Lymphocytic Panhypophysitis Research Articles

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

Lymphocytic hypophysitis (LYH) is a rare chronic inflammatory disease characterized by lymphocytic infiltration of the anterior or posterior pituitary gland and hypothalamus. LYH is subdivided into lymphocytic adenohypophysitis (LAH), lymphocytic infundibulo-neurohypophysitis (LINH), and lymphocytic panhypophysitis (LPH) depending on the primary site. Most cases occur in adults, with few cases reported in children, and it is especially important to distinguish LYH from suprasellar malignancies, such as germ cell tumors and other neoplastic diseases. Although a biopsy is necessary for definitive diagnosis, it is desirable to be able to diagnose the disease without biopsy if possible, especially in children, because of the surgical invasiveness of the procedure. Recently, serum anti-rabphilin-3A antibodies have attracted attention as diagnostic markers for LYH, especially in LINH, but there are only a few reports on pediatric patients. In the present study, we experienced two children with LPH and LAH, respectively, who tested positive for anti-rabphilin-3A antibodies. This is the first report of children with LYH other than LINH positive for anti-rabphilin-3A antibodies, and anti-rabphilin-3A antibodies may be a useful non-invasive diagnostic marker not only for LINH but also for LYH in general. We also discuss the sensitivity and specificity of anti-rabphilin-3A antibody testing in cases where histological diagnosis has been made.

Studies on anti-rabphilin-3A antibodies in 15 consecutive patients presenting with central diabetes insipidus at a single referral center

Central diabetes insipidus (CDI) is a rare condition caused by various underlying diseases including inflammatory and autoimmune diseases, and neoplasms. Obtaining an accurate definitive diagnosis of the underlying cause of CDI is difficult. Recently, anti-rabphilin-3A antibodies were demonstrated to be a highly sensitive and specific marker of lymphocytic infundibuloneurohypophysitis (LINH). Here, we report a detailed case series, and evaluated the significance of anti-rabphilin-3A antibodies in differentiating the etiologies of CDI. A prospective analysis was conducted in 15 consecutive patients with CDI from 2013 to 2020 at a single referral center. Anti-rabphilin-3A antibodies were measured and the relationship between antibody positivity and the clinical/histopathological diagnoses was evaluated. Among 15 CDI patients, the positive anti-rabphilin-3A antibodies were found in 4 of 5 LINH cases, 3 of 4 lymphocytic panhypophysitis (LPH) cases, one of 2 sarcoidosis cases, and one intracranial germinoma case, respectively. Two Rathke cleft cyst cases and one craniopharyngioma case were negative. This is the first report of anti-rabphilin-3A antibodies positivity in CDI patients with biopsy-proven LPH. Measurement of anti-rabphilin-3A antibodies may be valuable for differentiating CDI etiologies.

Clinical aspects of pregnancy-related lymphocytic hypophysitis

Objective: To analyze clinical features, diagnosis, treatment and prognosis of pregnancy-related lymphocytic hypophysitis (LyH). Methods: The clinical data of 16 cases diagnosed as pregnancy-related LyH at Chinese PLA General Hospital between October 2010 and November 2019 were reviewed. Results: Sixteen patients were included (aged 20-40 years). All patients' symptoms occurred from the last 2 months of pregnancy to 12 months postpartum, with 6 cases in the third trimester and 10 cases during postpartum, and all the patients were diagnosed after delivery. Six patients had lymphocytic adenohypophysitis (LAH), 4 patients had lymphocytic infundibuloneurohypophysitis (LINH), 4 patients had lymphocytic panhypophysitis (LPH), and 2 had lymphocytic hypothalamitis. Eight patients presented with symptoms of intracranial space-occupying lesions, 14 patients had symptoms of anteriorpituitary hormone deficiencies, 9 patients had central diabetes insipidus (CDI), and 2 had hyperprolactinemia. Pituitary MRI showed that the pituitary presented with diffuse enlargement, pituitary stalk thickening, disappearing of high-intensity signals in posterior pituitary and space-occupying lesions in the infundibulum of hypothalamus. Nine patients were treated with immunosuppressive agent, 3 patients alleviated the space-occupying effects after surgery, and 4 patients recovered spontaneously. Fourteen patients were followed up with a period of 3-98 months. Four patients had a relapse, 2 patients had a complete remission, and 12 patients needed long-term hormone replacement therapy. Conclusions: Clinical manifestations of pregnancy-related LyH are diverse. LyH should be suspected in pregnant or postpartum women with a sellar mass to avoid missed diagnosis or misdiagnosis. Immunosuppressant therapy is effective. Overall, LyH patients have a favorable prognosis.

