Rudolf Hoermann

Posterior Retroperitoneoscopy as a New Minimally Invasive Approach for Adrenalectomy: Results of 30 Adrenalectomies in 27 Patients

Abstract. Posterior retroperitoneoscopic adrenalectomy is a new minimally invasive method. It represents an alternative to conventional open procedures and laparoscopic techniques. Between July 1994 and November 1995 a total of 30 retroperitoneoscopic adrenalectomies were performed on 27 patients. In 24 patients, unilateral tumors were seen (size 1–7 cm): seven Cushing adenomas, five Conn adenomas, seven pheochromocytomas, four hormonally inactive tumors, one cyst. Three patients suffered from Cushing syndrome with bilateral adrenal gland hyperplasias (two inoperable pituitary gland tumors, one bronchial carcinoid with ACTH secretion). The operations were carried out in prone position. After balloon dilatation of the retroperitoneum and creation of a pneumoperitoneum the preparation of the adrenal gland was performed via three trocar sites positioned below the 12th rib. Twenty-five adrenalectomies were completed endoscopically, and five times (among four patients) conversion to the conventional posterior technique was necessary. The average operating time of complete endoscopic adrenalectomies was 124 minutes (45–225 minutes); blood loss was 10 to 120 ml. With minimal need for postoperative analgesia (average dosage 7.9 mg of piritramide), mobilization and adequate food uptake were possible on the day of operation. The posterior retroperitoneoscopic adrenalectomy is a relatively fast, safe method, with the advantages of the posterior open approach and minimally invasive surgery. It therefore represents an important addition to adrenal gland surgery.

Impact of smoking on the response to treatment of thyroid associated ophthalmopathy.

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.

Posterior Retroperitoneoscopic Adrenalectomy: Lessons Learned within Five Years

Abstract. Posterior retroperitoneoscopic adrenalectomy is one of the new endoscopic methods in endocrine surgery. In a prospective clinical study 142 posterior retroperitoneoscopic adrenalectomies (72 right, 70 left) were performed in 130 patients (52 males, 78 females, age 49.1 ± 14.9 years). Indications were primary adrenal tumors (unilateral, n= 118; bilateral, n= 2), adrenal metastases (n= 2), and bilateral ACTH-dependent hyperplasias (n= 10). Tumor size ranged from 0.5 to 7.0 cm (mean 2.7 ± 1.4 cm). Partial adrenalectomies were performed in 39 patients. Conversion to open posterior adrenalectomy was necessary in five patients and seven procedures (5%). Intraoperative and postoperative complications were minor and occurred in 5% and 13%, respectively. Mortality was zero. Operating time was 101 ± 39 minutes (range 35–285 minutes) and depended on tumor type (pheochromocytoma versus others; p < 0.01), tumor size (< 3 vs. ≥ 3 cm; p < 0.05), gender (p < 0.05), and extent of resection (partial versus complete, p < 0.05. Twenty-three adrenalectomies (17%) were performed within 1 hour or less. Blood loss was 54 ± 72 ml. Consumption of analgesics was low (mean 6 mg piritramide postoperatively). Median duration of hospitalization was 3 days. Posterior retroperitoneoscopic adrenalectomy is a safe method that has become a standard procedure in endocrine surgery.

Effect of testosterone treatment on glucose metabolism in men with type 2 diabetes: a randomized controlled trial.

OBJECTIVE To determine whether testosterone therapy improves glucose metabolism in men with type 2 diabetes (T2D) and lowered testosterone. RESEARCH DESIGN AND METHODS We conducted a randomized, double-blind, parallel, placebo-controlled trial in 88 men with T2D, aged 35–70 years with an HbA1c ≤8.5% (69 mmol/mol), and a total testosterone level, measured by immunoassay, of ≤12.0 nmol/L (346 ng/dL). Participants were randomly assigned to 40 weeks of intramuscular testosterone undecanoate (n = 45) or matching placebo (n = 43). All study subjects were included in the primary analysis. Seven men assigned to testosterone and six men receiving placebo did not complete the study. Main outcome measures were insulin resistance by homeostatic model assessment (HOMA-IR, primary outcome) and glycemic control by HbA1c (secondary outcome). RESULTS Testosterone therapy did not improve insulin resistance (mean adjusted difference [MAD] for HOMA-IR compared with placebo −0.08 [95% CI −0.31 to 0.47; P = 0.23]) or glycemic control (MAD HbA1c 0.36% [0.0–0.7]; P = 0.05), despite a decrease in fat mass (MAD −2.38 kg [−3.10 to −1.66]; P < 0.001) and an increase in lean mass (MAD 2.08 kg [1.52–2.64]; P < 0.001). Testosterone therapy reduced subcutaneous (MAD −320 cm3 [−477 to −163]; P < 0.001) but not visceral abdominal adipose tissue (MAD 140 cm3 [−89 to 369]; P = 0.90). CONCLUSIONS Testosterone therapy does not improve glucose metabolism or visceral adiposity in obese men with moderately controlled T2D and modest reductions in circulating testosterone levels typical for men with T2D.

