Rudolf Hoermann | Bonn Universität (original) (raw)

Papers by Rudolf Hoermann

$Research paper thumbnail of Testosterone levels increase in association with recovery from acute fracture in men$

Osteoporosis International, May 7, 2014

In this longitudinal case-control study, acute fracture was associated with low serum testosteron... more In this longitudinal case-control study, acute fracture was associated with low serum testosterone, which was transient in 43% of men. While assessment of gonadal status is part of the assessment of bone fragility, measurement of testosterone in the early period after fracture may overestimate the prevalence of androgen deficiency.

International Journal of Andrology, May 20, 2013

Our objective was to evaluate the effectiveness of implementing standardized guidelines to mitiga... more Our objective was to evaluate the effectiveness of implementing standardized guidelines to mitigate metabolic and bone side effects of androgen deprivation therapy (ADT) in men with non-metastatic prostate cancer. We conducted a 2-year prospective cohort study at a tertiary referral teaching hospital. Overall, 236 men (mean age 69.8 ± 7.1) commencing ADT for non-metastatic prostate cancer attended a baseline clinic visit between 2007 and 2011, and 153 men were eligible for follow-up after 2 years of continuous ADT. Of these, 113 men had data available for analysis at 2 years. At baseline, 87% of the men were overweight or obese, 61% had hypertension, 56% had hypercholesterolaemia, 27% prior cardiovascular disease, 11% osteoporosis and 40% osteopaenia. After 2 years of ADT, there was an increase in waist circumference (+2.8 ± 6.3 cm, p = 0.002), and, in men without diabetes, in HbA1c (+0.13 ± 0.34%, p = 0.019). Despite this, due to treatment, there were significant reductions in total cholesterol (-0.35 ± 1.00 mmol/L, p &amp;lt; 0.001), and blood pressure (systolic -7.6 ± 19.3 mmHg; diastolic -4.7 ± 11.6 mmHg, p &amp;lt; 0.001). After 2 years, men not receiving anti-resorptive therapy experienced a significant decline in lumbar spine (-0.042 ± 0.134 g/cm(2) , p = 0.012) and total hip bone mineral density (BMD) (-0.026 ± 0.036 g/cm(2) , p &amp;lt; 0.001), whereas bisphosphonate treatment maintained stable BMD. Prevalence of anaemia increased from 13.8 to 32.5%. Older age independently predicted a greater drop in haemoglobin (p = 0.005). We conclude that a structured approach to assess and treat men undergoing ADT effectively improves cardiovascular risk factors and prevents bone decay. Larger studies are needed to determine effects on cardiovascular outcomes, fracture prevention and survival.

Clinical Endocrinology, Feb 21, 2022

OBJECTIVE Roles for estradiol in modulating cognition in men remain uncertain. We assessed the is... more OBJECTIVE Roles for estradiol in modulating cognition in men remain uncertain. We assessed the isolated effects of estradiol on cognition in men in the absence of testosterone. DESIGN Randomised trial of transdermal estradiol 0.9mg daily, or matched placebo, for 6 months, hypothesizing that estradiol would improve verbal learning, verbal memory and spatial problem solving over time. PATIENTS Men receiving androgen deprivation therapy (ADT) for prostate cancer. MEASUREMENTS Cognition was assessed by a tablet-based cognitive battery (Cogstate) at baseline, month 1, month 3, and month 6. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale. RESULTS 78 participants were randomised. Baseline mean scores were 21.0 (sd 4.1) for the International Shopping List test (ISL), assessing verbal learning and memory (higher scores better), and 60.4 (sd 19.5) for the Groton Maze Learning test (GML), assessing spatial problem solving (lower scores better). There was no significant difference in performance over time for the estradiol group versus the placebo group for the ISL, mean adjusted difference (MAD) 0.7 (95% CI -1.2 - 2.5), p=0.36, or the GML, MAD -3.2 (95% CI -12.0 - 5.6), p-0.53. There was no significant difference between groups over time in performance in any other cognitive domain, or on depression or anxiety scores. CONCLUSIONS We found no major effects of estradiol on cognition in men with castrate testosterone concentrations. Although the cognitive effects of ADT are debated, this study suggests that any such effects are unlikely to be prevented by administration of estradiol. This article is protected by copyright. All rights reserved.

