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Biomedical subjects

D Sabatini

Publications and source records attributed to D Sabatini.

At least 19 recordsLinked to original sources
PubMed2001

FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse.

The FKBP-12-rapamycin associated protein (FRAP, also known as mTOR and RAFT-1) is a member of the phosphoinositide kinase related kinase family. FRAP has serine/threonine kinase activity and mediates the cellular response to mitogens through signaling to p70s6 kinase (p70(s6k)) and 4E-BP1, resulting in an increase in translation of subsets of cellular mRNAs. Translational up-regulation is blocked by inactivation of FRAP signaling by rapamycin, resulting in G(1) cell cycle arrest. Rapamycin is used as an immunosuppressant for kidney transplants and is currently under investigation as an antiproliferative agent in tumors because of its ability to block FRAP activity. Although the role of FRAP has been extensively studied in vitro, characterization of mammalian FRAP function in vivo has been limited to the immune system and tumor models. Here we report the identification of a loss-of-function mutation in the mouse FRAP gene, which illustrates a requirement for FRAP activity in embryonic development. Our studies also determined that rapamycin treatment of the early embryo results in a phenotype indistinguishable from the FRAP mutant, demonstrating that rapamycin has teratogenic activity.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Regulation of the rapamycin and FKBP-target 1/mammalian target of rapamycin and cap-dependent initiation of translation by the c-Abl protein-tyrosine kinase.

The c-Abl protein-tyrosine kinase is activated by ionizing radiation and certain other DNA-damaging agents. The rapamycin and FKBP-target 1 (RAFT1), also known as FKBP12-rapamycin-associated protein (FRAP, mTOR), regulates the p70S6 kinase (p70(S6k)) and the eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). The present results demonstrate that c-Abl binds directly to RAFT1 and phosphorylates RAFT1 in vitro and in vivo. c-Abl inhibits autophosphorylation of RAFT1 and RAFT1-mediated phosphorylation p70(S6k). The functional significance of the c-Abl-RAFT1 interaction is further supported by the finding that eIF4E-dependent translation in mouse embryo fibroblasts from Abl(-/-) mice is significantly higher than that compared in wild-type cells. The results also demonstrate that exposure of cells to ionizing radiation is associated with c-Abl-mediated binding of 4E-BP1 to eIF4E and inhibition of translation. These findings with the c-Abl tyrosine kinase represent the first demonstration of a negative physiologic regulator of RAFT1-mediated 5' cap-dependent translation.

Animals↗
PubMed2000

Functional interaction between RAFT1/FRAP/mTOR and protein kinase cdelta in the regulation of cap-dependent initiation of translation.

Hormones and growth factors induce protein translation in part by phosphorylation of the eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1). The rapamycin and FK506-binding protein (FKBP)-target 1 (RAFT1, also known as FRAP) is a mammalian homolog of the Saccharomyces cerevisiae target of rapamycin proteins (mTOR) that regulates 4E-BP1. However, the molecular mechanisms involved in growth factor-initiated phosphorylation of 4E-BP1 are not well understood. Here we demonstrate that protein kinase Cdelta (PKCdelta) associates with RAFT1 and that PKCdelta is required for the phosphorylation and inactivation of 4E-BP1. PKCdelta-mediated phosphorylation of 4E-BP1 is wortmannin resistant but rapamycin sensitive. As shown for serum, phosphorylation of 4E-BP1 by PKCdelta inhibits the interaction between 4E-BP1 and eIF4E and stimulates cap-dependent translation. Moreover, a dominant-negative mutant of PKCdelta inhibits serum-induced phosphorylation of 4E-BP1. These findings demonstrate that PKCdelta associates with RAFT1 and thereby regulates phosphorylation of 4E-BP1 and cap-dependent initiation of protein translation.

Androstadienes↗
PubMed2000

Localization of ribophorin II to the endoplasmic reticulum involves both its transmembrane and cytoplasmic domains.

