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PubMed1985

Zinc, copper, manganese, and selenium metabolism in patients with human growth hormone deficiency or acromegaly.

This study was designed to evaluate trace metal metabolism in patients with known abnormalities of human growth hormone (hGH). The mean concentration of zinc in plasma and urine decreased in patients with hGH deficiency after hGH injection, whereas, after adenomectomy, in patients with acromegaly, zinc increased in plasma, remained the same in erythrocytes, and decreased in urine. There was a negative correlation between plasma zinc and serum hGH levels and a positive correlation between urinary zinc excretion and serum hGH levels in acromegaly. In hGH deficiency, the copper content remained unchanged in plasma and erythrocytes and rose in urine after treatment; however, in acromegaly, the copper content increased in plasma and remained unchanged in erythrocytes and urine after surgery. The mean concentration of erythrocyte manganese did not change significantly after treatment in patients with hGH deficiency or acromegaly, but the pre-hGH treatment level of erythrocyte manganese in hGH deficiency was lower than in the controls. Plasma selenium concentrations were decreased in hGH deficiency and increased in acromegaly patients after therapy. These results suggest that hGH affects the metabolism of zinc, copper, manganese, and selenium.

Acromegaly↗
PubMed2002

Acromegaly caused by a growth hormone-releasing hormone-secreting carcinoid tumor: case report.

OBJECTIVE AND IMPORTANCE: We describe a patient with acromegaly and pituitary hyperplasia secondary to a growth hormone-releasing hormone-secreting gastrointestinal carcinoid tumor. This case report illustrates the importance of including this rare clinical syndrome in the differential diagnosis of acromegaly for patients with suspected or known neuroendocrine tumors. CLINICAL PRESENTATION: A 19-year-old, Asian-American, male patient with a 2-year history of a nonresectable, metastatic, intestinal carcinoid tumor presented with complaints of headaches, arthralgias, sweats, and changing features. The examination revealed a young subject with acromegalic features, without visual field deficits. Magnetic resonance imaging revealed a diffuse sellar mass that extended suprasellarly to compress the optic chiasm. Endocrinological studies demonstrated a growth hormone level of more than 100 ng/ml and an inappropriately elevated growth hormone-releasing hormone level. INTERVENTION: The patient underwent transsphenoidal resection of the pituitary mass for diagnostic and decompressive purposes. The pathological examination revealed pituitary hyperplasia, without evidence of an adenoma. Therapy with long-acting repeatable octreotide (Sandostatin LAR; Novartis AG, Basel, Switzerland) was initiated postoperatively, to further control the acromegaly and carcinoid tumor. The soft-tissue swelling resolved, and the patient remained free of headaches, arthralgias, and sweats at the 6-month follow-up examination. CONCLUSION: Ectopic acromegaly is a rare syndrome that must be recognized by neurosurgeons because its treatment differs from that of classic pituitary acromegaly. We describe a patient for whom this syndrome was documented with magnetic resonance imaging, endocrinological testing, and pathological examinations.

Acromegaly↗
PubMed2005

Alterations of protein metabolism in acromegaly.

PURPOSE OF REVIEW: Growth hormone is a powerful anabolic hormone necessary for normal growth, but its importance in maintaining the cellular and protein mass in adult life is still unclear. However, it is viewed as a drug capable of combating the tissue loss and some metabolic derangements of aging. Growth hormone excess causes acromegaly, a disease characterized by overgrowth of some tissues and multiple metabolic abnormalities. The purpose of this article is to review recent knowledge in acromegaly considering it as a model for clarifying aspects of growth hormone action on body composition, protein dynamics and molecular mechanisms in adult life. RECENT FINDINGS: Acromegaly induces well-documented changes in body fat (decreased), and bone density and water retention (increased), but there are less-clear changes in protein and body cell-mass accretion. Recent studies related insulin resistance to glucose metabolism to accelerated fat oxidation and described the reversibility of such alterations after surgical or pharmacologic therapy. Less attention was paid to changes in protein metabolism. Acromegalics are profoundly insulin-resistant to the antiproteolytic action of insulin, but amino acids are channelled towards protein synthesis because they are still normally spared from oxidation by insulin. This insulin resistance persists months after the surgical cure of acromegaly when glucose metabolism is already normalized. Recent studies suggested that increased use of fat for fuel by growth hormone may also promote protein anabolism and reduce amino acid oxidation. SUMMARY: Despite important advances in understanding molecular mechanisms in acromegaly, the specific effects on body cell and protein mass and the specific modulation of local protein dynamics remain poorly defined.

