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PubMed1993

Growth hormone and insulin-like growth factor-1 in blood and urine as response markers during treatment of acromegaly with octreotide: a double-blind placebo-controlled study.

Growth hormone (GH), insulin-like growth factor-1 (IGF-1) and prolactin (PRL) in blood and urine were observed in 20 patients with acromegaly in a double-blind placebo-controlled 14-day clinical trial with the somatostatin analog octreotide. Hormones were determined by the same radioimmunoassays in blood and urine. Significant reduction of GH and IGF-1 during octreotide treatment compared to placebo was seen in blood but not in urine. Patients with diabetes mellitus, 2 of the 20 patients, showed notably increased urinary GH and IGF-1 in relation to blood levels. Therefore, results without the two diabetic patients were calculated, showing significant reduction of urinary GH and IGF-I during treatment on some, but not all observation days. The intraindividual variations of GH and IGF-1 were greater in urine than in blood. PRL levels were not significantly affected by octreotide either with or without the two diabetic patients. In conclusion, this study indicates, that GH and IGF-1 in blood are preferable to urinary GH and IGF-1 as response markers during treatment of acromegaly with octreotide. One disadvantage with urinary assessments of GH and IGF-1 in acromegaly seems to be the relatively higher excretion in patients with diabetes mellitus.

Acromegaly↗
PubMed2006

[Therapeutic management of acromegaly].

BACKGROUND: Only 60% of the patients with acromegaly are biochemically cured (growth hormone [GH] nadir < 1.0 microg/l after an oral glucose load, normalized age- and gender-matched insulin-like growth factor-1 [IGF-1] levels) after transsphenoidal surgery of the pituitary gland. In the absence of a remission there are effective pharmacological treatment regimens available which are able to lower GH and IGF-1 serum levels. THERAPEUTIC STRATEGIES: Somatostatin analogs, a GH receptor antagonist and dopamine agonists have been shown to alleviate the comorbid features and to normalize GH and IGF-1 levels. CASE REPORTS: In this overview six case reports are presented to highlight the current pharmacological treatment options and to propose an algorithm for the clinical routine in patients with persisting acromegaly. CONCLUSION: Transsphenoidal surgery is the treatment of choice for the initial management of acromegaly. In the absence of a remission there are effective pharmacological treatment regimens available among which somatostatin analogs are recommended as the first-line treatment.

Acromegaly↗
PubMed2005

Treatment outcomes and mortality of 94 patients with acromegaly.

BACKGROUND: Due to new therapeutic modalities and modified therapeutic goals outcome of patients with acromegaly may change over time and differ by centre. We analysed treatment outcomes and mortality of our patients with acromegaly seen between 1971 and 2003. METHOD: The cohort consisted of 94 patients who had been followed for 0.3-31 years (mean 10.6 years). Remission criteria were a normalized IGF-I concentration, a nadir GH level during oral glucose load of <1.0 microg/l and a random GH value of <2.5 microg/l. FINDINGS: Transsphenoidal surgery achieved remission in 80% of patients with micro-adenomas (<1 cm), 65% with meso-adenomas (> or = 1 cm to <2 cm) and 27% with macro-adenomas (> or = 2 cm). Patients with meso-adenomas operated on after 1995 tended to have a better outcome compared to those operated on before 1995 (Remission in 83% vs. 38%). Radiotherapy resulted in disease control in 22 of 47 patients (47%). Intramuscular depot formulation of octreotide (Sandostatin LAR) led to disease control in 17 of 26 patients (65%). After multimodal therapy persistent acromegalic activity remained in 18% of the patients; only one of them had an adenoma of <2 cm. The standardized mortality ratio was 1.30 (95% CI 0.52-2.67) for patients in remission and 1.38 (95% CI 0.51-3.00) for patients with persistent acromegalic activity. CONCLUSIONS. Most patients with adenomas of <2 cm can be expected to achieve remission by transsphenoidal surgery alone. Furthermore, virtually all patients with adenomas of <2 cm and more than 80% of patients with adenomas of > or = 2 cm can be expected to achieve remission by adjuvant treatment. Aggressive multimodal therapy is critical in the management of acromegaly reducing mortality risk close to that of the general population.