Proteins that are concentrated in specific compartments of the endomembrane system in order to exert their organelle-specific function must possess specific localization signals that prevent their transport to distal regions of the exocytic pathway. Some resident proteins of the endoplasmic reticulum (ER) that are known to escape with low efficiency from this organelle to a post ER compartment are recognized by a recycling receptor and brought back to their site of residence. Other ER proteins, however, appear to be retained in the ER by mechanisms that operate in the organelle itself. The mammalian oligosaccharyltransferase (OST) is a protein complex that effects the cotranslational N-glycosylation of newly synthesized polypeptides, and is composed of at least four rough ER-specific membrane proteins: ribophorins I and II (RI and RII), OST48, and Dadl. The mechanism(s) by which the subunits of this complex are retained in the ER are not well understood. In an effort to identify the domains within RII responsible for its ER localization we have studied the fate of chimeric proteins in which one or more RII domains were replaced by the corresponding ones of the Tac antigen, the latter being a well characterized plasma membrane protein that lacks intrinsic ER retention signals and serves to provide a neutral framework for the identification of retention signals in other proteins. We found that the luminal domain of RII by itself does not contain retention information, while the cytoplasmic and transmembrane domains contain independent ER localization signals. We also show that the retention function of the transmembrane domain is strengthened by the presence of a flanking luminal region consisting of 15 amino acids.

Animals↗
PubMed1997

Growth hormone and heart performance. A novel mechanism of cardiac wall stress regulation in humans.

OBJECTIVES: This study was designed to assess systolic wall stress and ventricular function in patients with deranged growth hormone secretion, in an attempt to elucidate the mechanisms of growth hormone interaction with heart performance. DESIGN: A case-control study. SUBJECTS: Thirty patients with active acromegaly, free of diabetes mellitus and coronary artery disease, and 25 subjects with congenital growth hormone deficiency were studied. Twelve growth hormone-deficient subjects were reevaluated after 12 months of recombinant human growth hormone therapy. Two groups of 30 normal subjects each were used as controls for the acromegalic and growth hormone-deficient patients, respectively. RESULTS: In the acromegalics, end-systolic wall stress was reduced (-20%; P < 0.01) due to ventricular wall thickening (+ 26%; P < 0.001), whereas cardiac output was significantly increased (+ 20%; P < 0.01). The velocity of fibre shortening was unchanged. In growth hormone-deficient subjects, end-systolic wall stress was markedly increased (+ 38%; P < 0.001) due to a significant reduction of ventricular wall thickness (- 28%; P < 0.001), whereas cardiac output was significantly decreased (-44%; P < 0.001). Replacement therapy with recombinant human growth hormone produced a partial correction of wall thickness and stress. Consequently, systolic performance and cardiac output improved significantly. CONCLUSION: This study demonstrates that growth hormone plays a role in the control of cardiac wall stress and performance through a mechanism mediated by the effect of growth hormone on myocardial tissue growth. The data may have therapeutic implications in cardiac diseases that lead to heart failure.

Acromegaly↗
PubMed1996

A preliminary study of growth hormone in the treatment of dilated cardiomyopathy.

BACKGROUND: Cardiac hypertrophy is a physiologic response that allows the heart to adapt to an excess hemodynamic load. We hypothesized that inducing cardiac hypertrophy with recombinant human growth hormone might be an effective approach to the treatment of idiopathic dilated cardiomyopathy, a condition in which compensatory cardiac hypertrophy is believed to be deficient. METHODS: Seven patients with idiopathic dilated cardiomyopathy and moderate-to-severe heart failure were studied at base line, after three months of therapy with human growth hormone, and three months after the discontinuation of growth hormone. Standard therapy for heart failure was continued throughout the study. Cardiac function was evaluated with Doppler echocardiography, right-heart catheterization, and exercise testing. RESULTS: When administered at a dose of 14 IU per week, growth hormone doubled the serum concentrations of insulin-like growth factor I. Growth hormone increased left-ventricular-wall thickness and reduced chamber size significantly. Consequently, end-systolic wall stress (a function of both wall thickness and chamber size) fell markedly (from a mean [+/-SE] of 144+/-11 to 85+/-8 dyn per square centimeter, P<0.001). Growth hormone improved cardiac output, particularly during exercise (from 7.4+/-0.7 to 9.7+/-0.9 liters per minute, P=0.003), and enhanced ventricular work, despite reductions in myocardial oxygen consumption (from 56+/-6 to 39+/-5 ml per minute, P=0.005) and energy production (from 1014+/-100 to 701+/-80 J per minute, P=0.002). Thus, ventricular mechanical efficiency rose from 9+/-2 to 21+/-5 percent (P=0.006). Growth hormone also improved clinical symptoms, exercise capacity, and the patients' quality of life. The changes in cardiac size and shape, systolic function, and exercise tolerance were partially reversed three months after growth hormone was discontinued. CONCLUSIONS: Recombinant human growth hormone administered for three months to patients with idiopathic dilated cardiomyopathy increased myocardial mass and reduced the size of the left ventricular chamber, resulting in improvement in hemodynamics, myocardial energy metabolism, and clinical status.

