A 53-year old woman presented with a 6-month history of progressive lethargy, weakness and weight loss. Past medical history was significant for chronic relapsing intermittent optic neuropathy on methotrexate and AV nodal conduction disease necessitating permanent pacemaker. Baseline anterior pituitary function showed hypopituitarism with hyperprolactinaemia. Uniform enlargement of the anterior pituitary and infundibulum was evident on neuroimaging, suggestive of an inflammatory process. Pituitary biopsy reported numerous granulomas and mild lymphocytic infiltrate. Diabetes insipidus developed post-biopsy.
Additional investigations to exclude a secondary process included a high-normal ACE (62 u/L), 1,25-dihydroxyvitamin D (207 pmol/L), disproportionate to 25-hydroxyvitamin D (66 pmol/L). PET-CT showed uptake in the pituitary and inguinal lymph node, which showed reactive changes on biopsy. Treatment with prednisolone and subsequent mycophenolate resulted in a reduction in pituitary size and a fall in ACE and 1,25-dihydroxyvitamin D.
Hypophysitis can be primary or secondary. Primary hypophysitis includes lymphocytic, granulomatous, xanthomatous, and IgG4 hypophysitis. Pituitary granulomas are usually associated with systemic granulomatous diseases, including sarcoidosis, tuberculosis, syphilis, histiocytosis X, systemic mycoses and granulomatosis with polyangiitis, or Rathke’s cleft cyst rupture. Exclusion of these is required for a diagnosis of idiopathic granulomatous hypophysitis.
Our patient’s current diagnosis is idiopathic granulomatous hypophysitis, based on pituitary histopathology and the current lack of evidence for a systemic granulomatous disease; however the possibility of sarcoidosis remains. The pituitary biopsy was thought justified by the high suspicion of systemic disease, which may have developed whilst on immunosuppression. Diabetes insipidus has persisted, requiring desmopressin in addition to anterior pituitary replacement therapy.
The diagnosis of hypophysitis can be challenging and the decision whether to proceed with pituitary biopsy remains controversial. It is unclear whether idiopathic granulomatous hypophysitis can be reliably distinguished from isolated pituitary sarcoidosis. Further results from ongoing investigations and clinical monitoring will be available for presentation.