European Journal of Clinical Investigation, Nov 1, 1995

. Human chorionic gonadotropin (hCG)‐like molecules have been reported to be elevated in a substa... more . Human chorionic gonadotropin (hCG)‐like molecules have been reported to be elevated in a substantial fraction of serum samples from patients with various gynaecologic tumours and have been discussed as possible markers in these malignancies. Employing highly sensitive and specific immunoradio‐metric assays, we determined total hCG‐related immunoreactivity (hCG/hCGβ), as well as free α‐subunit (α‐SU), common to all glycoprotein hormones, in serum (n= 106) and malignant effusions (n= 26) of women with gynaecologic malignancies. For comparison, we also measured hCG/hCGβ in nonmalignant ascitic fluids (n= 21). HCG/hCGd̃ serum levels were elevated (>5 IU L‐1) in 39 of 106 patients (37%) with gynaecologic malignancies, whereas free α‐SU was above normal range only in seven (6.6%). Frequencies of hCG/hCGβ elevations were similar in women with endometrial (n= 39), cervical (n= 40) and ovarian (n= 27) cancer, being 30%, 35% and 41%, respectively. In malignant ascites (n= 15) and tumour cyst fluids (n= 11) of patients with ovarian cancer, hCG/ hCGβ concentrations were significantly higher than in the corresponding serum samples and benign ascitic samples. Free α‐SU, on the other hand, was increased in only one of 26 malignant effusions. In conclusion, hCG/hCGβ is frequently elevated in serum of patients with endometrial, cervical and ovarian cancer and may serve as a tumour marker in these malignancies, particularly in patients where other markers are negative. In this respect, analysis of ascitic or tumour cyst fluids may be of higher diagnostic value as serum measurements.

The New England Journal of Medicine, Apr 3, 2014

British Journal of Ophthalmology, Jun 1, 2003

Background: In patients with Graves' disease, smoking considerably increases the incidence and se... more Background: In patients with Graves' disease, smoking considerably increases the incidence and severity of thyroid associated ophthalmopathy (TAO). The authors sought to determine if smoking also influences the course of TAO during treatment, and the efficacy of therapy. Methods: 41 smokers and 19 non-smokers with moderate untreated TAO were included in this prospective study. All patients were treated with steroids and, 6 weeks after the beginning of drug therapy, with orbital irradiation. Follow up was performed 1.5, 4.5, 7.5, and 12 months after the beginning of the study. Proptosis, clinical activity score (CAS), and motility were evaluated. The extent of smoking was derived from the concentration of the haemoglobin adduct N-2-hydroxyethylvaline (HEV), a parameter of long term smoking. Results: There was no difference in the clinical manifestations of TAO between smokers and non-smokers at the beginning of treatment. However, CAS decreased (p<0.05) and motility improved (p<0.02) significantly faster and to a greater extent in non-smokers than smokers. Inverse correlations between the CAS decrease and the HEV levels observed 4.5 and 7.5 months after the beginning of treatment and between the improvement of motility and the HEV levels after 1.5, 4.5, and 7.5 months indicated a dose dependence. Mean HEV levels did not vary much during the follow up period and were significantly different in smokers (mean 5.4 (SD 2.7) µg/l) and non-smokers (mean 1.8 (1.3) µg/l; p<0.01). Conclusion: Smoking influences the course of TAO during treatment in a dose dependent manner. The response to treatment is delayed and considerably poorer in smokers.

