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Clinical Studies |
Departments of Endocrinology and Cardiology (J.L.M.-M.), Hospital Ramón y Cajal, Madrid, Spain
Address all correspondence and requests for reprints to: Dr. Rafael García-Robles, Servicio de Endocrinología, Hospital Ramón y Cajal, Crta. de Colmenar, Km 9.100, 28034 Madrid, Spain.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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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.
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Although acromegalic cardiomyopathy has been extensively studied, to date the relative contributions of GH hypersecretion and hypertension to the morphological and functional cardiac abnormalities described above have not been established. Moreover, there are few follow-up studies regarding the natural history of the cardiovascular abnormalities present in acromegalic patients and their responses to endocrine treatment (9, 10).
In the present study we studied cardiac abnormalities, by means of dynamic echocardiography-Doppler, in acromegalic patients. The relation of cardiac abnormalities to the presence and duration of GH hypersecretion and to the presence or absence of hypertension, and the potential reversibility of these abnormalities after treatment of acromegaly, were also evaluated.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Patients. Thirty-nine patients with active or cured acromegaly (18 men and 21 women; mean age, 50 ± 13 yr; median, 51 yr; range, 24–74 yr) were included in the study. The diagnosis of acromegaly was based on the presence of the classical clinical features, elevated serum GH concentration, serum insulin-like growth factor I (IGF-I) concentration elevated for age, lack of suppression of serum GH concentration below 2 µg/L during a 100-g oral glucose tolerance test (OGTT), and demonstration of a pituitary mass on a computed tomography scan or magnetic resonance imaging.
Patients were divided into those with active and those with nonactive acromegaly according to the present clinical evaluation and hormonal measurements. Acromegaly was considered nonactive when long term normal GH secretion (based on suppression of serum GH concentration below 2 µg/L during a 100-g OGTT and normal IGF-I concentration for age) was achieved with surgery and/or radiotherapy or with medical treatment for at least 1 yr before recruitment. In the later situation, medication was continued throughout the study. The approximate duration of active GH hypersecretion in each patient was estimated by the clinical history and by comparison of old photographs. All patients with partial or total hypopituitarism were maintained on appropriate replacement therapy throughout the study period.
In addition to the 39 patients included in the study, another 5 acromegalic patients followed-up in our department were finally excluded; 2 because of poor quality echocardiographic studies, and 3 of because concurrent illnesses that might cause cardiac abnormalities, such as hyperthyroidism (n = 1) and demonstrated excessive alcohol intake (n = 2).
Controls. A group of 17 healthy volunteers (8 men and 9 women; mean age, 54 ± 18 yr; median, 39 yr; range, 26–66 yr) and a group of 16 patients diagnosed with essential hypertension (8 men and 8 women; mean age, 51 ± 12 yr; median, 57 yr; range, 22–65 yr), with no symptoms or signs of cardiac disease, served as nonacromegalic controls for echocardiographic measurements.
Methods
Study protocol. A detailed clinical history and physical examination was performed in each patient and control. An effort was made to rule out ischemic heart disease, thyroid disease, excess alcohol consumption, and concomitant illnesses. Patients and controls were submitted to an initial evaluation, which consisted of determinations of casual blood pressure, echocardiographic studies, and hormonal evaluation of the somatotropic axis. Informed consent was obtained from every patient and control.
These parameters were evaluated again after 1 yr in 28 acromegalic patients; 10 of them had active GH hypersecretion in the initial study, whereas the other 18 showed no evidence of active acromegaly at this point. The remaining 11 patients were lost to follow-up.
During the follow-up period, 8 of the 10 patients with active acromegaly were treated with octreotide and bromocriptine (n = 4), transsphenoidal surgery (n = 3), and radiotherapy (n = 1, with persistent active disease despite later treatment with bromocriptine). In 4 patients (3 treated with octreotide and bromocriptine, and 1 treated with transsphenoidal surgery), GH secretion was normalized, and in the other patient, the initial response to transsphenoidal surgery during follow-up was considered acceptable, as the symptoms and signs of GH hypersecretion disappeared, the random serum GH measurements decreased below 5 µg/L, and serum IGF-I concentrations remained only minimally elevated. Two of the 10 patients with active acromegaly refused any treatment. None of the patients with nonactive acromegaly had a recurrence of GH hypersecretion.
