Hormone Research in Paediatrics最新文献

{"title":"Similarities and Differences in Diurnal Salivary Adrenal Hormones in Monozygotic Twins with Discordant Birthweight.","authors":"Thea Roedig, Nora Eberhardt, Peter Bartmann, Felix Schreiner, Paul-Martin Holterhus, Alexandra E Kulle, Sandra Schulte, Bettina Gohlke","doi":"10.1159/000542549","DOIUrl":"10.1159/000542549","url":null,"abstract":"<p><strong>Introduction: </strong>Dehydroepiandrosterone sulphate is increased in formerly small-for-gestational age singletons and in smaller twins compared to their normal-weight co-twin. Less is known concerning other adrenal hormones. We compared diurnal salivary profiles in monozygotic twins with intra-twin birthweight (bw) differences to analyse the long-term impact of bw and persistent intra-twin auxological differences on various adrenal hormones.</p><p><strong>Methods: </strong>Forty-six monozygotic pre-pubertal twin pairs with bw difference of <1 standard deviation score (SDS) (concordant; n = 29, 13 female) and ≥1 SDS (discordant; n = 17, 6 female) were recruited. At a mean age of 6.9 years, saliva samples were collected (7:00 a.m./waking, 1:00 p.m., 6:00 p.m., and 9:00 p.m.) and analysed with liquid chromatography-tandem mass spectrometry.</p><p><strong>Results: </strong>Diurnal salivary concentrations showed significant intra-twin correlations in all twin pairs for nearly all time points: progesterone and androstenedione (4/4 time points), 17-hydroxyprogesterone (2/4). However, in the discordant group, mean progesterone differed significantly (p = 0.018) between the smaller (3.27 nmol/L, SD 3.87) and the larger twin (0.72 nmol/L, SD 0.42) at 7:00 a.m., and intra-twin differences were observed at 3/4 time points. Regression analyses of intra-twin differences confirmed that actual hormonal parameters were explained mainly by the co-twin parameter. However, at 6:00 p.m., progesterone concentration of the smaller twin was explained by bw (Β -1.102; SE 0.563; p = 0.05) and actual weight (Β 0.799; SE 0.327; p = 0.019).</p><p><strong>Conclusion: </strong>The significant correlations within monozygotic twin pairs in all measured hormones at nearly all time points suggest a strong genetic influence on the adrenal axis. Among the discordant twin pairs, we found significant variations in progesterone, suggesting additional long-lasting influence from intrauterine conditions on adrenal hormones with possible metabolic consequences.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-13"},"PeriodicalIF":2.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility of Using Continuous Glucose Monitoring to Detect Glycemic Abnormalities in Children with Cystic Fibrosis.","authors":"Amanda Leonard, Isabel R Judware, Lori L Vanscoy, Shruti M Paranjape, Donna Peeler, Malinda Wu, Scott M Blackman, Peter J Mogayzel","doi":"10.1159/000542786","DOIUrl":"10.1159/000542786","url":null,"abstract":"<p><strong>Introduction: </strong>Cystic fibrosis-related diabetes (CFRD) is linked to worsening pulmonary function and increased mortality in people with cystic fibrosis (CF). Because of this correlation, early recognition of CFRD is important. Current recommendations for detecting glucose abnormalities using an oral glucose tolerance test (OGTT) can be difficult to achieve in a busy clinical setting.</p><p><strong>Methods: </strong>We trialed a 10-day continuous glucose monitoring (CGM) (Dexcom G6Pro) session in patients seen in our pediatric CF clinic that could not do an OGTT (reasons include emesis with OGTT or fear of needles) or that had an abnormal OGTT (to gather additional data to make treatment decisions).</p><p><strong>Results: </strong>Of the 36 sensors placed, 34 (94%) were returned. Devices were worn for a median of 10 days (range 4-10 days). Of the 34 CGMs returned, 20 (59%) met the criterion for referral to a pediatric endocrinologist.</p><p><strong>Conclusion: </strong>CGM placement is feasible in a busy CF clinic to detect glucose abnormalities in children.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-6"},"PeriodicalIF":2.