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Table of Contents    
Year : 2018  |  Volume : 66  |  Issue : 4  |  Page : 1176-1178

Pituitary aspergillosis - A report and review of the literature

1 Department of Infectious Diseases, Christian Medical College, Ida Scudder Road, Vellore, Tamil Nadu, India
2 Department of Neurosurgery, Christian Medical College, Ida Scudder Road, Vellore, Tamil Nadu, India
3 Department of Pathology, Christian Medical College, Ida Scudder Road, Vellore, Tamil Nadu, India

Date of Web Publication18-Jul-2018

Correspondence Address:
Dr. S Divyashree
Department of Infectious Diseases, Christian Medical College, 4th Floor, SP Complex, Ida Scudder Road, Vellore - 632 004, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.236975

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How to cite this article:
Divyashree S, Karthik R, Prabhu K, Chacko G. Pituitary aspergillosis - A report and review of the literature. Neurol India 2018;66:1176-8

How to cite this URL:
Divyashree S, Karthik R, Prabhu K, Chacko G. Pituitary aspergillosis - A report and review of the literature. Neurol India [serial online] 2018 [cited 2020 Jul 5];66:1176-8. Available from:


Aspergillus species (spp.) are ubiquitous fungi and are common colonizers of the respiratory tract including the paranasal sinuses.[1],[2] Invasive aspergillosis commonly involves the lung while involvement of the central nervous system (CNS) is rare. CNS involvement may take several forms like meningitis, mycetoma, arteritis, encephalitis, etc. Pituitary aspergillosis is extremely rare with less than 20 cases reported in the literature.[1],[2],[3] We report a case of pituitary aspergillosis successfully treated by a combination of surgery and anti-fungal therapy. We also discuss the diagnostic challenges and the management issues of this rare condition.

A 50-year old male patient presented to our institute with headache of 6-month duration. He also complained of generalized weakness and unquantified weight loss. His previous medical history was significant for diabetes and hypertension of 6 years duration. A year ago, he had been hospitalized elsewhere for bilateral pneumonia. During this hospitalization, he had a cardiac arrest and was resuscitated. No further details were available. His current medications included telmisartan, chlorthalidone, amlodipine, glipizide, metformin, aspirin, clopidogrel and atorvastatin. He denied any addictions, trauma, prior surgeries or high-risk behaviour. His clinical examination including a complete neurological examination was unremarkable. Magnetic resonance imaging (MRI) of the brain showed a sellar lesion, mainly in the left half of sella, with bony erosion and cavernous sinus involvement [Figure 1]. It was hypointense on T1–weighted image heterointense on T2 – weighted image and showed an intense post-contrast enhancement. The pituitary gland was not visualized separately from this lesion. However, the pituitary stalk was displaced to the right side. The roof of the sphenoid sinus was eroded. Routine blood investigations and the hormonal profile were normal. A clinical diagnosis of non-functional pituitary macroadenoma was made.
Figure 1: (a) Post contrast coronal T1 weighted image, shows a heterogenous intense enhancing lesion on the left side of sella with left parasellar extension; and (b) Coronal T2 weighted image shows a hypointense lesion seen in the left sellar and left parasellar regions displacing the cavernous segment of the left carotid artery

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He underwent binostril endoscopic trans-sphenoidal biopsy of the lesion. The histopathology showed fragments of adenohypophyseal tissue and parts of a cavitary lesion lined by inflammatory granulation tissue containing dense infiltrates of neutrophils, lymphocytes, plasma cells and histiocytes, including a few foamy histiocytes admixed with multinucleate giant cells. Also seen was separately lying necrotic debris within which were numerous septate fungal hyphae with acute angled branching suggestive of Aspergillus species [Figure 2]. There was no evidence of angioinvasion. Culture grew Aspergillus fumigatus. He had transient hyponatremia in the peri-operative period due to syndrome of inappropriate antidiuretic hormone (SIADH), which was managed appropriately. He received intravenous voriconazole for two weeks followed by oral voriconazole. By the end of 6 weeks, he was completely asymptomatic, and he was continued on voriconazole. At 6 months follow up, he continues to be asymptomatic with normal neurological examination. MRI evaluation 6 months later showed a residual lesion. However, since he was asymptomatic and the lesion had regressed, he was continued on voriconazole. Further follow up is awaited.
Figure 2: (a) Photomicrograph illustrating (a) adenohypophyseal tissue (top arrow) with adjoining wall of abscess (bottom blue arrow) [hematoxylin and eosin ×90]; and (b) Septate fungal hyphae with acute angled branching resembling Aspergillus species (periodic acid Schiff with diastase digestion ×400)