Blood pressure measurements. Blood pressure was determined in every patient and control before the beginning of the study as the mean of three manual sphygmomanometer readings taken 3 consecutive days in the sitting position. Hypertension was defined according to the recommendations of the Fourth Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (11). Antihypertensive medication was stopped for a minimum of 28 days before the study.
Hormonal determinations. Patients were admitted to the Metabolic Testing Unit of our department at 0800 h. An indwelling catheter was placed in an anterocubital vein, and after 30 min of acclimation, blood samples were obtained for measurement of serum concentrations of GH and IGF-I. Serum GH concentrations were assayed by commercial RIA (Nichols Institute, San Juan Capistrano, CA). The normal ranges for men and women, as reported by the manufacturer, were 1–5 and 1–10 µg/L, respectively. Serum IGF-I concentrations were measured by RIA after acid-ethanol extraction (Nichols Institute). The normal range for the following age ranges were as follows: 16–24 yr, 182–780; 25–39 yr, 114–492; 40–54 yr, 90–360; and 55 yr or older, 71–290 (in µg/L).
Echocardiographic studies. M-mode, two-dimensional, and pulsed Doppler echocardiographic studies, were performed during at least three consecutive cardiac cycles using a Toshiba sonos SSH-140 A ultrasound system (Toshiba, Tokyo, Japan) equipped with 2.7- and 3.5-MHz phased array transducers. The recordings were made by the same investigator in every patient and control. Obviously, the investigator was aware of the patient or control status of every individual tested, as physical appearance was unequivocal. On the contrary, data regarding the presence or absence of active GH secretion or hypertension were not available to the investigator at the time of echocardiographic testing. All subjects were studied when lying in the left lateral recumbent position after a 10-min resting period, according to the recommendations of the American Society of Echocardiography (12).
The following measurements were recorded on M-mode tracing: left ventricular end-diastolic and end-systolic diameters, percentage of fractional shortening of left ventricle, left atrial end-systolic diameter, interventricular septum thickness, and posterior wall thickness. All diameters as well as interventricular septum thickness and posterior wall thickness were expressed in millimeters. The relative thickness of the left ventricular wall with respect to the left ventricular end-diastolic diameter was also calculated. The left ventricular myocardial mass was calculated using Devereux’s formula from the M-mode measurements according to the Penn convention (13). Left ventricular hypertrophy was considered when left ventricular myocardial mass values, corrected for body surface area, were greater than 135 g/m2 in males and 110 g/m2 in females (13). The end-systolic stress (in dynes per cm2) was calculated according to previously described methods (14).
The Doppler studies provided indexes of ventricular filling, which were derived from the mitral flow velocities curves: maximal early diastolic flow velocity (E; in centimeters per s), maximal late diastolic flow velocity (A; in centimeters per s), and the E/A ratio (normal value, >1). The isovolumic relaxation time corrected for cardiac frequency (in milliseconds) also served as an index of left ventricular filling. Finally, stroke volume (in milliliters) and cardiac output (cardiac output = stroke volume x cardiac frequency, in liters per min) were also calculated.
Statistical analysis
The data are represented as the mean ± SD in
the text and tables and as the mean ± SE in the
figures. Comparisons between the subgroups of active and inactive and
of hypertensive and normotensive acromegalic patients and between the
acromegalic patients and the groups of healthy volunteers or patients
with essential hypertension were made by the Kruswall-Wallis test,
followed by multiple Mann-Whitney U tests, adjusting the level of
significance downward (15) for variables that were not normally
distributed, and by one-way ANOVA followed by Tukey’s HSD test for
multiple means comparison when the variables were normally distributed
or achieved a normal distribution after logarithmic transformation.
Categorical data were analyzed by the 
2 test.
P < 0.05 was considered significant.