Acromegaly↗
PubMed1979

Acromegaly and the heart. An echocardiographic study.

Twenty-seven patients with acromegaly had echocardiograms performed to delineate the ventricular septum, left ventricular posterior wall and mitral valve. Left ventricular function was assessed by calculating the systolic internal dimensional shortening of the left ventricle. Six patients met the criteria for asymmetric septal hypertrophy and eight had concentric left ventricular hypertrophy. The remaining 13 patients were categorized as "normal," although six had septal measurements greater than 11 mm. The group with asymmetric septal hypertrophy had significantly greater percentage of internal dimensional shortening during systole than either the normal group (p less than 0.05) or the group with left ventricular hypertrophy (p less than 0.01). Initial mean growth hormone levels were considerably higher in the group with left ventricular hypertrophy than in the normal group (93 versus 34 ng/ml). Thus, echocardiographic abnormalities are common in acromegaly, and patients with asymmetric septal hypertrophy and acromegaly appear to have significantly increased ventricular ejection. Many of the patients with left ventricular hypertrophy have no evidence of clinical cardiovascular disease, and their left ventricular hypertrophy may be related to higher initial growth hormone levels.

Acromegaly↗
PubMed1980

Sleep apnea in acromegaly.

In patients with acromegaly obstruction of the upper airway may develop due to enlargement of the tongue and thickening of the tissues of the larynx. The sleep apnea syndrome may develop in patients with upper airway obstruction from other causes. We studied a somnolent patient with acromegaly in whom we documented the sleep apnea syndrome. Endoscopy, while the patient was sleeping, revealed that periodic obstruction during sleep occurred because the large tongue bulged into the pharynx and obliterated the pharyngeal airway. Tracheostomy was followed by the disappearance of the somnolence. The upper airway obstruction in acromegaly may result in severe hypoxemia and disruption of normal sleep.

Acromegaly↗
PubMed1984

Ectopic secretion of a growth hormone-releasing factor. Report of a case of acromegaly with bronchial carcinoid tumor.

Rarely, acromegaly is produced by neuroendocrine neoplasms elaborating a substance similar to or identical with growth hormone-releasing factor. This report reviews the cases described to date and presents the clinicopathologic features of a patient with acromegaly, mild sellar enlargement, and elevated growth hormone levels associated with a large bronchial carcinoid tumor. Normalization of serum growth hormone levels and regression of acromegaly followed resection of the bronchial tumor, which was shown, by bioassay and immunocytochemistry, to contain a growth hormone-releasing factor.

Acromegaly↗
PubMed1987

Acromegaly.

At the time that acromegaly is diagnosed, more than half the pituitary adenomas are greater than 1 cm in diameter, and approximately half will not be cured by surgery or radiotherapy. Somatostatin, the natural hypophyseoportal peptide that inhibits the release of growth hormone, also inhibits the release of growth hormone from pituitary macroadenomas. Unfortunately, its plasma half-life is only a few minutes. With the development of a long-acting somatostatin analogue, SMS 201-995, prolonged therapy is possible. Several studies have demonstrated that when patients self-administer SMS 201-995 from two to three times daily at home, long-term inhibition of growth hormone release and remission of the clinical symptoms of acromegaly occur without significant side effects. SMS 201-995 is, therefore, a useful new palliative treatment for acromegaly.

Acromegaly↗
PubMed1993

Serum apolipoprotein(a) correlates with growth hormone levels in Chinese patients with acromegaly.

