J. Endocrinol. Invest. 15: 177-184,1992
Evaluation of hypothalamic-pituitary function in patients with thalassemia major L. Danesi*, M. Scacchi*, M. De Martin*, A. Dubini*, P. Massaro**, A.T. Majolo**, F. Cavagnini***, and E.E. Polli** *Centro Auxologico Italiano, Milano, **Istituto di Scienze Mediche, Universita di Milano, ***Cattedra di Endocrinologia II, Universita di Milano, Centro Auxologico Italiano, Milano, Italy ABSTRACT. The increased survival of patients with thalassemia major, made possible by more adequate therapeutic regimens, has emphasized the importance of the endocrine abnormalities often associated with this disease. In twelve thalassemic patients, we evaluated the hypothalamic- pituitary function by measuring plasma levels of anterior pituitary hormones under basal conditions and in the course of provocative tests. An impairment of growth hormone (GH) secretion was demonstrated in a considerable proportion (7/12) of these patients. In some of them failure of GH response to insulin-hypoglycemia and normal hormone rise after growth hormone-releasing hormone indicate a hypothalamic defect. A defective prolactin secretion was observed in the female hypogonadic
but not in the male thalassemic patients. This abnormality appears to be dependent on estrogen deficiency rather than on a hypothalamic-pituitary dysfunction. In our series a high prevalence (8/12) of hypogonadism was also noticed. In these cases, the low gonadotropin levels and their unresponsiveness to gonadotropin-releasing hormone are compatible with a hypothalamic and/or pituitary damage. Lastly, the enhanced ACTH responses to the stimuli associated to a reduced cortisol release suggest the existence, in these patients, of a diminished adrenocortical reserve. On the whole, this study has shown several derangements of the hypothalamic-pituitary function in thalassemia. This emphasizes the need for careful endocrine surveillance in this disease.
INTRODUCTION
MATERIALS AND METHODS
Endocrine abnormalities occur frequently in patients with thalassemia major (1-3). Among them, hypogonadism and short stature are the most important because of their high prevalence and their psychosocial implications. As far as the anterior pituitary function is concerned, studies on growth hormone (GH) (4-7) and gonadotropin (8-11) secretion have yielded conflicting results, while only scanty information is available regarding ACTH secretion (12, 13). A better knowledge of the hypothalamic-pituitary function appears most opportune in these patients, in view of their increased survival made possible by more adequate transfusion regimens and iron chelation. Along this line, we decided to investigate, under basal conditions and during dynamic testing, the anterior pituitary hormonal secretion in twelve thalassemic patients.
We studied 12 patients with homozygous B- thalassemia, 4 men and 8 women, aged 17-24 yr (median age 19 yr). The patients or their parents gave fully informed consent to participate in the study. Eighteen subjects, 7 men and 11 women, aged 1032 yr (median age 17 yr), undergone exploration of hypothalamic-pituitary function and eventually turned out to be normal, served as controls. Thalassemic patients initiated transfusion therapy within the first year of life and underwent splenectomy during childhood. Transfusion regimen at the moment of the study allowed to keep hemoglobin levels between 10.5 and 14.5 g/dl. All patients were receiving sc infusions of deferoxamine, 60-80 mg/kg body weight five days a week, since at least 5 yr. Serum ferritin levels ranged between 1360 and 7400 ng/ml. Auxometrical evaluation, roentgenographic assessment of skeletal maturation (14) and pubertal staging according to Tanner's criteria (15) were performed in all patients. The relevant clinical data are summarized in Table 1. Patients were all euthyroid and euglycemic and presented no evidence of heart disease or severe liver dysfunction. Both thalassemic patients and controls underwent, sev-
Key-wordS: Thalassemia major, pituitary, growth hormone. prolactin. gonadotropins. ACTH. cortisol. Correspondence: Prof. Francesco Cavagninl. Cattedra di Endocrinologia II. Unlverslta di Milano. Centro Auxologico Italiano, Via Spagnoletto. 3 20149 Milano, Italy. Received March 28,1991; accepted December 16.1991.
177
L. oanesi, M. Scacchi, M. De Martin, et a/.
Table 1 - Auxological and biochemical data of the patients. PT Sex no.