The influence of having active or inactive acromegaly or being
hypertensive (HT) and the interaction of both variables on
echocardiographic parameters were evaluated by multiple linear
regression analysis. Acromegaly was codified by two dummy variables to
eliminate lineal combinations (no acromegaly: X1 = 0,
X2 = 0; inactive acromegaly: X1 = 1,
X2 = 0; active acromegaly: X1 = 0,
X2 = 1), and two product variables, X1 x HT
and X2 x HT, were also created. The introduction of the
two product variables in the regression model, which represent the
interaction between acromegaly and hypertension, was estimated by
calculating the partial F statistic, according to the formula:
Fpar = {[SSR(HT, X1, X2, X1
x HT, X2x HT) - SSR(HT, X1,
X2)]/p}/MSE(HT, X1, X2,
X1 x HT, X2 x HT), where SSR is the sum of
squares, p is the number of new variables (2 in our model), and MSE is
the mean of squares. A statistically significant Fpar indicates the
existence of interaction between acromegaly and hypertension on the
dependent variable studied (16). The final regression model is
represented by the function y = 
0 +
1X1 + 2X2 +
3HT + 4X1 x HT +
5X2 x HT, where 0 is the
intercept of he regression line, which represents the estimated value
of the dependent variable when X1, X2, and HT
are 0 (that is, when the subject does not have active or inactive
acromegaly or hypertension), 1 is the additive effect of
having inactive acromegaly without hypertension, 2 is
the additive effect of having active acromegaly without hypertension,
1 + 3 + 4 is the additive
effect of having inactive acromegaly and hypertension, and
2 + 3 + 5 is the additive
effect of having active acromegaly and hypertension (16). The 95%
confidence intervals (included in parentheses) of these
effects were also estimated and were considered significant if the
interval did not include 0.
Finally, the effect of the amelioration of GH hypersecretion on echocardiographic parameters was prospectively evaluated in the five patients with initially active acromegaly in whom a satisfactory response to treatment was achieved 1 yr later, using the Wilcoxon matched pairs test for dependent samples. This test was also used in the follow-up comparison in the remaining patients who were reevaluated 1 yr later.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Clinical and hormonal data. Hypertension was present in 42.8%
of the patients with active GH hypersecretion and in 28.0% of the
patients in whom acromegaly was cured. Patients were divided into four
groups according to the presence of active GH secretion and arterial
hypertension. The following abbreviations will be used: NAC-NHT,
nonactive nonhypertensive patients (n = 18); NAC-HT, nonactive
hypertensive patients (n = 7); AC-NHT, active nonhypertensive
patients (n = 8); AC-HT, active hypertensive patients (n =
6); HT, hypertensive controls (n = 16); and C, nonhypertensive
controls (n = 17). The mean blood pressure and cardiac frequency
values of each group are summarized in Table 1
.
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). There was no difference in body surface area between any group of
patients or controls (Table 1). The estimated duration of active GH
hypersecretion was longer in AC-HT than in NAC-NHT patients (Table 1).
The estimated duration of controlled GH secretion or cured acromegaly
was longer in NAC-NHT than in NAC-HT patients (Table 1). According to
the OGTT results, 12.8% of the acromegalic patients had diabetes
mellitus, 18% had glucose intolerance, and 69.2% had normal
carbohydrate metabolism. Obesity was present in 30.7% of the
acromegalic patients, hyperlipidemia was present in 18%, and 46.2%
were smokers or had smoked. There were no differences among the
acromegalic groups in the percentage of glucose tolerance
abnormalities, obesity, or smoking, although there was a nonsignificant
tendency (P < 0.1) toward a higher percentage of
obesity and carbohydrate metabolic abnormalities in both the AC-HT and
AC-NHT groups. Three patients with active GH hypersecretion (21.4%) presented effort dyspnea [two in the AC-HT group (33.0%) and one in the AC-NHT group (12.5%)]. No patient showed signs or symptoms of overt cardiac failure or ischemic heart disease.
Basal serum GH concentrations and serum GH concentrations after a 100-g
OGTT were higher in AC-NHT and AC-HT groups than in NAC-NHT and NAC-HT
groups, but no differences were found between AC-NHT and AC-HT or
between NAC-NHT and NAC-HT patients (Table 1). The same results were
found for serum IGF-I concentrations (Table 1).