Complex relationship between free thyroxine and TSH in the regulation of thyroid function

OBJECTIVE The present study re-evaluates the inverse log TSH-free thyroxine (fT(4)) relationship, which has generally been assumed to characterize the thyroid pituitary hypothalamic feedback regulation in thyroid function. DESIGN AND METHODS The correlation between fT(4) and TSH was analyzed in two data sets from differing time periods involving 3223 and 6605 patients referred for thyroid testing, representing the whole range of thyroid functions from hypothyroidism to hyperthyroidism. RESULTS We found that the data do not support a linear log TSH-fT(4) relationship; instead, the correlations gradient varies with thyroid function. As a consequence, an alternate model, based on the error function, was introduced. When directly comparing the models by means of curve fitting, using F-test and Akaike criteria, the alternate model results in a significantly better fit. The model was verified in the independent second set of data. Subgroup analysis of untreated patients added further proof to the non-linear model. CONCLUSIONS We propose a refined non-linear model to describe the relationship between TSH and fT(4). It implies that TSH response to a deviating fT(4) value may not be log-linear, but may be disproportionally related to the extent of the deviation from an optimum set point. A better understanding of the complex nature of the TSH-fT(4) relationship may further the development of more precise clinical models and aid in better defining subclinical states of thyroid dysfunction. Also, it may encourage other biological interrelations to be reconsidered in the wake of advanced measurement techniques and more powerful computerized statistical procedures.

Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta‐analysis of randomized controlled clinical trials

The effects of testosterone treatment on glucose metabolism and other outcomes in men with type 2 diabetes (T2D) and/or the metabolic syndrome are controversial.

IMMUNOCHEMICAL MAPPING OF GONADOTROPINS

As a glycoprotein hormone, human chorionic gonadotropic (hCG) is not a single molecular entity but this term rather comprises an array of molecular variants such as hCG, hCG beta, hCGn, hCG beta n, hCG beta cf, -CTPhCG, hCG beta CTP, deglyhCG, asialohCG, hCGav and the closely related molecules hLH, hLH beta and hLH beta ef. The advent of monoclonal antibodies (MCA), the availability of ultrasensitive detection systems and the recent determination of the crystal structure of hCG, made it possible to design special purpose diagnostic and clinical research immunoassays for hCG-like molecules. For more than a decade we and others have tried to refine epitope maps for hCG and related molecules by means of a large panel of MCA, naturally occurring metabolic variants of hCG (hCGn, hCG beta, hCG alpha, hCG beta cf, hCG beta CTP), homologous hormones and subunits of various species (e.g. hLH, hLH beta, hFSH, hTSH, oLH, rLH beta), chemically modified molecules (deglyhCG, asialohCG, tryptic and chymotryptic hCG beta and hCG alpha fragments) and synthetic peptides (octapeptides and longer). It appeared that all epitopes on molecular hCG-variants recognized by our MCA are determined by the protein backbone. Except for the two major epitopes on hCG beta CTP and parts of two antigenic domains on hCG alpha, epitopes on hCG-derived molecules are determined by the tertiary and quarternary structure. Operationally useful descriptive epitope maps were designed including information on assay suitability of antigenic determinants. On this basis we established ultrasensitive time-resolved fluoroimmuno-assays for hCG, hCG and hCGn, hCG beta and hCG beta n and hCG beta cf, hCG alpha and additional assays recognizing different spectra of hCG-variants. Such assay have been applied by us and others to the detection of pregnancy, early pregnancy loss, choriocarcinoma, testicular cancer, other cancers and prenatal diagnosis. However, as the molecular structure of many epitopes utilized in immunoassays of different laboratories was not resolved, comparability of results was not satisfactory. Consequently, attempts were made to compare schematic epitope maps from different research institutions. The situation has been much improved by solving the three-dimensional (3D) structure of hCG. It has been shown that hCG is a member of the structural superfamily of cystine knot growth factors like NGF, PDGF-B and TGF-beta. Each of its subunits is stabilized in its topology by three disulfide bonds forming a cystine knot. Moreover, it turned out that the disulfide bridges in their majority have previously been wrongly assigned. Computer molecular modeling of crystallographic coordinates of hCG and subsequent selective combined--PCR-based and immunological--mutational analyses of hCG beta expressed via the transmembrane region of a MHC molecule made it possible to more precisely localize epitopes on hCG-derived molecules. Although the entire surface of hCG has to be regarded as potentially immunogenic there seems to be hot spots where epitopes are clustered in antigenic domains. These are located on the first and third loops protuding from the cystine knots of both subunits and are possibly centered around the knot itself. Ultimate answers on epitope localizations will be given by the crystal structure determination of hCG complexed with different Fabs.

