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PubMedDate not supplied

Role of insulin-like growth factor-I in diagnosis and management of acromegaly.

OBJECTIVE: To highlight the use of insulin-like growth factor-I (IGF-I) measurements in the management of acromegaly. METHODS: The physiologic and pathophysiologic regulation of growth hormone (GH) and IGF-I secretion and the role of measurements of these two variables for diagnosing and monitoring the acromegalic condition are discussed. RESULTS: Chronic GH hypersecretion by pituitary tumors leads to the clinical condition of acromegaly, characterized by enlargement of membranous bones and soft tissue overgrowth. Because of the frequent delay in diagnosis of acromegaly, disease management often involves the use of multiple therapeutic modalities. Therefore, adequate patient management necessitates precise diagnostic tests to (1) establish that the acromegalic condition exists, (2) determine the degree of severity, and (3) assess the effectiveness of treatment in patients who have received therapy. Because the predicted mortality rate among patients who have achieved a biochemical remission is substantially improved in comparison with those who have biochemical indices that indicate residual disease activity after therapy, a biochemical test is required to determine the necessity of undertaking further treatment. The GH-dependent peptide IGF-I provides useful information for making this decision. In addition to providing data about the degree of GH hypersecretion, IGF-I concentrations reflect the severity of disease at the time of initial assessment and the degree of improvement in response to any therapeutic intervention. Direct measurement of GH after glucose suppression is the best indicator of residual tumor secretory activity. IGF-I measurements should be performed in a reference laboratory with adequate age-adjusted normative ranges and a high degree of precision, which allows serial determinations over time to reflect the degree of biochemical improvement. Measurement of IGF-I often correlates with the degree of persistent GH hypersecretory abnormality after therapy, although no precise correlation is found in some cases. CONCLUSION: Measurements of GH suppression after glucose administration and of IGF-I after treatment of patients with acromegaly provide useful complementary information. Every effort should be made to achieve normalization of these biochemical indices so that patients are offered the best therapeutic prognosis.

Acromegaly↗
PubMed2000

Guidelines for the diagnosis and treatment of acromegaly: a Canadian perspective.

Acromegaly is a chronic, debilitating condition caused by excessive secretion of growth hormone (GH). In the majority of cases the condition results from benign pituitary adenomas or, rarely, from ectopic production of GH-releasing hormone. Regardless of the cause, excess GH results in physical disfigurement associated with arthropathy, diabetes, hypertension, cardiac dysfunction, obstructive sleep apnea and colonic neoplasia. The death rate for acromegalic patients is 2 to 3 times higher than that of the general population, but with appropriate reduction of GH hypersecretion it tends to shift into the normal range. Treatment is thus aimed at normalizing GH secretion; eradicating or stabilizing the pituitary tumour while preserving normal pituitary function, and managing the associated complications. The treatment modalities available to achieve these objectives include transsphenoidal surgery, pharmacotherapy and radiation, or various combinations of these. This review provides an update on our current understanding of the pathophysiology of GH hypersecretion in acromegaly, the newly defined diagnostic criteria and the end point for a cure for acromegaly, and on new developments in drug treatment with the advent of slow-release forms of somatostatin analogues and the longer-acting dopamine receptor agonists, as well as in the area of radiotherapy. Its main purpose is to guide any physician involved in the diagnosis and management of patients with acromegaly.

Acromegaly↗
PubMed2001

[Severe mitral insufficiency caused by the rupture of the chordae tendinae in acromegaly. Report of a case].

Cardiovascular disease is a common finding in patients with acromegaly. In such patients, heart failure frequently leads to death. Cardiovascular manifestations of acromegaly include cardiomegaly and very often hypertension, coronary atherosclerosis, and diabetes. Primary valvular disease is less commonly observed. Because it is not clear whether acromegaly-related cardiomyopathy is a specific entity and since there are not many necropsy reports regarding mitral valve prolapse in acromegalic patients, we report the case of severe mitral regurgitation due to rupture of the chordae tendinae in a patient with mitral valve prolapse and acromegaly.

Acromegaly↗
PubMed2002

Turner's syndrome followed by acromegaly in the third decade of life: an unusual coincidence of two rare conditions.

