Scoring method of a Situational Judgment Test: influence on internal consistency reliability, adverse impact and correlation with personality?

Situational Judgment Tests (SJTs) are increasingly used for medical school selection. Scoring an SJT is more complicated than scoring a knowledge test, because there are no objectively correct answers. The scoring method of an SJT may influence the construct and concurrent validity and the adverse impact with respect to non-traditional students. Previous research has compared only a small number of scoring methods and has not studied the effect of scoring method on internal consistency reliability. This study compared 28 different scoring methods for a rating SJT on internal consistency reliability, adverse impact and correlation with personality. The scoring methods varied on four aspects: the way of controlling for systematic error, and the type of reference group, distance and central tendency statistic. All scoring methods were applied to a previously validated integrity-based SJT, administered to 931 medical school applicants. Internal consistency reliability varied between .33 and .73, which is likely explained by the dependence of coefficient alpha on the total score variance. All scoring methods led to significantly higher scores for the ethnic majority than for the non-Western minorities, with effect sizes ranging from 0.48 to 0.66. Eighteen scoring methods showed a significant small positive correlation with agreeableness. Four scoring methods showed a significant small positive correlation with conscientiousness. The way of controlling for systematic error was the most influential scoring method aspect. These results suggest that the increased use of SJTs for selection into medical school must be accompanied by a thorough examination of the scoring method to be used.

Ethnic and social disparities in different types of examinations in undergraduate pre-clinical training.

Medical schools are increasingly faced with a more diverse student population. Generally, ethnic minority students are reported to underperform compared with those from the ethnic majority. However, there are inconsistencies in findings in different types of examinations. Additionally, little is known about the performance of first-generation university students and about performance differences across ethnic minority groups. This study aimed to investigate underperformance across ethnic minority groups and by first-generation university students in different types of written tests and clinical skills examinations during pre-clinical training. A longitudinal prospective cohort study of progress on a 3-year Dutch Bachelor of Medicine course was conducted. Participants included 2432 students who entered the course over a consecutive 6-year period (2008-2013). Compared with Dutch students, the three non-Western ethnic minority groups (Turkish/Moroccan/African, Surinamese/Antillean and Asian) underperformed in the clinical problem solving tests, the language test and the OSCEs. Findings on the theoretical end-of-block tests and writing skills tests, and results for Western minority students were less consistent. Age, gender, pre-university grade point average and additional socio-demographic variables (including first-generation university student, first language, and medical doctor parent) could explain the ethnicity-related differences in theoretical examinations, but not in language, clinical and writing skills examinations. First-generation university students only underperformed in the language test. Apparently, underperformance differs both across ethnic subgroups and between different types of written and clinical examinations. Medical schools should ensure their assessment strategies create a level playing field for all students and explore reasons for underperformance in the clinical and writing skills examinations.

Acute effects of acylated and unacylated ghrelin on total and high molecular weight adiponectin inmorbidly obese subjects.

BACKGROUND: Energy homeostasis and body weight are regulated by a highly complex network involving the brain, the digestive tract, and white adipose tissue (WAT). Knowledge about signaling pathways connecting digestive tract and WAT is limited. Gut hormone ghrelin and adipokine adiponectin are both decreased in obesity and they share a potent effect on insulin sensitivity: both adiponectin and the combination of acylated (AG) and unacylated ghrelin (UAG) improve insulin sensitivity. AIM: In the present study, we evaluated whether acute administration of UAG alone or combined with AG affects adiponectin concentrations. SUBJECTS AND METHODS: Eight morbidly obese non-diabetic subjects were treated with either UAG 200 µg, UAG 100 µg + AG 100 µg (Comb), or placebo in 3 episodes in a double blind randomized cross-over design. Study medication was administered as single iv bolus injections at 09:00 h after an overnight fast. High molecular weight (HMW) and total adiponectin, glucose, insulin, and total ghrelin and AG were measured up to 1 h after administration. RESULTS: HMW and total adiponectin concentrations did not change after administration of either UAG or Comb, nor were they different from placebo. Insulin concentrations decreased significantly after acute administration of Comb, reaching a minimum at 20 min: 58.2 ± 3.9% of baseline. CONCLUSIONS: Acute iv administration of UAG and the combination of UAG and AG in morbidly obese non-diabetic subjects without overt diabetes does not affect total or HMW adiponectin concentrations, neither directly nor indirectly by changing insulin concentrations.

