Successful pregnancy and delivery after removal of gonadotrope adenoma secreting follicle-stimulating hormone in a 29-year-old amenorrheic woman

We report a case of ovarian hyperstimulation related to a gonadotroph adenoma in a 29-year-old woman. The patient presented with amenorrhea and large cystic ovaries. Her serum estradiol was markedly elevated (up to 31,100 pmol/l). Serum LH was low, but serum FSH and PRL were normal. Cranial magnetic resonance imaging study revealed a pituitary macroadenoma. After successful removal of the pituitary tumor, FSH, LH and estradiol normalized and fluctuated within normal ranges thereafter. The patient resumed regular cycles of menstruation and conceived spontaneously. During pregnancy, estradiol increased and FSH and LH decreased. The finding confirms restoration of negative feedback of estradiol on FSH and LH secretion. The pregnancy course was uneventful and enlargement of ovaries did not occur.     

Exacerbation of ovarian hyperstimulation by leuprolide reveals a gonadotroph adenoma

OBJECTIVE: To report a case of a gonadotroph adenoma diagnosed after a dramatic increase in estradiol level and ovarian hyperstimulation in response to a gonadotropin-releasing hormone agonist. DESIGN: Case report. SETTING: Outpatient practice and university hospital. PATIENT(S): A 35-year-old woman who presented with infertility, amenorrhea, and an elevated basal estradiol concentration. INTERVENTION(S): Ultrasonography, laparoscopy, endocrinologic assays, magnetic resonance imaging, transsphenoidal surgery, and immunocytochemical staining. MAIN OUTCOME MEASURE(S): Ultrasonography and laparoscopy demonstrated bilaterally enlarged ovaries containing multiple preovulatory follicles, similar in appearance in those women undergoing controlled ovarian hyperstimulation with exogenous FSH. The serum estradiol level was moderately elevated, the FSH level was within the normal range, and LH was suppressed. Administration of leuprolide acetate resulted in very elevated estradiol concentrations and even larger ovarian cysts. Magnetic resonance imaging demonstrated a sellar mass. Examination of the tissue excised by transsphenoidal excision of the mass showed a pituitary adenoma that stained strongly for FSH. RESULT(S): Regular menses resumed soon after excision of the gonadotroph adenoma, followed by a spontaneous pregnancy. CONCLUSIONS: Gonadotroph adenoma should be suspected in a reproductive age woman with oligomenorrhea or amenorrhea, infertility, multiple preovulatory follicles, and a persistently elevated serum estradiol concentration. Exacerbation of the ovarian hyperstimulation in response to a gonadotropin-releasing hormone agonist in this setting also strongly suggests a gonadotroph adenoma but can be avoided by recognizing the presenting features of this condition.     

Ovarian hyperstimulation,hyperprolactinaemia and LH gonadotroph adenoma

This report considers a highly exceptional case of ovarian hyperstimulation syndrome due to a gonadotroph adenoma secreting LH in a 31-year-old patient who presented with amenorrhoea and galactorrhoea syndrome and a complex bilateral ovarian mass. Magnetic resonance imaging revealed a pituitary adenoma, and laboratory tests corroborated the hyperprolactinaemia without other hormonal pituitary abnormalities. Ovarian hyperstimulation syndrome due to a gonadotroph adenoma with normal gonadotrophins is extremely rare. Most of the described cases are caused by FSH adenomas. Due to the originality of the case, it was considered useful for understanding the management of this entity, and it is proposed that LH adenomas should also be considered in the differential diagnosis of patients with spontaneous ovarian hyperstimulation syndrome.     

Nonfunctioning pituitary macroadenoma presenting with mild hyperprolactinemia and amenorrhea.