We present an unusual coincidence of acromegaly and Turner's syndrome. A girl was diagnosed with Turner's syndrome when she presented with short stature, primary amenorrhea, Hashimoto's thyroiditis, and some heart and renal anomalies. No therapy with growth hormone and only a few months treatment with estrogen-progestin was given. A typical picture of acromegaly occurred in the third decade of her life. Bone radiographs and densitometry suggested the more pronounced influence of acromegaly within the skeleton, but no features typical for acromegaly were found in the cardiovascular system. To our knowledge no case of coincidence of the above mentioned conditions has been reported to date. The influence of both of these conditions on bones and heart is discussed.

Acromegaly↗
PubMed2002

[Acromegaly and pregnancy].

Acromegaly usually results from GH hypersecretion by a somatotroph adenoma. The fertility of acromegalic patients is often impaired. Several factors may impact the course of pregnancy in acromegaly. Disturbed pituitary function might lead to infertility or spontaneous abortion. GH is a powerful insulin antagonist, and pregnant acromegalic patients are prone to added glucose intolerance and diabetes. Pregnancy itself might also impact the course of the pituitary tumor. During pregnancy, the normal pituitary increases in size due to estrogens-mediated hyperplasia. Therefore, tumors are at risk for hemorrhage due to enhanced vascularity, and might compress the optic chiasm. In this article we summarize the data on the literature on the reciprocal influences between acromegaly and pregnancy, we discuss therapeutic options and advance diagnostic and surveillance schedules of acromegaly during pregnancy.

Acromegaly↗
PubMed2002

[Acromegaly--do we already know everything about treatment of the somatotroph pituitary adenomas?].

Acromegaly--do we already know everything about treatment of the somatotroph pituitary adenomas?--Acromegaly, an insidious neuroendocrine disorder, reduces life expectancy and leads to 3.5-fold increase in mortality. The main causes are cardiovascular, pulmonary and enhanced prevalence of deaths from malignancy. Successful therapy ought to normalize GH, IGF-I secretion, remove adenoma mass and its local pressure effects and preserve pituitary function to improve systemic morbidity and normalize mortality. The primary therapy for most patients with acromegaly caused by somatotroph pituitary adenoma is still transsphenoidal resection of the tumor. The results of the transsphenoidal surgery for pituitary adenoma for acromegaly depend on the volume of the tumor, its suprasellar and parasellar extension, especially to the cavernous sinus. The aim of this paper was to present the diagnostic criteria and principle therapy in these tumors. Our experience was based on the analysis of more than 150 patients operated on during the last five years and review of the literature.

Acromegaly↗
PubMed2002

[Acromegaly due to ectopic GH RH secretion by a bronchial carcinoid tumor: a case report].

Ectopic GH RH is a very uncommon cause of acromegaly (<1% of acromegaly). We report the case of an 41 year-old woman with acromegaly due to a GH-RH-secreting bronchial carcinoid tumor. Elevated serum GH (14 ng/ml) was paradoxically stimulated after glucose loading. Magnetic resonance imaging revealed a normal pituitary gland. The thoracic CT demonstrated a voluminous (8 cm) bronchial tumor visualised with octreotide scintigraphy. Acromegaly due to ectopic GH RH secretion was confirmed by very high plasma immunoreactive GH RH level. After removal of the carcinoid tumor, plasmat GH, IGF1 and GH RH levels were normalised.

Acromegaly↗
PubMed1992

[Acromegaly and bronchial carcinoid tumor. Apropos of a case].

Acromegaly due to ectopic secretion of growth hormone-releasing hormone (GHRH) is rare. A 29-year-old woman with acromegaly secondary to ectopic GHRH secretion by a bronchial carcinoid tumor is presented. Normalization of GHRH levels, reversal of pituitary hyperplasia and regression of acromegaly followed resection of the bronchial tumor. The authors stressed the interest of GHRH dosage in patients with acromegaly and pituitary hyperplasia.

Acromegaly↗
PubMed1992

Rheumatologic and skeletal changes in acromegaly.

The anabolic functions of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in cartilage and bone metabolism are important in the normal physiology of these tissues. The effects of chronic elevation of GH and IGF-I levels on bony structures produce the typical physical changes associated with acromegaly, whereas the effects on cartilage result in arthropathy, which is usually degenerative. This article presents an overview of the physiologic roles of GH and IGF-I in cartilage and bone metabolism, the clinical features of the degenerative arthropathy and other rheumatologic syndromes associated with acromegaly, effects of acromegaly on bone and mineral metabolism, and an unusual bone disease that is occasionally associated with acromegaly, the McCune-Albright syndrome.