Echocardiographic data. Cardiac morphology: The
left ventricular myocardial mass was increased, with respect to that in
the C group, in the HT and AC-HT groups (Fig. 1). The
maximum left ventricular myocardial mass was present in the AC-HT
group, which presented higher values than all the other groups with the
exception of NAC-HT (Fig. 1). The multiple linear regression analysis
showed that both hypertension and active acromegaly had an independent
positive effect on left ventricular myocardial mass [64 g (range,
36–92) and 68 g (range, 9–127), respectively; F = 10.9;
P < 0.0001; Fpar = 2.4; nonsignificant], which
was in agreement with a left ventricular hypertrophy prevalence of 0%
in C, 68.8% in HT, 22.2% in NAC-NHT, 57.1% in NAC-HTA, 62.5% in
AC-NHT, and 100% in AC-HT patients (Fig. 1; 2 (5 df;
n = 72) = 30.3; P < 0.0001].
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). The maximum
posterior wall thickness was present in the AC-HT group, which
presented higher values than all the nonhypertensive groups (Fig. 1).
Multiple linear regression analysis showed that hypertension was
related to an increase in posterior wall thickness, whereas nonactive
acromegaly was related to a mild decrease in this parameter [2.1 mm
(1.4–2.7) and -1.2 mm (-2.3 to -0.05), respectively; F = 15.2;
P < 0.0001; Fpar = 1.1; nonsignificant]. Active
acromegaly and the interaction between acromegaly and hypertension did
not had a significant effect on posterior wall thickness. Similar
results were found for the interventricular septum thickness
[hypertension had a positive effect of 2.1 mm (range, 1.4–2.8);
F = 14.1; P < 0.0001; Fpar = 1.3;
nonsignificant], although no differences were found between active
acromegalics depending on the presence of hypertension (Fig. 1). The
relative thickness of left ventricular wall was increased with respect
to the control value, only in the HT group (Fig. 1). However, the
relative thickness of the left ventricular wall was higher in the
NAC-HT group than in the NAC-NHT group (Fig. 1). Multiple linear
regression analysis showed that hypertension was related to an increase
in the relative thickness of left ventricular wall, whereas nonactive
acromegaly was related to a decrease in this variable [0.09 mm (range,
0.06–0.12) and -0.09 mm (-0.15 to -0.03), respectively; F =
10.7; P < 0.0001; Fpar = 0.5;
nonsignificant].
No differences between the groups were observed in the left ventricular
end-diastolic diameter, an index of preload, or in the left ventricular
end-systolic diameter (Fig. 1), and the model of multiple linear
regression analysis was nonsignificant for both diameters. There were
no differences between the control and acromegalic groups in their left
atrial end-systolic diameter, whereas this diameter was higher in the
HT group compared to that in the C group (Fig. 1). Accordingly, the
result of the multiple linear regression analysis showed that
hypertension was related to a moderate increase in left atrial
end-systolic diameter [2.6 mm (range, 0.7–4.5); F = 3.6;
P < 0.05; Fpar = 0.5; nonsignificant], whereas
active or inactive acromegaly and the interaction between hypertension
and acromegaly had no effect on this diameter.