Assessment of ovarian reserve in adult childhood cancer survivors using anti-Müllerian hormone.

BACKGROUND: The aim was to assess possible treatment-induced gonadal damage in a cohort of adult female childhood cancer survivors (CCS) using anti-Müllerian hormone (AMH), the most sensitive marker of ovarian reserve. METHODS: A total cohort of 185 survivors was compared with 42 control subjects. The median follow-up time was 18.1 years (range 4.1-43.2 year). RESULTS: Median AMH concentrations in the analysed cohort were not different from controls (median 1.7 versus 2.1 microg/l; P = 0.57). However, AMH levels were lower than the 10th percentile of normal values in 27% (49/182) of our survivors. In addition, 43% (79/182) had AMH levels lower than 1.4 microg/l, a previously established cut-off value which predicts ongoing pregnancy after assisted reproduction. There were no differences in AMH levels in subgroups classified according to disease. However, survivors treated with three or more procarbazine containing chemotherapy cycles had significantly lower AMH levels than controls (median 0.5 microg/l; P = 0.004). Also survivors treated with abdominal or total body irradiation had significantly lower AMH levels than controls (median < 0.1 microg/l; P < 0.001). CONCLUSIONS: AMH can be used to identify subgroups of CCS at risk for decreased fertility or premature ovarian failure. In these survivors, options for fertility preservation should be considered prior to starting treatment since they may be at risk for poor chances of pregnancy after assisted reproductive treatment.

Genetic polymorphisms of GnRH and gonadotrophic hormone receptors affect the phenotype of polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex genetic disorder. Multiple functional polymorphisms have been identified in genes that regulate the hypothalamic-pituitary-gonadal (HPG) axis that regulates ovarian function. The present study aims to examine the influence of genetic variants of the HPG-axis on the severity of clinical features of PCOS and disease susceptibility. METHODS: We included 518 Caucasian PCOS women and 2996 unselected controls from the general population (the Rotterdam study). Genotype distributions were compared between patients and controls. Subsequently, associations with clinical features of PCOS were studied. Single nucleotide polymorphisms were selected in GnRH (Trp16Ser [rs6185]), the FSH-receptor (FSHR, Ala307Thr [rs6165] and Asn680Ser [rs6166]) and the LH-receptor (18insLQ, Asn291Ser [rs12470652] and Ser312Asn [rs2293275]). RESULTS: FSHR Ser(680) was associated with higher levels of gonadotrophic hormones (FSH: P < 0.01, LH: P = 0.01), and testosterone (P = 0.05) and a higher frequency of hyperandrogenism (P = 0.04). No differences in risk for PCOS in association with the FSH-receptor variants were observed. CONCLUSION: Genetic variants of the HPG-axis were associated with a modest but significant effect on the phenotype of PCOS. FSHR variants were strongly associated with the severity of clinical features of PCOS, such as levels of gonadotrophic hormones and the presence of hyperandrogenism, but not disease risk.

Relationship of serum antimüllerian hormone concentration to age at menopause.

BACKGROUND: Serum antimüllerian hormone (AMH) levels are highly correlated with antral follicle counts, while being menstrual cycle independent and easily measurable. However, AMH, unlike antral follicle counts, has not been tested as yet as a predictor of reproductive status. By relating AMH levels to the age distribution of reproductive events like onset of menopause, we tested this hypothesis. METHODS: AMH levels were measured in 144 fertile normal volunteers and used to determine an estimate of mean AMH as a function of age. Data on the onset of menopause were obtained from the population-based Prospect-European Prospective Investigation into Cancer and Nutrition [Prospect-EPIC] cohort. Estimation of an AMH threshold to predict menopause was done by maximum likelihood using the observed (Prospect-EPIC) distribution of age at menopause and the predictive distribution from this AMH threshold. Predictions of age at menopause follow from an individual woman's AMH relative to percentiles of the distribution of AMH for a given age, and the corresponding percentiles of the predictive distribution of age at menopause. RESULTS: There was good conformity between the observed distribution of age at menopause and that predicted from declining AMH levels. CONCLUSIONS: The similarity between observed and predictive distributions of age at menopause supports the hypothesis that AMH levels are related to onset of menopause. Results of this study suggest that AMH is able to specify a woman's reproductive age more realistically than chronological age alone.

