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Current status and future opportunities for controlling acromegaly.

Growth-hormone (GH) secreting adenomas, including acromegaly, account for approximately one-sixth of all pituitary adenomas and are associated with mortality rates at least twice that of the general population. The ultimate goal of therapy for acromegaly is normalization of morbidity and mortality rates achieved through removal or reduction of the tumor mass and normalization of insulin-like growth factor I (IGF-I) levels. Previously published efficacy results of current treatment modalities (surgery, conventional radiation, and medical therapy with dopamine agonists and somatostatin analogs) are often difficult to compare because of the different criteria used to define cure (some of which are now considered inadequate). For each of these modalities, pooled data from a series of acromegaly studies were reviewed for rates of IGF-I normalization, a currently accepted definition of cure. The results showed overall cure rates of approximately 10% for bromocriptine, 34% for cabergoline, 36% for conventional radiation, 50-90% for surgery for microadenomas and less than 50% for macroadenomas, and 54-66% for octreotide. These cure rates based on IGF-I normalization are generally less than those reported for cure based solely on GH levels. Novel new therapies for acromegaly include the somatostatin analog, lanreotide, Gamma Knife radiosurgery, and pegvisomant, the first in its class of new GH receptor antagonists. Although it does not appear that Gamma Knife radiosurgery results in significantly higher cure rates or fewer complications, it does provide a notable improvement in delivery compared with conventional radiation. Early studies have reported IGF-I normalization in 48% of lanreotide-treated patients and up to 97% of pegvisomant-treated.

Acromegaly↗

Improvement of acromegaly after octreotide LAR treatment.

Octreotide is a somatostatin analog that inhibits growth hormone release showing higher potency than natural somatostatin so it has proved to be effective in acromegaly treatment. The objective of present study was to establish the effects of octreotide LAR (long acting release) preparation in patients with active acromegaly. The following parameters were assessed: clinical response, safety of medication, GH and IGF-1 serum concentrations and pituitary tumor size. Eleven patients (6 men and 5 women) range 41.4 years old with diagnosis of active acromegaly were included. Octreotide was administered at 0.1 mg subcutaneusly dose three times daily for four weeks to test the drug tolerability. Afterwards patients received octreotide LAR 20 mg intramuscularly separated by 28 days periods with an option to continue for 8 months. Basal average GH serum concentrations was 27.6 ng/mL. After 6 months treatment reduction to 5.03 +/- 5.38 ng/mL in 9 patients (p < 0.001) was observed. Basal IGF-1 average serum concentration was 889.55 +/- 167.29 ng/mL with a reduction value to 483.00 +/- 239.71 ng/mL in 9 of 11 patients after 6 months treatment (p < 0.005). The drug was well tolerated with few adverse effects Diarrhea, flatulence and steatorrhea were observed during the administration of subcutaneous octreotide in 18.2% of patients. Two patients had symptomatic biliary lithiasis that was successfully removed by surgery. Clinical symptoms improved and some of them dissapeared such as headaches and sweatings. Tumor shrinkage was observed in 66.7% of cases. Monthly injections of 20 mg of octreotide LAR were effective to reduce GH and IGF-1 levels in patients with active acromegaly accompanied by improvement of clinical symptoms and significant tumor size reduction.

Acromegaly↗

Selected speech and fundamental frequency characteristics of patients with acromegaly.

Selected speech characteristics of patients with acromegaly, a relatively uncommon endocrine disorder resulting from excessive secretion of growth hormone, are described. In patients with acromegaly, increased quantities of circulating growth hormone may cause hypertrophy of multiple bodily structures, including components of the phonatory and articulatory apparatus. Speech recordings of 11 patients with acromegaly (six women and five men) were subjected to fundamental frequency and articulation analysis. Despite clinically apparent lingual hypertrophy in each of the patients studied, no speech articulation errors were found. In contrast, acromegaly appeared to produce a lowering of voice fundamental frequency (fo) characteristics in some, but not all, patients. Women exhibited more striking changes in fo than did men.

Acromegaly↗

Men with acromegaly need higher doses of octreotide than women.

