J. Endocrinol. Invest. 7: 29, 1984
Serum thyroglobulin determinations in the differential diagnosis of congenital hypothyroidism
F. Pacini*, R. Lari*, P. La Ricca***, L. Grasso*, F. Di Bartolo***, G.F. Fenzi*, M. Ciampi*, S.G. Gragnani***, L. Baschieri*, and A. Pinchera** *Cattedra di Patologia Medica 2, **Gattedra di Endocrinologia e Medicina Costituzionale, Universita di Pisa, Via Roma 67, 56100 Pisa, and ***Divisione Pediatrica, Ospedale Civile di Cecina, 57023 Cecina, Italy
ABSTRACT. The value of serum thyroglobulin (Tg) determination in the differential diagnosis of congenital hypothyroidism was assessed by serum Tg measurements in 14 patients with proven congenital hypothyroidism, in 3 subjects with transient perinatal hypothyroidism, in 3 newborns with congenital thyroxine binding globulin (TBG) deficiency and in 34 normal controls. Serum Tg was undetectable in all 6 cases with thyroid agenesis, normal or moderately elevated in the 4 cases with ectopic thyroid, markedly increased in the 4 cases with dyshormonogenic goiter and normal in the 3 caseswith transient hypothyroidism and in the 3 with TBG deficiency. The present data indicate that serum Tg measurements may be useful in the differentiation of athyreotic hypothy-roidism from other conditions of congenital hypothyroidism.
INTRODUCTION Thyroglobulin (T g) is secreted by the thyroid gland and is detectable in the serum of normal adult subjects (1-3). Serum Tg is elevated in patients with hyperstimu-lated thyroids and in patients with metastatic differen-tiated thyroid cancer while it is low or undetectable in those free of recurrent disease after total thyroidec-tomy (4-6). T 9 is always detectable in the cord blood of normal newborns with mean values higher than those in normal adults and in pregnant women at delivery (7 -11). We confirmed these findings in a very large population of newborns and demonstrated that 1'g re-mains detectable during the. first week of life (12). Re-cently a few studies in newborns with congenital hypo-thyroidism have suggested that serum Tg measure-ments may be useful in the diagnosis of this condition (13, 14). In the present study we re port the results of serum Tg measurements in a group of newborns and children with proven congenital hypothyroidism of dif-ferent etiologies, some of whom were detected in our screening program for congenital hypothyroidism and others referred to us from other institutions. In addition, 3 newborns with congenital thyroxine bind-ing globulin (TBG) deficiency and 3 with transient hypo-thyroidism were studied.
MATERIALS AND METHODS Congenital hypothyraid subjects. A total of 14 patients
Key-words: Thyroglobulin, congenital hypothyroidism, TBG
Correspondence. F. Pac,n, MD. Cattedra di Patologia Medica 2. Universita di Pisa. V,a Roma 67. 56100 Pisa.ltaly
Rece,ved July 10. 1983; accepted September 10. 1983
with congenital hypothyroidism (6 newborns detected during our screening program and 1 newborn and 7 children diagnosed during the first year of life referred from other institutions) were available for study. In the seven patients diagnosed at birth, thyroxine (T4 ) and thyrotropin (TSH) were measured in dried filter paper spots obtained at 3-4 days of life . Hypothyroidism wa.s confirmed in all patients by measurements of serum concentrations of T 4' TSH, triiodothyronine (T 3) and T3 resine uptake (T 3U), at a later life. ' A thyroid scan was performed in all cases after more than 18 months of age. Serum Tg'was measured in all patients either before institution of thyroid medications and after withdrawal of therapy. In one patient serum cord blood was also available.
Transient hypothyroidism. This condition was present in 3 newborns in whom thyroid hormone levels were in the hypothyroid range at birth, but were in the normal range when they were recalled.
Congenital TBG deficiency. Three infants with congen-ital TBG deficiency were detected during our screen-ing program for congenital hypothyroidism. They were diagnosed on the 'basis of low T4 and normal TSH values with high T3U and low TBG values. Two were males with absent TBG and 1 was a female with low but detectable serum TBG concentration.
Normal contrals. Eight infants (1-3 months of age) and 26 children (5-16 years old) were studied as the normal control population for these age groups.