OBJECTIVE: To describe a patient with a clinically nonfunctioning pituitary macroadenoma who presented with mild hyperprolactinemia and amenorrhea. DESIGN: Case report. SETTING: Tertiary care medical facility. PATIENT(S): A 44-year-old woman with a 6-month history of amenorrhea. INTERVENTION(S): Pituitary testing, magnetic resonance imaging of the sella turcica, and transsphenoidal surgery. MAIN OUTCOME MEASURE(S): Pituitary function testing, magnetic resonance imaging, and return of menstrual cycles. RESULT(S): Baseline laboratory data revealed a serum prolactin level of 34 ng/mL (normal range, 3-20 ng/mL), normal thyroid function test results, and an FSH level of 6.7 mIU/mL. A second fasting prolactin level was 48 ng/mL. Magnetic resonance imaging of the sella turcica revealed a pituitary macroadenoma measuring 1.4 x 3.2 cm. Further testing of baseline pituitary function revealed normal findings. The patient underwent an uncomplicated transsphenoidal resection of the pituitary tumor and maintained normal pituitary function. Pathologic evaluation revealed a pituitary adenoma that stained positive for FSH and focally for the alpha subunit. The adenoma stained negative for GH, prolactin, ACTH, LH, and TSH. CONCLUSION(S): This patient had a nonsecreting gonadotroph macroadenoma that resulted in hypogonadotropic hypogonadism along with mild hyperprolactinemia, presumably secondary to interruption of normal transport down the pituitary stalk.     

The use of gonadotropins for the induction of ovulation in women with polycystic ovarian disease

Ten infertile patients with polycystic ovarian disease were treated with 18 cycles of "pure" human pituitary follicle-stimulating hormone (HP-FSH) and 10 cycles of human menopausal gonadotropin (HMG) consisting of FSH and luteinizing hormone (LH) in a 1:1 ratio. Human chorionic gonadotropin was used to trigger ovulation when optimal follicular development was achieved as judged by urinary estrogen determinations. Of the 18 cycles utilizing HP-FSH, 14 were presumptively ovulatory, 2 were conceptual, and in 5 cycles ovarian enlargement was noted. Of the 10 HMG cycles, none was ovulatory, no conceptions resulted, and 6 instances of hyperstimulation were noted. Pretreatment serum LH levels were significantly higher than normal follicular phase values. These observations suggest that endogenous LH levels in patients with polycystic ovaries are quite adequate for follicular development so that the administration of exogenous LH is unwarranted. Furthermore, the data suggest that HP-FSH or low-LH-containing HMG may prove to be an additional safe and effective nonsurgical treatment modality for patients who are anovulatory because of polycystic ovaries.     

The recovery of normal plasma progesterone levels in the postpartum female

The return of fertility in postpartum women is gradual. This may be related to ovarian hormonal deficiencies, in particular, inadequate stimulation of the endometrium by progesterone (P). The purpose of this study was to evaluate the recovery of normal luteal function in four postpartum women who were followed for four cycles with serum P, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and prolactin (PRL) taken three times weekly. PRL decreased immediately after delivery and was at normal levels before the first cyclic increases in serum LH and P. E2 and FSH cyclic changes were identical over the four menstrual cycles. LH peak values rose consistently from the first to the fourth cycle. P increased statistically each subsequent cycle in all parameters studied. These parameters of P were peak levels, days to the peak, duration of the luteal phase, and area under the P curve. The postpartum woman thus seems an excellent model for the study of ovarian hormonal disorders, particularly as they relate to disordered luteal P.     

The role of serum PRL bioactivity evaluation in hyperprolactinaemic women with different menstrual disorders

Objective.?The objective of the study was to characterize the bioactivity of prolactin (PRL) in hyperprolactinaemic patients with prolactinomas, irregular menstrual cycles, regular menstrual cycles and PCOS.

Methods.?Serum PRL, biological activity of PRL (after polyethylene glycol (PEG) precipitation) and serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), thyroid-stimulating hormone (TSH) concentrations were measured in all hyperprolactinaemic patients and control group (healthy subjects). Correlations between active PRL (PRL-PEG) and serum FSH, LH, E2, T, TSH concentrations were also evaluated.

Results.?Prolactinoma is characterized by high serum PRL levels and its high biological activity. Hyperprolactinaemic patients with irregular cycles were characterized by high biological activity of PRL. Patients with hyperprolactinaemia and regular cycles had low biological activity of PRL.

Conclusions.?Diagnosis of hyperprolactinaemia should be associated with estimation of PRL biological activity because it is important for type of hyperprolactinaemia management. Low biological activity of PRL does not impair FSH and LH secretion and does not cause hypoestrogenism.     

