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PubMed2003

Pitfalls in the biochemical assessment of acromegaly.

The biochemical assessment for newly recognized acromegaly is in most, but not all patients straightforward. Although significant improvements in the methods of biochemical testing for acromegaly have recently been made, major pitfalls to the assessment of this disease still exist. A number of different schemes have been employed for the assessment of GH secretion in clinical practice. Random GH levels have been often used, but remain unreliable for the assessment of acromegaly. Mean GH levels are also frequently used to assess GH status, but are not specific for the diagnosis of acromegaly. Measurement of glucose suppressed GH levels is the preferred method for assessing GH secretion in acromegaly. However, it is essential to recognize that when using highly sensitive and specific GH assays, nadir GH levels can be < 1 microg/L after oral glucose in some patients with newly diagnosed acromegaly and postoperative patients with active disease. On the other hand, when using most clinically available commercial GH assays which are less sensitive and specific than those used in research studies, failure of GH suppression into the normal range set in these studies is not alone diagnostic of active acromegaly. In order to diagnose acromegaly, documentation of GH excess should be accompanied by elevation in levels of the GH dependent peptide, insulin-like growth factor I (IGF-I). Consideration also needs to be given to the clinical context in which GH and IGF-I are being measured as both can be altered in a number of clinical settings other than acromegaly. Both IGF-I and GH evaluations are important and complimentary parts of the biochemical assessment of acromegaly.

Acromegaly↗
PubMed2001

Increased arterial intima-media thickness by B-M mode echodoppler ultrasonography in acromegaly.

BACKGROUND: Patients with acromegaly have an increased morbidity and mortality for cardiovascular diseases. Despite the increasing evidence for the existence of a specific cardiomyopathy in acromegaly, the presence of vascular abnormalities has been never investigated. OBJECTIVE: To evaluate the cardiovascular risk and premature atherosclerosis in acromegaly. SUBJECTS: Forty-five patients with acromegaly and 30 sex- and age-matched healthy subjects were included in this study: 30 patients were studied at the diagnosis of acromegaly and were in active disease (GH 59.3 +/- 10.2 mU/l, IGF-I 733 +/- 57.6 microg/l) while 15 patients were studied after surgery and/or radiotherapy and were cured from the disease (GH 4.5 +/- 0.7 mU/l, IGF-I 172.4 +/- 16.9 microg/l). METHODS: Body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), serum total, LDL- and HDL-cholesterol, triglycerides, and fibrinogen levels, prothrombin time (PT), activated partial thromboplastin time (APTT), glucose and insulin levels (fasting and after glucose load) were measured in all patients and controls. By echodoppler ultrasonography, blood systolic (SPV) and diastolic (DPV) peak velocity, and resistance index (RI) were measured at both common and internal carotid arteries where presence, size and location of atherosclerotic plaques were evaluated by B-Mode ultrasonography. Intima-media thickness (IMT) of both common carotids was measured by M-Mode ultrasonography. RESULTS: SBP, but not DBP, was significantly higher in patients with active disease than in cured patients and controls (P = 0.003). Hypertension was found in nine (30%) patients with active disease, in two (13.3%) of those cured from acromegaly and in none of controls (chi2 = 10.81, P < 0.004). Fasting blood glucose levels were significantly higher both in patients with active disease and in those cured from the disease than in controls (P < 0.001). Circulating insulin levels were significantly higher in patients with active disease than in cured patients and controls (P < 0.001) and in cured patients than in controls (P < 0.001). Glucose tolerance abnormalities were found in 13 (43.3%) patients with active disease, in four (26.6%) patients with inactive disease and in four controls (13.3%) (chi2 = 6.71, P = 0.03). Total blood cholesterol levels were similar in the three groups, LDL-cholesterol and triglycerides levels were significantly higher, whereas HDL-cholesterol levels were significantly lower both in patients with active disease and in those cured from the disease than in controls (P < 0.001). Serum fibrinogen levels were significantly higher both in patients with active disease and in those cured from the disease than in controls (P < 0.001). No difference was found in PT and APTT levels among the three groups. At the level of right and left common carotid arteries, IMT was significantly higher both in patients with active disease and in those cured from the disease than in controls (P < 0.001). Both right and left SPV, but not DPV, were significantly higher in patients with active disease than in those cured from the disease and in controls (P < 0.01). Well defined carotid wall plaques were detected in two patients (6.6%) with active disease, in one patient cured from the disease (6.6%) and in two controls (6.6%). At the level of right and left internal carotid arteries, SPV, DPV and RI were similar among the three groups. Well defined carotid wall plaques were detected in three patients with active disease (10%), two patients cured from the disease (13.3%) and in one control (3.3%). CONCLUSIONS: A significant increase of IMT of both common carotid arteries was observed in patients with active acromegaly, this was also found in those cured from acromegaly. However, the prevalence of well defined carotid plaques was not increased in both groups of patients with acromegaly as compared to controls. On this basis, heart more than vessels seems to be affected by chronic GH and IGF-I excess in acromegaly.

