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PubMed1991

Acromegaly due to ectopic growth hormone-releasing hormone secretion by a bronchial carcinoid tumour. Dynamic hormonal responses to various stimuli.

Ectopic GHRH is a relatively uncommon cause of acromegaly, which should be differentiated from pituitary adenoma, in order to avoid damage to the pituitary gland from unnecessary interventions. We report here on a 66-year-old man with acromegaly due to a GHRH-secreting bronchial carcinoid tumour, who recovered completely following removal of the tumour. His hormonal status was studied before and after the operation. Basal GH, GHRH, IGF-I and PRL levels, as well as plasma GH response to glucose load and TRH administration were abnormal before the operation, and became normal thereafter. The somatostatin analogue SMS 201-995 was found to be a potent inhibitor of the ectopic GHRH and the GH secretion (greater than 500 to 42 ng/l and 15.4 micrograms/l to 0.8 microgram/l, respectively). The effect on GHRH proved to be due to direct effect of somatostatin on the tumour cells, as demonstrated in tissue culture studies. A mixed meal was found immediately to suppress GHRH levels without such an effect on GH secretion. We conclude that the neuroendocrine tests usually practised in acromegaly cannot differentiate between ectopic GHRH secretion and pituitary adenoma. High plasma GHRH levels may serve as a diagnostic test for excessive GHRH production, which is almost always ectopic. These high levels are suppressible by somatostatin and a mixed meal.

Acromegaly↗
PubMed1992

Bromocriptine treatment over 12 years in acromegaly: effect on growth hormone and prolactin secretion.

It is not known whether bromocriptine treatment in acromegaly can be implemented for a life-long period. To elucidate this problem, the secretory GH and PRL states of 12 patients with acromegaly were determined, before bromocriptine treatment, under therapy (15.0 +/- 6.8 mg/day for 12 +/- 3 years; mean +/- SD) and during two-weeks long drug withdrawal after long-term treatment, respectively. Before therapy, all patients showed a non-sufficient GH suppression after oral glucose load (greater than 2 micrograms/l), whereas under dopaminergic treatment the post-glucose GH levels of three patients fell below 2 micrograms/l; normal IGF-I concentrations were found in five patients. However, under bromocriptine, only two patients showed GH suppressions below 2 micrograms/l following glucose, accompanied with normal IGF-I levels. During bromocriptine withdrawal, GH secretion at 60 min in the oral glucose tolerance test increased significantly (17.0 +/- 15.5 vs 5.7 +/- 5.2 micrograms/l; p less than 0.01); the mean IGF-I level rose from 2.1 +/- 0.8 to 4.9 +/- 2.2 kU/l (p less than 0.01). IGF-I was normal during bromocriptine cessation in only one patient; none of the 12 patients showed a GH suppression below 2 micrograms/l after oral glucose load. Under dopaminergic treatment hyperprolactinemia could not be detected. In conclusion, bromocriptine led to a stable suppression of both GH hypersecretion and--if present--concomitantly elevated PRL levels. Severe side effects or a further tumor growth could not be observed. Thus, the data of the longest follow-up investigation that has so far been published indicate that effective life-long bromocriptine therapy seems to be possible in selected patients with acromegaly.

Acromegaly↗
PubMed1993

Evaluation of acromegaly by measurement of 24-hourly urinary growth hormone excretion.

Twenty-four hourly urinary growth hormone excretion (24-h uGH) has been quantified using a combination of ultrafiltration and conventional immunoradiometric assay. Twenty-four hourly uGH was measured in 20 normal adults and in 42 patients with acromegaly (9 untreated, 28 treated but with above-normal IGF-I levels, and 5 treated and cured). The means and ranges were as follows: 3.7 (1-9) ng/24 h for normals and 160 (40-540), 66 (2-380) and 5.2 (4-8) ng/24 h for the three groups of acromegalic patients, respectively. Ten patients with pituitary adenomas without acromegaly had 24-h uGH within the normal range. Twenty-four hourly uGH therefore gives a clear differentiation between controls and untreated patients. Log-transformed values for subjects with acromegaly showed significant correlations between 24-h uGH and levels of IGF-I (r = 0.63, p < 0.01), fasting plasma GH (r = 0.92, p < 0.001) and plasma GH after glucose loading (r = 0.85, p < 0.001). Twenty-four hourly uGH was also determined in three acromegalic patients before and during SMS 201-995 therapy. Twenty-four hourly uGH reflected the corresponding changes in mean levels for hourly sampling over 12 h of plasma GH and IGF-I and in clinical signs after 3-6 months of therapy. The results of this study indicate that 24-h uGH is an accurate indicator of GH secretion in acromegalic patients and could therefore be used both in diagnosis and in monitoring the progress of therapy in these patients.

