IB); group II, 12 nonanemic women with untreated hypothyroid- ism; group III, 30 women known to be heterozygous for 0- thalassemia; and group IV, 50 healthy ...
0021-972X/83/5702-0344$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1983 by The Endocrine Society
Vol. 57, No. 2 Printed in U.S.A.
Influence of Thyroid Status on Hemoglobin A2 Expression JEAN-MARC KUHN, MAX RIEU, JACQUES ROCHETTE, RAJAGOPAL KRISHNAMOORTHY, DOMINIQUE LABIE, JACQUES ELION, JEANPIERRE LUTON, AND HENRI BRICAIRE Service d'Endocrinologie (J.-M.K., M.R., J.-P.L, H.B.), and the Institut de Pathologie Moleculaire, INSERM U15 (J.R., R.K., D.L., J.E.), Hopital Cochin, Paris, France
group III (5.26 ± 0.12%). The mean HbA2 level was lower (P < 0.001) in group II (1.99 ± 0.08%) than in group IV. Hb fetal was detectable in eight patients of subgroup IA and undetectable in subgroup IB and groups II and IV. The mean cellular volume was lower (P < 0.001) in subgroup IA than in other nonanemic groups. The mean cellular volume was higher (P < 0.001) in group II than in group IV. Follow-up of nine patients who became euthyroid with treatment showed the normalization of these erythrocyte parameters. These results suggest that thyroid hormones can modulate the synthesis of 5- and 7-globin chains. (J Clin Endocrinol Metab 57: 344,1983)
ABSTRACT. We studied the electrophoretic pattern of hemoglobin (Hb) and red blood cell indices in 128 women divided into four groups: group I, 36 nonanemic hyperthyroid women, divided in two subgroups: 36 with untreated hyperthyroidism (subgroup IA) and 9 made euthyroid by antithyroid drug therapy (subgroup IB); group II, 12 nonanemic women with untreated hypothyroidism; group III, 30 women known to be heterozygous for 0thalassemia; and group IV, 50 healthy women. The mean (±SEM) HbA2 level was higher (P < 0.001) in subgroup IA (3.21 ± 0.06%) than in subgroup IB (2.42 ± 0.09%) and group IV (2.48 ± 0.04%), but lower (P < 0.001) than in
A
Subjects
Received August 18,1982. Address requests for reprints to: Jean-Marc Kuhn, Hopital Cochin, 27 rue du Faubourg Saint Jacques, 75674 Paris Cedex 14, France.
Five groups of patients were studied. Group I included 36 nonanemic (Hb, ^12 g/dl) hyperthyroid women (29 with Graves' disease and 7 with toxic nodular goitre). Their age range was 25-60 yr. They were taking no hematinic or estrogenic medication, had no history of hematological disease, and had normal liver and renal function. Anemic patients were excluded from this study in order to establish the effects of uncomplicated hyperthyroidism on minor Hb fractions and RBC parameters. Group I was divided into two subgroups. Subgroup IA included 36 patients with untreated hyperthyroidism (serum T4 and/or T 3 levels above the mean + 2 SD of normal). Subgroup IB included 9 patients (from subgroup IA) made euthyroid [serum T4 and T3 levels within the normal range: (mean ± 2 SD)] by benzyl-thio-uracil (BTU). The minimum length of treatment was 3 months. Group II included 12 nonanemic women with untreated hypothyroidism. Their age range was 40-70 yr. Group III included 30 women with known heterozygous /3-thalassemia. Their age range was 25-50 yr. Group IV included 50 healthy women from the medical staff. Their age range was 20-48 yr. Group V included 5 nonanemic (Hb, 5=13 g/dl) hyperthyroid men with Graves' disease. Their age range was 30-50 yr. This group was divided into two subgroups. Subgroup VA included 5 patients with untreated hyperthyroidism. Subgroup VB included 3 patients (from subgroup VA) made euthyroid by BTU. The minimum duration of treatment was 3 months. In group V, the parameters for
Subjects and Methods
BNORMALITIES in red blood cell (RBC) mean L cellular volume (MCV) are known to occur in nonanemic untreated hyper- and hypothyroid patients (1). However, Hb subtype status has not previously been carefully studied in these patients, probably because blood Hb concentrations are usually in the normal range (1, 2). In untreated hyperthyroidism, the existence of an elevated total RBC mass (3), mediated by increased erythropoietin production, has been reported (4), but is masked by a concomitant increase in plasma volume (1, 3). Inverse findings have been found in untreated hypothyroidism (5). In untreated hyperthyroidism, a slight elevation of the fetal Hb (HbF) percentage has been found occasionally, raising the question of the effect of thyroid hormones on globin chain synthesis and/or globin gene expression (6). We have recently described a specific increase in the percentage of HbA2 in untreated hyperthyroid patients (7); a similar observation was simultaneously reported by Kendall and Bastomsky (8). The purpose of the present study was to investigate minor Hb fractions and RBC indices in nonanemic patients with hyper- and hypothyroidism and to correlate them with the hormonal status of the patients.
