Resistance to thyroid hormone with a mutation of the thyroid β receptor gene in an eight-month-old infant — a case report

Introduction: Resistance to thyroid hormone (RTHβ) is a rare syndrome of impaired tissue responsiveness to thyroid hormones (THs). The disorder has an autosomal dominant or recessive pattern of inheritance. Most of the reported mutations have been detected in the thyroid hormone receptor β gene (THRβ). Case report: Authors present an eight-month-old infant with poor linear growth, decreased body weight, tachycardia, positive family history, and neonatal features suggestive of RTHβ. Both our patient and his mother had elevated free thyroxine, free triiodothyronine, and non-suppressed thyrotropin (TSH) concentration. The fluorescent sequencing analysis showed a heterozygous mutation c.728G > A in TRβ gene. This pathogenic variant is known to be associated with THR. Conclusions: The clinical presentation of RTHb is variable, ranging from isolated biochemical abnormalities to symptoms of thyrotoxicosis or hypothyroidism. The syndrome should be suspected in patients with increased serum TH level, accompanied by a normal or elevated TSH concentration. The affected patients require individualised management.Introduction: Resistance to thyroid hormone (RTHβ) is a rare syndrome of impaired tissue responsiveness to thyroid hormones (THs). The disorder has an autosomal dominant or recessive pattern of inheritance. Most of the reported mutations have been detected in the thyroid hormone receptor β gene (THRβ). Case report: Authors present an eight-month-old infant with poor linear growth, decreased body weight, tachycardia, positive family history, and neonatal features suggestive of RTHβ. Both our patient and his mother had elevated free thyroxine, free triiodothyronine, and non-suppressed thyrotropin (TSH) concentration. The fluorescent sequencing analysis showed a heterozygous mutation c.728G > A in TRβ gene. This pathogenic variant is known to be associated with THR. Conclusions: The clinical presentation of RTHb is variable, ranging from isolated biochemical abnormalities to symptoms of thyrotoxicosis or hypothyroidism. The syndrome should be suspected in patients with increased serum TH level, accompanied by a normal or elevated TSH concentration. The affected patients require individualised management

GHD Diagnostics in Europe and the US: An Audit of National Guidelines and Practice

Introduction: Almost 20 years after the first international guidelines on the diagnosis and treatment of GHD have been published, clinical practice varies significantly. The low accuracy of endocrine tests for GHD and the burden caused by ineffective treatment of individual patients were strong motives for national endocrine societies to set up national guidelines regarding how to diagnose GHD in childhood. This audit aims to review the current state and identify common changes, which may improve the diagnostic procedure. Methods: A group of eight German pediatric endocrinologists contacted eight pediatric endocrinologists from Spain, France, Poland, the UK, the Netherlands, Denmark, Italy, and the US. Each colleague responded as a representative for the own country to a detailed questionnaire containing 22 open questions about national rules, guidelines, and practice with respect to GHD diagnostics and GH prescription. The results were presented and discussed in a workshop and then documented in this study which was reviewed by all participants. Results: National guidelines are available in 7 of 9 countries. GH is prescribed by pediatric endocrinologists in most countries. Some countries have established boards that review and monitor prescriptions. Preferred GH stimulation tests and chosen cutoffs vary substantially. Overall, a trend to lowering the GH cutoff was identified. Priming is becoming more popular and now recommended in 5 out of 9 countries; however, with different protocols. The definition of pretest-conditions that qualify the patient to undergo GH testing varies substantially in content and strictness. The most frequently used clinical sign is low height velocity, but definition varies. Height, IGF-1, and bone age are additional parameters recommended in some countries. Conclusions: GHD diagnostics varies substantially in eight European countries and in the US. It seems appropriate to undertake further efforts to harmonize endocrine diagnostics in Europe and the US based on available scientific evidence

Metabolic Issues in Adolescence

The article resumes the main metabolic syndrome definitions and the main pathophysiologic mechanisms of the metabolic syndrome