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PubMed1992

Prevalence of gastritis in patients with acromegaly: untreated and during treatment with octreotide.

OBJECTIVE: It has previously been suggested that acromegalic patients treated with the somatostatin analogue octreotide invariably have chronic gastritis. We have examined the prevalence of gastritis in a large group of acromegalic patients, untreated and during treatment with octreotide. DESIGN: We studied three groups of acromegalic patients: (A) untreated; (B) octreotide-treated; (C) a subgroup of these studied both before and during octreotide therapy. PATIENTS: Forty-eight patients, grouped as above, with active acromegaly were examined for the presence of gastritis. MEASUREMENTS: Gastroscopy and histological examination of gastric biopsies for the presence of gastritis and Helicobacter organisms were undertaken. The principal outcome was quantification of the prevalence of gastritis in the various study groups. RESULTS: Group A: 10 of the 33 patients (30%) had gastritis before any therapy with octreotide. Group B: 17 of 36 patients (47%) on octreotide treatment for 6-59 months (mean 20.5) had gastritis, and this was present in five out of the sub-group of eight patients (62%) treated for over 3 years. Group C: three of 21 patients (14%) developed gastritis during treatment with octreotide for between 6 and 23 months (mean 12.4). There was a highly significant association between the presence of gastritis and the presence of Helicobacter pylori organisms. CONCLUSIONS: Octreotide therapy of acromegaly may predispose to the development of gastritis, but this remains statistically unproven. Certainly, gastritis is not an invariable consequence of octreotide therapy, even after prolonged periods of treatment. The presence of gastritis is associated with H. pylori infection.

Acromegaly↗
PubMed1993

Relationships between insulin-like growth factor-1 levels and growth hormone concentrations during diurnal profiles and following oral glucose in acromegaly.

OBJECTIVE: The aim of this study was to refine the biochemical definition of disease activity in acromegaly by comparing serum growth hormone (GH) measurements during a 10-hour day profile with serum GH values during an oral glucose tolerance test. DESIGN: Using plasma insulin-like growth factor-1 (IGF-1) levels as a measure of disease activity, serum GH data from a day profile and from an oral glucose tolerance test were compared. PATIENTS: Thirty-five acromegalic patients were studied, 13 of whom had serum GH measured during a day profile and 22 during an oral glucose tolerance test. In addition, basal plasma IGF-1 levels were estimated in all acromegalic patients, and in 24 normal subjects. MEASUREMENTS: Following acid-ethanol extraction of the plasma samples, IGF-1 levels were measured by radioimmunoassay using a polyclonal antibody. In a day profile, six to eight blood samples for serum GH estimation were taken at hourly intervals during the day; during an oral glucose tolerance test samples for serum GH estimation were taken in the fasting state and every 30 minutes for 2 hours and measured by a two-site IRMA for GH. RESULTS: Ninety-four per cent of acromegalic patients with raised plasma IGF-1 levels had serum GH concentrations > 10 mU/l whilst 98% of acromegalic patients with plasma IGF-1 levels in the normal range had serum GH concentrations < 6 mU/l. A highly significant positive correlation was found between the mean serum GH concentrations (r = 0.67), the minimum serum GH concentration (r = 0.65) and the area under the GH curve (r = 0.66) estimated during an oral glucose tolerance test and plasma IGF-1 concentrations. The relations between identical indices of serum GH concentration measured during a day profile and plasma IGF-1 levels, although significant, show a less powerful correlation. The relation between serum GH and plasma IGF-1 levels describes a curvilinear model, plasma IGF-1 levels exhibiting a plateau at serum GH concentrations > 40 mU/l but maintaining a linear relationship with serum GH levels < 20 mU/l. CONCLUSIONS: A highly significant correlation exists between plasma IGF-1 levels and various parameters of serum GH levels in acromegalic patients. Hormonal assessment of disease activity in acromegaly is more accurately reflected by the serum GH concentration during an oral glucose tolerance test rather than by the serum GH level during a day profile. Normalization of plasma IGF-1 levels is rarely achieved unless the mean serum GH level is reduced to < 6 mU/l.

Acromegaly↗
PubMed1994

Cholelithiasis and acromegaly: therapeutic strategies.