Adult↗
PubMed1996

Diastolic dysfunction in patients with non-insulin-dependent diabetes mellitus of short duration.

To determine whether abnormal left ventricular diastolic function is present at an early stage of non-insulin-dependent diabetes mellitus (NIDDM), left ventricular diastolic filling was evaluated by pulsed doppler echocardiography in 16 normotensive patients with NIDDM of short duration (1.8 +/- 1 years, mean +/- SD) and no evidence of microangiopathy, and in 16 healthy volunteers comparable for age, body mass index, and sex distribution. All patients showed normal systolic function. The interventricular septum thickness, left atrial diameter, and left ventricular mass index were increased in the diabetic as compared with the control group (p < 0.01, p < 0.01, and p < 0.02, respectively). Isovolumic relaxation time and atrial peak filling velocity were greater in diabetic patients (p < 0.001, and p < 0.01, respectively), whereas early to atrial peak filling velocity ratio was significantly reduced (p < 0.05). This study demonstrates that an impairment of left ventricular diastolic function occurs early in the natural history of NIDDM, and that this abnormality is unlikely to be related to clinical evidence of microangiopathic complications.

Acute Disease↗
PubMed1996

Impaired cardiac reserve and exercise capacity in patients receiving long-term thyrotropin suppressive therapy with levothyroxine.

To assess cardiac function and exercise tolerance in patients receiving long term TSH-suppressive therapy with levothyroxine (L-T4), we studied maximal exercise capacity with a bicycle ergometer and left ventricular function at rest and during physical exercise by radionuclide angiography. The evaluation was performed in 10 patients receiving L-T4 therapy (2.31 +/- 0.13 microgram/kg) for 5-9 yr, presenting with effort dyspnea and symptoms of adrenergic overactivity, and 10 matched control subjects. The patients were reassessed after 4 months of administration of the selective beta-adrenergic blocker bisoprolol (4.25 +/- 0.4 mg/day); L-T4 therapy remained unchanged. The results showed that at rest, left ventricular diastolic filling was impaired in the patients (P < 0.05), whereas systolic function was unaltered. During submaximal physical exercise, left ventricular ejection fraction increased in the controls from 58 +/- 2% to 65 +/- 2% (P < 0.001), whereas in the patients it fell from 63 +/- 2% to 53 +/- 2% (P < 0.01), mainly because of increased end-systolic left ventricular volume (P < 0.05). Exercise capacity was markedly reduced in the patients in terms of both peak workload (P < 0.001) and exercise duration (P < 0.001). beta-Adrenergic blockade prevented both the fall in ejection fraction and the increase in end-systolic volume during exercise, and improved exercise tolerance. In conclusion, our data show that long term TSH-suppressive therapy with L-T4 is not as harmless as believed, because it may cause marked impairment of cardiac functional reserve and physical exercise capacity. Administration of a beta-blocking drug for 4 months caused significant improvement of cardiac performance and exercise tolerance.

Adrenergic beta-Antagonists↗
PubMed1995

Optimal determination of right ventricular filling dynamics in systemic hypertension.

To determine the optimal method of normalizing peak filling rate (PFR) determinations and apply it to the assessment of right ventricular (RV) and left ventricular (LV) filling characteristics and their interactions, 41 subjects with hypertension and 40 matched normals underwent echo-Doppler and nuclear study. Conventional normalization of PFR to end-diastolic volume (EDV) yielded poor correlations between nuclear- and echo-derived PFR (RV, r = 0.34; LV, r = 0.42), whereas nuclear and echo PFR normalized to stroke volume (SV) were closely correlated (RV, r = 0.87; LV, r = 0.92). Further, use of PFR normalized to SV revealed to close relation between RV and LV filling characteristics. Multivariate analysis confirmed that, in contrast to normalization to EDV or early to late filling-velocity ratios (E/A), peak filling rate normalized to SV was independent of ejection fraction and heart rate. In addition, RV filling impairment was related to LV filling impairment, and the effects of hypertension eliminated the independent influence of age on both LV and RV filling. In conclusion, normalization of PFR to SV may be preferable to use of EDV or E/A in evaluating RV and LV filling dynamics.

Adult↗
PubMed1995

Diastolic dysfunction in patients on thyroid-stimulating hormone suppressive therapy with levothyroxine: beneficial effect of beta-blockade.

