Performance of renin assays in selecting fludrocortisone dose in children with adrenal disorders.

Children with salt-wasting adrenal insufficiency are managed with glucocorticoid and mineralocorticoid replacement. Measurement of renin activity or concentration alongside blood electrolyte levels is used to monitor the adequacy of mineralocorticoid replacement. Our unit changed from using renin activity to renin concentration and carried out a service review to assess whether this influenced decision-making for fludrocortisone dosing. In total, 50 measurements of plasma renin activity and 50 of renin concentration were analysed on separate cohorts before and after the assay change, with values standardised to multiples of the upper limit of normal (MoU) to allow comparison between assays. We were more likely to increase the fludrocortisone dose for a raised renin concentration than a raised renin activity. The renin concentration MoU was more strongly related to plasma sodium (negatively) and 17α-hydroxyprogesterone (17α-OHP) (positively) than the renin activity MoU. Using a MoU cut-off of 1.5, a decision to increase the dose of fludrocortisone was more likely to be made when using the renin concentration assay compared with the activity assay. Using a cut-off of 40 nmol/L for 17α-OHP, a decision not to change the fludrocortisone dose when 17α-OHP was <40 was more likely when using the renin concentration assay. For both assays, a plasma sodium <140 mmol/L was more likely to lead to a fludrocortisone dose increase, and most likely for the renin concentration assay. Overall, the decision to adjust fludrocortisone dose in this cohort of children with adrenal insufficiency was better supported by the biochemical parameters when based on renin concentration results and clinical status.

Cortisol Levels During Acute Illnesses in Children and Adolescents: A Systematic Review.

Importance: Endogenous cortisol levels in children and adolescents during acute illnesses can contribute to the evidence base required to optimize glucocorticoid (GC) stress doses for children and adolescents known to have GC deficiency. Objective: To identify endogenous cortisol levels during a range of acute illnesses in children and adolescents without GC deficiency from published evidence. Evidence Review: CINAHL, Cochrane Library, Cochrane Database of Systematic Reviews, Embase, and MEDLINE were searched for studies published between January 1, 2000, and June 30, 2020. Two reviewers independently identified relevant studies. Differences were resolved by joint discussion. Inclusion criteria were common acute illnesses, age from 1 month to 18 years, and basal blood cortisol levels obtained within 48 hours of presentation. Studies with fewer than 5 participants and those that included participants known to have GC deficiency or a history of treatment that could affect cortisol levels were excluded from the review. Data for predefined fields were extracted and independently checked by separate pairs of reviewers. Overall weighted means and pooled SDs for cortisol levels were calculated. Findings: All 15 studies included were hospital based and included 864 unique participants: 14 studies were prospective observational studies, 1 was part of a trial, and 5 included control individuals. Mean cortisol levels were higher in all participants with an acute illness (n = 689) than in controls (n = 175) (difference in weighted means, 18.95 µg/dL; 95% CI, 16.68-21.22 µg/dL). Cortisol levels were highest in patients with bacterial meningitis (weighted mean [pooled SD], 46.42 [22.24] µg/dL) and were more than 3-fold higher in the group with severe gastroenteritis (weighted mean [pooled SD], 39.64 [21.34] µg/dL) than in the control group. Among the subgroups with sepsis, those with shock had lower cortisol levels than those without shock (weighted mean [pooled SD], 27.83 [36.39] µg/dL vs 37.00 [23.30] µg/dL), but levels in nonsurvivors did not differ from levels in survivors (weighted mean [pooled SD], 24.89 [51.65] µg/dL vs 30.53 [30.60] µg/dL). Conclusions and Relevance: This systematic review found that, in children and adolescents without GC deficiency, circulating cortisol levels were higher during acute illnesses than those in controls and also varied across a range of acute illnesses. Whether these levels need to be achieved with exogenous GC stress doses tailored according to the nature and severity of the illness in children and adolescents with GC deficiency warrants investigation.

Notes for the general paediatrician: managing thyrotoxicosis in children and young people.

Thyrotoxicosis due to hyperthyroidism is a serious disorder in childhood often presenting to general paediatricians with a range of clinical manifestations. The commonest cause is Graves' disease, an autoimmune disorder resulting from thyrotropin receptor stimulation by autoantibodies. Early recognition and accurate interpretation of investigations are essential to achieve and maintain a euthyroid state. This will not only optimise growth, development and transition from childhood to young adult life but also avoid the potentially severe and life-threatening complications of acute thyrotoxicosis. In this review, we have focussed on the general paediatrician's perspective of the presentation and management of thyrotoxicosis and the need to network with specialist paediatric endocrine centres to optimise patient care. We have discussed nuances of therapy, side effects and long-term outcomes, while recognising that limited remission rates in this age group often necessitate more definitive management. While carbimazole is usually used as first-line medical therapy, we have provided useful information to guide paediatricians in the discussion of individualised safe and effective treatment plans for both short-term and long-term management.

Thyroid scintigraphy differentiates subtypes of congenital hypothyroidism.

INTRODUCTION: UK screening for congenital hypothyroidism (CH) is based on dried blood spot Thyroid Stimulating Hormone (TSH). Scintigraphy may identify CH subtypes classified as dysplasia, gland in situ (GIS) and ectopia, but is not performed in all centres. We retrospectively investigated the role of scintigraphy to identify CH subtypes in a single tertiary centre cohort. METHODS: Babies who screened positive for CH between 2007 and 2017 were studied (n=418 of 534 783). Scintigraphy outcomes were correlated with TSH and levothyroxine dose. GIS patients were analysed for 3-year outcomes. RESULTS: 303 patients started levothyroxine. Scintigraphy demonstrated three subtypes: GIS (n=139, 46%) ectopia (n=84, 28%) and dysplasia (n=80, 26%). Three-year follow up demonstrated permanence in 54% of 37 GIS cases. DISCUSSION: Thyroid scintigraphy differentiates subtypes of CH and suggests a higher than expected proportion of patients with GIS and ectopia. CH is permanent in half of those with GIS.

No evidence of an increase in early infant mortality from congenital adrenal hyperplasia in the absence of screening.

OBJECTIVE: Congenital adrenal hyperplasia (CAH) is not currently included in the UK newborn screening programme. We investigated the hypothesis that, owing to non-specificity of symptoms, a proportion of males affected by salt-wasting (SW) CAH have died in infancy without being diagnosed. DESIGN: Stored newborn screening blood spot samples were analysed for 17α-hydroxyprogesterone (17-OHP) in the following groups: Infants born in the North West of England, 1994 to 2006, who had died by 6 months age; (n=1198), a neonatal reference group (full-term n=100; preterm n=100) and a CAH positive control group. A newborn blood spot sample collected before diagnosis was available in 29/61 CAH patients recruited. SW CAH was present in 18/29 patients (16 males and 2 females). Samples from the deceased group with elevated 17-OHP were analysed for 8 common mutations in the 21-hydroxylase gene (CYP21A2). SETTING: North West of England. RESULTS: Grouped by gestational age, mean (maximum) blood spot 17-OHP in nmol/L was as follows. Deceased full-term n=279, 6 (107); deceased premature n=365, 28 (251); deceased unknown gestational age n=553, 13 (>394). In the SW positive control group, the lowest level of 17-OHP was 179 nmol/L and 14 had levels greater than the highest standard (>268 to >420 nmol/L). All samples from the deceased group with 17-OHP results >179 nmol/L (n=6) and a further 13 samples underwent mutation analysis. No mutations were identified. CONCLUSIONS: Our findings do not support the hypothesis that, in our unscreened population, males affected by SW CAH are dying prior to diagnosis.