OBJECTIVE: The aims of this study were (i) to evaluate gall-bladder form and contents, (ii) to assess the prevalence of gallstones in acromegalic patients before octreotide treatment and the incidence of gallstone formation in patients with acromegaly during long-term (6-90 months, mean 44 months) octreotide treatment, and (iii) to test the efficacy of ursodeoxycholic acid in preventing and treating octreotide-induced cholelithiasis. DESIGN: Forty-nine patients (23 men and 26 women, aged 19-81 years) were studied by repeated gall-bladder ultrasonography performed at baseline and then every 6 months during octreotide therapy. All ultrasound scans were evaluated by the same radiologist. Statistical analysis was performed using the Chi-squared and regression analysis tests. RESULTS: Asymptomatic stones were recorded in 13/49 patients (26.5%) prior to octreotide treatment (the prevalence of cholelithiasis in the Italian population is 9.5% in men and 18.9% in women). During octreotide therapy gallstones developed in 10/36 patients (27.7%). No significant correlations with sex, age, body mass index, duration of the disease, daily dose and duration of octreotide therapy, altered gall-bladder form, family history of gallbladder stones, basal plasma values of cholesterol and triglycerides were found between the patients (10/36) who developed stones during octreotide treatment and the ones who did not (26/36). Fourteen patients (10 with newly developed stones and four with cholelithiasis diagnosed prior to octreotide) were put on ursodeoxycholic acid at the daily dose of 10 mg/kg. Gallstones completely disappeared in 6/14 patients (42.8%; five patients with newly developed stones and one with stones prior to octreotide therapy) after a mean of 30.8 months of ursodeoxycholic acid treatment. In addition, seven patients were treated with ursodeoxycholic acid at the preventive dose of 450 mg, administered as a once-a-day oral preparation in the evening. However, stones developed in one of these seven patients who was thereafter cured (gallstones completely disappeared) by the therapeutic dose of ursodeoxycholic acid of 10 mg/kg/day after 23 months of treatment. CONCLUSIONS: This study indicates that (i) acromegaly by itself is correlated with a high prevalence of gallbladder stones, (ii) the long-term treatment with octreotide increases the incidence of cholelithiasis, and (iii) ursodeoxycholic acid is useful in the treatment of gallstones in acromegalic patients but its prophylactic effect in patients on octreotide treatment requires further assessment.

Acromegaly↗
PubMed1995

Bioactive GH-like immunoglobulins G in active acromegaly: response to long-term treatment with bromocriptine.

In acromegaly, certain forms of circulating immunoreactive hGH are not true GH but IgGs which possess GH biological activity (bioactive GH-like IgGs). In this study, we tested the effect of bromocriptine on circulating bioactive GH-like IgGs in an acromegalic woman. Increasing doses of oral bromocriptine (2.5, 5.0 and 7.5 mg/day) were administered (for 2, 8 and 6 months respectively). TRH tests were performed before treatment and at the end of treatment with each dose. The patient was without detectable pituitary or extra-pituitary tumour by magnetic resonance imaging. Her serum contained bioactive GH-like IgGs equivalent to 240 mU/l of hGH and elevated insulin-like growth factor I (IGF-I; 9500 U/l). Basal hGH was 12.8 mU/l and increased to 220 mU/l 15 min after TRH (200 micrograms, i.v.). In addition, in the basal samples of each test we measured total IgGs (radial immunodiffusion), bioactive GH-like IgGs (isolated by Sephadex and protein A affinity chromatography and assayed using the Nb2 cell assay) and IGF-I(RIA). Bromocriptine treatment gradually reduced serum levels of bioactive GH-like IgGs and IGF-I, with significant falls observed first at 10 months of treatment. Bioactive GH-like IgGs were 240, 240, 36.0 and < 0.124 mU/l and IGF-I levels were 9500, 8700, 4000 and 3100 U/l at 0, 2, 10 and 16 months of treatment, respectively. In contrast, IR-hGH response to TRH decreased after 2 months of treatment to 89 mU/l and to 49.2 mU/l at the end of the study while basal IR-hGH remained between 13 and 8.4 mU/l. Basal PRL fell to almost undetectable levels. Bromocriptine treatment decreased the GH response to TRH and the serum concentration of bioactive GH-like IgGs and IGF-I. The striking similarity between the pattern of decrease of serum bioactive GH-like IgGs and IGF-I supports the presence of an immuno component in our patient's acromegaly.