Acromegaly↗
PubMed1987

Acromegaly.

A personal series of 256 cases of acromegaly/gigantism seen over a 20-year period from 1963 is described. The insidious nature of the condition resulted in delay in diagnosis which was often made by a doctor when seeing the patient for an unrelated problem. Other features which commonly led to the diagnosis being made were headache, change in appearance, carpal tunnel syndrome, amenorrhoea and diabetes. The Hardy system for grading the radiological appearance of the pituitary tumour was used. Widely invasive tumours were not common but tended to occur in patients with younger age of onset and high GH levels. The occurrence of various symptoms and clinical features was noted and the changes resulting from reducing the GH level to normal. The incidence of hypertension, but not of coronary artery disease, is increased and the blood pressure may be reduced following successful treatment. The effects on the upper and lower respiratory tract are reported as well as sleep apnoea and problems associated with anaesthesia. Skin manifestations included sweating, pigmented skin tags, acanthosis nigricans and cutis verticis gyrata. In the skeletal system the incidence of kyphoscoliosis and osteoarthritis especially of the hip is reported: the question of hip replacement is discussed. Diabetes mellitus disappeared in most cases if the acromegaly was cured. In men but not in women the incidence of colloid nodular goitre was increased as was hyperthyroidism in middle-aged women. In two patients a parathyroid adenoma was present: hypercalcaemia was present in five additional patients, but the cause was not determined. The common occurrence of amenorrhoea in the younger women was noted, it was not always associated with hyperprolactinaemia, and often responded to successful treatment of the acromegaly. The association of acromegaly with hirsutism and galactorrhoea is confirmed. The incidence of impotence and loss of libid in the men is discussed: in a proportion of those in whom the acromegaly was cured, potency returned, but in a number depression occurred and what was believed to be psychogenic impotence persisted. Hyperprolactinaemia was found in 49 out of 151 patients with active acromegaly in whom the prolactin level was measured. Previous reports have indicated a doubling of death rates in acromegalics. In this series there were 47 deaths observed compared to 37.2 expected. The increased death rate was in women of all ages and in men under the age of 55, The increased deaths in the women were from cardiovascular and cerebrovascular causes and from breast cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Acromegaly↗
PubMed1994

Body composition in active acromegaly during treatment with octreotide: a double-blind, placebo-controlled cross-over study.

OBJECTIVE: In active acromegaly body composition is characteristically altered by an increase in lean body mass and a corresponding reduction in fat mass. These changes are induced by an excessive secretion of GH and insulin-like growth factor I (IGF-I). Growth hormone is an anabolic hormone and leads to stimulation of protein synthesis and an increased lipolysis in adipose tissue. Treatment with the somatostatin analogue, octreotide, has been shown to reduce GH levels causing reduced hormonal effects on target tissues. We have studied changes in body composition during short-term reduction in GH level by octreotide in active acromegaly. DESIGN: Octreotide was compared to placebo in a double-blind, cross-over trial. Dual-energy X-ray absorptiometry scanning was employed to calculate body composition. Relations between body composition parameters and clinical signs of acromegaly (finger circumference and foot volume) were studied. PATIENTS: Twelve patients with active acromegaly, confirmed by lack of GH suppression during oral glucose loading, were included. All had pituitary adenomas diagnosed by computed tomography. MEASUREMENTS: Serum GH and IGF-I. Lean body mass, fat mass and total weight, foot volume and finger circumference. RESULTS: Four weeks of octreotide treatment caused a 75% decrease in GH levels (n = 10), a reduction in IGF-I from 476 +/- 51.9 (mean +/- SEM) to 233 micrograms/l +/- 46.3 (P < 0.005) and a corresponding decrease in both body weight (2.51 kg +/- 0.41) (P < 0.005) and lean body mass (2.44 kg +/- 0.48) (P < 0.005). No significant changes in fat mass were observed. These findings were paralleled by significant reductions in foot volume (44.50 ml +/- 17) (P < 0.05) and finger circumference (1.3 mm +/- 0.3) (P < 0.05). CONCLUSIONS: Short-term octreotide therapy reduces growth hormone levels leading to a significant reduction in lean body mass as assessed by dual-energy X-ray absorptiometry. Alterations in lean body mass were positively correlated with reductions in foot volume. Thus, simple clinical tests may be valuable in judging the effects of treatment in active acromegaly.