Chronological age (yr)
Bone age (yr)
Height Percentile Pubertal staging (cm) (height for chronological age) (Tanner)
Peak GH values ITT
(pmol/I) GHRH
694.6
391.0
F
18
18
152
4°
2
M
20
20
168
22°
IV
529.0
621.0
3
M
18
15
167
15°
IV
2001.0
657.8
4
M
21
17
174
50°
IV
22310
1959.6
5
F
24
17
165
65°
II
92.0
188.6
6
F
23
20
164
60°
496.8
648.6
7
M
18
18
158
3°
243.8
423.2
8
F
18
15
144
Evaluation of hypothalamic-pituitary function in patients with thalassemia major L. Danesi*, M. Scacchi*, M. De Martin*, A. Dubini*, P. Massaro**, A.T. Majolo**, F. Cavagnini***, and E.E. Polli** *Centro Auxologico Italiano, Milano, **Istituto di Scienze Mediche, Universita di Milano, ***Cattedra di Endocrinologia II, Universita di Milano, Centro Auxologico Italiano, Milano, Italy ABSTRACT. The increased survival of patients with thalassemia major, made possible by more adequate therapeutic regimens, has emphasized the importance of the endocrine abnormalities often associated with this disease. In twelve thalassemic patients, we evaluated the hypothalamic- pituitary function by measuring plasma levels of anterior pituitary hormones under basal conditions and in the course of provocative tests. An impairment of growth hormone (GH) secretion was demonstrated in a considerable proportion (7/12) of these patients. In some of them failure of GH response to insulin-hypoglycemia and normal hormone rise after growth hormone-releasing hormone indicate a hypothalamic defect. A defective prolactin secretion was observed in the female hypogonadic
but not in the male thalassemic patients. This abnormality appears to be dependent on estrogen deficiency rather than on a hypothalamic-pituitary dysfunction. In our series a high prevalence (8/12) of hypogonadism was also noticed. In these cases, the low gonadotropin levels and their unresponsiveness to gonadotropin-releasing hormone are compatible with a hypothalamic and/or pituitary damage. Lastly, the enhanced ACTH responses to the stimuli associated to a reduced cortisol release suggest the existence, in these patients, of a diminished adrenocortical reserve. On the whole, this study has shown several derangements of the hypothalamic-pituitary function in thalassemia. This emphasizes the need for careful endocrine surveillance in this disease.
INTRODUCTION
MATERIALS AND METHODS
Endocrine abnormalities occur frequently in patients with thalassemia major (1-3). Among them, hypogonadism and short stature are the most important because of their high prevalence and their psychosocial implications. As far as the anterior pituitary function is concerned, studies on growth hormone (GH) (4-7) and gonadotropin (8-11) secretion have yielded conflicting results, while only scanty information is available regarding ACTH secretion (12, 13). A better knowledge of the hypothalamic-pituitary function appears most opportune in these patients, in view of their increased survival made possible by more adequate transfusion regimens and iron chelation. Along this line, we decided to investigate, under basal conditions and during dynamic testing, the anterior pituitary hormonal secretion in twelve thalassemic patients.
We studied 12 patients with homozygous B- thalassemia, 4 men and 8 women, aged 17-24 yr (median age 19 yr). The patients or their parents gave fully informed consent to participate in the study. Eighteen subjects, 7 men and 11 women, aged 1032 yr (median age 17 yr), undergone exploration of hypothalamic-pituitary function and eventually turned out to be normal, served as controls. Thalassemic patients initiated transfusion therapy within the first year of life and underwent splenectomy during childhood. Transfusion regimen at the moment of the study allowed to keep hemoglobin levels between 10.5 and 14.5 g/dl. All patients were receiving sc infusions of deferoxamine, 60-80 mg/kg body weight five days a week, since at least 5 yr. Serum ferritin levels ranged between 1360 and 7400 ng/ml. Auxometrical evaluation, roentgenographic assessment of skeletal maturation (14) and pubertal staging according to Tanner's criteria (15) were performed in all patients. The relevant clinical data are summarized in Table 1. Patients were all euthyroid and euglycemic and presented no evidence of heart disease or severe liver dysfunction. Both thalassemic patients and controls underwent, sev-
Key-wordS: Thalassemia major, pituitary, growth hormone. prolactin. gonadotropins. ACTH. cortisol. Correspondence: Prof. Francesco Cavagninl. Cattedra di Endocrinologia II. Unlverslta di Milano. Centro Auxologico Italiano, Via Spagnoletto. 3 20149 Milano, Italy. Received March 28,1991; accepted December 16.1991.
177
L. oanesi, M. Scacchi, M. De Martin, et a/.
Table 1 - Auxological and biochemical data of the patients. PT Sex no.
Chronological age (yr)
Bone age (yr)
Height Percentile Pubertal staging (cm) (height for chronological age) (Tanner)
Peak GH values ITT
(pmol/I) GHRH
694.6
391.0
F
18
18
152
4°
2
M
20
20
168
22°
IV
529.0
621.0
3
M
18
15
167
15°
IV
2001.0
657.8
4
M
21
17
174
50°
IV
22310
1959.6
5
F
24
17
165
65°
II
92.0
188.6
6
F
23
20
164
60°
496.8
648.6
7
M
18
18
158
3°
243.8
423.2
8
F
18
15
144