Acromegaly↗
PubMed2005

The nadir growth hormone after an octreotide test dose predicts the long-term efficacy of somatostatin analogue therapy in acromegaly.

OBJECTIVE: In the treatment of acromegaly, a 'test dose' of octreotide is recommended prior to the use of depot somatostatin analogue (SSA) therapy. However, there remains no consensus regarding the criteria that predict a response to treatment. The ability to select patients who may benefit most from medical therapy is potentially of great value in clinical practice. The aim of the study was to determine the predictive value of both the nadir GH and the mean GH following an octreotide test dose in identifying patients who subsequently achieved disease remission with depot SSA therapy. Remission was defined as a mean GH < 5 mU/l (< 2 microg/l). DESIGN: Retrospective case-control study. PATIENTS: A group of 41 patients with acromegaly underwent an octreotide test dose where GH was measured hourly for a total of 6 h following an injection of octreotide 50 microg subcutaneously. Nadir GH and mean GH following the octreotide test dose were determined. Thirty-three patients were subsequently treated with depot SSA therapy and mean GH and IGF-I levels were determined at follow-up. RESULTS: The nadir GH demonstrated superior predictive power to that of mean GH across a range of GH cut-off values. A nadir GH < 5 mU/l demonstrated 80% sensitivity and 83% specificity in predicting remission with depot SSA therapy. A nadir GH < 10 mU/l demonstrated 100% sensitivity and 56% specificity. CONCLUSIONS: The nadir GH following an octreotide test dose is a useful predictive marker of achieving disease remission with depot SSA therapy used as either a primary or an adjuvant agent.

Acromegaly↗
PubMed2005

High prevalence of differentiated thyroid carcinoma in acromegaly.

OBJECTIVE: Acromegaly is a chronic disease caused by increased GH secretion and associated with a greater risk of developing both benign and malignant tumours. In the present study we evaluated the prevalence of thyroid disorders and thyroid malignancies in a series of acromegalic subjects. DESIGN AND PATIENTS: We studied, retrospectively, a continuous series of 125 acromegalic patients referred to the Endocrinology Centres at the University Hospitals of Catania and Ferrara, Italy, over a 22-year period. MEASUREMENTS: Diagnosis and management of acromegaly were based on standardized criteria. In all patients thyroid function and morphology were evaluated by serum free T4, free T3, TSH measurements and ultrasound scanning, respectively. Fine-needle aspiration biopsy (FNAB) was performed in all solid-mixed thyroid nodules of diameter greater than 1 cm. IGF-1 expression was assessed by semiquantitative immunohistochemical analysis in some patients with differentiated thyroid cancer. RESULTS: Abnormal thyroid function was found in eight cases (6%). A diffuse or nodular goitre was present in 102 cases (82%). Thyroidectomy was performed in 17 patients. Histological examination revealed a differentiated thyroid cancer in seven of the patients. No significant association of thyroid cancer with GH or IGF-1 levels was found. Semiquantitative assessment of IGF-1 expression by immunohistochemistry revealed a more intense staining in thyroid cancer from acromegalic subjects than in papillary thyroid cancer from nonacromegalic subjects. CONCLUSIONS: The frequency of thyroid disorders in our series of acromegalic subjects was similar to that previously observed in these patients. However, the prevalence of thyroid cancer was not only strikingly elevated (5.6%) in comparison to the estimated prevalence in the general population (0.093%), but it was even higher than that reported for acromegalic subjects. Sustained exposure to high serum IGF-1 levels is likely to play a role in the development of thyroid cancer in this disease. An additive role for the autocrine/paracrine action of locally produced IGF-1 is also possible. Our results suggest that thyroid function and morphology should be carefully monitored in all acromegalic patients.

Acromegaly↗
PubMed2005

Effect of gender and gonadal status on the long-term response to somatostatin analogue treatment in acromegaly.

