No detectable prolactin in human saliva.
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Animals↗
Biomedical subjects
J H Thijssen
Publications and source records attributed to J H Thijssen.
[Role of prasterone (dehydroepiandrosterone) in substitution therapy for adrenocortical insufficiency].
Prasterone (dehydroepiandrosterone; DHEA) is a steroid hormone from the adrenal cortex with weak androgenic properties. It can be converted into stronger acting steroids with both androgenic and oestrogenic properties. DHEA also appears to have an affinity with certain receptors in the brain and can act as a neurosteroid. Patients with primary or secondary adrenocortical insufficiency exhibit a marked decrease in DHEA production and the added value of DHEA replacement in these patients has been investigated in three recently published trials. With a daily dose of 50 mg DHEA, the plasma levels of DHEAS (the sulphate of DHEA) increase to levels within the normal range and beneficial effects have been demonstrated for several psychological parameters such as mood, fatigue, general well-being and sexual function. The androgenic side effects on skin and hair appear to be both moderate and acceptable. For patients with adrenocortical insufficiency who function suboptimally despite adequate replacement therapy with glucocorticosteroids and (if indicated) mineralocorticosteroids, these results would seem to justify treatment with a replacement dose of DHEA.
Adrenal Insufficiency↗
Progesterone receptor isoform expression in human meningiomas.
The majority of meningiomas express the progesterone receptor (PR), and therefore meningiomas are considered to be progesterone-responsive. In addition, an association has been reported between PR and prognosis. At least two PR isoforms exist, PR-B (116--120 kDa) and PR-A (81 kDa), each of which are likely to have different biological functions. Knowledge of the differential expression of both isoforms is necessary to understand the effects of progesterone on meningioma growth. Therefore, in this study, PR-A and PR-B expression levels were determined in 61 human meningiomas by immunoblotting. Total PR expression levels were determined with a ligand binding assay (LBA) (total PR(LBA)). Both PR isoforms and an additional PR 78 kDa protein (PR-78) were expressed in the meningiomas. Meningiomas expressing more PR-A than PR-B had significantly higher total PR(LBA) levels (P<0.001). The PR-78 band intensity was negatively associated with that of PR-B (r(s)=-0.76, P<0.0001). PR-78 may represent an endogenous degradation product, but a similar regulation pathway in the biogenesis of both PR-B and PR-78 is not excluded. Meningiomas contain both PR isoforms, but in highly variable ratios and this variability may have some biological significance. Most meningiomas express more PR-A than PR-B. Therefore in meningioma, assuming that PR-B is more transcriptionally active than PR-A, progesterone responsiveness could be based on transrepression rather than on transactivation of target genes, and progesterone blockade may only be effective in certain subsets of meningiomas.
Aged↗
Medullary thyroid carcinoma: role of genetic testing and calcitonin measurement.
All patients with a thyroid nodule should have their plasma CT measured. Stimulated CT is generally better than basal, but in the lower ranges false negatives and false positives still occur. In families with hereditary MTC, RET gene mutation analysis has superseded measurement of plasma CT in the detection of asymptomatic disease gene carriers. All individuals with apparently sporadic MTC, but in whom there is some suspicion of familial disease, should also have RET genetic analysis. A negative DNA result practically excludes the possibility of hereditary MTC in families where an index case has been investigated and obviates the need for further biochemical evaluation. Disease gene carriers may be divided into three distinct risk groups depending on the specific RET gene mutation in the family. The age at which presymptomatic surgery has to be performed depends on the risk group to which the patient belongs. Compared with the results of DNA analysis, the results of CT stimulation tests have become less important in the assessment of timing of surgery. During follow-up of patients who underwent surgery, measurement of plasma basal CT is still useful. The high sensitivity of measuring stimulated CT levels does not outweigh the burden of life-long periodic stimulation tests and the limited clinical consequences of slightly elevated levels. Stimulation tests are inevitable for persons at risk who prefer not to have genetic testing.
Calcitonin↗
Urinary phytoestrogens and postmenopausal breast cancer risk.
