Heart size and function in acromegaly.

Cardiac size and function was studied in 23 acromegalic patients using echocardiography and systolic time interval measurements. Thirteen patients (56%) had increased left ventricular mass, and in the 20 treated patients this correlated well with the mean of the recent basal growth hormone levels. It is suggested that myocardial hypertrophy may regress in proportion to the degree of control of growth hormone levels. The ejection fraction was normal in all patients except one, and increased left ventricular mass was not associated with detectable impairment of left ventricular performance. Thus, most acromegalic hearts function normally even when their mass is considerably increased, though the long-term effects of this are unknown, Echocardiography will be valuable in the serial monitoring of the cardiac effects of acromegaly.     

Cardiac size and function in acromegaly.

Sixteen acromegalic patients underwent echocardiography, phonocardiography, stress electrocardiography with Thallium perfusion scanning and gated radioisotope left ventricular angiocardiograms. Abnormalities consisting of increased echo left ventricular mass index, low velocity of circumferential fiber shortening or elevated pre-ejection period to left ventricular ejection time ratio were found in six patients with coexistent hypertension or coronary disease. Concentric left ventricular hypertrophy was also found in three patients with no known etiology other than acromegaly of greater than thirteen years' duration or with fasting growth hormone concentrations greater than 100 ng/ml. One of these three also had left ventricular dysfunction. Neither hypertrophy nor ventricular dysfunction was found in other acromegalics with shorter duration of disease or lower growth hormone concentrations or with normal growth hormone concentrations after therapy. A high prevalence of coronary artery and hypertensive heart disease is associated with acromegaly. A few patients with acromegaly have a specific, potentially reversible cardiomyopathy probably related to prolonged acromegaly or very high growth hormone concentrations.     

Cardiac hypertrophy and function in asymptomatic acromegaly.

Heart disease frequently occurs in advanced acromegaly. In order to investigate cardiac mass and function in acromegaly in the absence of obvious cardiac disease, we performed Doppler echocardiography in 15 asymptomatic acromegalic patients (six of them had systemic hypertension). The data were compared with those of a group of 10 age-matched controls. Left ventricular mass index (LVMI) was increased in acromegaly (110 +/- 32 vs 32 +/- 12 g m-2, P = 0.02), but shortening fraction and systolic time intervals did not differ. Mitral EF slope was decreased (80 +/- 21 vs 101 +/- 30 mms-1, P less than 0.02), while the duration of the isovolumic relaxation period (IRP) was increased (92 +/- 13 vs 69 +/- 16 ms, P less than 0.01). Hypertensive acromegalic patients (n = 6) had a higher LVMI than normotensive acromegalic patients (n = 9) (133 +/- 27 vs 94 +/- 24 g m-2, P = 0.02) and this was confirmed by a meta-analysis of data in the literature: the prevalence of hypertrophy was 76% in the presence of hypertension vs 50% in its absence, P less than 0.002. IRP was prolonged in normotensive acromegalic patients vs normal controls (90 +/- 11 vs 69 +/- 16 ms, P less than 0.01). In conclusion, subclinical cardiac abnormalities occur frequently in acromegaly in the absence of obvious heart disease, and hypertrophy is observed in asymptomatic hypertensive acromegaly. Moreover, diastolic abnormalities are found in asymptomatic acromegaly and could be caused by several heart-related factors.     

Cardiovascular function in acromegaly

Even with modern treatment, acromegaly is associated with a 2- to 3-fold increase in mortality, mainly from vascular disease, which is probably a result of the long exposure of tissues to excess GH before diagnosis and treatment. There is accumulating evidence that effective treatment to lower serum GH levels to less than 1-2 ng/ml (glucose suppressed or random, respectively) and normalize IGF-I improves long-term outcome and survival. In addition to recognized cardiovascular risk factors of hypertension, type 2 diabetes mellitus, and dyslipidemia, there is accumulating evidence of specific structural and functional changes in the heart in acromegaly. Along with endothelial dysfunction, these changes may contribute to the increased mortality in this disease. There are specific structural changes in the myocardium with increased myocyte size and interstitial fibrosis of both ventricles. Left ventricular hypertrophy is common even in young patients with short duration of disease. Some of these structural changes can be reversed by effective treatment. Functionally, the main consequence of these changes is impaired left ventricular diastolic function, particularly when exercising, such that exercise tolerance is reduced. Diastolic function improves with treatment, but the effect on exercise tolerance is more variable, and more longitudinal data are required to assess the benefits. What scant data there are on rhythm changes suggest an increase in complex ventricular arrhythmias, possibly as a result of the disordered left ventricular architecture. The functional consequences of these changes are unclear, but they may provide a useful early marker for the ventricular remodeling that occurs in the acromegalic heart. Endothelial dysfunction, especially flow-mediated dilatation, is an early marker of atherosclerosis, and limited data imply that this is impaired in active acromegaly and can be improved with treatment. Similarly, early arterial structural changes, such as thickened intima media layer, appear more common in acromegalics, and there are hints that this may diminish with effective treatment, although more studies are required for a definite conclusion on this topic. In conclusion, impaired cardiac and endothelial structure and function in acromegaly are risk factors for vascular mortality and should be regarded as legitimate therapeutic targets in the overall management of this condition.     