Untreated acromegaly is associated with an increased cardiovascular morbidity and mortality. The contribution of altered lipid metabolism remains unclear. We investigated the relationship between serum apolipoprotein(a) (apo(a)) and growth hormone (GH) levels in 15 patients with acromegaly before and during treatment with octreotide, a long-acting somatostatin analogue, 288-600 micrograms/day s.c., for 6 months. Before treatment serum apo(a) was significantly elevated in acromegalic patients (geometric mean being 323 U/l vs. 142 U/l in controls (n = 92; P < 0.01)). Octreotide treatment resulted in significant reductions in serum apo(a) concentration (F = 7.22; P < 0.01; geometric mean being 232 U/l and 248 U/l at 3 months and 6 months respectively) and apo(a) concentrations on treatment were not significantly different from control values. There were significant reductions in serum GH (F = 7.30; P < 0.01), insulin growth factor 1 (IGF1) (F = 31.4, P < 0.001) and insulin (F = 4.57; P < 0.05) concentrations. Plasma glycosylated haemoglobin levels were unchanged. Apo(a) levels correlated with serum GH (r = 0.450; P < 0.01) but showed no correlation with basal insulin concentrations. Serum HDL cholesterol increased on treatment (F = 4.29; P < 0.05). Triglycerides were reduced only in the 12 patients without diabetes mellitus (F = 4.75; P < 0.05). No significant change in LDL cholesterol occurred. Our findings suggest that apo(a) may constitute another cardiovascular risk factor in untreated acromegaly and that GH may be involved in the regulation of circulating apo(a) concentration.

Acromegaly↗
PubMed1977

Lack of effect of thyroid hormones on the growth hormone response to thyrotropin-releasing hormone in acromegaly.

Serum growth hormone (GH) responses to thyrotropin-releasing hormone (TRH) were evaluated in 14 patients with acromegaly following treatment with thyroid hormones. After an initial TRH test, seven patients received L-triiodothyronine, 100 mug daily for seven days; the GH response to TRH was not significantly altered by this treatment. Similar findings were noted in two acromegalic subjects who were tested with TRH before and after longer periods of administration of L-thyroxine. Four of five additional subjects with acromegaly who had received replacement doses of thyroid hormones for an average of 6.6 yr demonstrated GH responses to TRH which were similar to those seen in subjects not receiving thyroid hormones. Acute or long-term administration of replacement doses of thyroid hormones seems to have minimal effect on the GH response to TRH in acromegaly.

Acromegaly↗
PubMed1978

Parameters of thyroid function in patients with active acromegaly.

In order to determine if acromegaly per se may be associated with abnormalities in thyroidal economy, serum thyroxine-binding globulin (TBG), resin T3 uptake, total and free T4, T3, and reverse T3 concentrations were measured in 21 patients with active acromegaly. Mean (+/- SE) total T4, T3, and reverse T3 levels were 7.1 +/- 0.2 microgram/dl, 111 +/- 4 ng/dl, and 45 +/- 2 ng/dl, respectively, and the mean TBG concentration was 3.6 +/- 0.2 mg/dl. Similarly, mean free T4, T3, and reverse T3 concentrations were 2.4 +/- 0.09 ng/dl, 383 +/- 22 pg/dl, and 118 +/- 7 pg/dl, respectively. None of these values is significantly different from normal and the thyrotropin response to thyrotropin-releasing hormone was also normal. In contrast to several earlier reports, these data suggest that parameters of thyroid function are generally normal in patients with active acromegaly.

Acromegaly↗
PubMed1994

Insulin-like growth factors (IGF)-I and -II and IGF binding protein-1, -2, and -3 in patients with acromegaly before and after adenomectomy.