Acromegaly↗
PubMed2003

Lessons from 6 years of GH receptor antagonist therapy for acromegaly.

Pegvisomant is a GH receptor antagonist and a new agent for the medical management of acromegaly. The clinical efficacy and safety of pegvisomant in the treatment of active acromegaly were demonstrated in a 12-week, placebo-controlled trial of 112 patients. After a washout period, patients were randomized to a fixed dose of pegvisomant (10, 15 or 20 mg/day) or placebo given by sc injection. Serum IGF-I levels were within the normal age-adjusted reference range in 54, 81 and 89% of patients in the 10-, 15- and 20-mg/day groups, respectively. The decrease in serum IGF-I levels was accompanied by considerable improvement in the signs and symptoms of active acromegaly. This efficacy profile was maintained in a long-term continuation trial, with normalization of serum IGF-I at 12 months occurring in 97% of patients. Pegvisomant has been well tolerated with an adverse event profile similar to placebo. Two patients had elevations in liver function tests that resolved after discontinuing treatment with pegvisomant. During treatment with pegvisomant, liver function tests should be monitored on a regular basis. Two patients had an increase in pituitary tumor volume during pegvisomant therapy; however, the relationship to pegvisomant therapy was not clear. In 131 patients treated for at least 6 months, there was no increase in mean tumor volume, regardless of whether they underwent previous radiotherapy. Pegvisomant is an effective new treatment for the management of patients with acromegaly. Longer-term data are needed to confirm the safety profile that has been demonstrated in studies up to 18 months.

Acromegaly↗
PubMed2004

New therapeutic options for acromegaly.

Acromegaly is a slowly developing disfiguring disease characterized by chronic growth hormone (GH) and insulin-like growth factor-I (IGF-I) excess and caused by a pituitary somatotroph adenoma. It is associated to 2- to 3 fold increased mortality, compared to normal population, mostly due to cardiovascular and cerebro-vascular diseases, and to several co-morbid systemic illnesses, such as diabetes mellitus, hypertension, severe arthropathies, a specific cardio-myopathy, goitre, sleep-apnoea, intractable headache. The morbidity and excess mortality of acromegaly are usually the consequence of the metabolic actions of excess GH and IGF-I secretion, while only in rare patients mortality is due to the mass effects of the pituitary tumour. Since, serum IGF-I concentrations within age-adjusted normal range, and a tight GH control have to be achieved to normalize life-expectancy in these patients, an aggressive, and often multi-modality treatment is required for acromegaly. In recent years, new drugs, and new formulations of old drugs, have been developed that are able to effectively inhibit GH secretion or GH action, and may represent important adjuncts or even alternatives to the traditional approaches of surgery and radiotherapy. This review briefly summarizes the therapeutic options nowadays available for acromegaly. A brief note about innovative drugs under study, is also given.

Acromegaly↗
PubMed2005

Severe systemic complications of acromegaly.

It is well accepted that mortality in acromegaly is increased because of cardiovascular and respiratory diseases while neoplastic complications account less to mortality. Amongst different cardiovascular complications the most frequent is biventricular hypertrophy, which occurs independently of hypertension and metabolic complications that, in turn, aggravate the cardiomyopathy. Diastolic and systolic dysfunction develops in a variable number of patients, depending on age and disease duration. Other cardiac disorders, such as arrhythmias, valve disease, hypertension, atherosclerosis and endothelial dysfunction have been less characterized but all appear to be present in acromegaly, depicting the so called "acromegalic cardiomyopathy". The best characterized respiratory disease is the sleep apnea. Ventilatory dysfunction recognizes bony changes of thoracic cage and lung overgrowth as relevant pathogenetic factors. Earlier evidences that patients with acromegaly have an increased risk of developing malignancies have become more realistic in recent years. Most studies have reported an increased risk of colonic polyps, which more frequently recur in patients not controlled after treatment. Malignancies in other organs have also been described, but less convincingly than at the gastrointestinal level and are not a main cause of mortality. Bone changes are also feature of the disease. They involve theoretically all bones and, particularly, the appendicular and the axial skeleton. Patients with long-standing disease are more prone to develop degenerative changes. Control of acromegaly by surgery or pharmacotherapy, especially by somatostatin analogs, improves cardiovascular morbidity and sleep apnea. There is still no demonstration that improvement of different complications corresponds a reduction in mortality.