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult Height in Girls with Central Precocious Puberty with Onset after 6 Years: Effects of Gonadotropin-Releasing Hormone Analog Therapy.","authors":"Reiko Saito, Kayo Ozaki, Yoshiro Baba, Kento Ikegawa, Keisuke Nagasaki, Akie Nakamura, Takashi Hamajima, Shinji Higuchi, Yukihiro Hasegawa","doi":"10.1159/000542038","DOIUrl":"10.1159/000542038","url":null,"abstract":"<p><strong>Introduction: </strong>Precocious puberty (PP), which is sometimes divided into gonadotropin-dependent or gonadotropin-independent PP, is a pathological condition characterized by premature secretion of gonadal steroids resulting in the early development of secondary sexual characteristics. Girls younger than 6 years with idiopathic gonadotropin-dependent PP (referred to as central PP or CPP) who receive gonadotropin-releasing hormone analog (GnRHa) therapy experience an increase in their adult height (AH) in contrast to girls who are aged 6 years or more, who show no consistent pattern of increase even with GnRHa therapy.</p><p><strong>Methods: </strong>In total, 133 girls aged 6 years or more who visited any one of the seven study centers between April 2000 and March 2020 and who met the diagnostic criteria for PP in Japan were retrospectively examined. The participants were divided into a treatment (n = 56) and no-treatment group (n = 77). The AH and target height (TH) were compared between the groups, and the factors influencing the AH were examined.</p><p><strong>Results: </strong>The patients receiving GnRHa therapy achieved significantly greater increase in their AH, AH - TH, and predicted AH at the age of 6, 7, and 8 years (6 ≤ years < 9) than those without the treatment. The TH and height at the start and end of treatment influenced the AH of the former group.</p><p><strong>Conclusion: </strong>GnRHa therapy was effective in improving the AH in girls with CPP onset at the age of 6, 7, or 8 years. The TH was a strong determinant of the AH.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-8"},"PeriodicalIF":2.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Predictors of Good/Poor Response to Growth Hormone Treatment in Children with Idiopathic Short Stature.","authors":"Andrew Dauber, Moshe Phillip, Jean-Marc Ferran, Nicky Kelepouris, Navid Nedjatian, Anne Helene Olsen, Alexander Augusto de Lima Jorge","doi":"10.1159/000542579","DOIUrl":"https://doi.org/10.1159/000542579","url":null,"abstract":"<p><strong>Introduction: </strong>Children with idiopathic short stature (ISS) are known to have varying responses to growth hormone (GH) treatment (GHT).</p><p><strong>Methods: </strong>We conducted a post hoc analysis to identify clinical characteristics predictive of good and poor response during year 1 of GHT. Data from the NordiNet® IOS (NCT00960128) and the ANSWER Program (NCT01009905) were used. Patients were grouped according to their response to GHT; good, middle, and poor responders had a change in HSDS of >1.0, 0.4-1.0, and <0.4, respectively. Patients were also grouped according to their responsiveness to GH dose. Logistic regression modelling was performed to identify clinical characteristics predictive of response to GHT.</p><p><strong>Results: </strong>The response analysis set included 207 patients. Patients were 3-11 years old (males) or 3-10 years old (females) at treatment start and were prepubertal throughout year 1 of treatment. Age at treatment start (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.5;0.9, p = 0.0169) and distance from target HSDS (OR 2.05, 95% CI 1.1;3.9, p = 0.0259) were found to be significant independent predictors of being in the good- versus poor-response groups. When patients were grouped according to their responsiveness to GH dose, a positive correlation between GH dose and change in HSDS was observed.</p><p><strong>Conclusion: </strong>We identified younger age and further distance from target HSDS as clinical predictors of response to GHT in a heterogenous population of children with ISS. Future studies, designed to identify the genetic determinants of response to GHT could further facilitate individualisation of GHT. .</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-20"},"PeriodicalIF":2.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Influence of X Chromosome Parent-of-Origin on Glycemia in Individuals with Turner Syndrome.","authors":"Catherina T Pinnaro, Blake Irvin Zimmerman, Kelli K Ryckman, Benjamin W Darbro, Andrew W Norris","doi":"10.1159/000542677","DOIUrl":"10.1159/000542677","url":null,"abstract":"<p><strong>Introduction: </strong>The cause of increased diabetes mellitus (DM) risk in individuals with Turner syndrome (TS) is poorly understood. Parent-of-origin effects related to whether the maternal or paternal X chromosome (Xchr) remains intact have been found for several TS phenotypes, including hypercholesterolemia. Therefore, Xchr parent-of-origin may impact DM risk in TS. The aim of this study was to determine whether Xchr parent-of-origin affects glycaemia, as measured by oral glucose tolerance test (OGTT), in TS.