glucocorticoid ( gc ) excess , including cushing 's syndrome , is a common cause of secondary osteoporosis .
several reports have confirmed the high prevalence of various degrees of osteopenia / osteoporosis in patients with hypercortisolism .
the prevalence of osteopenia and osteoporosis in cushing 's syndrome is diverse among studies , with approximate ranges from 60 - 80% and 30 - 65% , respectively .
also , 30 - 50% of patients with cushing 's syndrome experience non - traumatic fractures , which can be the presenting manifestation of cushing 's syndrome .
approximately one third of patients develop vertebral fractures , especially at the level of the thoracic and lumbar vertebral bodies .
spontaneous fractures may also occur in the ribs and pelvis , and less commonly in the long bones .  
however , there are rare cases diagnosed as cushing 's syndrome based solely on bony manifestations . in korea
, only two cases have been reported in which cushing 's syndrome was diagnosed after pathologic vertebral fractures occurred in young females .
we described a case where cushing 's syndrome was diagnosed in a 44-year - old woman who visited our hospital due to multiple non - traumatic rib fractures .
a 44-year - old woman was referred to our hospital on may 2009 due to an abnormal chest x - ray finding . she had a chest x - ray before a gastrofibroscopy at a local hospital .
, she had a chest computed tomography ( ct ) scan done before visiting our hospital .
the chest ct revealed multiple sclerotic masses with bone destruction in both hemithoraxes ( right 2nd , 4th , 5th , 6th , 7th , and 10th ribs , left 2nd , 4th , 7th , 8th , and 9th ribs ) of variable size ( fig .
initially she was admitted to the pulmonology department to rule out bony metastases from a cancer of unknown origin .
she had taken the bone densitometry of the l1-l4 lumbar spine by dual energy x - ray absorptiometry ( dxa ) , at the local department of gynecology 1.5 years ago .
the result of bone mineral density ( bmd ) was 0.726 g / cm and the average t - score of the l1-l4 lumbar spine was -2.6 .
therefore , she was taking calcium , vitamin d supplements and hormone replacement therapy for osteoporosis .
she also had a conization in 2002 due to squamous cell carcinoma in situ at the uterine cervix and thereafter received a total hysterectomy in 2005 due to uterine leiomyoma .
there were no abnormal findings in her family history . also , she had no trauma history .
she did n't have any pain on her ribs . on the physical examination , there was n't tenderness around fracture sites .
her height and weight were 153 cm and 53 kg , respectively , with a body mass index ( bmi ) of 22 kg / m .
her waist measurement was 83 cm , and she had experienced no recent weight changes .
her blood pressure was 140/80 mmhg with a pulse of 96 beats / min , a respiratory rate of 20 breaths / min , and a body temperature of 36.8. on the blood test , the leukocyte , hemoglobin , and platelet counts were 8,900/mm ( neutrophils 85.9% , lymphocyte 8.4% , monocyte 5.7% ) , 14.9 g / dl , and 184,000/l , respectively .
fasting glucose , albumin , aspartate aminotransferase , alanine aminotransferase , alkaline phosphatase , and creatinine were 93 mg / dl , 4.0 g / dl , 45 iu / l , 81 iu / l , 49 iu / l , and 0.56 mg / dl , respectively .
total calcium and phosphate were 10.5 mg / dl and 3.5 mg / dl , respectively .
in addition , serum intact parathyroid hormone ( pth ) was 35.6 pg / ml ( normal range , 13 - 54 pg / ml ) . to evaluate the patient for metastatic cancer ,
a bone biopsy was performed at the right 6th rib posterior arc in the pulmonology department .
also a bone scan and the bone densitometry of the l1-l4 lumbar spine and an abdominal ct were performed .
fragmented bony particles with small amounts of marrow tissue were observed in the biopsy tissue . there were no cancer cells nor cytokeratin ( ck)-positive epithelial cells on immunohistochemical staining .
there was no cancerous lesion in abdomen ct , except a left adrenal incidentaloma , a well - marginated soft tissue mass 25 mm in diameter , was found ( fig .
