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  • 1
    Online Resource
    Online Resource
    Recovery of male reproductive endocrine function after ceasing prolonged testosterone undecanoate injections
    Oxford University Press (OUP) ; 2022
    In:  European Journal of Endocrinology Vol. 186, No. 3 ( 2022-03-01), p. 307-318
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 186, No. 3 ( 2022-03-01), p. 307-318
    Abstract: The time course of male reproductive hormone recovery after stopping injectable testosterone undecanoate (TU) treatment is not known. Objective The aim of this study was to investigate the rate, extent, and determinants of reproductive hormone recovery over 12 months after stopping TU injections. Materials and Methods Men ( n  = 303) with glucose intolerance but without pathologic hypogonadism who completed a 2-year placebo (P)-controlled randomized clinical trial of TU treatment were recruited for further 12 months while remaining blinded to treatment. Sex steroids (testosterone (T), dihydrotestosterone, oestradiol, oestrone) by liquid chromatography-mass sprectometry, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) by immunoassays and sexual function questionnaires (Psychosexual Diary Questionnaire, International Index of Erectile Function, and short form survey (SF-12)) were measured at entry (3 months after the last injection) and 6, 12, 18, 24, 40, and 52 weeks later. Results In the nested cohort of TU-treated men, serum T was initially higher but declined at 12 weeks remaining stable thereafter with serum T and SHBG at 11 and 13%, respectively, lower than P-treated men. Similarly, both questionnaires showed initial carry-over higher scores in T-treated men but after 18 weeks showed no difference between T- and P-treated men. Initially, fully suppressed serum LH and FSH recovered slowly towards the participant’s own pre-treatment baseline over 12 months since the last injection. Conclusions After stopping 2 years of 1000 mg injectable TU treatment, full reproductive hormone recovery is slow and progressive over 15 months since the last testosterone injection but may take longer than 12 months to be complete. Persistent proportionate reduction in serum SHBG and T reflects lasting exogenous T effects on hepatic SHBG secretion rather than androgen deficiency.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-21-0608
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1485160-X
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  • 2
    Online Resource
    Online Resource
    Transcription factor immunohistochemistry in the diagnosis of pituitary tumours
    Oxford University Press (OUP) ; 2021
    In:  European Journal of Endocrinology Vol. 184, No. 6 ( 2021-06-01), p. 891-901
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 184, No. 6 ( 2021-06-01), p. 891-901
    Abstract: The clinical utility and prognostic value of WHO 2017 lineage-based classification of pituitary tumours have not been assessed. This study aimed to (1) determine the clinical utility of transcription factor analysis for classification of pituitary tumours and (2) determine the prognostic value of improved lineage-based classification of pituitary tumours. Methods This was a retrospective evaluation of patients who underwent surgical resection of pituitary tumours at St Vincent’s Public and Private Hospitals, Sydney, Australia between 1990 and 2016. Included patients were at least 18 years of age and had complete histopathological data, forming the 'histological cohort'. Patients with at least 12 months of post-surgical follow-up were included in the subgroup 'clinical cohort'. The diagnostic efficacy of transcription factor immunohistochemistry in conjunction with hormone immunohistochemistry was compared with hormone immunohistochemistry alone. The prognostic value of identifying 'higher-risk' histological subtypes was assessed. Results There were 171 patient tumour samples analyzed in the histological cohort. Of these, there were 95 patients forming the clinical cohort. Subtype diagnosis was changed in 20/171 (12%) of tumours. Within the clinical cohort, there were 21/95 (22%) patients identified with higher-risk histological subtype tumours. These were associated with tumour invasiveness ( P  = 0.050), early recurrence (12–24 months, P  = 0.013), shorter median time to recurrence (49 (IQR: 22.5–73.0) vs 15 (IQR: 12.0–25.0) months, P  = 0.005) and reduced recurrence-free survival ( P  = 0.031). Conclusions Application of transcription factor analysis, in addition to hormone immunohistochemistry, allows for refined pituitary tumour classification and may facilitate an improved approach to prognostication.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-20-1273
