Transient Hyperthyrotropinemia Research Articles

Heterogeneity of congenital primary hypothyroidism: the importance of thyroid scintigraphy.

Current newborn screening programs in California and most of the U.S. depend for diagnosis of congenital primary hypothyroidism on demonstrating an elevated thyrotropin (TSH) level in infants with the lowest 5% to 10% of thyroxine (T4) levels by filter-paper bloodspot test. The diagnosis of primary congenital hypothyroidism based on low T4 with high TSH fails to distinguish between transient hypothyroidism, ectopic or hypoplastic thyroid, athyrosis, dyshormonogenesis, and transient hyperthyrotropinemia. We screened 166,300 newborn infants for primary congenital hypothyroidism for 6.5 years and confirmed the diagnosis in 46 cases; none of these patients had a goiter. Thyroid scintigraphy was performed in 40 with technetium-99m (Tc-99m) in the first eight cases tested and iodine-123 (I-123) in 29 of the last 32 cases. Fifteen infants were athyroid and seven had ectopic or hypoplastic glands; in 18 the thyroid gland appeared normal (present, normal location). Congenital hypothyroidism represents a spectrum of diseases from transient underactivity to complete absence of the thyroid gland. We recommend that, before starting treatment, a specific anatomic and functional diagnosis be confirmed by thyroid scintigraphy and other thyroid function tests.

Analysis of Thyrotropin‐Thyroxine Secretory Dynamics in Infantile Hyperthyrotropinemia: An Aid for Early Differential Diagnosis

AbstractFor the purpose of differentiating neonatal hyperthyrotropinemia, the interrelation between serum thyrotropin (TSH) and thyroxine (T4) was examined in 10 infants with primary hypothyroidism during 12 months of T4 replacement therapy. A significant inverse correlation was obtained between elevated TSH (Y) (above 12 μU/ml) and T4 (X) levels; Y = 324 ‐ 22 X (r = ‐0.801, p < 0.001). One patient had an abnormally high threshold of TSH‐inhibition by T4. Based on this regression line, a scattergram of TSH‐T4 correlation and changes in the time course was analyzed in 13 infants with neonatal hyperthyrotropinemia, including eight with transient hyperthyrotropinemia (t‐TSH), three with compensated hypothyroidism (c‐Hypo) and two with transient hypothyroidism (t‐Hypo). All plots from t‐TSH were distributed under the regression line and shifted downward with concomitant rise in T4 and free T4 levels. In contrast, plots from c‐Hypo and t‐Hypo showed a vertical upward shift above the line during 3–4 months of observation without treatment. These results indicate that (1) using the TSH‐T4 regression line, differentiation of c‐Hypo from t‐TSH is possible by 3 months of age, (2) the cause of t‐TSH is not an elevated threshold for TSH release, but rather the maturational delay in responsiveness of the thyroid to TSH, and (3) suppression of TSH alone should not be used as the index of adequate T4 dose in infantile hypothyroidism, because of the existence of patients with a high threshold of TSH‐inhibition by T4.

Transient impairment of thyroid function in newborn from an area of endemic goiter.

Thyroid function was studied in newborn from 3 areas of Sicily in which iodine intake is normal (area A), moderately decreased (area B), and severely decreased (area C). In the latter 2 areas, there is a high incidence of goiter and in area C endemic cretinism is present. TSH and T4 were measured in the cord serum of 5673 newborn from area A, 2096 from area B, and 184 from area C. The mean TSH value was significantly higher in areas C (P less than 0.001) and B (P less than 0.005) when compared to area A; moreover, in both endemic goiter areas the mean cord serum T4 was significantly reduced (P less than 0.01). All infants with cord serum TSH levels above 50 microU/ml were recalled because of the suspicion of congenital hypothyroidism. Such values were found in 41 of the 7953 infants (0.52%) with an increasing frequency from area A (9:5673 = 0.16%) to area B (14:2096 = 0.67%) to area C (18:184 = 9.78%). At the time of the recall examination [mean age, 32 +/- 8 (SD) days], 3 of the 41 recalled infants had died. Of the remaining 38 infants, 3 patterns evolved: 1) 23 had normal serum TSH and T4 values and were not studied further (false positives). 2) Eleven had elevated serum TSH and normal T4 values. They were reevaluated again after 3-6 weeks: all had normal values (transient hyperthyropinemia ). 3) Four infants had both high serum TSH and low serum T4 values (2 from area A and 2 from area C). They were diagnosed as having congenital hypothyroidism and treated with T4. At 10-13 months of age, after treatment withdrawal, the 2 infants from area A had permanent congenital hypothyroidism due to thyroid agenesis whereas the 2 infants from area C were euthyroid (transient congenital hypothyroidism). The present studies indicate, therefore, that in newborn from areas of iodine deficiency there is a higher frequency of elevated TSH levels and low T4 values than is found in areas where iodine intake is normal. This frequency is correlated to the degree of the iodine deficiency. The data suggest that the impairment of thyroid function at birth may be a transient phenomenon. The duration and the severity of the transient neonatal hypothyroidism, however, is greatly variable and its evolution unpredictable.