Hypothesis: aberrant puberty and the Stein-Leventhal syndrome

We hypothesize that the Stein-Leventhal syndrome (type 1 polycystic ovarian disease: SLS-PCOD-I) results from an aberrant puberty. Abnormal neural development in the brain decreases the hypophyseal set-point for negative and positive ovarian hormone feedback. This generates a condition whereby hypophyseal luteinizing hormone (LH) secretion is inappropriately elevated compared to hypophyseal follicle-stimulating hormone (FSH) secretion and is thus termed inappropriate gonadotropin secretion (IGS). The events which create an initial state of IGS are referred to as the "generator" stage. IGS is maintained by ovarian-derived hyperandrogenemia and increased peripheral aromatization of androgens yielding elevated free serum estrone (E1) and unbound estradiol (E2) levels. E1 suppresses release of hypophyseal FSH while E2 exerts positive feedback on LH pulsatile release by increasing pituitary sensitivity to gonadotropin-releasing hormone (GnRH). Diminished circulating FSH levels decrease granulosa cell aromatase activity sufficiently to cause suboptimal ovarian conversion of LH-induced thecal androgens into estrogens. Consequently, chronic local ovarian hyperandrogenemia with associated arrested follicle maturation results in chronic anovulation. Furthermore, an elevated circulating LH/FSH ratio stimulates early development and proliferation of immature follicles causing the appearance of polyfollicular ovaries. In this effector stage of PCOD-I, a vicious cycle is fashioned wherein IGS causes polyfollicular ovaries and increased ovarian androgen production which, in turn, promotes IGS. We suggest that the etiology of this disease involves an aberrant puberty that establishes a persistent faulty hypothalamic-hypophyseal-ovarian axis.     

Infertility in women with apparently ovulatory cycles. I. Comparison of their plasma sex steroid and gonadotrophin profiles with those in the normal cycle.

Serial daily plasma profiles of luteinizing hormone (LH), follicle stimulating hormone (FSH), progesterone, 17alpha-hydroxyprogesterone and oestradiol 17beta throughout single menstrual cycles from seven patients with a history of infertility but with normal menstrual rhythm and no apparent ovarian dysfunction were compared with those from apparently normally menstruating women. This comparison showed that the infertile group produced poor corpora lutea after poor follicular growth. The poor follicular growth may be related to depressed pituitary release of FSH in response to a negative feedback effect of elevated progesterone levels.     

Normal ovarian function in a mild form of late-onset 3 beta-hydroxysteroid dehydrogenase deficiency

Late-onset 3 beta-hydroxysteroid dehydrogenase (HSD) deficiency was diagnosed in a 30-year-old woman with hirsutism and normal menstrual cycles. No genital abnormalities were present. Elevated basal serum levels of delta 5-3 beta-hydroxysteroids were demonstrated. Serum pregnenolone (P5) was 3.0 ng/ml, and dehydroepiandrosterone sulphate (DHEA-S) 3245 ng/ml. Basal serum levels of delta 4 steroids were low or within normal limits. Serum progesterone (P) was 0.5 ng/ml, 17 alpha-hydroxyprogesterone (17-OHP) 0.2 ng/ml, androstenedione (delta 4A) 0.4 ng/ml, and testosterone (T) 0.1 ng/ml. All delta 5/delta 4 steroid ratios were elevated. Dexamethasone (DEX) administration normalized the elevated levels of delta 5-3 beta-hydroxysteroids, whereas delta 4-3-ketometabolites exhibited only minor modifications. The DHEA-S/delta 4A ratio increased more than five times over the basal ratio, and P5/P and 17 alpha-hydroxypregnenolone (17-OHP5)/17-OHP ratios did not increase after adrenocorticotrophic hormone ACTH stimulation. Studies of basal ovarian function revealed 17 beta-estradiol (E2) and gonadotropins within normal limits according to the menstrual cycle. In the follicular phase, follicle-stimulating hormone (FSH) was 101.3 ng/ml, luteinizing hormone (LH) 46.0 ng/ml, and E2 49.7 pg/ml; in the luteal phase, FSH was 180.0 ng/ml, LH 69.3 ng/ml, and E2 50.1 pg/ml. The presence of ovulatory cycles was documented on the basis of the biphasic pattern of the basal body temperature cycles and the increment in P levels. This case demonstrates the existence of normal ovulatory function in a woman with late-onset of a mild form of HSD.     