The interrelationship between insulin-like growth factors (IGFs) and their major binding proteins (IGFBPs) as a function of disease activity in acromegaly has not previously been prospectively evaluated. We studied basal and insulin-stimulated serum levels of IGF-I and -II and IGFBP-1, -2, and -3 in six acromegalic patients before and 2 months after successful adenomectomy compared with a group of sex- and age-matched healthy, untreated subjects. All were studied postabsorptively (11 AM) and at the end of a 2-hour euglycemic glucose clamp (0.4 mU insulin/kg x min). Serum IGF-I levels (mean +/- SE) were elevated in acromegaly but were normalized following therapy (basal state IGF-I [micrograms/L], 857 +/- 119 [active] v 255 +/- 65 [postoperative] v 190 +/- 20 [control]). Serum IGF-II levels did not change following therapy and were similar to those of the control group. IGF levels did not change during the clamp. Serum IGFBP-3 levels were elevated in active acromegaly, but were normalized after therapy (basal state IGFBP-3 [micrograms/L] 6,983 +/- 612 [active] v 3,939 +/- 504 [postop] v 3,358 +/- 125 [control]). The molar ratio of (IGF-I+IGF-II): IGFBP-3 was similar in all studies. Serum IGFBP-1 interacted significantly with time in all studies, exhibiting a gradual decrease in the basal state and ensued by further suppression during the clamp. Insulin and IGFBP-1 correlated inversely in the pooled data and in the acromegalic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1987

A rare cause of acromegaly: ectopic production of growth hormone-releasing factor by a bronchial carcinoid tumor.

Ectopic production of growth hormone-releasing factor (GRF) is a rare cause of acromegaly. In addition to its production by gangliocytomas, both hypothalamic and intrasellar, in rare cases various neuroendocrine neoplasms produce the substance, with resultant growth hormone cell hyperplasia of the pituitary and acromegaly. We report an endocrinologically well-documented case of a GRF-producing bronchial carcinoid tumor in which the associated acromegaly was cured by lobectomy.

Acromegaly↗
PubMed1992

A further study on the stimulatory effect of peptide histidine methionine on growth hormone secretion in acromegaly: a dose-related study and a comparison with vasoactive intestinal peptide.

We examined whether the GH-releasing effect of peptide histidine methionine (PHM) in acromegaly may be mediated by activation of pituitary receptors for vasoactive intestinal peptide (VIP), which is structurally similar to but more powerful than PHM in stimulating GH secretion in acromegaly. VIP (50 or 100 micrograms) or PHM (50, 100, or 200 micrograms) was given as an i.v. bolus to 11 patients with active acromegaly, and plasma GH levels were measured before and at intervals up to 120 min after the injection. A paradoxical GH response (> 50% and > 6 micrograms/l above the basal) to 50 or 100 micrograms of VIP was observed in 4 (36%) or 5 (45%) patients, respectively. 2 (18%) patients showed paradoxical GH responses to both 50 and 100 micrograms of PHM, and, interestingly, as many as 5 (45%) patients showed positive GH responses to 200 micrograms of PHM. 3 of these 5 responders to 200 micrograms of PHM were also responders to both doses of VIP. To add to, one of the responders to 100 micrograms of VIP did not show a positive GH response to even 200 micrograms of PHM. These results may suggest that in at least some acromegalics the PHM stimulation of GH secretion is mediated by activation of pituitary VIP receptors by PHM and/or by PHM binding to its specific receptors which may have appeared concomitantly with VIP receptors. However, the occasional heterogeneity of the VIP- and PHM-induced GH responses may suggest that on some somatotroph adenomas either VIP or PHM receptors may appear independently.

Acromegaly↗
PubMed2005

Effect of pituitary surgery in patients with acromegaly on adiponectin serum concentrations and alanine aminotransferase activity.

BACKGROUND: Thiazolidinediones increase adiponectin concentrations, improve insulin sensitivity and fatty liver disease (reflected by decreased alanine aminotransferase [ALT] activity) in type 2 diabetes. This study was performed to test the effect of neurosurgery in acromegaly (sharing at baseline insulin resistance but not increased visceral fat with type 2 diabetes) on insulin sensitivity, adiponectin concentrations and ALT activity. METHODS: Sixteen patients with acromegaly undergoing pituitary surgery (and 16 patients with type 2 diabetes treated with pioglitazone) were included. Insulin sensitivity, adiponectin concentrations and ALT activity were determined at baseline and after 4 months. RESULTS: Pituitary surgery in acromegalic patients increased adiponectin concentrations from mean (+/-S.D.) 9.3+/-3.8 to 10.2+/-4.4 mg/L (p<0.05). HOMA scores fell from 6.8+/-4 at baseline to 3.5+/-0.9 following neurosurgery (p<0.005) and ALT activity decreased from median (range) 21 (13-30) to 13 (10-42) U/L (p<0.05). In type 2 diabetics, pioglitazone treatment increased adiponectin concentrations; HOMA scores and ALT activity fell significantly. CONCLUSION: Pituitary surgery in patients with acromegaly led to a marked increase in insulin sensitivity and a slight increase in adiponectin serum concentrations, whereas ALT activity significantly decreased.