UNLABELLED: :GH and IGF-I secretion is related to gender and age. OBJECTIVE: To evaluate the impact of gender and gonadal status on the long-term sensitivity to the somatostatin analogues depot octreotide long-acting release (OCT-LAR) and lanreotide (LAN). PATIENTS: Seventy-three patients with active acromegaly (37 women, median age 34 years; 36 men, median age 38 years) who had not previously been treated with somatostatin analogues were studied: 24 women and 23 men were newly diagnosed; 22 men (61.1%) and 17 women (45.9%) had hypogonadism (P=0.28). Exclusion criteria were age >45 years, follow-up less than 12 months, mixed GH/PRL-secreting adenomas. Study design Observational, analytical, retrospective. Outcome measures (1) Disease control measured as serum GH< 2.5 microg/l and IGF-I normal for age and gender; (2) reduction in tumour volume graded as absent (< 25%), mild (25-50%) and notable (>50%). Results Basal GH, but not IGF-I, levels were higher in women than in men both in the entire series and in 'de novo' patients (97.8+/- 42.2 vs. 71.1+/- 32.6 microg/l, P=0.021). After 12 and 24 months of treatment, respectively, disease control was achieved similarly in men (57.1 and 86.7%) and women (48.6 and 86.7%). Hypogonadal men had longer disease duration than eugonadal men (P=0.022), without any difference in the other parameters. No difference was found between eugonadal and hypogonadal women. Eugonadal men had a smaller tumour volume at baseline than eugonadal women (1396+/- 794 vs. 2896+/- 2871 mm(3), P=0.025). In men undergoing testosterone replacement and withdrawal, there was no change in GH and IGF-I levels after 12 and 24 months of treatment with either LAR or LAN. In the seven women receiving oestro-progestinic replacement, after 24 months of LAR or LAN treatment GH levels were higher during replacement than at withdrawal and IGF-I levels were lower during replacement than withdrawal. Tumour volume decreased significantly in both women and men without any difference between them: the percentage tumour shrinkage in men and women was similar either after 12 (34.4+/-24.4 vs. 40.7+/-22.5%, P=0.38) or 24 months of treatment (58.5+/- 17.4 vs. 56.1+/- 23.6%, P=0.75). Similarly, there was no difference in tumour volume between hypogonadal and eugonadal women and men. CONCLUSIONS: The results of this study demonstrate that long-term responsiveness to OCT-LAR is similar in women and men. Care should be taken in women with acromegaly and hypogonadism treated with somatostatin analogues and oral oestro-progestinic as in this case GH levels are higher while IGF-I levels are lower than after the somatostatin analogues alone.

Acromegaly↗
PubMed2005

Pharmacokinetic profile of lanreotide Autogel in patients with acromegaly after four deep subcutaneous injections of 60, 90 or 120 mg every 28 days.

OBJECTIVE: To investigate the pharmacokinetic profile of a prolonged release, aqueous Autogel formulation of the somatostatin analogue lanreotide (Lan-ATG). DESIGN: A phase II, randomized, double-blind study, during which patients received 60, 90 or 120 mg Lan-ATG for four fixed administrations at 28-day intervals. PATIENTS: A total of 18 patients with acromegaly were recruited; six patients were randomized to each treatment. MEASUREMENTS: Lanreotide minimum concentration (C(min)), maximum serum concentration (C(max)) and area under the concentration-time curve during a dosing interval (AUC(tau)) were assessed after a single dose and at steady state (ss). Serum GH and IGF-1 levels were assessed before each administration and at the end of the study. RESULTS: After a single administration, dose proportionality for C(min,1), C(max) and AUC(tau) was demonstrated statistically. After repeated administrations, Lan-ATG exhibited linear pharmacokinetics over the dose range and ss values of C(min), C(max) and AUC(tau) increased in a dose-dependent, linear manner. Mean C(max,ss) values were only two- to fourfold greater than C(min,ss) values, and there was good control over the entire release profile. Serum levels of GH and IGF-1 declined over the course of the study and acromegaly symptoms improved. The treatment was well tolerated. CONCLUSIONS: Lan-ATG showed linear pharmacokinetic profiles over the three dose levels after both single and repeated dosing, no initial burst effect and good control over the entire release profile. Despite the absence of dose adaptation, four injections of Lan-ATG were effective in lowering serum levels of GH and IGF-1.