Phytoestrogens are defined as plant substances that are structurally or functionally similar to estradiol. We report the associations of two major phytoestrogens, genistein and enterolactone, with breast cancer risk, using urinary specimens collected 1-9 years before breast cancer was diagnosed. The subjects were 88 breast cancer cases and 268 controls, selected from a cohort of postmenopausal women (n = 14,697) who participated in a breast cancer screening program. Mean levels of urinary genistein and enterolactone were determined by time resolved fluoroimmunoassay, using an average of two overnight urinary samples obtained from each participant on the first and the second screening rounds with a time interval of approximately 1 year. Odds ratios (ORs) of the highest to the lowest tertile of urinary phytoestrogen/creatinine concentrations and 95% confidence intervals (CIs) were computed. Higher urinary genistein excretion was weakly and nonsignificantly associated with a reduced breast cancer risk. OR for the highest tertile compared with lowest tertile was 0.83; 95% CI, 0.46-1.51. Higher urinary enterolactone excretion was weakly and nonsignificantly associated with an increased breast cancer risk. OR for the highest tertile compared with the lowest tertile was 1.43; 95% CI, 0.79-2.59. Tests for trends for both phytoestrogens were nonsignificant. We were not able to detect the previously reported protective effects of genistein and enterolactone on breast cancer risk in our postmenopausal population of Dutch women. Such an effect may be smaller than expected and/or limited to specific subgroups of the population.
4-Butyrolactone↗
Peroperative measurement of PTH in the management of primary hyperparathyroidism.
UNLABELLED: This study was performed to prospectively evaluate the efficacy of a newly developed, non-expensive and non-commercial perioperative PTH-assay as indicator of successful surgery in minimally invasive adenomectomy (MIA) for primary hyperparathyroidism (pHPT). METHODS: A chemoluminescence-based PTH-assay was modified to significantly shorten the incubation time, producing results in a total of 45-60 minutes. Its reliability was tested in 19 patients undergoing MIA for pHPT. Patients were selected for MIA based on preoperative imaging including ultrasound and CT. After verification of its reliability, the PTH assay was incorporated into our treatment protocol and its results registered and correlated with serum calcium levels and surgical outcome. RESULTS: The PTH assay was found to fully correlate with the current gold standard, i.e. serum calcium levels on the first postoperative day after MIA. It was subsequently used in 55 patients selected for MIA, as well as in 26 patients undergoing conventional neck exploration (CNE). In all cases it correctly indicated surgical failure/success. The conventional re-exploration that was required in 3 patients after unsuccessful MIA, was also correctly interpreted on the basis of the PTH-assay. In 2 cases an unexpected delay was encountered in the decline of PTH-levels following adenomectomy. CONCLUSION: The perioperative PTH-assay described is a reliable, inexpensive, and relatively fast predictor of surgical outcome, and should be considered essential for minimally invasive surgery in patients with pHPT.
Adult↗
Pituitary-adrenal function in adolescent psychiatric patients: impact of depressive symptoms.
BACKGROUND: The aim of this study was to determine whether depressive symptoms affect pituitary-adrenal function in adolescents, as they do in adults. METHODS: Salivary cortisol was measured before and after physical exercise in 23 hospitalized adolescent psychiatric patients and 13 age- and sex-matched healthy controls in a placebo-controlled design. In patients, cortisol profiles were assessed from 08:00 to 20:00 h before and after administration of low doses of dexamethasone or the natural steroid hydrocortisone. Patients were classified according to DSM III-R criteria and assigned to either a depressed group (n=10) or a non-depressed group (n=13). Subjective depressive symptoms were rated with the 90-item symptom checklist. RESULTS: Physical exercise increased cortisol output significantly in all subjects, but there were no differences between groups. In patients, no differences in basal cortisol levels were found between the depressed and non-depressed groups. Dexamethasone, but not hydrocortisone, was able to suppress cortisol levels in both groups. Differences between groups were only found in total cortisol output over the 3 days when data were analyzed according to the patients 'subjective' feelings of depression, with the highest cortisol levels in the 'subjectively more depressed' patients. CONCLUSIONS: The results obtained only partially support the hypothesis that depressive symptoms in adolescent psychiatric patients determine pituitary-adrenal (mal)function, and appear to depend on the strategy used.
Adolescent↗
Evaluation of testosterone/epitestosterone ratio influential factors as determined in doping analysis.