The influence of weight loss on the reproductive function of the female rat: changes in the estrous cycle and hypothalamo-pituitary-ovarian function during feed restriction and subsequent refeeding period

Twelve-week-old female SD rats were restricted to an 8 g/day feed intake for 2 months followed by feeding ad libitum for 3 weeks. Feed restriction resulted in weight loss and constant diestrous. A persistent increase in the hypothalamic GnRH content was observed during the underfed period. Serum LH and PRL levels dropped throughout the period but the initial reduction in the serum FSH level was observed on the 60th day. The reductions in the pituitary content of these hormones were observed on the 30th day. The decrease in the serum and ovarian E2 levels were detected on the 14th day. Anterior pituitary showed a significant response to GnRH + TRH during the course, and the relative increases in LH, FSH and PRL were greater than those in the pretreatment rats. In the course of refeeding, the body weight returned to the control level and regular estrous cycles were reestablished on the 15th and 21st day, respectively. Elevated hypothalamic GnRH content returned to the control level on the 16th day. The changes in the pituitary-ovarian axis were prompt rebound rises in serum FSH and PRL levels and pituitary FSH content, delayed restoration of serum and pituitary LH levels and serum and ovarian E2 levels, and a marked increase in the serum and ovarian progesterone levels on the 16th day. The relative increases in FSH and PRL after GnRH + TRH injection were smaller than those in the underfed period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrinological development in girls during puberty

I) Endocrinological changes in girls during puberty are characterized by the progressive elevation of pituitary, ovarian and adrenal hormones except PRL. Longitudinal study revealed significant increases in both LH, FSH and estradiol occurred between 2 years to one year before menarche. PRL levels, however, increased between 3 to 2 years before menarche and the levels dropped significantly one year before the onset of the first menses. Serum levels of androstenedione and estrone in girls were higher than that in boys. Among steroids, the levels of 5 alpha-androstanediol decreased significantly before the menarche suggesting the physiological role of this hormone on the onset of puberty. In regard to the correlation between hormone levels and sexual developments, DHA-S levels and body weights correlated well with the breast development. Grasping power correlated well with serum testosterone levels in girls. II) The clinical and endocrinological aspect of menstrual disorders during adolescent were also examined. The majority of the patients complaining of functional uterine bleeding and amenorrhea showed high LH and normal FSH levels. Episodic secretion of LH was absent in girls of primary and secondary amenorrhea due to hypothalamic impairment.     

Cytogenetic and endocrine studies in a 45,X female subject with spontaneous sexual development.

Cytogenetic and endocrine evaluation of a postpubertal 45,X female subject with Turner's stigmas and spontaneous sexual development was performed. A 45,X chromosomal complement was found in the peripheral blood lymphocytes, bone marrow, and fibroblasts derived from skin and ovaries. Menarche, pubarche, and thelarche occurred at age 12; at age 16 she developed menstrual irregularities, with endometrial bleeding occurring every 60 to 90 days. The ovaries were normal in size, and histologic examination revealed a marked paucity of primordial follicles, increased collagenization, and absence of corpora albicans. Anovulatory cycles with moderately elevated levels of luteinizing hormone (LH) and low follicle-stimulating hormone (FSH) levels were observed. LH-releasing hormone pituitary stimulation induced a normal LH release with a very slight FSH increase. Administration of clomiphene citrate successfully induced a normal-length ovulatory cycle. Similarities in the hormonal situation of this patient and that seen in the Stein-Leventhal syndrome are pointed out.     

