Steroid Responsive Xanthomatous Hypophysitis Associated with Autoimmune Thyroiditis: A Case Report
A 36-year-old woman was referred for the evaluation of a pituitary mass detected by brain magnetic resonance image (MRI). She had a 4-month history of amenorrhea and had suffered from headache for 2 months. One month prior to admission, she visited a different hospital emergency room for headache, fever, and vomiting. She was noted to be febrile with a body temperature of 38.5℃. A cerebrospinal fluid (CSF) examination was performed given concerns for meningitis and the CSF findings displayed an elevated white cell count of 350/mm3 (48% lymphocyte), a glucose level of 2.39 mmol/L (normal range, 2.77 to 4.99), and protein 112.7 g/L (normal range, 200 to 400), suggestive of aseptic meningitis. No bacteria or fungi were grown from culture. There was no leukocytosis (white blood count, 7,200/mm3). Her fever resolved after several days of conservative therapies and supportive care. However, her headache still persisted, prompting further imaging. Brain MRI scans showed a cystic pituitary mass prompting her transfer to our hospital.\nOn admission, she also had complaints of general weakness, polydipsia, and polyuria. Her urine volume was more than 5 L per day (specific gravity, 1.006). There was no family history of endocrine disease except for her brother who has hyperthyroidism. She was dehydrated and appeared clinically unwell. She had no visual disturbance and no neurologic deficits such as an abnormal extraocular movement. Her body temperature was 36.4℃ with stable vital signs (blood pressure, 102/77 mm Hg; pulse rate, 96 beats/min). Laboratory investigation showed mild hypernatremia (sodium of 147 mmol/L; normal range, 136 to 145). The patient's serum and urinary osmolarity were 304 and 111 mmol/kg, respectively. Morning serum levels of cortisol (38.64 nmol/L; normal range, 49.66 to 717.34) and estradiol (11.01 pmol/L; normal range, 36.7 to 1,618.4) were low. A mildly elevated level of prolactin (2,756.50 pmol/L; normal range, 156.52 to 821.73) was also noted. Her thyroid function test revealed hyperthyroidism with a high free T4 (34.75 pmol/L; normal range, 8.24 to 22.14) and low thyroid stimulating hormone (0.01 mIU/L; normal range, 0.3 to 6.50). While antithyroglobulin antibody (1,457 kIU/L; normal range, <60) and antimicrosomal antibody (1,720 kIU/L; normal range, <60) were high, anti-TSH receptor antibody (0.1 kIU/L; normal range, 0.1 to 1.0) levels were normal (). Thyroid gland ultrasonography showed a normal volume with diffuse heterogeneous background echotexture of both thyroid glands. Stimulation test with gonadotropin releasing hormone (GnRH) and insulin revealed poor responsiveness to gonadotroph, somatotroph, and corticotrophs. Other routine laboratory findings were all unremarkable. A MRI disclosed a 1.0×0.9 cm sized cystic mass enlarging the sella turcica. The mass had heterogeneous signal intensity and mainly peripheral enhancement was observed after administration of contrast material. There was no extension of the mass into the suprasellar cistern or cavernous sinus (). After 0.2 mg of desmopressin was given orally twice a day, urine volume, serum sodium, and osmolarity normalized. Glucocorticoids were administrated before neurosurgical exploration was performed. Surgical resection via the endoscopic transsphenoidal route was performed. On the pituitary gland, a friable, encapsulated mass with moderate vascularity was found. Histological examination of the resected lesion showed that the pituitary gland was destroyed by infiltration of lymphoplasma cells and foamy histiocytes, fibrosis, and focal necrosis. Foamy histiocytes were positive for CD68 and negative for CD1a and S-100 protein. There was no evidence of an associated adenoma or granuloma (). A postoperative Gadolinium-enhanced MRI was performed on day one postoperatively and showed a residual soft tissue lesion in the superior aspect of pituitary fossa and pituitary stalk (). The patient continued to take desmopressin 0.2 mg twice daily and prednisolone 5 mg once daily after surgery. Two months later, the patient underwent an endocrine work-up. Poor responsiveness to gonadotroph, somatotroph, and corticotrophs was still shown on the anterior pituitary stimulation test with GnRH and insulin. Desmopressin was also not able to be withdrawn. In comparison to her previous study, the level of TSH was still under the normal range (0.02 mIU/L), but her free T4 had decreased (5.53 pmol/L) significantly, which is consistent with secondary hypothyroidism, prompting thyroxin replacement (). At 5 months after operation, the patient still had amenorrhea with low estradiol (11.01 pmol/L) and normal serum follicle stimulating hormone/luteinizing hormone (0.3/1.3 IU/L), and she started estrogen replacement.\nAt the 10-month postoperative visit, the patient complained of progressive visual impairment and headaches. An MRI performed immediately showed that the residual mass seen on the previous MRI had increased in size and infiltrated the suprasellar lesion (). The patient refused to undergo surgery again, prompting a trial of high dose steroid therapy. High dose (500 mg intravenous) methylprednisolone was administered for 3 days. During the methyprednisolone pulse therapy, the patient's visual acuity became clear and her headache resolved. An MRI taken 4 days after methyprednisolone initiation revealed a decreased mass size (). After confirmation of steroid effect on the lesion, high doses of prednisolone (50 mg) were given orally and tapered gradually by 5 to 10 mg per week until her dose reached 10 mg a day. Three months later, a MRI was performed after maintaining prednisolone treatment at 10 mg a day, which demonstrated a marked mass reduction at the sella and suprasellar area ().