Aging-accumulated methylmalonic acid serum levels at breast cancer diagnosis are not associated with distant metastases.

PURPOSE: Recent evidence suggests that age-accumulated methylmalonic acid (MMA) promotes breast cancer progression in mice. This study aims to investigate the association between baseline serum MMA concentrations in patients with breast cancer and the development of subsequent distant metastases. METHODS: We included 32 patients with early Luminal B-like breast cancer (LumB, median age 62.4y) and 52 patients with early triple-negative breast cancer (TNBC, median age 50.5y) who developed distant metastases within 5 years. They were matched to an equal number of early breast cancer patients (median age 62.2y for LumB and 50.5y for TNBC) who did not develop distant metastases with at least 5 years of follow-up. RESULTS: Baseline serum MMA levels at breast cancer diagnosis showed a positive correlation with age (P < 0.001) and a negative correlation with renal function and vitamin B12 (all P < 0.02), but no statistical association was found with BMI or tumor stage (P > 0.6). Between matched pairs, no significant difference was observed in MMA levels, after adjusting for kidney function and age (P = 0.19). Additionally, in a mouse model, a significant decline in MMA levels was observed in the tumor-bearing group compared to the group without tumors before and after tumor establishment or at identical times for the control group (P = 0.03). CONCLUSION: Baseline serum MMA levels in patients with breast cancer are not correlated with secondary distant metastasis. Evidence in the mouse model suggests that the presence of a tumor perturbates MMA levels.

Comparison of the ADNEX and ROMA risk prediction models for the diagnosis of ovarian cancer: a multicentre external validation in patients who underwent surgery.

BACKGROUND: Several diagnostic prediction models to help clinicians discriminate between benign and malignant adnexal masses are available. This study is a head-to-head comparison of the performance of the Assessment of Different NEoplasias in the adneXa (ADNEX) model with that of the Risk of Ovarian Malignancy Algorithm (ROMA). METHODS: This is a retrospective study based on prospectively included consecutive women with an adnexal tumour scheduled for surgery at five oncology centres and one non-oncology centre in four countries between 2015 and 2019. The reference standard was histology. Model performance for ADNEX and ROMA was evaluated regarding discrimination, calibration, and clinical utility. RESULTS: The primary analysis included 894 patients, of whom 434 (49%) had a malignant tumour. The area under the receiver operating characteristic curve (AUC) was 0.92 (95% CI 0.88-0.95) for ADNEX with CA125, 0.90 (0.84-0.94) for ADNEX without CA125, and 0.85 (0.80-0.89) for ROMA. ROMA, and to a lesser extent ADNEX, underestimated the risk of malignancy. Clinical utility was highest for ADNEX. ROMA had no clinical utility at decision thresholds <27%. CONCLUSIONS: ADNEX had better ability to discriminate between benign and malignant adnexal tumours and higher clinical utility than ROMA. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT01698632 and NCT02847832.

Serum methylmalonic acid concentrations at breast cancer diagnosis significantly correlate with clinical frailty.

Methylmalonic acid (MMA), a by-product of propionate metabolism, is known to increase with age. This study investigates the potential of serum MMA concentrations as a biomarker for age-related clinical frailty in older patients with breast cancer. One hundred nineteen patients ≥ 70 years old with early-stage breast cancer were included (median age 76 years). G8 screening, full geriatric assessment, clinical parameters (i.e., estimated glomerular filtration rate (eGFR) and body mass index (BMI)), and serum sample collection were collected at breast cancer diagnosis before any therapy was administered. MMA concentrations were measured via liquid chromatography with tandem mass spectrometry. MMA concentrations significantly increased with age and eGFR (all P < 0.001) in this older population. The group with an abnormal G8 (≤ 14, 51% of patients) had significantly higher MMA levels than the group with normal G8 (> 14, 49%): 260 nmol/L vs. 188 nmol/L, respectively (P = 0.0004), even after correcting for age and eGFR (P = 0.001). Furthermore, in the detailed assessment, MMA concentrations correlated most with mobility (Eastern Cooperative Oncology Group (ECOG) Performance Status and Activities of Daily Living (ADL) tools, all P ≤ 0.02), comorbidity (Charlson Comorbidity Index (CCI) tool, P = 0.005), and polypharmacy (P < 0.001), whereas no significant associations were noted for instrumental ADL (IADL), Mini-Mental State Examination (MMSE), Geriatric Depression Scale-15 (GDS15), Mini Nutritional Assessment-Short Form (MNA-SF), and pain (all P > 0.1). In addition, our results showed that higher MMA levels correlate with poor overall survival in breast cancer patients (P = 0.003). Elevated serum MMA concentrations at initial diagnosis are significantly associated, not only with age but also independently with clinical frailty, suggesting a possible influence of MMA on clinical frailty in older patients with early-stage breast cancer.