Acromegaly↗
PubMed2004

The role of somatostatin receptors in the medical treatment of acromegaly.

Somatostatin is a hypothalamic inhibitor of pituitary growth hormone secretion and cell proliferation, binding to five distinct receptor subtypes (sstr1-5). Since native somatostatin has a short half-life, somatostatin analogues with a longer half-life have been developed for therapeutic purposes. Octreotide and lanreotide are currently available for treatment of acromegaly, binding with high-affinity sstr2 and sstr5. Octreotide, the first somatostatin analogue used in the medical therapy of acromegaly, was initially given subcutaneously at doses of 100-500 microg three times daily. The introduction of new depot formulations, such as octreotide long-acting release, slow-release lanreotide and lanreotide-autogel, improved patients compliance of long-term therapy, overcoming the inconvenience of multiple daily administration. The treatment with somatostatin analogues induces biochemical control and tumour shrinkage in about 50-70% and 30-60% of patients with acromegaly, respectively. However, the efficacy of this therapy lies on an adequate expression of sstr2 and sstr5 on tumor cells. In the past, somatostatin receptor expression was tested in vivo by (111)In-diethylenetriaminepentaacetate-D-Phe-octreotide scintigraphy: this method has been abandoned since normal pituitary tissue can be visualised by (111)In-diethylenetriaminepentaacetate-D-Phe-octreotide scintigraphy. Currently, the somatostatin receptorial profile can be characterised by autoradiography, molecular biology techniques and immunohistochemistry on surgically removed tumor tissue. These methods may offer an individualised approach sparing patients from unnecessary treatment.

Acromegaly↗
PubMed2005

Intravenous octreotide test predicts the long term outcome of treatment with octreotide-long-acting repeatable in active acromegaly.

OBJECTIVE: Depot formulations of somatostatin analogues are increasingly used in the treatment of active acromegaly. A priori knowledge of the efficacy of these drugs in controlling GH excess is clinically relevant, because only approximately 60% of the patients respond with adequate control of GH (GH levels < 5 mU/L) and/or IGF-1 levels upon this treatment. Therefore, we assessed the acute responses of serum GH levels to a new octreotide test (intravenous administration of 50 microg) in 98 consecutive patients with active acromegaly and we measured the predictive value of this test for the efficacy of chronic octreotide-long acting repeatable (octreotide-LAR) treatment in 18 patients. DESIGN: Serum GH concentrations were measured before and at 20, 30, 45, 60, 90, 120, 150 and 180 min following 50 microg i.v. octreotide. The minimal achieved GH was used for analysis. Octreotide-LAR was individually titrated aiming at a normal serum IGF-I for age and a serum GH < 5 mU/L. The mean of 3-6 monthly serum GH and IGF-I measurements after individual dose adjustment was used for evaluating the efficacy of chronic therapy. RESULTS: Octreotide decreased GH levels to values below 5 mU/L in only 49% of unselected consecutive patients and the response was inversely related to basal GH levels. In patients with baseline GH above 50 mU/L, 50 microg i.v. octreotide reduced GH to < 5 mU/L in only 15% of cases (n = 41), whereas in patients with baseline GH levels below 50 mU/L this goal was achieved in 77% of cases. The fractional decrease in GH levels upon octreotide injection was similar in microadenomas and macroadenomas. The minimally achieved serum GH concentration during the intravenous octreotide test was a good predictor for the GH concentrations during long-term octreotide-LAR treatment as assessed in 18 patients. The intravenous octreotide test, using a minimal GH level of < 5 mU/L, had a sensitivity, positive and negative predictive value of 100% for prediction of GH suppression to below 5 mU/L during long term octreotide-LAR treatment. For predicting the response of IGF-I during long-term treatment, the test performed with a sensitivity of 73% and a positive predictive value of 73%. CONCLUSION: Intravenous octreotide reduces GH to concentrations < 5 mU/L in approximately 50% of consecutive patients with active acromegaly, which predicts a good response to chronic octreotide-LAR treatment.

