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Pituitary resistance to thyroid hormone in cystinosis
Insights
Children with cystinosis show elevated thyroid-stimulating hormone (TSH) levels, suggesting pituitary resistance to thyroid hormone feedback. This finding links a metabolic disorder with abnormal pituitary function.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Pediatrics
Background:
- Nephropathic cystinosis is a rare genetic disorder.
- Thyroid dysfunction is not a typical feature of cystinosis.
Purpose of the Study:
- To investigate thyroid function in children with nephropathic cystinosis.
- To explore the relationship between cystinosis and pituitary hormone regulation.
Main Methods:
- Assessed thyroid function tests (TSH, T4, free T4, T3) in 11 children with cystinosis.
- Administered thyrotropin-releasing hormone (TRH) stimulation test.
- Evaluated clinical parameters and hormone feedback mechanisms.
Main Results:
- Elevated serum TSH levels were observed in children with cystinosis, despite normal thyroid hormone levels.
- TRH stimulation showed exaggerated TSH response in most patients.
- Parameters suggested euthyroidism clinically, but pulse wave arrival time indicated hyperthyroidism.
- High doses of thyroid hormone replacement were needed to suppress TSH.
Conclusions:
- Children with cystinosis exhibit pituitary resistance to thyroid hormone feedback.
- This is the first reported association between cystinosis and pituitary resistance.
- Further research is needed to understand the implications of this finding.
Abstract:
Eleven children with nephropathic cystinosis without clinical features of hyperthyroidism or hypothyroidism had elevated serum levels of immunoreactive TSH. The mean TSH level (+/- SE) was 37.4 +/- 12.3 microM/ml. Serial determinations of thyroid function during 1 yr were: mean (+/- SE) serum T4, 10.8 +/- 0.7 microgram/dl; free T4, 2.1 +/- 0.2 ng/dl; and T3, 239 +/- 6 ng/dl. After 500 microgram TRH iv, the peak TSH level exceeded 100 microU/ml in 6 of 10 patients, whereas T3 responses were variable. Studies of parameters influenced by thyroid hormone, including red cell sodium content, serum cholesterol, and 24-h urinary hydroxylysine excretion, were consistent with euthyroidism. On the other hand, the mean pulse wave arrival time was significantly reduced, consistent with hyperthyroidism. Three control patients, 2 with Lowe's syndrome and 1 with benign cystinosis, had normal thyroid studies. Eight of the patients were given either exogenous L-T4 or T3 in doses which were increased at weekly intervals. The serum TSH concentrations were suppressed to normal only after elevation of serum levels of thyroid hormones and with high exogenous thyroid replacement doses. The data suggest abnormal pituitary resistance to feedback by thyroid hormone in patients with cystinosis. We believe this to be the first description of the association of a heritable metabolic disease with such pituitary resistance.