Lymphocytic hypophysitis and central diabetes insipidus during adolescence: what are the criteria for diagnosis?

Abstract

Sir: We read with interest the paper of Cemeroglu et al [1] describing a 14-year-old girl with acute central diabetes insipidus (DI), secondary amenorrhoea and normal neurological and visual examinations. MRI of the brain revealed a 10 10 10 mm mass involving the pituitary stalk and hypothalamus which spontaneously reduced within 3 months and returned to 10 8 10 mm 3 months later. At 6 months the T1-weighted posterior pituitary hyperintensity was absent (no mention of the posterior pituitary status on initial MRI). Endocrine evaluation revealed hypogonadotropic hypogonadism and low insulin-like-growth-factor-I (IGF-I) level. Histological examination showed signs of chronic in ammation with a predominant lymphocytic in®ltrate compatible with lymphocytic hypophysitis. We wish to make some comments and suggestions: We have described an 8-year-old girl with acute onset central DI and acquired growth hormone (GH) insuciency in whom the ®rst MRI showed a thick pituitary stalk and undetectable posterior pituitary hyperintensity [2]. Serial MRI studies were unchanged for 5 years when a huge mass involving the pituitary stalk and hypothalamus was documented togeher with clinical and laboratory features of panhypopituitarism. Histopathology revealed perivascular in ammatory lymphoplasmatic in®ltrates with absence of granulomatosis and necrosis and negative staining for S-100 protein. The patient was treated with high dose prednisolone (30 mg/kg per day, total dose of 2.4 g in 20 min infusion for 3 days). MRI performed 1 month later showed an approximately 50% decrease in the mass, with partial anterior pituitary recovery (thyroid and adrenal) maintained for 2 years after treatment began. In our opinion, the features reported by Cemeroglu et al. [1] do not permit a convincing diagnosis of classical lymphocytic hypophysitis as traditionally conceived: the disease onset is unrelated to pregnancy, the posterior pituitary is involved, the mass on coronal MRI is con®ned to the pituitary stalk and hypothalamus while the anterior pituitary is spared, there is no evidence of lymphocyte in®ltration and/or destruction of the anterior pituitary tissue and no other co-existing auto-immune disorders are associated [3]. We believe that the disease reported by Cemeroglu et al. [1] belong to a unique spectrum of in ammatory auto-immune vascular-mediated conditions variably affecting the hypothalamic-pituitary area. The statement that ``the loss of the normal posterior pituitary T1-weighted hyperintensity may have been a clue to the diagnosis of lymphocytic hypophysitis before biopsy in this case'' is rather misleading because the lack of posterior pituitary hyperintensity in central DI is a nonspeci®c hallmark of a hypothalamic-neurohypophyseal axis lesion [2, 4]. The conservative management of these tumour-like conditions appears reasonable but in the patient reported by Cemeroglu et al., the chronic growth pattern and the size of the mass as well as the documentation of an in ammatory process after pituitary stalk biopsy require in our opinion a tentative treatment approach. Only few controversial data with di€erent treatment modalities and outcome have been reported but the favourable response to glucocorticoids in our patient underlines the possible role of steroids in the management of such in ammatory masses. We believe that the low IGF-I level and patient weight increase (6.8 kg.) may have been due to acquired GH insuciency which is frequently associated with such lesions. Thus, evaluation of GH secretion and clinical indication for GH treatment (metabolic and quality of life e€ects in adults) in case of GH de®ciency merit consideration.