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Department of Molecular and Clinical Endocrinology and Oncology (A.Co., C.D.S., G.C., R.L., G.L.), Nuclear Medicine Center of the National Council of Research, Department of Biomorphological and Functional Sciences (A.Cu., A.M.D.M., E.N., M.S.), Federico II University of Naples, 80131 Naples; and INM Neuromed (A. Cu.), Pozzilli, Italy
Address all correspondence and requests for reprints to: Annamaria Colao, M.D., Ph.D,Department of Molecular and Clinical Endocrinology and Oncology, Federico II, University of Naples, Via S. Pansini 5, 80131 Naples, Italy. E-mail: colao{at}unina.it
Several evidences indicate that GH and/or insulin-like growth factor I (IGF-I) are involved in the regulation of cardiovascular function. In patients with childhood and adulthood-onset GH deficiency (GHD), the impairment of cardiac performance is manifest primarily as a reduction in the left ventricular (LV) mass (LVM), inadequacy of LV ejection fraction both at rest and at peak exercise, and abnormalities of LV diastolic filling. No study has been reported to date in elderly GHD patients that investigated cardiac function. In particular, it is unknown whether cardiac function is modified in accordance with patients’ age as a physiological response to aging, as in normal subjects the rate and extent of LV filling are reduced with age. This study was designed to evaluate heart morphology and function, by echocardiography and equilibrium radionuclide angiography, respectively, in rigorously selected elderly patients with GHD but without evidence of other complications able to affect cardiac performance.
Eleven patients with hypopituitarism (6 men and 5 women, aged 60–72 yr) and 11 sex- age- and body mass index-matched healthy subjects entered this study. None of the patients and controls presented with or had previously suffered from other concomitant diseases, such as diabetes mellitus, coronary artery diseases, long-standing hypertension, and hyperthyroidism, which could affect cardiac function. All patients had been previously operated on via the transsphenoidal and/or transcranic route for nonfunctioning pituitary adenoma, meningioma, or craniopharyngioma, and 6 of them had been irradiated. Eight patients had FSH/LH insufficiency, 5 had TSH insufficiency, and 6 had ACTH insufficiency, appropriately replaced. All subjects were tested with the combined arginine plus GHRH test showing a GH response below 9 µg/L.
No significant difference was found in plasma IGF-I levels (49.2
± 8.5 vs. 71.8 ± 7.5 µg/L) between patients and
controls. However, IGF-I levels were lower than the normal range in 8
patients and 3 controls. Interventricular septum thickness (9.1 ±
0.2 vs. 9.1 ± 0.2 mm), LV posterior wall thickness
(9.1 ± 0.2 vs. 9.0 ± 0.2 mm), and LVM after
correction for body surface area (97.6 ± 1.8 vs.
99.9 ± 1.5 g/m2) were similar in patients and
controls. Similarly, the LV ejection fraction at rest was similar in
patients and controls (57.1 ± 2% vs. 63.2 ±
2.5%; P = NS), and it was normal (
50%) in all
controls and in 10 of 11 patients. By contrast, the LV ejection
fraction at peak exercise was markedly depressed in elderly GHD
patients compared to age-matched controls (51 ± 2.5%
vs. 73.3 ± 3%; P < 0.001). A
normal response (5% increase compared to basal value) of LV ejection
fraction at peak exercise was found in 8 controls (72.7%) and in 2 of
11 patients (18.2%). No difference was found in the peak rate of LV
filling, whether peak filling rate was normalized to end-diastolic
volume (2.5 ± 0.2 vs. 2.6 ± 0.2
end-diastolic volume/s) or stroke volume (4.3 ± 0.3
vs. 4.0 ± 0.3 stroke volume/s), between patients
and controls. Finally, exercise duration was significantly shorter in
elderly GHD patients than in age-matched controls (7.2 ± 2.1
vs. 9.1 ± 0.2 min; P < 0.01).
In the patient group, the GH peak after arginine plus GHRH test was
significantly correlated with the LV ejection fraction at rest (r
= 0.822; P < 0.01), whereas IGF-I was
significantly correlated with the peak rate of LV filling whether the
peak filling rate was normalized to end-diastolic volume (r =
-0.863; P < 0.001) or stroke volume (r =
-0.616; P < 0.05) or expressed as the ratio of
peak filling rate to peak ejection fraction rate (r = -0.736;
P < 0.01). Disease duration was significantly
correlated with heart rate at peak exercise (r = 0.614;
P < 0.05) and with systolic and diastolic blood
pressures both at rest (r = 0.745; P < 0.01
and r = 0.650; P < 0.05) and at peak exercise
(r = 0.684; P < 0.05 and r = 0.617;
P < 0.05).
The results of the present study demonstrated that, as in young and adult GHD patients, cardiac performance was impaired in elderly GHD patients, whereas cardiac mass was normal. These findings further support the potential usefulness of GH replacement in elderly hypopituitary patients.
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