Data obtained during long-term follow-up of 68 girls with premature thelarche were analysed. In 85% onset was before the age of 2 years, in 30.8% being present at birth. In 44.1% there was a regression after 3 2/12 +/- 2 8/12 years (SD). Basal levels of plasma FSH and response to LH-RH were significantly higher than prepubertal controls (1.93 +/- 1.56 vs. 0.8 +/- 0.1 mU/ml and peaks 12.3 +/- 5.4 vs. 7.9 +/- 1.0 mU/ml respectively; p less than 0.001). Twenty-seven of 52 patients tested had increased plasma estradiol and in 27 of 40 patients tested, urocytograms or vaginal smear showed estrogenization. Basal levels of LH and response to LH-RH were prepubertal. The girls with premature thelarche were significantly taller than normal controls of the same age (p less than 0.001). These results suggest that premature thelarche is an incomplete form of precocious sexual development probably due to derangement in the maturation of the hypothalamo-pituitary-gonadal axis which results in a higher than normal secretion of FSH, as well as a defect in the peripheral sensitivity to the sex hormones.

Length/height was studied from birth to 6 years of age in 103 children with congenital hypothyroidism identified by the Norwegian or Swedish screening programs. We used the "infancy-childhood-puberty (ICP) growth model". This model describes normal linear growth during the first 3 years of life by an infancy component with the addition of a childhood component, the latter acting from the second half of the first year. In comparison with reference children, children with hypothyroidism had reduced growth from 6 to 12 months, and increased growth after 12 months of age. Mean onset of the childhood component of growth was delayed from 8.1 months (SD 1.9) to 10.4 months (SD 2.2) in girls, and from 8.9 months (SD 2.0) to 11.0 months (SD 2.1) in boys. Age at onset of the childhood component was correlated with age at start of treatment (r = 0.24), and in children with more severe hypothyroidism (pretreatment serum thyroxine < 40 nmol/l) inversely correlated with the L-thyroxine dose at start of treatment (r = -0.40). Change in height standard deviation score from 1 to 3 years of age was correlated with the serum thyroxine concentration at age 1 year (r = 0.30). The delay in the onset of the childhood component of growth and the association with age at start of treatment and initial L-thyroxine dose indicate that thyroid hormones during the first months of life are essential for normal onset of the childhood component of growth, which otherwise is assumed to be growth hormone-dependent.

TSH receptor antibodies are generally held responsible for the stimulation of the thyroid that characterizes patients with Graves' disease. Here, we describe nine patients with hyperthyroidism (triiodothyronine 4.9, 3.2-6.7 nmol/L; median, range) who were referred for radioiodine treatment and who had increased thyroid radioiodine uptake values but lacked TSH receptor antibodies determined by a radioreceptor assay. Furthermore, when serum immunoglobulins were studied in a bioassay based on a rat thyroid cell line (FRTL-5), no evidence of stimulant activity was observed. Subsequent to radioiodine therapy, TSH receptor antibodies appeared in all nine patients. The antibodies competed for TSH in the radioreceptor assay and, of the eight patient samples studied with the bioassay, six stimulated cAMP production whereas another two blocked the latter. The results show that a small proportion of patients with active hyperthyroid Graves' disease, in this study 9 out of 130 cases, do not have detectable TSH receptor stimulatory antibodies. A local production of antibodies within the thyroid can be suggested, although a more likely explanation might be that the thyroid in Graves' disease is activated also by other mechanisms than antibody-dependent ones.