The endocrine and follicular growth dynamics throughout the menstrual cycle in women with consistently or variably elevated early follicular phase FSH compared with controls.

BACKGROUND: Elevated early follicular phase (EFP) FSH is frequently observed in subfertile patients. In these women, temporary normalization of FSH concentrations is known to occur. We studied the complete endocrine cycle profile of subfertile young women with elevated basal FSH compared with controls. METHODS Daily bloodsampling and ultrasound monitoring in the follicular phase was performed in 22 patients with elevated basal FSH levels (identified in screening) and in 16 controls during one menstrual cycle and for 5 days of the next cycle. RESULTS: Eleven patients showed elevated basal FSH levels in the study cycle ('High, High'; H,H group) whereas 11 had normalized basal FSH levels ('High, Low'; H,L group). Anti-Müllerian hormone (AMH) was lower in both groups. In the H,H group, FSH was higher in all phases of the cycle and both inhibin A and B were lower during the EFP. In the H,L group, FSH was also higher than in controls in the EFP and the late luteal phase and inhibin A was higher in the periovulatory phase. 'Normalization' of Day 3 FSH in women with previously elevated FSH was associated with normalization of inhibin B levels in the preceding luteal phase. CONCLUSIONS: The endocrine cycle profile in younger subfertile patients with consistently elevated basal FSH resembles that in published data from older women and also reflects a low ovarian reserve. Normalization of FSH in association with normal inhibin B suggests a temporary increase of the available cohort.

Anti-müllerian hormone as a marker of ovarian function in women after chemotherapy and radiotherapy for haematological malignancies.

BACKGROUND: In female cancer survivors, the accelerated loss of primordial follicles as a result of gonadal damage may lead to premature ovarian failure (POF). However, the extent of the damage is unpredictable. Anti-Müllerian hormone (AMH) constitutes a sensitive marker of ovarian reserve. Serum AMH levels were measured to assess sub-clinical ovarian damage in patients treated with gonadotoxic therapy. METHODS: In 25 patients with haematological malignancies, serum AMH concentrations were measured prior to and after cancer therapy and were compared with normo-ovulatory controls. RESULTS: In all patients, AMH concentrations were lower than controls prior to treatment. Thirteen patients were treated with multi-drug chemotherapy. Although in most patients treated with chemotherapy menstrual cyclicity was restored, median serum AMH levels were lower than in controls. Twelve patients had stem cell transplantation (SCT) after total body irradiation. They all developed POF and their serum AMH concentrations were undetectable. CONCLUSIONS: Female cancer survivors treated with SCT all developed POF. Hence, in these patients fertility preservation should be considered. In patients treated with chemotherapy, ovarian reserve seems to be compromised as well.

A new LH receptor splice mutation responsible for male hypogonadism with subnormal sperm production in the propositus, and infertility with regular cycles in an affected sister.

BACKGROUND: Inactivating LH receptor (LHR) mutations have been described so far in men as well as in women. Phenotypes in men have been variable with in nearly all cases impairment of sex differentiation or azoospermia. We report a milder reproductive phenotype both in a male patient and his sister. METHODS AND RESULTS: We describe a family that carries a homozygous mutation G-->A at position -1 at the intron 10-exon 11 boundary of the LHR gene. The male patient presented with delayed puberty, micropenis and oligospermia. Two of his sisters were homozygous for the same mutation and were infertile. Surprisingly, one of them was found to have had regular ovarian cycles for years and showed normal LH values (6.5 and 10.6 mIU/ml for LH and FSH, respectively). In vitro analysis showed that this altered splicing resulted in an LHR from which eight amino acids are deleted from the extracellular domain (Delta Tyr(317)-Ser(324)). In vitro expression has shown that the receptor was expressed and capable of LH-induced signaling, albeit with reduced potency (P < 0.001). CONCLUSIONS: LHR mutations may represent an underestimated cause of infertility in women, in addition to being responsible for male hypogonadism with reduced spermatogenesis.