The ratio of the concentration of testosterone glucuronide to the concentration of epitestosterone glucuronide (T/E ratio) as determined in urine is the most frequently used method to prove testosterone abuse by athletes. A T/E ratio higher than 6 has been considered as proof of abuse in the past; however, cases of naturally occurring higher T/E ratios have been described. Since the introduction of the T/E ratio in doping analysis, the parameters that may or may not influence the T/E ratio, possibly leading to false-positive results, have been debated. To achieve more insight on the influencing circumstances, an overview is given to obtain an objective view on the merits of the urinary T/E ratio. Relevant analytical aspects of the T/E ratio, potential parameters of endogenous and exogenous origins, as well as some alternative methods to determine testosterone abuse, such as the urinary testosterone/luteinizing hormone ratio, gas chromatography-combustion-isotope-ratio mass spectrometry, hair analysis, and high-performance liquid chromatography-mass spectrometry, are discussed.
Chromatography, High Pressure Liquid↗
Increased adrenal androgen functioning in children with oppositional defiant disorder: a comparison with psychiatric and normal controls.
OBJECTIVE: To examine the relationship between adrenal androgens and aggression in children with oppositional and antisocial behavior and to compare their levels with those of psychiatric and normal controls. METHOD: Dehydroepiandrosterone sulfate (DHEAS) was measured in 24 children with oppositional defiant disorder (ODD), 42 psychiatric controls (including 20 children with attention-deficit/hyperactivity disorder [ADHD]), and 30 normal controls. The children's parents filled out the Child Behavior Checklist (CBCL). RESULTS: Children with ODD had higher DHEAS levels than either the psychiatric control or normal control groups; DHEAS levels of the latter groups did not differ. Moreover, it was possible to classify children as having either ODD or ADHD on the basis of their DHEAS levels, whereas this was not the case on the basis of the CBCL data. CONCLUSIONS: The results indicate that adrenal androgen functioning is specifically elevated in children with ODD. It is speculated that the mechanism could be a shift in balance of ACTH-beta-endorphin functioning in the hypothalamic-pituitary-adrenal axis due to early stress or genetic factors.
Adrenal Glands↗
None of four commercially available assays detects prolactin in human saliva.
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Adolescent↗
The truncated estrogen receptor alpha variant lacking exon 5 is not involved in progesterone receptor expression in meningiomas.
Human meningioma tissues are mostly estrogen receptor (ER) negative and progesterone receptor (PR) positive in ligand binding and enzyme immuno assays. To explain this apparently ER independent PR expression, we investigated the existence of a 'hidden' ER variant, which would be capable of activating transcription of the PR gene. Total RNA of seven meningiomas, two breast cancer tissues and of MCF7 cells was analyzed by RT-PCR using primers situated in exon 4 and exon 6. Differential hybridization of the PCR transcripts with probes in exon 4 and 5 respectively, revealed a wild type ER (wtER) fragment and an exon 5 deleted ER variant (ERDelta5). PCR products of two meningiomas were cloned for sequence analysis. The result confirmed the existence of a wtER and ERDelta5.RT-PCR followed by Southern analysis was performed on mRNA of 23 meningiomas to determine the amount of ERDelta5 relative to wtER, which was compared to the PR content of the tissues. In contrast to our initial hypothesis and literature data on breast cancer, there was no relationship between the ERDelta5/wtER ratio and PR protein concentration. It is therefore concluded that ERDelta5 mRNA does not play the dominant role in PR synthesis in meningioma tissue.
Blotting, Southern↗
Recommendations for estrogen and progestin replacement in the climacteric and postmenopause. European Progestin Club.
The diversity of function that sex steroids have proven to have in the female body, gives them a position of central importance in gynaecology. Scientific research demonstrates not only the well known genital functions of sexual steroids, furthermore, various extragenital organs are influenced and modulated by ovarian hormones. Therefore, the general benefit of HRT for the female organism becomes clearer and the clinical management of menopause is developing to a broad new discipline, the gender specific medicine. In clinical practise, phytosteroids are claimed by the patient and therefore, also of high interest for the scientific research. Also, tissue specificity of the endocrine treatment and the biological relevance of different steroid receptors of HRT are discussed, leading to the development of new HrT preparations. Individualisation, the tailoring of HRT, according to the patients needs, and low dose steroids management, will also become an important aspect in the recommendations for estrogen and progestin replacement therapy.