Acromegaly↗
PubMed1993

Effect of long-term treatment with bromocriptine on the growth hormone response to galanin in patients with acromegaly.

Galanin elicits growth hormone (GH) secretion in normal man but may cause a paradoxical fall of GH in acromegaly. The aim of our study was to investigate the effects of long-term treatment with bromocriptine on the galanin-induced GH decrease in acromegalic subjects. Six acromegalic patients (5F, 1M) chronically treated with bromocriptine underwent in randomized order: (i) iv infusion of 100 ml saline from 0 to 45 min and (ii) iv infusion of synthetic porcine galanin (0.5 mg in 100 ml saline) from 0 to 45 min. In acromegalic patients, GH values fell from baseline (10.5 +/- 2.7 micrograms/l) to a mean nadir of 6.9 +/- 2.2 micrograms/l after galanin infusion (57.8 +/- 9.4% vs basal levels). Saline infusion did not cause any change in circulating GH levels. The mean change in GH values with respect to baseline after galanin in these subjects significantly differed from that observed after saline from time 15 to 90 min. Serum prolactin levels were not significantly affected by galanin. Our results confirm that the dose of galanin capable of increasing plasma GH levels in normal subjects can decrease GH values in patients with acromegaly. Moreover, our data show that this paradoxical GH decrease induced by galanin can also be observed in patients chronically treated with bromocriptine. Therefore, the paradoxical decreasing effect of galanin on plasma GH levels in acromegaly seems not to be mediated via dopaminergic pathways.

Acromegaly↗
PubMed1993

Skeletal muscle sodium and potassium changes after successful surgery in acromegaly: relation to body composition, blood glucose, plasma insulin and blood pressure.

The aim of this study was to investigate the skeletal muscle sodium/potassium (Na/K) ratio in acromegaly before and 1 year after trans-sphenoidal removal of a growth hormone (GH)-secreting pituitary adenoma. Muscle biopsies were taken and skeletal muscle electrolytes, body composition, glucose, insulin and blood pressure were studied. Fasting blood glucose and plasma insulin levels, but not blood pressure, were higher in acromegalic patients (N = 9) than in controls (N = 6). The skeletal muscle potassium content was higher (p < 0.01) but the sodium content and the Na/K ratio were lower (p < 0.05 and p < 0.001, respectively) in untreated patients with acromegaly as compared to weight-matched healthy controls. Elevated GH, glucose and insulin levels normalized after surgery. Blood pressure remained unchanged. The total body potassium content, the lean body mass and the total body water content decreased and the body fat content increased while the body weight was unchanged. The skeletal muscle potassium content decreased from [medium (range)] 9.8 (9.2-11.5) to 7.7 (5.7-9.5) mmol/100 g wet wt (p < 0.001). The skeletal muscle sodium content increased from 2.8 (2.5-3.9) to 5.1 (4.3-6.7) mmol/100 g wet wt (p < 0.001) and the Na/K ratio increased from 0.28 (0.26-0.38) to 0.56 (0.51-1.18) (p < 0.001) after surgery, which is a higher level than the controls with a Na/K ratio of 0.47 (0.39-0.84) (p < 0.01). These changes seem to be mediated by a decreased GH effect on the Na/K pump after successful trans-sphenoidal surgery in acromegaly.

Acromegaly↗
PubMed1994

McCune-Albright syndrome and acromegaly: clinical studies and responses to treatment in five cases.

We report here five new patients with McCune-Albright syndrome and acromegaly. In the five patients studied (three males and two females aged 18-42 years), acromegaly began before the age of 20 years and was recognized after the diagnosis of fibrous dysplasia, which was polyostotic in three cases and monostotic in two. Bone fibrous dysplasia always involved the base of the skull and in four patients prevented surgical removal of the pituitary adenoma, which was visualized easily by magnetic resonance imaging. Serum growth hormone (GH) levels ranged between 20 and 48 micrograms/l and were not suppressed by an oral glucose load. Thyrotropin-releasing hormone administration produced a paradoxical increase in serum GH levels in all the patients. Four of the five patients had hyperprolactinemia (43-670 micrograms/l). In the sole patient who could be operated on, a typical adenoma with positive immunostaining for GH was incompletely removed and postoperative radiation therapy failed to cure the acromegaly. In two patients, medical therapy with bromocriptine and/or octreotide was partially or totally ineffective whatever the dose (up to 1.5 mg per day) and duration (2-4 years) of octreotide treatment.