Absorptiometry, Photon↗
PubMed1994

Determinants of clinical outcome and survival in acromegaly.

OBJECTIVE: The extent to which treatment modifies the excess in morbidity and mortality in acromegaly remains uncertain. This study investigates the determinants of final outcome following therapy for acromegaly. DESIGN: A retrospective analysis of patients treated at the Departments of Endocrinology and Neurosurgery, Auckland Hospital, New Zealand. PATIENTS: One hundred and fifty-one patients (63 females and 88 males) with acromegaly or gigantism treated between the years 1964 and 1989. The mean duration of follow-up was 12 years (median 11 years). MEASUREMENTS: Patients had their age, estimated duration of symptoms preceding diagnosis, serum GH at diagnosis, presence of diabetes mellitus, cardiovascular disease, hypertension and/or osteoarthritis at diagnosis and the last known serum GH documented. The final outcome at the time of study was graded under three classes: dead (n = 32), those with major complications (n = 47) and those with minor/no complications (n = 67). RESULTS: The mean age at diagnosis of acromegaly was 41 years and the average estimated duration of symptoms prior to diagnosis was 7 years, with older patients showing longer duration of symptoms preceding diagnosis (P = 0.0002). Final outcome (dead, alive with major complications, alive and well) was significantly worse in those with older age at diagnosis (P = 0.008), longer duration of symptoms before diagnosis (P = 0.03) and higher GH at last follow-up (P = 0.0001). In multivariate analysis, survival was significantly influenced by the last known GH (P = 0.0001), presence of hypertension (P = 0.02) or cardiac disease (P = 0.03) at diagnosis, and duration of symptoms prior to diagnosis (P = 0.04). Survival in the acromegalic group, irrespective of treatment, was reduced by an average of 10 years compared with the non-acromegalic population. CONCLUSIONS: Acromegaly has a significant adverse effect on well-being and survival. The predominant determinant of outcome is the final serum GH level following treatment.

Acromegaly↗
PubMed2005

Determination of large bowel length and loop complexity in patients with acromegaly undergoing screening colonoscopy.

BACKGROUND: Patients with acromegaly are at moderately increased risk of developing colorectal cancer and may be considered for screening colonoscopy. In turn, large bowel dimensions may be increased in these patients, factors that predict for increased risk of serious complications such as perforation. OBJECTIVE: To evaluate this risk potential, we measured large bowel length and loop complexity using magnetic endoscopic imaging (MEI). DESIGN: Case-control study in 25 unselected patients with acromegaly (mean age 56 years) vs. 41 nonacromegalic controls (mean age 60 years) undergoing screening colonoscopy. MEASUREMENTS: MEI parameters were determined and age- and sex-adjusted mean differences calculated. The dependency of total large bowel length on various demographic and disease-related factors (e.g. GH exposure, IGF-I and IGFBP-3 concentrations) was assessed using regression techniques. RESULTS: Total large bowel length was increased by 20%[95% confidence interval (CI) 9-31%] in patients with acromegaly compared with controls (unadjusted and adjusted; P-values < 0.001). Acromegaly was also associated with increased time taken to reach the caecum (P = 0.01) and increased pelvic loop complexities (5/25 vs. 1/41, Fisher's exact test: P = 0.03). Total large bowel length was predicted by age at colonoscopy (P = 0.003) and patient height (P = 0.03), but not by surrogate biochemical markers of disease activity. CONCLUSIONS: Acromegaly is associated with increased large bowel length and loop complexity making colonoscopy technically challenging, and theoretically increasing the risk of serious complications. Patients need to be counselled accordingly, and appropriate resources with experienced staff allocated.

