Abstract

Bone disease and short stature are frequent clinical features of patients with beta-thalassaemia major. Dysfunction of the GH-IGF-1 axis has been described in many thalassaemic children and adolescents with short stature and reduced growth velocity.

Assessment of the GH-IGF-1 axis in short adults with TM after attainment of final height may be required to select those who are candidates for replacement therapy and to prevent the development of bone disease. The aim of our study was to investigate GH secretion in adult thalassaemic patients in relation to their bone mineral density (BMD) and serum ferritin concentrations.

Patients and methods

We performed clonidine stimulation test in 30 thalassaemic patients (18 males, 12 females) with a mean age of 31.5 +/- 7.2 years. The cut-off level for GH response was set at 7 microg/l, according to the literature. Serum ferritin, IGF-1, liver enzymes, alkaline phosphatase (ALP) and and type1 Collagen CarboxyTelopeptide (CCT1) were also determined.

Results

We diagnosed GH deficiency (GHD) in 12 patients (40 %) and IGF-I deficiency (IGF-I SDS < -2) was diagnosed in 20 patients (67 %). Adult patients with TM had significantly decreased IGF-I concentrations and bone mineral density (BMD) at the femur neck and lumbar spine compared to normal controls. Thalassemic patients with GHD and IGF-I deficiency had significantly lower BMD T score at the lumbar spine compared to patients with normal GH and IGF-I levels. Thalassemic patients had higher serum CCT1 concentrations compared to normal controls. Peak GH levels were correlated significantly with IGF- I concentrations and IGF-I levels were correlated significantly with the height SDS (HtSDS) of thalassemic patients. Neither GH peak nor IGF-I concentrations were correlated to serum ferritin concentrations.

Conclusions

We conclude that GH status should be tested in adult thalassaemic patients especially those with short stature and/or decreased BMD. If the diagnosis of adult GHD is established, GH treatment may be considered for possible improvement of bone mineral density and heart function in thalassaemic patients.

Table 1

Biochemical data for patients and controls

Adults with TMNormal Controls
Number 30 50 
Age years 31.5 +/- 7.2 29.8 +/- 5.2 
HtSDS -2.05 +/- 0.4 -0.4 +/- 0.3* 
Calcium mmol/L 2.28 +/- 0.1 2.31 +/- 0.1 
Phosphate mmol/L 1.7 +/- 0.2 1.75 +/- 0.18 
ALP U/L 219 +/- 106 196 +/- 97 
25 OH D ng/ml 22.3 +/- 7.5 26.5 +/- 7.6 
PTH pg/ml 36 +/- 11.8 33.5 +/- 9.5 
IGF-I ng/ml 173 +/- 65 339 +/- 102* 
Type 1 collagen telopeptide 1798 +/- 562 408 +/- 207 * 
Adults with TMNormal Controls
Number 30 50 
Age years 31.5 +/- 7.2 29.8 +/- 5.2 
HtSDS -2.05 +/- 0.4 -0.4 +/- 0.3* 
Calcium mmol/L 2.28 +/- 0.1 2.31 +/- 0.1 
Phosphate mmol/L 1.7 +/- 0.2 1.75 +/- 0.18 
ALP U/L 219 +/- 106 196 +/- 97 
25 OH D ng/ml 22.3 +/- 7.5 26.5 +/- 7.6 
PTH pg/ml 36 +/- 11.8 33.5 +/- 9.5 
IGF-I ng/ml 173 +/- 65 339 +/- 102* 
Type 1 collagen telopeptide 1798 +/- 562 408 +/- 207 * 

(* p < 0.05)

Table 2

Comparison between GH deficient versus GH sufficient thalassemic patients

AgeHtSDSGH- basalGH-PeakferritinIGF-ISDSFemur-TLumbar- T
GHD Thal Mean 24.0 -2.48* 0.52 5.03* 2335 -3.62* -2.71 -2.90* 
n = 12 SD 4.45 0.95 0.57 1.66 1145 0.79 0.21 0.41 
GH S Thal Mean 21.4 -1.72 2.44 11.64 2566 -1.97 -2.75 -2.70 
n = 18 SD 4.58 0.78 5.52 3.72 1222 1.22 0.18 0.12 
AgeHtSDSGH- basalGH-PeakferritinIGF-ISDSFemur-TLumbar- T
GHD Thal Mean 24.0 -2.48* 0.52 5.03* 2335 -3.62* -2.71 -2.90* 
n = 12 SD 4.45 0.95 0.57 1.66 1145 0.79 0.21 0.41 
GH S Thal Mean 21.4 -1.72 2.44 11.64 2566 -1.97 -2.75 -2.70 
n = 18 SD 4.58 0.78 5.52 3.72 1222 1.22 0.18 0.12 

GHD = GH deficient, GHS = GH sufficient; *P < 0.05 GHD vs GH sufficient thalassemics

Table 3

comparison between IGF-I deficient and sufficient thalassemic patients.

AgeHtSDSGH- basalGH-PeakFerritinIGF-ISDSFemur-TLumbar- T
IGF-I Deficient Mean 23.35 -2.46* 0.34* 7.34* 2411 -3.42* -2.74 -2.85* 
n = 20 SD 4.61 0.90 0.46 4.50 1122 0.81 0.20 0.32 
IGF-I Sufficient Mean 19.9 -1.26 4.29 12.36 2519 -1.11 -2.74 -2.67 
n =10 SD 4.01 0.32 7.00 1.51 1140 0.69 0.16 0.09 
AgeHtSDSGH- basalGH-PeakFerritinIGF-ISDSFemur-TLumbar- T
IGF-I Deficient Mean 23.35 -2.46* 0.34* 7.34* 2411 -3.42* -2.74 -2.85* 
n = 20 SD 4.61 0.90 0.46 4.50 1122 0.81 0.20 0.32 
IGF-I Sufficient Mean 19.9 -1.26 4.29 12.36 2519 -1.11 -2.74 -2.67 
n =10 SD 4.01 0.32 7.00 1.51 1140 0.69 0.16 0.09 
*

p < 0.05

Table 4

Correlations between variable in adult thalassemic patients

AgeHtSDSGH- basalGH-PeakIGF1IGF-ISDSFemur-TLumbar- T
Age 1.00        
HtSDS -0.26 1.00       
GH- basal -0.25 0.26 1.00      
GH-Peak -0.35 0.26 0.24 1.00     
IGF1 -0.39 0.86 * 0.49 * 0.47* 1.00    
IGF-ISDS -0.39 0.86 * 0.49 * 0.47* 1.00 1.00   
Femur-T 0.09 -0.02 -0.09 0.18 -0.05 -0.05 1.00  
Lumbar- T 0.02 -0.19 0.17 0.26* 0.02 0.02 0.05 1.00 
AgeHtSDSGH- basalGH-PeakIGF1IGF-ISDSFemur-TLumbar- T
Age 1.00        
HtSDS -0.26 1.00       
GH- basal -0.25 0.26 1.00      
GH-Peak -0.35 0.26 0.24 1.00     
IGF1 -0.39 0.86 * 0.49 * 0.47* 1.00    
IGF-ISDS -0.39 0.86 * 0.49 * 0.47* 1.00 1.00   
Femur-T 0.09 -0.02 -0.09 0.18 -0.05 -0.05 1.00  
Lumbar- T 0.02 -0.19 0.17 0.26* 0.02 0.02 0.05 1.00 
*

p < 0.05

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.