Friedrich Jockenhövel

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.

Osteoporosis in Male Hypogonadism: Responses to Androgen Substitution Differ among Men with Primary and Secondary Hypogonadism

Background: No randomized study exists comparing the effects of different modes of androgen substitution on bone mineral density (BMD). Methods: We performed a prospective, randomized, trial assigning 53 hypogonadal men to the following treatment groups: mesterolone 100 mg p.o. daily, testosterone undecanoate 160 mg p.o. daily, testosterone enanthate 250 mg i.m. every 21 days, or a single subcutaneous implantation of 1,200 mg crystalline testosterone. The BMD was determined by peripheral quantitative computed tomography. Results: At baseline, men with secondary hypogonadism (n = 33) had a lower BMD (–1.52 ± 0.23 SDS; Z-scores) than men with primary hypogonadism (n = 20, –0.87 ± 0.23 SDS, p < 0.01). In men with primary hypogonadism, the BMD increased dose dependently (crystalline testosterone +7.0 ± 1.3%, testosterone enanthate +4.8 ± 0.2%, testosterone undecanoate +3.4 ± 2.5%, mesterolone +0.8 ± 1.6%) after 6 months of therapy. Only secondary hypogonadal men treated with testosterone enanthate experienced an increase of the BMD. Conclusions: In primary hypogonadal men the BMD responds dose dependently to testosterone substitution, whereas in secondary hypogonadism only testosterone enanthate treatment significantly increased the BMD.

Comparison of long-acting testosterone undecanoate formulation versus testosterone enanthate on sexual function and mood in hypogonadal men

OBJECTIVE To compare the effects of two treatment modalities of testosterone on sexual functioning and mood. Design Forty men were randomized to receive either parenteral testosterone enanthate (TE) or long-acting parenteral testosterone undecanoate (TU) over a period of 30 weeks. Thereafter, 20 men who had received TU and 16 men who had received TE continued with TU and completed another 65 weeks to study longer-term effects of TU. METHODS The following variables of sexual functioning were studied: sexual thoughts and fantasy, sexual interest and desire, satisfaction with sex life, number of erections and ejaculations per week, and number of spontaneous morning erections per week. Also variables related to mood were analyzed. RESULTS Improvements in these variables were significant and were of a similar magnitude in the group treated with TU and TE for 30 weeks. Improvements were maintained at the same levels over a period of another 65 weeks when all men received TU. Effects on mood were recorded for 30 weeks, but were more difficult to establish in the study population. There were significant differences in baseline values between the two groups and scores showed wide s.d. CONCLUSIONS Both TE and TU were effective in improving sexual functions in hypogonadal men. An advantage of TU over TE is its lower frequency of administration and its better tolerability and safety profile.

Timetable of effects of testosterone administration to hypogonadal men on variables of sex and mood.

Introduction. The effects of testosterone have been extensively characterized, but little attention has been given to the timetable of occurrence of the various effects of testosterone. Methods. The timetables of effects on sexual and psychological variables in 40 hypogonadal men receiving treatment with either parenteral testosterone enanthate (TE) or undecanoate (TU). Results. Sexual thoughts/fantasies and sexual interest/desire/spontaneous morning erections emerged quickly and plateaued after 3 weeks. Total erections rose to a maximum over 9 weeks and then plateaued. Ejaculations per week/satisfaction with sex life rose over the first 3 weeks, increasing steadily to a plateau at 12 weeks. Depression scores decreased to reach a plateau after 6 weeks. Aggressiveness did not change. Scores of concentration improved and reached a plateau after 3 weeks in the group treated with TE and after 9 weeks in the group treated with TU. Good mood improved after 6–9 weeks. Positive effects on self-confidence appeared between 3–6 weeks and on fatigue after 9–12 weeks. Conclusion. Insight into the emergence of effects may be useful information for the patient and for the attending physician in monitoring clinical effects of testosterone treatment of hypogonadal men.