Anti-Müllerian hormone: a marker for oocyte quantity, oocyte quality and embryo quality?

Serum anti-Müllerian hormone (AMH) concentrations decline with increasing age and constitute a sensitive marker for ovarian ageing. In addition, basal serum AMH concentrations predict ovarian response during IVF cycles. Concomitantly, oocyte quantity and embryo quality decrease with advancing age. Hence, it was postulated that AMH in serum constitutes a marker for embryo quality. Women aged 37 years and younger with regular menstrual cycles, normal body mass index and partners with normal semen parameters were randomly assigned to either a standard or mild stimulation protocol for IVF treatment. Blood samples were drawn at cycle day 3 and at the day of human chorionic gonadotrophin administration. Embryo quality was assessed using embryo morphology score and preimplantation genetic screening. Serum AMH concentrations on cycle day 3 were correlated with the number of oocytes retrieved in both groups. AMH and embryo morphology were correlated after mild stimulation, but not after conventional ovarian stimulation. AMH and the chromosomal competence of embryos were not correlated. Serum AMH is predictive for ovarian response to stimulation. However, the lack of a consistent correlation with embryo morphology and embryo aneuploidy rate is not in favour of a direct relationship between oocyte quantity and embryo quality.

[Impact of ethnicity and social background on examination results of medical students]. / De invloed van afkomst op studieresultaten.

OBJECTIVE: To investigate underperformance across ethnic minority groups and by first-generation university students in different types of examinations during pre-clinical training. DESIGN: Prospective cohort study METHODS: Participants included Erasmus MC students from the 2008-2013 cohorts (n=2432). Outcome measures were pass/fail on three types of written examinations: 1) theoretical knowledge: clinical problem solving tests (CPSTs) (Year 1-3) and end-of-block tests (Year 1c2-c3), 2) language skills test (Year 1) and 3) writing skills tests (Year 1-3), and OSCEs (Year 2-3). Odds ratios with 95% confidence intervals were estimated by logistic regression analysis for ethnic subgroups (Surinamese/Antillean, Turkish/Moroccan/African, Asian, Western) compared with Dutch students, adjusted for age, gender, pre-university Grade Point Average (pu-GPA), additional socio-demographic variables (first-generation immigrant, urban background, first-generation university student, first language, medical doctor as parent). Similar analyses were conducted for first-generation university students. RESULTS: Compared with Dutch students, the three non-Western ethnic minority groups underperformed in the CPSTs, the language test and the OSCEs. Findings on the end-of-block and writing skills tests, and results for Western minority students were less consistent. Age, gender, pu-GPA and additional socio-demographic variables could explain the ethnicity-related differences in theoretical examinations, but not in language, clinical and writing skills examinations. First-generation university students only underperformed in the language test. CONCLUSION: Ethnic minority students underperform in pre-clinical training, but there are differences both across ethnic subgroups and between different types of examinations. In designing assessment programs care should be taken to avoid unintended effects of certain types of examinations for certain groups of students.

Leydig cell hypoplasia: absent luteinizing hormone receptor cell surface expression caused by a novel homozygous mutation in the extracellular domain.