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THYROID STATUS AND HbA2 which mean levels are identical in normal men and women [MCV, mean cellular Hb (MCH), mean cell Hb concentration (MCHC), and HbA2] (9, 10) were compared to those in the groups of women. The parameters whose mean levels are different in normal men and women [RBC count, Hb, packed cellular volume (PCV), serum iron (I), and total iron binding capacity (TIBC)] were compared to those of normal men, as described previously (10). In all of these subjects, the Hb electrophoretic pattern, levels of minor Hb fractions, and RBC indices were measured. In all patients from groups I and V, serum T4 and T 3 were measured. In group II, serum T4 (*£l0 nmol/liter) and T 3 (s£l nmol/liter) were undetectable, and TSH levels were always above the upper limit of normal (>7 ^U/ml). I and TIBC were determined in 34 patients in group I (subgroup IA, n = 25; subgroup IB, n = 9), in 25 patients in group IV, and in all patients in groups II andV. Methods HbA2 was measured by previously described methods (11). RBC indices were determined using a Coulter model S counter (Coulter Electronics, Hialeah, FL). Serum T4, T3, and TSH levels were assayed by RIA. Statistics Conventional methods were used for comparison of mean and paired values (Student's t test) and for correlation and regression analysis.
Results RBC parameters (Fig. 1) HbA2) HbF, RBC count, mean corpuscular volume (MCV), and MCH. In subgroup IA, the mean (±SEM) HbA2 value .&5
.Hi: 15. .35
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.25
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.15
50. VA VB
VA VB GROUPS
GROUPS
FIG. 1. RBC parameters in five groups of subjects: • , women with untreated and nonanemic hyperthyroidism (subgroup IA); O, women with treated and nonanemic hyperthyroidism (subgroup IB); • , women with untreated and nonanemic hypothyroidism (group II); x, women with heterozygote /3-thalassemia (group III); A, men with untreated and nonanemic hyperthyroidism (subgroup VA); and A, men with treated and nonanemic hyperthyroidism (subgroup VB).
345
(3.21 ± 0.06%) was higher (P < 0.001) than in subgroup IB (2.42 ± 0.09%) and group IV (2.48 ± 0.04%). In group II, the mean HbA2 value (1.99 ± 0.08%) was lower (P < 0.001) than in groups IB and IV. HbA2 levels were above the normal range (mean + 2 SD) in four of the five patients from subgroup VA and within the normal range in all three patients from subgroup VB. HbF values exceeding 1% were found in eight patients of subgroup IA; all of them also had elevated HbA2 levels. In all patients of subgroup IB and groups II, IV, and V, HbF levels were lower than 1%. In subgroup IA, the mean RBC count (4.61 ± 0.06 X 1012/liter) was higher (P < 0.02) than in subgroup IB (4.35 ± 0.07 X 1012/liter). In group II, the mean RBC count (3.78 ± 0.16 x 1012/liter) was lower (P < 0.001) than in subgroup IB and group IV (4.43 ± 0.03 X 1012/ liter). RBC count was above the normal range in three of the five patients from subgroup VA and within the normal range in all patients from subgroup VB. In subgroup IA, the mean MCV (81.8 ± 0.6 fl) and MCH (28.2 ± 0.3 pg) were lower (P < 0.001) than in subgroup IB (MCV, 87.3 ± 0.7 fl; MCH, 31.1 ± 0.7 pg). In group II, the mean MCV (97.6 ± 1.5 fl) and MCH (33.5 ± 0.5 pg) were higher (P < 0.001) than in subgroup IB and group IV (MCV, 88.5 ± 0.5 fl; MCH, 29.8 ± 0.2 pg). In subgroup VA, MCV and MCH levels were below the normal range in two and four patients, respectively. MCV and MCH levels were within the normal range in all patients from subgroup VB. The mean HbA2, RBC count, MCV, and MCH were not significantly different (P > 0.05) between subgroup IB and group IV, and between patients with Graves' disease and those with toxic nodular goiter in subgroup IA. In group III, the means of these parameters (HbA2, 5.26 ± 0.12%; HbF, 2 ± 0.2%; RBC count, 5.47 ± 0.08 X 1012/liter; MCV, 65.3 ± 0.5 fl; MCH, 20.1 ± 0.6 pg) were different (P < 0.001) from those of subgroups IA and IB and groups II and IV. There was no overlap between subgroup IA and group III or between subgroup VA and group III in HbA2, HbF, and MCV levels. Hb, PCV, MCHC, serum I, and TIBC. The results in women are summarized in Table 1. The means of all of these indices were not significantly different (P > 0.05) among subgroup IA, subgroup IB, group II, and group IV. The Hb, PCV, and MCHC means in group III differed significantly (P < 0.005 or less) from those in subgroups IA and IB and groups II and IV. In all patients of subgroups VA and VB, Hb, PCV, serum I, and TIBC levels were within the normal range. Relations between hematological parameters in groups I, II, and V No correlations between hematological parameters were found within each group (IA, IB, II, and V), but
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346
JCE & M • 1983 Vol57«No2
KUHN ET AL.
TABLE 1. Means (±SEMs) of Hb, PCV, MCHC, I, and TIBC levels in four groups of women (see Materials and Methods and Fig. 1) Group I IA 13.1 ± 38.1 ± 34.3 ± 19.6 ± 55.2 ±
Hb (g/dl) PCV (%) MCHC (g/dl) I (/amol/liter) TIBC (/xmol/liter)
IB 13 ± 0.3 37.8 ± 0.8 33.7 ± 0.6 19.3 ± 1.3 57.1 ± 2.9
0.1 0.5 0.1 1.1 2.4
Group II
Group III
Group IV
13.3 ± 38.2 ± 34.2 ± 19.7 ± 54.2 ±
10.9 ± 35.6 ± 30.6 ± 22.7 ±
13.2 ± 39.1 ± 33.8 ± 21.4 ± 57.4 ±
0.3 1.8 0.8 2.2 3.2
0.2° 0.7° 0.6° 1.6
ND"
0.1 0.3 0.2 0.6 2.1
These means were not significantly (P > 0.05) different between subgroups IA and IB and groups II and IV. 0 P < 0.005 (or less) us. subgroups IA and IB and groups II and IV. b Not determined.
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