Determinants of 25-hydroxyvitamin D Status in a Cutaneous Melanoma Population.

Vitamin D status is influenced by well-known determinants, but factors associated with low 25-hydroxyvitamin D levels in the cutaneous melanoma population are not well defined. The aim of this study was to confirm the well-known determinants and to assess new determinants for 25-hydroxyvitamin D levels in a cutaneous melanoma population. In a prospectively included cohort of 387 patients with cutaneous melanoma the association of 25-hydroxyvitamin D levels with sex, age, body mass index, time of blood withdrawal, Fitzpatrick phototype, vitamin D supplementation, score for intensity of lifetime sun exposure, smoking, education level, hair and skin colour, eye colour, total number of benign naevi, freckles and parameters of chronic sun damage was investigated. In addition, 25-hydroxyvitamin D levels were correlated with pathological parameters of the primary tumour and melanoma stage (8th edition of the American Joint Committee on Cancer (AJCC). Univariate and multivariate logistic regressions were performed using R software. The following factors had a significant effect on vitamin D status: body mass index, seasonal time of blood sampling, vitamin D supplementation, and a subtype of skin, and hair colour.

Testicular Vein Sampling Can Reveal Gonadotropin-Independent Unilateral Steroidogenesis Supporting Spermatogenesis.

Suppressed gonadotropins combined with high-normal serum testosterone concentrations in oligozoospermic men suggest either use of exogenous testosterone or presence of a testosterone-producing tumor. We describe the case of a 31-year-old man referred for primary infertility. Gonadotropins were undetectably low, but testosterone and estradiol were in the high-normal range. Semen analysis showed oligoasthenospermia. He denied using exogenous testosterone. Scrotal ultrasound showed microlithiasis and millimetric hypolucent lesions in the left testis but no intratesticular mass. Human chorionic gonadotropin was low. To investigate unilateral hormone secretion, selective testicular venous sampling was performed. Testosterone and estradiol were clearly higher on the left side than on the right (130 vs 26 nmol/L and 1388 vs 62 pmol/L, respectively), with a left spermatic vein-to-periphery gradient of 4.3 for testosterone and 13 for estradiol; there were no similar gradients on the right side. This finding confirms that all sex steroid secretion came from the left testis. The patient was therefore referred for left orchidectomy. Histopathology revealed multifocal seminoma, germ cell neoplasia in situ, and Leydig cell hyperplasia but no choriocarcinoma. However, gonadotrophin levels increased after orchidectomy, indicating that the source of gonadotropin-independent sex steroid secretion was removed. Testosterone and estradiol decreased to the mid-normal range. Sperm concentration improved. This report thus shows that endogenous testosterone secretion in one testicle supports spermatogenesis without measurable levels of gonadotropins. Selective testicular venous sampling is useful to identify the site of unilateral secretion when the clinical picture is inconclusive. However, histopathology could not reveal the factor that stimulated Leydig cell steroidogenesis.

Prognostic Value of Stimulated Thyroglobulin Levels at the Time of Radioiodine Administration in Differentiated Thyroid Cancer.

OBJECTIVE: The prognostic value of stimulated thyroglobulin (sTg) and Tg-related parameters prior to and immediately after radioactive iodine (RAI) administration was assessed in a cohort of patients presenting with differentiated thyroid cancer (DTC) as a predictor of recurrent or progressive structural disease. METHODS: Clinical records of 180 DTC patients were retrospectively reviewed, and serum TSH, Tg, and Tg antibodies were recorded just before RAI administration (pre-) and at the time of whole body scanning (post-). Based on the results of initial staging and RAI scintigraphy, patients were divided into two groups: those who were considered to be structurally disease-free after thyroidectomy and RAI (group 1) and those who were not (group 2). Univariate analyses were performed for pre-Tg, ratioTg (post-Tg/pre-Tg), and other clinical and pathological markers for long-term outcome, as well as separate bivariate analyses focusing on pre-Tg to correct for possible confounders. Different pre-Tg cut-off values for predicting structural disease recurrence were assessed in a subgroup of patients in group 1 prepared with thyroid hormone withdrawal. RESULTS: In group 1, (n = 166) male gender, higher T-stage and both Tg-related parameters proved to be significant risk factors for structural disease relapse. Of all candidate variables, only higher T-stage served to predict progressive structural disease in group 2 (n = 14). Subgroup analysis showed a negative predictive value of 91.67$ for pre-Tg < 10 µg/L. CONCLUSION: The sTg value at the time of RAI administration may be helpful in predicting structural disease recurrence in patients with DTC.

