Hormonal changes in thalassaemia major.

Abstract

(1976). Archives of Disease in Childhood, 51, 828. Hormonal changes in thalassaemia major. Patients with severe thalassaemia major suffer endocrine and other abnormalities before their eventual death from iron overload due to repeated blood transfusions. The endocrine status of 31 thalassaemic patients aged 2 -5 to 23 years was investigated. Exact data were available on the rate and duration of blood transfusion in all of them and in many the liver iron concentration was also known. Although the patients were euthyroid, the mean serum thyroxine level was significantly lower, and the mean thyrotrophic hormone level significantly higher, compared with the values found in normal children. Forty oral glucose tolerance tests with simultaneous insulin levels were performed in 19 children, of whom 5 developed symptomatic diabetes and one had impaired tolerance. Previous tests on all 6 patients were available and some showed raised insulin levels possibly due to insulin resistance. 2 patients had clinical hypoparathyroidism and are described. The parathyroid hormone levels determined by radioimmunoassay in 25 patients were below the mean for the age group in all and outside the reference range in 16. Nonfasting plasma calcium levels were not reduced. Puberty was delayed in some patients. Concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measured in urine from 7 girls and 5 boys showed considerable variation. In the boys there was an overall tendency for FSH and LH excretion to be low with regard to age, but with respect to puberty rating FSH excretions were normal or low and LH normal or raised. The girls showed a tendency for LH but not FSH excretion to be raised in relation to puberty rating. The severity of the endocrine changes was related to the degree of iron loading and is discussed in relation to previous work in which the iron loading has rarely been accurately indicated nor parathyroid status assessed.Patients with untreated severe thalassaemia major die in early childhood from the complications of anaemia. With transfusions, life is prolonged to age 15-25 years and growth and wellbeing are improved. However, heavily transfused patients develop endocrine failure, hepatic cirrhosis, and later cardiac failure which is the usual cause of death. It is thought that iron overload is the major cause of these abnormalities, and it has been shown that chelating agents are of some value in diminishing both the liver iron concentration (Barry et al., 1974) and the amount of hepatic fibrosis with which the iron load is associated (Risdon, Barry, and Flynn, 1975). Patients with

A Review of Endocrine Disorders in Thalassaemia

“…Thyroxine levels have been reported normal in majority of patients [5,27,31,66] suggesting insensitivity of the thyroid gland to iron overload. However low or normal T4 values with elevated TSH have been also reported suggesting sub-clinical primary hypothyroidism [5,31,67,68]. An exaggerated TSH response to stimulation by thyrotrophin-releasing-hormone (TRH) was found by De Sanctis et al [69] in 8 of 24 thalassaemics studied and a third of those went on to develop subclinical or overt hypothyroidism three to eleven years later.…”

Final height of thalassemic patients who underwent bone marrow transplantation during childhood

“…Some studies indicate that patients treated with conventional therapy have normal GH secretion after pharmacological stimuli, 5,6,[16][17][18] while others indicate either reduced GH secretion following stimulation with GHRH [19][20][21] or reduced spontaneous GH secretion all day with a low number of pulses and reduced mean pulse amplitude. 22 In short-stature patients with a normal GH response to provocative stimulation tests, abnormal pulsatile GH secretion has been reported (neurosecretory dysfunction).…”

“…The increasing number of long-term survivors after bone marrow transplantation has focused attention on the impaired growth of these patients. Many factors have been implicated in the growth retardation: deranged function of the hypothalamic-pituitary-gonadal axis, [5][6][7][8][9][10][11] abnormal hepatic conversion of steroid hormones to their active metabolites 12 and defective hepatic biosynthesis of insulin like growth factor (IGF-I). 13 It is possible that iron overload is primarily involved in this phenomenon.…”

Bone growth in thalassaemic children.

“…The medullary width was greater in thalassaemic than in normal children. Johnston et al (1966) and Flynn et al (1976) suggested that the retardation of skeletal maturation in thalassaemic children is due to hormonal disturbances resulting from chronic anaemia, or to chronic iron deposition in the glands responsible for the growth spurt. The retardation of bone growth in thalassaemic children found in the present study, which was more obvious as the children became older, could be attributed to the same factors.…”