Acromegaly↗
PubMed2006

Pulsed tissue Doppler identifies subclinical myocardial biventricular dysfunction in active acromegaly.

OBJECTIVE: The aim of this study was to assess the role of pulsed tissue Doppler (TD) to identify left (LV) and right ventricular (RV) myocardial regional involvement in acromegaly. PATIENTS AND MEASUREMENTS: Thirty active acromegaly patients, free of diabetes mellitus, thyroid dysfunction, valvular and coronary heart disease, clinically overt heart failure, and 30 sex- and age-matched healthy controls underwent standard Doppler echocardiography and pulsed TD, by placing the sample volume at the level of basal posterior septum, LV lateral mitral annulus and RV lateral tricuspid annulus. Myocardial systolic (S(m)) and diastolic velocities (E(m)/A(m) ratio) and time-intervals of relaxation (RT(m)), precontraction (PCT(m)) and contraction (CT(m)) and the PCT(m)/CT(m) ratio were measured at each level. RESULTS: The two groups had similar heart rate, whereas acromegaly patients had higher body mass index, systolic and diastolic blood pressure, LV mass and impaired Doppler indexes of LV and RV diastolic function, without any difference in the global systolic function. At TD, acromegaly patients showed significantly delayed RT(m) and PCT(m,) reduced E(m)/A(m), S(m) and increased PCT(m)/CT(m) of posterior septum, mitral annulus and tricuspid annulus in comparison with controls. By separate multilinear regression analyses, after adjusting for body mass index, heart rate, diastolic blood pressure and LV mass index, age was the main independent determinant of tissue Doppler diastolic but not of systolic indexes. CONCLUSIONS: In active acromegaly, pulsed TD confirms LV and RV diastolic abnormalities detectable by standard Doppler, additionally identifying subclinical biventricular impairment of systolic function.

Acromegaly↗
PubMed2005

Tensegrity and type 1 dermal dendrocytes in acromegaly.

BACKGROUND: Skin is enlarged and doughy in acromegaly. Alterations have been reported in the structure of the extracellular matrix (ECM) and in the mechanical properties of the dermis. It is recognized that internal tensions in the dermis give rise to active cell-ECM and cell-cell mechanical interactions. This mechanobiological aspect can lead to functional and conformational changes in the cells. Such alterations in connective tissue cells have not been explored so far in acromegaly. The aim of the study was to assess structural changes in the dermal ECM, and in the number and shape of factor XIIIa-positive type I dermal dendrocytes (DDs) in acromegaly. MATERIALS AND METHOD: A total of 32 patients with acromegaly (three untreated, 17 with active disease under somatostatin analogues and 12 cured) were examined. Both the maximum and the most recent IGF-1 (insulin-like growth factor) dosages recorded in the patients' files were retrieved. Skin biopsies were taken from their forearms. Histochemistry, immunohistochemistry, morphometry and electron microscopy were used. RESULTS: Collagen-bundle coarsening and acidic glycosaminoglycan deposits were found irrespective of the current endocrine status. Dermal dendrocytes were often markedly reduced in numbers, but those present were plump with few dendrites. A negative correlation was found between DD numbers and the maximum IGF-1 dosages recorded in the patients' files. A similar although weaker trend was found with the most recent IGF-1 dosages. CONCLUSIONS: Collagen, glycosaminoglycans and DDs appeared affected in acromegaly, even when the hormonal status was controlled after surgery and/or somatostatin analogue treatment. The persisting conformational change of DDs suggests a modification in cellular tensegrity, perhaps initiated by hormonal effects and probably maintained by alterations in the ECM interactions.

Acromegaly↗
PubMed1997

An audit of long-term octreotide therapy for acromegaly.