Human Chorionic Gonadotropin Regression Curves after Partial or Complete Molar Pregnancy in Flanders: Are They Different from Regression Curves from the Eighties?

BACKGROUND/AIMS: We updated human chorionic gonadotropin (hCG) regression curves created in the eighties after evacuation of complete and partial molar (CM and PM, respectively) pregnancies using modern hCG assays. We created similar curves for patients in need of chemotherapy (gestational trophoblastic neoplasia [GTN]). METHODS: A total of 126 patients who were diagnosed with gestational trophoblastic disease from 1990 to 2014 were included. We compared curves from 2 groups, CM and PM, with historical ones. The third group was a comparison of GTN patients receiving first-line chemotherapy and patients in need of a switch of chemotherapy. RESULTS: The regression curves were comparable to historical ones. According to the latter, mean time to normalization was 14-15 weeks after evacuation. We observed a normalization within 12 (CM) and 12.7 (PM) weeks. In addition, a remarkable but not statistically significant vertical shift (20 IU/L higher) was observed prior to day 60 compared with historical curves. The comparison in GTN patients showed a statistical significant difference, even at day 7. CONCLUSION: The presented hCG regression curves in the Flemish region were comparable with the ones of the eighties but with a vertical shift, hypothetically due to more sensitive assays. In addition, regression curves in GTN patients receiving chemotherapy can be used to evaluate response.

Determination of human reference values for serum total 1,25-dihydroxyvitamin D using an extensively validated 2D ID-UPLC-MS/MS method.

BACKGROUND: To assess a patient's vitamin D status the precursor metabolite 25-hydroxyvitamin D can be determined. However, measurement of 1,25-dihydroxyvitamin D is required when disorders of 1a-hydroxylation, extrarenal 1a-hydroxylation, or vitamin D receptor defects are suspected. METHODS: The aim of this study was to determine reference values for 1,25-dihydroxyvitamin D3 and D2 using a 2D ID-UPLC-MS/MS method. RESULTS: The LC-MS/MS method, able to measure picomolar concentrations of both 1,25-dihydroxyvitamin D3 and D2 in human serum, was extensively validated. Intra-assay variations were <5% and 8.5% and <7.5% and 11%, for 1,25-dihydroxyvitamin D3 and D2, respectively, over the whole dynamic range (3.1-376 and 3.1-652pmol/L). Limit of quantitation was 3.4pmol/L for both compounds. Our method correlated well with a published LC-MS/MS method (r=0.87) and with the average 1,25-dihydroxyvitamin D3 results of the vitamin D External Quality Assessment Scheme (DEQAS) determined with LC-MS/MS (r=0.93). Reference ranges, determined in 96 plasma samples of healthy volunteers were 59-159pmol/L and <17pmol/L for respectively 1,25-dihydroxyvitamin D3 and D2. The female part of the reference group showed a statistically significant decrease of 1,25-dihydroxyvitamin D3 concentrations with age. The presence of significantly higher average 1,25-dihydroxyvitamin D3 levels in premenopausal women taking oral contraceptive pills compared to postmenopausal women suggests that this effect is estrogen-related, as estrogens lead to a higher vitamin D binding protein. CONCLUSIONS: The major finding of the present study is a reference interval of 59-159pmol/L for 1,25-dihydroxyvitamin D3 determined with a highly sensitive and precise LC-MS/MS method.

Lanreotide Reduces Liver Volume, But Might Not Improve Muscle Wasting or Weight Loss, in Patients With Symptomatic Polycystic Liver Disease.