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1485160-X
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  • 3
    Online Resource
    Online Resource
    Pulmonary transit of agitated contrast is associated with enhanced pulmonary vascular reserve and right ventricular function during exercise
    American Physiological Society ; 2010
    In:  Journal of Applied Physiology Vol. 109, No. 5 ( 2010-11), p. 1307-1317
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 109, No. 5 ( 2010-11), p. 1307-1317
    Abstract: Pulmonary transit of agitated contrast (PTAC) occurs to variable extents during exercise. We tested the hypothesis that the onset of PTAC signifies flow through larger-caliber vessels, resulting in improved pulmonary vascular reserve during exercise. Forty athletes and fifteen nonathletes performed maximal exercise with continuous echocardiographic Doppler measures [cardiac output (CO), pulmonary artery systolic pressure (PASP), and myocardial velocities] and invasive blood pressure (BP). Arterial gases and B-type natriuretic peptide (BNP) were measured at baseline and peak exercise. Pulmonary vascular resistance (PVR) was determined as the regression of PASP/CO and was compared according to athletic and PTAC status. At peak exercise, athletes had greater CO (16.0 ± 2.9 vs. 12.4 ± 3.2 l/min, P 〈 0.001) and higher PASP (60.8 ± 12.6 vs. 47.0 ± 6.5 mmHg, P 〈 0.001), but PVR was similar to nonathletes ( P = 0.71). High PTAC (defined by contrast filling of the left ventricle) occurred in a similar proportion of athletes and nonathletes (18/40 vs. 10/15, P = 0.35) and was associated with higher peak-exercise CO (16.1 ± 3.4 vs. 13.9 ± 2.9 l/min, P = 0.010), lower PASP (52.3 ± 9.8 vs. 62.6 ± 13.7 mmHg, P = 0.003), and 37% lower PVR ( P 〈 0.0001) relative to low PTAC. Right ventricular (RV) myocardial velocities increased more and BNP increased less in high vs. low PTAC subjects. On multivariate analysis, maximal oxygen consumption (V̇o 2max ) ( P = 0.009) and maximal exercise output ( P = 0.049) were greater in high PTAC subjects. An exercise-induced decrease in arterial oxygen saturation (98.0 ± 0.4 vs. 96.7 ± 1.4%, P 〈 0.0001) was not influenced by PTAC status ( P = 0.96). Increased PTAC during exercise is a marker of pulmonary vascular reserve reflected by greater flow, reduced PVR, and enhanced RV function.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/japplphysiol.00457.2010
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2010
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 4
    Online Resource
    Online Resource
    Secondary adrenal insufficiency and pituitary dysfunction in oral/transdermal opioid users with non-cancer pain
    Oxford University Press (OUP) ; 2018
    In:  European Journal of Endocrinology Vol. 179, No. 6 ( 2018-12), p. 353-362
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 179, No. 6 ( 2018-12), p. 353-362
    Abstract: To evaluate pituitary function, sexual function and quality of life (QoL) in patients on oral or transdermal opioids. Design and methods Cross-sectional study comparing pituitary function, QoL and sexual function in people on long-term opioid therapy ( n  = 40) vs an age- and sex-matched control group ( n  = 25). Baseline pituitary function was assessed on blood samples collected prior to 0900 h. Further testing with corticotropin (250 µg IV) and metyrapone (30 mg/kg) stimulation tests was undertaken on participants with serum cortisol 〈 250 nmol/L. Validated questionnaires completed to assess QoL, fatigue and sexual function. Results Secondary adrenal insufficiency (SAI) was identified on the basis of a failed stimulation test in 22.5% of opioid users vs no controls ( P  = 0.01). Opioid users with SAI had a higher median morphine-equivalent daily dose (MEDD), P  = 0.037 – 50% with MEDD 〉 200 mg and 0% with MEDD 〈 60 mg had SAI. Among male participants, testosterone was inversely associated with BMI ( P  = 0.001) but not opioid use. A non-significant trend to low testosterone 〈 8 nmol/L in male opioid users (11/24 opioid users vs 2/14 control, P  = 0.08) suggests a small subgroup with opioid-induced androgen deficiency. Opioid users had greater fatigue, reduced quality of life in all subsections of the SF-36 and impaired sexual function in both males and females (all scores P   〈  0.001 compared to controls). Conclusion Long-term opioid therapy was associated with dose-related SAI in over 20% of chronic pain patients and is associated with poor quality of life, fatigue and sexual dysfunction. Obesity confounds the interpretation of opioid-induced male androgen deficiency.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-18-0530