Serum Tg measurements. Serum Tg was measured by radioimmunoassay as previously described(2). All se-ra were screened for the presence of anti-T 9 autoan-tibodies and were negative in all subjects.
F. Pacini, R. Lari, P. La Ricca, et al.
Serum T4 , T3 , T3U, TSH, TBG and spotT4 andTSH were all measured using commercial kits (T3 , T4 and T3U kits were from Miles Lab., Cavenago, Milano; TSH kit was from Diagnostic Product Corporation, Los Angeles, Cal-ifornia; TBG kit was from Corning, Medfield, Massa-chussets; spot T 4 and spot TSH kits were from Biodata, Roma).
In 7 patients in whom hypothyroidism was diagnosed during the first week of life Tg was measured in serum sampies collected during the first two months of life. In the 7 patients who were not screened at birth, hypothy-
roidism was detected during the first year of life and Tg measured on serum sampies obtained at the time of referral to our clinic, between the age of 3 and 16 years; they were off thyroid replacement therapy. Results of thyroid function tests, Tg measurements and thyroid scans in patients with congenital hypothyroidism, tran-sient hypothyroidism and congenital TBG deficiency are summarized in Table 1. In 6 patients hypothyroid-ism was due to thyroid agenesis. In 8 patients with undetectable or low T 4 and high TSH values, thyroid scan revealed the presence of an ectopic (sublingual) thyroid in 4, and a diffuse goiter in the other 4. In 3 subjects hypothyroidism was suspected on the basis of low T 4 and high TSH values on blood spot but they were
Table 1 - Tg, thyroid hormones, TSH, TBG and thyroid scan in subjects with congenital hypothyroidism, transient hypothyroidism, congenital TBG deficiency and in normal subjects.
Blood spot 1.2 SERUM
Subject Sex T4 TSH Tg T3U T4 T3 TSH TBG Age ThyrOid scan No !lg/dl !lU/mi ng/ml % !lg/dl ng/dl !lU/mi !lg/ml
M 7.8 > 200 < 1253 33 < 1.5 < 37.5 > 100 30 days Agenesis
2 4.2 185 < 1.25 27.9 < 1.5 < 37.5 >100 45 days Agenesis
3 200 < 1.25 19A < 1.5 51 >100 22 days Agenesis
1.9 >200 < 1.25 < 1.5 < 37.5 > 100 14 days Agenesis
6 3.5 >200 < 1.25 < 1.5 >100 14 days Agenesis
M 3.0 > 200 200 38.4 4.6 156 > 100 30 days Ectop'c
8 44 28.5 2.9 129 100 12 years Ectop'c
9 M 167 50.1 < 1.5 < 37.5 66 3 years Ectopic
10 M 45.1 2.9 82.0 100 16 years Ectop'c
11 500 33 < 1.5 < 37.5 45 16 years Goitre4
12 1000 3.1 >100 8 years GOitre4
13 1000 4.8 >100 9 years GOitre5
14 M 450 2.5 > 100 7 days Goitre6
Congenltal TBG deflciency
15 M 2.3 < 12.5 82 85.2 28 55.0 3.3 < 0.5 27 days Normal
16 M 2.6 < t2.5 41 52.5 2.0 80.0 2.6 < 0.5 28 days Normal
17 4.8 < 12.5 130 717 6.9 201 < 0.5 125 48 days Normal
18 M 7.2 > 200 96 24.8 5A 204 23.9 21 days Normal
19 M 3.1 52 120 31.5 < 1.5 154 > 100 30 days Normal
54 300 9.3 247 1.2 3 months
20 7.2 130 106 44A .11.0 319 15 60 days Normal
(8)7 68 11 8 38 1.8 8A 0.6 211 16 2.4 OA 1-3 months
(26)7 15 22 30 0.9 7.0 0.3 203 6.6 2.6 02 5-16 years
1 Blood spot determinations were carried out in day 3-4 of life; they are available only in newborns detected in our screening program
2Normal spot T4 and spot TSH values in our laboratory are> 7.2119/dl and < 5011U/ml, respectively. 31n this patient Tg was also undetectable in the cord blood serum.
4Perchlorate dlscarge test positive. 5Dehalogenase defect.
6Not yet studled 7Number in parenthesis represents the number of subjects studied. 8M SE