Incidence of iodine contamination in neonatal transient hyperthyrotropinemia.

Transient hyperthyrotropinemia and/or hypothyroidism have been found in many newborn infants during thyroid screening programs. In Europe the most likely causes are iodine deficiency and iodine overload. Because of the high incidence of transient hyperthyrotropinemia in Berlin we measured iodine concentrations in casual urine samples of newborns with TSH elevations. Urine and blood samples were collected on the 5th day of life. In the prospective study 99 out of 9320 newborns (1.06%) displayed TSH concentrations ranging from 20 to 152 microU/ml. All infants had normal TSH levels during a control examination. The urinary iodine concentrations were significantly elevated in 76 out of the 99 newborns. Most of the patients were born in obstetric departments where iodine-containing antiseptic agents were routinely used for disinfection during labor. The use of iodine-containing antiseptic agents not only results in unnecessary control determinations for the thyroid screening program but also causes an undesirable metabolic situation that may be a potential hazard for the development of the central nervous system.

Distribution of TSH levels in dried blood spot among 137,207 Greek newborns: incidence of Primary Congenital Hypothyroidism and Transient Hyperthyrotropinemia

In September 1979 screening for Congenital Hypothyroidism (C.H.) was started in Greece. As the screening method Thyroid-Stimulating Hormone (TSH) determination in dried blood spots collected on the 5th day of life was chosen. To date 137,207 newborns (65% of all live births in Greece) have been screened. The distribution of TSH levels in a single estimation was as follows: < 12.5μIU/ml 87.7%, 12.5-30μIU/ml 11.4% and > 30μIU/ml 0.9%.Values > 30μIU/ml were confirmed by a second estimation from the initial card in 171 cases, which were recalled for a new blood specimen (recall rate 0.12%). Among them 97 had TSH values between 30 and 50μIU/ml and TSH estimation from a blood spot on a new card 1-3 months later showed TSH values < 12.5μIU/ml. In 41 cases with TSH values 50-80μIU/ml, serum TSH and T4 revealed 4 cases of C.H. (9.7%), while 37 cases had serum TSH and T4 values within normal limits and were considered as Transient Hyperthyrotropinemias (T.H.). Finally among 33 cases with initial TSH values > 80μIU/ml, in 29 (88%) the diagnosis of C.H. was confirmed on biochemical and clinical grounds, while 4 were considered as T.H. The overall incidence of primary C.H. in our population was 1:4,157.

Neonatal screening in Italy for congenital hypothyroidism and metabolic disorders: hyperphenylalaninemia, maple syrup urine disease and homocystinuria.

A multiple screening program to establish the frequency of congenital hypothyroidism (CH), phenylketonuria (PKU), maple syrup urine disease (MSUD), homocystinuria and hypertyrosinemia in endemic and sporadic goitrous regions of Italy is being carried out. Valine, methionine, leucine, isoleucine, tyrosine and phenylalanine, eluted from a single spot and separated by column chromatography, are measured, using whole blood adsorbed on filter paper. CH is detected by RIA assay of TSH eluted from dried blood spot. A cut-off of 100 microU/ml for TSH is used providing a recall rate of 0.38%. Out of 116,000 newborn infants screened for aminoacidopathies (since 1974), 16 PKU patients, 3 affected by MSUD, 2 homocystinuric babies have been detected. Out of 25,400 newborn infants screened for CH, 5 patients were affected by permanent CH and 29 by transient hyperthyrotropinemia. Thus PKU shows a frequency of 1:7,200 newborn infants, and permanent congenital hypothyroidism 1:5,080. The coordination of screening programs for congenital metabolic diseases in a single central unit allows:--the unification of the input of samples and output of data in a single data bank;--a minimization of the physical and psychological stress to the patients and their families;--and a more satisfactory cost/benefit ratio.