propylthiouracil and Growth-Disorders

Hyperthyroidism is rare in early childhood and most commonly caused by Graves' disease. We report 14 children (4 boys, 10 girls) aged 3.4-7.5 yr. At diagnosis, all patients had weight loss, hyperkinetic activity, tachycardia, difficulty sleeping, and poor concentration and 11 presented with proptosis. Four patients developed long-term neuropsychological problems. There was a family history in 7 cases. All patients had goiters, clinically assessed to be large and diffuse in 21%, medium-sized in 43%, and small in 36%. At diagnosis, height was increased with median (range) height; 1.25 standard deviation score (SDS) (-0.2-5.24) and body mass index (BMI) was decreased; -0.48 SDS (-1.65-1.26). Height and BMI SDS values were statistically different (p<0.032) Bone age was advanced in 4 of 5 children, who had assessments. Total or free T4 levels were elevated and TSH was undetectable. Ninety percent of patients (12/14) had positive thyroid peroxidase autoantibodies, mean level 680 IU/ml (range 50-1347). Initial treatment was with antithyroid medication using carbimazole; median dose 0.75 mg/kg/day (no.=13) or propylthiouracyl 15 mg/kg/day (no.=1). T4 was added in 6 patients. Normalisation of serum T4 occurred at 4 months (1- 9) and TSH at 7 months (3-24) after start of therapy. Treatment was discontinued after a minimum of 2 yr in 11 patients, relapse occurring in 9. Median duration of total therapy was 58 months (18-132). During adolescence, 4 patients had curative therapy by surgery (no.=2) or radioiodine (no.=2). In conclusion, disturbance of growth, behavioral difficulties and infrequent spontaneous remission are key features of Graves' disease in early childhood.

Topics: Age of Onset; Antithyroid Agents; Attention Deficit Disorder with Hyperactivity; Carbimazole; Child; Child, Preschool; Exophthalmos; Female; Graves Disease; Growth Disorders; Humans; Hyperkinesis; Iodide Peroxidase; Male; Propylthiouracil; Recurrence; Retrospective Studies; Sleep Wake Disorders; Tachycardia; Thyrotropin; Thyroxine; Weight Loss

Newborn rats of both sexes were treated from birth with the anti-thyroid goitrogen, n-propylthiouracil (PTU) given in the drinking water of the litter (0.1% w/v). One group received the treatment for 25 days, another for 50 days, and a third group for 120 days. The experimental rats showed growth retardation as well as all other classical signs of developmental arrest or delays induced by postnatal hypothyroidism. In order to assess the ability of the hypothyroid animals to recover spontaneously from the retarded state, at days 25, 50 and 120 postnatal the PTU water was replaced with tap water. In each case, within 5-7 days after PTU withdrawal the animals began to show marked compensatory growth accompanied by many signs of behavioral and physiological recovery. In general, the male rats showed higher compensatory growth rates as compared to the females, enabling them to attain significantly higher body weights. However, when growth recovery was followed for up to 6 months it was found that the male rats were unable to attain complete catch-up growth, regardless of the age at which recovery began, while the females of all age groups were able to achieve this goal. In view of the severity of PTU-induced growth retardation, these results suggest significant plasticity of growth processes in the rat, especially in the female. It is suggested that male and female rats recovering from prolonged PTU-induced growth retardation offer a good model system for the study of biochemical, anatomical and physiological aspects of growth recovery and catch-up growth at both the cellular and organismic levels, particularly in relation to the effects of thyroid, growth hormone, and other growth-promoting factors.

Topics: Aging; Animals; Animals, Newborn; Animals, Suckling; Body Weight; Female; Growth Disorders; Hypothyroidism; Male; Propylthiouracil; Rats; Sex Factors; Sexual Maturation; Weaning

Topics: Animals; Body Weight; Cortisone; Fasting; Growth Disorders; Growth Hormone; Iodine Radioisotopes; Male; Metabolic Clearance Rate; Propylthiouracil; Rats

To study the possible mechanisms involved in growth retardation associated with hypothyroidism, serum T4, GH, the GH-dependent somatomedin, insulin-like growth factor (IGF), and its carrier protein (CP) were measured in hypothyroid rats and their age-matched controls. Three groups of rats were studied: infant, immature, and adult. Marked hypothyroidism (serum T4, less than 1 microgram/dl) was produced in experimental animals by providing them with drinking water containing 0.05% propylthiouracil. Infant and immature hypothyroid rats weighed markedly less than normal controls and had significantly reduced serum levels of GH, IGF, and CP. Normal adult rats, treated with propylthiouracil for 60 days, also weighed considerably less than control animals and exhibited a significant drop in serum GH, IGF, and CP during this period. The administration of bovine GH to hypothyroid adult rats for 7 days did not restore either IGF or CP levels to normal, indicating that their decrease in serum was, in part, a direct result of hypothyroidism per se. These results indicate that serum levels of GH, IGF, and CP are at least partly under thyroid hormone control. Furthermore, these studies suggest that the growth retardation associated with hypothyroidism may be mediated through somatomedin activity.

Topics: Aging; Animals; Body Weight; Carrier Proteins; Female; Growth Disorders; Growth Hormone; Hypothyroidism; Male; Nonsuppressible Insulin-Like Activity; Propylthiouracil; Rats; Somatomedins; Thyroxine

Topics: Animals; Body Weight; Brain Injuries; Cartilage; Cortisone; Disease Models, Animal; Fasting; Growth; Growth Disorders; Growth Hormone; Humans; Intellectual Disability; Pituitary Gland; Propylthiouracil; Radiation Injuries, Experimental; Rats; Somatomedins; Sulfates

Topics: Age Determination by Skeleton; Age Factors; Body Height; Bone Development; Child; Child Development; Child, Preschool; Evaluation Studies as Topic; Female; Follow-Up Studies; Growth Disorders; Humans; Hyperthyroidism; Infant; Male; Propylthiouracil

Topics: Age Factors; Animals; Cats; Conditioning, Classical; Fixation, Ocular; Galvanic Skin Response; Growth Disorders; Habituation, Psychophysiologic; Heart Rate; Orientation; Propylthiouracil; Respiration

Topics: Animals; Biometry; Body Weight; Bone Development; Cortisone; Fasting; Female; Growth; Growth Disorders; Male; Propylthiouracil; Rats; Tail