Acromegaly↗
PubMed1995

Octreotide, but not bromocriptine, increases circulating insulin-like growth factor binding protein 1 levels in acromegaly.

Twenty-three patients with active acromegaly underwent serum sampling for growth hormone (GH), insulin and insulin-like growth factor binding protein 1 (IGFBP-1) after placebo or single doses of octreotide or bromocriptine. Integrated 24-h serum GH levels decreased by 90% after octreotide and 49% after bromocriptine. A statistically significant correlation between the course of GH levels after octreotide and bromocriptine was observed (p < 0.001). Octreotide, but not bromocriptine, induced a significant increase in integrated 24-h serum IGFBP-1 levels to 37.4 times the baseline values. Bromocriptine caused a non-significant increase in integrated 24-h serum IGFBP-1 levels, which argues against a direct regulatory effect of GH on IGFBP-1 production in acromegaly. In conclusion, octreotide induces in acromegaly the production of IGFBP-1, which occurs independently of the number of somatostatin receptors on the GH-secreting pituitary adenoma. The supposed inhibitory effect of IGFBP-1 on the biological effect of IGF-1 might result in an additional clinical benefit in acromegalic patients as compared to treatment directed at the pituitary level.

Acromegaly↗
PubMed1999

Differing effects on gall-bladder motility of lanreotide SR and octreotide LAR for treatment of acromegaly.

BACKGROUND: Octreotide treatment may be associated with gall stone development in up to 50% of patients with acromegaly. Two new sustained-release formulations of somatostatin analogue have been recently developed: lanreotide SR (Somatuline) and octreotide LAR (Sandostatin LAR). The incidence of gall-stone development in patients receiving these drugs has been shown to be less than 20%, but the duration of follow-up has been limited. OBJECTIVE: Prospectively to assess and compare the effects of the two new long-acting somatostatin agonists on gall bladder motility in patients with acromegaly. METHOD AND PATIENTS: Eleven patients with active acromegaly were studied. Three patients had asymptomatic gall stones at the start of the study. Ultrasound scans were performed before commencement of the treatment, and repeated during treatment with lanreotide SR and octreotide LAR. The presence of gall stones, fasting gall bladder volume (FV), residual volume (RV) and maximal percentage gall bladder emptying were measured. RESULTS: One patient developed asymptomatic small gall stones after treatment with octreotide LAR for 4 months. FV and RV were both significantly larger when patients received treatment with lanreotide SR or octreotide LAR compared with pretreatment values (P<0.05 for both). Maximal percentage gall bladder emptying was significantly reduced in patients receiving lanreotide SR or octreotide LAR compared with pretreatment (P<0.01), but was less impaired in patients receiving lanreotide SR than in those receiving octreotide LAR (P<0.01). CONCLUSIONS: Gall bladder motility is impaired in patients receiving either of these new long-acting preparations, and long-term follow-up will be needed to establish the true incidence of gall stones.

Acromegaly↗
PubMed2001

Conventional pituitary irradiation is effective in normalising plasma IGF-I in patients with acromegaly.

