leptin as a neuroendocrine hormone has effects on the glucose metabolism , sexual maturation , reproduction , pituitary - adrenal axis , immune system , thyroid , and growth hormones level [ 36 ] .
probably this hormone is an important risk factor in carcinogenesis , because obesity itself can promote tumorgenesis and is a risk factor for cancer over time [ 7 , 8 ] . on the other hand
, leptin plays an important role in the oxidation reactions such as fatty acid oxidation   and angiogenesis .
there are many reports concerning the effect of leptin on stimulation of cell mitosis and its involvement in carcinogenic stages of breast , clone , prostate , lung , kidney , and ovary cells [ 1116 ] .
studies have shown that leptin by increase of cell proliferation and inhibition of apoptosis is involved in creating certain types of tumors [ 1719 ] .
leptin acts through its receptor on the cell surface and its receptor expression also increases following the activity of pi3k / akt pathway and increases the activity of antiapoptosis molecules such as bcl - xl and xiap . in some cancer cells ,
expression of leptin receptor levels and stimulation by leptin will lead to increase of cell proliferation .
leptin stimulates expression of some molecules such as cyclind1 , cdk2 and c - myc that result in cell cycle progression and cell proliferation [ 21 , 22 ] .
the important molecular pathways , such as jak / stat3 , pi3k / akt , erk / mapk , in many cancer cells can be activated by leptin / leptin receptors [ 2124 ] . furthermore , leptin with the induction of vegf and vegf - r2 molecules expression plays an important role in the tumorigenesis .
these molecules are involved in many malignancies such as colon , stomach , endometrial , ovarian , and breast cancer [ 2630 ] .
additionally , increased serum levels of leptin and its receptor have been associated with distant metastases , disease recurrence , and lower survival in patients with breast cancer .
this hormone probably through its receptor and activation of the pi3k / akt pathway plays an important role in papillary thyroid cancer pathogenesis .
it also seems that the oncogenic effects of leptin on papillary thyroid carcinoma cells are related to the stimulating cell proliferation and apoptosis inhibition .
involvement of thyroid hormones on basal metabolism and regulating appetite and weight control in many scientific reports is given explicitly [ 10 , 3234 ] .
the most common endocrine malignancy is thyroid cancer , and papillary form of thyroid cancer is the most common type of thyroid cancer ( 8090% ) .
the aim of this study was determining the serum leptin levels in patients with papillary thyroid cancer and its comparison with healthy subjects .

 patientsthe case population consisted of 83 individuals , including 35 males and 48 females , 14 to 62 years ( mean age 38.6 years ) with papillary thyroid cancer ( ptc ) .
they were referred to research institute for endocrine sciences , shahid beheshti university of medical science .
also , 90 persons were selected as control group ( 40 male and 50 females ) from referred to the laboratory with normal thyroid function tests ( tsh : 0.3 = 3.5  miu / l , t4 : 4.5 = 12.5  g / dl , t = up : 25 = 35% and t3 : 75 = 210  ng / ml ) with age , sex , bmi matched with case group .
this study has been approved by institutional review board and ethics committee of obesity research center , research institute for endocrine sciences , shahid beheshti university of medical sciences . 
 