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 1485160-X
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  • 5
    Online Resource
    Online Resource
    Thrombospondin-1 is a glucocorticoid responsive protein in humans
    Oxford University Press (OUP) ; 2016
    In:  European Journal of Endocrinology Vol. 174, No. 2 ( 2016-02), p. 193-201
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 174, No. 2 ( 2016-02), p. 193-201
    Abstract: Thrombospondin-1 (TSP1) is a matricellular protein whose gene expression has previously been shown to increase acutely after exposure to dexamethasone in vitro . The aim of this study was to determine if TSP1 is altered by acute and chronic states of glucocorticoid excess in human subjects. Design and methods Three studies have been undertaken to assess the difference or change in TSP1 in response to altered glucocorticoid activity: i) an acute interventional study assessed the effects of a single 4 mg dose of dexamethasone in 20 healthy volunteers; ii) a cross-sectional study compared plasma TSP1 in 20 healthy volunteers and eight patients with Cushing's syndrome; iii) an interventional study assessed the effect on plasma TSP1 of an increase in hydrocortisone dose from ≤20 mg/day to 30 mg/day for 7 days in 16 patients with secondary adrenal insufficiency. Results In healthy volunteers, 4 mg dexamethasone significantly increased peripheral blood mononuclear cell (PBMC) TSP1 mRNA levels ( P 〈 0.0001) and plasma TSP1 concentrations ( P 〈 0.0001), peaking at 12 h. Median (interquartile range) plasma TSP1 was higher in Cushing's, 638 (535–756) ng/ml, than in healthy volunteers, 272 (237–336) ng/ml ( P 〈 0.0001). Plasma TSP1 〉 400 ng/ml diagnosed Cushing's syndrome with sensitivity of 100% and specificity of 85%. The higher hydrocortisone dose increased plasma TSP1 from 139 (86–199) to 256 (133–516) ng/ml, ( P 〈 0.01) in patients with secondary adrenal insufficiency. Conclusions TSP1 is a glucocorticoid responsive protein in humans. Further research is required to determine if plasma TSP1 has a role as a glucocorticoid biomarker.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-15-0964
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 1485160-X
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  • 6
    Online Resource
    Online Resource
    Obesity and “functional hypogonadism”—mechanisms and management: commentary on EJE-22-1110 “leflutrozole in male obesity-associated hypogonadotropic hypogonadism: Ph 2b double-blind RCT”
    Oxford University Press (OUP) ; 2023
    In:  European Journal of Endocrinology Vol. 189, No. 3 ( 2023-09-01), p. R7-R9
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 189, No. 3 ( 2023-09-01), p. R7-R9
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1093/ejendo/lvad100
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1485160-X
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  • 7
    Online Resource
    Online Resource
    Skeletal muscle 11β hydroxysteroid dehydrogenase type 1 activity is upregulated following elective abdominal surgery
    Oxford University Press (OUP) ; 2009
    In:  European Journal of Endocrinology Vol. 160, No. 2 ( 2009-02), p. 249-255
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 160, No. 2 ( 2009-02), p. 249-255
    Abstract: Cortisol has been traditionally implicated in the causation of peri-operative skeletal muscle (SkM) insulin resistance, but cortisol levels return to normal within 72 h of surgery. Tissue cortisol bioactivity may be prolonged by local upregulation of the enzyme 11βHSD1. We aimed to investigate the changes of SkM 11βHSD1 enzyme activity and mRNA expression, relative to plasma cortisol, insulin and glucose levels following elective abdominal surgery. Patients and design Eight non-diabetic subjects (two male, six female) underwent serial plasma hormone sampling and muscle biopsy of vastus lateralis at baseline and on day 5 following elective laparoscopic cholecystectomy. Methods SkM 11βHSD1 and H6PDH mRNA levels were