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Increased Arterial Intima-Media Thickness in Childhood-Onset Growth Hormone Deficiency

Departments of Internal Medicine and Endocrinology, University Federico II, Naples

Address all correspondence and requests for reprints to: Brunella Capaldo, M.D., Medicina Interna, via Pansini 5, 80131 Napoli, Italy.

	Abstract

Top Abstract Introduction Patients and Methods Results Discussion References

 
Very little is known about the atherosclerotic risk in patients with childhood-onset growth hormone deficiency (GHD). Such data may be relevant to reconstructing the natural course of the cardiovascular abnormalities associated with GHD. To this end, the intima-media thickness (IMT) of the carotid arteries and the vascular risk factors were evaluated in 14 childhood-onset GHD patients (age 25 ± 1 yr, BMI 22 ± 0.6 Kg/m²) and in 14 age-, sex-, and BMI-matched control subjects.

IMT was greater in GHD patients (0.83 ± 0.06 and 0.81 ± 0.06 mmol/L for the right and left carotid artery) than in controls (0.64 ± 0.03 and 0.64 ± 0.04 mmol/L, P < 0.01 and P < 0.02, respectively). Serum total and lipoprotein cholesterol, and serum total triglycerides did not differ between the two groups. However, a significant increase in low density lipid triglycerides was present in GHD patients (0.27 ± 0.02 mmol/L) compared with controls (0.19 ± 0.01; P = 0.007). No difference was found in plasma fibrinogen and serum Lp(a) levels. Plasma glucose and insulin concentrations were similar in GHD and control subjects both in the fasted state and after an oral glucose load.

In conclusion, young patients with childhood-onset GHD show an increased IMT in the absence of clear-cut abnormalities of the classic vascular risk factors. This suggests a role for GH deficiency per se in increasing the atherosclerotic risk.

	Introduction

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THE MECHANISMS accounting for the higher cardiovascular risk in patients with hypopituitarism remain poorly understood (1). A significant increase in intima-media thickness (IMT) and a higher number of atheromatous plaques have been reported in hypopituitary adults, despite adequate hormonal therapy except growth hormone (GH) (2). These data support a causal role for GH deficiency (GHD) in determining premature atherosclerosis in patients with hypopituitarism.

GHD is also associated with abnormalities of lipid and carbohydrate metabolism, which may contribute to the increased risk for vascular disease (3, 4, 5, 6, 7, 8, 9, 10, 11). Elevations of low density lipoprotein (LDL)-cholesterol, apo B, and triglycerides, and a reduction in high density lipoprotein (HDL)-cholesterol have been described in adult GHD patients (3, 4, 5, 6, 7, 8). In addition, the presence of insulin resistance due to a defective muscle glucose storage has been documented (8, 9, 10, 11).

Most of the data available in GHD are derived from patients who acquired the syndrome during adulthood; therefore, it cannot be excluded that some metabolic and/or vascular abnormalities were already present when hypopituitarism set in. To resolve the issue, the model of childhood-onset GHD might be particularly useful. Indeed, the question as to whether these patients also have increased atheroscelorotic risk is significant, as both the metabolic and cardiovascular abnormalities worsen in parallel with the duration of GHD (12). It is conceivable, therefore, that the lack of GH since the developmental period may have greater consequences on the vascular system and may predict a higher risk for vascular disease.

These considerations prompted us to investigate the atherosclerotic risk factors and the vascular risk factors in a group of selected GHD patients in whom the diagnosis was made very early in childhood. The atherosclerotic risk was evaluated by means of high resolution ultrasonography of the carotid arteries.

	Patients and Methods

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Patients

Fourteen patients (6 males and 8 females, age 18–36 yr, BMI 22 ± 0.8 Kg/m²) diagnosed as GHD patients and 14 healthy controls, comparable for age, sex distribution, and body mass index participated in the study (Table 1). GHD had been diagnosed in their childhood by means of at least two stimulation tests (arginine infusion, exercise, insulin-induced hypoglycemia). In all patients, the diagnosis was confirmed by the GH-releasing hormone plus pyridostigmine test (GHRH+PD) and the clonidine test, according to the methods described by Ghigo et al. (13) and by Gil-Aid et al (14). Inclusion criteria were a GH response after GHRH+PD and clonidine tests <7 µg/L and insulin-like growth factor I (IGF-I) below the normal range for age.

