BACKGROUND Pituitary apoplexy following a major surgical procedure is a catastrophic event and the diagnosis can be delayed in a previously asymptomatic patient. The decision on thromboprophylaxis in shoulder replacements in the absence of definite guidelines, rests on a careful clinical judgment. METHODS A previously healthy 62-year-old Caucasian male patient who underwent shoulder arthroplasty developed hyponatremia resistant to correction with saline replacement. The patient had a positive family history of deep vein thrombosis and pulmonary embolism and heparin thromboprophylaxis was considered on clinical grounds. The patient developed hyponatremia resistant to conventional treatment and later developed ocular localizing signs with oculomotor nerve palsy. The diagnosis was delayed due to other confounding factors in the immediate post-operative period. Subsequent workup confirmed a pituitary adenoma with features of pituitary insufficiency. The patient was managed successfully on conservative lines with a multidisciplinary approach. CONCLUSIONS A high index of suspicion is required in the presence of isolated post-operative hyponatremia resistant to medical correction. A central cause, in particular pituitary adenoma, should be suspected early. Thromboprophylaxis in shoulder replacements needs careful consideration as it may be a contributory factor in precipitating this life-threatening condition.