Evaluation of dynamic pituitary function testing in patients with hyperprolactinemia on diagnosis of pituitary prolactin-secreting adenoma (author's transl)

Thirty hyperprolactinemic women were divided into four group according to radiological and computed tomographic findings of sella turcica as follows; sulpiride-induced (N = 7), functional (N = 6), microadenoma (N = 9) and macroadenoma (N = 8). It was measured the serum basal level of pituitary LH, FSH, PRL, TSH and GH, and the responsiveness to LH-RH, TRH, insulin administration, respectively. These values were compared to that during bromocriptine treatment (5mg/day, 2 weeks). Before and during treatment with bromocriptine, there were not significant changes of basal level of LH, FSH and TSH, and also the responsiveness to LH-RH administration in four group. In pretreatment period, PRL responsiveness to TRH was good in sulpiride-induced and functional groups, but decreased in microadenoma and macroadenoma groups. During bromocriptine treatment period, basal PRL level was significantly suppressed in three groups except sulpiride-induced group, and PRL responsiveness to TRH was good in three groups except macroadenoma group. These findings ae concluded as follows: 1) Mechanism of the disturbance of ovulation in hyperprolactinemia does not closely related to pituitary gonadotroph dysfunction. 2) Decreased PRL responsiveness to TRH (maximal fold increase: under 40%) is of diagnostic value of pituitary adenomas. 3) Difference of PRL responsiveness to TRH during treatment with bromocriptine is distinguishing the microadenoma from macroadenoma.     

A follicle-stimulating hormone-secreting gonadotroph adenoma with ovarian enlargement in a 10-year-old girl.

OBJECTIVE: To report a rare case of gonadotroph adenoma accompanied by ovarian enlargement in a child. DESIGN: Case report. SETTING: A university hospital. PATIENT(S): A 10-year-old Japanese girl with multiple cysts of both ovaries. INTERVENTION(S): Endocrinologic assays, immunohistochemical staining, ultrastructural observations, and in vitro analysis. MAIN OUTCOME MEASURE(S): The endocrinologic assays showed an elevated serum FSH level. The tumor cells excised from the gonadotroph adenoma were immunohistochemically positive for antihuman FSH monoclonal antibody. When cultured in vitro, the tumor cells secreted FSH in the primary culture. RESULT(S): The gonadotroph adenoma produced FSH. After transsphenoidal surgery, both ovaries decreased in size. CONCLUSION(S): The ovarian enlargement was induced by endogenous FSH from the gonadotroph adenoma. To our knowledge, this is the first reported case of gonadotroph adenoma accompanied by ovarian enlargement in childhood or adolescence.     

Anti-goat antibodies as a rare cause of high gonadotropin levels during menopausal transition

Abstract

Objective: To understand the origin of extremely high gonadotropin levels in a perimenopausal woman.

Methods: A 52-year-old woman with a 2?months of amenorrhea followed spontaneous menstrual cycles recovery was referred to our outpatient clinic with elevated follicle-stimulating hormone (FSH, 483 mUI/ml), luteinizing hormone (LH, 475 mUI/ml) and prolactin (PRL, 173?ng/ml). She was known to take levosulpiride. The gonadotropin levels did not fit with the clinical features.

Results: A gonadotroph tumor was ruled out. Further analysis confirmed constantly high FSH, LH and PRL levels. The measurements were repeated using different analytical platforms with different results. After serial dilutions, nonlinearity was present suggesting an immunoassay interference. After post-polyethylene glycol recovery, hormone levels appeared in the normal range. Anti-goat antibodies were recognized in the serum of the patient.

Conclusions: This case report shows a case of falsely abnormal high gonadotropin and PRL levels in a woman during menopause transition. In the clinical practice the evaluation of gonadotropin profile is not recommended at this age, but the abnormal levels stimulated further evaluation. An interference in the assay due to anti-goat antibodies resulted in abnormally high level of FSH and LH. A strict collaboration between clinicians and the laboratory is needed, when laboratory findings do not correspond to clinical findings.     

Steroid,follicle-stimulating hormone,and luteinizing hormone profiles in identical twins with polycystic ovaries

Identical twins (age 16) with polycystic ovarian disease documented by laparoscopy are compared to a “normal” 18-year-old sibling. Fractionation and individual estimation of urinary 17-ketosteroids, 17-ketogenic steroids, pregnanetriol, and total estrogen were performed on both amenorrheic twins and their normal menstruating sibling. Steroid values were obtained during adrenal suppression and after adrenal provocation with adrenocorticotropic hormone nd metyrapone. Serum levels for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were obtained periodically over a period of 16 months on the twins with polycystic ovarian disease. All 3 siblings gave evidence of androgen overproduction on the part of the ovaries and adrenals. Serum LH values in the twins were elevated but exhibited considerable fluctuation. Serum FSH values were lower but also manifested considerable variation. The similar steroid profile in the 3 siblings and the LH/FSH pattern in the identical twins are discussed.     