OBJECTIVE: For patients in whom acromegaly persists despite pituitary surgery, conventional pituitary irradiation represents an additional treatment option. A 30-60% cure rate is described in the literature, but these studies did not utilise strict rules of remission, such as "safe" GH levels <2.5 microg/l, and age-adjusted normal IGF-I levels. DESIGN AND METHODS: We report the outcome of 41 patients with acromegaly who received pituitary conventional external irradiation. The median follow-up time was 12.8 years (3.7-43.4 years) post-radiotherapy. RESULTS: The median pre-irradiation GH level was 31.0 microg/l (7.0-210 microg/l). Information on IGF-I levels was only available for 6 patients prior to therapy. Utilising strict rules of remission, one-third (14/41) of our patients had normal biochemical parameters, i.e. "safe" GH (0.5 microg/l (range 0.2-1.6 microg/l)) and normal age-adjusted IGF-I levels (multiple of upper limit of normal range (xULN); 0.45 (0.2-1.0)) at the end of the follow-up period. An additional 9 patients achieved normal levels with adjunctive drug therapy. Furthermore, disease activity was reduced in a considerable proportion of the 18 patients who did not achieve normal biochemical levels (GH: 3.6 microg/l (1.9-15.7 microg/l); xULN of IGF-I: 1.6 (0.9-2.6)). In retrospect, remission is unlikely in patients who had a GH level greater than 52 microg/l (mean+2 s.d. of cured patients) prior to radiotherapy. In addition to the 12 patients with pre-irradiation pituitary functional deficiency, another 11 patients developed symptoms of panhypopituitarism during the 3-year period following irradiation. Within a 6-year period, partial pituitary insufficiency was observed in a further 7 patients, thus necessitating hormone substitution treatment. CONCLUSION: Using strict rules of remission, in our cohort we found both a normalisation of IGF-I and safe GH levels in 34% of patients treated for acromegaly with conventional irradiation therapy.

Acromegaly↗
PubMed2001

Successful treatment of resistant acromegaly with a growth hormone receptor antagonist.

BACKGROUND/OBJECTIVE: Pegvisomant is a pegylated analogue of human GH and functions as a potent GH receptor antagonist. This novel mode of action gives it the potential to achieve biochemical control in patients with acromegaly whose disease activity cannot be satisfactorily controlled by conventional therapy. We have documented the clinical details of seven patients with residual active acromegaly after surgery and/or radiation therapy successfully treated with pegvisomant. PATIENTS/METHODS: Seven patients (four male, mean age 47 years, range 34-67 years) who participated in two separate clinical trials of pegvisomant have completed 2 years (four patients) or 1 year (three patients) of treatment. All had active acromegaly (mean serum GH level >5 mU/l; serum IGF-I elevated for age) that could not be controlled with standard medical therapy (dopamine agonist and/or a somatostatin analogue) following appropriate primary treatment with surgery and/or radiotherapy. RESULTS: On a median dose of 20 mg/day (range 15-40) pegvisomant, serum IGF-I fell from a mean of 920+/-351 ng/ml (s.d.) to 258+/-91 ng/ml and was normalised in all seven patients. These changes were associated with improvements in soft tissue enlargement and general well being. Treatment was well tolerated and no change in pituitary tumour size was evident on MRI scans performed every 6 months. CONCLUSIONS: Treatment with pegvisomant is safe and efficacy is maintained after 2 years. Serum IGF-I may be normalised in patients who are refractory to conventional therapy.

Acromegaly↗
PubMed2003

Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant.

AIM AND METHOD: Insulin resistance leading, in some cases, to glucose intolerance is an important contributory factor to the cardiovascular morbidity and mortality associated with acromegaly. The aim of this study was to document changes in insulin sensitivity (IS) in a group of seven patients with acromegaly (three male, four female, mean+/-s.d. age 59+/-13 Years) treated initially with a stable dose of depot octreotide (OT; median dose 30 mg four times weekly, range 10-30 mg) for a median of 18 Months (range 16-19 Months) and who were then transferred to treatment with pegvisomant (median dose 15 mg daily, range 10-20 mg) for a median of 8 Months (range 7-9 Months). IS was assessed by homeostatic model assessment (HOMA) using fasting glucose and insulin concentrations and by a short insulin tolerance test (sITT). Body composition was assessed by dual energy X-ray absorptiometry. RESULTS: Mean+/-s.d. serum IGF-I concentrations during therapy with OT and with pegvisomant were not statistically different (283+/-119 ng/ml on OT vs 191+/-39 ng/ml on pegvisomant (P=0.4)). However, mean+/-s.d. fasting plasma glucose fell from 6.2+/-1.0 mmol/l on OT to 5.2+/-0.6 mmol/l on pegvisomant (P=0.017) and was lower on pegvisomant in all seven patients. In four patients, fasting plasma glucose fell from values diagnostic of diabetes mellitus or impaired fasting glucose on OT to within the normal range on pegvisomant. Mean+/-s.d. peripheral IS (by sITT) increased from 139+/-39 micromol/l per min on OT to 169+/-59 micromol/l per min on pegvisomant (P=0.037). Mean+/-s.d. IS (by HOMA %S) was unchanged over the course of the study (149.1+/-43.7% on OT vs 139.9+/-76.6% on pegvisomant, P=0.28). Mean+/-s.d. pancreatic beta-cell secretory function (HOMA %B) improved significantly on pegvisomant compared with OT (49.4+/-19.2% vs 82.4+/-43.5%, P=0.01). No statistically significant change in total fat (P=0.3), % fat (P=0.28) or circulating non-esterified fatty acids (P=0.35) was observed. CONCLUSIONS: IS and glucose tolerance improved in patients converted from OT therapy to pegvisomant, without a change in body composition and even when serum IGF-I concentrations remained equally well controlled. This may be an important factor in the choice of medical therapy for patients with acromegaly.