Acromegaly↗
PubMed2005

Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women.

UNLABELLED: This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. In patients with active acromegaly, vertebral fractures occur even in presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD. INTRODUCTION: We studied the frequency of radiological vertebral fractures in a cohort of postmenopausal women with active or controlled acromegaly. MATERIALS AND METHODS: Thirty-six postmenopausal acromegalic patients (15 with active and 21 with controlled disease) were evaluated for BMD, bone metabolism (serum 25-hydroxyvitamin D, PTH, bone-specific alkaline phosphatase [BSALP], and urinary deoxypyridinoline [Dpd]), and vertebral quantitative morphometry. Thirty-six nonacromegalic postmenopausal women, matched for age, were selected among the patients consulting the Bone Center as a control group for BMD evaluation and vertebral quantitative morphometry. RESULTS: Vertebral fractures were shown in 19 patients (52.8%) and 11 controls (30.6%; chi2: 3.7; p=0.06). Fractured acromegalic women were older and had higher serum IGF-1, Dpd, and BSALP and lower T score and serum vitamin D values compared with nonfractured patients. Moreover, the fractured women had a longer diagnosis and were in the postmenopausal period for a longer period than the nonfractured women. The fracture rate was significantly higher in active than in controlled acromegaly (80% versus 33.3%; chi2: 7.6; p=0.008). The patients with active acromegaly who fractured (12 cases) had significantly higher serum IGF-1 values (356 ng/ml; range: 212-950 versus 120 ng/ml; range: 84-217; p<0.001) and T scores (-1.3 SD, range: -2.9 to +1.3 versus -2.7 SD, range: -3.4 to -1.5, p=0.04) compared with the fractured women whose disease was controlled (7 cases). All fractured women with controlled acromegaly had T scores<-1.0 SD (57.1% of them had osteoporosis, and 42.9% were osteopenic). In contrast, 41.7% of women whose fractures were associated with active disease had a normal T score (>-1.0 SD), whereas osteopenia and osteoporosis were found only in 33.3% and 25.0% of them, respectively. CONCLUSIONS: This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. Furthermore, our study shows that, in patients with active acromegaly, vertebral fractures occur even in the presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD.

Acromegaly↗
PubMed1978

Lung function in acromegaly.

Lung function has been assessed by spirometry, body plethysmography, flow volume loops and single breath transfer factor in thirty patients with acromegaly. Having excluded eight patients with kyphosis and/or clinical or radiological evidence of pulmonary venous hypertension we have found a significant correlation between duration of acromegaly and lung size as assessed by total lung capacity. Excluding the same eight patients we have found evidence of small airways narrowing in eight patients, seven of these eight had had acromegaly for nine years or longer, and the duration of acromegaly was significantly longer in the patients with small airways narrowing than in those without. In the absence of other recognized causes it is possible that small airways narrowing in acromegaly is caused either by the increased whole blood volume with pulmonary vascular engorgement, or by increase in size of the soft tissues of the small conducting airways. Six of the eight patients with kyphosis and/or pulmonary venous hypertension also had evidence of small airways narrowing. Thus fourteen of the thirty patients with acromegaly had small airways narrowing. Five men had evidence of extra thoracic airway narrowing and in four the duration of acromegaly was ten years or longer. We conclude that the increase in total lung capacity, the incidence of small airways narrowing and the incidence of upper airway narrowing are all related to the duration of acromegaly. It seems that once duration exceeds eight years patients are very likely to develop abnormalities of lung function either primarily from the effects of acromegaly on the airways and lung or secondarily from the associated cardiovascular and thoracic skeletal abnormalities. It seems probable that the small airways and upper airway narrowing contribute to the morbidity and mortality of this disease. This study provides further evidence that acromegaly should be treated early.

Acromegaly↗
PubMed2001

Occurrence of ventricular late potentials in patients with active acromegaly.