Diagnostic evaluation of progesterone challenge test in amenorrheic patients (author's transl)

Diagnostic evaluation of progesterone (P) challenge test (menstrual response and serum LH changes after P administration) was studied in 223 patients with secondary amenorrhea. Based on the serum FSH an prolactin (PRL) values amenorrheic patients were divided into three major groups; low or normal levels of FSH and PRL (Group I), high levels of PRL (Group II), high levels of FSH (Group III). Serum estradiol levels in patients with normal menstrual response to P were significantly higher than those with absent or scanty bleeding following P. Although the Group III patients with absent or scanty bleeding (Group IIIb) represented patients with ovarian failure, those with normal menstrual response to P (Group IIIa) clinically appeared to have high developed ovarian follicles. Based on the LH responses after P administration the Group I patients were further subdivided into two groups, one with LH increase following P (Group Ia) and the second with no LH increase (Group Ib). In Group Ia 92 percent ovulated with clomiphene but all in Group Ib failed to ovulate. Therefore the LH changes after P administration gave good prediction of ovulatory as well as anovulatory responses to clomiphene.     

19例下丘脑性闭经的诊断及助孕治疗分析

目的:探讨下丘脑性闭经(hypothalamic amenorrhea,HA)的临床特征和助孕治疗方法。方法:对19例HA患者进行病例回顾分析,总结临床特征,并与19例月经规律的正常妇女进行对照,比较血FSH、LH、E2、PRL、T水平及子宫体积、卵巢体积和基础窦卵泡数。对HA患者进行人工周期和hMG促排卵治疗,总结治疗方法和效果。结果:HA患者无或部分或不全性征发育,无潮热症状,染色体核型正常;血FSH、LH和PRL水平明显低于正常妇女(P<0.01),血FSH和LH呈低～正常水平,血E2和T水平与对照组比无明显差异。HA患者子宫和平均卵巢体积明显小于对照组,基础窦卵泡数明显少于对照组(P<0.01)。HA组行人工周期治疗,其中11例行hMG促排卵治疗后有排卵,7例临床妊娠。结论:人工周期和hMG促排卵治疗是对有生育要求的HA患者的经济有效的治疗,但需从低剂量起始,按逐渐加量和减量的原则进行,预防卵巢过度刺激综合征和多胎。出现多卵泡发育时穿刺多余卵泡或中转IVF,都是较好的补救措施。     

Effects of low day 3 luteinizing hormone levels on in vitro fertilization treatment outcome.

In a previous study we demonstrated that women with day 3 luteinizing hormone (LH) values < 3 IU/l subjected to controlled ovarian hyperstimulation without pituitary desensitization responded with a lower number of follicles > 15 mm compared to women with a higher basal LH level. The aim of this study was to determine whether in patients with day 3 LH levels < 3 IU/l a further reduction of serum LH concentration by gonadotropin-releasing hormone (GnRH) analog impairs follicular response to follicle stimulating hormone (FSH) and treatment outcome in in vitro fertilization (IVF) cycles. For this purpose we retrospectively studied 249 consecutive women subjected to standard IVF treatment employing pituitary desensitization with buserelin and follicular stimulation with urinary highly purified FSH. The patients were divided into two groups according to their day 3 LH value. The first group (group A) showed day 3 LH levels < 3 IU/l and the second (group B) had day 3 LH levels > 3 IU/l. Group A and B patients did not show statistically significant differences in the ovarian response to FSH, nor in IVF treatment outcome, showing that in FSH treated GnRH analog suppressed cycles, the ovarian responsiveness and IVF outcome do not differ according to basal LH values. However, the high dosage of FSH we employed in group A and B patients could account, at least in part, for this result. Indeed, comparative evaluations with unsuppressed cycles (our previous study) strongly suggest that a reduced ovarian responsiveness to gonadotropins in patients with day 3 LH values < 3 IU/l should be considered in clinical practice.