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Paper text:
cushing s syndrome is characterized by supraphysiological cortisol levels , and may be exogenous , due to steroid therapy , or endogenous when secondary to a functioning tumor of the pituitary or adrenal glands . regardless of etiology ,
all cases of endogenous cushing s syndrome are due to an increased production of cortisol by the adrenal gland .
excessive corticosteroid impairs the cell - mediated immunity , and therefore , patients with cushing s syndrome are prone to infection .
there have been several reports of cryptococcosis in patients with endogenous cushing s syndrome , but most of these have hyperproduction of corticosteroid due to ectopic acth syndrome or adrenal tumors . moreover , most cases are the pulmonary or meningeal forms of cryptococcosis , with disseminated cryptococcosis rarely reported . in this report ,
a case of rapidly fatal , disseminated cryptococcosis , in a patient with pituitary cushing s disease , is reported .
a 49-year - old woman was admitted to seoul national university hospital , due to a headache and fever .
a compression fracture of the lumbar spine had been diagnosed 1 year prior to her admission , for which she had been in a nearly bed - ridden state . in the 2 weeks prior to her admission , she developed a sudden headache and fever , which was treated with antipyretics and analgesics .
a physical examination showed a temperature of 38.2c , a blood pressure of 170/100 mmhg , a pulse rate of 102 beats / min , and normal respirations . the patient had a moon face , truncal obesity and neck stiffness .
on oscultation of the lungs , there were fine crackles in the left lower lung field .
the patient had a painful erythematous bullous lesion in the left leg , but doppler ultrasonography of the lower extremity showed no evidence of deep vein thrombosis .
the values obtained during the initial laboratory examination were as follows : wbc count 9,450 cells / mm , hemoglobin 11.4 g / dl , hematocrit 32.6% , platelet count 230,000 cells / mm , sodium 126 mmol / l , potassium 2.6 mmol / l , and creatinine 0.7 mg / dl . the liver function tests , and prothrombin and partial thromboplastin times , were all within normal limits .
an examination of the cerebrospinal fluid ( csf ) showed no red ( rbc ) or white blood cells ( wbc ) , a protein level of 118 mg / dl and a glucose level of 50 mg / dl .
cultures of the aspirate of the erythematous bullous lesion in the leg , and blood and csf samples , obtained at the time of admission , yielded cryptococcus neoformans .
she was treated with intravenous amphotericin - b at a dose of 0.6 mg / kg / day , and was investigated for the presence of an underlying immunocompromised state , especially for cushing s syndrome .
she had no evidence of liver cirrhosis , and the serology for the human immunodeficiency virus was negative .
the level of cortisol in her 24-hour urine was raised , with a value of 385.7 g/24 hours ( normal 39200 ) .
her serum acth concentration was also raised , with a level of 230 pg / ml ( normal 060 ) .
a brain mri revealed an extensive pituitary mass lesion , involving the sellar fossa , cavernous sinus and skull base , which extended to the suprasellar area and sphenoid sinus ( figure 1 ) .
in addition to intravenous amphotericin - b , cortisol lowering therapy , with ketoconazole and octreotide , was initiated . to further evaluate the consolidation of the left lung ,
this showed segmental , or mass - like , consolidations in the posterior segment of the left upper lobe left lower lobe , and the right middle lobes , which were combined with small nodules , with ground - glass opacity . despite antifungal treatment , with amphotericin - b ,
repeated cultures of the csf and the wound , which were performed on the 14 -hospital day , still grew cryptococcus neoformans . despite 15 days of the antifungal therapy the patient died on the 19 day of hospitalization .
corticosteroid therapy impairs the immunity , and predisposes the patient to various viral , bacterial , fungal and parasitic infections .
patients with endogenous cushing s syndrome can have the same spectrum of infections as occurring in patients treated with corticosteroids .
the extent of immunological impairment and the risk of infection correlate with the degree of cortisol excess .
an opportunistic infection is therefore less likely to occur in patients with pituitary cushing s disease than in those with greater levels of corticosteroid overproduction due to adrenal tumors or ectopic acth syndrome . in this report
, it is noted that disseminated cryptococcosis developed in a patient with pituitary cushing s disease .
cryptococcus neoformans is an encapsulated yeast , found ubiquitously in soil . despite the high prevalence of the organism in the environment , human cryptococcal infections are rare , with the exception of patients with cell - mediated immunity disorders , such as aids , and organ transplantation , or in patients undergoing corticosteroid therapy .
disseminated cryptococcosis has been reported in patients with severe impairment of their cell - mediated immunity , such as liver cirrhosis , acute leukemia , solid organ transplantion , or aids . to our knowledge
, there are no reports of disseminated cryptococcosis in patients with endogenous cushing s syndrome .
this case emphasizes that cryptococcosis can be rapidly fatal , with multi - organ dissemination , in patients with endogenous cushing s syndrome , even in pituitary cushing s disease .
pharmacological and surgical treatment for lowering the plasma cortisol concentrations , to physiological ranges , should be promptly initiated .
disseminated cryptococcosis mainly occurs in patients with cell - mediated immunity disorders . 
 a case of disseminated cryptococcosis , in a patient with pituitary cushing s disease , is reported . 
 cultures of blood , cerebrospinal fluid ( csf ) and aspirates of a skin lesion all grew cryptococcus neoformans . despite antifungal treatment , with amphotericin - b , 
 the patient died within 3 weeks .