OBJECTIVE: Patients with acromegaly have an increased risk of ventricular dysrhythmias and sudden death. Late potentials in a signal-averaged electrocardiogram (SAECG), a predictor of ventricular dysrhythmias, are frequently seen in patients after previous myocardial infarction, but little is known about the prevalence of late potentials in acromegaly. The aim of our study was to investigate the prevalence of late potentials in patients with acromegaly and their relation to the activity of the disease and to myocardial hypertrophy. PATIENTS: The study included 48 patients with acromegaly [27 males, 21 females, mean age 52.3 +/- 14.2 years, 16 active disease, 32 cured or 'well controlled', under treatment with sandostatin analogues (12/32)] and 38 healthy volunteers as a control group. RESULTS: Late potentials were detected in 9/16 (56%) patients with active acromegaly vs. 2/32 (6%) with cured/well controlled acromegaly (P = 0.001), defined as normal age-related IGF-1 levels and GH levels suppressible below 1 microg/l after an oral glucose load (75 g). Late potentials were not related to muscle mass index (127 +/- 35 active vs. 123 +/- 34 g/m2 cured/well controlled). The association of disease activity with the detection of late potentials was independent of age, gender, duration of the disease and body mass index. In comparison to the control group, the prevalence of late potentials was significantly higher in patients with acromegaly (23%) than in the control group (0%; P < 0.001). CONCLUSIONS: Late potentials in the SAECG are frequently seen in active acromegaly and may represent an early and sensitive parameter to detect myocardial injury in acromegaly.

Acromegaly↗
PubMed2001

Monitoring of treatment success in patients with acromegaly: the value of serum insulin-like growth factor binding protein-3 and serum leptin measurements in comparison to plasma insulin-like growth factor I determination.

The aim of the present study was to determine the value of serum insulin-like growth factor binding protein-3 (IGFBP-3) and serum leptin measurements in comparison with plasma insulin-like growth factor I (IGF-I) measurements as indicators of treatment success in patients with acromegaly. Thirty-five acromegaly patients, 25 female and 10 male, divided into groups of patients with postadenomectomy "active" acromegaly (n = 20) and patients with postadenomectomy "controlled" acromegaly (n = 15), and 44 healthy volunteers sex- and age-matched with the acromegaly patients were included in the present study. We comparatively analyzed plasma IGF-I, serum IGFBP-3, and serum leptin levels in the aforementioned groups. Because serum leptin has sex dimorphism, the groups were divided into sexes when leptin was evaluated. As expected, the patients with active acromegaly had significantly higher mean values of plasma IGF-I and serum IGFBP-3 and lower mean values of serum leptin (only in women) than the control group. However, individual evaluation showed that 1 of 20, 9 of 20, and many patients with postadenomectomy active acromegaly patients had values that overlapped values of control subjects for plasma standard deviation score (SDS)-IGF-I, serum SDS-IGFBP-3, and sex-adjusted serum leptin, respectively. Application of the receiver operating characteristic (ROC) curves method shows that plasma IGF-I measurement has the best discriminatory power to differentiate patients with postsurgical active acromegaly from healthy people. Its area under the curve (AUC) was 0.95, with a sensitivity and specificity of 86% and 94%, respectively. Its positive and negative likelihood ratios were 14 and 0.15. Serum IGFBP-3 has certain discriminatory power, its AUC being 0.89, with a sensitivity and specificity of 83% and 77%. Its positive and negative likelihood ratios were 3.6 and 0.22. Serum leptin, both in women and in men, has a poor performance with sensitivity and specificity of 53% and 50% for women and 55% and 56% for men and positive and negative likelihood ratios of 1.06 and 0.94 for women and 1.26 and 0.8 for men. Application of the ROC curves method and the determination of positive and negative likelihood ratios in comparative evaluation of serum IGFBP-3 and serum leptin with plasma IGF-I as indicators of treatment success in acromegalic patients showed that neither serum IGFBP-3 nor serum leptin determinations have accuracy better than or similar to that of plasma IGF-I for monitoring treatment success in acromegaly patients. Serum IGFBP-3 is accurate but does not increase accuracy for age-adjusted plasma IGF-I, whereas determination of serum leptin level has no value in monitoring these patients.

Acromegaly↗
PubMed2005

Acromegaly due to a growth hormone-releasing hormone-secreting intracranial gangliocytoma.

