human chorionic gonadotropin ( hcg ) is a heterodimeric hormone secreted by the trophoblastic tissue of the placenta as well as certain tumors .
small amounts of hcg have been reported to be secreted by the pituitary gland in non - pregnant females and males .
various commercial assays are available in the market to detect hcg in both serum and urine .
they are also used in the diagnosis , management and follow - up of ectopic pregnancy , trophoblastic diseases and germ cell tumors . in the absence of pregnancy and neoplasia , elevated hcg in females
studies have attributed this to false positivity due to the presence of heterophilic antibodies or a physiologic increase in hcg in post - menopausal females .
low positive hcg values have led to empirical chemotherapy in some and delay or cancellation of important medical procedures in others .
we report a series of non - pregnant female patients with chronic renal failure with positive serum hcg over a period of 1 year from our center .
the database of all patients who underwent renal transplant at our center from july 2007 through july 2008 was reviewed .
a total of 171 patients with end - stage renal disease were screened for renal transplantation during that year , 109 males and 62 females .
the mean age of female patients was 53.7 years ( range 23 - 79 years ) .
for pre - transplant screening , all the female patients underwent serum hcg screening to rule out pregnancy , irrespective of their ages .
hcg screening was carried out using  hcg plus kit  from roche pharmaceuticals , usa ( 0 - 5 iu /
five out of 62 ( 8% ) female patients had a positive hcg test ( 5
the test was repeated in 4 four out of five patients to rule out any discrepancy .
a total of 3 patients underwent successful renal transplantation while one is still on the waiting list .
two patients were dialysis - dependent while the remaining was being worked up for pre - emptive transplant .
the mean value of hcg in post - menopausal patients was 8.4 ( range 6 - 10 ) . however , hcg was slightly higher in premenopausal patient .
epstein - barr virus serologies were positive in all patients ; two were cytomegalovirus positive .
no other common environmental exposures , which could have led to the production of heterophilic antibody , could be identified in them .
hcg- is identical to the -subunit of luteinizing hormone ( lh ) , follicle stimulating hormone ( fsh ) and thyroid stimulating hormone while  subunit is exclusive to each hormone .
normally produced by syncytiotrophoblast cells of placenta , hcg is also secreted by trophoblastic and gastrointestinal tumors .
hcg is produced in very small amounts in men and non - pregnant women , primarily from the anterior pituitary gland . in pregnancy , 30% of hcg
the remainder is cleared by other pathways , likely by metabolism in the liver and kidneys .
the biological function of hcg is maintaining secretion of progesterone from corpus luteum until the placenta takes over this function .
various other degraded and dissociated forms of hcg are present in the serum and urine , with little or no biological activity . besides being used as a marker of pregnancy and certain tumors , hcg screening tests are also carried out before most medical interventions in female patients .
most immunoassays use different combinations of antibodies against different sites on hcg or its subunits .
some assays detect non - nicked hcg alone , some detect non - nicked hcg and free  hcg while others detect both nicked ( biologically inactive ) and non - nicked hcg . though these tests have high sensitivity and specificity , the heterogeneity in the assays may lead to false positive results .
heterophilic antibodies in humans may cross - react with animal immunoglobulin used in the assay and can result in falsely positive tests .
these antibodies develop following exposure to serum or tissue antigens of animals and occur in about 3 - 15% of healthy individuals . as a consequence ,
however , it has been observed that the values in such cases of false positive results range from 100 iu / l to 500 iu / l , a good deal higher than our results .
moreover , the assay used in our patients contained blocking antibodies , which bind these heterophilic antibodies and prevent cross reactions .
studies have shown that the serum concentration of hcg increases in post - menopausal females .
suginami and kawaoi obtained serial sections of pituitary glands at autopsy from women of various chronological ages .
they concluded that hcg - like substance was localized in the gonadotrophs of the pituitary glands obtained from post - menopausal females .
stenman et al . , in their study , showed that treatment of post - menopausal women with a combination of estrogen and progesterone reduced their serum hcg levels by half .
this further points towards the pituitary production of hcg in them . in studies on female cohorts , hcg levels have been found to be proportionate to increases in fsh after menopause .
other authors consider pituitary hcg to be produced with increasing menopausal production of lh , owing to the decreased negative feedback by progesterone .
case reports have implied that hcg concentrations 5.0 iu / l should not be considered abnormal in post - menopausal women . in a study in females more than 55 years of age , hcg levels > 5 iu / l in 16/240 ( 6.7% ) were observed .
, in their paper , suggested that the upper limits of normal of serum hcg for post - menopausal women be increased to 14.0 iu / l .
thus , this post - menopausal rise in hcg may explain the elevated hcg in four of our patients .
the role of chronic kidney disease ( ckd ) as a cause of elevated hcg levels has not been studied .
it is well - known that 30% of hcg being produced is cleared by the kidney and an additional fraction metabolized by it . in our cohort of female ckd patients , hcg levels > 5 iu /
l were observed in 5/62 ( 8.1% ) . in the subset of patients with age > 55 ,
hcg levels more than 5 iu / ml were noted in 4/30 ( 13.3% ) .
thus , the presence of ckd in our patients may have served to elevate the hcg levels further in them .
however , the factors , which elevate the hcg levels in only some patients with ckd remain poorly understood .
a prospective cross - sectional study on pregnant patients showed that mild renal or hepatic impairment has no effect on maternal serum screening , which includes hcg .
whether more severe renal disease ( such as in our patients ) has an effect on hcg excretion is yet to be ascertained .
reduced testosterone concentration with the increase in level of gonadotropins , including lh and fsh , in has been attributed to a wide range of factors including aging , chronic inflammation , malnutrition and vascular disease . in these circumstances ,
a pituitary overproduction of hcg in parallel to fsh / lh , akin to the reports above , also appears plausible .
many women experience delays in their management and postponement of surgical procedures because of elevated hcg .
instances of needless chemotherapy administered to such women because of the presumption of cancer have also been reported .
our patients also had to undergo various other investigations increasing the overall cost and delaying treatment .
these included obstetrics / gynecology referrals with follow - up , pelvic ultrasound examinations ( one or more ) and serial blood testing .
the transplant procedure itself was rescheduled in one of the patients on account of the positive hcg . in summary ,
healthy non - pregnant females can have elevated hcg either due to false positive results or menopausal status .
large - scale studies are needed to ascertain the prevalence of a positive hcg test by conventional criteria in post - menopausal females in the general population .
correcting hcg levels for age and co - morbidities may be prudent in reducing procedural delays and treatment costs in such women .
 women are often subjected to serum human chorionic gonadotropin ( hcg ) testing prior to diagnostic and therapeutic interventions . 
 a positive result leads to further testing to rule out pregnancy and avoid possible fetal teratogenicity . 
 the impact of chronic kidney disease ( ckd ) on hcg testing has not been studied . 
 we report a series of 5 women out of 62 with ckd , who had a positive hcg test on routine pre - transplant screening at a single transplant center . 
 we analyzed their case records retrospectively . despite aggressive investigation 
 , their elevated hcg levels remained unexplained . 
 the positive test contributed to delays in transplantation and increased overall cost of treatment . 
Introduction
Materials and Methods
Results
Discussion