BACKGROUND: Octreotide has been successfully used for the treatment of acromegaly, but little long-term data are available. AIMS: To determine the long-term efficacy and safety of octreotide in the treatment of acromegaly. METHODS: Twenty-seven patients with acromegaly were treated with octreotide in a non randomised study. Six patients had not had previous surgery or radiotherapy, and were treated with octreotide alone. Symptoms of acromegaly, IGF-I levels, growth hormone suppression by glucose, pituitary tumour size, and side effects were monitored. The median duration of treatment was 44 months (range six-102). RESULTS: Symptom control was excellent. Twenty (74%) patients had a reduction of IGF-I into the normal range. IGF-I levels fell after one year from 94.2 +/- 6.1 nmol/L (mean +/- SEM) to 50.0 +/- 2.7 nmol/L (p < 0.0001). Ten of 13 (77%) patients had normal IGF-I levels after four years. These reductions have persisted for up to nine years of octreotide therapy. The GH response to glucose was normalised in 14 of 16 (88%) subjects. Eleven of 25 (44%) patients had a reduction in pituitary gland height. Side effects were common, but usually of a minor nature. Cholelithiasis occurred in 39% of patients. Two patients ceased octreotide because of side effects. CONCLUSIONS: We conclude that octreotide is an effective and safe long-term treatment for acromegaly. It is a useful adjunct to surgery, and may be offered as sole therapy for patients with smaller adenomas.

Acromegaly↗
PubMed1980

Central corneal thickness and intraocular tension in patients with acromegaly.

In 27 patients with pituitary adenomas the central corneal thickness and the intraocular tension were measured. Thirteen of the patients were suffering from acromegaly, and in this group the central corneal thickness was 0.561 mm +/- 0.35 (mean +/- SD). In the 14 patients with pituitary adenomas but no acromegaly the central corneal thickness was 0.526 mm +/- 0.030 (mean +/- SD). This difference is statistically significant 0.01 greater than P greater than 0.001. In the 13 patients with acromegaly the intraocular tension measured by applanation was 16.9 mmHg +/- 2.3 (mean +/- SD) and in the control group 14.7 mmHg +/- 2.4 (mean +/- SD). This difference is statistically significant (0.05 greater than P greater than 0.02). When the applanation reading is corrected for the difference in the central corneal thickness, the patients suffering from acromegaly have an intraocular tension of 14.1 mmHg, which is of the same magnitude as the tension in the patients without acromegaly.

Acromegaly↗
PubMed2006

Is there still a role for radiotherapy in acromegaly?

External radiotherapy (ideally 3-field radiotherapy with a daily fractional dose no higher than 1.8 Gy or conformal irradiation) has been used extensively in the treatment of acromegaly, and virtually all studies have documented a predictable but slow reduction in growth hormone (GH) excess, which is at its maximum in the first year after treatment (30-50%) and continues at an average rate of 10-15% thereafter in the long term. Therefore, achievement of 'safe' GH concentrations in an acceptable time interval after radiotherapy will be realized only in those patients who have lower GH concentrations prior to irradiation either as a result of mild disease or previous surgery. Recent studies have demonstrated the value of stereotactic radiotherapy (either as multiple arc X-irradiation or as 'gamma knife' therapy) in the post-surgical treatment of acromegaly or as salvage therapy for disease persisting after conventional external irradiation. The development of potent medical therapies for acromegaly (somatostatin analogues and the GH receptor antagonist) has called into question the role of radiotherapy in the treatment of this disease. However, even if the concept of primary, open-ended medical therapy for selected patients is accepted, reference to the success rates of surgery and response rates to somatostatin analogues indicates that approximately 10-20% of all patients with acromegaly will require consideration of radiotherapy for hormonal or tumour mass control. For these reasons, radiotherapy (both conventional external and stereotactic irradiation) continues to have a major role in controlling acromegaly in selected patients.

Acromegaly↗
PubMed1992

Hepatobiliary and gastrointestinal manifestations of acromegaly.

