prolactinomas are pituitary adenomas that secrete prolactin . these represent the most common hormone - secreting adenomas occurring in the pituitary gland , accounting for around 40% of all clinically recognized pituitary adenomas .
they are diagnosed more frequently in women than in men , especially between the ages of 20 and 40 years , because premenopausal women are sensitive to hypogonadism , which manifests as infertility and menstrual disorders , whereas postmenopausal women are already hypogonadal and men may ignore or not recognize symptoms of hypogonadism manifesting as decreased libido , impotence , or erectile dysfunction . moreover ,
galactorrhea is rare for both postmenopausal women and men ( and is also relatively rarer than hypogonadism in premenopausal women ) , so symptoms due to tumor growth such as headache or visual field loss can represent chances for diagnosis in postmenopausal women or men . herein , we present the case of a 44-year - old nulliparous woman who had experienced irregular menstruation cycles for about 10 years and developed both pituitary prolactinoma and endometrioid endometrial carcinoma . in premenopausal women
, hyperprolactinemia causes hypogonadism by inhibiting the secretion of gonadotropin - releasing hormone , which in turn suppresses luteinizing hormone levels and can cause menstrual disorders ranging from amenorrhea , oligomenorrhea and chronic anovulatory cycle to short luteal phases of the menstrual cycle [ 35 ] .
chronic anovulatory menstrual cycle is the most common cause of long - term exposure of the endometrium to endogenous estrogen without adequate opposition from progestins , which can lead to endometrioid endometrial carcinoma [ 6 , 7 ] .
thus , in this case , pituitary prolactinoma may have caused the chronic anovulatory cycle and indirectly led to the development of endometrioid endometrial carcinoma .
a nulliparous 44-year - old woman with a 10-year history of irregular menstrual cycles presented with massive abnormal uterine bleeding , shortness of breath , and exhaustion .
she had experienced abnormal uterine bleeding for about 1 year , and it had increased over the previous 10 days . she had no past illnesses of note , including no history of hypertension or glucose intolerance , and no special history of taking pharmacotherapies . on presentation , she was obese with a height of 152 cm and weighing 73.0 kg .
vital signs were stable , with : blood pressure , 152/96 mm hg ; heart rate , 88 beats / min ; axillary temperature , 100.2f ; and oxygen saturation by pulse oximetry , 99% ( room air ) .
general physical examination revealed hirsutism without any other signs of androgen excess such as acne , male pattern baldness , or lowering of the voice , and there was no evidence of galactorrhea .
gynecological examination revealed an almost normal - sized uterus , impalpable bilateral adnexa , and unremarkable vagina and vulva .
ultrasonographic examination and magnetic resonance imaging ( mri ) showed thickening of the endometrium and collapse of the junctional zone .
both ovaries appeared normal and no fluid was evident in the pelvic cavity ( fig .
surgical resection was planned for the endometrial carcinoma . while waiting for the operation , correction of anemia by iron supplementation and exploration of the reasons for irregular menstruation
endocrinological survey yielded the following results : serum prolactin , 243.8 ng / ml ( institutional normal range , 4.128.6 ) ; luteinizing hormone , 2.0 miu / ml ( follicular phase , 1.713.3 ) ; follicle - stimulating hormone , 7.2 miu / ml ( follicular phase , 4.511.0 ) ; estradiol , < 25.0 pg / ml ( follicular phase , 40.7224.0 ) ; testosterone , 23 ng / dl ( normal , 956 ) ; growth hormone , 0.05 ng / ml ( normal , 0.281.64 ) ; adrenocorticotrophic hormone , 16.2 pg / ml ( normal , 7.263.3 ) ; thyroid - stimulating hormone , 2.95 iu / ml ( normal , 0.384.31 ) .
marked hyperprolactinemia led us to suspect pituitary prolactinoma , and mri of the hypophysis was therefore performed .
t1-weighted mri showed an 8.4  7.8-mm tumor in the right anterior lobe of the hypophysis ( fig .
no evidence of headache or visual field loss was present , so surgery did not seem to be indicated for the pituitary prolactinoma .
a few days later , total abdominal hysterectomy was performed with bilateral salpingo - oophorectomy and pelvic and para - aortic lymphadenectomy .
histological examination confirmed grade 2 , well- to moderately differentiated endometrioid endometrial carcinoma tumors with less than half myometrial invasion and without involvement of any other organs , including regional lymph nodes . during the 10 months of follow - up ,
serum prolactin levels have been stable at around 160 ng / ml , and no signs of recurrence of endometrial carcinoma have been present .
the prognosis of advanced - stage endometrial carcinoma is still poor relative to early - stage carcinoma , although many improvements have been made in treatment modalities such as surgery , chemotherapy , radiotherapy and others in recent years .