International Journal of Obesity, Mar 22, 2016

Quantification of abdominal visceral adipose tissue (VAT) is important to understand obesity-rela... more Quantification of abdominal visceral adipose tissue (VAT) is important to understand obesity-related comorbidities. We hypothesized that dual X-ray absorptiometry (DXA) measurements of VAT would correlate with traditional gold standards of magnetic resonance imaging (MRI) and computed tomography (CT) in older men. Deming regression and Bland–Altman plots were used to assess the agreement between VAT measured simultaneously by DXA and MRI (n=95) in a cohort of older males participating in a randomized trial of testosterone replacement for diabetes. We also correlated DXA with single-slice CT (n=102) in a cohort of older males undergoing testosterone deprivation for prostate cancer. Lunar Prodigy DXA scanners using enCORE software was used to measure VAT. DXA VAT volume strongly correlated with MRI VAT volume (r=0.90, P<0.0001) and CT VAT area (r=0.83, P<0.0001). As DXA assesses VAT volume in a smaller compartment than MRI, Bland–Altman analysis demonstrated DXA systematically underestimated VAT by an approximately 30% proportional bias. DXA VAT volume measured by Lunar Prodigy DXA scanners correlate well with gold standard MRI and CT quantification methods, and provides a low radiation, efficient, cost-effective option. Future clinical studies examining the effects of interventions on body composition and regional fat distribution may find DXA an appropriate volumetric method to quantify VAT.

Endocrine connections, Jul 1, 2023

Purpose We previously demonstrated that 12 months of aromatase inhibitor (AI) treatment was not a... more Purpose We previously demonstrated that 12 months of aromatase inhibitor (AI) treatment was not associated with a difference in body composition or other markers of cardiometabolic health when compared to controls. Here we report on the pre-planned extension of the study. The pre-specified primary hypothesis was that AI therapy for 24 months would lead to increased visceral adipose tissue (VAT) area when compared to controls. Methods We completed a 12-month extension to our prospective 12-month cohort study of 52 women commencing AI treatment (median age 64.5 years) and 52 women with breast pathology not requiring endocrine therapy (63.5 years). Our primary outcome of interest was VAT area. Secondary and exploratory outcomes included other measures of body composition, hepatic steatosis, measures of atherosclerosis and vascular reactivity. Using mixed models and the addition of a fourth time point, we increased the number of study observations by 79 and were able to rigorously determine the treatment effect. Results Among study completers (AI = 39, controls = 40), VAT area was comparable between groups over 24 months, the mean-adjusted difference was −1.54 cm2 (95% CI: −14.9; 11.9, P = 0.79). Both groups demonstrated parallel and continuous increases in VAT area over the observation period that did not diverge or change between groups. No statistically significant difference in our secondary and exploratory outcomes was observed between groups. Conclusions While these findings provide reassurance that short-to-medium-term exposure to AI therapy is not associated with metabolically adverse changes when compared to controls, risk evolution should be less focussed on the AI-associated effect and more on the general development of cardiovascular risk over time.

Springer eBooks, 1991

The determination of microsomal antibodies (MAb) has a long tradition in the diagnosis of thyroid... more The determination of microsomal antibodies (MAb) has a long tradition in the diagnosis of thyroid autoimmune disease [1]. The antigen, however, against which those antibodies are directed has only recently been identified and appears to be closely related to or identical with thyroid peroxidase (TPO) [2–5]. These advances in defining the microsomal antigen offer a chance to develop new assay techniques for measuring MAb. Hence, new assays rely on the use of molecularly well-defined antigens instead of crude microsomal fractions being employed in current routine assays for MAb. In the present study we were interested from a clinical point of view to investigate the interaction of MAb with microsomal antigen by three different techniques: (a) a conventional hemagglutination test (HAT), which measures MAb reaction with a crude thyroid microsomal preparation; (b) Western blot analysis, which shows the reaction of MAb with distinct microsomal proteins; and (c) anti-TPO radioimmunoassay, which determines the reaction of MAb with purified human TPO.