, multi - focal increased uptake was observed in both ribs , suggesting non - traumatic micro - fractures caused by osteoporosis ( fig .
4a ) . the average bmd , t - score and z - score of the l1-l4 lumbar spine was 0.761 g / cm , -2.1 and -1.7 , respectively .
therefore , an endocrine cause of osteoporotic fracture was suspected , and a hormonal study for adrenal incidentaloma was performed .
free cortisol in the urine and 17-hydroxycorticosteroid were 580.4 g / day ( normal range , 20 - 90 g / day ) and 12.93 mg / day ( normal range , 3 - 15 mg / day ) , respectively .
a low - dose dexamethasone suppression test showed that the serum adrenocorticotrophic hormone level was 1.4 pg / ml ( normal < 130 pg / ml ) , the basal cortisol was 26.3 g / dl and the cortisol on the 3rd day was 35.4 g / dl ( normal , 3 - 6 g / dl ) .
finally , she was diagnosed with cushing 's syndrome due to the left adrenocortical adenoma .
a month after the laparoscopic left adrenalectomy , 24-hr urine free cortisol was checked , and was below 1.8 g / day .
a bone scan taken 1 year after the operation showed decreased multifocal uptake in the bilateral ribs ( fig .
4b ) and the patient 's bmd improved gradually , reaching 0.822 g / cm in 2012 ( fig .
5 ) . also , the average t - score and z - score of the l1-l4 lumbar spine improved , reaching -1.6 and -1.0 , respectively .
currently , she is being regularly followed - up and taking calcium and vitamin d for osteopenia .
cushing 's syndrome encompasses a variety of clinical features that result from chronic exposure to excess gcs of any etiology .
cushing 's syndrome occurs with an incidence of 1 - 2 per 100,000 persons per year .
the clinical manifestations of cushing 's syndrome are central obesity with supraclavicular fat accumulation , a cervical fat pad , thinned skin , purple striae , proximal muscle weakness , fatigue , hypertension , glucose intolerance , acne , hirsutism , menstrual irregularity , and osteoporotic vertebral fractures .
however , the clinical manifestations of cushing 's syndrome are not always definite so that sometimes clinical suspicion should arise preferentially by the physician . furthermore , because of its variable pattern of the biochemical parameters , diagnosis of cushing 's syndrome is often difficult for clinicians .
the prevalence of osteoporosis due to endogenous gc excess has been reported to be present in 50 - 59% of cases , and approximately 30 - 50% of patients with the condition experience non - traumatic fractures .
secondary osteoporosis is defined as bone loss , microarchitectural alterations , and fragility fractures due to an underlying disease or concurrent medication .
clinicians should be suspicious and evaluate for secondary osteoporosis in male or premenopausal female patients with unexplained bone loss , a history of fragility fractures or very low bmd values and fractures despite anti - osteoporotic therapy , as in this case .
moreover , because osteoporotic fractures can be the only presenting manifestation of cushing 's syndrome , secondary osteoporosis caused by cushing 's syndrome should be considered in patients with unclear causes of osteoporotic fractures .
although the patient in this case was a relatively young female who had already taken calcium , vitamin d supplements and hormonal replacement therapy for osteoporosis , asymptomatic multiple pathologic rib fractures were incidentally discovered in a routine chest x - ray . because she exhibited no typical signs of cushing 's syndrome such as moon face , truncal obesity , thinned skin or purple striae and showed no associated features of cushing 's syndrome , such as diabetes mellitus or hypertension , she was not initially suspected of cushing 's syndrome . at first
however , they did not find any evidence of metastatic cancer , and incidentally found the left adrenal adenoma on abdominal ct .
then , we suspected cushing 's syndrome and performed endocrine function tests , which confirmed the diagnosis .
there have only been two korean cases of cushing 's syndrome previously diagnosed after recurrent non - traumatic fractures occurring in young females .