Single center study of 53 consecutive patients with pituitary stalk lesions.

The etiological spectrum of pituitary stalk lesions (PSL) is wide and yet specific compared to the other diseases of the sellar and suprasellar region. Because of the pituitary stalk's (PS) critical location and role, biopsies of these lesions are rarely performed, and their underlying pathology is often a conundrum for clinicians. A pituitary MRI in association with a clinical context can facilitate their diagnosis. To present the various causes of PSL-their clinical, hormonal, histopathological, and MRI characteristics in order to gain better insight into this pathology. A retrospective observational study consisting of 53 consecutive patients with PSL of the mean age 32 ± 4.2years (range 6-67), conducted at the Department for Neuroendocrinology, Clinical Center of Serbia 2010-2018. Congenital malformations were the most common cause of PSL in 25 of 53 patients (47.1%), followed by inflammatory (9/53; 16.9%) and neoplastic lesions (9/53; 16.9%). The exact cause of PSL was established in 31 (58.4%) patients, of whom 23 were with congenital PS abnormalities and 8 with histopathology of PSL (7 neoplastic and 1 Langerhans Cell Hystiocytosis). A probable diagnosis of PSL was stated in 12 patients (22.6%): 6 with lymphocytic panhypophysitis, while Rathke cleft cyst, tuberculosis, dissemination of malignancy in PS were each diagnosed in 2 patients. In 10 patients (18.8%), the etiology of PSL remained unknown. Due to the inability of establishing an exact diagnosis, the management and prognosis of PSL are difficult in many patients. By presenting a wide array of causes implicated in this condition, we believe that our study can aid clinicians in the challenging cases of this pathology.

Clinical features and prognosis of 18 cases of primary lymphocytic hypophysitis

Objective: To analyze clinical features, prognosis and treatment of lymphocytic hypophysitis (LYH). Methods: The clinical data, treatments and outcomes of 18 cases diagnosed as LYH at Chinese PLA General Hospital between January 2001 and July 2017 was respectively reviewed. Results: Eighteen patients with histology-proven LYH (13 females and 5 males ) were identified. All lymphocytic adenohypophysitis (LAH) were females(n=6), two of whom were associated with pregnancy. Eleven patients (6 females and 5 males) had lymphocytic panhypophysitis (LPH) and one(female) had hypothalamitis. Pre-treatment evaluation revealed that 11 patients presented with symptoms of intracranial space-occupying lesions, 12 patients had symptoms of anterior pituitary hormone deficiencies, and 12 patients had central diabetes insipidus (CDI). All patients had space-occupying lesions on magnetic resonance imaging (MRI), which were symmetrically enlarged and homogenously enhanced with or without pituitary stalk thickening. Before or after surgery, 11 patients received immunosuppressant therapy or radiotherapy to alleviate space-occupying effect. After 4-204 months follow-up, 5 patients had a relapse and received immunosuppressants, radiotherapy or surgery to achieve remission. Full recovery (both symptomatic and radiographic) was seen in 6 patients, and 11 patients maintained stable replacement therapy. Conclusions: LYH presents with acute space-occupying effects such as headache, visual disturbances, hypopituitarism, CDI and mild hyperprolactinemia, especially with characteristic radiographic manifestations. Usually, surgery reliably establishes diagnosis, and immunosuppressant therapy is a necessity. On the whole, LYH has a good prognosis.

Pituitary autoimmune disease: nuances in clinical presentation

Pituitary autoimmune disease is considered an autoimmune organ-specific disorder, characterized by a pituitary infiltration of lymphocytes, macrophages, and plasma cells that could lead to loss of pituitary function. Hypophysitis may be secondary to systemic diseases or infections. Primary pituitary hypophysitis is classified into lymphocytic, granulomatous, xanthomatous, mixed forms (lymphogranulomatous, xanthogranulomatous), necrotizing and IgG4 plasmacytic, according to the histological findings. Concerning lymphocytic hypophysitis (LH), it is characterized by lymphocytic infiltration and can be subclassified according to the affected area on: lymphocytic adenohypophysitis, lymphocytic infundibulo-neurohypophysitis and lymphocytic panhypophysitis. LH had always been considered a rare disease. Nevertheless, with improved imaging techniques, especially magnetic resonance imaging (MRI), LH diagnosis has been increased. This disease usually affects young women during pregnancy or postpartum period with headache, visual impairment, ACTH deficiency and a homogenous sellar mass with thickening of pituitary stalk in MRI. Definitive diagnosis depends on histopathological evaluation; nevertheless, a presumptive diagnosis could be done in a typical case. As no specific autoantigen was identified in LH, there is no antipituitary antibody (APA) method available for helping diagnosis. However, APA used in some centers for research could support an autoimmune origin for some hypopituitarism previously named as idiopathic, confirming nuances in clinical presentation of pituitary autoimmune disease. Therapeutic approach should be based on the grade of suspicious and clinical manifestations of LH.

