-
Inquiry : a Journal of Medical Care... 2021Primary congenital hypothyroidism (CH) is a common endocrine and metabolic disease. Various genetic factors, including the thyroid hormone receptor (TSHR), play an...
BACKGROUND
Primary congenital hypothyroidism (CH) is a common endocrine and metabolic disease. Various genetic factors, including the thyroid hormone receptor (TSHR), play an important role in CH.
AIM
To explore the occurrence of pathogenic variants in CH.
METHODS
We searched published articles in PubMed, Web of Science, and Cochrane Library databases, from the establishment of the database to September 26, 2021. Studies with sequencing partial or full exons of in CH patients were included. Gene polymorphism was excluded.
RESULTS
A total of 66 articles (44 case-control studies and 22 case reports) were selected from the database. Though case-control studies, we found the incidence of pathogenic variants were not rare (range from 0% to 30.6%) and varied greatly in different countries and race. The pathogenic genotypes varied in different regions. All the variants were "loss-of-function" mutations, in which the p.(Arg450His) variant was the most common variant. In addition, we analyzed the case reports and found that CH patients with a family genetic background expressed homozygous genotypes. Homozygotes had more obvious symptoms of hypothyroidism and higher risk of comorbidities than heterozygotes.
CONCLUSION
Pathogenic variants are not uncommon cause of the CH, especially in the Arabs. The role of gene detection in the treatment of children with CH needs to be further studied.
Topics: Child; Congenital Hypothyroidism; Humans; Mutation; Receptors, Thyroid Hormone; Receptors, Thyrotropin
PubMed: 34919466
DOI: 10.1177/00469580211067943 -
Clinical Endocrinology Apr 2023Growth hormone stimulation testing (GHST) is used to diagnose growth hormone deficiency (GHD) in children. As sex steroids impact on anterior pituitary function, there...
OBJECTIVE
Growth hormone stimulation testing (GHST) is used to diagnose growth hormone deficiency (GHD) in children. As sex steroids impact on anterior pituitary function, there is concern around the efficacy of GHST in peripubertal children, where endogenous sex steroid levels are low. Sex steroid priming before GHST is thought to improve test efficacy in these children, however evidence to support its use in clinical practice is limited. In this systematic review, we addressed the following research questions: Does priming increase GH stimulation test efficacy in peripubertal children? Does priming identify those who would benefit most from treatment in terms of final height? Is there evidence for an optimal sex-steroid priming regimen?
DESIGN, PATIENTS, MEASUREMENTS
The study was registered with PROSPERO and conducted according to PRISMA guidelines. We searched Medline, Cochrane-Library, Scopus, EMBASE and Web-of-Science and included all studies that included GHST in both primed and unprimed children. A GH cut-off of 7 µg/L was used as a threshold for GHD. Study quality was assessed using the Risk-Of-Bias in Non- Randomized Studies (ROBINS-I) tool or the revised Cochrane risk-of-bias tool for Randomised trials.
RESULTS
Fifteen studies met our inclusion criteria, of which 4/15 (27%) were randomised control trials. The majority (9/15) of the studies indicated that priming increases growth hormone response upon GHST in peripubertal children, increasing test specificity. Two studies investigated final height after treatment based on the results of primed versus unprimed GHST. These results indicate that growth hormone treatment based on results of a primed GHST improve outcomes compared with treatment based on an unprimed test.
CONCLUSION
Sex-steroid priming increases the growth hormone response during GHST, resulting in fewer patients meeting the threshold required for a diagnosis of GHD. Unnecessary GH treatment may be avoided in some patients without a detrimental effect on final height. Numerous sex-steroid priming regimens have been used in clinical practice and the majority appear to be effective, but an optimal regimen has not been determined.
Topics: Humans; Child; Adolescent; Growth Hormone; Human Growth Hormone; Gonadal Steroid Hormones; Dwarfism, Pituitary; Growth Disorders; Body Height; Steroids
PubMed: 36515075
DOI: 10.1111/cen.14862 -
Hormone Research in Paediatrics 2023The link between the effects of recombinant human growth hormone (rhGH) therapy in patients with growth hormone deficiency (GHD) and Chiari malformation type I (CM-1) is...
BACKGROUND
The link between the effects of recombinant human growth hormone (rhGH) therapy in patients with growth hormone deficiency (GHD) and Chiari malformation type I (CM-1) is controversial.
SUMMARY
We report the case of a patient with an unusual association of GHD due to ectopic posterior pituitary and CM-1. Our patient developed a headache and worsening of CM-1 after the initiation of rhGH therapy. Following an atlo-occipital decompression surgery, the patient was able to resume therapy with a marked growth improvement. Based on this observation, we provide a systematic review of the current literature about these two pathologies.
KEY MESSAGES
A careful follow-up of all patients with CM-1 treated with GH is mandatory, paying particular attention to the appearance of any neurological signs and symptoms.
Topics: Humans; Arnold-Chiari Malformation; Human Growth Hormone; Dwarfism, Pituitary; Recombinant Proteins
PubMed: 36001954
DOI: 10.1159/000526617