Acromegaly↗
PubMed2005

An overview of the epidemiology and genetics of acromegaly.

Historical data indicate that pituitary tumors represent 10% of intracranial tumors, while adenomas are noted in approximately 14-23% of normal subjects on autopsy or magnetic resonance imaging (MRI). About 2.5% of these tumors stain positive for GH in histopathologic studies. In contrast, the prevalence of clinically diagnosed acromegaly is lower at 36-69 per million population. Ongoing studies indicate that the actual prevalence of acromegaly in the community may be higher than previous epidemiologic data suggest. Acromegaly can occur both sporadically and in the setting of familial conditions, such as multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). Isolated familial somatotropinoma has been described and newer data suggest that acromegaly may also occur in non-MEN1/CNC families in combination with other pituitary tumor phenotypes.

Acromegaly↗
PubMed2005

GH and mortality in acromegaly.

Effective biochemical control of GH and IGF-I levels in subjects with acromegaly can reduce mortality to that of the general population. Several retrospective studies have reported that the increased mortality is improved if GH levels are reduced to <2.5 microg/l, measured as mean of GH day profile or random GH level. It has been proposed that control or "cure" of disease is achieved when mean GH levels are <2.5 microg/l, nadir GH after an oral glucose load is <1 microg/l, and circulating IGF-I is reduced to an age- and sex-adjusted normal range. However, virtually all evidence from epidemiological studies has related GH values and not IGF-I values to long-term morbidity and mortality; controversy remains regarding the relative importance of these 2 parameters in determining post-treatment control status. Review of the West Midlands Acromegaly Database (419 patients) revealed that mortality was increased in the subgroup of patients with GH levels >2 microg/l (measured either as mean GH day profile or GH values across an oral glucose tolerance test, or random GH level). Factors influencing mortality in acromegaly were analyzed in a study from New Zealand of 208 acromegalic subjects. Serum GH at last follow-up was the most significant predictor of mortality, with mortality rates reduced to normal by achieving GH concentrations <1-2 microg/l. A nationwide survey of mortality in 334 patients with acromegaly from Finland has reported no difference in overall mortality between patients and general population; however, patients with last known basal serum GH >2.5 microg/l showed excess mortality (SMR 1.61, p<0.001). These 3 analyses of 961 patients indicate unequivocally that a GH value of 1-2 microg/l is an appropriate therapeutic target, as values above this level are associated with increased mortality.

Acromegaly↗
PubMedDate not supplied

Circulating cytokines in relation to bone mineral density changes in patients with acromegaly.

OBJECTIVES: Elevated cytokines levels were observed as a marker of increased bone resorption in certain diseases. The aim was to assess serum levels of selected cytokines in acromegaly, regarding to different disease's stages, gonadal function, gender and character of BMD change. METHODS: The study was carried out in 62 patients with acromegaly (40 women, 22 men) aged 26-75 years in various stages of the disease. The controls were 30 healthy, age- and sex-matched subjects. Serum cytokines concentration was assessed using ELISA method. RESULTS: We have shown higher (p=0.044) concentrations of TGF-beta in male patients with active acromegaly than in cured males. When the influence of all cytokines studied on BMD using multiple regression analysis was carried out, the borderline (p=0.099) statistical significance was achieved (regression coefficient B=0.68271) according to TGF-beta and trochanter major BMD. IL-6 and TNF-alpha were higher (p=0.062, and p=0.098, respectively) in these acromegalic patients, in which gain of trochanter major BMD occurred. IL-1beta levels were lower in patients with ultradistal radius and 1/3 distal radius BMD gain (p=0.007, and p=0.009, respectively). Lower TGF-beta levels (p=0.077) were shown in patients with 1/3 distal radius gain. IL-6 levels were higher in patients with total body BMD gain (p=0.059). CONCLUSIONS: The relations between TGF-beta and acromegaly activity in men, and trochanter major BMD in both sexes were documented. Concentrations of all cytokines studied correlated with the BMD changes in different bone sites. Noteworthy is homogeneity of the secretory character of cytokines studied according to BMD changes within particular skeleton sites.

Absorptiometry, Photon↗
PubMed2006

A follow-up of 130 patients with acromegaly in a single centre.