OBJECTIVE: To investigate the effect of gender on the response of GH to short-acting octreotide in patients with acromegaly, and on the GH and IGF-1 levels during long-term treatment with a slow-release formulation of octreotide. STUDY DESIGN AND PATIENTS: Twenty-one men (mean age 54 years; range 26-78) and 15 women (mean age 54 years; range 22-74) with acromegaly were treated with subcutaneous injections of 100 microg short-acting octreotide twice daily. Serum samples for GH were taken before start of treatment, in the morning prior to the injection, and 1, 3, 5 and 7 h after the injection. Thirteen men (mean age 56 years; range 34-78) and 12 women (mean age 64 years; range 28-81) with acromegaly were switched from ongoing treatment with short-acting octreotide to injections of the slow-release formulation. A 4-h GH-profile and morning IGF-1 were taken at start and after 3, 9, 15 and 21 months of treatment. RESULTS: Subcutaneous injections of 100 microg octreotide reduced the mean level of GH during a 7-h period to a similar extent in men and women compared to the GH levels prior to the injections. During long-term treatment with similar doses of the depot formulation of octreotide, the mean IGF-1 level remained significantly higher in the men than in the women, whereas there were no differences in the mean GH levels between the two groups. CONCLUSIONS: The responses to short- and long-acting octreotide illustrate an effect of gender, due to different sensitivity to GH in the periphery. Furthermore, the results show that in the treatment of acromegaly, men will need higher doses of octreotide than women to normalize IGF-1.

Acromegaly↗

Increased incidence of neoplasia in females with acromegaly.

OBJECTIVE: Some studies have indicated an increased incidence of neoplasia, particularly breast and colon, in acromegaly. We have determined the incidence of benign and malignant neoplasms in an Australian population of patients with acromegaly. DESIGN: Retrospective review, with comparison against cancer data for the local population obtained from a State Cancer Registry. PATIENTS: Fifty patients with documented acromegaly. RESULTS: There were 7 cases of malignancy (2 in men, 5 in women) in the period of follow-up (435 patient years). With logistic regression analysis, there was a relative risk of malignancy, of 1.2 (95% confidence interval 0.31-5.0) for men (P = 0.8) and 4.3 (95% confidence interval 1.7-10.5) for women (P = 0.001), when compared to the local population. There were 2 cases of breast and renal carcinoma, and one each of prostatic, colonic and parotid carcinoma. Of the most common benign tumours 35% of patients had thyroid nodules, 10% had colonic polyps and 6% had nasal polyps. CONCLUSION: The incidence of malignancy was found to be increased in female patients with acromegaly in this series. Routine screening procedures for malignancy, particularly in female patients, should therefore be considered.

Acromegaly↗

Decreased regional blood flow in patients with acromegaly.

BACKGROUND AND AIMS: One-third of acromegalic patients have hypertension. Acromegaly is also associated with intrinsic cardiac abnormalities known collectively as a hyperkinetic heart syndrome, which is characterized by an increased cardiac index and decreased systemic vascular resistance. As a result, blood flow should be increased in the regional vascular beds of acromegalic patients. The aim of the study was to measure, using direct methods, blood flow and vascular resistance at the level of the brachial artery in acromegalic patients with a confirmed hyperkinetic heart syndrome. PATIENTS AND CONTROLS: Twelve patients with active acromegaly (five females, seven males; mean (+/- SD) age, 43 +/- 10 years) were studied. Twelve age- and sex-matched normal subjects served as controls. METHODS: Right heart catheterization was used to measure the cardiac index and stroke volume and to calculate systemic vascular resistance in the acromegalic patients. Brachial haemodynamics were evaluated with a two-dimensional pulsed Doppler system (double transducer probe and range-gated time system of reception). The mean diameter of the brachial artery and mean blood velocity were measured and used to calculate mean blood flow. Vascular resistance was calculated in the brachial artery as the mean arterial pressure/blood flow ratio. RESULTS: Age, body weight, height, body surface area and heart rate were similar in the acromegalic patients and controls, while mean arterial pressure was higher in patients. The cardiac index and stroke volume were increased in the acromegalic patients, at 4.08 +/- 0.47 (mean +/- SD) l/min/m2 body surface area and 116.7 +/- 19.4 ml, respectively, while systemic vascular resistance was low (12.5 +/- 2.1 U). Brachial artery diameter was similar in the patients and controls. Brachial artery mean blood velocity (P < 0.01) and mean blood flow (P < 0.05) were lower in the patients than in the controls (3.35 +/- 1.26 vs. 5.12 +/- 1.74 cm/s, and 16.4 +/- 9.4 vs. 25.6 +/- 11.6 ml/min/m2, respectively). The higher mean arterial pressure and lower mean blood flow resulted in higher forearm vascular resistance in the patients than in the controls (132 +/- 61 vs. 83.8 +/- 47 mmHg/ml/s/m2, respectively, P < 0.01). CONCLUSION: While cardiac output is increased and systemic vascular resistance is decreased in active acromegaly, direct measurement of brachial artery haemodynamics showed lower regional blood flow and increased local resistance relative to healthy controls. These results suggest a heterogeneous distribution of cardiac output in acromegaly.