Acromegaly↗
PubMed2006

Biochemical evaluation of disease activity after pituitary surgery in acromegaly: a critical analysis of patients who spontaneously change disease status.

BACKGROUND: The definition of biochemical cure in acromegaly involves both the normalization of IGF-1 and a glucose-suppressed GH level of < 1 ng/ml. These criteria were reached by several consensus meetings, although no evidence-based recommendations as to the optimal time to perform biochemical evaluations were made, nor was the fact that several patients may change biochemically upon long-term follow-up taken into consideration. OBJECTIVES: To identify and characterize biochemical changes in the follow-up of acromegaly. PATIENTS AND METHODS: One hundred and twenty-six acromegalic patients seen at a referral centre were followed prospectively (6-108 months) with regard to glucose-suppressed GH levels and IGF-1 concentrations. RESULTS: Eighty-nine patients did not change biochemical status, whereas in 37 (29.3%), one or more changes were identified, mostly during the first year. When glucose-suppressed GH values were discordant with the IGF-1 results, the likelihood of biochemical status modification was significantly greater than when such results were concordant [concordant 19.4%, discordant 57.6%, odds ratio (OR) = 5.6, 95% confidence interval (CI) = 2.3-13.3, P = 0.0001]. Among the changing patients, four out of the nine subjects initially considered as cured remained so at the last follow-up, whereas five became discordant; of the nine initially categorized as active, only three kept such a status at the last evaluation, whereas five became GH discordant and one achieved full biochemical criteria of cure; of 17 initially GH-discordant patients, seven remained so upon the last evaluation, whereas six became concordantly active and four concordantly cured. CONCLUSION: A significant proportion of acromegalic patients change biochemical status upon long-term follow-up after surgery. Most of these changes occur within the first postoperative year and are more likely to take place if the initial GH postglucose and IGF-1 levels are discordant.

Acromegaly↗
PubMed2006

Effectiveness and tolerability of 3-year lanreotide Autogel treatment in patients with acromegaly.

OBJECTIVE: During short-term treatment, monthly subcutaneous injections of lanreotide Autogel are effective in controlling GH/IGF-1 hypersecretion and are well tolerated in patients with acromegaly. This study reports the effectiveness and the tolerability of lanreotide Autogel for at least 3 years in acromegalic patients. PATIENTS: Fourteen patients (nine females, five males) were treated with titrated doses of lanreotide Autogel. DESIGN: This clinical study was an extension of a previous trial. After three fixed-dose lanreotide Autogel injections, treatment was adjusted according to mean GH and IGF-I levels. After 3 years of treatment, patients were receiving 120 (n=7), 90 (n=2) and 60 mg (n=4) monthly injections of lanreotide Autogel. MEASUREMENTS: Acromegalic symptoms, GH and IGF-1 concentrations were analysed at the end of lanreotide microparticle treatment, and after 4, 8, 12, 24, 30 and 36 months of lanreotide Autogel therapy. Tolerance and side-effects were monitored throughout the 3-year study. RESULTS Hormonal control (GH <or= 2.5 microg/l and age- and sex-normalized IGF-1) was achieved in six (46%) patients. With the exception of an unrelated death due to pulmonary embolism, no patient withdrew from study. The number of patients reporting digestive adverse events was seven (12 episodes) for the fixed-dose period, and four (eight episodes), two (six episodes) and one (three episodes) at the end of the first, second and third year of treatment, respectively. Persistent induration at the injection sites was reported by two patients, and histological findings were consistent with benign injection-site granulomas. New cholelithiasis or sludge occurred in five (35%) patients during the lanreotide Autogel treatment. CONCLUSION: This 3-year study shows that lanreotide Autogel is effective in controlling GH/IGF-1 hypersecretion and is well tolerated during long-term treatment of patients with acromegaly.

Acromegaly↗
PubMed2006

First-line octreotide-LAR therapy induces tumour shrinkage and controls hormone excess in patients with acromegaly: results from an open, prospective, multicentre trial.