Protocol

All participants were studied in the postabsorptive state after a 12–14 h overnight fast. Arterial blood pressure was measured at least twice (at 5–10 min intervals) in the sitting position after resting for 20 min. The mean of all readings was used. The waist-to-hip ratio (WHR) was determined by measuring the waist and the hip circumferences. Blood samples were taken for lipids, lipoproteins, fibrinogen, and Lp(a) analysis. Then, a 75 g oral glucose tolerance test (OGTT) was performed, and glucose and insulin were measured every 30 min for 2 h. At the end of the test, the subjects underwent ultrasonographic scanning of the carotid arteries. The evaluation was performed by means of a real-time high resolution echo-color Doppler system (Acuson Corporation, Mountain View, CA). The system was equipped with a multifrequency 7.5 MHz probe. In all subjects, carotid sonography was performed according to a standardized protocol (15) by a trained physician and was recorded on videotapes. Ultrasonographic scanning was recorded with the subject in supine position, with a slight rotation of the neck. The probe was placed along the vessel axis to obtain a longitudinal scan of the common carotid arteries. IMT was measured 1.5 cm proximal to carotid artery bifurcation. For each subject, three measurements were performed on both sides, and the mean for each artery was used in the present study. The coefficients of variation of the measurements were less than 3%. All scannings were read by an independent physician, blinded as to the clinical status of the subjects.

Analytical methods

The separation of the major lipoprotein classes (VLDL and LDL) was performed by sequential preparative ultracentrifugation (16). HDL were isolated by precipitation method (17). Cholesterol, triglycerides, and phospholipids were assayed in serum and in isolated lipoprotein on an autoanalyzer Cobas-MIRA (Roche, Basilea, Switzerland) by enzymatic methods using commercially available kits (Boehringer Mannheim, Mannheim, Germany) modified to obtain the highest sensitivity. Quality control of lipid analysis is regularly ensured by the WHO Prague Reference (18). Recovery of single constituents (sum of their concentration in each isolated lipoprotein as percent of total concentration) was 99 ± 0.5% for cholesterol, 102 ± 0.7% for triglyceride, and 99 ± 0.7% for phospholipids with no difference between patients and controls. Serum Lp(a) was assayed by an ELISA method using a commercially available kit (Macra Lp(a) by Terumo Medical Corporation, Elkton, MD). The inter- and intraassay coefficients of variation were 6.8% and 3.6%, and 0.24% and 4.1% for low and high concentration, respectively. Plasma fibrinogen was measured by the Clauss method (19). Serum insulin and GH levels were determined by radioimmunoassay.

Statistical analysis

Data are expressed as mean ± SE. Comparisons between GH-deficient and control subjects were made using the two-tailed unpaired Student’s t test. P < 0.05 was considered significant.

	Results

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The prevalence of familial hypertension, diabetes mellitus, and cigarette smoking was similar in GHD and in control subjects. Systolic and diastolic blood pressures were significantly lower in GHD patients than in controls. WHR ratio was greater in GHD patients than in controls (P < 0.001) (Table 1).

The IMT of the common carotid arteries was significantly greater in GHD patients (0.83 ± 0.06 and 0.81 ± 0.06 for the right and left carotid artery) than in controls (0.64 ± 0.03 and 0.64 ± 0.04 mm, P < 0.01 and P < 0.01, respectively) (Fig. 1). Serum total cholesterol was similar in the two groups. Likewise, no difference was observed in cholesterol distribution among lipoprotein classes, except a slight, but not significant, reduction in HDL-cholesterol in GHD patients (P = 0.07). Serum triglyceride concentrations were similar in GHD and control subjects. However, the distribution of triglycerides in lipoproteins was different (Table 2). In particular, GHD patients showed a significant increase in LDL-triglycerides compared with controls (0.27 ± 0.02 mmol/L vs. 0.19 ± 0.01; P = 0.007). Serum LP(a) was 6.4 ± 2.4 and 3.0 ± 1.1 mg/dL in both GHD and control subjects (P = NS). Plasma fibrinogen was 1.85 ± 0.07 g/L and 1.85 ± 0.18 g/L in control and GHD subjects, respectively. Fasting plasma glucose and insulin were similar in the two groups. In the whole group, only one subject with GHD had impaired glucose tolerance according to the WHO criteria (20). The area under the curve for both glucose and insulin was not different in the control group (612 ± 28 mmol/L · 120 min and 4052 ± 455 mU/L · 120 min, respectively) and in GHD subjects (664 ± 37 mmol/L· 120 min and 4599 ± 603 mU/L· 120 min).

