associated with PH were tested in two separate groups of patients and in the control group. APA and anti-arginine vasopressin (AAVP) levels in PH, CD and healthy controls, respectively M [IQR]: 542 [178-607];164 [125-243]; 82 [74-107] ng/dL (p=0.001), 174 [52-218]; 60 [47-82]; 59 [48-76] ng/dL (p=0.008) were detected. The presence of an HLA-DQ2/8 haplotype correlates with posterior hypophysitis and panhypophysitis (r=0.598, p=0.04 and r=0.657, p=0.02, respectively). Although patients with PH were found to have significant levels of HLA-DQ2/8, no CD was found in the tissue. Higher levels of pituitary antibodies were detected in celiac patients compared with healthy controls, but no hypophysitis clinic was observed at follow-up. Although these findings suggest that the two diseases may share a common genetic and autoimmune basis, the development of the disease may be partially explained by exposure to environmental factors.