BACKGROUND & AIMS: Polycystic liver disease (PCLD) can induce malnutrition owing to extensive hepatomegaly and patients might require liver transplantation. Six months of treatment with the somatostatin analogue lanreotide (120 mg) reduces liver volume. We investigated the efficacy of a lower dose of lanreotide and its effects on nutritional status. METHODS: We performed an 18-month prospective study at 2 tertiary medical centers in Belgium from January 2011 through August 2012. Fifty-nine patients with symptomatic PCLD were given lanreotide (90 mg, every 4 weeks) for 6 months. Patients with reductions in liver volume of more than 100 mL (responders, primary end point) continued to receive lanreotide (90 mg) for an additional year (18 months total). Nonresponders were offered increased doses, up to 120 mg lanreotide, until 18 months. Liver volume and body composition were measured by computed tomography at baseline and at months 6 and 18. Patients also were assessed by the PCLD-specific complaint assessment at these time points. RESULTS: Fifty-three patients completed the study; 21 patients (40%) were responders. Nineteen of the responders (90%) continued as responders until 18 months. At this time point, they had a mean reduction in absolute liver volume of 430 ± 92 mL. In nonresponders (n = 32), liver volume increased by a mean volume of 120 ± 42 mL at 6 months. However, no further increase was observed after dose escalation in the 24 patients who continued to the 18-month end point. All subjects had decreased scores on all subscales of the PCLD-specific complaint assessment, including better food intake (P = .04). Subjects did not have a mean change in subcutaneous or visceral fat mass, but did have decreases in mean body weight (2 kg) and total muscle mass (1.06 cm(2)/h(2)). Subjects also had a significant mean reduction in their level of insulin-like growth factor 1, from 19% below the age-adjusted normal range level at baseline to 50% at 18 months (P = .002). CONCLUSIONS: In a prospective study, we observed that low doses of lanreotide (90 mg every 4 weeks) reduced liver volumes and symptoms in patients with PCLD. However, patients continued to lose weight and muscle mass. The effects of somatostatin analogues on sarcopenia require investigation. Clinicaltrials.gov: NCT01315795.

Skin Metabolites Define a New Paradigm in the Localization of Skin Tropic Memory T Cells.

The localization of memory T cells to human skin is essential for long-term immune surveillance and the maintenance of barrier integrity. The expression of CCR8 during naive T cell activation is controlled by skin-specific factors derived from epidermal keratinocytes and not by resident dendritic cells. In this study, we show that the CCR8-inducing factors are heat stable and protease resistant and include the vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 and PGE2. The effect of either metabolite alone on CCR8 expression was weak, whereas their combination resulted in robust CCR8 expression. Elevation of intracellular cAMP was essential because PGE2 could be substituted with the adenylyl cyclase agonist forskolin, and CCR8 expression was sensitive to protein kinase A inhibition. For effective induction, exposure of naive T cells to these epidermal factors needed to occur either prior to or during T cell activation even though CCR8 was only detected 4-5 d later in proliferating T cells. The importance of tissue environments in maintaining cellular immune surveillance networks within distinct healthy tissues provides a paradigm shift in adaptive immunity. Epidermal-derived vitamin D3 metabolites and PGs provide an essential cue for the localization of CCR8(+) immune surveillance T cells within healthy human skin.

Arthralgia induced by endocrine treatment for breast cancer: A prospective study of serum levels of insulin like growth factor-I, its binding protein and oestrogens.

BACKGROUND: Aromatase inhibitors (AIs) frequently induce or enhance musculoskeletal problems (AI-induced musculoskeletal syndrome (AIMSS)) which sometimes are debilitating. Apart from low oestrogen levels, underlying mechanisms are unknown and likely multiple. We previously hypothesised a role for the growth hormone/insulin like growth factor-I (IGF-I) axis. Here, we report the effect of tamoxifen and AI on IGF-I, IGF binding protein-3 (IGFBP-3) and oestrogen levels from a prospective study. MATERIALS AND METHODS: Postmenopausal women with an early breast cancer scheduled to start adjuvant endocrine therapy with an AI or tamoxifen were recruited. A rheumatologic questionnaire was completed and serum was collected for assessment of IGF-I, IGFBP-3 and oestrogen levels. Re-evaluation was done after 3, 6 and 1 2months of therapy. RESULTS: 84 patients started on tamoxifen (n=42) or an AI (n=42). 66% of the latter group experienced worsening of pre-existing or de novo complaints in joint and/or muscle, compared to 29% of tamoxifen-treated patients. AI therapy resulted in elevated IGF-I levels with a statistically significant increase at 6months (p=0.0088), whereas tamoxifen users were characterised by a decrease in IGF-I levels at all follow-up times (p<0.0004). No effect on IGFBP-3 was seen in the latter group. AI-users, however, showed decreased IGFBP-3 levels at 12 months (p=0.0467). AIMSS was characterised by a decrease in IGFBP-3 levels (p=0.0007) and a trend towards increased IGF-I/IGFBP-3 ratio (p=0.0710). CONCLUSION: These findings provide preliminary evidence that AI-induced musculoskeletal symptoms are associated with changes in the growth hormone (GH)/IGF-I axis.