Estrogen Replacement Therapy↗
[Peroperative parathyroid hormone assay: assurance of successful surgical treatment of primary hyperparathyroidism].
OBJECTIVE: To study the reliability and applicability of a rapid parathormone (PTH) test as predictor of successful surgical treatment of primary hyperparathyroidism. DESIGN: Prospective. METHOD: All 35 consecutive patients undergoing surgery for primary hyperparathyroidism in the University Hospital Utrecht, the Netherlands, in august 1997-august 1998, were tested just prior to surgery, and immediately following adenomectomy. The rapid PTH test consisted of a modification of the computerized immunometric detection by chemoluminescence. The decrease of serum PTH as estimated with the rapid test was correlated with surgical findings as well as postoperative serum calcium levels. In the first 25 patients (group A) the reliability of the test was investigated. In the next 10 patients (group B) the PTH test results were allowed to have implications for surgical management, i.e. an insufficient (< 50%) decrease of serum PTH following adenomectomy resulted in immediate re-exploration. RESULTS: The 35 patients, 22 women and 13 men, had a median age of 58 years (range: 22-80). The results obtained with our rapid PTH test correlated fully with both conventional PTH measurement techniques and postoperative serum calcium levels. In group A 21/25 patients showed adequate (> 50%) decrease of their serum PTH levels; the 4 patients without such decrease were the ones displaying persistent postoperative hypercalcaemia. In group B 9/10 patients had adequate PTH decrease immediately following adenomectomy, while in one patient this was only attained after further exploration and excision of a second adenoma. No false-positive or false-negative measurements were encountered. CONCLUSION: The rapid PTH test used is a reliable predictor of successful adenomectomy for primary hyperparathyroidism, also in minimally invasive surgery.
Adult↗
Extensive islet amyloid formation is induced by development of Type II diabetes mellitus and contributes to its progression: pathogenesis of diabetes in a mouse model.
AIMS/HYPOTHESIS: Type II (non-insulin-dependent) diabetes mellitus is a multifactorial disease in which pancreatic islet amyloid is a characteristic histopathological finding. Islet amyloid fibrils consist of the beta-cell protein "islet amyloid polypeptide" (IAPP)/"amylin". Unlike human IAPP (hIAPP), mouse IAPP cannot form amyloid. In previously generated transgenic mice, high expression of hIAPP as such did not induce islet amyloid formation. To further explore the potential diabetogenic role of amyloidogenic IAPP, we introduced a diabetogenic trait ("ob" mutation) in hIAPP transgenic mice. METHODS: Plasma concentrations of IAPP, insulin and glucose were determined at 3.5 (t1), 6 (t2), and 16-19 months of age (t3). At t3, the mice were killed and the pancreas was analysed (immuno)histochemically. RESULTS: In non-transgenic ob/ob mice, insulin resistance caused a compensatory increase in insulin production, normalizing the initial hyperglycaemia. In transgenic ob/ob mice, concurrent increase in hIAPP production resulted in extensive islet amyloid formation (more often and more extensive than in transgenic non-ob/ob mice), insulin insufficiency and persistent hyperglycaemia: At t3, plasma insulin levels in transgenic ob/ob mice with amyloid were fourfold lower than in non-transgenic ob/ob mice (p < 0.05), and plasma glucose concentrations in transgenic ob/ ob mice were almost twofold higher (p < 0.05). In addition, the degree of islet amyloid formation in ob/ob mice was positively correlated to the glucose:insulin ratio (r(s) = 0.53, p < 0.05). CONCLUSION/INTERPRETATION: Islet amyloid is a secondary diabetogenic factor which can be both a consequence of insulin resistance and a cause of insulin insufficiency. [Diabetol
Amyloid↗
High-affinity growth hormone (GH)-binding protein (GHBP), body fat mass, and insulin-like growth factor-binding protein-3 predict the GHBP response to GH therapy in adult GH deficiency syndrome.