Systolic function indexes: The stroke volume was elevated in
the NAC-NHT, NAC-HT, and AC-NHT groups with respect to that in the C
group, but was not different from those in the HT and AC-HT groups
(Fig. 2). The multiple linear regression analysis showed
positive independent effects of active acromegaly and hypertension on
stroke volume, as well as a significant interaction between active and
nonactive acromegaly and hypertension on stroke volume [hypertension,
9 mL (range, 2–17); active acromegaly, 71 mL (range, 35–107); active
acromegaly and hypertension, 42 mL (range, 24–60); nonactive
acromegaly and hypertension, 25 mL (range, 10–39); F = 5.4;
P < 0.001; Fpar = 5.0; P <
0.01]. Cardiac output was increased in the HT and AC-NHT groups with
respect to that in the C group (Fig. 2), and the multiple linear
regression analysis showed an increase in cardiac output depending on
the presence of active acromegaly and a significant effect of
hypertension only in active acromegaly [5.8 L/min (range, 2.2–9.5)
and 3.4 L/min (range, 1.5–5.2), respectively; F = 3.0;
P < 0.02; Fpar = 3.3; P <
0.05]. The fractional shortening was increased only in the NAC-HT
group with respect to those in the nonhypertensive control and
nonhypertensive acromegalic groups (Fig. 2), and multiple linear
regression analysis showed that only hypertension had a positive effect
on this variable [3.7% (range, 1.4–6.0); F = 4.1;
P < 0.01; Fpar = 2.7; nonsignificant]. The
end-systolic stress, an index of afterload, was increased in the HT and
NAC-HT groups with respect to those in the C, NAC-NHT, and AC-NHT
groups (Fig. 2). The AC-HT group presented intermediate end-systolic
stress values that were not different from those in any other group
(Fig. 2). The multiple linear regression analysis showed that
hypertension had a positive effect on end-systolic stress, whereas both
active and nonactive acromegaly had a negative independent effect on
this variable [31 (range, 21–40), -32 (range, -53 to -12), and
-22 (range, -38 to -6) dynes/cm2, respectively; F =
15.9; P < 0.0001; Fpar = 1.8;
nonsignificant].
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). Accordingly, the results of the
multiple linear regression analysis showed that the model was not valid
for E, the increase in A was only related to hypertension [0.10 cm/s
(range, 0.04–0.15); F = 4.2; P < 0.01; Fpar
= 2.7; nonsignificant], and there was an interaction between
hypertension and acromegaly in the E/A ratio, with hypertension
reducing its values, and nonactive acromegaly increasing them [-0.16
(-0.26 to -0.06) and 0.49 (range, 0.13–0.85), respectively; F =
7.4; P < 0.0001; Fpar = 4.8; P <
0.05].
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). The multiple regression analysis showed
independent positive effects of hypertension and active acromegaly on
isovolumic relaxation time [14 ms (range, 5–24) and 22 ms (range,
2–41); F = 5.6; P < 0.02; Fpar = 2.7;
nonsignificant]. Follow-up study
As stated above, 18 of the 28 patients who were reevaluated 1 yr later had nonactive acromegaly at the initial evaluation and remained so throughout the follow-up period. Taken together, no differences were noticed in any of the hormonal or echocardiographic parameters studied with respect to the initial evaluation in these 18 patients (data not shown). However, 6 of the 18 patients with nonactive acromegaly who also had hypertension presented a reduction in end-systolic stress (147 ± 27 vs. 34 ± 16 dynes/cm2; P < 0.05) and an increase in E (0.56 ± 0.12 vs. 0.67 ± 0.22 cm/s; P < 0.05) during the year of follow-up. In 5 of the 10 patients with active acromegaly, GH hypersecretion was ameliorated by means of several treatments (see Materials and Methods). These patients presented a significant decrease in basal serum GH (8.8 ± 7.8 vs. 2.2 ± 1.8; P < 0.05) and IGF-I (549 ± 128 vs. 396 ± 101; P < 0.05) concentrations and in left ventricular myocardial mass (231 ± 54 vs. 157 ± 92 g; P < 0.05) and posterior wall thickness (9.7 ± 2.0 vs. 7.1 ± 4.2 mm; P < 0.05) as well as a nonsignificant tendency (P < 0.10) for decreases in the relative thickness of left ventricular wall, fractional shortening and end-systolic stress and for an increase in the E/A ratio. In the remaining 5 patients in whom GH hypersecretion was not controlled with treatment, no change in any of the echocardiographic parameter studied was found (data not shown).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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In our series, hypertension was involved in the development of almost all of the echocardiographic abnormalities found in acromegalic patients. Hypertension was independently related to undesirable changes in morphological (increases in left ventricular myocardial mass, posterior wall thickness, interventricular septum thickness, relative thickness of left ventricular wall, and left atrial end-systolic diameter) and functional systolic (increases in stroke volume, fractional shortening, and end-systolic stress) and diastolic (increases in A and isovolumic relaxation time, and decrease in E/A ratio) echocardiographic indexes.