Sensitive routine liquid chromatography-tandem mass spectrometry method for serum estradiol and estrone without derivatization.

The need for a routinely applicable assay to measure low estradiol levels in adult men, postmenopausal women, and young adolescents was recently discussed in an Endocrine Society position statement. Our aim was to develop a sensitive liquid chromatography-tandem mass spectrometry method for estradiol and estrone in human serum without the need for derivatization or extended extraction protocols. After protein precipitation of serum with a mixture of methanol/acetonitrile (85/15) (v/v) containing isotopic internal standards (17ß-estradiol-16,16,17-d 3 and estrone-2,3,4-(13)C), we quantified estradiol and estrone by two-dimensional liquid chromatography-tandem mass spectrometry with electrospray ionization in the negative mode monitoring 5 × 271.20→145.00 (17ß-estradiol) and 269.20→145.00 (estrone). Sensitivity was increased by using fluoride and summation of 5 identical transitions for estradiol. Our method was analytically validated, compared against direct immunoassays using serum of 25 adult men, and clinically tested by measuring samples of 3 men at baseline and after chemical castration, 30 postmenopausal women and 15 patients receiving aromatase inhibitors. Total imprecision was below 20% for the low quality controls. Limit of quantification was 1.3 ng/L (4.8 pmol/L) for estradiol and 1.2 ng/L (4.4 pmol/L) for estrone. Estradiol in Certified Reference Material BCR-576 was within specified uncertainty limits. No significant ion suppression or interference was observed. Our method showed modest correlation with direct immunoassay for estradiol (r(2) = 0.64) but no correlation for estrone (r(2) = 0.12). Patient sample results were within expected ranges. In conclusion, we developed a routinely applicable liquid chromatography-tandem mass spectrometry method for estradiol and estrone measurement which is sensitive enough for use in men, postmenopausal women, and young adolescents.

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European Male Aging Study (EMAS).

CONTEXT: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover. OBJECTIVE: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men. DESIGN, SETTING, AND PARTICIPANTS: Men aged 40-79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (ß-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers. MAIN OUTCOME MEASURE(S): QUS of the heel, bone markers P1NP and ß-cTX, and DXA of the hip and lumbar spine were measured. RESULTS: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with ß-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest ß-cTX levels. CONCLUSIONS: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.

Serum procalcitonin is not an early marker of pulmonary exacerbation in children with cystic fibrosis.

UNLABELLED: Serum procalcitonin (PCT) has been proposed as a marker to identify bacterial infection in children. For optimal management of cystic fibrosis (CF) patients, early recognition of pulmonary exacerbations is necessary, but sensitive biomarkers to do so are lacking. Our study was done to establish baseline values for PCT in children with CF and to compare these to values at onset of a pulmonary exacerbation. Serum PCT values were determined in CF children during an outpatient clinic visit and at onset of treatment with intravenous (IV) antibiotics for a pulmonary exacerbation. Serum PCT was measured using a quantitative immunoassay (BRAHMS Kryptor PCTsensitive, Henningsdorf, Germany). In 92 outpatients (mean age 10.0 years, SD 4.8 years; mean forced expiratory volume in 1 s 91%, SD 18; 9 chronically colonized with Pseudomonas aeruginosa), mean baseline PCT was 0.05 ng/ml (SD 0.07). Mean PCT on admission for IV treatment of pulmonary exacerbation was 0.07 ng/ml (SD 0.06) (n = 22) and not different from the baseline value. PCT values were markedly higher in two CF patients with an acute nonrespiratory infection (central venous catheter-associated bloodstream infection, acute gastroenteritis), demonstrating that they can mount a PCT response. CONCLUSION: PCT values in CF children are not different from values reported in healthy children. In CF children, PCT values do not rise significantly at the onset of a respiratory exacerbation and thus hold no promise as an early marker to identify a pulmonary exacerbation.

Oncogenic osteomalacia illustrating the effect of fibroblast growth factor 23 on phosphate homeostasis.

In oncogenic osteomalacia (OOM), fibroblast growth factor 23 (FGF23) induces renal phosphate wasting and inhibits the appropriate increase of calcitriol. A patient suffering from OOM is described. Serum calcium, phosphate, biointact parathyroid hormone and intact FGF23 as well as the calcitriol and 24,25-vitamin D levels were measured before and after tumour removal. The clinical approach to a patient with hypophosphataemia is discussed and the changes in mineral metabolism after removal of a FGF23-producing tumour are described.

