Hans-Jürgen Quabbe

Results of surgical and somatostatin analog therapies and their combination in acromegaly: a retrospective analysis of the German Acromegaly Register

BACKGROUND Data on surgical and medical treatment outcomes in acromegaly mostly originate from specialized centers. We retrospectively analyzed the data on surgery, primary somatostatin analog (SSA) therapy, surgery preceded by SSA, and SSA preceded by surgery in 1485 patients from the German Acromegaly Register. METHODS Two trained nurses visited all centers (N=42) for data acquisition. RESULTS Primary surgery: out of 889 patients, 554 yielded analyzable data (microadenomas 22.9%, macroadenomas 77.1%). GH and IGF1 normalized in 54.3 and 67.2%. Partial or total pituitary insufficiency occurred in 28.6% initially and 41.2% post-surgery. Primary SSA (>or=3 months): out of 329 patients, 145 yielded analyzable data (microadenomas 26.7%, macroadenomas 73.3%). GH and IGF1 normalized in 36.3 and 30.5%, increasing to 40.8 and 41.5% with longer SSA (>or=360 days) in 54 patients. Pituitary function did not change. SSA (>or=3 months) prior to surgery: out of 234 patients, 93 yielded analyzable data. Post-surgery GH and IGF1 was normalized in 62.9 and 68.4%. GH improvement was slightly, but significantly better after SSA pretreatment. Surgery followed by SSA: out of 122 patients, 34 yielded analyzable data. GH and IGF1 normalized during SSA in 24.1 and 45.5%. Relative GH decrease was significantly larger compared with primary SSA. CONCLUSIONS Pituitary surgery was more effective to lower GH and IGF1 concentrations than primary SSA. Primary SSA may be an option in selected patients. SSA prior to surgery only marginally improved surgical outcome. Debulking surgery may result in better final outcome in patients with a high GH concentration and a large tumor.

Chronobiology of Growth Hormone Secretion

The secretion of growth hormone (GH) in man occurs in episodic bursts during day and night (1). During trough periods, concentrations are below the sensitivity of the usual radioimmunoassay (approximately 0.5-1.0 ng/ml). Peak concentrations are often around 20 ng/ml, but may attain 50 ng/ml (or even more), especially in younger subjects. In man, the secretory episodes occur approximately every 4 h. Although some of these GH peaks are often missing in 24-h profiles, the rhythmicity probably persists with low-amplitude peaks occurring below the sensitivity of most current assay systems (2).

Age and sex as predictors of biochemical activity in acromegaly: analysis of 1485 patients from the German Acromegaly Register

Objective  We evaluated the German Acromegaly Register for clinical variables associated with the initial biochemical activity of patients with acromegaly.

Expression of Functional GABAA Receptors in Isolated Human Insulinoma Cells

Pancreatic islets contain and release high concentrations of GABA. GABA is thought to play a paracrine role in beta-cells. Searching for a paracrine function of GABA in neoplastic beta-cells we performed patch-clamp studies in isolated human insulinoma cells. We show that human insulinoma cells can express functional GABAA receptors. Activation of GABAA receptors caused a reversible membrane depolarization in a subgroup of insulinoma cells. Membrane depolarization resulted in transmembraneous calcium influx through voltage-gated calcium channels and stimulation of insulin secretion. Insulin secretion was increased by the GABAA receptor agonist muscimol (50 microM) by about 280%. Thus, GABAA receptors can be expressed in human insulinoma cells and can regulate their insulin release.