In more than 95% of cases acromegaly is due to GH hypersecretion by a pituitary adenoma. GHRH hypersecretion accounts for about 0.5% of cases of acromegaly. Intracranial GHRH-secreting tumors are extremely rare and only a few well-documented cases have been reported. The clinical features of acromegaly due to intracranial GHRH-secreting tumor are indistinguishable from those of other patients with "classical acromegaly". In cases of intrasellar gangliocytomas, not even radiological findings help to make the correct diagnosis, which can only be made with the hystological study. We present the case of a woman with acromegaly; the magnetic resonance demonstrated a 2x1.8x1.2 cm mass in the jugum sphenoidalis region, associated with a partial empty sella. There was a partial response to high-dose lanreotide therapy, so surgical treatment was decided, although only part of the tumor could be removed. Histopathological diagnosis was consistent with gangliocytoma, and immunostaining in the ganglionic cells was positive for GHRH. After surgery, hormone hypersecretion persisted, so medical treatment was reintroduced. In summary, we report a well-documented case of an intracranial GHRH-secreting gangliocytoma, an exceedingly rare cause of acromegaly. Clinical and biochemical data did not allow to make the correct diagnosis, which was only made on the pathological study. This case underscores that acromegaly can be due to causes other than a GH-secreting adenoma, and underlines that finding an image not typical of a pituitary adenoma should raise the suspicion that an unusual cause subsides the acromegaly.

Acromegaly↗
PubMed2006

Bone mineral density and turnover in patients with acromegaly in relation to sex, disease activity, and gonadal function.

Acromegaly is a rare disease caused by growth hormone (GH) hypersecretion. GH and insulin-like growth factor-I (IGF-I) exert anabolic activity in bones. Nevertheless, bone mineral density (BMD) loss is not uncommon in patients with acromegaly. It is assumed to be due to hypogonadism associated with the acromegaly. The aim of the study was to examine BMD at various skeletal sites and bone turnover and to assess the influence of impaired gonadal function and disease activity on BMD and turnover changes in acromegaly. A total of 62 patients were studied (40 women, 22 men). Among the women, 22 had active disease and 18 were cured; 16 women had normal gonadal function, and 24 were hypogonadal. Altogether, 12 men presented with active acromegaly, and 10 were cured; normal gonadal function was found in 10 men, and hypogonadism was diagnosed in 12 men. Controls were 30 healthy subjects. Densitometry using dual-energy X-ray absorptiometry of the lumbar spine, proximal femur, forearm, and total body was carried out. Bone turnover was studied based on serum osteocalcin, C-terminal collagen type 1 crosslinks, and bone alkaline phosphatase concentration. A disadvantageous effect of acromegaly on bone density was associated with hypogonadism in the distal radius (in women), the proximal femur (in men), and the total body (both sexes). An anabolic effect of GH during active acromegaly was present in the proximal femur only in men. We confirmed increased bone turnover in the presence of acromegaly, and these changes were similar regarding the activity of the disease and the gonadal status.

Absorptiometry, Photon↗
PubMed2001

Gender and age in the biochemical assessment of cure of acromegaly.

The principal biochemical criteria for cure in acromegaly are normalization of both glucose-suppressed GH levels and IGF-I levels. As we have reported previously, measurement of GH by highly sensitive assay in conjunction with IGF-I levels has led to a re-appraisal of "normal" GH suppression criteria during an OGTT in subjects with acromegaly. In some patients with active acromegaly, glucose-suppressed GH levels as measured by highly sensitive assay are much lower than could previously be appreciated with less sensitive GH assays and some other patients in apparent remission have subtle abnormalities of GH suppression. A question to arise is whether gender differences in glucose-suppressed GH levels as found by others in young healthy subjects should be considered in our interpretation of OGTT criteria for cure in acromegaly. Therefore, we have evaluated parameters of GH secretion in a larger number of subjects from our cohort of postoperative patients with acromegaly and in healthy subjects in order to determine if gender or age associated differences in these parameters exist. Ninety-two subjects with acromegaly (49 men, 43 women) and 46 age-matched healthy subjects (26 men, 20 women) were evaluated with baseline GH and IGF-I levels and nadir GH levels after a 100 g. OGTT. GH was assayed by highly sensitive IRMA (DSL). Basal GH levels were higher in female than in male healthy subjects, but the fall in GH from baseline (% suppression) was also greater in females resulting in no significant difference in mean nadir GH levels in female vs. male healthy subjects (0.09 vs. 0.08 microg/L). In the subjects with acromegaly, there were no significant gender differences in basal, %GH suppression or nadir GH levels. Basal and nadir GH levels correlated significantly only in subjects with active disease (r=0.84, p<.0001). Similarly, IGF-I levels correlated significantly with basal (r=0.573, p=.0012), and nadir (r=.702, p<.0001) GH levels only in subjects with active disease. Gender differences in IGF-I levels were not apparent in any group of subjects. As expected, IGF-I levels declined with age in those groups of subjects with normal IGF-I levels. Nadir GH levels did not vary with age. In conclusion, we have not found significant gender or age-related differences in nadir GH levels and thus our data does not support separate OGTT criteria for cure in men and women with acromegaly.