Parameters of thyroid function in patients with active acromegaly.

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

Biventricular impairment of diastolic function in acromegaly

AIM: Left ventricle impairment is very common in acromegaly. Concentric hypertrophy and diastolic dysfunction are observed at an early stage. Late left ventricle dilatation with systolic dysfunction may appear. Few reports have studied right ventricle diastolic function. METHODS: Twenty-seven acromegalic patients were included. Biventricular diastolic function was assessed using Doppler-echocardiography. Possible associations with hormonal activity, evolution time of illness, hypertension, left ventricular hypertrophy and systolic impairment on echocardiography were studied. RESULTS: Fifteen patients showed left ventricular diastolic dysfunction, whereas thirteen patients showed right ventricular diastolic dysfunction. A good correlation was observed between E/A relation of both ventricles (r = 0.70; p < 0.01) and isovolumetric relaxation time (r = -0.60; p < 0.01). The right ventricular E/A relation correlated with left ventricular mass index and significance was almost achieved with the presence of hypertension. There was no statistical correlations between the right ventricular E/A relation and hormone values or evolution time of illness. The left ventricular E/A relation showed a significant association with left ventricular mass index, isovolumetric time index and evolution time of illness. There were no statistical association with hormone values. CONCLUSIONS: The high prevalence of right ventricular diastolic dysfunction observed in acromegaly suggests the presence of acromegalic myocardiopathy.     

Cancer in acromegaly.

In recent years, it has become increasingly recognized that acromegaly predisposes to a variety of cancers, particularly colorectal and breast cancers, and perhaps haematological malignancies. However, these associations have been based mostly on small epidemiological surveys, and a propensity towards other malignancies might also become apparent in the future. This review assesses these three malignancies together with those of the thyroid and prostate, and discusses their pathogenesis, concentrating on the role of the growth hormone/insulin-like growth factor I (IGF-I) axis.     

Pulmonary function testing and chest tomography in patients with acromegaly

Background

Despite the gradual improvement in treatment procedures and cure rates of acromegaly, a steady increase in the mortality rate due to respiratory disease has been documented in recent decades. In this study, our objectives were to describe the abnormalities in lung structure and function that occur in acromegalic patients and to correlate these changes with hormonal levels.

Methods

This cross-sectional study included 20 acromegalic patients and 20 age-and height-matched control subjects, all non-smokers. All subjects underwent spirometry, whole body plethysmography, carbon monoxide diffusing capacity, and respiratory muscle strength. Acromegalic patients also performed high-resolution computed tomography (HRCT).

Results

Most patients were female (65%), with a mean age of 52.5?±?13 years. Acromegalic patients showed lower values of maximum expiratory pressure (55.9?±?17.1 vs. 103.7?±?19.2%; p < 0.001) and maximum inspiratory pressure (71.4?±?27.8 vs. 85.3?±?24.1%; p = 0.005) compared to control subjects. The values of forced vital capacity (107.1?±?15.9 vs. 98.9?±?21.4%; p = 0.028), total lung capacity – TLC (107.3?±?12.9 vs. 93.7?±?7.60%; p = 0.002), residual volume (114.1?±?22.7 vs. 90.0?±?14.6%; p < 0.001), and airways’ resistance (3.82 vs. 2.31 cmH₂O/L/s; p = 0.039) were greater in acromegalic patients than in control subjects. The difference between the TLC measured by plethysmography and the V_A (alveolar volume) measured during the DL_CO maneuver was higher in acromegalic patients than in control subjects (0.69?±?0.46 vs. 0.19?±?0.61 L; p = 0.021). The main findings in HRCT in acromegalic patients were air trapping, airway calcification and bronchiectasis, which were observed in 60%, 40% and 35% of cases, respectively. There was no significant correlation between the levels of growth hormone and insulin-like growth factor I, the lung function and the air trapping.

Conclusions

Acromegalic patients show changes consistent with the involvement of the small airways and ventilation inhomogeneity, both in terms of lung function and structure. However, air trapping cannot be explained either by hormone levels or changes in lung function.