The study objective was to investigate which baseline factors can accurately predict plasma high-affinity growth hormone (GH)-binding protein (GHBP) levels after GH replacement therapy in patients with GH deficiency (GHD). The study group consisted of 36 GHD patients (22 men and 14 women; mean age, 43.1 years; (range, 21 to 60) known to have adult-onset GHD for many years (range, 4 to 22). They were randomly divided into a GH-treated group (n = 19) and a placebo group (n = 17). Body composition (assessed by bioelectrical impendance analysis [BIA]), plasma GHBP (fast protein liquid chromatography [FPLC] size-exclusion gel chromatography), insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 ([IGFBP-3] radioimmunoassays) were measured before and after 6 months. A stepwise multiple linear regression analysis with the plasma GHBP level after 6 months as the dependent variable was used to unravel significant explanatory (or predictor) variables. In contrast to placebo therapy, GH replacement therapy increased the mean plasma levels of IGF-I and IGFBP-3 to the normal range, whereas a small but statistically significant increase in plasma GHBP was observed. The combination of baseline plasma GHBP, body fat mass, and IGFBP-3 predicts posttreatment GHBP levels accurately (adjusted R2 = .97), indicating that baseline variables such as age, gender, fat-free mass, and IGF-I have no contribution. Furthermore, reliability analysis showed that the observed and predicted values for GHBP fit a strict parallel model. These findings indicate that the variations in body fat mass and IGFBP-3 among adult GHD subjects explain the reported variable response of GHBP to GH replacement therapy.
Adipose Tissue↗
Stress and self-injurious behavior; hormonal and serotonergic parameters in mentally retarded subjects.
Self-injurious behavior (SIB) and stereotyped behavior (SB) are major challenges for professionals in the field of mental retardation. From animal experiments it has become obvious that these behavioral disturbances are not purposeless but may emerge secondary to restrictive environment and may serve de-arousing objectives. In mentally retarded subjects, several hypotheses have been formulated concerning the pathogenesis of SIB, particularly about the involvement of serotonin and beta-endorphin, which are supported by beneficial treatment effects of the opiate antagonist naltrexone and serotonin modulating compounds, respectively. The present study was designed to investigate basal levels of stress-hormonal and serotonergic parameters as well as plasma levels of amino-acids and the beta-carboline norharman in a group of 64 mentally retarded subjects with SB and/or SIB. Allocation to three different groups comprising 17 retarded controls, 26 subjects with mainly SIB and 21 subjects with mainly SB, was originally performed using the scores on the factors Irritability, Stereotypic Behaviour and Hyperactivity of the Aberrant Behavioral Checklist. Because of the overlapping nature of the behavioral parameters, subjects were subsequently divided into three maximally contrasting groups, viz. predominantly SIB, predominantly SB and retarded controls, each comprising 11 subjects. With respect to beta-endorphin, no differences were found either between both the original and maximally contrasting groups or in comparison to nonretarded controls. As compared to retarded controls, a tendency to lower values for total cortisol and cortisol binding globulin appeared to be present in the SIB group, whereas in the SB group a tendency toward higher levels of the major serotonin metabolite 5-HIAA was found. In the contrasting SB group, a trend toward decreased total cortisol level was observed as compared to the retarded control group. In addition, significantly lower values for norharman and tryptophan were demonstrated in the total group of mentally retarded subjects as compared to non-retarded controls. The results of the present study, yielding co-existent disturbances in stress-hormonal and monoaminergic mechanisms as well as in the metabolism of norharman, are in line with the hypothesis that mentally retarded subjects are at risk for the development of stress-related behavioral disorders such as SIB and SB.
Adult↗
Undetectable serum thyroglobulin in a patient with metastatic follicular thyroid cancer.
The case of a 54-year-old woman with metastatic follicular thyroid cancer and undetectable serum thyroglobulin is presented. Many years after the patient had a subtotal thyroidectomy for a large goiter that had no clear evidence of malignancy, metastatic bone disease developed. When the bone metastases were detected and during the follow-up period, serum thyroglobulin values remained undetectable, but radioiodine uptake in the metastases was abundant. This case indicates that the combination of 1-131 scintigraphy and serum thyroglobulin values is superior to the measurement of serum thyroglobulin alone in detecting well-differentiated, metastatic thyroid cancer.
Adenocarcinoma, Follicular↗
Quantitative assessment of bone mineral density during estrogen replacement therapy.
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Absorptiometry, Photon↗