Acromegaly↗
PubMed2002

Oncological complications of excess GH in acromegaly.

Around fifteen percent of the deaths reported in acromegaly are attributable to malignancy (SM Melmed, J Clin Endocrinol Metab 2001;86:2929-2934; A Mestrón, SM Webb, In: Endocrine Society, San Francisco, June 2002 (abstract)), uncontrolled disease is associated with a growth advantage for concurrent neoplasms, which are more likely to be aggressive; however, there is no clear evidence of de novo cancer initiation in acromegaly and no proven causal relationship of acromegaly with malignant disease. Overall and cancer mortality in acromegaly have been shown to correlate with the degree of GH control; if post therapy GH is controlled, both the overall and cancer mortality do not appear to differ from that of the normal population (SM Orme et al., J Clin Endocrinol Metab 1998;83:2730-2734; JD Nabarro, Clin Endocrinol 1987;26:481-512). However, no long-term prospective evaluation of cancer prevalence or its relation to biochemical or clinical disease activity is available. IGF-1 appears to exert a permissive effect on tumorigenesis; there is no clear evidence that tumor initiation is triggered by IGF-1 in acromegaly; nevertheless, since IGF-1 may be higher in neoplasms, aggressive treatment aimed at controlling the disease activity will theoretically be advantageous for acromegalic patients with cancer. The prevalence of colon polyps and colon cancer appear to be incresed in acromegaly as is mortality for colon cancer (Orme et al., 1998), so regular colonoscopy screening and polypectomy would seem advisable, especially in older patients with active acromegaly. Surveillance for prostate cancer in elderly males with high IGF-1, especially if also receiving testosterone replacement therapy, is recommendable, by measurement of serum PSA, rectal examination and/or prostatic ultrasound. In women, mammography should be offered, especially after the age of 50 years, as in the normal population. Neither prostate nor breast cancer have been consistently shown to have an increased prevalence in acromegaly, but larger prospective epidemiological studies are required to study this further.

Acromegaly↗
PubMed2003

Basal and glucose-suppressed GH levels less than 1 microg/L in newly diagnosed acromegaly.

The development of highly sensitive and specific GH assays has necessitated a critical re-evaluation of the biochemical criteria needed for the diagnosis of acromegaly. Use of these assays has revealed that GH levels after oral glucose in healthy subjects and postoperative patients with active acromegaly can be significantly less than previously recognized with older GH assays. In order to assess GH criteria for newly diagnosed acromegaly with a modern assay we have evaluated GH levels in 25 patients referred to our Neuroendocrine Unit for evaluation of untreated acromegaly. All patients underwent measurement of basal GH and IGF-I levels and 15 of these patients also underwent oral glucose tolerance testing for GH suppression (OGTT). Basal GH levels were < 1.0 microg/L at diagnosis in 5 of these 25 patients. Nadir GH levels were less than 1 microg/L also in 5 of 15 patients, and as low as 0.42 microg/L. All patients had elevated IGF-I levels preoperatively and pathological confirmation of a GH secreting pituitary tumor at the time of transsphenoidal surgery. The clinical presentations of these patients was variable. Most patients presented with classical manifestations of acromegaly, but 3 of the 5 patients with low nadir GH values had only very subtle signs of acromegaly. Although most newly diagnosed patients have classically elevated GH levels and obvious clinical features of acromegaly, early recognition of disease may uncover patients with milder biochemical and clinical abnormalities. The diagnosis should not be discounted in patients who have elevated IGF-I levels, but have basal or nadir GH levels less than 1 microg/L. Conventional GH criteria for the diagnosis of acromegaly cannot be applied to the use of modern sensitive and specific GH assays.