Acromegaly is a unique condition characterized by chronic growth hormone (GH) and insulin-like growth factor-1 (IGF-1) hypersecretion usually due to a pituitary adenoma. Rarely, acromegaly can result from a GH-releasing hormone carcinoid or pancreatic neoplasm which stimulates the normal pituitary to secrete GH. This review describes the interactions between acromegaly and the gastrointestinal system. In contrast to the soft tissue and skeletal changes, clinical organomegaly of the liver, kidney, and spleen is unusual in patients with acromegaly and should warrant further investigations. The prevalence of cholelithiasis is notably increased by the use of the otherwise effective GH-lowering somatostatin analog, octreotide. Patients on long-term therapy with this agent may require anticholelithogenic treatment. The frequency of malignant and premalignant polyps of the colon justify the routine screening for these lesions in newly diagnosed patients with acromegaly.

Acromegaly↗
PubMedDate not supplied

Acromegaly: a new therapy.

BACKGROUND: The treatment of acromegaly can be challenging. Despite a multimodality approach (surgery,radiation, dopamine agonists, somatostatin analogs), many patients do not achieve normalization of serum insulin-like growth factor I (IGF-I) concentrations. METHODS: The author discusses the characteristics and indications of pegvisomant therapy for patients with acromegaly and compares the use of this newly developed GH receptor antagonist with other pharmacological agents such as somatostatin and dopamine agonists. RESULTS: Therapy with pegvisomant allows serum IGF-I concentrations to be normalized in up to 97% of patients with acromegaly, including those who have failed other treatment modalities. With this agent,circulating GH levels increase as a result of the drop in IGF-I levels. The rise is rapid (within 2 weeks) and does not appear to be progressive over time. CONCLUSIONS: Published studies have shown pegvisomant to have efficacy in the treatment of acromegaly. As it appears to be well tolerated and safe, this novel compound may be an important therapeutic option for patients with acromegaly. Additional study of this novel agent and its mode of action is warranted.

Acromegaly↗
PubMed2003

Serum ghrelin levels in acromegaly: effects of surgical and long-acting octreotide therapy.

The orexigenic peptide, ghrelin, is regulated by acute and chronic nutritional state. Although exogenously administered ghrelin stimulates pituitary GH secretion, little is known about the role of ghrelin in endogenous GH secretion or how high GH and IGF-I levels in acromegaly could affect ghrelin secretion and vice versa. Therefore, we evaluated fasting and post oral glucose tolerance test serum ghrelin levels in 19 patients with active acromegaly at baseline and after either surgery in 9 of these or administration of long-acting octreotide (Sandostatin LAR) in the other 10 patients. After surgical cure, fasting ghrelin rose from 312 +/- 56 pg/ml to 548 +/- 97 pg/ml (P = 0.013). Fasting serum ghrelin levels were higher in all patients after surgery and ranged between 112% and 349% of presurgery levels. Ghrelin levels fell significantly during long-acting octreotide therapy from 447 +/- 34 pg/ml to 206 +/- 15 pg/ml (P < 0.0001); ghrelin levels on octreotide ranged between 26% and 70% of baseline levels. Serum ghrelin levels were suppressed significantly during the oral glucose tolerance test in both groups. Pretherapy ghrelin levels correlated negatively with serum insulin levels (r = -0.494; P = 0.03) and insulin resistance as estimated by the homeostasis model assessment score (r = -0.573; P = 0.01). In patients without diabetes mellitus, serum insulin levels in the surgical group were 19.7 +/- 5.4 microU/ml before surgery and fell to 9.7 +/- 0.93 microU/ml after surgery (P = 0.05); levels in the octreotide group were 13.9 +/- 2.8 microU/ml before and fell to 11.2 +/- 2.8 microU/ml on octreotide (P = 0.03). Pretherapy ghrelin levels did not correlate with weight or body mass index, but after therapy in the surgery group ghrelin correlated negatively with weight (r = -0.823, P = 0.012) as has been demonstrated by others in healthy subjects. Ghrelin secretion is dysregulated in active acromegaly; lowered serum levels of ghrelin in active acromegaly rise along with the postsurgery normalization of GH and IGF-I and improved insulin resistance. In contrast to surgical therapy, long-acting octreotide therapy persistently suppressed serum ghrelin levels. It remains to be determined whether altered circulating ghrelin concentrations could impact on body composition changes in acromegaly.