Undetectable antimüllerian hormone levels and recovery of chemotherapy-induced ovarian failure in women with breast cancer on an oral aromatase inhibitor.

OBJECTIVE: Knowledge of the menopause status of a woman with breast cancer is important for good clinical practice. Long-lasting amenorrhea is frequent in this population, often for reasons other than definitive menopause. Antiestrogens like tamoxifen or oral aromatase inhibitors (AIs) may reactivate the ovary causing vaginal bleeding, menstruation, pregnancy, and unopposed endometrial stimulation. In contrast to tamoxifen, AIs are not active against breast cancer in the presence of functional ovaries. Antimüllerian hormone (AMH) is a potential marker of residual ovarian function that can predict not only the onset of menopause but also chemotherapy-induced amenorrhea (CIA) and fertility. We assess the value of AMH in women who recovered from CIA on an AI. METHODS: This is a series of six women with clinical and biochemical evidence of ovarian recovery during AI treatment. All six were premenopausal at breast cancer diagnosis and developed CIA. AMH, follicle-stimulating hormone, and estradiol levels were measured when patients developed clinical signs of ovarian recovery and/or when a gynecological procedure showed evidence of this. RESULTS: In all six AI-treated women, AMH levels were undetectable despite clinical, biochemical, or pathological evidence of ovarian reactivation after a long period of amenorrhea and sensitive biochemical markers indicating definitive menopause status. CONCLUSIONS: Repeated biochemical monitoring of ovarian function remains important in women with breast cancer undergoing AI treatment because ovarian function can recover, AIs are not active with functional ovaries, and amenorrhea does not, by itself, confirm definitive menopause. Undetectable AMH levels do not exclude residual ovarian function in women with breast cancer on an AI.

The role of inhibins B and antimüllerian hormone for diagnosis and follow-up of granulosa cell tumors.

The peptide hormones inhibin and antimüllerian hormone (AMH), both produced by the granulosa cells, are potential candidates for diagnosis and follow-up of granulosa cell tumors (GCTs). The objective was to evaluate the usefulness of serum levels of inhibin B and AMH in the diagnosis and follow-up of GCT. The review summarizes and discusses the value and limitations of the laboratory tests of these hormones by investigating the performance characteristics of the serum analyses. A search in PubMed database was accomplished to find articles describing serum inhibin and/or AMH as a diagnostic test or for follow-up of GCT. The literature search included articles published between 1989 and September 2008. The sensitivity of inhibin B and AMH for diagnosing patients with a progressive disease is rather equivalent. Antimüllerian hormone is a more specific serum parameter than inhibin, because inhibin may also increase in some (mucinous) epithelial ovarian tumors. Nowadays, specific and ultrasensitive assays are commercially available as well for inhibin B as for AMH, so that early detection of GCT might be possible. For patients with elevated levels of inhibin B and/or AMH at initial diagnosis of GCT, inhibin B and/or AMH seemed to be reliable markers during follow-up for early detection of residual or recurrent disease. Elevated concentrations of these hormones predict relapse earlier than clinical symptoms, which leads to less morbidity of the patients. In conclusion, inhibin B and AMH are both useful serum markers for diagnosis and especially for follow-up of patients with a GCT. Currently, there is no evidence-based preference for inhibin B or AMH as tumor marker.

Serum transferrin receptor in the evaluation of the iron status in elderly hospitalized patients with anemia.

The aim of the present study is to evaluate in an elderly hospitalized population the diagnostic value of the serum transferrin receptor (sTfR) in distinguishing IDA (iron deficiency anemia) from ACD (anemia of chronic disease) as compared to conventional laboratory tests of iron metabolism, especially serum ferritin. In a prospective study, 34 patients with IDA and 38 patients with ACD (a chronic disorder in 23 and an acute infection in 15) were evaluated using iron status tests including serum transferrin receptor assay. The iron stores were assessed by bone marrow examination. sTfR levels were elevated (>28.1 nmol/L) in 68% of the IDA patients but also in 43% of the patients with ACD-chronic inflammation and 33% with ACD-acute infection. Serum ferritin was the best test to differentiate IDA from ACD patients. We conclude that serum ferritin is a more sensitive and specific parameter than the sTfR assay to predict the bone marrow iron status in an elderly anemic population.