measured by quantitative RT-PCR and enzyme activity by % conversion of 3 H cortisone to cortisol. Plasma glucose, insulin, free fatty acids (FFA), tumour necrosis factor-α and cortisol by standardised assays. Results Compared with baseline, SkM 11βHSD1 activity was significantly increased on day 5 after surgery (14.7±2.1 vs 20.4±3.2%, P =0.005). Neither 11βHSD1 nor H6PDH mRNA levels were altered after surgery. Plasma cortisol ( P =0.027), FFA ( P =0.01) and glucose ( P =0.004) rose rapidly following surgery and had returned to baseline values by 24 h post-surgery. There was no significant change in plasma insulin. Conclusions This is the first study to demonstrate an upregulation of SkM 11βHSD1 activity in response to a physiological stressor. Sustained activation of this enzyme may increase tissue cortisol bioactivity.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-08-0619
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2009
    detail.hit.zdb_id: 1485160-X
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  • 8
    Online Resource
    Online Resource
    Long-acting porcine sequence ACTH in the diagnosis of adrenal insufficiency: a cost-effective alternative to the ACTH1–24 test
    Oxford University Press (OUP) ; 2020
    In:  European Journal of Endocrinology Vol. 182, No. 2 ( 2020-02), p. C5-C7
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 182, No. 2 ( 2020-02), p. C5-C7
    Abstract: While the ACTH 1–24 test has some well-documented shortcomings, it is the most widely used test to diagnose primary and secondary adrenal insufficiency. However, this synthetic ACTH preparation is not readily available in some countries. Research from India has demonstrated that using a long-acting porcine sequence ACTH has similar diagnostic performance to ACTH 1–24 at around 25% of the cost. This may allow access to a robust test for adrenal insufficiency to developing countries and potentially allow thousands of patients to be identified and appropriately treated.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-19-0923
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1485160-X
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  • 9
    Online Resource
    Online Resource
    Mediation analysis of the testosterone treatment effect to prevent type 2 diabetes in the Testosterone for Prevention of Type 2 Diabetes Mellitus trial
    Oxford University Press (OUP) ; 2023
    In:  European Journal of Endocrinology Vol. 189, No. 1 ( 2023-07-20), p. 50-57
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 189, No. 1 ( 2023-07-20), p. 50-57
    Abstract: To determine if testosterone treatment effect on glycaemia is mediated through changes in total fat mass, abdominal fat mass, skeletal muscle mass, non-dominant hand-grip, oestradiol (E2), and sex hormone-binding globulin (SHBG). Design Mediation analysis of a randomised placebo-controlled trial of testosterone. Methods Six Australian tertiary care centres recruited 1007 males, aged 50-74 years, with waist circumference ≥95 cm, serum total testosterone ≤14 nmol/L (immunoassay), and either impaired glucose tolerance or newly diagnosed type 2 diabetes on an oral glucose tolerance test (OGTT). Participants were enrolled in a lifestyle programme and randomised 1:1 to 3 monthly injections of 1000 mg testosterone undecanoate or placebo for 2 years. Complete data were available for 709 participants (70%). Mediation analyses for the primary outcomes of type 2 diabetes at 2 years (OGTT ≥ 11.1 mmol/L and change in 2-h glucose from baseline), incorporating potential mediators: changes in fat mass, % abdominal fat, skeletal muscle mass, non-dominant hand-grip strength, E2, and SHBG, were performed. Results For type 2 diabetes at 2 years, the unadjusted OR for treatment was 0.53 (95% CI:.35-.79), which became 0.48 (95% CI:.30-.76) after adjustment for covariates. Including potential mediators attenuated the treatment effect (OR 0.77; 95% CI:.44-1.35; direct effect) with 65% mediated. Only fat mass remained prognostic in the full model (OR: 1.23; 95% CI: 1.09-1.39; P & lt; .001). Conclusion At least part of the testosterone treatment effect was found to be mediated by changes in fat mass, abdominal fat, skeletal muscle mass, grip strength, SHBG, and E2, but predominantly by changes in fat mass.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1093/ejendo/lvad074
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1485160-X
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