Acromegaly↗
PubMed2005

Late potentials and ventricular arrhythmias in acromegaly.

BACKGROUND: Sudden death and increased prevalence of ventricular arrhythmias have already been described in acromegaly. Although late potentials (LPs) have been proved to be a new technique in detecting patients at risk for ventricular tachyarrhythmias its use in acromegaly is still unknown. METHODS: We studied 70 acromegalic patients [32 males, 38 females; age 49+/-12 years (mean+/-S.D.)] and 70 control subjects age- and sex-matched [(35 males and 35 females; 46+/-12 years (mean+/-S.D.)]. Besides hormonal tests, we performed the following cardiovascular investigations: ECG, 24-h ECG Holter monitoring, echocardiography, and signal-averaged ECG (SAECG) time-domain analysis. RESULTS: LPs occurrence was significantly higher in acromegalic patients as compared to the control group (22.9% vs. 2.9%; p=0.001). A greater duration of disease in patients with positive LPs compared to negative ones was pointed out (18 vs. 12 years; p=0.024). In the group of acromegalic patients with positive LPs we observed a significant association with premature ventricular complexes (PVCs) detected by means of 24-h Holter ECG recording (13 out of 15 patients: 86.7%; p=0.024). The positivity or negativity of LPs proved to be significantly associated with Lown scale PVC trends recorded by 24-h Holter ECG (p=0.014). In the group of patients with left ventricular hypertrophy a significant and pathological worsening of SAECG signals (QRS, LAS, RMS) was documented. CONCLUSIONS: We observed a higher prevalence of LPs in acromegaly which significantly correlated with Lown scale of PVCs.

Acromegaly↗
PubMed2006

Multiple bronchioloalveolar carcinomas in acromegaly: a potential role of insulin-like growth factor I in carcinogenesis.

The molecular pathogenesis of lung cancer, especially multiple and synchronous bronchioloalveolar carcinomas (BACs), is still unknown. Here, we report two cases of multiple BACs associated with acromegaly, and discuss about the possible relationship between these two pathological condition. The first patient was a 52-year-old female with a history of Hardy's surgery for pituitary growth hormone cell adenoma 2 years earlier. The second patient was a 57-year-old female with acromegaly and obstructive sleep apnea syndrome. Both patients were non-smokers and showed a high serum level of insulin-like growth factor I (IGF-I) at the time of admission, even though the level of growth hormone had decreased. High-resolution computed tomography (HRCT) revealed multiple small nodules with pure ground-glass opacity (GGO) in both lungs of the first patient and a small nodule with pure GGO in the right lung of the second one. Partial resection for these tumors were performed under video-assisted thoracoscopic surgery. Resected lung specimens of the first case revealed one papillary adenocarcinoma, seven BACs, and 11 atypical adenomatous hyperplasias (AAHs). The second case showed two foci of BACs. Immunohistochemically, all BACs were strongly positive for IGF-IR which is a specific receptor for IGF-I, and all AAHs were also weakly positive for IGF-IR. Since IGF-I is known as a potent growth factor for normal as well as cancerous cells, it might play an important role for tumorigenesis and/or tumor progression of BACs through its interaction with and/or upregulation of IGF-IR. In addition, much attention should be paid to detect lung lesions in acromegaly with high serum level of IGF-I.

Acromegaly↗