Acromegaly↗
PubMed1998

Outpatient assessment of residual growth hormone secretion in treated acromegaly with overnight urinary growth hormone excretion, random serum growth hormone and insulin like growth factor-1.

OBJECTIVE: To assess the outpatient investigations, overnight urinary growth hormone (uGH) excretion, random serum GH and insulin like growth factor 1 (IGF-1), and GH indices from the oral glucose tolerance test (OGTT) (fasting, nadir and mean GH), as measures of mean GH secretion in treated acromegaly, in comparison with a GH day series, which served as a gold standard. DESIGN: Prospective cross-sectional study, with patients admitted to a metabolic ward for the following investigations: random GH, IGF-1, 6 point GH day series (day 1), 9 h timed overnight uGH excretion, OGTT with GH response (day 2). Agreements between the mean GH during the day series and the other outcome measures, and the diagnostic performance of the latter, for the presence or absence of active acromegaly (mean GH during day series > or = 5 or < 5 mU/l, respectively) were determined. PATIENTS: 26 patients with treated acromegaly (11 with inactive acromegaly off drug therapy). MEASUREMENTS: Serum GH and uGH were measured by immunoradiometric assays and IGF-1 by radioimmunoassay. RESULTS: Agreements with the mean GH during the day series were perfect for the nadir GH during the OGTT with a 2 mU/l cutoff (Cohen's kappa (kappa) = 1, P < 0.00001), almost perfect for the fasting and mean GH throughout the OGTT (both kappa = 0.92, P < 0.0001) and random GH (kappa = 0.85, P < 0.0001), and substantial for the nadir GH with a 5 mU/l cutoff (kappa = 0.77, P < 0.0001), IGF-1 (kappa = 0.62, P < 0.001) and overnight uGH excretion (kappa = 0.61, P = 0.002). Nadir GH with a 2 mU/l cutoff was completely accurate for diagnosing the presence or absence of active acromegaly (positive and negative predictive values (% +/- standard error percentage) 100 +/- 8% and 100 +/- 10%). None of the outpatient tests used alone was an adequate diagnostic test (positive and negative predictive values: overnight uGH excretion -86 +/- 10% and 75 +/- 13%; random GH -100 +/- 11% and 85 +/- 11%; IGF-1 -92 +/- 10% and 71 +/- 13%) and so combinations of tests were assessed. The best was overnight uGH excretion plus random GH (positive and negative predictive values 88 +/- 9% and 100 +/- 12%). Using all three outpatient investigations, the positive predictive value of three raised results was 100 +/- 13%. CONCLUSIONS: In treated acromegaly, residual GH secretion can be reliably assessed with the OGTT, using standard diagnostic criteria. It can also be assessed on an outpatient basis with overnight uGH excretion and random GH, as direct measures, and IGF-1. If these are all normal, active acromegaly is excluded. Three raised results denote active acromegaly, and one or two raised results would need further investigation with a GH day series.

Acromegaly↗
PubMed2004

Colonoscopic screening and follow-up in patients with acromegaly: a multicenter study in Italy.

Acromegaly is an infrequent disease attributable to endogenous excess of GH and IGF-I. Human studies have associated the GH-IGF-I axis with the development of colorectal cancer; however, the question of whether colorectal cancer is a problem in acromegaly is currently unresolved. We performed a cross-sectional study to assess the risk of colonic neoplasia in patients with acromegaly. Colonoscopic screening was performed in 235 patients with acromegaly at five tertiary care hospitals in Italy between January 1, 1996, and December 31, 2001. A repeat colonoscopy was performed in 121 patients after a mean interval of 32.1 months. Colonoscopic findings in patients with acromegaly were compared with those of 233 patients with nonspecific abdominal complaints who were referred for endoscopy during the study period. A total of 65 patients (27.7%) and 36 controls (15.5%) had colonic neoplasia. In 55 patients (23.4%) and 34 control subjects (14.6%), the most important findings were adenomas (odds ratio, 1.7; range, 1.1-2.5), whereas 10 patients (4.3%) and two control subjects (0.9%) had carcinoma (odds ratio, 4.9; range, 1.1-22.4). The risk of colonic neoplasia was higher for younger patients with acromegaly compared with age-matched controls. Patients with acromegaly with or without colonic neoplasia did not differ significantly for IGF-I levels or duration of disease. A neoplastic recurrence was found in 16.5% of patients who underwent follow-up; 90% of them had had a neoplasm removed at the first colonoscopy. Acromegaly carries with it a moderate, but definitive, increase in the risk of colonic neoplasia that occurs at a younger age than in the general population. Patients who are found to harbor a colonic neoplasia are at risk for recurrence.

