Lymphocytic panhypophysitis and anti-rabphilin-3A antibody with pulmonary sarcoidosis

Abstract

Purpose: To explore the clinical significance of anti-rabphillin-3A antibody for the differential diagnosis of lymphocytic panhypophysitis. Methods and Results: A 58-year-old Japanese man developed uveitis of unknown cause in 2017. In 2019, he became aware of polyuria. In August 2020, he noticed transient diplopia and was diagnosed with right abducens nerve palsy. At the same time, he complained of fatigue and loss of appetite. Head magnetic resonance imaging demonstrated enlargement of the pituitary stalk and pituitary gland, corresponding to hypophysitis. Hormone stimulation tests showed blunted responses with respect to all anterior pituitary hormones. Central diabetes insipidus was diagnosed on the basis of a hypertonic saline loading test. Taking these findings together, a diagnosis of panhypopituitarism was made. Computed tomography showed enlargement of hilar lymph nodes. Biopsies of the hilar lymph nodes revealed non-caseating epithelioid cell granulomas that were consistent with sarcoidosis. Biopsy of the anterior pituitary revealed mild lymphocyte infiltration in the absence of IgG4-positive cells, non-caseating granulomas, or neoplasia. Western blotting revealed the presence of anti-rabphilin-3A antibody, supporting a diagnosis of lymphocytic panhypophysitis. Because the patient had no visual impairment or severe uveitis, we continued physiological hormone replacement therapy and topical steroid therapy for the uveitis. Conclusion: To the best of our knowledge, this is the first case of anti-rabphilin 3A antibody positive lymphocytic panhypophysitis comorbid with sarcoidosis, diagnosed by both pituitary and hilar lymph node biopsy. The utility of anti-rabphilin-3A antibody for the differential diagnosis of hypophysitis like this case should be clarified with further 4 case studies.

Two children with lymphocytic hypophysitis presenting with positive anti-rabphilin-3A antibody

“…In children with LYH, even if some degree of mild inflammation occurs in the posterior pituitary gland, it may not lead to CDI onset in the early stage of the disease, and inflammation may spread to the anterior pituitary gland, leading to anterior lobe dysfunction. Thus our Case 2 is currently in the pre-onset stage of CDI and may develop CDI in the future, so follow-up imaging and endocrino- [9,17]. Our Case 1 is the first report of pediatric LPH with positive anti-rabphilin-3A antibodies.…”

“…Table 1 summarizes the positive and negative cases of anti-rabphilin-3A antibody in histologically confirmed pituitary diseases from previous reports [9,11,16,17]. The sensitivity was 100% for LINH, 11.1% for LAH, 75.0% for LPH, 87.5% for LINH and LPH.…”

“…The detection of serum anti-rabphilin-3A antibodies has been reported not only in LINH, but also in LPH and LAH [9,11,16,17]. Case 1 presented with anterior and posterior pituitary dysfunction and a histopathological diagnosis of LPH was determined.…”