PubMed, Apr 21, 1997

Recently, two clinical trials demonstrated an antitumour effect of systemic high-dose beta-hCG th... more Recently, two clinical trials demonstrated an antitumour effect of systemic high-dose beta-hCG therapy and of different regimens of local beta-hCG injections in AIDS-related Kaposi's sarcoma. We report the efficacy and safety of subcutaneous beta-hCG treatment (low-dose (2500-25000 IU/day) or high dose (25000-100000 IU/day)) in eight patients with advanced HIV disease in whom systemic chemotherapy and radiation were contraindicated or had failed. During therapy, serum hCG-concentrations as well as LH and FSH were measured. In the low-dose regimen one partial response was achieved. In the high-dose regimen, one patient maintained his response without further improvement. Three patients had stable disease and four patients disease progression. Serious side effects related to beta-hCG therapy were not observed. In conclusion, systemic beta-hCG-therapy for Kaposi's sarcoma is safe but associated with regression only in a minority of patients with advanced HIV-disease.

European journal of endocrinology, Sep 29, 2022

Objective: Most men undergoing androgen deprivation therapy (ADT) for prostate cancer experience ... more Objective: Most men undergoing androgen deprivation therapy (ADT) for prostate cancer experience hot flushes. Current treatments have low or limited evidence of efficacy. It is likely that oestradiol depletion is the mediator of these hot flushes, and transdermal oestradiol might be an effective treatment. Design: This is a 6-month randomised, placebo-controlled trial with the hypothesis that oestradiol would reduce hot flush frequency and intensity and improve quality of life (QoL). Methods: Seventy-eight participants receiving ADT were randomised to 0.9 mg of 0.1% oestradiol gel per day or matched placebo. Hot flush frequency and severity were assessed by 7-day diary at baseline, month 1, month 3, and month 6. QoL was assessed by validated questionnaire. Results: Oestradiol reduced daily hot flush frequency, with a mean adjusted difference (MAD) of-1.6 hot flushes per day (95% CI:-2.7 to-0.5; P = 0.04). The effect on weekly hot flush score was non-significant, with a MAD-19.6 (95% CI:-35.5 to-3.8; P = 0.11). On per protocol analysis, E2 significantly reduced daily hot flush frequency, with a MAD of-2.2 hot flushes per day (95% CI:-3.2 to-1.1; P = 0.001), and weekly hot flush score, with a MAD of-27.0 (-44.7 to-9.3; P = 0.02). Oestradiol had no significant effect on QoL. Conclusion: We confirmed our hypothesis of a clinical effect of assignment to oestradiol to reduce hot flush frequency in men with castrate testosterone due to ADT. Transdermal oestradiol could be considered for men with burdensome hot flushes in whom other treatments have failed as long as the risk of breast effects and fat gain are considered. experience decrements in self-reported QoL scores (4), with an important contributor being the burden of hot flushes (4, 5). Most men undergoing ADT experience hot flushes (6), and these may cause discomfort and embarrassment, interrupt sleep, and represent a recurring reminder of the prostate cancer diagnosis (7). Currently used treatments for ADT-induced hot flushes include antidepressants

Der Nuklearmediziner, 2004

The Journal of Clinical Endocrinology and Metabolism, Dec 1, 1996

Previous studies have indicated that in addition to other glycoprotein hormones, the pituitary gl... more Previous studies have indicated that in addition to other glycoprotein hormones, the pituitary gland produces small amounts of hCGP, the classical pregnancy and tumor marker. At the gene transcription level, definitive proof for hCGp messenger ribonucleic acid transcription was still lacking, largely due to the 90% homology to hLHp at the DNA sequence level, which renders specific hCG detection in the presence of a vast excess of LH difficult. We investigated both the presence of hCGp messenger ribonucleic acid and the protein itself in normal human female postmenopausal (n = 4) and male pituitaries (n = 2). Reverse transcription-PCR and subsequent restriction enzyme analysis revealed that the hCG@ 3,5, 7, and 8 genes coding for genuine hCGp were transcribed in all

Digestive Diseases and Sciences, Dec 1, 1991

A patient with ileus due to a calcified gallstone obstructing the je junum was treated by extraco... more A patient with ileus due to a calcified gallstone obstructing the je junum was treated by extracorporeal shock-wave therapy. The stone was visualized well by ul t rasonography. Using an electrohydrauiic lithotripter, 1600 discharges at a mean discharge energy-of 25.000 V were applied. Target ing to the stone was guided by ultrasonography. The stone was sufficiently disintegrated after one lithotripsy session, and the fragments thereafter passed with the feces. The symptoms and signs of intestinal obstruction resolved.