Acromegaly↗
PubMed1997

Cardiac involvement in acromegaly: specific myocardiopathy or consequence of systemic hypertension?

To evaluate the relative contributions of past or present GH hypersecretion and of hypertension to the cardiac abnormalities present in acromegaly, we have studied the serum GH and insulin-like growth factor I concentrations, systolic and diastolic blood pressures, and morphological and functional cardiac indexes as measured by echocardiography-Doppler, in 39 patients with active or cured acromegaly, 16 hypertensive controls, and 17 normotensive controls. Hypertension was present in 42.8% of patients with active acromegaly and in 28.0% of patients in which acromegaly was cured. Hypertension was independently related to an increase in indexes of cardiac morphology (left ventricular mass, left ventricular posterior wall thickness, interventricular septum thickness, relative wall thickness with respect to the diastolic diameter of the left ventricle, and left atrial end-systolic diameter), systolic function (stroke volume, fractional shortening, and end-systolic stress), and diastolic function (isovolumic relaxation time and maximal late diastolic flow velocity) and to a reduction in the early to late maximal diastolic flow velocity ratio. Acromegaly was related to an increase in left ventricular mass, stroke volume, cardiac output, and isovolumic relaxation time, which were independent from the presence of hypertension. End-systolic stress was reduced by acromegaly. In the five patients in which active acromegaly was successfully treated, left ventricular mass and left ventricular posterior wall thickness were reduced 1 yr later. In conclusion, the asymptomatic morphological and functional cardiac abnormalities present in acromegalic patients are independently related to acromegaly and hypertension, pointing to the existence to a specific acromegalic myocardiopathy that might be aggravated by the coexistence of hypertension.

Acromegaly↗
PubMed2006

Acromegaly presenting with diabetic ketoacidosis, associated with retinitis pigmentosa and octreotide-induced bradycardia: a case report and a review of the literature.

Carbohydrate intolerance is a common feature of acromegaly. Frank diabetes mellitus is seen in about 10-20% of patients. There is no report of acromegaly presenting with diabetic ketoacidosis (DKA), associated with retinitis pigmentosa (RP), in the literature. We report the occurrence of DKA and RP in a patient with acromegaly. A 39-year-old Turkish man was admitted to the emergency ward with a 1-mo history of thirst, polyuria, weight loss of 10 kg, and loss of consciousness for 2 d. Physical examination revealed findings suggestive of acromegaly, including coarse facial features and enlargement of his hands and feet. At ophthalmological examination, funduscopy showed RP. Laboratory studies confirmed the diagnoses of DKA and acromegaly. Magnetic resonance imaging disclosed the presence of a pituitary adenoma. During the medical treatment with octreotide, symptomatic sinusoidal bradycardia was developed (pulse rate 45 bpm, and blood pressure 70/40 mmHg). Octreotide therapy was stopped. Pituitary adenoma was removed surgically. For treatment of DKA, insulin need was very high in the first days after the onset of ketoacidosis, but decreased after initiation of treatment with octreotide and after successful operation. Insulin was stopped 7 d after surgery. Follow-up showed normalization of growth hormone levels and plasma glucose levels. Only six other cases of DKA associated with acromegaly and only three other cases of RP associated with acromegaly were found in the medical literature. In conclusion, to our knowledge, the present case is a first report of DKA and RP in patient with acromegaly.

Acromegaly↗
PubMed2005

Persistent diastolic dysfunction despite successful long-term octreotide treatment in acromegaly.