Acromegaly↗

Effect of Sandostatin LAR on serum leptin levels in patients with acromegaly.

Serum leptin levels are decreased in patients with acromegaly and rise after GH is normalized by surgical treatment. We have evaluated the effect of Sandostatin LAR on leptin levels in acromegalic patients since there are recent data to suggest that somatostatin, in addition to its GH lowering effect, also reduces serum leptin levels in humans. Nineteen patients with active acromegaly were studied. Eleven patients received monthly injection of Sandostatin LAR and eight patients underwent transsphenoidal surgery. Serum concentrations of leptin, GH, IGF-1 and insulin were measured before and after treatment. Serum leptin concentrations were lower in patients with active acromegaly than controls matched for age, sex and body mass index (BMI) [2.79 microg/l (2.60) vs. 4.41 microg/l (5.07); median (inter-quartile range); P < 0.01]. A positive correlation between serum leptin concentrations and BMI was observed in the controls (r = 0.46, P < 0.05) but not in the acromegalic patients before treatment (r = 0.32, ns). In the group of patients treated with Sandostatin LAR, a marked reduction in GH and IGF-1 was achieved by week 8 and GH and IGF-1 remained suppressed throughout the 6 months of treatment. There was no change in BMI. A significant increase in leptin levels only became evident after 6 months of treatment [2.99 microg/l (2.60) vs. 4.21 microg/l (3.84), P < 0.05]. Leptin levels also significantly increased after transsphenoidal surgery [3.05 microg/l (5.73) vs. 5.19 microg/l (4.93), P < 0.05]. The positive correlation between serum leptin concentrations and BMI was restored in acromegalic patients both after treatment with Sandostatin LAR (r = 0.62, P < 0.05) and after surgery (r = 0.81, P < 0.05). Leptin concentrations were decreased in patients with active acromegaly and lowering GH by either Sandostatin LAR or transsphenoidal surgery led to an increase in leptin concentrations.

Acromegaly↗

Bone metabolism and body composition in Japanese patients with active acromegaly.

OBJECTIVE: Skeletal involvement is a common clinical feature in acromegalic patients. Although several recent reports are available concerning bone mineral density (BMD) in acromegaly, the controversy still exists as to whether BMD of acromegalic patients is increased or not. The present study was performed to examine biochemical bone metabolic indices and BMD as well as body composition in 26 Japanese patients with active acromegaly and 26 control subjects matched for age, sex, race and height in a cross-sectional study. MEASUREMENTS: BMD of the lumbar spine and femoral neck, as well as body composition, was measured by dual-energy X-ray absorptiometry. Mid-radial BMD was measured by single-photon absorptiometry. We also determined serum levels of IGF-I, IGFBP-3 and osteocalcin (OC) as well as urinary levels of deoxy-pyridinoline (D-Pyr) and CrossLaps. RESULTS: Percent lean body mass was increased and percent fat mass was decreased in the acromegalic patients compared to control subjects. Serum levels of OC, as well as urinary levels of D-Pyr and CrossLaps, were significantly higher in acromegalic patients compared to control subjects (9.8 +/- 1.2 vs. 5.7 +/- 0.77 for OC; 11.8 +/- 1.66 vs. 5.0 +/- 0.49 for D-Pyr; 437.6 +/- 68.4 vs. 156.5 +/- 39.6 for CrossLaps). Z scores of BMD at mid-radius as well as lumbar spine and femoral neck were significantly higher in acromegalic patients compared to control subjects (1.086 +/- 0.311 vs. -0.060 +/- 0.274 for mid-radius; 1.022 +/- 0.280 vs. 0.319 +/- 0.165 for lumbar spine; 1.292 +/- 0.347 vs. 0.232 +/- 0.264 for femoral neck). CONCLUSIONS: The present study revealed that a decrease in percent fat mass and an increase in percent lean body mass were observed in Japanese patients with active acromegaly. Bone mineral density at all sites and bone metabolic markers were also increased in acromegaly. The present findings provide additional evidence that the GH/IGF-I axis might play an important role in the maintenance of bone mass as well as the regulation of body composition in Japanese adults.