</p><p><strong>Methods: </strong>A total of 81 individuals with 45,X karyotype from the TS: Genotype Phenotype study had Xchr parent-of-origin assessment and completed a 3-h OGTT. Parallel-slopes multiple linear regression modeling was used to test whether Xchr parent-of-origin, age, and/or body mass index (BMI) significantly predicted incremental area under the glucose curve (iAUC). A second analysis included 62 additional individuals with 45,X mosaicism.</p><p><strong>Results: </strong>All three factors predicted iAUC glucose in the 81 individuals with 45,X karyotype (age: β = 0.36, p = 0.0004; BMI: β = 0.33, p = 0.001; Xchr parent-of-origin: β = 0.21; p = 0.01). The overall model remained statistically significant when including individuals with 45,X mosaicism, but Xchr parent-of-origin was no longer significant.</p><p><strong>Conclusions: </strong>Maternal Xchr monosomy predicts higher glucose concentration than paternal Xchr monosomy in response to oral glucose in 45,X individuals. This effect is obscured when including individuals who are mosaic, potentially due to the presence of both parent Xchrs in the non-45,X cell line.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-9"},"PeriodicalIF":2.6,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Recombinant Human Growth Hormone Therapy in Short Children Born at Very Low Birth Weight.","authors":"Thais Kataoka Homma, Naiara Castelo Branco Dantas, Bruna Lucheze Freire, Laurana de Polli Cellin, Ana Maria Santillán Vásconez, Ivo Jorge Prado Arnhold, Renata Cunha Scalco, Alexsandra Christianne Malaquias, Alexander Augusto de Lima Jorge","doi":"10.1159/000542570","DOIUrl":"10.1159/000542570","url":null,"abstract":"<p><strong>Introduction: </strong>Although the clinical benefits of long-term recombinant human growth hormone (rhGH) therapy have been well demonstrated in children born small for gestational age (SGA), little is known about the outcomes of this therapy in children born with very low birth weight (VLBW). This study aimed to report the short- and long-term response to rhGH therapy in a cohort of VLBW patients, comparing subgroups according to size, gestational age (GA), and causal factors associated with VLBW.</p><p><strong>Methods: </strong>We describe 33 patients born at VLBW treated with rhGH; 16 also received GnRHa. Medical records were analyzed at baseline and after 1 year of rhGH treatment. Data on the adult height SDS from 23 patients were also collected. Growth velocities and height SDS changes were calculated, along with the differences between the observed and predicted growth velocities.</p><p><strong>Results: </strong>The first-year growth velocity (7.5 ± 2.1 cm/year) was aligned with prediction models for SGA children. After 1 year of rhGH treatment, height SDS improved from -3.0 ± 1.1 to -2.6 ± 1.3, with no differences among subgroups. Among patients reaching adult height, 73.9% remained short (-2.5 ± 1.3) after long-term therapy (6.7 ± 3.3 years). The initial height SDS, height SDS change in the first year of treatment, and target height SDS were key independent predictors of height gain.</p><p><strong>Conclusion: </strong>The response to rhGH treatment was suboptimal in the VLBW group, independent of the size, GA, or etiological diagnosis. However, adult height may be improved in patients receiving rhGH treatment. This underscores the need for tailored protocols and further investigations to optimize outcomes in this population.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-11"},"PeriodicalIF":2.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype-phenotype correlation and feminizing surgery in Danish children with congenital adrenal hyperplasia.","authors":"Marie Lind-Holst, Agnethe Berglund, Morten Duno, Gitte Hvistendahl, Magdalena Fossum, Anders Juul, Niels Jørgensen, Katharina M Main, Claus H Gravholt, Dorte Hansen","doi":"10.1159/000541775","DOIUrl":"https://doi.org/10.1159/000541775","url":null,"abstract":"<p><strong>Introduction: </strong>Congenital adrenal hyperplasia (CAH) is characterized by a broad spectrum of symptoms. This study aims to describe genotype-phenotype correlations, clinical manifestations at diagnosis, and the frequency of feminizing surgery in childhood.