Despite the broad deleterious effect of hypertension on echocardiographic parameters, the multiple linear regression analysis disclosed that acromegaly has several effects on cardiac morphology and function that are independent of the coexistence of hypertension, suggesting the existence of a specific acromegalic myocardiopathy. Both active acromegaly and hypertension were independently related to an increase in left ventricular myocardial mass, leading to a striking 100% prevalence in the patients with active acromegaly and hypertension. Systolic function was affected by acromegaly, as an increase in the cardiac output in our series was only related to active acromegaly, and this effect was favored by hypertension in this specific subset of patients, but not in controls. The stroke volume was increased by both active acromegaly and hypertension, with a significant interaction between both variables, whereas end-systolic stress was decreased by acromegaly and increased by hypertension. The increase in stroke volume together with the reduction of end-systolic stress (an index of afterload) related to acromegaly result in an augmented peripheral blood flow that might be involved in the development of hypertension in this disease (28). When hypertension appears, end-systolic stress increases, and systolic function deteriorates, a tendency also shown by our data. The isovolumic relaxation time, an index of diastolic function, was prolonged independently by active acromegaly and hypertension.
The causal relationship between GH hypersecretion and the echocardiographic abnormalities related to active acromegaly is also favored by the decrease in left ventricular myocardial mass and posterior wall thickness observed in our five patients with active acromegaly in whom significant amelioration of GH hypersecretion was achieved 1 yr later. This later result seems to be related to the decrease in GH and IGF-I concentrations rather than to a successful treatment of hypertension, as only one patient in this group had elevated blood pressure initially. Similar results were also found by another study as early as 1 week after the beginning of treatment with the somatostatin analog octreotide (30) and were found after longer periods of normalization of GH secretion (31, 32, 33).
The echocardiographic evolution in the groups of nonactive acromegalics and noncontrolled active acromegalics needs further explanation. On the one hand, no changes were noticed in nonactive nonhypertensive patients, but antihypertensive treatment with converting enzyme inhibitors in nonactive hypertensive patients had favorable effects on systolic (end-systolic stress) and diastolic (maximal early diastolic flow velocity) function. On the contrary, such a favorable effect was not noticed in the patients with active acromegaly and hypertension in whom GH hypersecretion was not controlled despite similar treatment for hypertension. The latter further supports the pathophysiological role of GH hypersecretion in the cardiac abnormalities present in acromegaly and reflects the frequent resistance to conventional therapy present in these patients when acromegaly remains active (4).
The existence of a specific acromegalic heart disease is also supported by animal and human investigations. Rats implanted with GH-secreting tumors present a disproportionate cardiac enlargement (34), a finding that is also frequent in necropsies of patients with acromegaly (35). Moreover, as stated above, cardiac disease is present in acromegalic patients in whom an obvious accompanying disease, such as hypertension, hyperthyroidism, ischemic heart disease, or diabetes mellitus, can not be found (5).
Hypertension is intimately related to GH hypersecretion in acromegaly (4). Several GH-dependent mechanisms have been postulated to explain this relationship, such as an increase in peripheral resistances (36), which appears to be related to an increased vascular responsiveness to angiotensin II (37); sodium and water retention (38); and an increase in cardiac output (28), which might also contribute to an increase in peripheral resistances. Several clinical findings in our patients provide further indirect evidence favoring this hypothesis. 1) The estimated duration of GH hypersecretion was longer in active hypertensive acromegalics patients with respect to nonactive nonhypertensive patients. 2) The estimated period of normal GH secretion after successful treatment was longer in nonactive nonhypertensive patients than that in nonactive hypertensive patients. However, the latter result might have been influenced by the older age of nonactive hypertensive patients, as the prevalence of hypertension increases with age in the general population. Finally, we have not been able to confirm previous reports suggesting a pathophysiological role of circulating IGF-I (39) or GH in essential hypertension, as we have not found any difference in the serum concentrations of these hormones between normotensive and hypertensive controls.