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Pituitary aspergillosis is an extremely rare manifestation of invasive aspergillosis. Vijayvargia et al.,[2] found only 13 cases of pituitary aspergillosis. Liu et al., reviewed ten reported cases of fungal pituitary abscess; aspergillus was the etiological agent in 90% of these cases.[3]

The clinical and radiological presentation often mimicks a pituitary adenoma.[2],[4],[5] Some radiological features have been suggested to favour the possibility of aspergilloma over an adenoma. An important radiological feature of aspergilloma is hypointensity on T2-weighted (W) image.[4] This possibly is due to a high concentration of iron and other ferro-magnetic elements in aspergilloma.[6] The enhancement on contrast MRI is often heterogenous,[4] but can be homogenous, as seen in our case. Sphenoidal sinus involvement has been reported in a few cases.[3] In spite of these features, a correct pre-operative diagnosis is often not reached. Vijayvargiya et al., in their review of 13 reported cases in the literature, found that only 5 cases had a correct pre-operative diagnosis. Similarly, in a report from Andhra Pradesh on 8 cases with isolated central nervous system aspergillosis, none of the patients had a correct preoperative diagnosis.[7] The present case showed intense homogenous enhancement and no hypointensity on T2W images. Since his MRI features were not very characteristic, the diagnosis was not suspected pre-operatively.

Although invasive aspergillosis is commonly seen only in immunocompromised patients, pituitary aspergilloma may be seen without any known immunosuppressive factors. Vijayvargiya et al., reported that 8 of 13 patients did not have any immunosuppressive condition. All the remaining five patients had diabetes. Two of these 5 patients had additional immunosuppresion (in form of long-term steroid therapy). In contrast to his, all of the 8 patients in the study reported by Challa and colleagues were immunocompetent.[7] However, whether or not these patients had diabetes mellitus has not been reported.[7] The present case also had diabetes mellitus.

There is general agreement on the surgical management of suspected pituitary aspergillosis. Several authors suggest that endoscopic transnasal surgery is the preferred surgical option.[1],[2],[3] There is some suggestion that craniotomy increases the risk of subarachnoid spread of aspergillosis and is better avoided.[1],[2],[3]

There is no consensus regarding post-operative antifungal therapy. Although most authors agree that anti-fungal therapy is needed, there are some reports which suggest that antifungal therapy might not be needed at all.[8] Others suggest that patients with non-invasive aspergilloma may not need antifungal therapy following complete surgical evacuation.[2] Thus, the need for postoperative antifungal therapy, particularly in non-invasive cases, is an open question which needs further research. For invasive cases, there is a consensus that post-operative antifungal medication is needed. However, distinguishing invasive from non-invasive aspergillosis in pituitary biopsy specimens may be difficult [2] and till further data is available, we suggest treating all patients with antifungal medicines.

The choice of antifungal medicines is a less controversial issue. Whereas amphotericin was favoured in the past, voriconazole is the preferred drug in recent reports.[3] Voriconazole has better blood-brain penetration compared to amphotericin.[2] Additionally, it has the distinct advantage of being available in an oral formulation and with lesser toxicity. Moreover, a randomised trial has shown better survival with voriconazole compared to amphotericin.[9] For these reasons, voriconazole has currently been considered the drug of choice. The current Infectious Disease Society of America guidelines also recommend the use of voriconazole for central nervous system aspergillosis.[10]

Another area of controversy is the optimal duration of antifungal therapy. For patients receiving azoles, successful cases have reported a duration of treatment of 5-6 weeks.[1],[3] However, this information is not available in many published cases.[4],[5],[6] Also, the randomised trial comparing voriconazole to amphotericin did not specify the planned treatment duration. The median duration of therapy in the voriconazole arm was 11 weeks.[9] However, that trial was done in the setting of invasive aspergillosis. It is unclear whether these results can be applied to an environment where the fungal lesion has already been surgically removed or debrided. In the present case, although all symptoms had resolved by 6 weeks, radiological resolution was not complete even at 6 months. It should be noted here that the surgical procedure in this case was only a biopsy and not complete debridement. We would suggest a minimum duration of therapy for six weeks in patients who have had complete debridement or excision based on the available data; cases without complete surgical debridement may need longer duration of therapy.