</p><p><strong>Methods: </strong>A nationwide retrospective cohort study of patients diagnosed with CAH, aged ≤18, between 1943 and 2018. CAH was identified in national registries and validated through medical record reviews and phenotypically classified as salt-wasting (SW), simple virilizing (SV), or non-classic (NC) CAH. In a sub-cohort (diagnosed between 1999 and 2018) clinical data and feminizing surgery data were investigated. CYP21A2 variants were grouped as Null, A, B, C, and D.</p><p><strong>Results: </strong>The cohort comprised 379 patients with CAH. Genotype-phenotype correlations were as follows: Null and SW (100%), A and SW (94%), B and SV (51%), and C and NC (75%). In the subcohort (n=159, females=99) the female-to-male ratios were: SW=1.5, SV=1.1, and NC=2.3. Symptoms of precocious pseudopuberty dominated at diagnosis (39%). Males presented with significantly advanced bone age by the time of diagnosis (p=0.0009). In 53% of females (n=53), virilization of the external genitalia was present at the time of diagnosis, and in 46% (n=46) this developed already prenatally. Of the prenatal virilized females 85% underwent early feminizing genitoplasty. Virilization was identified in both mild and severe genotypes.</p><p><strong>Conclusion: </strong>Milder genotypes do not accurately predict CAH phenotype or prenatally reject serious outcomes such as virilization. The frequency of early genitoplasty is high among females with prenatal virilization. The delayed diagnosis and non-diagnosis of especially males with mild CAH advocate for a more prominent role of genetic testing in the diagnostic and screening for CAH.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-20"},"PeriodicalIF":2.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of First-Morning-Voided Urinary Total Luteinizing Hormone in Detecting the Onset of Central Puberty.","authors":"And Demir, Matti Hero, Katharina M Main, Anders Juul","doi":"10.1159/000541586","DOIUrl":"https://doi.org/10.1159/000541586","url":null,"abstract":"<p><strong>Introduction: </strong>Early morning basal serum luteinizing hormone (S-LH) ≥0.3 IU/L is a specific marker for the onset of central puberty. In this study, we aimed to investigate the sensitivity and specificity of the first-morning-voided (FMV) total urinary LH (U-LH) to replace this marker.</p><p><strong>Methods: </strong>We re-analyzed our previously published data set of 297 children (145 boys and 152 girls, aged 5-15 years, across Tanner stages 1 through 5) using receiver operating characteristic (ROC) analysis and determined cutoff values for FMV total U-LH in predicting early morning S-LH concentration at or above 0.3 IU/L. We also determined S-LH and serum follicle-stimulating hormone (S-FSH) concentrations in girls at different stages of sexual maturation.</p><p><strong>Results: </strong>ROC analysis showed that FMV total U-LH levels of 0.60 and 0.63 IU/L in girls and boys, respectively, predicted early morning S-LH levels of 0.3 IU/L or higher with 97.4% sensitivity and 90.6% specificity. Higher cutoff levels for U-LH (0.78 IU/L for boys and 0.79 IU/L for girls) yielded 94.7% specificity at the expense of a relatively lower level of sensitivity (94.1%). The areas under the curve were 0.98 in boys and 0.99 in girls, respectively. Additionally, the increase in FMV total U-LH (or S-LH) levels identified the activation of central pubertal development at the mean age of 10.3 (10.3) in boys and 10.5 (10.6) in girls. The S-FSH concentrations of the six biochemically prepubertal girls with thelarche, ranging between 2.3 and 2.7 IU/L, were significantly higher than those measured in biochemically and clinically prepubertal girls of the same 10-12-year-old age group and significantly lower than those measured in both biochemically and clinically pubertal girls (p = 0.039 and p = 0.018, respectively).</p><p><strong>Conclusions: </strong>A FMV total U-LH concentration of 0.6 IU/L or above reliably reflects pubertal morning S-LH levels and is effective in detecting the onset of central puberty, which occurs at similar ages in both sexes. Concurrent S-FSH or noninvasive FMV U-FSH determinations may be useful in the differential diagnosis of isolated thelarche.