Absorptiometry, Photon↗

Serum lipoprotein changes following IGF-I normalization using a growth hormone receptor antagonist in acromegaly.

OBJECTIVE: Active acromegaly is associated with altered lipid metabolism. The purpose of this study was to investigate the effect of serum IGF-I normalization on serum lipoproteins and insulin, in patients with acromegaly receiving the GH receptor antagonist pegvisomant. PATIENTS: Twenty patients (9 male, mean age 58.7 years, range 28-79) with active acromegaly (baseline serum IGF-I > 130% the age-related upper limit of normal) received pegvisomant and achieved a normal serum IGF-I [585.2 +/- 54.3 (mean +/- SEM) to 169.2 +/- 13.9 ng/ml, P < 0.0001]. MEASUREMENTS: Total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein B (apo B), apolipoprotein A1 (apo A1), lipoprotein a [Lp(a)] and insulin were measured in a single batch analysis on samples obtained at baseline and the first occasion of serum IGF-I normalization. Low-density lipoprotein (LDL) was calculated using the Friedewald formula. Paired analysis was performed using Student's paired t-test and the Wilcoxon signed rank test. RESULTS: Normalization of serum IGF-I resulted in an increase in TC (5.0 +/- 0.3 to 5.7 +/- 0.4 mmol/l, P = 0.0068), an increase in LDL (3.0 +/- 0.25 to 3.7 +/- 0.31 mmol/l, P = 0.0093) and an increase in apo B (110.6 +/- 7.76 to 127.1 +/- 8.86 mg/l, P = 0.014). TC and LDL increased in all but four patients. Despite a significant fall in fasting insulin levels (9.9 to 8.3 mU/l, range 8.85-19.8 to 6.33-11.6, P < 0.001) and insulin resistance (2.7 to 1.9, range 1.2-10.4 to 1-6.2, P < 0.001), mean serum TG and HDL levels were unaffected by IGF-I normalization. The protein component of HDL, apo A1, increased (153 +/- 4 to 166.4 +/- 5.43 mg/l, P = 0.026) and Lp(a) declined (median 342 to 235 mg/l, range 60-1013 to 74-671), P = 0.0035). Baseline serum TC and LDL were below the age- and sex-matched mean population value but after normalization of serum IGF-I the distribution of serum TC and LDL values was similar to that of the general population. CONCLUSIONS: Active acromegaly is associated with lowered mean serum TC and LDL. Successful management using pegvisomant increases lowered baseline serum TC and LDL levels, restoring the distribution of values to that of the general population, and improves insulin resistance. These findings are consistent with the reported lipoprotein changes following GH administration to normal and GH-deficient individuals.

Acromegaly↗

Postoperative persistent thyrotrophin releasing hormone-induced growth hormone release predicts recurrence in patients with acromegaly.

OBJECTIVE: To assess the predictive value of postoperative thyrotrophin releasing hormone (TRH)-induced GH responsiveness in relation to (late) postoperative outcome in patients in remission after surgery for acromegaly. PATIENTS: and methods One hundred and twenty-nine patients underwent surgery for acromegaly in our institution between 1977 and 1996. TRH tests and oral glucose tolerance tests (GTT) were performed and serum IGF-I concentrations were measured pre- and postoperatively and during follow-up. Criteria for postoperative remission were a mean serum GH concentration < 5 mU/l and/or serum GH after an oral glucose tolerance test < 1 mU/l immunofluorometric assay (IFMA) or < 2.5 mU/l (radioimmunosassay), together with a normal serum IGF-I concentration. RESULTS: Preoperatively, the TRH-induced GH response was highly variable, with gradual overlap between 'nonresponders' and 'responders'. Arbitrarily defined as a doubling of serum GH concentration, 45.6% of patients were 'responders' to TRH. GH response after TRH injection was significantly correlated to the TRH-induced prolactin response but not to preoperative GH concentration or adenoma size. After surgery, remission was achieved in 83 of the 129 patients. Postoperative remission was significantly correlated to mean preoperative serum GH concentration and preoperative glucose-suppressed serum GH but not to tumour class. Seventy-one patients with early postoperative remission were followed without adjuvant treatment for a mean of 9.4 +/- 0.7 years (range 0-23 years). Forty-one of these patients were TRH responsive as defined by at least doubling of the serum GH concentration preoperatively. Of the 71 patients, 12 developed recurrence of disease, as defined by insufficient GH suppression during oral GTT, and elevated IGF-I and mean serum GH concentration. Irrespective of the preoperative response to TRH, the initial postoperative TRH test was predictive of developing disease recurrence with a sensitivity of 75% and a specificity of 100% when an absolute GH increase of 3.75 mU/l was chosen to define paradoxical responsiveness. A stimulated GH 1.6 times basal was predictive of recurrence with a sensitivity of 83% and a specificity of 73%, and 2.1 times basal was predictive with a sensitivity of 75% and a specificity of 80%. None of the 32 patients with postoperative normalization of the preoperatively present TRH-induced GH response, defined as a postoperative GH increase < 3.75 mU/l, developed recurrence of disease, while all nine patients with a GH increase above this level developed recurrence of acromegaly. CONCLUSION: To our knowledge this is the first report which addresses the value of early postoperative TRH-induced GH responsiveness in predicting late surgical outcome using receiver-operating characteristic (ROC) curves to redefine a postoperative paradoxical response instead of arbitrarily chosen criteria. An absolute postoperative GH response of more than 3.75 mU/l was associated with recurrence in all nine patients, while all 32 patients with normalization of previously paradoxical response are still in remission. Our findings from this study demonstrate that the TRH test is a valuable tool in the early identification of patients at risk of developing postoperative recurrence of acromegaly.