BACKGROUND: The majority of patients with acromegaly have large tumours and the outcome of conventional management remains poor. OBJECTIVE: To investigate the clinical application of octreotide-LAR as primary treatment in newly diagnosed patients with GH-secreting pituitary tumours. DESIGN: Open, prospective, multicentre, 24-week follow-up study. PATIENTS: Thirty-four patients were enrolled (20 men, 14 women; mean age, 50 years); 13 had microadenoma [median tumour volume 327 mm(3) (range 31-629 mm(3))], 21 had macroadenoma [median tumour volume 1,325 mm(3) (range 503-11,583 mm(3))]. Interventions Octreotide-LAR at the dosage of 20 mg every 28 days for the first 12 weeks increased to 30 mg every 28 days to control GH and/or IGF-I excess in 20 patients (64.7%). MAIN OUTCOME MEASURES: Primary endpoints were control of GH (fasting < 2.5 microg/l) and IGF-I secretion (gender- and age-normalized) and presence and entity of tumour mass shrinkage. Secondary endpoint was improvement of symptoms score. RESULTS: In patients with micro- and macroadenomas GH levels decreased to < 2.5 microg/l in 84.6% and 45%, serum IGF-I levels normalized for age and gender in 61.5% and 35% of cases. Failure in achieving either GH < 2.5 microg/l or normal IGF-I levels was found in none of the patients with micro- and in 45% of patients with macroadenoma. Median tumour volume was reduced by 54% (range: -90% to +350%) in micro- and by 49% (range -94% to -14%) in macroadenomas. Headache, perspiration and osteo-arthralgias disappeared in 21%, paresthesias in 38%, fatigue in 26% and carpal tunnel syndrome in 15%. The treatment was well tolerated: more frequent adverse events were gastrointestinal (in 44%). CONCLUSIONS: In both patients with micro- or macroadenoma, primary octreotide-LAR treatment controls hormone excess, induces tumour shrinkage and improves symptoms of acromegaly with limited side effects and can be therefore successfully employed in patients with contraindications for surgery or in those who refuse surgery.

Acromegaly↗
PubMed2006

Age changes the diagnostic accuracy of mean profile and nadir growth hormone levels after oral glucose in postoperative patients with acromegaly.

BACKGROUND: This analytical, retrospective study was designed to select cut-off thresholds of mean GH levels during a diurnal profile and nadir GH levels after oral glucose tolerance test (OGTT) according to age to diagnose surgical remission of acromegaly. METHODS: One hundred forty-one patients (76 women, aged 44 +/- 15 years and 65 men, aged 43 +/- 13 years) were included in this study. For the purpose of this study, remission was based on insulin-like growth factor-I (IGF-I) levels in the normal range for age. Diagnostic accuracy was analysed by receiving-operator characteristics (ROC) curves in the entire series, and in young (20-40 years), middle-aged (41-60 years) and older patients (> 60 years), separately. RESULTS: Sixty patients (42.6%) had normal IGF-I levels after surgery. In the entire series, in young and in middle-aged patients, the ROC analysis showed that optimum cut-off for mean GH levels was 2.3 microg/l (diagnostic accuracy range, 94-97%) whereas that for nadir GH after OGTT were, respectively, 0.85, 0.9 and 0.8 microg/l (diagnostic accuracy range, 90-95%). In the older patients, the optimum cut-off selected for mean GH levels was 1.4 microg/l and that for nadir GH after OGTT was 0.5 microg/l (diagnostic accuracy, 100% for both). The comparative analysis of the ROC curves did not show any significant difference between mean GH and nadir GH after OGTT (P = 0.21). CONCLUSIONS: The criteria currently accepted for diagnosing post-surgical remission of acromegaly have high diagnostic accuracy only in the patients aged below 60 years. In older patients, lower cut-offs (i.e. = 1.4 microg/l for fasting GH and = 0.5 microg/l for nadir GH after OGTT) predict normal IGF-I levels. Mean GH levels during a diurnal profile have similar diagnostic accuracy of nadir GH levels after OGTT. This suggests that OGTT is not necessary to establish surgical cure.

Acromegaly↗
PubMed1982

The value of plasma prolactin levels in the prediction of the responsiveness of growth hormone secretion to bromocriptine and TRH in acromegaly.