Ｐａｔｔｅｒｎ ｒｅｖｅｒｓａｌ ＶＥＰにて視神経炎が示唆されたリンパ球性下垂体炎の１例

Lymphocytic hypophysitis (LYH) is a rare neuroendocrine disorder characterized by autoimmune inflammation of the pituitary gland. Visual disturbance is one of the most common and serious symptoms of LYH. Most of the visual symptoms in LYH are secondary to compression of the optic chiasm and some reports have described direct inflammatory involvement of the optic pathways. We describe a 30-year-old man with a 9-day history of bilateral blurred vision. Ophthalmic examination demonstrated severely impaired vision without temporal hemianopsia. Hypothyroidism, hypocortisolism, and hypogonadism were detected in laboratory tests. Central diabetes insipidus was diagnosed by a hypertonic saline infusion test. MRI revealed thickening of the pituitary stalk and enlargement of the hypophysis, which was enhanced with gadolinium. High intensity of the posterior lobe was not recognized on T1-weighted images. These findings established a clinical diagnosis of lymphocytic panhypophysitis. Methylprednisolone pulse therapy was introduced and his visual acuity gradually recovered. The anterior pituitary function improved, but desmopressin was still required. Pattern-reversal visual evoked potentials (VEP) have been widely used to detect optic nerve lesions caused by multiple sclerosis and brain tumors. However, there have been no previous reports of their usefulness for LYH. The P100 latency in our case was slightly prolonged and the amplitude was markedly reduced. These findings are similar to ischemic optic neuropathy and other conditions in which axonal damage is prominent. The prolonged latency and low amplitude on VEP examination in this case showed rapid improvement in parallel with the recovery of visual acuity. Taken together, our case implies the usefulness of pattern-reversal VEP for the diagnosis of optic neuritis in LYH, especially for the evaluation of its pathogenic mechanisms.

A case of lymphocytic panhypophysitis (LPH) during pregnancy

A 37-year-old pregnant woman developed continuous headache in the 10th week of pregnancy, followed by bilateral visual field defect and general malaise in the 24th week. The brain magnetic resonance imaging showed a pituitary mass. In laboratory examination, plasma concentration of free thyroxine, thyroid stimulating hormone (TSH), cortisol, and adrenocorticotropic hormone (ACTH) was low. General malaise vanished shortly after the replacement therapy of glucocorticoid and thyroid hormone, but partial central diabetes insipidus (CDI) appeared, which could be treated with desmopressin acetate (DDAVP). The visual field defect having enlarged, transsphenoidal surgery was performed in the 31st week of pregnancy. Adenohypophysis could be resected, and it showed infiltration of mature lymphocytes. After the surgery, the visual defect had improved, but hormone replacement was still necessary. She delivered a baby in the 38th week without any trouble. Provocative tests after delivery revealed a low response in TSH, prolactin (PRL), and follicle stimulating hormone (FSH). Hormone replacement and DDAVP administration was necessary in the same doses after delivery. The diagnosis was lymphocytic panhypophysitis (LPH). In the case of pregnant woman, LPH should be included in the differential diagnosis of pituitary mass for the fetomaternal safety.

Lymphocytic panhypophysitis in a young man with involvement of the cavernous sinus and clivus

Lymphocytic hypophysitis is an unusual inflammatory lesion that is caused by autoimmune destruction of the pituitary gland. We report a case of 42-year-old man who presented with a 6-month history of severe headache, blurred vision in the right eye, hearing loss, polyuria, polydipsia, and impotence. Medical history showed that he and his mother had osteopetrosis. The results of the physical examination and laboratory tests showed that secondary hypothyroidism, hypogonadism, and hypocortisolism had developed. Central diabetes insipidus was diagnosed by water deprivation test. MRI of the sella showed pituitary enlargement with symmetrical suprasellar expansion, compression of the chiasma, thickened infundibulum, and involvement of both bilateral cavernous sinuses and clivus. Hormonal substitution with hydrocortisone, levothyroxine, and DDAVP resulted in rapid improvement of all symptoms and signs. Transsphenoidal biopsy was diagnostic of lymphocytic hypophysitis. In spite of extensive literature reviewing, we have not been aware of any case of lymphocytic hypophysitis with clivus involvement. The present case represents a variant of lymphocytic hypophysitis which has progressed to involve bilateral cavernous sinuses and the clivus.