Thyroid-stimulating hormone (TSH) suppressive therapy with levothyroxine (L-T4) may cause adverse cardiac effects such as rhythm disturbances and ventricular hypertrophy. The latter is a predisposing condition to diastolic dysfunction. Thus, this study was designed to assess the effect of long-term TSH suppressive therapy on cardiac diastolic function. Because beta-blockade is known to reduce ventricular hypertrophy in patients on L-T4 therapy, we also tried to determine whether the addition of a beta-blocker to L-T4 improved diastolic function. Twenty-five patients (21 female and 4 male; mean age 41 +/- 10 yr) on TSH suppressive therapy for 3-9 yr (9 for differentiated carcinoma and 16 for nontoxic goiter) and 20 control subjects were studied. A subgroup of 10 patients, selected for the presence of symptoms and signs of adrenergic overactivity, was treated for 4 months with the beta-blocker bisoprolol (4.25 +/- 1.2 mg/day), and their maintaining L-T4 therapy was unchanged. In the patient group, left ventricular mass was significantly increased (P < 0.001), isovolumic relaxation time was prolonged (P < 0.001), and early diastolic filling velocity was markedly reduced (P < 0.001), whereas late diastolic filling was increased (P < 0.005). Consequently, the early-to-late diastolic flow velocity ratio was markedly decreased (P < 0.001). These alterations were more pronounced in the subgroup of patients with evidence of adrenergic overactivity. In these patients, beta-blockade induced a significant regression of cardiac hypertrophy and improved diastolic dysfunction. In particular, isovolumic relaxation time decreased (P < 0.01) and the early-to-late flow velocity ratio increased significantly (P < 0.01). Both indices reached values after beta-blockade that were no longer different from those of asymptomatic patients. It is concluded that long-term L-T4 therapy increases myocardial mass and causes relevant diastolic dysfunction, particularly in those patients with evidence of mild hyperthyroidism and adrenergic overactivity. Both myocardial hypertrophy and diastolic dysfunction are significantly improved by adrenergic beta-blockade.

Adult↗
PubMed1994

Impaired cardiac performance in GH-deficient adults and its improvement after GH replacement.

Cardiac performance was investigated by radionuclide angiography in 11 patients with childhood-onset growth hormone (GH) deficiency and in 12 control subjects. Both at rest and during maximal physical exercise, systolic function was markedly depressed in GH-deficient patients. Ejection fraction rose from 66 +/- 6 to 76 +/- 7% during exercise in control subjects, whereas in GH-deficient patients it remained unchanged or even decreased (55 +/- 6 and 54 +/- 9% at rest and after exercise, respectively; P < 0.01 vs. controls). Cardiac index was significantly lower in GH-deficient patients than in controls, both at rest (2.7 +/- 0.6 vs. 3.7 +/- 0.5 l.min-1.m-2; P < 0.001) and during exercise (8 +/- 1.2 vs. 10 +/- 1.5 l.min-1.m-2; P < 0.01). Five GH-deficient patients were treated with recombinant human (rh) GH for 6 mo at a dose of 0.05 IU.kg-1.day-1. Cardiac index at rest improved from 2.8 +/- 0.6 to 3.3 +/- 0.8 l.min-1.m-2 (P < 0.01) after rhGH. Also, cardiac index response to exercise improved markedly and became similar to that of controls (7.5 +/- 1.2 and 10.1 +/- 1.1 l.min-1.m-2 before and after rhGH, respectively; P < 0.005). Exercise tolerance was impaired in GH-deficient patients and was restored by rhGH treatment. The data support the hypothesis that GH plays an important role in the maintenance of a normal cardiac performance in humans.

Adult↗
PubMed1994

Control of adrenergic overactivity by beta-blockade improves the quality of life in patients receiving long term suppressive therapy with levothyroxine.