UNLABELLED: The mechanism of the inhibition of growth hormone secretion in response to bromocriptine and the ability of thyrotropin releasing hormone to stimulate growth secretion in acromegaly is unknown. In the present study the relationship between the plasma prolactin concentration of untreated acromegalic patients and the reaction of growth hormone to thyrotropin releasing hormone and bromocriptine was investigated. Plasma prolactin levels were elevated in thirty-three (42%) of seventy-nine untreated acromegalic patients. Seventeen patients had mildly elevated prolactin levels, but in sixteen the plasma prolactin concentration was higher than 30 ng/ml. Bromocriptine (2.5 mg) inhibited growth hormone secretion by more than 50% in 22% of the normoprolactinaemic, in 53% of the mild hyperprolactinaemic and in 88% of the patients with a prolactin level above 30 ng/ml (P less than 0.01 v. normoprolactinaemic; P less than 0.01 v. mildly elevated prolactin levels). An increase of growth hormone secretion by more than 100% of the basal value in response to thyrotropin releasing hormone was observed in 44% of the normoprolactinaemic, in 59% of the mildly hyperprolactinaemic and in 75% of the clearly hyperprolactinaemic patients; (P less than 0.01 v. normo- and mildly hyperprolactinaemic patients). CONCLUSION: An increased plasma prolactin concentration in patients with acromegaly is accompanied in most patients by a higher sensitivity of growth hormone secretion to bromocriptine.

Acromegaly↗
PubMed1991

Early postoperative basal serum GH level and the GH response to TRH in relation to the long-term outcome of surgical treatment for acromegaly: a report on 39 patients.

During a 10-year period 39 patients with acromegaly, aged 23-73 years, underwent selective adenomectomy via a trans-sphenoidal or transfrontal (one case) approach. Six to 12 months after the operation, the serum level of growth hormone (GH) was reduced to less than 5 micrograms l-1 in 28 patients (74%) in at least two of three random samples and/or suppressed to less than 3 micrograms l-1 during an oral glucose load, thus fulfilling the commonly used criteria for a successful operation. In 10 patients these criteria for adequate GH reduction were not fulfilled, but their median S-GH level was reduced from 38 to 11 micrograms l-1 (P less than 0.01) after the operation. Surgery was successful in 11 of 13 (85%) patients with a microadenoma (less than 10 mm in diameter), in 10 of 14 (71%) patients with an adenoma of diameter greater than 10 mm but still enclosed in the sella, and in seven of 11 (64%) patients with locally invasive tumours. Impaired pituitary function was observed in 23% of the patients after surgery, independent of tumour size. In one patient the postoperative period was complicated by a lethal intracranial infection. During follow-up for 1-10 years, four patients relapsed, after 1, 1.5, 6 and 9 years, respectively. Patients for whom surgery appeared to have been ineffective at the evaluation 6-12 months postoperatively, or who later relapsed were identified by early (within 7 d) postoperative serum GH with a sensitivity of 90%. The accuracy for identification of a satisfactory outcome of surgery was 85%, and the predictive value was 90%. The corresponding values for the GH response to TRH measured 6-12 months postoperatively were 47, 40 and 54%, respectively. It is concluded that the basal level of serum GH measured 1-7 d postoperatively has higher sensitivity and specificity than the GH response to TRH 6-12 months postoperatively for evaluation of the effect of surgery on GH overproduction, and that it has a higher predictive power with regard to the long-term outcome of surgery for acromegaly.

Acromegaly↗
PubMed2004

Idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells in a patient with acromegaly.

Idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells (IDHPNC) is a rare disorder that most often presents clinically as obliterative bronchiolitis, but has also been associated with ectopic corticotropin syndrome. We describe a 49-year-old lifetime non-smoking female with longstanding cough, progressive exertional dyspnoea, and fixed airflow limitation, who presented with acromegaly. Head magnetic resonance imaging revealed a pituitary microadenoma and open lung biopsy revealed a multifocal proliferation of neuroendocrine cells which were immunopositive for both corticotropin and growth hormone-releasing hormone. To our knowledge, this is the first report of acromegaly associated with IDHPNC, and supports the possibility that IDHPNC may fall at one extreme of the spectrum of disorders encountered in multiple endocrine neoplasia type 1.

