histoplasmosis is the most common systemic mycosis , characteristically affecting the reticuloendothelial system , blood , and its components . body 's defense mechanisms including both cellular and humoral immunity prevent the affliction by histoplasma . impaired cellular immunity as in uncontrolled diabetes , aids or malignancy could result in invasion and dissemination of the histoplasma . adrenals are a common site of invasion by the histoplasma . in overwhelming acute invasion by the histoplasma , however , chronic forms present as subtle features of adrenal insufficiency such as lethargy , hyperpigmentation , weight loss , and gastrointestinal symptoms . treatment of adrenal histoplasmosis includes antifungals given over a variable period of 6 months to 2 years . however , whether prolonged antifungal treatment can totally eradicate histoplasmosis is unclear . we report here a case whereby the patient diagnosed as adrenal histoplasmosis was treated with 9-month itraconazole therapy and was continued on steroid replacement . there was no regression in the adrenal size and an adrenal biopsy performed 7 years later revealed persistence of histoplasma . a 50 year old male , a diagnosed case of addison 's disease , presented to the endocrine clinic of this hospital for reevaluation . his clinical history dated 7 years back when he presented with complaints of hyperpigmentation and weight loss for 10 months . a diagnosis of primary adrenal insufficiency was made ( acth 743 pg / ml , post - acth cortisol 4.8 mcg / dl , pra 24.7 ng / ml / h ( 1.3 - 3.95 ) and aldosterone 16.6 ng / dl ( 4 - 31 ) and the patient initiated on glucocorticoids and mineralocorticoids . both the adrenals were enlarged on ct imaging ( rt adrena l6.8  3.2 cm and lt adrenal  5.8  4.0 cm ) . adrenal biopsy revealed numerous tiny unstained elliptical yeast - like bodies , some of them showing budding . he received itraconazol 400 mg daily for 9 months which was then stopped and the patient continued on steroid replacement therapy . he had developed diabetes for the past 2 years and had been receiving oral hypoglycemics . present evaluation revealed a 75 kg male with no cutaneous striae ; blood pressure was 151/93 mm hg . investigations revealed a normal hemogram with esr-40 , and normal liver and kidney function tests and thyroid function tests , acth 19.5 pg / ml and post - acth cortisol levels 4.3 mcg / dl after 1 day of missing the steroid preparation . a repeat ct imaging revealed bilaterally enlarged adrenals with no significant change in either the size or the morphology of the adrenals when compared to the previous ct imaging . repeat adrenal biopsy revealed necrotic tissue with numerous spores of histoplasma capsulatum that stained positive with the pas stain and grocott methanamine silver stain [ figure 2 ] . adrenal biopsy shows numerous tiny unstained elliptical yeast - like bodies ( staining positive with periodic acid schiff stain ) , some of them showing budding ( 1000 ) adrenal biopsy 7 years after initial therapy shows numerous spores of histoplasma capsulatum that stain positive with the pas stain ( 400 ) the fungus has a predilection for the reticuloendothelial system mainly lymph nodes , spleen , and liver . most symptomatic patients present with variety of self - limited manifestations , the most common being influenza like syndrome and fever . the chronic form of the disease is mainly localized to the lung and manifests with tuberculosis like picture and sequelae . disseminated histoplasmosis is rare occurring mostly in acute rather than chronic forms ; however , the frequency of dissemination in acute histoplasma infections is 1:2000 . an acute rapidly fatal course with diffuse reticuloendothelial involvement characterizes the infection in infants and others who are severely immunosuppressed , while a chronic course with focal organ distribution is more typical in nonimmunocompromised individuals . adrenal involvement in histoplasmosis could be either a part of disseminated form in immunosuppressed patients or may occur as a localized adrenal disease . godwin et al . reported acute adrenal crisis in 7% of patients presenting with disseminated histoplasmosis . however , subtle or chronic forms of adrenal insufficiency due to focal adrenal involvement may be more common . ct features of adrenal histoplasmosis vary depending on the stage of the disease . typically , it includes bilateral adrenal masses with peripheral enhancement and central hypodensities , with calcification seen in the healing phase . these changes are usually bilateral and symmetrical and the shape of adrenal gland is usually preserved . treatment of histoplasmosis involves systemic antifungal therapy  ketoconazole or itraconazole for mild to moderate forms and amphotericin b for severe infections . the duration of therapy is unknown with therapy given for adrenal forms for a period ranging from 6 months to 2 years . mukherjee et al . reported two immunocompetent patients with histoplasmosis who were treatment with oral itraconazole 200 mg daily for 6 months and 18 months respectively . while the adrenal function was normal 9 years after therapy in the first patient , the second patient continued to have enlarged adrenals 18 months after therapy . however , there was no reduction in the adrenal size and histoplasma could still be demonstrated in the adrenal biopsy 7 years later . it is unclear whether steroid overdose , development of diabetes or patient 's own immune status was responsible for persistence of histoplasma . whether histoplasma could remain in dormant , latent or subclinical forms for prolonged periods is not known . reported an immunocompetent patient who developed a reactivation of a latent histoplasma infection , presenting as subacute progressive disseminated histoplasmosis acquired during a previous stay in africa more than 10 years before . reported a patient with chronic disseminated histoplasmosis who was followed after successful treatment with amphotericin b for 10 years until his death from chronic obstructive airways disease . necropsy showed that histoplasma organisms could still be identified in the adrenal and pancreatic abscesses , though none appeared viable on electron microscopy . in conclusion , this was a rare case of adrenal histoplasmosis who showed persistence of histoplasma in the adrenal lesions 7 years after itraconazole therapy .
adrenal histoplasmosis is an uncommon cause for adrenal insufficiency . 
 the duration of treatment for adrenal histoplasmosis is not clear . 
 existing treatment regimens advocate antifungals given for periods ranging from 6 months to 2 years . 
 we report here a rare case who showed persistence of histoplasma in adrenal biopsy 7 years after being initially treated with itraconazole for 9 months . 
 this calls for a prolonged therapy with regular review of adrenal morphology and histology in these patients .