Leydig cell hypoplasia is a rare autosomal recessive condition that interferes with normal development of male external genitalia in 46,XY individuals. We have studied a family with a 46,XY girl due to a new homozygous mutation (V144F) in the extracellular ligand-binding domain. HEK 293 cells transfected with the mutant LH receptor exhibited a marked impairment of human chorionic gonadotropin binding. Using Western blotting of the expressed V144F mutant LH receptor protein showed the absence of the glycosylated cell surface form. Treatment of the mutant LH receptor with N-glycosidase F or endoglycosidase-H demonstrated that the mutant receptor is retained in the endoplasmic reticulum. Expression and study of enhanced green fluorescent protein-tagged receptors confirmed that the mutant LHR-V144F receptors do not migrate to the cell surface, and the fluorescence remains intracellular and colocalizes with an endoplasmic reticulum marker, ER-tracker Blue-white DPX. Comparison of the theoretical molecular models of the extracellular domain of the wild-type and the mutant receptor suggests that the mutation LHR-V144F, located in the outer circumference in a alpha-helix of the leucine-rich repeat 4, may induce a conformational strain on the molecule. F144 of the mutant LH receptor has overlapping interactions with F119, which V144 in the wild-type receptor has not.

Luteinizing hormone signaling and breast cancer: polymorphisms and age of onset.

Estrogen exposure has repeatedly been shown to associate with the risk of developing breast cancer. Estrogen synthesis is under the control of LH and FSH, where LH, through its receptor (LHR), stimulates production of ovarian androgens; and FSH, their aromatization to estrogens. Here, we investigated whether functional polymorphic variants in the LH signaling pathway are associated with the risk of breast cancer or its clinical phenotype. A PCR-restriction fragment length polymorphism genotyping approach was used to investigate this in 266 breast cancers. The LHR18insLQ allele does not seem to influence breast cancer risk. However, women who were homozygous for the LHR18insLQ allele were, on average, 8.3 yr younger at diagnosis, compared with those homozygous for the wild-type LHR allele (mean age, 51.9 yr vs. 60.2 yr; P = 0.03). Trends were observed for associations between LHR18insLQ carriers and nodal involvement or larger tumor size. Patients who were LHR18insLQ carriers revealed a significantly worse overall survival, compared with those who were homozygous for LHR [hazard ratio = 2.4; 95% CI (1.3-4.3); P = 0.006]. In contrast, no associations between the LH genotype and any of the clinical parameters were observed. Our findings suggest that the LHR18insLQ gene polymorphism determines an earlier age of disease onset and is prognostic for poor outcome of breast cancer.

Mutant luteinizing hormone receptors in a compound heterozygous patient with complete Leydig cell hypoplasia: abnormal processing causes signaling deficiency.

Over the past 5 yr several inactivating mutations in the LH receptor gene have been demonstrated to cause Leydig cell hypoplasia, a rare autosomal recessive form of male pseudohermaphroditism. Here, we report the identification of two new LH receptor mutations in a compound heterozygous case of complete Leydig hypoplasia and determine the cause of the signaling deficiency at a molecular level. On the paternal allele of the patient we identified in codon 343 a T to A transversion that changes a conserved cysteine in the hinge region of the receptor to serine (C343S); on the maternal allele a T to C transition causes another conserved cysteine at codon 543 in trans-membrane segment 5 to be altered to arginine (C543R). Both of these mutant receptors are completely devoid of hormone-induced cAMP reporter gene activation. Using Western blotting of expressed LH receptor protein with a hemagglutinin tag, we further show that despite complete absence of total and cell surface hormone binding, protein levels of both mutant LH receptors are only moderately affected. The expression and study of enhanced green fluorescent protein-tagged receptors confirmed this view and further indicated that initial translocation to the endoplasmic reticulum of these mutant receptors is normal. After that, however, translocation is halted or misrouted, and as a result, neither mutant ever reaches the cell surface, and they cannot bind hormone. This lack of processing is also indicated by reduced presence of an 80-kDa protein, the only N-linked glycosylated protein in the LH receptor protein profile. Thus, complete lack of signaling by the identified mutant LH receptors is caused by insufficient processing from the endoplasmic reticulum to the cell surface and results in complete Leydig cell hypoplasia in this patient.

Desacyl ghrelin is influenced by changes in insulin concentration during an insulin tolerance test.