International Journal of Obesity, Dec 28, 2016

Symptomatic response to testosterone treatment in dieting obese men with low testosterone levels ... more Symptomatic response to testosterone treatment in dieting obese men with low testosterone levels in a randomized, placebo-controlled clinical trial,

PubMed, 1993

Recent advances in our understanding of hCG/hCG beta synthesis by trophoblastic and nontrophoblas... more Recent advances in our understanding of hCG/hCG beta synthesis by trophoblastic and nontrophoblastic tissues together with improved techniques for measuring hCG have helped to define the role of hCG as a clinical marker. HCG determination by sensitive immunometric assay enables detection of hCG immunoreactivity in normal men and women. It facilitates early detection of normal pregnancy and significantly contributes to the diagnosis of various pregnancy-related disorders, such as ectopic pregnancy, spontaneous abortion, hydatidiform mole, choriocarcinoma or Trisomy 21. Further, determination of this marker is immensely helpful to guide curative intervention in testicular cancer. For diagnosis and follow-up of patients with testicular cancer, a method measuring both hCG and hCG beta or separate methods for each component are recommended, because a significant portion of seminoma exclusively secrete free hCG beta. Also, hCG beta production by other than trophoblastic malignancies has been well recognized. A possible clinical use of hCG beta as a marker of cancers of the bladder, pancreas or biliary tract is currently debated.

PubMed, Sep 1, 1995

Spontaneous regression of cancer is a rare phenomenon seldom described in patients with hepatocel... more Spontaneous regression of cancer is a rare phenomenon seldom described in patients with hepatocellular carcinoma. A case of spontaneous regression of hepatocellular carcinoma is reported and compared with the reports published in the English literature. A 52-yr-old man presented with biopsy-proven hepatocellular carcinoma, which was considered to be unresectable at initial laparotomy. The tumor subsequently regressed without specific treatment, as assessed radiologically and by normalization of a previously elevated alpha-fetoprotein level. At repeat laparotomy 14 months after initial diagnosis, intraoperative ultrasound failed to disclose a hepatic mass, and multiple biopsies showed no evidence of malignancy. To date, only nine case reports of apparently spontaneous regression of hepatocellular carcinoma have been published in the English literature. Clinical characteristics discriminating these patients from less fortunate patients with hepatocellular carcinoma could not be identified. The mechanisms underlying this intriguing phenomenon remain unknown.

Journal of Hepatology, 2019

designed the study, prepared the manuscript and liaised with co-authors and statistician regardin... more designed the study, prepared the manuscript and liaised with co-authors and statistician regarding results interpretation. Brooke Chapman and Thomas Scodellaro assisted in database creation and reviewed the final manuscript. Rudolf Hoermann provided statistical support. Peter Angus, Adam Testro and Paul Gow provided guidance in interpretation of results and preparation of manuscript.

Research Square (Research Square), Jun 27, 2023

The fundamental models of physiological regulation and homeostasis remain uncertain and controver... more The fundamental models of physiological regulation and homeostasis remain uncertain and controversial. We aimed to derive quantitative evidence regarding these models from the study of population data of balance points of different parameters and their respective controlling hormones in terms of the slopes of correlations between parameters and controlling hormones, and the slopes of derived estimates of the physiological responses of parameters to their respective regulating hormones. Our simulations showed that changes to the population distribution of, or dependence between, feedback loop limbs alter these slopes of population data derived correlations and estimates in speci c ways. Our corresponding empirical ndings were similar across multiple systems and support a general model of regulation whereby the balance points of parameters are generated peripherally under the in uence of feedback loops, both limbs of which may interdependent. This interdependence potentially bestows evolutionary homeostatic and regulatory advantages.