OBJECTIVES: Acromegaly is a rare disease with increased mortality rate. The aim was to present our centre experience in the diagnosis and treatment of a series of patients suffering from acromegaly. METHODS: 130 patients (55 men, 75 women) aged 19-84 years presenting with clinical and hormonal features of acromegaly, attending Department of Endocrinology and Out-patient Clinic between 1990 and 2004 were studied. They were analyzed their GH and IGF-1 levels, CT and MRI scans, and they were administered medical therapy, neurosurgery and radiotherapy. RESULTS: We have observed 106 macro-, 16 microadenomas and 1 case of ectopic GHRH. 115 patients were operated, as cured were recognized 74 of them. Pituitary irradiation was applied to 11 patients, in 4 of them it did not cure the disease. Medical therapy was efficacious in 12% patients treated with bromocriptine, 73% with long-acting lanreotide and 58% with long-acting octreotide. In 7 patients other malignant neoplasm were detected. 11 patients died during the follow-up. CONCLUSIONS: There is possible underdiagnosis of acromegaly in our region, especially in males. We have observed better diagnostic opportunities in recent years when MRI was available. It was accompanied by better outcome of surgical and pharmacological treatment and better control of the complications of the disease.

Acromegaly↗
PubMed1991

Plasma concentrations of atrial natriuretic hormone in acromegaly: relationship to hypertension.

Atrial natriuretic hormone is involved in the control of blood pressure and water-electrolyte balance. In order to assess the relationship between atrial natriuretic hormone and hypertension in acromegaly, 34 subjects were studied, 18 with acromegaly (10 normotensive and 8 hypertensive) and 16 healthy controls. Plasma atrial natriuretic hormone levels, as well as plasma renin activity, aldosterone and growth hormone levels were measured in basal conditions in all subjects. Additionally, plasma renin activity and aldosterone levels were determined after standard stimulation. In hypertensive acromegalic patients, atrial natriuretic hormone plasma concentrations (39.8 +/- 3.5 ng/l) were significantly higher than in patients without hypertension (27.9 +/- 4.1 ng/l), and in controls (28.6 +/- 1.3 ng/l) (p less than 0.01 in both comparisons). Stimulated plasma renin activity values were decreased in hypertensive acromegalic patients when compared with those in normotensive patients (1.14 +/- 0.29 vs 4.03 +/- 0.66 micrograms.l-1.h-1, p less than 0.01). In acromegaly, atrial natriuretic hormone levels correlated with mean arterial pressure (r = 0.58, p = 0.01). These results suggest that atrial natriuretic hormone plasma levels are slightly increased in patients with acromegaly and hypertension.

Acromegaly↗
PubMed1990

[Role of arterial hypertension in the cardiac involvement of acromegaly].

Cardiac disease is common in acromegaly. Several mechanisms have been implicated: hypertension, coronary artery disease, valvular heart disease, endocrinopathies including "acromegalic cardiomyopathy". Fifteen consecutive patients with acromegaly, aged 48 +/- 13 years and treated for 4 +/- 5 years, underwent Doppler echocardiography. The patients had no cardiovascular symptoms: 6 had hypertension for 10 +/- 7 years and were compared with a group of 10 control subjects of the same age (48 +/- 17 years). The myocardial mass index (MMI) was higher in acromegaly (110 +/- 32 vs 82 +/- 12 g/m2, p = 0.02), left ventricular enddiastolic dimensions where comparable (48 +/- 7 vs 48 +/- 5 mm, NS) fractional shortening was slightly greater (0.37 +/- 0.04 vs 0.34 +/- 0.04, p = 0.07) as was velocity of shortening (NS) and the ratio of systolic time intervals (NS). The mitral EF slope was decreased (80 +/- 21 vs 101 +/- 30 ms; p less than 0.02); the ratio of the amplitudes of the E and A waves was a little decreased and the isovolumic relaxation phase was increased (92 +/- 13 vs 69 +/- 16 ms; p less than 0.01). Hypertensives (N = 6) had higher MMI (133 +/- 27 vs 94 +/- 24 g/m2, p = 0.02). Normotensive patients had larger isovolumic relaxation periods than control subjects (90 +/- 11 vs 69 +/- 16 ms, p less than 0.05). These results show that in the infraclinical phase, the heart in acromegaly is hypertrophied, not dilated. Hypertension plays a significant role in the development of this hypertrophy. Left ventricular systolic function is normal but diastolic function is impaired.

Acromegaly↗