Acromegaly↗
PubMed2003

The effects of depot long-acting somatostatin analog on central aortic pressure and arterial stiffness in acromegaly.

Acromegaly is associated with increased cardiovascular risk. Although conventional risk factors such as glucose intolerance, hypertension, and dyslipidemia probably contribute, there may also be direct effects of GH/IGF-I excess on the vasculature. To study the effects of GH excess on the vasculature, we have assessed arterial stiffness in acromegalic subjects with and without active disease and have investigated the effects of Sandostatin LAR (OCT-LAR) on vascular function. Sixteen normotensive subjects with acromegaly (10 males and 6 females) and 8 healthy controls were studied. Of the acromegalic subjects, eight had active disease (group A), and eight were cured (GH < 2.5 mU/liter; group B). The three groups were age, sex, and blood pressure matched. Group A subjects were restudied after 3 and 6 months of OCT-LAR therapy. Arterial stiffness was assessed by analyzing central arterial pressure waveforms derived from measured radial artery waveforms. This allowed determination of the augmentation of central pressure and the augmentation index. Lipids, glucose, and IGF-I were also measured. Comparing the three groups (ANOVA; mean +/- SD), the augmentation index was higher in group A (28 +/- 12 vs. 12 +/- 13%; P < 0.01) but not in group B (22 +/- 7 vs. 12 +/- 13%; P = 0.60), compared with controls. IGF-I was higher in group A (50.3 +/- 21.2 nmol/liter; P < 0.01), compared with group B (22.5 +/- 8.9 nmol/liter) and controls (19.5 +/- 5.3 nmol/liter). On regression analysis, IGF-I concentration was identified as a strong independent predictor of the augmentation index (beta = 0.50; P = 0.007). There were no significant differences in aortic systolic pressure, aortic diastolic pressure, lipids, or glucose. Compared with baseline, OCT-LAR treatment resulted in a lowering of augmentation index at 3 months (20 +/- 15 vs. 28 +/- 12%; P < 0.05), but at 6 months (24 +/- 16%; P = 0.21) there was no significant change. IGF-I was reduced from 50.3 +/- 21.2 nmol/liter at baseline to 31.4 +/- 13.2 nmol/liter at 3 months (P < 0.05) and 26.6 +/- 15.8 nmol/liter at 6 months (P < 0.05). In conclusion, acromegaly is associated with changes in the central arterial pressure waveform, suggesting large artery stiffening. This may have important implications for cardiac morphology and performance in acromegaly as well as increasing the susceptibility to atheromatous disease. Large artery stiffness is reduced in cured acromegaly and partially reversed after pharmacological treatment of active disease.

Acromegaly↗
PubMed2005

Relationship between disease-related morbidity and biochemical markers of activity in patients with acromegaly.

The criteria for biochemical control of acromegaly that will best reduce disease-related morbidity in acromegaly are debated. We therefore studied the relationship of biochemical markers with an important metabolic parameter, insulin sensitivity, and clinical parameters reflecting disease activity in acromegaly. Newly diagnosed and postoperative patients with acromegaly underwent assessment of fasting IGF-I and fasting and postoral glucose tolerance test GH and insulin levels and completed a numeric signs and symptoms questionnaire. Insulin sensitivity was estimated by the quantitative insulin sensitivity check index (QUICKI) and the composite insulin sensitivity index. Patients were divided into three groups: group I, normal IGF-I and nadir GH less than 0.14 mug/liter (n = 21); group II, normal IGF-I and nadir GH 0.14 mug/liter or more (n = 20); group III (active), elevated IGF-I (n = 25). Age, sex, and body mass index were comparable in these groups. Insulin sensitivity was reduced in group III (QUICKI: 0.33 +/- 0.01 and composite index: 3.44 +/- 0.54), compared with group II (0.38 +/- 0.01, P = 0.002 and 8.18 +/- 1.21, P = 0.0008), group I (0.38 +/- 0.01, P = 0.0008 and 8.91 +/- 1.34, P = 0.00001), and healthy controls (0.37 +/- 0.008, P = 0.009). When other nadir GH cut-offs were analyzed, insulin sensitivity remained relatively reduced in the elevated IGF-I group. IGF-I was a significant predictor for decreasing insulin sensitivity as calculated by QUICKI (r = 0.6, P < 0.0001) independently of nadir GH. Signs and symptom scores were higher in group III (mean 38.5 +/- 3.6%), compared with group II (mean 23.5 +/- 3.2%, P = 0.004) and group I (mean 20.5 +/- 3.7%, P = 0.0008) but not between the latter two groups. Our data indicate that overall and specifically in the presence of discordant serum IGF-I and nadir GH levels, IGF-I was more predictive than GH levels of insulin sensitivity and clinical symptom score in patients with acromegaly.