$Research paper thumbnail of Testosterone levels increase in association with recovery from acute fracture in men$

Osteoporosis International, May 7, 2014

International Journal of Andrology, May 20, 2013

Clinical Endocrinology, Feb 21, 2022

European Journal of Clinical Investigation, Nov 1, 1995

The New England Journal of Medicine, Apr 3, 2014

British Journal of Ophthalmology, Jun 1, 2003

International Journal of Obesity, Mar 22, 2016

Endocrine connections, Jul 1, 2023

Springer eBooks, 1991

PubMed, Apr 21, 1997

European journal of endocrinology, Sep 29, 2022

Der Nuklearmediziner, 2004

The Journal of Clinical Endocrinology and Metabolism, Dec 1, 1996

Digestive Diseases and Sciences, Dec 1, 1991

International Journal of Obesity, Dec 28, 2016

PubMed, 1993

PubMed, Sep 1, 1995

Journal of Hepatology, 2019

Research Square (Research Square), Jun 27, 2023

Homeostasis and Allostasis of Thyroid Function, 2018

The discovery of the negative feedback of thyroid hormones on pituitary thyroid-stimulating hormo... more The discovery of the negative feedback of thyroid hormones on pituitary thyroid-stimulating hormone (TSH) secretion, a classical endocrine feedback control system, has shaped diagnosis and treatment of thyroid disease for the last decades. Based on this concept, a unique diagnostic category of subclinical thyroid disorders was introduced, being defined exclusively by an abnormal TSH response in the presence of thyroid hormone concentrations within the reference range. Although this approach was able to deliver a conceptually straightforward disease definition problems surfaced in clinical practice as neither the diagnostic reference range nor the appropriate threshold for initiating substitution treatment are universally agreed upon for subclinical thyroid disorders. The situation is further aggravated by the so-called syndrome T, which comprises a substantial but heterogeneous group of L-T4 treated patients with hypothyroidism with reduced quality of life despite “normal” TSH values.
A limited understanding of the physiological relationships between TSH and thyroid hormones may be a main reason for clinical difficulties in dealing with the causes of syndrome T and tailoring substitution therapy for hypothyroid patients with subclinical thyroid disorders.
Feedback regulation has recently been shown to be much more complex than previously assumed. The concept of homeostatic control has also been extended to include the lesser known but equally important allostatic thyroid regulation.The latter aims at adaptive homeostasis or stability through changing setpoints and modulating structural parameters of feedback control, as may be appropriate to adapt to a vast array of conditions spanning from fetal life, aging, pregnancy, exercise, starvation, obesity, psychiatric disorders to the severe non-thyroidal illness syndrome.
A better understanding of homeostatic and allostatic mechanisms, which govern the behaviour of pituitary-thyroid feedback control, is on the horizon. This promises to improve the diagnostic utility of laboratory methods, laying the foundation for personalised methods to optimise dosage and modality of substitution therapy. The emerging new world of thyroid physiology is reflected on the side of clinical medicine in a new, relational paradigm for diagnosis and treatment.
Considerable progress has been made in this respect in the following key areas:
• the significance of complementary information processing structures within the feedback loop, in particular ultrashort feedback of TSH on its own secretion and the action of a TSH-T3 shunt unburdening the thyroid from T4 synthesis in imminent thyroid failure,
• the unravelling of spatio-temporal dynamics of hormone concentrations ranging from ultradian to circannual rhythms and including hysteresis effects,
• the emergence of “non-canonical” mechanisms of thyroid hormone signalling beyond transcriptional control of gene expression,
• the physiological actions of thyronine metabolites, which have been previously regarded as biologically inactive, such as thyronamines and iodothyroacetates,
• the characterisation of distinct patterns in the adaptive processes to stress and strain and their conclusive explanation through reactions to type 1 and type 2 allostatic load.
This collective volume contains the contributions to the Research Topic “Homeostasis and Allostasis of Thyroid Function”, which was originally published by the journal Frontiers in Endocrinology. Authored by an international team of experts from three continents ,the book provides a comprehensive overview on thyroid control from recent research in basic, computational and clinical thyroidology. Many aspects addressed here can be expected to stimulate future research. A more comprehensive view and better integration of in-vitro, in-silico and in-vivo investigations will be invaluable in paving the way to this new world of thyroidology.