OBJECTIVE: Ghrelin, a gut-brain peptide, regulates energy homeostasis and glucose metabolism and is present in acylated and nonacylated form in the circulation. Although desacyl ghrelin (DAG), the predominant form of ghrelin, is associated with insulin sensitivity and improved metabolic state, not much is known about its direct regulation by insulin. We aimed to assess changes in DAG in response to the rapid increase in insulin concentration during an insulin tolerance test (ITT) in normal weight and obese subjects. DESIGN: We performed an observational single center study. An ITT was assessed in eight subjects (four males), median age of 29.9 years (range 19.6-42.0). DAG concentrations were measured at 20, 40, 60 and 90 min after insulin infusion. Homeostatic Model Assessment (HOMA) was calculated from fasting insulin and glucose. Body mass index (BMI) and waist circumference were assessed. RESULTS: Three subjects were obese (BMI ≥ 30 kg/m(2)), one subject was overweight (BMI = 25-30 kg/m(2)) and four subjects had normal weight (BMI = 18.5-25 kg/m(2)). Median DAG decreased after insulin infusion (90 pg/mL, p = 0.028), especially in normal weight subjects. Baseline DAG was lower in subjects with higher BMI (ρ = -0.76, p = 0.028) and higher fasting insulin (ρ = -0.76, p = 0.030). DAG changes correlated with fasting insulin levels (ρ = -0.85, p = 0.007), HOMA (ρ = -0.86, p = 0.007), BMI (ρ = -0.83, p = 0.010) and waist circumference (ρ = -0.93, p < 0.001). CONCLUSION: DAG levels rapidly decreased in response to insulin administration in normal subjects, but not in insulin-resistant obese who are in a state of relative DAG deficiency.

Menopausal status and adjuvant hormonal therapy for breast cancer patients: a practical guideline.

Breast cancer is the most common malignancy amongst women in the developed world. For patients with hormone-sensitive breast cancer eligible for adjuvant hormonal therapy, it is important to know if the ovaries are (still) functional or not. Indeed, the choice for a specific adjuvant hormonal treatment depends on the menopausal status of an individual woman. The currently available measures to determine the menopausal status are conflicting. Until better measures become available, we propose a practical guideline enabling an optimal choice of adjuvant hormonal therapy for women with a hormone receptor positive breast cancer taking into account uncertainties about their menopausal status.

Serum anti-müllerian hormone levels in healthy females: a nomogram ranging from infancy to adulthood.

CONTEXT: Anti-müllerian hormone (AMH) is an accurate marker of ovarian reserve. However, sufficiently large sets of normative data from infancy to the end of reproductive life are scarce. OBJECTIVE: This study was an assessment of serum AMH levels in healthy females. SUBJECTS: In 804 healthy females ranging from infancy until the end of the reproductive period, serum AMH levels were measured with an enzyme-linked immunometric assay. All adults had regular menstrual cycles. The majority was proven fertile and none of them had used oral contraceptive pills prior to study inclusion. RESULTS: In the total cohort, AMH was inversely correlated with age (r = -0.24; P < 0.001). The age at which the maximum AMH value was attained was at 15.8 yr. In girls younger than 15.8 yr, serum AMH and age were positively correlated (r = +0.18; P = 0.007). Thereafter AMH levels remained stable (r = -0.33; P = 0.66), whereas from the age of 25.0 yr onward, an inverse correlation between AMH and age (r = -0.47; P < 0.001) was observed. At any given age, considerable interindividual differences in serum AMH levels were observed. CONCLUSION: During infancy AMH levels increase, whereas during adolescence, a plateau until the age of 25 yr was observed. From the age of 25 yr onward, serum AMH levels correlate inversely with age, implying that AMH is applicable as a marker of ovarian reserve only in women of 25 yr old and older. Our nomogram may facilitate counseling women on their reproductive potential.

Anti-mullerian hormone predicts menopause: a long-term follow-up study in normoovulatory women.