The prognosis of CNS aspergillosis has been considered to be grim with a reported mortality of about 90%.[4] However, the prognosis of pituitary aspergillosis seems to be much better. Two recent reports reviewing published cases have reported survival in 11 of 13 cases [2] and 8 of 9 cases.[3] Most of these patients with a favourable outcome have been treated with transsphenoidal surgery followed by antifungal therapy.[2],[3] Of these 3 patients who did not have successful outcome, 2 had been treated with a craniotomy. Both these patients also did not receive antifungal therapy. The third patient was an elderly lady who was a renal transplant recipient and was on immunosuppresive therapy. In the study from India,[7] 2 of 8 (25%) patients died post operatively and another 2 (25%) had recurrence of infection. Although long term follow up was unavailable for the remaining 4 patients, all these 4 (50%) were free from infection at their last follow up.[7] The present patient also had an improvement in all his symptoms by 6 weeks of antifungal therapy. Although there was still some residual disease at 6 months, there were no features to indicate treatment failure.

To conclude, pituitary aspergillosis is a rare condition closely mimicking a pituitary adenoma. Immunosuppression predisposes to this condition but is not always present. A contrast MRI can often, but not always, help in suspecting this diagnosis pre-operatively. A trans-sphenoidal approach with debridement of the lesion is recommended. The postoperative need for antifungal medication is an unanswered question, but medication is probably necessary in cases with vascular invasion. When used, the drug of choice is voriconazole. The optimum duration of therapy is unknown. However, it seems likely that at least six weeks of treatment is needed. With appropriate treatment, most patients are likely to have a prolonged survival.

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There are no conflicts of interest.

  References Top

Hong W, Liu Y, Chen M, Lin K, Liao Z, Huang S. Secondary headache due to aspergillus sellar abscess simulating a pituitary neoplasm: Case report and review of literature. Springerplus. 2015 Sep 24;4:550. doi: 10.1186/s40064-015-1343-6.eCollection 2015.  Back to cited text no. 1
Vijayvargiya P, Javed I, Moreno J, Mynt MA, Kotapka M, Zaki R, et al. Pituitary aspergillosis in a kidney transplant recipient and review of the literature. Transpl Infect Dis 2013;15:E196-200.  Back to cited text no. 2
Liu J, You C, Tang J, Chen L. Fungal pituitary abscess: Case report and review of the literature. Neurol India 2013;61:210-2.  Back to cited text no. 3
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Ahmadzai H, Raley DA, Masters L, Davies M. An unusual case of a pituitary fossa aspergilloma in an immunocompetent patient mimicking infiltrative tumour. J Surg Case Rep. 2013 Apr 18;2013(4). pii: rjt018. doi: 10.1093/jscr/rjt018.  Back to cited text no. 4
Lee JH, Park YS, Kim KM, Lee JH, Park YS, Kim KM, et al. Pituitary aspergillosis mimicking pituitary tumor. Am J Radiol 2000;175:1570-72.  Back to cited text no. 5
Liu W, Chen H, Cai B, Li G, You C, Li H. Successful treatment of sellar aspergillus abscess. J Clin Neurosci 2010;17:1587-9.  Back to cited text no. 6
Challa S, Uppin SG, Purohit AK. Isolated cerebral aspergillus granuloma with no obvious source of infection. Neurol India 2007;55:289-91.  Back to cited text no. 7
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Kalaycı CB, Cevik H. Isolated sphenoid fungal sinusitis and coexisting intrasellar mass lesion presenting with headache as the sole symptom. Acta Radiol Short Rep 2014;3:2047981614546794. doi: 10.1177/2047981614546794.  Back to cited text no. 8
Herbrecht R1, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408-15.  Back to cited text no. 9
Patterson TF, Thompson GR 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016;63:e1-e60.  Back to cited text no. 10


  [Figure 1], [Figure 2]


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