Evaluation of a repeatable depot-bromocriptine preparation(Parlodel LAR®) for the treatment of acromegaly

The effectiveness and side effects of a newly developed, repeatable depot-bromocriptine preparation, (Parlodel LAR®, depot-bromocriptine), were studied in 7 acromegalic patients. A dose of 100 mg was injected at intervals of 28 days for 4 months, followed by 200 mg for 2 months. GH profiles (14 h) and an oral glucose load (oGTT) were performed prior to each injection. Depot-bromocriptine suppressed the mean serum profile GH concentration to less than 50% of the pretreatment value in 3 out of 7 patients (responders). Normalization of GH secretion was not achieved. During oGTT the mean serum GH concentration declined to 73%, 19% and 56% of the pretreatment value in the three responders (while on depot-bromocriptine 200 mg). IGF-I was reduced to 84% and 65% with 200 mg depot-bromocriptine in 2 GH responders only. No tumour shrinkage was observed in 3 patients with a visible tumor mass in NMR tomography. Side effects consisted of pronounced orthostatic dysregulation, nausea and vomiting on the day of injection in 3/7 patients. These results are comparable to the reported effectiveness and side effects of oral bromocriptine therapy. Depot-bromocriptine may be useful in selected responsive patients, particularly when compliance during oral therapy is a problem.

The Rational Use of Pituitary Stimulation Tests

BACKGROUND Diseases of the pituitary gland can lead to the dysfunction of individual hormonal axes and to the corresponding clinical manifestations. The diagnostic assessment of pituitary function has not yet been standardized. METHODS The members of the Neuroendocrinology Section and the Pituitary Study Group of the German Society for Endocrinology (Deutsche Gesellschaft für Endokrinologie) prepared outlines of diagnostic methods for the evaluation of each of the pituitary hormonal axes. These outlines were discussed in open session in recent annual meetings of the Section and the Study Group. RESULTS For the evaluation of the thyrotropic axis, basal TSH and free T4 usually suffice. For the evaluation of the gonadotropic axis in men, the testosterone level should be measured; if the overall testosterone level is near normal, then calculating the free testosterone level may be additionally useful. In women, an intact menstrual cycle is sufficient proof of normal function. In the absence of regular menstruation, measurement of the basal estradiol and gonadotropin levels aids in the diagnosis of the disturbance. For the evaluation of the adrenocorticotropic axis, the basal cortisol level may be helpful; provocative testing is in many cases necessary for precise characterization. The evaluation of the somato-tropic axis requires provocative testing. Aside from the insulin tolerance test, the GHRH-arginine test has become well established. Reference ranges normed to the body mass index (BMI) are available. CONCLUSION The diagnostic evaluation of pituitary insufficiency should proceed in stepwise fashion, depending on the patients clinical manifestations and underlying disease. For some pituitary axes, measurement of basal hormone levels suffices; for others, stimulation tests are required. In general, the performance of combined pituitary tests should be viewed with caution.

Double-lumen flow-through swivel for chronic experiments with unrestrained monkeys ☆

Two modifications of a flow-through swivel are described for prolonged infusions into and simultaneous blood-sampling from chronically implanted catheters of large, unrestrained animals, e.g., rhesus monkeys. In addition, both offer easy access to the catheters proximal to the swivel and to the lumen of the reinforced nylon tubing which connects the animal to the swivel.

Absence of muscle capillary basement membrane thickening and retinopathy in patients with myocardial infarction and impaired I.V. glucose tolerance

SummaryWe have investigated the possible contribution of an early capillaropathy to the increased incidence of myocardial infarction (MI) in patients who had impaired glucose tolerence (IGT) during an i.v. glucose tolerance test (IVGTT). In lieu of the myocardium, biopsies from the quadriceps femoris muscle were studied for muscle capillary basement membrane (MCBM) thickening. Fluorescence angiography was performed to detect capillary retinopathy. Plasma growth hormone (GH) concentrations were determined during IGT. Data were obtained from 14 male patients with MI and IGT on IVGTT. Nine healthy subjects served as controls. MCBM thickness was similar in patients and controls (1,107±55vs 1,067±88 Å). None of the patients had signs of capillary retinopathy, and plasma GH concentrations were not higher in the patients as compared to control subjects. It is concluded that, in patients with IGT on IVGTT, MCBM thickening is probably not a factor for the development of MI.