CONTEXT: It has been hypothesized that a fixed interval exists between age at natural sterility and age at menopause. Both events show considerable individual variability, with a range of 20 yr. Correct prediction of age at menopause could open avenues of individualized prevention of age-related infertility and other menopause-related conditions, like cardiovascular disease and breast carcinoma. OBJECTIVE: The aim of this study was to explore the ability of ovarian reserve tests to predict age at menopause. DESIGN AND SETTING: We conducted a long-term follow-up study at an academic hospital. PARTICIPANTS: A total of 257 normoovulatory women (age, 21-46 yr) were derived from three cohorts with highly comparable selection criteria. INTERVENTIONS: Anti-Müllerian hormone (AMH), antral follicle count, and FSH were assessed at time 1 (T1). At time 2 (T2), approximately 11 yr later, cycle status (strictly regular, menopausal transition, or postmenopause) and age at menopause were inventoried. MAIN OUTCOME MEASURES: Accuracy of the ovarian reserve tests in predicting time to menopause was assessed by Cox regression, and a nomogram was constructed for the relationship between age-specific AMH concentrations at T1 and age at menopause. RESULTS: A total of 48 (19%) women had reached postmenopause at T2. Age, AMH, and antral follicle count at T1 were significantly related with time to menopause (P < 0.001) and showed a good percentage of correct predictions (C-statistic, 0.87, 0.86, and 0.84, respectively). After adjusting for age, only AMH added to this prediction (C-statistic, 0.90). From the constructed nomogram, it appeared that the normal distribution of age at menopause will shift considerably, depending on the individual age-specific AMH level. CONCLUSIONS: AMH is highly predictive for timing of menopause. Using age and AMH, the age range in which menopause will subsequently occur can be individually calculated.

Anti-Müllerian hormone (AMH): regulator and marker of ovarian function.

In this review, the role of anti-Müllerian hormone (AMH) as a regulator and marker of ovarian function is described. Studies in mice showed that AMH is one of the intra-ovarian growth factors regulating primordial follicle recruitment and follicle-stimulating hormone (FSH) sensitivity of growing follicles in an inhibitory manner. Association studies of common variants of the AMH and AMHRII gene suggest that AMH may have a similar role in the human ovary. When it was discovered that serum levels AMH are correlated with the number of growing follicles, AMH gained further clinical interest as a marker for the quantitative aspect of ovarian reserve and as a diagnostic marker for polycystic ovary syndrome (PCOS).

Aberrant expression of multiple hormone receptors in ACTH-independent macronodular adrenal hyperplasia causing Cushing's syndrome.

OBJECTIVE: Aberrant adrenal expression of various hormone receptors has been identified in ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing cortisol hypersecretion regulated by hormones other than ACTH. We aimed to determine aberrant expression of multiple hormone receptors in vivo and in vitro in adrenal tissue of a patient with AIMAH. DESIGN: The design of the study includes clinical case description, and biochemical and immunohistochemical analysis to demonstrate aberrant expression of multiple hormone receptors in AIMAH. METHODS: The subject of the study is a male diagnosed with Cushing's syndrome because of AIMAH. Directly after laparoscopic removal of the adrenals, adrenal tissue was incubated with and without test substances (ACTH, forskolin, arginine vasopressin (AVP), desmopressin, epinephrine, norepinephrine, purified human chorionic gonadotropin (hCG), metoclopramide and the combinations of AVP with ACTH, epinephrine and metoclopramide). LH/hCG-receptor (hCG-R) immunohistochemistry and RT-PCR analyses were performed to demonstrate aberrant expression of LH/hCG-R and V(1-3)-AVPR. RESULTS: AIMAH was characterized by in vivo cortisol responsiveness to AVP and in vitro cortisol responses to AVP, hCG, epinephrine, and norepinephrine suggesting aberrant adrenal expression of the receptors for AVP (the V(1-3)-AVPRs), catecholamines (the beta-AR), and LH (the LH/hCG-R). Incubation with combinations of AVP and ACTH and of AVP with epinephrine induced a stronger cortisol response compared with incubation with the individual agents. Moreover, we demonstrated adrenal V(1-3)-AVPR and LH/hCG-R expression. CONCLUSIONS: AIMAH tissue may simultaneously express multiple aberrant hormone receptors, and individual ligands may potentiate each other regarding cell proliferation and cortisol production.