Histoplasmosis infection is endemic in Asia and disseminated histoplasmosis (DH) is one
form of its presentation (Benevides et al., 2007). DH commonly affects both adrenal glands. We describe a case of disseminated histoplasmosis complicated with hypercalcaemia in a 75-year-old immunosuppressed patient who presented with bilateral adrenal masses. The fine needle aspiration cytology of the adrenal mass was positive for Histoplasma capsulatum

Nor Azmi, Kamaruddin

Norasyikin, A. Wahab

Rozita, Mohd

Suehazlyn, Zainudin

Eldorado - Repository of the TU Dortmund

EXCLI Journal 2013;12:1-4 – ISSN 1611-2156 Received: December 03, 2012, accepted: December 19, 2012, published: January 11, 2013  1 Case report:  ADRENAL INVOLVEMENT IN HISTOPLASMOSIS  Norasyikin A. Wahab*, Rozita Mohd, Suehazlyn Zainudin, Nor Azmi Kamaruddin  * corresponding author: Norasyikin A.Wahab, Department of Medicine, Pusat Perubatan  Universiti Kebangsaan Malaysia (PPUKM), Jalan Yaacob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. Tel: +603-91456934 E-mail: Naw8282kt@gmail.com   ABSTRACT Histoplasmosis infection is endemic in Asia and disseminated histoplasmosis (DH) is one form of its presentation (Benevides et al., 2007). DH commonly affects both adrenal glands. We describe a case of disseminated histoplasmosis complicated with hypercalcaemia in a 75-year-old immunosuppressed patient who presented with bilateral adrenal masses. The fine needle aspiration cytology of the adrenal mass was positive for Histoplasma capsulatum.  Keywords: Histoplasma capsulatum, disseminated histoplasmosis, adrenal masses, hypo-adrenalism    INTRODUCTION Histoplasmosis is a fungal disease caused by the dimorphic fungus Histoplas-ma capsulatum (H. Capsulatum) The dis-ease is endemic in certain parts of the world including Asia (Benevides et al., 2007). Spores containing H. capsulatum can be found in soils contaminated by droppings from birds and bats. Patients are infected via inhalation of these spores and up to 80 % of them are skin test positive with his-toplasmin (Jombo et al., 2010). Most in-fected patients are asymptomatic or have a self-limiting disease (Rana et al., 2011; Mahajan et al., 2000). Histoplasmosis usu-ally presents in 2 forms; pulmonary and ex-trapulmonary, which is also known as dis-seminated histoplasmosis (DH). Dissemi-nated histoplasmosis is uncommon but fre-quently (80 %) affects the adrenal glands (Goodwin et al., 1980). In such cases, pa-tients often present with bilateral adrenal masses (Kumar et al., 2003). However, the incidence of hypoadrenalism amongst these group of patients is rare and was reported to be ranging between 7 to 20 % (Subramanian et al., 2005; Rajesh et al., 2010). Hence, a high index of suspicion is prudent as the presentation may mimic oth-er chronic infections or malignancy espe-cially in the elderly or the immunosup-pressed host (Jaiswal et al., 2011). We re-port a case of an elderly man with bilateral adrenal histoplasmosis and normal cortisol response who presented with vague symp-toms and hypercalcaemia.  CASE REPORT  A 75-year-old man, with a background medical history of diabetes and hyperten-sion for 10 years, presented to a private hospital with a history of prolonged fever, malaise and marked weight lost for a month. Computed tomography (CT) scan of the abdomen revealed bilateral adrenal masses measuring 3.4 x 2.9 cm (right) and 3.9 x 3.1 cm (left) respectively. A biopsy of the adrenal mass was inconclusive. After being treated empirically with oral flucona-zole 200 mg daily for 2 months, his symp-EXCLI Journal 2013;12:1-4 – ISSN 1611-2156 Received: December 03, 2012, accepted: December 19, 2012, published: January 11, 2013  2 toms disappeared and he did not attend sub-sequent clinic appointments. Six months later, he presented to our in-stitution with similar symptoms of general-ized bodyaches and 4 month’s duration of significant loss of appetite and weight. On further questioning, he revealed a history of contact with birds. Clinically, he was dehy-drated with no lymphadenopathy or organo-megaly. He had normocytic anaemia (he-moglobin 10.6 x 109/L), mild thrombocyto-penia (133 x 109/L) and acute kidney injury with urea of 17.8 mmol/L, potassium 4.4 mmol/L, sodium 144 mmol/L and creat-inine 365 mmol/L. Both corrected serum calcium and alkaline phosphates were ele-vated with levels of 3.40 mmol/L and 319 U/L