Phosphorylation of sterol regulatory element-binding protein (SREBP)-1a links growth hormone action to lipid metabolism in hepatocytes

OBJECTIVE Increased lipid accumulation in cells and tissues is a key phenomenon in the development of obesity, insulin resistance, and atherosclerosis. In the regulation of lipid content of cells and tissues the SREBPs play a dominant role as transcription factors. METHODS Since growth hormone (GH) affects lipid metabolism and function of fat as well as liver cells, we have investigated the role of SREBP-1a, SREBP-1c and SREBP-2 in the gene regulatory action of GH in the human liver cell line HepG2 and primary mouse hepatocytes. RESULTS These experiments showed that SREBP-1a couples the stimulatory effect of GH on cholesterol regulated genes, e.g. LDL receptor gene, via sterol sensitive binding cis-element (sre-1). This effect was not depending on RNA expression, but related to phosphorylation of SREBP-1a protein. The result was supported by experiments with the mutant variant SREBP-1a S117A, which is not phosphorylated by Erk-MAP kinases. To analyse a possible role of GH-induced SREBP-1a phosphorylation in cellular physiology we investigated an expression profile of genes coding for central players in lipid transport or lipid metabolism as well as for transcription factors by real time PCR in primary mouse hepatocytes and human hepatoma cell line stably overexpressing the mature form of SREBP-1a or mutated form. CONCLUSION These experiments emphasize the role SREBP-1a and its phosphorylation for gene regulatory effects of GH.

A four-year efficacy and safety study of the long-acting parenteral testosterone undecanoate

Introduction. This is a four-year follow-up of 25 men who received parenteral testosterone undecanoate (TU), 1000 mg every 12 weeks for at least four years. This study was a continuation of a 30-week study wherein the effects of TU had been compared to those of parenteral testosterone enanthate. Methods & Results. Plasma testosterone (T) trough values of the injection interval of 12 weeks): median 11.9 – 15.9 nmol/L (N 10.0–30.0). E2 and SHBG were stable. Body weight, BMI, waist-to-hip ratio remained stable. Total cholesterol, and triglycerides were unchanged but plasma LDL declined while HDL, after an initial reduction over the first 30 weeks, had increased significantly after three years. Leptin levels, bone mineral density, blood pressure, liver function tests, haemoglobin and haematocrit levels remained stable without values above the upper limit of normal. Over the first 12 months of the study there was an increase in prostate volume from 19.7 ± 8.8 mL to 22.0 ± 8.4 mL (p < 0.05) but thereafter volumes remained stable, paralleled by an increase in PSA from 0.67 ± 0.38 µg/dL to 0.75 ± 0.35 µg/dL (p < 0.05) without any further changes after 12 months. Conclusion. TU appears to be a stable and safe treatment modality of hypogonadal men.

Free Androgen Index Is Superior to Total Testosterone for Short-Term Assessment of the Gonadal Axis after Renal Transplantation

Objective: Recent studies have assessed gonadal function in association with different immunosuppressive drugs in transplanted patients mainly relying on the measurement of total testosterone. It is the aim of this study to assess the short-term changes of the hypothalamic-pituitary-gonadal axis following renal transplantation using the free androgen index (FAI). Patients and Methods: The sequential changes in total testosterone, sex hormone-binding globulin (SHBG), gonadotropin and prolactin concentrations were measured in 22 male patients before and after 1–3 days, and 1, 2 and 3 weeks following renal transplantation. Results: Total testosterone and SHBG concentrations dropped significantly after transplantation (total testosterone: baseline: 15.2 ± 1.6 nmol/l vs. 1 week: 7.9 ± 0.8 nmol/l vs. 2 weeks: 9.8 ± 0.9 nmol/l, SHBG: baseline: 29.9 ± 3.2 nmol/l vs. 1 week: 19.9 ± 2.1 nmol/l, 2 weeks: 18.9 ± 2.4 nmol/l, p < 0.01). FAI decreased significantly after day 1–3 returning to values near baseline thereafter (baseline: 60 ± 9% vs. day 1–3: 38 ± 6%, 2 weeks: 61 ± 7%; p < 0.01). There was a significant positive correlation between FAI and renal function. Conclusion: Measurement of the free androgen index is superior to total testosterone for assessment of the pituitary-gonadal axis in the first weeks after renal transplantation.

Tumors of the Adrenals

Recent advances in imaging techniques (e.g. computed tomography, nuclear resonance imaging) have led to the discovery of unexpected adrenal tumors in about 2% of the patients. The incidental discovery