Lymphocytic hypophysitis: non-invasive diagnosis and treatment by high dose methylprednisolone pulse therapy?

Abstract

Criteria for the non-invasive diagnosis of lymphocytic hypophysitis (LyHy) and the results of the first prospective trial of high dose methylprednisolone pulse therapy (HDMPT) in nine patients are presented. In three patients, the diagnosis was established histologically, and in the others by clinical and endocrinological assessment, MRI, CSF examination, and measurement of thyroglobulin autoantibody concentration. After HDMPT, adenopituitary function improved in four of the nine patients and diabetes insipidus ceased or improved in all four concerned patients. The MRI findings improved in seven patients. LyHy has to be considered in the diVerential diagnosis of sellar lesions. The presumptive non-invasive diagnosis of LyHy seems possible in a high proportion of patients. HDMPT may result in the improvement of clinical, endocrinological, and MRI findings. (J Neurol Neurosurg Psychiatry 1999;67:398-402) Keywords: lymphocytic hypophysitis; high dose methylprednisolone pulse therapy Lymphocytic hypophysitis (LyHy) is a rare chronic inflammatory disease with little known natural history, 1-7 usually diagnosed unexpectedly at surgery for presumptive pituitary adenoma.1 5 8 9 Experience in the treatment of LyHy is scarce. Non-invasive diagnostic criteria and results of standardised HDMPT are presented. Patients and methodsAll patients with LyHy (mean age 41 years, seven women) diagnosed at our institution are reported on. Adenohypophyseal function was dynamically assessed as described by Thorner et al. 13 Neurohypophyseal function was assessed as described by Reeves and Andreoli.14 Evaluation of the sellar region by MRI was carried out as described by Elster. 15 In the six patients not operated on, CSF was evaluated by white cell count, cytology, global protein content, and neurotropic virus serology (herpes simplex, varicella zoster, mumps). The thyroglobulin autoantibody concentration was measured in four patients. In three patients, LyHy was diagnosed histologically. In the others, diVerential diagnosis was considered for tuberculosis, sarcoidosis, and syphilis by clinical, laboratory (tuberculin test, angiotensin I converting enzyme measurement, treponema pallidum haemaglutination test), and chest radiograhy evaluation.The high dose short lasting methylprednisolone administration aimed at minimising the side eVects of chronic corticosteroid therapy and at diVerentiating therapeutic eVects from longterm natural course of LyHy. HDMPT consisted of 120 mg methylprednisolone daily for 2 weeks, followed by a dose reduction to 80, 60, 40, and 20 mg daily for 1 week each. Each patient received one course of HDMPT.Results were assessed by endocrinology and MRI as presented above, at 3, 6, and 12 month intervals thereafter. The average follow up amounted to 29 (19-38) months.Literature research was done using the Medline program and the key word hypophysitis. ResultsThe patient's details and courses of disease are listed in the table.Two of the three patients operated on were only biopsied because the intraoperat...

Primary hypophysitis: clinical-pathological correlations

“…Initial treatment with immunosuppressive drugs like glucocorticoids is generally recommended in cases suspected for lymphocytic or granulomatous hypophysitis where vision is not endangered by pituitary mass lesion (8,10). However, endocrinological and neuroradiological improvement under pre-or postoperative high-dose corticosteroids is most often not only incomplete, but also only transient or even fails (8,10,14,20,(23)(24)(25)(26)(27)(28)(29).…”

“…Its treatment at the moment is only symptomatic and aimed at reducing the size of the enlarged pituitary. Pituitary surgery (5,6), lympholytic drugs such as glucocorticoids (7,8), azathioprine (9), and methotrexate (10), or radiotherapy (11) are the current approaches.…”

Lymphocytic hypophysitis and headache in pregnancy

“…Previous investigators have supported biopsy of the pituitary mass and, in some cases, total hypophysectomy in order to obtain the correct diagnosis 2,4 . Current medical opinion, however, suggests that in the typical clinical setting of the peripartum period and the characteristic endocrine deficits described in our case, biopsy may be avoided 3,6 . In the absence of visual failure, pituitary replacement therapy with repeated visual field and radiologic assessment may be all that is required.…”

“…In the absence of visual failure, pituitary replacement therapy with repeated visual field and radiologic assessment may be all that is required. High doses of corticosteroids have been used in some patients to ameliorate visual impairment 6 , but their use has not been vigorously evaluated. Indications for surgery include progressive visual failure and uncertain diagnosis 2,3 .…”

Primary non-necrotizing granulomatous hypophysitis mimicking pituitary adenomas

“…Insufficient treatment has been associated with granuloma formation and sudden death in hypophysitis cases (4,10). Considerable side effects of long-term steroid therapy and recurrence of lesions following steroid withdrawal have been identified (19,21,22,26,28,33). Transsphenoidal surgery is performed for both diagnosis and therapy.…”