Testosterone therapy increases muscle mass in men with cirrhosis and low testosterone: A randomised controlled trial

BACKGROUND & AIMS Low testosterone and sarcopenia are common in men with cirrhosis and both are associated with increased mortality. Whether testosterone therapy in cirrhosis improves muscle mass and other outcomes is unknown. METHODS We conducted a 12-month, double-blinded, placebo-controlled trial of intramuscular testosterone undecanoate in 101 men with established cirrhosis and low serum testosterone (total testosterone <12nmol/L or free testosterone <230pmol/L) in a single tertiary centre. Body composition was assessed using dual-energy X-ray absorptiometry at baseline, 6 and 12months. RESULTS At study completion, appendicular lean mass was significant higher in testosterone-treated subjects, with a mean adjusted difference (MAD) of +1.69kg, (CI +0.40; +2.97kg, p=0.021). Secondary outcomes included a substantially higher total lean mass in the active group (MAD +4.74kg, CI +1.75; +7.74kg, p=0.008), matched by reduced fat mass (MAD -4.34kg, CI -6.65; -2.04, p<0.001). Total bone mass increased (MAD +0.08kg, CI +0.01; +0.15kg, p=0.009) as did bone mineral density at the femoral neck (MAD +0.287points, CI +0.140; +0.434, p<0.001). Haemoglobin was higher with testosterone therapy (MAD +10.2g/L, CI +1.50; +18.9g/L, p=0.041) and percentage glycosylated haemoglobin (HbA1c) lower (MAD -0.35%, CI -0.05; -0.54, p=0.028). Mortality was non-significantly lower in testosterone-treated patients (16% vs. 25.5%, p=0.352). There was no increase in adverse events in testosterone-treated subjects. CONCLUSION Testosterone therapy in men with cirrhosis and low serum testosterone safely increases muscle mass, bone mass and haemoglobin, and reduces fat mass and HbA1c. This is the first evidence-based therapy for sarcopenia in cirrhosis and thus requires larger-scale investigation into its potential impact on mortality. LAY SUMMARY Both low testosterone and muscle wasting are associated with increased risk of death in men with severe liver disease. Administering testosterone to men with liver disease who have low testosterone levels significantly increases their muscle mass. In addition, testosterone has non-muscle beneficial effects which may be able to increase survival in this population. CLINICAL TRIAL NUMBER Australian New Zealand Clinical Trials Registry trial number ACTRN 12614000526673.

Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment

We examined the interrelationships of pituitary thyrotropin (TSH) with circulating thyroid hormones to determine whether they were expressed either invariably or conditionally and distinctively related to influences such as levothyroxine (L‐T4) treatment.

Alpha‐subunit and human chorionic gonadotropin‐β immunoreactivity in patients with malignant endocrine gastroenteropancreatic tumours

Abstract. In the serum of patients with malignant endocrine gastroenteropancreatic (GEP) tumours, both α‐subunit (α‐SU), common to all glycoprotein hormones, as well as free β‐subunit of human chorionic gonadotropin (hCG‐β) have been reported to be elevated in a substantial fraction. Both have been discussed as markers of malignancy in these neoplasms. In the present study we evaluated the diagnostic significance of α‐SU and hCG‐β as serum markers in patients with malignant endocrine gastroenteropancreatic tumours.