Pituitary mass with vision loss is not always a pituitary adenoma
A 63-year-old man presented for evaluation of 4 months of headaches and sudden right eye loss of vision. He complained of severe bifrontal throbbing headaches associated with nausea, poor appetite and a 30-lb weight loss during a 4-month period.
He denied any history of fever, easy bruising, muscle weakness, changes in shoe or ring sizes, loss of libido, excessive thirst or polyuria. He was evaluated by a neurologist 2 months before this presentation. CT and MRI scans of the brain were obtained at that time and reportedly demonstrated no abnormalities. A diagnosis of giant cell arteritis was made, and the patient was started on corticosteroid therapy about 1 week before presentation.
On the day of hospital admission, the patient developed acute loss of vision in the right eye while driving to the grocery store. He then drove himself to the hospital ED. His past medical history included hypertension, dyslipidemia, obstructive sleep apnea, heart failure and type 2 diabetes, which was being treated with metformin, glyburide, acarbose and intermediate-acting insulin (recent HbA1c, 7.9%).
MRI scan of the brain with gadolinium was obtained, demonstrating a heterogeneous contrast-enhancing lesion occupying the sella that measured 1.5 ï¿½ 1.7 ï¿½ 1.5 cm (Figure 1). Urgent ophthalmology consultation with visual field testing showed complete loss of vision in the right eye and left temporal hemianopsia.
Endocrine testing performed at 8:30 a.m. documented an increased prolactin level of 31 ng/mL; decreased insulin-like growth factor I (63 ng/mL; reference range 75 ng/mL-228 ng/mL) and decreased testosterone (223 ng/dL; reference range 250 ng/dL-1,100 ng/dL). Testing showed normal follicle-stimulating hormone 10.2 mU/mL; luteinizing hormone 8.7 mU/mL; thyroid-stimulating hormone 1.5 mIU/L; total thyroxine 5 mcg/dL; triiodothyronine uptake 33.8%; free T4 index 1.7; adrenocorticotropic hormone (ACTH) 28 pg/mL; cortisol 9.8 mcg/dL; and alpha subunit 0.8 ng/mL (reference range, 0.6 ng/mL or less). The patient had a normal response to a 250-mcg ACTH stimulation test (baseline cortisol, 7.4 mcg/dL; 30-minute cortisol, 19.1 mcg/dL). Serum sodium and osmolarity were normal, and HIV antibody was negative.
A concerning sella mass
Of concern with a rapidly progressing sella mass in this patient with diabetes was the possibility that this was a rhino-orbital-cerebral zygomycosis (or mucormycosis). The patient underwent endoscopic transsphenoidal resection of the sellar lesion. Pathology revealed the presence of fungal hyphae, confirmed by Gomoriï¿½s methenamine silver (GMS) staining, among fragments of mucosal and meningeal tissue that also demonstrated inflammation and focal necrosis (Figure 2). The synaptophysin immunostaining performed to indicate anterior pituitary tissue was negative. Evaluation of hyphal morphology was limited by the fragmented nature of the organisms in the sections. Although the pathology findings were diagnostic of a fungal infection, there was no growth on fungal cultures and the organism was not identified.
Empirical antifungal therapy with IV amphotericin B lipid complex was initiated. After 10 days, however, the patient developed significant nephrotoxicity and treatment was substituted with oral posaconazole (Noxafil, Schering). He clinically responded to this treatment and was discharged home. The patient did not continue his antifungal agent and did not return for his outpatient follow-up.
He presented again 3 weeks after hospital discharge with worsening headaches, progressive loss of vision in the left eye and severe hyperglycemia. Despite multiple transsphenoidal debridements, a craniotomy with debridement of the sellar area and combination of antifungal therapies, including amphotericin B lipid complex, caspofungin and posaconazole, MRI scan of the brain with gadolinium showed rapid progression of the sellar lesion (Figure 1). The fungal mass completely filled the sphenoid sinus, cavernous sinus and supersellar cistern with encasement of the optic chiasm and optic nerves. His hospital course was further complicated by worsening mental status, hypotension and acute renal failure. Subsequently, the patientï¿½s family requested that comfort measures be initiated, and the patient expired with the family at bedside.
Photos courtesy of: Stephanie L. Lee, MD, PhD
A rare cause of vision loss
Pituitary infections are rare, with bacteria as the most common etiology; fungal infections occur much less frequently. Among patients with fungal infections involving the central nervous system, pituitary involvement is uncommon, occurring in six of 40 patients (15%) in a reported case series.
Patients who are immunocompromised due to hematological malignancies, recipients of solid organ or bone marrow transplants, and those with AIDS or diabetes are known to be at increased risk for systemic fungal infections. However, cases have also been reported in immunocompetent patients.
The pathogenesis of intrasellar fungal infection involves either direct extension from adjacent structures (sphenoid sinus, cavernous sinus or skull base), hematologic spread from disseminated infection or iatrogenic inoculation during transsphenoidal surgical procedures.
The most common fungal infections involving the pituitary include aspergillosis, zygomycosis (including mucormycosis), cryptococcosis, candidiasis, coccidiomycosis, paracoccidioidomycosis and pneumocystosis. In the same case series of intracranial fungal infections, microbiological cultures were positive in 28 of 40 (70%) patients.
Clinical features of pituitary infection are difficult to distinguish from other pituitary processes and include headache, nausea, visual field defects and ophthalmoplegia. Fever, peripheral leukocytosis and signs of meningeal irritation are present only in a minority of patients with bacterial or fungal pituitary infections. Most infections do not result in overt endocrine dysfunction, but cases presenting with hypogonadotropic hypogonadism, hyperprolactinemia or diabetes insipidus have been reported.
Aggressive, uncommon condition
Evaluation of our patient demonstrated an elevated prolactin level, a decreased IGF-I level and findings suggestive of central hypogonadism. Radiological findings of intrasellar fungal infections are difficult to distinguish from bacterial infections and neoplasms; however, it has been suggested that peripheral enhancement, hypointensity and calcifications seen on T2-weighted images favor an infectious process over a tumor. Due to the lack of specific clinical and radiological presentations, most patients with pituitary fungal infections are diagnosed only after surgery or at the time of autopsy.
Treatment of intrasellar fungal infections includes reversal of immunosuppression or, in the case of diabetes, improvement in glycemic control. All patients should undergo surgical debridement of the lesion, and antifungal therapies are warranted. Voriconazole and amphotericin B are the preferred agents for the treatment of aspergillosis, whereas amphotericin B and/or caspofungin (Cancidas, Merck) are preferred for mucormycosis. As demonstrated by our patient, despite surgical and pharmacological treatments, the overall mortality remains high, exceeding 60% to 70%. It is important that endocrinologists recognize this uncommon cause of a pituitary mass as the risk for death increases as a result of delayed diagnoses and treatment of these aggressive infections.
Pornpoj Pramyothin, MD, is a fellow in endocrinology and Philip E. Knapp, MD, is an assistant professor of medicine, both in the section of endocrinology, diabetes and nutrition at Boston Medical Center.
For more information:
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