Several symptoms and signs of hyperthyroidism are frequently shared by patients receiving L-T4 suppressive therapy. The aim of this study was to evaluate whether a beta-adrenergic blocking drug could reduce the severity of these symptoms and signs in these patients, as previously reported in patients with hyperthyroidism. Eleven patients (mean age, 42 +/- 11 yr; 10 females and one male) affected with differentiated thyroid carcinoma or nontoxic goiter were selected from a more numerous group of patients receiving suppressive therapy based on the presence of palpitations, increased heart rate, left ventricular systolic function, and other symptoms mimicking exaggerated beta-adrenergic activity. In these patients the cardioselective beta-blocking drug bisoprolol was added to the L-T4 suppressive therapy at a dose of 2.5-5 mg/day. Blood samples were collected for the determination of thyroid hormones and TSH concentration during L-T4 therapy and after 3 and 6 months of associated L-T4 plus bisoprolol therapy. Cardiac function was assessed by clinical evaluation, standard and Holter electrocardiogram, as well as one- and two-dimensional echocardiography. Furthermore, we applied the symptom-rating scale previously used by Klein et al. in hyperthyroid patients to assess the quality of life in our group of patients. Our findings show that the addition of bisoprolol to L-T4 suppressive therapy produces a normalization of heart rate, which was significantly increased during TSH suppressive therapy, and the disappearance of atrial arrhythmias with considerable reduction of palpitations. Furthermore, bisoprolol produced an effective improvement in measures of the hyperthyroid symptom scale, with significant reduction of the mean score. The echocardiographic data showed an increased left ventricular mass index with significantly enhanced systolic function at the basal evaluation. After 6 months of combined L-T4 plus bisoprolol therapy, left ventricular mass index normalized, and the indices of left ventricular systolic function were reduced, with a tendency to normalize. Further studies conducted on a larger series of patients are required to verify the long term implications of cardiac parameter variations on cardiovascular morbidity and mortality. Our results, however, show that the addition of bisoprolol to L-T4 suppressive therapy improves the quality of life in those patients with clinical features of enhanced adrenergic activity.

Adult↗
PubMed1994

Impaired cardiac performance is a distinct feature of uncomplicated acromegaly.

This study was designed to assess right and left ventricular function in patients with active acromegaly. To this end, 26 acromegalic patients (9 of whom had arterial hypertension) and 15 normal subjects of comparable age and sex distribution were studied by radionuclide angiography at rest and during supine bicycle-ergometer exercise and echocardiography. At rest, the filling rates of left (-19%; P < 0.005) and right ventricle (-32%; P < 0.001) were significantly reduced in acromegalic patients, whereas right and left ventricle ejection fractions (EFs) were normal. During physical exercise, EF was considerably lower in the acromegalic patients than in controls. This was true for both left (61 +/- 11% vs. 75 +/- 8%; P < 0.001) and right ventricle (45 +/- 13 vs. 58 +/- 11%; P < 0.002). In as many as 73% of patients, EF increased less than 5%, thus fulfilling the criteria for impaired cardiac performance. Left ventricular mass index was 60% greater in acromegalics than in controls (P < 0.001). A significant difference in left ventricular mass index was also present when normotensive acromegalic patients were compared with controls (P < 0.001). No significant difference in the indices of systolic and diastolic function was observed between the subgroups of normotensive and hypertensive acromegalics, either at rest or during exercise. The data demonstrate that in uncomplicated acromegaly, besides cardiac hypertrophy, there are also important alterations of systolic and diastolic function of both ventricles, leading to a significant impairment of cardiac performance.

Acromegaly↗
PubMed1993

Evidence for biventricular involvement in acromegaly: a Doppler echocardiographic study.

To investigate left and right ventricular involvement in acromegaly, 20 patients were studied by Doppler echocardiography. Nine of them had systemic hypertension. Right ventricular free wall thickness was significantly increased in acromegalic patients (8 +/- 2 vs 4 +/- 1 mm; P < 0.001). Left ventricular mass index was augmented both in the whole group and in the subgroup of normotensive acromegalics, as compared with normals (134 +/- 33 and 115 +/- 20 vs 80 +/- 18 g.m-2; P < 0.01). Ejection phase indices were normal in the patient group, while impaired left and right ventricular diastolic filling was found. In fact isovolumic relaxation time was prolonged (118 +/- 21 vs 78 +/- 12 ms; P < 0.001), ratio of early to late mitral (0.9 +/- 0.3 vs 1.8 +/- 0.5; P < 0.001) and tricuspid (1.0 +/- 0.2 vs 1.4 +/- 0.3; P < 0.001) flow velocities were significantly decreased as compared with controls. Superior vena cava flowmetry was also abnormal showing a marked decrease of diastolic filling wave and, consequently, of the ratio between peak diastolic and peak systolic flow velocity. No significant differences were observed between normotensive and hypertensive acromegalics, except for left ventricular mass index (115 +/- 20 vs 156 +/- 31 g.m-2; P < 0.01). These findings indicate that abnormal diastolic filling patterns of transmitral, transtricuspid, and superior vena cava flowmetry suggesting 'impaired relaxation' associated with increased left and right ventricular mass, frequently occur in acromegaly.