respectively. Diabetic control was good with HbA1c of 5.6 %. His random serum cortisol was normal (467 nmol/L) with adequate responses on synacthen test. Serology for syphilis, hepatitis A, B, C, toxoplasma antibodies and tumour markers (alpha fetoprotein, CEA 125, CA 19-9) were negative. Serum iron and TIBC were low with levels of 8.7 umol/L and 35 umol/L respectively. Sputum samples stained for acid fast bacilli were negative. Multiple myeloma workouts and HIV screening were also negative. Chest radio-graph was unremarkable. A repeated CT scan of the adrenals showed persistent bi-lateral adrenal masses measuring 5 x 4 cm on the left and 4 x 3.6 cm on the right re-spectively (Figure 1 and 2). Fine needle as-piration cytology of the left adrenal gland was consistent with histoplasmosis infec-tion (Figure 3).  The patient was treated with liposomal form of amphotericin B 180 mg daily for 2 weeks followed by oral itraconazole 200 mg bd. His serum calcium normalised and creatinine level stabilized at 171 mmol/L after adequate rehydration. The patient was discharged home after 2 months of hospital stay with oral itracona-zole which was continued for a total of 1 year duration of treament. On his subse-quent clinic appointments, he was asymp-tomatic, gained weight and tolerated his treatment well. Repeated CT scan showed a significant reduction in sizes of his adrenal masses.     Figure 1: Axial computed tomography scan showed heterogenous enhancing bilateral ad-renal enlargement (arrow) measuring 5.0 x 4.0 cm on the left (attenuation value, 30-40 HU) and 4 x 3.6cm on the right (attenuation value, 40-50 HU) with peripheral enhancement and septations.     Figure 2: Sagital computed tomography scan showed heterogenous enhancing bilateral ad-renal enlargement (arrow).  EXCLI Journal 2013;12:1-4 – ISSN 1611-2156 Received: December 03, 2012, accepted: December 19, 2012, published: January 11, 2013  3   Figure 3: Histopathology of biopsy specimen from the left adrenal mass which showed nu-merous thin-walled rounded yeast liked bodies and some with budding (arrow), seen especially within the necrotic area (Grocott stain, x 1000).   DISCUSSION The presentation of disseminated histo-plasmosis usually mimics other chronic in-fections or malignancy as illustrated in this case. The differential diagnoses that should be considered include tuberculosis, histo-plasmosis, sarcoidosis, adrenal haemor-rhage, metastatic carcinoma and lymphoma (Mukherjee et al., 2005; Narang et al., 2009).  Inhalation of H. capsulatum leading to pulmonary infection is usually asymptomat-ic or without any sequelae. However, pre-vious study had shown that the reactivation of infection can manifest in severe forms and usually occurs in extreme age and in an immunocompromised or immunosup-pressed state such as in a diabetic patient (Jaiswal et al., 2011). Our patient is an el-derly man with underlying diabetes and had history of contact with pigeons. Once in-fected, the period of latency may extend up to 60 years (Jaiswal et al., 2011).  Hypoadrenalism is rarely reported in disseminated histoplasmosis with adrenal involvement. Kauffman showed only 12 out of 58 elderly patients with histoplasmosis were found to have adrenal involvement and none of them had adrenal failure (Kauffman, 2001). This was consistent with the findings in our patient. Typically, patients with adrenal histo-plasmosis present with bilateral adrenal en-largement with normal configuration, pe-ripheral enhancement and central hypoden-sity as a result of necrosis or haemorrhage on the CT scan (Mukherjee et al., 2005). However, bilateral adrenal enlargement with similar characteristics may be also be seen in adrenal haemorrhage, lymphoma, metastatic or disseminated infections such as histoplasmosis, tuberculosis, cryptococ-cosis, blastomycosis, or aspergilosis (Mukherjee et al., 2005). The presence of central necrosis and pe-ripheral rim enhancements of the adrenals would narrow down the above differentials to tuberculosis and histoplasmosis. Hence, cytology or histopathological examination of the adrenal mass after a fine needle aspi-ration or percutaneous biopsy which exhib-its typical microscopic features of H. capsu-latum would be the best method to differen-tiate these two diagnoses especially in the absence of conclusive supporting history which would point to either one. H. capsu-latum is an