Acromegaly↗

Effects of a growth hormone receptor antagonist on bone markers in acromegaly.

OBJECTIVE: Excess GH secretion, as occurs in acromegaly, is associated with abnormalities in bone turnover markers and bone mineral density (BMD). GH administration in GH deficient patients causes an increase in bone turnover. IGF-I mediates many of the metabolic actions of GH, although GH may have direct effects upon bone. In patients with acromegaly who are treated with a GH receptor antagonist, selective blockade of the GH receptor results in a decrease in circulating IGF-I levels in the majority of cases. We hypothesized that, in acromegaly, antagonism of GH receptors would result in a decrease in serum markers of bone turnover, including serum procollagen I carboxy-terminal propeptide (PICP), osteocalcin and N-telopeptide (NTx). DESIGN AND SUBJECTS: Twenty-seven patients with acromegaly were enrolled as part of a multicentre 12-week trial of a GH receptor antagonist and were randomized to placebo (n = 7) or 10, 15 or 20 mg of pegvisomant (n = 20). MEASUREMENTS: Serum markers of bone turnover were determined at baseline and 12 weeks. RESULTS: Baseline bone turnover markers were above the upper limit of normal in 23%, 19% and 32% of subjects for osteocalcin, PICP and NTx, respectively. During the 12-week placebo-controlled period, there were significant decreases in serum markers of bone formation, osteocalcin (-2.2 +/- 0.44 vs. placebo +0.01 +/- 0.39 nmol/l, P = 0.009) and PICP (-23.6 +/- 9.6 vs. placebo +18.1 +/- 12.8 micro g/l, P = 0.022) and a serum marker of bone resorption, NTx (-4.4 +/- 1.4, placebo +1.0 +/- 0.3 nm, P = 0.024). CONCLUSIONS: Using a specific GH receptor antagonist, we found that normalization of IGF-I is associated with rapid reductions in markers of both bone formation and resorption, and that these processes remain coupled. These data confirm the highly significant effects of GH and IGF-I in modulating bone turnover. The independent contributions of GH and IGF-I to these effects and the long-term effects on BMD in this population remain to be determined.

Acromegaly↗

Improved assessment of body cell mass by segmental bioimpedance analysis in malnourished subjects and acromegaly.

BACKGROUND: Estimation of body cell mass (BCM) has been regarded valuable for the assessment of malnutrition. AIM: To investigate the value of segmental bioelectrical impedance analysis (BIA) for BCM estimation in malnourished subjects and acromegaly. METHODS: Nineteen controls and 63 patients with either reduced (liver cirrhosis without and with ascites, Cushing's disease) or increased BCM (acromegaly) were included. Whole-body and segmental BIA (separately measuring arm, trunk, leg) at 50 kHz was compared with BCM measured by total-body potassium. Multiple regression analysis was used to develop specific equations for BCM in each subgroup. RESULTS: Compared to whole-body BIA equations, the inclusion of arm resistance improved the specific equation in cirrhotic patients without ascites and in Cushing's disease resulting in excellent prediction of BCM (R(2) = 0.93 and 0.92, respectively; both P<0.001). In acromegaly, inclusion of resistance and reactance of the trunk best described BCM (R(2) = 0.94, P<0.001). In controls and in cirrhotic patients with ascites, segmental impedance parameters did not improve BCM prediction (best values obtained by whole-body measurements: R(2)=0.88 and 0.60; P<0.001 and <0.003, respectively). CONCLUSION: Segmental BIA improves the assessment of BCM in malnourished patients and acromegaly, but not in patients with severe fluid overload.