Acromegaly↗
PubMed2006

Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance.

OBJECTIVE: We aimed to investigate the efficacy of pegvisomant in patients with acromegaly resistant to long-term (> or = 24-month), high-dose treatment with octreotide-LAR (40 mg/month) or lanreotide (120 mg/month). DESIGN: This was an open, prospective study. SUBJECTS AND METHODS: We studied 16 patients with acromegaly (nine women; aged 28-61 years). The main outcome measures were IGF-I levels, blood pressure, glucose tolerance and safety (liver function and tumor size). Pegvisomant was given at doses of 10-40 mg s.c. daily. Dose titration was performed every month by IGF-I assay. RESULTS: Three patients spontaneously stopped pegvisomant treatment after 6-9 months because of poor compliance; from the measurement of serum pegvisomant, another patient was found not to inject herself properly. After 6 months, IGF-I levels decreased by 63 +/- 19% (767.8 +/- 152.9 vs 299.8 +/- 162.9 microg/l, P < 0.0001, t-test); serum IGF-I levels normalized in 57%. After 12 months, IGF-I levels normalized in nine (75%) patients and were reduced by over 50% in another three (25%). The mean tumor volume remained stable during the study (1198 +/- 1234 vs 1196 +/- 1351 mm(3), P = 0.37): it did not change ( +/- 25% vs basal) in nine patients, increased by 39.4% and 40.8% in two and decreased by 30.8-46.5% in four. The total/high-density lipoprotein (HDL):cholesterol ratio (from 4.4 +/- 1.0 to 3.7 +/- 0.6, P = 0.0012), glucose levels (from 5.6 +/- 1.2 to 4.4 +/- 1.4 mmol/l, P = 0.026), insulin levels (from 12.4 +/- 6.7 to 8.1 +/- 3.0 mUl/l, P = 0.0023) and homeostasis model assessment (HOMA) index (from 3.4 +/- 2.1 to 1.9 +/- 1.0, P = 0.0017) decreased. CONCLUSIONS: Treatment for 12 months with pegvisomant normalized IGF-I levels, and improved cardiovascular risk parameters and insulin sensitivity in patients with acromegaly resistant to long-term, high-dose treatment with somatostatin analogs. The tolerance of treatment was good.

Acromegaly↗
PubMed2006

Ghrelin test for the assessment of GH status in successfully treated patients with acromegaly.

OBJECTIVE: Posttreatment assessment of disease activity and definition of cure of acromegaly, using measurement of GH secretion, remains problematic. Furthermore, with our efforts to achieve tight biochemical control of the disease it is foreseeable that a proportion of patients may be rendered GH deficient, thus requiring testing for GH deficiency. The aim of our study was to evaluate residual GH secretion in cured patients with acromegaly. DESIGN AND METHODS: At baseline, circulating GH, IGF-I, IGFBP-3, leptin and lipid (cholesterol and tri-glycerides) levels were measured in 33 acromegalic patients nine years after treatment with surgery of whom 6 were additionally irradiated. Two tests were performed: the GH suppression test--oral glucose tolerance test (OGTT) and the GH provocation test--ghrelin test (1 microg/kg i.v. bolus) and the results were compared with 11 age- and sex-matched control subjects. RESULTS: According to the consensus criteria (normal IGF-I levels and post-OGTT GH nadir <1 microg/l), 21 treated acromegalic patients were cured, 6 had discordant IGF-I and GH nadir values during OGTT, while 6 had persistent acromegaly. After the GH provocative test with ghrelin (cut-off for severe GH deficiency is GH <3 microg/l), we detected 9 severely GH deficient patients (GHD) among 21 cured acromegalic patients. Mean GH peak (+/-s.e.m.) response to the ghrelin test in GHD acromegalics was significantly lower compared with acromegalics with sufficient GH secretory capacity and control subjects (1.2 +/- 0.2 microg/l vs 20.1 +/- 2.4 microg/l vs 31.1 +/- 2.5 microg/l respectively, P<0.0001). Mean IGF-I and IGFBP-3 levels were not different between GHD and GH-sufficient cured acromegalics. Leptin levels and body mass index (BMI) were significantly higher in GHD male acromegalics compared with GH-sufficient male acromegalics. GHD female acromegalics tended to have higher BMIs while leptin levels were not different. CONCLUSIONS: The assessment of residual GH secretory capacity by the GH provocation test is necessary in the long-term follow-up of successfully treated acromegalics since a large proportion of these patients are rendered GH deficient.