remembering risk factors for endometrial carcinoma , detecting patients in high - risk groups , and dealing properly with them , are thus important for catching early - stage patients and decreasing the morbidity and mortality rates of this life - threatening disease .
in particular , in endometrioid endometrial carcinoma , which comprises about 80% of endometrial carcinomas , long - term exposure to excess estrogen unopposed by progestin is well known as the most important risk factor [ 7 , 8 ] .
chronic anovulatory menstrual cycle remains the most common cause of long - term , unopposed exposure of the endometrium to endogenous estrogen [ 6 , 7 ] .
many endocrinological disorders cause ovulatory disorders , with polycystic ovary syndrome ( pcos ) as the most representative .
because the patient was obese with hirsutism , the ovulatory disorder was initially attributed to pcos .
although the causes of hyperprolactinemia vary widely , marked hyperprolactinemia over 200250 ng / ml is usually due to pituitary prolactinoma or pregnancy , and this was also evident in the present patient . in premenopausal women , hyperprolactinemia causes hypogonadism by inhibiting secretion of gonadotropin - releasing hormone followed by suppression of luteinizing hormone levels and can cause menstrual disorders ranging from amenorrhea , oligomenorrhea and chronic anovulatory cycle to short luteal phases of the menstrual cycle . as mentioned above , chronic anovulatory cycle can be a risk factor for endometrioid endometrial carcinoma , and this patient had a 10-year history of irregular menstruation .
pituitary prolactinoma could thus have indirectly resulted in endometrioid endometrial carcinoma through chronic anovulatory cycle in this case .
indeed , some anecdotal evidence from similar cases suggests a relationship between hyperprolactinemia and endometrioid carcinoma [ 1012 ] . in this case , obesity could also have been a cause of ovulatory disorder , in addition to pituitary prolactinoma .
obesity is thought to have various carcinogenic effects other than ovulatory disorder for endometrial carcinoma .
however , cases of endometrial carcinoma correlating with hyperprolactinemia have involved younger patients compared to the more common obese cases without hyperprolactinemia [ 10 , 12 ] .
pituitary prolactinoma could thus have been more important than obesity as a cause of carcinoma in this case .
one apparent inconsistency is that plasma estrogen concentrations on presentation were subnormal , while estrogen exposure is theoretically needed for carcinogenesis .
actually , we do not have any information about her hormone levels ( including prolactin ) prior to her presentation to our hospital , after irregular menstruation had been ongoing for a long period .
however , some studies have proposed that increased plasma estrogen concentration is not important for carcinogenesis ; rather , long - term exposure to low concentrations of estrogen unopposed by progesterone ( that is , under conditions of progesterone deficiency ) plays an essential role [ 6 , 7 , 11 ] .
another area of uncertainty involves the direct effect of prolactin on the endometrium , rather than the indirect effect mentioned above . although some studies have reported that serum concentrations of prolactin are significantly elevated in patients with endometrial carcinoma compared to healthy individuals [ 13 , 14 ] and that prolactin receptors are expressed in both normal endometrial and carcinoma tissue [ 14 , 15 ] , the direct effects of prolactin on the endometrium , in terms of proliferative or differentiative effects , remain unclear .
the utility of correcting hyperprolactinemia using dopamine agonists for the purpose of preventing the development of endometrial carcinoma has yet to be determined . in the present case ,
levels of serum prolactin have remained stable and no evidence of recurrent endometrial carcinoma has been identified during follow - up . in conclusion , hyperprolactinemia indirectly induces endometrioid endometrial carcinoma after causing chronic anovulation . in patients with irregular menstruation and chronic anovulation that may be attributable to hyperprolactinemia , exploration of both the hypophysis and endometrium
 we present the case of a 44-year - old nulliparous woman who experienced irregular menstrual cycles for about 10 years and developed both pituitary prolactinoma and endometrioid endometrial carcinoma . in premenopausal women 
 , hyperprolactinemia causes hypogonadism by inhibiting secretion of gonadotropin - releasing hormone and thus suppressing luteinizing hormone levels , which can cause menstrual disorders ranging from amenorrhea , oligomenorrhea and chronic anovulatory cycle to short luteal phase of the menstrual cycle . 
 a chronic anovulatory menstrual cycle is the most common cause of long - term exposure of the endometrium to endogenous estrogen without adequate opposition from progestins , which can lead to endometrioid endometrial carcinoma . in this case , 
 pituitary prolactinoma may have caused the chronic anovulatory cycle and indirectly led to the endometrioid endometrial carcinoma . in patients for whom 
 the cause of irregular menstruation and chronic anovulatory cycle is suspected to be hyperprolactinemia , explorations of both the hypophysis and endometrium are essential . 