Acromegaly↗
PubMed1993

Platelet aggregability in patients with a VVI pacemaker.

Several studies have suggested an increased incidence of thromboembolic events in patients with VVI pacemaker (VVI patients); furthermore, other authors have demonstrated that a treatment with anticoagulants or antiplatelet drugs may be effective in reducing thromboembolic events, thus suggesting an increased formation of platelet thrombi in these patients. In this respect, platelet aggregability was investigated in ten VVI patients and ten age- and sex-matched subjects. beta-thromboglobulin (beta-Tg) and platelet factor 4 (PF4) plasma levels were determined as well as platelet aggregation induced by ADP, collagen, epinephrine, and arachidonic acid. Plasma beta-Tg levels were increased in the patient group (86 +/- 24 vs 24 +/- 13 ng/mL; P < 0.001) in presence of normal PF4 values (14 +/- 11 vs 13 +/- 6 ng/mL; NS). Aggregation curves showed abnormal values of maximal amplitude, slope, and lag time. In particular, maximal amplitude was significantly higher in VVI patients as compared with controls (ADP P < 0.01, collagen P < 0.001, adrenaline P < 0.01, arachidonic acid P < 0.05). These findings strongly suggest an increase of platelet activity in VVI patients.

Adenosine Diphosphate↗
PubMed1993

Chronic treatment with the somatostatin analog octreotide improves cardiac abnormalities in acromegaly.

The aim of this study was to investigate the effects of a 6-month octreotide treatment on cardiac mass and function by means of Doppler echocardiography in 11 normotensive patients affected with active acromegaly. The GH and insulin-like growth factor-I levels were normalized during octreotide therapy from 34 +/- 6.5 and 767.4 +/- 72.4 micrograms/L to 4.6 +/- 0.9 and 235 +/- 10.3 micrograms/L, respectively (P < 0.001; mean +/- SEM). After the 6-month treatment, we observed a significant decrease in the left ventricular mass index from 138 +/- 11 to 116 +/- 13 g/m2 (P < 0.001) and in the mean wall thickness/internal end-diastolic radius ratio from 0.47 +/- 0.1 to 0.44 +/- 0.1 (P < 0.001). No significant differences were found in systolic function indices, whereas diastolic filling indices improved over the course of the therapy; the isovolumic relaxation time decreased from 115 +/- 6 to 100 +/- 6 ms (P < 0.05), tricuspid late diastolic filling velocities decreased from 41 +/- 3 to 36 +/- 2 cm/s (P < 0.03), and tricuspid deceleration time decreased from 280 +/- 28 to 198 +/- 15 ms (P < 0.005); the ratio of early to late peak velocity of the right ventricular filling significantly increased from 1 +/- 0.01 to 1.3 +/- 0.1 (P < 0.03). A significant correlation was detected between left ventricular mass regression and increase in the early to late peak velocity ratio of the left ventricular filling (r = 0.62; P < 0.05). The results of this study show an improvement in cardiac structural and functional abnormalities during chronic treatment with octreotide, thus supporting the hypothesis of a specific heart disease secondary to high circulating GH levels.

Acromegaly↗
PubMed1993

Cardiac structural and functional abnormalities in adult patients with growth hormone deficiency.

Little information is available on cardiac involvement in GH-deficient adults. Thus, we evaluated cardiac structure and function by means of one- and two-dimensional echocardiography in 11 adult patients [3 women and 8 men; mean age, 27.2 +/- 3.8 (+/- SD) yr] affected with GH deficiency. Twelve age- and sex-matched normal subjects served as the control group. All patients had been treated with extractive GH over 9 yr, and therapy withdrawal had been performed at least 3 yr before entering the study. GH-deficient patients had significantly lower values of interventricular septum (7.1 +/- 1 vs. 9 +/- 0.4 mm; P < 0.01) and left ventricular posterior wall thickness (6.1 +/- 1 vs. 9 +/- 0.4 mm; P < 0.01), which resulted in a significantly smaller left ventricular mass index (54 +/- 11 vs. 85 +/- 15 g/m2; P < 0.001). The left ventricular end-diastolic and end-systolic diameters did not differ significantly after correction for body area surface, whereas ejection phase indices showed lower values, with a fractional shortening of 34 +/- 4% vs. 38 +/- 5% (P < 0.05) and an ejection fraction of 59 +/- 9% vs. 69 +/- 10% (P < 0.05). In conclusion, the results of this study demonstrate the involvement of cardiac muscle in patients affected with GH deficiency.

Adult↗