the case population consisted of 83 individuals , including 35 males and 48 females , 14 to 62 years ( mean age 38.6 years ) with papillary thyroid cancer ( ptc ) .
they were referred to research institute for endocrine sciences , shahid beheshti university of medical science .
also , 90 persons were selected as control group ( 40 male and 50 females ) from referred to the laboratory with normal thyroid function tests ( tsh : 0.3 = 3.5  miu / l , t4 : 4.5 = 12.5  g / dl , t = up : 25 = 35% and t3 : 75 = 210  ng / ml ) with age , sex , bmi matched with case group .
this study has been approved by institutional review board and ethics committee of obesity research center , research institute for endocrine sciences , shahid beheshti university of medical sciences .
blood sampling was performed in both studied groups . for preparation of serum , 3  ml of whole blood
was collected from antecubital vein in sitting position and was incubated 10  min in rt for coagulation .
then sera separated by 10  min centrifugation at 3000  rpm and the obtained sera were aliquoted in three 0.5  ml microtubes .
the isolated serum samples from each individual were stored in 1  ml eppendorf microtubes at 80c ( japan 's sanyo c company ) .
anthropometric characteristics , including height and weight of patients and control group , were measured by height measuring scaled balance ( seca , german company ) ; height with 0.5  cm and weight with 250  g sensitivity were reported .
these data were used to calculate the body mass index ( kg / m ) .
those individuals , who were using drugs affecting thyroid function and obesity drugs , were excluded . in groups
the used kits were prepared from the canadian company ( dbc company , ontario , canada ) .
human thyrotropin and leptin hormones were determined based on sandwich elisa method , whereas a thyroxin hormone was measured according to the competitive eia method .
the sensitivity of thyroxine , thyrotropin , and leptin kits was 0.6  g / dl , 0.1  mu / l , and 0.4  ng / ml , respectively .
additionally , the coefficients of variation for these assays were 6.2% , 7.1% , and 6.5% , respectively . according to the normal distribution of data obtained by testing kolmogorov - smirnov ( ks ) ( p = 0.68 for case group and p = 0.52 for control group ) , the frequency , mean and standard deviation were used to describe characteristics .
the independent t - test was used to compare mean ( except leptin with geometric mean and ci 95% ) of variables between two groups
further , data was analyzed using statistical software ( spss 15 ) , and significant level was considered at 0.05 .
the results of thyroid hormones test , including thyroxine and thyrotropin in both control and patients groups , are given in table 2 .
since the leptin hormone secreted from adipose tissue is different in male and female , therefore the different levels of measured leptin hormone in two groups are shown in table 3 ( gender based ) .
height , weight , and body mass index between males and females of both groups were significant ( p < 0.05 ) .
in addition , a significant difference ( p < 0.05 ) was observed between the leptin hormone levels in males and females in both healthy and cancer groups .
the amount of leptin hormone in cancer patients was higher than that in normal individuals , significantly ( p < 0.05 ) .
our data showed that the serum leptin levels of iranian patients with papillary thyroid carcinoma were significantly higher than those in control group subjects .
this increased level was observed in both males and females with papillary thyroid carcinoma . as this increased level
was observed in both gender and different ages , so it could be related to thyroid carcinoma and it is independent of sex and age .
even though in this study the leptin level was higher in females than males in both groups , this is probably related to more adipose tissue mass in women .
both leptin and thyroid hormones cause thermogenesis and reduce body weight therefore maybe it is considered as a first association between the two hormones .
but the most studies have not shown significant changes in leptin levels in hypothyroidism and hyperthyroidism disorders [ 36 , 37 ] .
but in their study only 34 cases were investigated , the status of thyroid function in patients and healthy group was not evaluated , and age - matching was not considered . in our study , 83 persons were matched for age , sex , and bmi .
assessing thyroid function in patients and healthy individuals was performed , and no significant difference was observed in both groups . in both above studies , bmi in women was higher than in men , which was quite predictable . in both studies
leptin levels in women were higher than those in men that is because of increased fat mass in women . in one study cheng et al
. showed that expression of leptin and/or leptin receptor in papillary thyroid cancer was associated with neoplasm aggressiveness , including tumor size and lymph node metastasis .
interestingly , in another study , uddin et al . demonstrated that leptin plays an important role in papillary thyroid cancer pathogenesis through pi3k / akt pathway via its receptor ( ob - r ) and is a potential prognostic marker associated with an aggressive phenotype and poor survival .
one of the limitations of our study was inability to followup the patients after surgery .
therefore , reduction or normalization of high leptin levels in thyroid cancer patients was not assessed . however , a significant increase of serum leptin levels in iranian patients with papillary thyroid carcinoma maybe used as a reliable marker to diagnose or confirm papillary thyroid cancer .
in addition if the leptin levels in cancer patients decrease after thyroidectomy , it will be used for the followup treatment , possibly .
so a before - after study is recommended for future investigations instead of case control study .
thus , leptin level measurement can be used to followup the treatment of patients . strongly high leptin level in papillary thyroid cancer patients in comparison with health subject
it means that adipose tissue secreted hormones , proteins , and peptides potentially may have application in diagnosis , confirmation , and/or treatment followup .
 
 introduction . 
 leptin as an adipose - tissue - related peptide hormone contributes to the control of food intake , energy expenditure , and other activities such as cell proliferation . 
 therefore , association of leptin level with thyroid cancer has been suggested recently . 
 considering that thyroid cancer is the most common endocrine cancer , the aim of this study was evaluation of leptin levels in thyroid cancer . 
 materials and methods . 
 83 patients with papillary thyroid cancer ( 35 males and 48 females ) with 90 healthy persons as control group ( 40 male and 50 females ) were selected . 
 serum thyroxine , thyrotropin , and leptin levels were determined in both groups . as a body fat tissue affects leptin level , 
 so height and weight were measured and body mass index was calculated too . results . 
 there was no statistically significant difference in age , serum thyroxine , and thyrotropin levels . 
 bmi in women was more than in men in both groups . 
 serum leptin levels in thyroid cancer group were significantly higher than control group ( p < 0.05 ) . 
 conclusion . 
 the results of this study showed an acceptable association between the hormone leptin levels with papillary thyroid cancer , so it may be considerad as a correlated peptide which may help in the diagnosis or confirmation of thyroid cancer beside in other specific tumor markers . 
1. Introduction
2. Materials and Methods
3. Results
4. Discussion