Acromegaly↗
PubMed1989

Long-term effects of megavoltage radiotherapy in acromegaly.

The progress of 41 Chinese patients with acromegaly treated with megavoltage radiotherapy was reviewed after a mean follow-up of 4.5 (one-ten) years. Nine received prior surgery. Radiotherapy was delivered by a 3-field technique to a total of 4000-5000 cGy in 25 fractions. By life table analysis successful treatment of growth hormone (GH) hypersecretion, as defined by a mean GH concentration of less than or equal to 10 mu/L, could be expected in 6, 11, 26, 64 and 67% of the patients after one, two, five, eight and ten years respectively. Median intervals before achieving a mean GH level of less than or equal to 10 mu/L were 6.6 and 8.6 years following radiotherapy with the higher (4500-5000 cGy) and lower (4000 cGy) doses respectively, suggesting a tendency towards earlier response following radiotherapy with the higher dose. The prevalence of acquired hypopituitarism in patients followed up for over five years was 40% for gonadotrophins, 30% for TSH and 20% for ACTH deficiency respectively. In the majority of patients, acquired hypopituitarism was not apparent within five years after radiotherapy. No mortality or major side effects were noted following radiotherapy. In 34 patients on long-term bromocriptine treatment, mean GH concentrations were normalised in 26.5% of patients. We conclude that with judicious selection of patients and use of adjunctive medical therapy, megavoltage radiotherapy remains a safe and satisfactory form of treatment for acromegaly especially if expert transphenoidal surgery is not readily available.

Acromegaly↗
PubMed2000

Treatment of Chinese acromegaly with a combination of bromocriptine and octreotide.

BACKGROUND: Good results have been reported with combined use of octreotide and bromocriptine in acromegalic Caucasians. Data concerning the efficacy and tolerability of this combination treatment in Chinese acromegalic patients are scanty. AIM: The aim of this study was to assess the efficacy and tolerability of combined therapy using bromocriptine and octreotide in the treatment of acromegaly in Chinese patients and to compare the cost-effectiveness of various regimes. METHODS: Sixteen Chinese acromegalic patients with growth hormone (GH) concentration not suppressible to below 5 mU/L (2 microg/L) during an extended OGTT were recruited to undergo four phases of the study. During the study period, the patients were given bromocriptine alone, bromocriptine and low dose octreotide, bromocriptine and medium dose octreotide, and medium dose octreotide alone. Plasma concentrations of GH and insulin-like growth factor-1 (IGF-1) were measured before and after the completion of each phase. RESULTS: The number of patients reaching target GH concentrations was significantly higher when treated with octreotide compared to baseline (p<0.05). Bromocriptine alone had a significant effect but not to the extent of octreotide alone. A combination of low dose octreotide and bromocriptine is as efficacious in the treatment of acromegaly as high dose octreotide. None of the patients suffered from serious adverse effects. CONCLUSION: The results confirmed the usefulness and tolerability of bromocriptine and octreotide in Chinese acromegalics. The most cost-effective regime in this study was a combination of low dose octreotide and bromocriptine.

Acromegaly↗
PubMed2004

A case of secondary diabetes mellitus with acromegaly improved by pioglitazone.

AIM: The acromegaly patient was diagnosed with Type 2 diabetes mellitus. His HbA1c was 10.6% and fasting blood glucose (FBG) 15.3 mmol/l. We prescribed glibenclamide (10 mg/day), but his HbA1c and FBG remained high. At this stage, treatment with short-acting insulin was instigated at a dose of 20 U/day. However, the patient's blood glucose level remained unsatisfactory. We tried using pioglitazone. METHOD: Pioglitazone was prescribed at 30 mg/day in combination with the insulin. RESULTS: The FBG and HbA1c value decreased to 7.2 mmol/l and 7.3%, respectively, within 2 months and insulin was discontinued. Pioglitazone alone was able to control the FBG level. CONCLUSIONS: Pioglitazone treatment might be considered as a choice for similar cases of diabetes secondary to acromegaly.

Acromegaly↗