View larger version (13K): [in this window] [in a new window]   Figure 1. Carotid intima-media thickness in control and GHD subjects. The values represent the mean ± SE thickness of both carotid arteries.

	Discussion

Top Abstract Introduction Patients and Methods Results Discussion References

In a previous study by Markussis et al. (2), IMT was found to be increased in patients with hypopituitarism at middle and old age, but not in patients below 40 yr. In the multiple regression analysis, age accounted for as much as 76% of the variation in IMT, although hypopituitarism per se conferred an additional risk. By demonstrating that the vascular risk is already elevated in GHD patients of young age, our study provides evidence that GH deficiency per se is an important determinant of vascular disease.

The mechanisms responsible for the increased vascular risk in our patients with childhood-onset GHD are not completely clear. Studies performed in adult-onset GHD have shown that this condition is associated with a cluster of cardiovascular risk factors (5). Altered lipid profile, increased prevalence of hypertension, insulin-resistance, and visceral adiposity may all contribute to premature atherosclerosis. Treatment with human recombinant GH induces a rapid correction of these abnormalities, although its long-term impact on cardiovascular morbidity and mortality remains elusive.

Analysis of the cardiovascular risk factor profile in our patients reveals a paucity of metabolic abnormalities. Despite accurate matching for body mass index, the visceral distribution of adiposity was greater in the GHD group, as demonstrated by their higher ratio of waist-to-hip circumference. Total cholesterol and its lipoprotein distribution were not different in the two groups. In contrast, a triglyceride enrichment of the LDL particles was found in GHD patients. This compositional alteration is considered a reliable index of the presence of small, dense LDL, which has been associated with increased risk for cardiovascular disease in some conditions of insulin resistance (24, 25).

The glycemic and insulinemic responses to oral glucose load did not differ in GHD and control subjects. To the extent that oral glucose load can be viewed as an index of insulin resistance, our data indicate that childhood-onset GHD patients have no gross abnormalities of insulin sensitivity. Studies focusing specifically on the relation of GHD to insulin action have shown the presence of insulin resistance in adult patients (9, 10, 11). To date, no direct evaluation of insulin action has been performed in young GHD patients. However, the increased propensity of these subjects to develop fasting hypoglycemia suggests that insulin sensitivity, if anything, is enhanced (26).

In the present study, we also explored the thrombotic risk of GHD patients by measuring Lp(a) and plasma fibrinogen concentrations, both of which are considered to play an independent role in the atherosclerotic process (27, 28). No difference was demonstrable in the level of these variables between the GHD and the control group, which supports the idea that congenital GHD is associated with a normal function of the coagulation/fibrinolytic system.

The possibility that the increased IMT might be in part a consequence of previous imperfect hormonal replacement cannot be totally excluded. However, this possibility is quite remote because the dosage of GH used in our patients is the same as that commonly administered for replacement purpose. In addition, an augmented carotid IMT has been documented in adult GHD patients who had never received GH therapy, supporting the view that GH deficiency per se largely contributes to the premature atherosclerosis of these patients.

Our data do not clarify the mechanism(s) underlying the intimal thickening observed in GHD patients. However, recent knowledge of the interaction between GH and nitric oxide (NO) formation (29) may open a new line of reasoning. It is known that GH and its tissue effector IGF-I are important vasodilator agents through an NO-mediated mechanism. In addition, recent evidence shows that systemic NO production is reduced in untreated GHD patients (30). Given the central role of NO in regulating endothelial function and inhibiting muscle cell proliferation (31), it is reasonable to hypothesize that a reduced NO synthesis might be implicated in the endothelial dysfunction of patients with GHD. On the other hand, it cannot be overlooked that, in GHD, the stimulatory effect of IGF-I on muscle cell proliferation drops out. However, it is possible that the adverse consequences of NO deficiency on arterial walls prevail over the lack-of-growth vascular effect of IGF-I.