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-9"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Genetic Mechanisms in Patients with MC2R Deficiency Presenting with Early Puberty.","authors":"Esin Karakilic Ozturan, Zehra Yavas Abali, Volkan Karaman, Sukran Poyrazoglu, Zehra Oya Uyguner, Feyza Darendeliler, Firdevs Bas","doi":"10.1159/000542307","DOIUrl":"10.1159/000542307","url":null,"abstract":"<p><strong>Introduction: </strong>Melanocortin receptor 2 (MC2R) in the adrenal cortex controls the hypothalamic-pituitary-adrenal axis. The melanocortin system, influenced by leptin, regulates GnRH neurons, crucial for puberty onset and fertility. This study evaluates early puberty in primary adrenal insufficiency (PAI) patients due to MC2R gene alterations.</p><p><strong>Methods: </strong>Seven patients with PAI (P1-P7) from five unrelated families, all presenting with early or precocious puberty, were included. MC2R deficiency diagnosis ranged from 1 day to 11 months. MKRN3, DLK1, KISS1, and KISS1R genes were analyzed using Sanger sequencing in four cases (P2, P4, P6, and P7). All clinical data were obtained retrospectively.</p><p><strong>Results: </strong>Puberty onset mean age was 8.6 years (7.4-9.5) in boys (P1, P2, P3, P7) and 8.5 years (7.4-9.5) in girls (P4, P5, P6). Tumor markers were negative; no adrenal rest or tumors were found. GnRH analogs were used for rapid puberty in P2, P3, P6. Final height in P1 and P2 was below target (-2.6 SDS, -0.7 SDS). Menarche occurred at 11 and 11.3 years in P4 and P5. No pathogenic variants were found.</p><p><strong>Conclusion: </strong>Genetic causes of early puberty were not identified. Elevated ACTH may stimulate kisspeptin neurons, triggering puberty. Close monitoring of these patients for pubertal development is recommended.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-8"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinical and Genetic Diversity of Thyroid Hormone Resistance: Four Clinical Vignettes.","authors":"Asma Deeb, Rochita Rajesh Kadam, Imad Mohamad El-Kebbi","doi":"10.1159/000542303","DOIUrl":"10.1159/000542303","url":null,"abstract":"<p><strong>Introduction: </strong>Resistance to thyroid hormones (RTH) is a rare but important genetic cause of decreased peripheral tissue responses to the actions of thyroxine. Most RTH cases are caused by mutations in thyroid hormone receptor β (TRβ, THRB), while a few are caused by mutations in thyroid hormone receptor α (TRα, THRA). RTH is clinically heterogeneous, and the biochemical features are often confusing, resulting in misdiagnoses, mismanagement, and life-long consequences for affected individuals. An awareness of the clinical and genetic spectrum of RTH is therefore essential to avoid misdiagnosis and to ensure timely referral for definitive management.</p><p><strong>Case presentation: </strong>Here we present four clinical vignettes describing three children and one adult with RTH encountered in our \"real-world\" tertiary pediatric endocrinology practice. We describe a novel THRA (NM_199334.3:c.-298 + 5G>A) missense mutation in the first intron in the 5' untranslated region (UTR) of THRA, with causal variant prediction with Combined Annotation Dependent Depletion placing the mutation in the top 1% most deleterious variants (scaled C-score 21.7). We speculate that this mutation causes an exon skipping event affecting the 5'UTR and protein-coding region, thereby resulting in abnormal or absent TRα1, although supporting clinical, genetic, and/or functional analyses are required to upgrade the pathogenicity classification from uncertain significance to pathogenic/likely pathogenic. The three cases describing \"classical\" RTH caused by THRB mutations showcase the consequences of misdiagnosis, with 2 patients prescribed medications that could exacerbate symptoms and one child presenting with behavioral problems that might benefit from tailored management with hormone therapies.</p><p><strong>Conclusion: </strong>This report not only highlights the importance of a high index of suspicion for RTH to prompt the genetic diagnosis but also contributes to a growing appreciation of the pathogenic role of non-coding variants in rare diseases.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":" ","pages":"1-9"},"PeriodicalIF":2.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}