INTRODUCTION: This study was designed to evaluate potential reversibility of left-ventricular (LV) dysfunction in patients with acromegaly following long-term control of disease. It is unknown whether the cardiac changes induced by acromegaly can be reversed completely by long-term strict control of growth hormone excess by octreotide. PATIENTS AND METHODS: We compared LV systolic and diastolic function in inactive patients with acromegaly (n = 22), who were divided into patients with long-term control by octreotide (n = 14) and patients with long-term cure by surgery/radiotherapy (n = 8). We also assessed these parameters in patients with active acromegaly (n = 17). RESULTS: In patients with active acromegaly, systolic function at rest was decreased by 18% (P < 0.01), LV mass index increased by 40% (P < 0.04) and isovolumetric relaxation time increased by 19% (P < 0.01), compared with patients with inactive acromegaly. These parameters were not different between well-controlled and cured patients. Using tissue Doppler imaging, the ratio between early and late diastolic velocity (E'/A' ratio) was decreased in active, compared with inactive acromegaly (0.75+/-0.07 versus 1.24+/-0.15; P < 0.01). This E'/A' ratio was considerably higher in cured, compared with octreotide-treated, patients (1.75+/-0.41 versus 1.05+/-0.1; P < 0.01). CONCLUSION: Diastolic function is persistently and significantly more impaired in acromegalic patients with long-term control by octreotide than in surgically cured patients, which points to biological effects of subtle abnormalities in growth hormone secretion. Criteria for strict biochemical control of acromegaly should thus be reconsidered.

Acromegaly↗
PubMedDate not supplied

Successful pregnancy in a woman with acromegaly treated with octreotide.

OBJECTIVE: To report a successful pregnancy in a 43-year-old woman with acromegaly and treatment during pregnancy with the somatostatin analogue octreotide, to review the physiologic aspects of acromegaly during pregnancy, and to discuss treatment options. METHODS: A case report is presented, and the current literature is reviewed. RESULTS: In a 40-year-old woman with acromegaly and secondary amenorrhea, menstrual periods resumed after treatment with octreotide. At age 43 years, she became pregnant and decided to continue octreotide therapy because of the relatively large size of the tumor and severe headaches when use of the medication was discontinued. Growth hormone and insulin-like growth factor I levels remained normal throughout pregnancy, and a normal full-term infant was born. Several months after delivery, severe cholecystitis developed, and the patient underwent laparoscopic cholecystectomy. CONCLUSIONS: This case report describes the oldest documented woman with acromegaly who has completed a pregnancy and only the second patient treated with octreotide for the entire pregnancy. During a normal pregnancy, placental growth hormone suppresses pituitary growth hormone secretion; in patients with acromegaly, pituitary growth hormone secretion remains autonomous. Treatment of acromegaly with octreotide, bromocriptine, irradiation, or surgical intervention may restore menses and fertility to women of reproductive age. Bromocriptine has been used throughout pregnancy without teratogenic effects in many patients. Octreotide has been used during the first trimester of pregnancy in seven other women with acromegaly (throughout pregnancy in one of those patients) and for the entire pregnancy in one woman with a thyrotropin-secreting pituitary tumor; no adverse effects were noted. Lanreotide was also used in one patient briefly during the first trimester without adverse consequences. Although the outcomes of the current and previous pregnancies have been favorable, insufficient data are available to recommend the routine use of octreotide in all pregnant women with acromegaly.

Acromegaly↗
PubMed2002

Serum leptin levels in acromegaly--a significant role for adipose tissue and fasting insulin/glucose ratio.

BACKGROUND: Leptin plays an important role in controlling satiety and maintaining energy balance. Acromegaly is characterized by decreased fat, which increases after the disease is cured. Our objective was to investigate serum leptin in acromegaly in terms of disease activity, body fat content, insulin and glucose levels, and selected anthropometric variables. MATERIAL/METHODS: We examined 40 patients with acromegaly and 20 sex- and age-matched controls for the levels of serum GH, IGF-I, leptin, glucose, and insulin, and for body composition by DEXA, BMI and WHR. In 10 cases the acute effect on serum leptin of a somatostatin analogue, lanreotide, was studied. RESULTS: We observed lower leptin in patients with active acromegaly than in cured patients and controls. Body fat was higher in cured than active patients. In the patients, we found significant correlations (p<0.05) between leptin and percent body fat (r=0.77), leptin and body fat mass (r=0.74), leptin and fasting insulin (r=0.62), leptin and fasting insulin/glucose ratio (r=0.97), leptin and BMI (r=0.44), leptin and height (r=-0.47). In the controls there was a significant correlation (p<0.05) only between leptin and WHR (r=-0.45). A paradoxical decrease of the leptin level after lanreotide was observed in 7 out of 10 patients with active acromegaly. CONCLUSIONS: Changes in leptin release in acromegaly are related to differences in body fat content and mass, and in insulin resistance. Leptin in acromegaly is not influenced directly by GH or IGF-I secretion. The acute effect of medical treatment of acromegaly by a somatostatin analogue on leptin levels differs from the effect of a radical cure following pituitary adenoma surgery.

Acromegaly↗