Acromegaly↗

[Urinary excretion of hydroxyproline in acromegaly (author's transl)].

Urinary excretion of hydroxyproline was examined with the Hypronosticon test in 25 patients with acromegaly (13 men, 12 women) and 15 healthy persons. At the same time, plasma levels and urinary excretion of phosphorus and calcium were also measured. Patients with active acromegaly had a significantly higher urinary hydroxyproline output (32.55 +/- 8.68 mg/24 h m2) than healthy persons (12.12 +/- 2.33 mg/24 h-m2). They also excreted considerably more hydroxyproline than patients with successfully treated acromegaly. Effective treatment was proved by STH levels and good suppressibility by 100 mg glucose. Unsucessfully treated patients, on the contrary, had a raised urinary excretion of hydroxyproline (31.23 +/- 16.61 mg/24 h-m2) and high fasting plasma levels of somatotropic hormone. Hydroxyprolinuria proved, therefore, of value in assessing the development and treatment of acromegaly.

Acromegaly↗

Acromegaly in a family without a mutation in the menin gene.

Familial pituitary tumors are rare. Only 45 cases in 20 families with acromegaly have been reported. A third of the cases (30%) is related to multiple endocrine neoplasia type 1 (MEN 1). We report two cases of acromegaly in one family with pituitary macroadenomas. A 46-year-old woman with elevated serum growth hormone (GH) and insulin-like growth factor (IGF-1) and a failure to supress GH in the glucose tolerance test underwent transsphenoidal surgery 4 years ago. Three years later her 24-year-old son also presented with typical signs of acromegaly. A pituitary macroadenoma was identified by MRT and he also underwent transsphenoidal surgery. There were no symptoms of McCune-Albright syndrome or other forms of endocrine hyperfunction in the two patients. In an attempt to identify the molecular etiology of the tumours DNA was extracted from paraffin fixed tissue from both patients. Exon 7 to 13 of the Gsp-protein and exons 1 to 10 of the menin gene were amplified by PCR. Although Gsp mutations have been identified in 40% of somatotroph tumors, direct sequencing of the PCR products showed no mutations in exons 7 to 13 of Gs alpha. Moreover no mutations were found in exons 1 to 10 of the menin gene. Therefore, molecular causes other than Gsp or menin gene mutations have to be considered as the molecular etiology of acromegaly in this family.

Acromegaly↗

Acromegaly due to GHRH-secreting large bronchial carcinoid. Complete recovery following tumor surgery.

A case of acromegaly, secondary to GHRH secretion by a large bronchial carcinoid is reported. A 61-year-old woman presented with typical symptoms and signs of acromegaly for at least 10 years. She suffered from recurrent pneumonias, but repeated chest X-ray examinations failed to demonstrate the bronchial tumor. The diagnosis was confirmed by elevated GH, IGF-1 and GHRH secretion. We have shown an enlarged pituitary gland without focal lesions together with a cerebral meningioma on MRI and the presence of a bronchial carcinoid tumor. The latter was confirmed by histology carried out after bronchoscopy and tumor excision. We observed partial suppression of GH secretion following short-term oral bromocriptine administration in this patient. Surgical removal of the carcinoid tumor resulted in a complete clinical, hormonal and radiological cure of acromegaly. This case of acromegaly due to ectopic GHRH secretion by bronchial carcinoid differs from others described in the literature by an atypical large tumor size, the suppression of elevated GH secretion by oral bromocriptine and a concomitant meningioma.

Acromegaly↗

The German Acromegaly Registry: description of the database and initial results.

