Endometrial carcinoma in Turner's syndrome

A case of endometrial carcinoma in a patient with Turner's syndrome is presented and the literature is reviewed. Ten similar cases were already published and the clinical and laboratory findings in all 11 cases are tabulated and analyzed. One or more of three possible etiological factors contributing to the development of this very unusual situation are discussed :(i) the prolonged unopposed use of estrogen, (ii) the use of the contraceptive pill (particularly the sequential type), and (iii) a genetic predisposition to cancer in patients with Turner's syndrome.     

Endometrial carcinoma following estrogen-progestogen therapy in Turner's syndrome: a case report and review of the literature.

A case of Turner's syndrome in which the patient developed a well-differentiated adenocarcinoma of the endometrium after 15 years of sequential estrogen-progestogen therapy and 3 additional years of combined therapy is reported. A survey of the literature revealed 10 other cases of Turner's syndrome in which endometrial carcinoma developed after long-term replacement hormonal therapy and one additonal case without a definitive diagnosis of carcinoma. Including the one described here, four patients developed endometrial carcinoma after either combined or sequential estrogen-progestogen therapy. Seven patients were given estrogen alone as substitution therapy. One patient was given progestogens alone for 19 weeks after 9 years of stilbestrol. It appears that the addition of progestogens to the therapeutic regimen does not always prevent the development of endometrial carcinoma. It is advocated that all patients with Turner's syndrome on replacement therapy with estrogens alone or with sequential or combined estrogen-progestogens be closely followed for the development of endometrial carcinoma.     

Endometrial carcinoma associated with Sheehan's syndrome and stilbestrol therapy

At the age of 25, pregnant with her 2nd child, a woman was diagnosed as having pituitary necrosis resulting from hemorrhagic shock, in turn the result of a clotting defect caused by an amniotic fluid embolism. For the next 17 years, her daily replacement therapy included 50 mg ma of cortisone, 120 mg of thyroid, and .5-1 mg of diethylstilbestrol given cyclically (21 days). When an exploratory laparotomy was performed on her at age 42 because of abdominal mass,an endometrial adenocarcinoma and varying degrees of hyperplasia were found. A total abdominal hysterectomy was performed, but a year later it became clear that the patient had diffuse carcinomatosis, and 2 months later she died. Prolonged unopposed estrogen therapy is suggested as the cause of the endometrial cancer, rather than pituitary disturbance.     

Endometrial resection after radiotherapy for cervical carcinoma.

A patient with persistent chaotic menses during hormone replacement therapy after radiotherapy for cervical cancer was rendered amenorrheic by transcervical endometrial resection.     

Turner's syndrome and procreation. Ovarian function and Turner's syndrome

Ovarian failure is a typical feature in Turner's syndrome. The majority of follicles disappears prematurely after a normal determination of the ovary. This results from an accelerated loss of oocytes from the ovaries after the 18th week of fetal life or over a few postnatal years, usually before the onset of puberty. The cause and mechanism of this loss are unknown. X chromosomal anomaly due to deletions or haploinsufficiency of genes can explain the various degrees of ovarian failure. Spontaneous puberty occurs in 20-30% of Turner syndrome patients and their fertility rates vary from 5 to 10%. This indicates the possible presence and maturation of follicles in their ovaries in adolescence. In ovarian failure, the hormone replacement therapy (HRT) is necessary to achieve the development of normal female sexual characteristics, the self image or social functioning and to prevent osteoporosis. Pregnancy is now possible with oocyte donation. A careful cardiovascular follow-up is necessary. Cryoconservation represents one way for preserving the future fertility, but the optimal age of ovarian biopsy has to be studied.     

Menstrual function in Turner's syndrome.

This report describes 2 patients with menstrual dysfunction associated with a 45,X0 karotype. One patient had 2 pregnancies before becoming oligomenorrheic. The other had dysfunctional uterine bleeding associated with excessive estrogen production by her streak gonads.     