In conclusion, young patients with childhood-onset GHD show an increased IMT in the absence of clear-cut abnormalities of the common vascular risk factors. Although the underlying mechanisms remain unclear, the present study suggests a role for GH deficiency per se in increasing the atherosclerotic risk.

Received October 1, 1996.

Accepted February 11, 1997.

	References

Top Abstract Introduction Patients and Methods Results Discussion References

 

1. Rosen T, Bengtsson B-Å. 1990 Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. 336:285–288.[CrossRef][Medline]
2. Markussis V, Beshyah SA, Fisher, Sharp P, Nicolaides AN, Johnston DG. 1992 Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults. Lancet. 340:1188–1192.[CrossRef][Medline]
3. Merimee TJ, Hollander W, Fineberg SE. 1972 Studies of hyperlipidemia in the HG-deficient state. Metabolism. 21:1053–1061.[CrossRef][Medline]
4. Libber SM, Plotnick LP, Johanson AJ, Blizzard RM, Kwiterovitch PO, Migeon CJ. 1990 Long-term follow-up of hypopituitary patients treated with human growth hormone. Medicine. 69:46–55.[Medline]
5. Rosen TE, Eden S, Larson G, Wilhelmsen L, Bengtsson B-Å. 1993 Cardiovascular risk factors in adult patients with growth hormone deficiency. Acta Endocrinol (Copenh). 129:195–200.[Medline]
6. DeBoer H, Blok GJ, Voerman HJ, Philips M, Schouten JA. 1994 Serum lipid levels in growth hormone-deficient men. Metab Clin Exp. 43:199–202.
7. Cuneo FC, Salomon F, Watts GF, Hesp R, Sönksen PH. 1993 Growth hormone treatment improves serum lipids and lipoproteins in adults with growth hormone deficiency. Metabolism. 42:1519–1523.[CrossRef][Medline]
8. Snel Yem, Doerga ME, Brummer RM, Zelissen PMJ, Koppeschaar HPF. 1995 Magnetic resonance imaging-assessed adipose tissue and serum lipid and insulin concentrations in growth hormone-deficient adults. Arterioscler Thromb Vasc Biol. 15:1543–1548.[Abstract/Free Full Text]
9. Alford F, Hew FL, Koschmann M, Cristopher M, Rantzau C, Ward G. 1994 Defects of glucose metabolism in growth hormone deficient (GHD) adults. Endocrinol Metab. [Suppl B]1:27.
10. O’Neal DN, Kalfas A, Dunning PL, et al. 1994 The effects of three months of recombinant human growth hormone (rhGH) therapy on insulin and glucose-mediated glucose disposal and insulin secretion in GH-deficient adults. J Clin Endocrinol Metab. 79:975–983.[Abstract]
11. Hew FL, Koschman M, Christopher M, et al. 1996 Insulin resistance in growth hormone-deficient adults: defects in glucose utilization and glycogen synthase activity. J Clin Endocrinol Metab. 81:555–564.[Abstract]
12. Saccà L, Cittadini A, Fazio S. 1994 Growth hormone and the heart. Endocr Rev. 15:555–573.[CrossRef][Medline]
13. Ghigo E, Mazza E, Imperiale E, et al. 1987 The enhancement of the colinergic tone by pyridostigmine promotes both basal and growth hormone (GH)-releasing hormone induced GH secretion in children of short stature. J Clin Endocrinol Metab. 65:452–456.[Abstract]
14. Gil-Aid I, Topper E, Laron L. 1977 Oral clonidine as a growth hormone stimulation test. Lancet. 2:278–279.[Medline]
15. Cocozza M, Picano T, Oliviero U, Russo N, Coto V, Milani M. 1995 Effects of the picotamide, an antithromboxane agent, on carotid atherosclerosis evolution. A two-year double blind placebo-controlled study in diabetic patients. Stroke. 26:597–601.[Abstract/Free Full Text]
16. Hatch FT, Lees RS. 1969 Practical methods for plasma lipoprotein analysis. In: Paoletti R, Kritchevsky D, eds. Advances in lipid research. London: Academic Press; 1–68.
17. Lopes-Virella MF, Stone P, Ellis S, Colwell JA. 1977 Cholesterol determination in high density lipoproteins separated by three different methods. Clin Chem. 23:882–884.[Abstract/Free Full Text]