UNLABELLED: Patient registries are valuable tools to study long-term morbidity and mortality of rare diseases. Acromegaly is rare (incidence 3-4/mill/year, prevalence 40-70/mill; approx. 300 new patients/yr and up to 5700 patients in Germany). Diagnostic and therapeutic possibilities have considerably improved, but treatment results remain often unsatisfactory. The main cause is residual disease activity after surgery, most importantly due to invasive macroadenomas. The German Acromegaly Registry is an initiative of the Pituitary Study Group of the German Endocrine Society (DGE). Formally established in January 2003 by the Board of the DGE, long-term financial support is guaranteed by an unrestricted grant from Novartis Pharma GmbH to the DGE. The registry cooperates closely with the United Kingdom and the Austrian registries. The aim of the German Acromegaly Registry is to establish a database of sufficient epidemiological strength in order to (1) document co-morbidity and mortality, (2) provide data on diagnostic and therapeutic procedures/effectiveness, (3) enable comparison of procedures in different national centres, (4) provide information for patient support groups/interaction with health care providers, (5) enable comparison with other national registries within Europe. The registry has at present 82 participating centres, and 42 have included patients (20 university clinics, 8 non-university hospitals, 14 centres in private practice). The database aims to include all acromegalic patients in Germany who are cared for and treated at present. Up to December 2005 1543 patients have been entered in a retrospective manner. Data collection is by external monitoring by highly trained study nurses who visit the individual centres. Inclusion is planned to continue at a rate of 500 per year. Starting in 2005 centres are revisited every 3 years at a rate of 500 per year (prospective phase of the registry). Quality of the data has been validated by an independent monitoring team which demonstrated high data concordance. CONCLUSIONS: Initial results of the German Acromegaly Registry show that it was possible to include a large number of patients within 3 years into the registry. Data quality has been validated and shown to be satisfactory. Therefore, the registry will be a useful tool to study long-term morbidity and mortality in a large series of patients.

Acromegaly↗

Acromegaly with 'normal' serum growth hormone levels. Clinical features, diagnosis and results of transsphenoidal microsurgery.

Among 216 consecutive patients with growth hormone secreting pituitary adenomas who underwent primary neurosurgical treatment at the University of Erlangen-Nürnberg, 8 cases of acromegaly with 'normal' basal growth hormone levels (less than or equal to 5 ng/ml) were seen. They all had the typical clinical features of acromegaly, exhibited an abnormal growth hormone secretion following an oral glucose load, and had markedly elevated somatomedin C levels. The GRH- and TRH/GnRH-tests were not found helpful in establishing the diagnosis. Neuroradiology could demonstrate a pituitary adenoma in all of the patients. Following transsphenoidal microsurgical resection of the tumours, growth hormone secretion during oral glucose tolerance testing was normalised in 7 of the 8 patients. Immunohistology and explant culture studies documented growth hormone secreting pituitary adenomas in all cases. The authors conclude that even the finding of repetitive 'normal' (less than or equal to 5 ng/ml) serum GH levels does not exclude active acromegaly and when the clinical diagnosis of acromegaly is suspected, dynamic endocrine testing may reveal abnormal secretion patterns of GH in these cases. Transsphenoidal microsurgical resection of a pituitary adenoma offers a good chance of clinical and endocrinological remission in these cases.

Acromegaly↗

[Diagnosis in acromegaly. Insulin-like growth factor as a parameter of activity].

The peripheral actions of growth hormone (STH) are mediated by somatomedins or "insulin-like growth factors" (IGF I and II). In untreated acromegaly (n = 24) IGF I was always found increased, IGF II, however, was unchanged. The mean IGF-I-level (+/- SEM) was 553 +/- 75 (range 319-1066) ng/ml in active acromegaly and 193 +/- 10 (range 120-300) ng/ml in control persons. The corresponding IGF-II-values were 533 +/- 38 (range 187-720) and 647 +/- 21 (range 400-900) ng/ml. After treatment of acromegaly IGF I followed changes of the basal STH level with a delay of 4-8 weeks independent of the mode of treatment. This was in contrast to behaviour of IGF II. When STH was suppressible below 1 ng/ml after oral administration of 100 g glucose IGF I was never increased. STH after glucose of more than 5 ng/ml was always associated with increased IGF I. STH values between 1 and 5 ng/ml after glucose were combined with IGF-I-increases in 3 out of 6 cases. Thus, IGF I represents a valuable diagnostic criterion for assessment of activity of acromegaly, particularly in borderline cases, in contrast to IGF II. The criterion of normal somatotrophic function is suggested to be suppressibility of STH level below 1 ng/ml after oral administration of 100 g glucose.

Acromegaly↗