Acromegaly↗
PubMed2006

GH deficiency in patients irradiated for acromegaly: significance of GH stimulatory tests in relation to the 24 h GH secretion.

BACKGROUND: Radiotherapy for pituitary adenomas frequently leads to GH deficiency (GHD). The characteristics of GH secretion in GHD induced by postoperative radiotherapy for acromegaly are not known. HYPOTHESIS: In the long term, stimulated and spontaneous GH release is not different between patients with GHD treated by postoperative radiotherapy for acromegaly or for other pituitary adenomas. DESIGN/SUBJECTS: We compared the characteristics of basal and stimulated GH secretion in patients with GHD, who had previously received adjunct radiotherapy after surgery for GH-producing adenomas (n=10) vs for other pituitary adenomas (n=10). All patients had a maximal GH concentration by insulin tolerance test (ITT) of 3 microg/l or less, compatible with severe GHD. Mean time after radiation was 17 and 18.7 years, respectively. Stimulated GH release was also evaluated by infusion of growth hormone-releasing hormone (GHRH), GHRH-arginine and arginine, and spontaneous GH by 10 min blood sampling for 24 h. Pulse analyses were performed by Cluster and approximate entropy. OUTCOMES: There were no differences between both patient groups in stimulated GH concentrations in any test. Spontaneous GH secretion was not different between both patient groups, including basal GH release, pulsatility and regularity. Pulsatile secretion was lost in two acromegalic and three non-acromegalic patients. Insulin-like growth factor-I (IGF-I) was below -2 s.d. score in nine patients in each group. CONCLUSION: Acromegalic patients treated by surgery and postoperative radiotherapy with an impaired response to the ITT do not differ, in the long term, in GH secretory characteristics from patients treated similarly for other pituitary tumors with an impaired response to the ITT. The ITT (or the GHRH-arginine test) is therefore reliable in establishing the diagnosis of GHD in patients treated for acromegaly by surgery and radiotherapy.

Acromegaly↗
PubMed2007

Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: safety and efficacy evaluation from the German Pegvisomant Observational Study.

OBJECTIVE: The GH receptor antagonist pegvisomant is a highly effective new treatment option in acromegaly. The German Pegvisomant Observational Study (GPOS) was started to monitor long-term safety and efficacy of pegvisomant as prescribed in clinical practice. DESIGN: GPOS is an observational, multi-center, surveillance study, which comprises non-interventional data collection. METHODS: Of the 229 patients included in the study, 90.4% had previous pituitary surgery, 43.2% were treated by radiation therapy, and 94.3% had previous medical therapy for acromegaly that had been discontinued mainly due to persistent IGF-I elevation or side effects. The intention-to-treat population included 177 patients with at least one post-baseline efficacy measurement. RESULTS: IGF-I levels decreased from 1.75+/-0.91-fold the upper limit of normal at baseline to 1.05+/- 0.62 at the 6-month visit, 0.96+/-0.60 at the 12-month visit, and to 0.89+/-0.41-fold after 24 months (P<0.0001). Mean duration of pegvisomant therapy was 51.8+/-35.8 weeks (median=51.9 weeks). IGF-I was normalized in 64.4% at 6 months with a median dose of 15.0 mg/day, in 70.9% at 12 months, and in 76.3% at 24 months. Fasting glucose levels improved from 114.4+/-45.9 to 101.5+/- 42.8 mg/dl after 6 months (P<0.01) and to 100.6+/-33.2 mg/ml after 12 months (P<0.01). General physical condition measured by specific signs and symptoms score improved significantly. Adverse events occurring in >1% were injection site reactions in 7.4%, elevated liver enzymes (>3 times of normal) in 5.2% (3.1% spontaneously normalized during continued treatment), reported increase of pituitary tumor volume in 5.2% (which was verified in 3.1%), and headache in 1.7%. CONCLUSIONS: Pegvisomant is generally well tolerated with a safety profile similar to that reported in clinical trials and can effectively reduce IGF-I in patients with acromegaly refractory to conventional therapy.