18. Grafnetter D. 1977 World Health Organization (WHO) coordinated quality control in lipid laboratory. Giorn Arterioscl. 2:113–128.
19. Marbet GA, Duckert F. 1992 Fibrinogen. In: Jesperson J, Bertina RM, Haverkate F, eds. ECAT assay procedures. A manual of laboratory results. Dordrecht, Netherlands: Kluwer; 47–55.
20. WHO. 1980 Expert Committee on Diabetes Mellitus. 2nd Report. Technical report series no. 646. Geneva: World Health Organization.
21. Powrie J, Weissberger A, Sönksen P. 1995 Growth hormone replacement therapy for growth hormone-deficient adults. Drugs. 49:656–663.[Medline]
22. Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. 1986 Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation. 74:1399–1406.[Abstract/Free Full Text]
23. Bonithon-Kopp C, Touboul P-J, Berr C, et al. 1996 Relation of intima-media thickness to atherosclerotic plaques in carotid arteries. The vascular aging (EVA) study. Arterioscler Thromb Vasc Biol. 16:310–316.[Abstract/Free Full Text]
24. Stewart MW, Laker MF, Dyer RG, et al. 1993 Lipoprotein compositional abnormalities and insulin resistance in type II diabetic patients with mild hyperinsulinemia. Arterioscler Thromb. 13:1046–1052.[Abstract/Free Full Text]
25. Selby JV, Austin MA, Newman B, et al. 1993 LDL subclasses phenotypes and the insulin resistance syndrome in women. Circulation. 88:381–387.[Abstract/Free Full Text]
26. Wolfsdorf JI, Sadeghi-Hejad A, Senior B. 1983 Hypoketonaemia and age-related fasting hypoglycemia in growth hormone deficiency. Metab Clin Exp. 32:457–462.
27. Scanu AM, Fless GM. 1990 Lipoprotein (a). Heterogeneity and biological relevance. J Clin Invest. 85:1709–1715.
28. Ernst E. 1991 Fibrinogen: an independent risk factor for cardiovascular disease. Br Med J. 303:596–597.
29. Tsukahara H, Gordienko DV, Tonshoff B, Gelato MC, Goligorsky MS. 1994 Direct demonstration of insulin-like growth factor-1-induced nitric oxide production by endothelial cells. Kidney Int. 45:598–604.[Medline]
30. Boger RH, Skamira C, Bode-Boger SM, Brabant G, von zur Muhlen A, Frolich JC. 1996 Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study. J Clin Invest. 98:2706–2713.[Medline]
31. Radomski MW, Salas E. 1995 Nitric oxide-biological mediator, modulator and factor of injury: its role in the pathogenesis of atherosclerosis. Atherosclerosis. 118(Suppl):S69–S80.

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				Discontinuation of Growth Hormone (GH) Treatment: Metabolic Effects in GH-Deficient and GH-Sufficient Adolescent Patients Compared with Control Subjects J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4516 - 4524. [Abstract] [Full Text]

				F. Borson-Chazot, A. Serusclat, Y. Kalfallah, X. Ducottet, G. Sassolas, S. Bernard, F. Labrousse, J. Pastene, A. Sassolas, Y. Roux, et al. Decrease in Carotid Intima-Media Thickness after One Year Growth Hormone (GH) Treatment in Adults with GH Deficiency J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1329 - 1333. [Abstract] [Full Text]

				M. Pfeifer, R. Verhovec, B. Zizek, J. Prezelj, P. Poredos, and R. N. Clayton Growth Hormone (GH) Treatment Reverses Early Atherosclerotic Changes in GH-Deficient Adults J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 453 - 457. [Abstract] [Full Text]

				R. Kuromaru, H. Kohno, N. Ueyama, H. M. S. Hassan, S. Honda, and T. Hara Long-Term Prospective Study of Body Composition and Lipid Profiles during and after Growth Hormone (GH) Treatment in Children with GH Deficiency: Gender-Specific Metabolic Effects J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 3890 - 3896. [Abstract] [Full Text]

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