Endometrial carcinoma using GnRH analogues therapy in endometriosis

Endometriosis affects a 10 % of women during their reproductive years. Unequoral statistics concerning the incidence of adenomyosis are not available although a combined occurrence of both diseases is found in a 20 % of cases. The risk that malignancy arises from endometrioid tissue typical for endometriosis is between a 0.3-1 %. 75 % of these malignancies are ovarian cancer in conjunction with pre-existing ovarian endometriosis; less frequently extraovarian malignancies are found. The development of malignancy of adenomyosis is very rarely reported. In this report we present the case of a 35 year old patient who suffered from both, endometriosis and adenomyosis and who underwent a therapy using GnRH analogues. After five months and before the completion of the therapy a hysterectomy with conservation of the ovaries was performed at the request of the patient (carcinophobia). The histology confirmed the diagnosis of adenomyosis and demonstrated the unexpected finding of an endometrium carcinoma. This latter arose from a complex atypical hyperplasia surrounded by hypoplastic endometrium. There is some evidence that suggests a slightly elevated risk of breast and ovarian cancer as well as haematological malignancies amongst patients with endometriosis. However, there does not appear to be an increased risk of endometrial carcinoma. Adipositas leads to an increased risk for the development of endometrial carcinoma due to the increased conversion of testosterone to estrone in fat. The peripheral synthesis of estrone is unaffected by GnRHa-therapy. A progesterone containing HRT should be added to a GnRHa-therapy in overweight patients to prevent the development of endometrial hyperplasia and/or carcinoma. In conclusion a careful indication has to be made for GnRHa-therapy in overweight patients and before and during the therapy high resolution ultrasound scan should be performed to evaluate the endometrium in those patients.     

Endometrial squamous cell carcinoma.

Endometrial squamous cell carcinoma is an extremely rare female genital malignancy. Only 26 cases which fulfil the Fluhmann criteria have been reported in the literature. In this report, 2 cases of endometrial squamous cell carcinoma are presented, with a review of related current knowledge.     

Endometrial carcinoma associated with azathioprine and cortisone therapy. A case report

Endometrial carcinoma is sometimes associated with unopposed estrogen activity. Carcinoma of the endometrium developed in a patient treated with prednisone for 16 months and azathioprine for 14 months. This patient had amenorrhea for 20 years, which probably was due to high levels of gonadotropin and was secondary to ovarian failure. There is no previously reported case of endometrial carcinoma related to immunosuppressive therapy.     

Klinefelter's syndrome and Turner's syndrome. For a better management

Klinefelter's syndrome (KS) affects one in 600 men and Turner's syndrome (TS), one in 2500 women. These 2 diseases are the most sex chromosome disorders characterized by one extra X in the SK male (47XXY) and the loss of an X in the girls with ST (45 X). Their common characteristic is the gonadal dysgenesis, which is the main cause of male or female infertility. Called “the forgotten syndrome”, KS is under-diagnosed because apart from the large size, there are no dysmorphic features, along with a great ignorance of cognitive and language disorders in children. There are often comorbidities that lead to diagnosis such as autoimmune diseases or metabolic syndrome. TS is often diagnosed by the short stature. Management of Turner's girls has profoundly changed with Growth hormone therapy. There is an international consensus for a better management of associated diseases such as ORL, cardiac, renal, hepatic, autoimmune and metabolic diseases. Prenatal diagnosis allows early detection and management of cognitive deficiencies and of associated diseases.     

Gonadotropin levels in Turner's syndrome: correlation with breast development and hormone replacement therapy.

We conducted a study of the basal levels of gonadotropins in 38 patients with Turner's syndrome, 14 of whom were using hormone replacement therapy (HRT). The gonadotropin levels were compared with pubertal development and HRT. Seven patients had presented spontaneous menarche; five patients maintained their periods and normal gonadotropin levels, and two developed secondary amenorrhea and high gonadotropin levels. The majority of patients on HRT had high gonadotropin levels. Follicle stimulating hormone (FSH) levels were significantly lower (p = 0.001) in patients with breast development at stage 5, regardless of whether the patient had undergone a spontaneous or a hormonally induced puberty. We concluded that gonadotropin levels are normal in those patients with spontaneous periods, and are high in most patients on HRT; and that FSH levels are significantly lower in those patients with breasts at stage 5.     

Renal malformations in children with Turner's syndrome.

Between 1988 and 1999, renal sonography and intravenous urography were performed to detect renal malformations in 54 patients with Turner's syndrome (TS). The mean age of these patients at diagnosis of TS was 9.2 +/- 4.6 years. Renal malformations were detected in 21 patients by intravenous urography and there was no significant difference in the frequency of renal malformations among different karyotype groups. Horseshoe kidney was the most common renal malformation, followed by duplex kidney. Fifteen of 21 renal malformations were not detected by renal sonography. We conclude that these TS patients had a high frequency of renal malformations, and that the detection rate of horseshoe kidney and duplex kidney by renal sonography was not satisfactory. Although renal sonography alone can be used to detect more severe renal malformations that may need further management, it may underestimate the frequency of renal malformation in children with TS.