In conclusion, asymptomatic morphological and functional cardiac abnormalities are a frequent finding in acromegaly and might finally lead to overt heart disease. Most of these abnormalities are independently related to hypertension and active acromegaly, suggesting the existence of a specific acromegalic myocardiopathy. The fact that at least some of these abnormalities can be reverted by controlling GH hypersecretion must encourage clinicians to an early diagnosis, monitoring their evolution after successful treatment of acromegaly, and focusing on an aggressive treatment of hypertension when present.
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Acknowledgments |
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Footnotes |
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Received October 23, 1996.
Revised December 23, 1996.
Accepted January 10, 1997.
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References |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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A. Colao, A. Cuocolo, P. Marzullo, E. Nicolai, D. Ferone, A. M. Della Morte, R. Pivonello, M. Salvatore, and G. Lombardi Is the Acromegalic Cardiomyopathy Reversible? Effect of 5-Year Normalization of Growth Hormone and Insulin-Like Growth Factor I Levels on Cardiac Performance J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1551 - 1557. [Abstract] [Full Text]
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T. Sas, P. Mulder, and A. Hokken-Koelega Body Composition, Blood Pressure, and Lipid Metabolism before and during Long-Term Growth Hormone (GH) Treatment in Children with Short Stature Born Small for Gestational Age Either with or without GH Deficiency J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3786 - 3792. [Abstract] [Full Text]
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A. Colao, P. Marzullo, D. Ferone, L. Spinelli, A. Cuocolo, D. Bonaduce, M. Salvatore, V. Boerlin, I. Lancranjan, and G. Lombardi Cardiovascular Effects of Depot Long-Acting Somatostatin Analog Sandostatin LAR in Acromegaly J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3132 - 3140. [Abstract] [Full Text]
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 E. Bollano, E. Omerovic, M. Bohlooly-Y, V. Kujacic, B. Madhu, J. Tornell, O. Isaksson, B. Soussi, W. Schulze, M. L. X. Fu, et al. Impairment of Cardiac Function and Bioenergetics in Adult Transgenic Mice Overexpressing the Bovine Growth Hormone Gene Endocrinology, June 1, 2000; 141(6): 2229 - 2235. [Abstract] [Full Text] [PDF]
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P. Marzullo, A. Cuocolo, D. Ferone, R. Pivonello, M. Salvatore, G. Lombardi, and A. Colao Cardiac Effect of Thyrotoxicosis in Acromegaly J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1426 - 1432. [Abstract] [Full Text]
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A. Colao, R. Baldelli, P. Marzullo, E. Ferretti, D. Ferone, P. Gargiulo, M. Petretta, G. Tamburrano, G. Lombardi, and A. Liuzzi Systemic Hypertension and Impaired Glucose Tolerance Are Independently Correlated to the Severity of the Acromegalic Cardiomyopathy J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 193 - 199. [Abstract] [Full Text]
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A. Colao, A. Cuocolo, P. Marzullo, E. Nicolai, D. Ferone, A. M. D. Morte, M. Petretta, M. Salvatore, and G. Lombardi Impact of Patient's Age and Disease Duration on Cardiac Performance in Acromegaly: A Radionuclide Angiography Study J. Clin. Endocrinol. Metab., May 1, 1999; 84(5): 1518 - 1523. [Abstract] [Full Text]
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R. Baldelli, E. Ferretti, M.-L. Jaffrain-Rea, G. Iacobellis, G. Minniti, B. Caracciolo, C. Moroni, R. Cassone, A. Gulino, and G. Tamburrano Cardiac Effects of Slow-Release Lanreotide, a Slow-Release Somatostatin Analog, in Acromegalic Patients J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 527 - 532. [Abstract] [Full Text]
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A. Colao, A. Cuocolo, P. Marzullo, E. Nicolai, D. Ferone, L. Florimonte, M. Salvatore, and G. Lombardi Effects of 1-Year Treatment with Octreotide on Cardiac Performance in Patients with Acromegaly J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 17 - 23. [Abstract] [Full Text]
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, At least
P < 0.05 with respect to C, HT, NAC-NHT, and
AC-NHT. 
, At least P < 0.05 with respect to C
and NAC-NHT. §, At least P < 0.05 with respect to
C, NAC-NHT, and AC-NHT. ||, At least P < 0.05
with respect to NAC-NHT.