Acromegaly↗
PubMed2006

Acromegaly and coronary disease: an integrated evaluation of conventional coronary risk factors and coronary calcifications detected by computed tomography.

CONTEXT: Coronary atherosclerosis in acromegaly was not extensively investigated in the literature until now. At autopsy, it was demonstrated in about 20% of patients with long-lasting disease, and myocardial infarction was reported as cause of death in a quarter of acromegalics. OBJECTIVE: The objective of the study was to evaluate coronary atherosclerosis in a cohort of acromegalics with controlled or uncontrolled disease. DESIGN: Coronary risk was evaluated by the Framingham algorithm, according to the Framingham score (FS). Patients were stratified into low (<6%), intermediate (6-20%), and high (>20%) midterm risk. Coronary calcium deposits were detected by multidetector computed tomography and measured by the Agatston algorithm. Coronary artery calcium [Agatston score (AS)] was quantified at the level of left main artery, left anterior descendent artery, left circumflex artery, right coronary artery, and posterior descendent artery. Total AS values in healthy persons are less than 50 (aged < 60 yr) and less than 300 (age > or = 60 yr). PATIENTS: Thirty-nine patients (12 males and 27 females, aged 53.0 +/- 2.1 yr) were evaluated. In each patient, the mean of at least four determinations of serum IGF-I, assayed during the last 2 yr before study, was normalized for the age-matched normal range, and the result was presented as sd value (IGF-I sd). On the basis of serum IGF-I sd, acromegaly was considered controlled (< or =1.9 sd; n = 24) or uncontrolled (> or = 2.0 sd; n = 15). RESULTS: The FS was intermediate in 12 and high in two acromegalics. Overall, the FS was not correlated with serum GH values and IGF-I sd. Mean FS was not significantly different between patients with controlled and uncontrolled acromegaly. Total AS was increased in nine patients, most frequently in left anterior descendent, left circumflex, and left main arteries. In these nine patients, mean AS was similar in individuals with controlled and those with uncontrolled acromegaly, and the rate of 17% patients with controlled disease having increased AS was not statistically different from the rate of 33% uncontrolled acromegalics. Total AS was increased in six of 12 males and in three of 27 females (chi(2) 7.1, P < 0.01). Overall, total AS correlated with FS (r(2) = 0.4, P < 0.0002) but not age, body mass index, disease duration, indexed left ventricular mass, serum cholesterol, triglycerides, GH, or IGF-I levels. Increased AS was more frequently observed in acromegalics with diabetes mellitus (chi(2) = 5.2, P < 0.05) or hypertension (chi(2) = 9.8, P < 0.002) but not in smokers (chi(2) = 1.34, P = NS). Seven of nine patients with coronary calcium deposits had a FS greater than 6%. In six of 13 patients with FS greater than 6%, multidetector computed tomography did not demonstrate coronary calcifications. CONCLUSIONS: In our study, the integrated evaluation of FS and AS showed that 41% of acromegalics are at risk for coronary atherosclerosis and that coronary calcifications were evident in about half of them despite the fact that myocardial infarction was not more frequent in acromegalic patients than the general population. Moreover, the control of acromegaly did not influence significantly the extent of coronary atherosclerosis.

Acromegaly↗