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Thyrotropin Behavior in Thyroid Disorders of Childhood

Abstract: Through the use of a double antibody radioimmunoassay method, the mean serum concentration of thyrotropin (TSH) in 51 normal children aged 1 month-18 years was 3.7 ng/ml. There was no change with age, sex, or time of the day at which the sample was obtained.In six of nine newly diagnosed hyperthyroid children concentrations of TSH fell below the limit of detection, whereas in the remaining three concentrations were in the low normal range. Knowledge of the TSH fluctuations during medical treatment (antithyroid drugs or radioactive iodine plus 127I) were useful in insuring a smooth clinical course. Elevations in TSH above 10 ng/ml served to indicate a need for change in therapy. Radical subtotal thyroidectomy evoked an acute compensatory rise (> 20 ng/ml) in TSH levels which was sometimes sufficient to maintain the level of serum thyroxine above 4 μg/100 ml. Hemithyroidectomy did not influence TSH or other thyroid parameters in previously euthyroid subjects.There was a clear separation between normal subjects and patients with primary hypothyroidism with values for TSH always exceeding 20 ng/ml in the latter. The TSH levels were below 3.7 ng/ml in pituitary hypothyroidism. In hypothyroid patients receiving adequate replacement therapy, elevations of serum TSH of > 20 ng/ml were encountered 2 weeks after discontinuation of treatment.Investigation of the pituitary-thyroidal axis in two untreated cretinous infants showed preservation of the functional integrity of the pituitary-thyroidal feedback system despite prenatal thyroid insufficiency as evidenced by a fall of TSH from levels >80 to <5 ng/ml in the presence of free thyroxine (FT4) levels >2 ng/100 ml.In three patients (two females and one male) with longstanding juvenile hypothyroidism and TSH levels >80 ng/ml, pituitary dysfunctions characterized by luteinizing hormone (LH) concentrations above 20 mIU/ml and blunted growth hormone (HGH) responses to hypoglycemia were documented prior to therapy. Only the male had evidence of sexual precocity on physical examination. All three showed an abnormal circadian rhythm of cortisol secretion manifested by 8 PM values greater than 10 7mu;g/100 ml. Acute restoration of euthyroidism in the two girls by means of paren-teral thyroxine (T4) improved the HGH response and normalized the cortisol rhythms in 72 hr, coincident with a sharp decline in TSH levels toward normal. In contrast, the high levels of LH declined much more slowly, failing to reach normal for as long as 7 weeks posttreatment.TSH in company with T4 measurements permitted segregation of patients with Hashimoto's thyroiditis into three groups: (a) euthyroid with normal TSH and T4. (b) compensated with TSH values ranging between 19 and 28 ng/ml and T4 in the 6-8 /μg/100 ml range, and (c) hypothyroid with T4 below 3 μg/100 ml and TSH values greater than 40 ng/ml.Speculation: High peripheral concentrations of serum TSH appear to be the most sensitive index of primary hypothyroidism and will thus be useful both in establishing diagnosis and in determining the adequacy of treatment.Elevated gonadotropin levels appear to be the rule in longstanding juvenile hypothyroidism, but physical evidence of sexual precocity seems to be an unusual feature in the syndrome. This may suggest subnormal secretory responsiveness of the gonadal target organs, or subnormal sensitivity of the tissues responsible for secondary sexual differentiation.The observation that patients with cretinism and juvenile myxedema can be safely rendered euthyroid by therapy which abruptly returns serum thyroxine concentration to normal and promptly corrects the associated hypothalamic and pituitary dysfunctions suggests that conventional therapy can be improved. A more aggressive approach to treatment of the infant cretin may reduce the still high incidence of mental subnormality as has been suggested recently [32].