however , both of these cases were accompanied by vertebral fractures , not rib fractures .
our case is the first report that diagnosed cushing 's syndrome by multiple ribfractures without vertebral fractures , which are the most affected fracture site in cushing 's syndrome .
they act in two phases : a rapid , early phase in which bmd falls by excessive bone resorption , and a slower , more progressive phase in which bmd declines as a result of impaired bone formation .
an early phase of excessive bone resorption is due to the action of gcs on calcium metabolism by inhibition of calcium absorption from the gut through a mechanism independent of vitamin d , increasing the urinary excretion of calcium and increasing osteoclast activity .
. however , most studies have found differences between gc - induced osteoporosis ( gio ) and the hyperparathyroid state . in gio
, preferential bone loss tends to occur in cancellous bone , in contrast to primary hyperparathyroidism where preferential bone loss occurs in cortical skeletal bone . as a result ,
greater bone mineral loss in the vertebral spine is commonly observed in patients with cushing 's syndrome .
moreover , gio shows reduced bone turnover , whereas bone turnover is enhanced in primary hyperparathyroidism . also , the slower phase of impaired bone formation is due to a decrease in osteoblast number and function .
hypercortisolism inhibits replication of cells of osteoblastic lineage and osteoblastogenic differentiation , decreases osteoblast function and increases apoptosis of osteoblasts and osteocytes . in addition , gcs inhibit alkaline phosphatase activity , production of type i collagen and synthesis of non - collagenous bone protein like osteocalcin .
many studies that evaluated bone formation with serum osteocalcin levels found that it was greatly suppressed in endogenous gio . an important feature of gio is that it is reversible . after cure of hypercortisolism by both
an adrenalectomy or pituitary adenomectomy , an increase in bmd , which can even reach normal levels , has been described and a time - dependent rise was observed . manning et al .
reported that the bmd of 17 adult cushing 's syndrome patients , who had been cured , recovered to normal values and there was a positive relationship between bone density and the time since cure by a unilateral adrenalectomy , which requires approximately 10 years for complete recovery .
they also observed a time - dependent rise in bmd , which was paralleled by increased osteocalcin .
one of the two korean cases did not report progress in the bony manifestations of cushing 's syndrome after treatment , while the other case showed a slight improvement in bmd , but new compression fractures developed during the course of treatment .
interestingly , we showed that multifocal increased uptake of the ribs on bone scan completely disappeared one year after left adrenalectomy .
furthermore , bmd significantly increased after 2 years with no additional fractures . in conclusion , although a patient may not exhibit typical features of cushing 's syndrome , this disease should be considered in young adults with multifocal non - traumatic rib fractures , as they could be bony manifestations that can be completely eliminated by treatment .
 glucocorticoid ( gc ) excess , including cushing 's syndrome , is a common cause of secondary osteoporosis 
 . thirty to fifty percent of cushing 's syndrome patients experience non - traumatic fractures , which is often the presenting manifestation of cushing 's syndrome . however , there have been rare cases of cushing 's syndrome diagnosed only based upon bone manifestations . 
 we describe a case of cushing 's syndrome that was diagnosed in a 44-year - old woman who initially visited our hospital due to multiple non - traumatic rib fractures . 
 she did not exhibit any other manifestations of cushing 's syndrome such as moon face , buffalo hump or abdominal striae . 
 initially , we evaluated her for bone metastases from a cancer of unknown origin , but there was no evidence of metastatic cancer . 
 instead , we found a left adrenal incidentaloma . as a result of the hormone study , 
 she was diagnosed as having cushing 's syndrome . 
 interestingly , her bony manifestation of cushing 's syndrome , which was evident in the bone scan and bone mineral densitometry , completely recovered after a left adrenalectomy . 
 therefore , the possibility of cushing 's syndrome as a cause of secondary osteoporosis should be considered in young patients with non - traumatic multiple fractures , with or without any other typical features of cushing 's syndrome . 
INTRODUCTION
CASE
DISCUSSION