Acromegaly↗
PubMed1979

Abnormal growth hormone responses to CB-154 and thyrotropin-releasing hormone (TRH) in patients with acromegaly.

CB-154 (2-Br-alpha-ergocriptine) stimulates growth hormone (GH) release in normal subjects. In acromegaly, however, this agent often decreases plasma GH level paradoxically. In order to examine the mechanism of the so-called "paradoxical decrease" in plasma GH with CB-154, GH responses to CB-154 were compared with GH responses to thyrotropin-releasing hormone (TRH), arginine, and luteinizing hormone-releasing hormone (LH-RH) in 20 cases of acromegaly. CB-154, as well as L-dopa, elicited decrease in GH in those patients whose GH secretion was more responsive to TRH and less responsive to arginine. These results suggest that, like L-dopa, CB-154 has similar dual actions of TRH antagonistic GH decrease and GH-RF (GH-releasing factor) facilitative GH increase. Moreover, it was speculated from this study that CB-154 has no significant effect on LH-RH release. The value of (increase ratio of GH on TRH)/(increase ratio of GH on arginine) can be used as an index for the indication of chronic CB-154 therapy in patients with acromegaly.

Acromegaly↗
PubMed1997

A risk-benefit assessment of octreotide in the treatment of acromegaly.

Acromegaly was the first pituitary disease to be recognised as a clinical entity, although initially it was not clear whether the eosinophilic adenomas causing pituitary enlargement were causative or just a manifestation of the syndrome itself. Following the documented clinical improvement of patients with acromegaly after partial hypophysectomy, it was proven that the pituitary adenomas were aetiological. The treatment of acromegaly has changed during the last decades; the introduction of the somatostatin (SMS) analogue octreotide has had major implications. Octreotide was the first SMS analogue to become available for clinical use. It is generally well tolerated, but is associated with the development of gallstones in 15 to 20% of patients. Other adverse effects include transient injection-site pain, abdominal, diarrhoea, gastritis (long term therapy) and loss of scalp hair. No long haematological or biochemical adverse effects have been reported. Desensitisation to the beneficial effects of octreotide therapy is highly unusual. A long-acting formulation of octreotide is being studied, and should be available by the end of 1997.

Acromegaly↗
PubMed2004

Pharmacological therapy for acromegaly: a critical review.

The treatment of acromegaly has changed considerably over the last few decades. In the late 1970s, the introduction of the dopamine receptor agonists made it possible to reduce growth hormone (GH) secretion by somatotropinomas for the first time. Thereafter, the introduction of the somatostatin analogues in the early 1980s had major implications. Recently, the first data on the use of genetically engineered human GH receptor (GHR) antagonists that block GH actions have become available. These GHR antagonists reduce both the biochemical abnormalities of acromegaly, as well as improve clinical signs and symptomatology. In this article we firstly review available data on dopamine agonists. Currently these compounds should be considered in patients with a mixed GH-prolactin secreting pituitary adenoma and/or those in whom pre-treatment insulin-like growth factor (IGF)-I concentrations are below 750 microg/L. We then discuss the somatostatin analogues. These compounds are capable of achieving biochemical control of GH and IGF-I in 50-60% of patients and tumour shrinkage in some 30%. In particular, candidates for treatment with these compounds are those patients who have undergone an unsuccessful transsphenoidal operation or who await the therapeutic effect of external pituitary irradiation. In selected patients primary medical therapy with somatostatin analogues is certainly a feasible option. To date, pegvisomant is the only available member of a new class of drugs that was especially designed to block the GHR. Pegvisomant is the most effective treatment for normalising IGF-I concentrations and appears to have a good safety profile. However, liver function tests should be regularly monitored and tumour size should be closely followed. Finally, we propose a treatment algorithm for acromegaly.

Acromegaly↗