intracellular dimorphic fungus which is usually seen in the macrophages cytoplasm and exhibits narrow based bud-ding (Fitzhugh et al., 2010; Gopal et al., 2010). Our patient underwent adrenal biop-sies twice as the earlier biopsy was unsuc-cessful. Histopathological examination from the repeat adrenal biopsy done a year later was consistent with histoplasmosis. The mortality in untreated DH patients was as high as 80-100 % but if treated with antifungal, this very high mortality rate is remarkably reduced to less than 25 % (Subramanian et al., 2005). The recom-mended treatment for adrenal histoplasmo-sis is similar to the disseminated histoplas-mosis by using amphotericin B. Previous study recommended a total dose of 3 to 4 g of amphotheracin B (Johnston et al., 1996). Once the condition improves, the therapy can be switched to itraconazole 200 mg bd. In our patient, the primary antifungal thera-py instituted was liposomal amphoteracin B for 2 weeks. Upon discharge, it was changed to itraconazole and was continued for one year. Apart from less nephrotoxici-ty, the liposomal amphothericin B achieves EXCLI Journal 2013;12:1-4 – ISSN 1611-2156 Received: December 03, 2012, accepted: December 19, 2012, published: January 11, 2013  4 the cumulative target dose faster than regu-lar amphotericin B, resulting in shortened hospital stay. Recurrence of disease has been reported after 9 years after cessation of therapy (Rana et al., 2011). A treatment duration of between 1 to 2 years is recom-mended to reduce recurrence (Rana et al., 2011).  CONCLUSION When faced with a patient with bilateral adrenal masses, physicians should always be suspicious of adrenal histoplasmosis es-pecially in endemic areas. It is prudent to obtain a cytological or histopathological examination to confirm the diagnosis so that the appropriate treatment can be insti-tuted to avoid fatal complications.  REFERENCES Benevides CF, Duraes RO, Aquino B, Schiavon Lde L, Narciso-Schiavon JL, Buzzoleti Fda C. Bilateral adrenal histo-plasmosis in an immunocompetent man. Rev Soc Brasil Med Trop 2007;40:230-3.  Fitzhugh VA, Maniar KP, Kim MK, Chen H, Schainker BA. Adrenal histoplasmosis. Diagn Cytopathol 2010;38:188-9.  Goodwin RA Jr., Shapiro JL, Thurman GH, Thurman SS, Des Prez RM. Disseminated histoplasmosis: clinical and pathologic correlations. Medicine 1980;59:1-33.  Gopal K, Singh S, Gupta R. Fine needle aspiration cytology in bilateral adrenal masses in a 58-year-old man. Acta Cytol 2010;54:234-6.  Jaiswal S, Vij M, Chand G, Misra R, Pandey R. Diagnosis of adrenal histoplas-mosis by fine needle aspiration cytology: an analysis based on five cases. Cytopatholo-gy: official journal of the British Society for Clinical Cytology 2011;22:323-8.  Johnston AW, Brown PA, Ewen SW. Histoplasmosis - a ten year follow-up. J Infect 1996;33:111-3.  Jombo GTA, Denen Akaa P, Banwat EB, Dauda M. A review of literature on unusual clinical presentations and potential challenges in diagnosis of histoplasmosis. J Clin Med Res 2010;2:159-66.  Kauffman CA. Fungal infections in older adults. Clin Infect Dis 2001;33:550-5.  Kumar N, Singh S, Govil S. Adrenal histo-plasmosis: clinical presentation and imag-ing features in nine cases. Abdom Imag 2003;28:703-8.  Mahajan R, Sharma U, Trivedi N, Prasad M, Kansra U, Bhandari S et al. Histoplasma capsulatum in adrenal gland aspirate--a case report. Ind J Pathol Microbiol 2000;43: 165-8.  Mukherjee JJ, Villa ML, Tan L, Lee KO. Bilateral adrenal masses due to histoplas-mosis. J Clin Endocrinol Metabol 2005;90: 6725-6.  Narang V, Sinha T, Sandhu AS, Karan SC, Srivastava A, Sethi GS et al. Clinically inapparent bilateral adrenal masses due to histoplasmosis. Europ Urol 2009;55:518-21.  Rajesh KF, Warrier V, Gayathri R, Chellen-ton J, Geetha P, Thulaseedharan NK. A case of histoplasmosis. Calicut Med J 2010;8(2):e7.  Rana C, Kumari N, Krishnani N. Adrenal histoplasmosis: a diagnosis on fine needle aspiration cytology. Diagn Cytopathol 2011;39:438-42.  Subramanian S, Abraham OC, Rupali P, Zachariah A, Mathews MS, Mathai D. Disseminated histoplasmosis. J Assoc Physicians India 2005;53:185-9.  

Adrenal invovement in histoplasmosis

https://eldorado.tu-dortmund.de/bitstream/2003/30493/1/Norasyikin_11012013_proof.pdf

Adrenal invovement in histoplasmosis

Abstract

Similar works

Full text

Available Versions

Eldorado - Repository of the TU Dortmund