A 43-year-old woman with a past medical history of ileal and colonic CD for 9 years was referred to the Pituitary Center for a sellar mass. Written informed consent was obtained from the patient to report the details of her case. She had been experiencing intermittent debilitating headaches associated with photophobia, diplopia and subjective loss of peripheral vision for 9 months. During one of these episodes, she presented to an outside emergency room where MRI of the brain reportedly showed a pituitary macroadenoma. She was also seen by an ophthalmologist, and underwent formal visual field testing which was normal. Review of systems was positive for worsening fatigue, nausea and secondary amenorrhea for 5 months. She denied symptoms of polyuria or polydipsia. Her CD was considered to be in remission off of medications, but she had been on mesalamine 1 year prior, and corticosteroids were last prescribed 2 years ago. She had no family history of endocrinopathies or pituitary tumors. Her physical examination was notable for a sallow complexion, but was otherwise unremarkable.
Hormonal testing revealed secondary hypothyroidism with a low TSH of 0.271 (0.45-4.5 muIU/mL) and low free T4 of 0.57 (0.82-1.77 ng/dL), secondary adrenal insufficiency with a low cortisol of 1.5 mug/mL with an inappropriately normal ACTH of 8 (6-58 pg/mL), and mildly elevated prolactin of 62.2 (4.8-23.3 ng/mL). There was no symptomatic or laboratory evidence of diabetes insipidus (DI) and her urine osmolality was 651 mOsm/kg concurrent with a serum sodium of 141 mEq/L. MRI brain revealed a 12 mm anterior-posterior x 12 mm craniocaudal x 19 mm transverse sellar lesion abutting the optic chiasm. It was reported as a pituitary adenoma, but infundibular thickening was visible upon closer examination (Figure 1A). The presumed posterior pituitary "bright spot" was visible on the MRI T1 pre-contrast sagittal view (Figure 1A, left panel).
The patient was initiated on levothyroxine and hydrocortisone replacement. She underwent endoscopic transsphenoidal biopsy and partial resection of the pituitary lesion, with the surgical cavity visible on the post-operative MRI (Figure 1B). The first five surgical specimens contained adenohypophysis with lymphocytic infiltrates (anti-CD45 positive) and multiple foci of epithelioid histiocytes with focal multinucleation (anti-CD68 positive) as shown in Figure 2. The sixth specimen was a dural biopsy showing fibroconnective tissue consistent with dura, with mild chronic inflammation.
Pathology was consistent with a diagnosis of GrHy (Figure 2). Special stains for fungi, acid-fast organisms and bacterial organisms were negative. Further evaluation for secondary causes of GrHy, apart from CD, including tuberculosis (TB), syphilis, vasculitis and sarcoidosis was negative (Table 1). Additionally, there was no clinical or histological suspicion for dendritic cell disorders such as Langerhans cell histiocytosis or Erdheim-Chester disease.
A timeline of therapeutic interventions after surgery is depicted in Figure 3. The patient was prescribed high dose oral prednisone, starting at 60 mg daily for 2 weeks, and tapering over 8 more weeks to 5 mg. However, she continued to have a worsening clinical course, including the development of new-onset disruptive polyuria and polydipsia with a serum sodium 142 mEq/L concurrent with a urine Osmolality 320 mOsm/kg, treated successfully with demopressin 0.1 mg daily. MRI revealed relapse of her mass lesion on MRI (Figure 1C).
In conjunction with her specialists in Rheumatology and Gastroenterology, a personalized medicine approach was proposed using an anti-tumor necrosis factor (TNF)-alpha inhibitor because of the efficacy of these agents in CD. Initially, she was started on infliximab. Within 3 months of therapy, she experienced a marked improvement in symptoms and resolution of the mass on MRI (Figure 1D). Azathioprine was added 3 months after infliximab, as per advice from Rheumatology, to reduce the risk for development of neutralizing human anti-chimeric antibodies against the infliximab, as they decrease its efficacy.
While she has persistent central hypothyroidism and adrenal insufficiency, the symptoms of DI resolved within 4 months of initiation of immunosuppressive therapy, and she does not require desmopressin. She had temporary resumption of regular menstrual cycles as well. However, 6 months later her cycles were again interrupted due to recurrence of mild hyperprolactinemia to 33.2 ng/mL, which was thought to be due to infiltration of the stalk. She was started on low-dose cabergoline 0.25 mg weekly, with resolution of amenorrhea and hyperprolactinemia. Her course has been complicated by development of plaque psoriasis which could be due to her predisposition to autoimmunity, but can also be seen paradoxically as a side effect of infliximab. She was switched to a fully humanized anti-TNF-alpha inhibitor adalimumab at 18 months post-operatively, and azathioprine was continued (Figure 3). Subsequent MRI at nearly one and a half years after initiation of immunosuppressive therapy, including 2 months on adalimumab, revealed sustained resolution of the pituitary lesion (Figure 1E).