propylthiouracil and Intellectual-Disability

Topics: Abortion, Spontaneous; Congenital Hypothyroidism; Female; Fetal Death; Humans; Hyperthyroidism; Infant, Newborn; Infant, Newborn, Diseases; Intellectual Disability; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroidectomy; Triiodothyronine

Mutations of the monocarboxylate transporter 8 (MCT8) gene determine a distinct X-linked phenotype of severe psychomotor retardation and consistently elevated T(3) levels. Lack of MCT8 transport of T(3) in neurons could explain the neurological phenotype.. Our objective was to determine whether the high T(3) levels could also contribute to some critical features observed in these patients.. A 16-yr-old boy with severe psychomotor retardation and hypotonia was hospitalized for malnutrition (body weight = 25 kg) and delayed puberty. He had tachycardia (104 beats/min), high SHBG level (261 nmol/liter), and elevated serum free T(3) (FT(3)) level (11.3 pmol/liter), without FT(4) and TSH abnormalities. A missense mutation of the MCT8 gene was present. Oral overfeeding was unsuccessful. The therapeutic effect of propylthiouracil (PTU) and then PTU plus levothyroxine (LT(4)) was tested. After PTU (200 mg/d), serum FT(4) was undetectable, FT(3) was reduced (3.1 pmol/liter) with high TSH levels (50.1 mU/liter). Serum SHBG levels were reduced (72 nmol/liter). While PTU prescription was continued, high LT(4) doses (100 microg/d) were needed to normalize serum TSH levels (3.18 mU/liter). At that time, serum FT(4) was normal (16.4 pmol/liter), and FT(3) was slightly high (6.6 pmol/liter). Tachycardia was abated (84 beats/min), weight gain was 3 kg in 1 yr, and SHBG was 102 nmol/liter.. 1) When thyroid hormone production was reduced by PTU, high doses of LT(4) (3.7 microg/kg.d) were needed to normalize serum TSH, confirming that mutation of MCT8 is a cause of resistance to thyroid hormone. 2) High T(3) levels might exhibit some deleterious effects on adipose, hepatic, and cardiac levels. 3) PTU plus LT(4) could be an effective therapy to reduce general adverse features, unfortunately without benefit on the psychomotor retardation.

Topics: Adolescent; Antithyroid Agents; Humans; Intellectual Disability; Male; Monocarboxylic Acid Transporters; Muscle Hypotonia; Mutation, Missense; Propylthiouracil; Puberty, Delayed; Symporters; Syndrome; Tachycardia; Thyroid Hormone Resistance Syndrome; Thyroid Hormones; Thyroxine; Treatment Outcome

Presented are two case studies which investigate the adverse effects of Graves' disease in pregnant women. Particular attention has been paid to the therapeutic regimen and its implications for the maternal, fetal and neonatal well-being. The first case study illustrates that Graves' disease complicating pregnancy can be treated by bed rest and careful observation of mother and fetus. The first pregnancy of our second case study confirms these results. Her second pregnancy, in which the symptoms of Graves' disease were far more severe, illustrates that it is possible to treat fetal hyperthyroidism by treating the pregnant mother with antithyroid drugs. If great care is taken to avoid overtreatment of the fetus, the treatment with antithyroid drugs is superior to surgical treatment, since surgery completely neglects the problem of fetal hyperthyroidism.

Topics: Abortion, Spontaneous; Adult; Female; Fetal Diseases; Graves Disease; Humans; Hypothyroidism; Intellectual Disability; Pregnancy; Pregnancy Complications; Propylthiouracil

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: Adolescent; Adult; Bone Development; Child; Child, Preschool; Craniosynostoses; Female; Fingers; Graves Disease; Humans; Hyperthyroidism; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intellectual Disability; Long-Acting Thyroid Stimulator; Male; Pedigree; Propylthiouracil