Thyrotoxicosis due to hyperthyroidism is a serious disorder in childhood often presenting to gene... more 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 longterm management.
Anti-oestrogen therapy is being used in an attempt to prevent breast cancer but no intermediate e... more Anti-oestrogen therapy is being used in an attempt to prevent breast cancer but no intermediate end points of the effect of tamoxifen on the normal breast are available. Therefore, the purpose of this study was to develop a physiological measure of oestrogen action on the breast. We measured oestrogen-stimulated and -inhibited proteins in breast secretions from women on and off anti-oestrogen therapy. Two oestrogen-stimulated proteins (pS2 and cathepsin D) and oestrogen-inhibited proteins (CP15, gross cystic disease fluid protein 15; Apo ,: apolipoprotein D) were measured. Premenopausal women had significantly higher pS2 and cathepsin D in association with lower Apo D and CP15 secretion levels compared to post-menopausal women. Sequential nipple aspirates from women treated with the luteinizing hormone releasing hormone agonist goserelin (n = 9), tamoxifen (n = 9) and hormone replacement therapy (HRT) (n = 26) were measured. Following treatment with goserelin, median nipple secretion levels of pS2 fell (P < 0.02) and Apo D and CP15 rose significantly (P < 0.03 and P < 0.05 respectively). Similar changes were seen on tamoxifen therapy but not in untreated control women. Treatment with HRT resulted in a rise of pS2 (P < 0.001) and a fall in Apo D (P < 0.05). Measurement of pS2 and Apo D in nipple aspirates may prove useful intermediate end point of breast responsiveness to anti-oestrogens.
40th Meeting of the British Society for Paediatric Endocrinology and Diabetes, Mar 1, 2012
Context: Childhood obesity is increasingly associated with type 2 diabetes (T2D). Metformin reduc... more Context: Childhood obesity is increasingly associated with type 2 diabetes (T2D). Metformin reduces the risk for T2D in adult obese nondiabetic patients, but the evidence in obese children and young people is inconclusive. Objective: The objective of the study was to assess the effect of metformin on body mass index SD score (BMI-SDS), metabolic risk factors, and adipokines. Design: This was a prospective, randomized, double-blind, placebo-controlled trial. Setting: The study was conducted at six pediatric endocrine centers in the United Kingdom. Participants: One hundred fifty-one obese children and young people with hyperinsulinemia and/or impaired fasting glucose or impaired glucose tolerance (metformin: 74, placebo: 77). The study was comprised of 67.5% females, 65.6% postpubertal individuals, and 23.8% British Asian or Afro-Caribbean participants. The age range was 8-18 yr, the mean age was 13.7 (SD 2.3) yr, and the mean BMI-SDS was ϩ3.4 (SD 0.5). Interventions: The intervention included metformin 1 g in the morning and 500 mg in the evening vs. placebo for 6 months. Main Outcome Measure: The main outcome measure was a reduction in BMI-SDS at 6 months. Secondary outcomes included insulin and glucose levels from oral glucose tolerance tests, alanine aminotransferase (ALT), and adiponectin to leptin ratio (ALR) at 3 and 6 months. Results: Metformin was associated with a significant reduction in BMI-SDS compared with placebo at 6 months [mean difference Ϫ0.1 SD (95% confidence interval Ϫ0.18 to Ϫ0.02), P ϭ 0.02]. Significant improvements at 3 months were found in the metformin group: fasting glucose, Ϫ0.16 mmol/liter (Ϫ0.31 to Ϫ0.00), P ϭ 0.047; ALT, 19% (5-36%), P ϭ 0.008; and ALR, 32% (4-67%), P ϭ 0.02. Conclusions: Metformin therapy has a beneficial treatment effect over placebo for BMI-SDS, fasting glucose, ALT, and ALR ratio at 3 months, with changes in BMI-SDS sustained at 6 months.
instruments, and to population-specific reference intervals created using conventional methods sh... more instruments, and to population-specific reference intervals created using conventional methods showed a high concordance of reference limits and their age-dependent dynamics. Cutoff points which would favor partitioning reference intervals into separate (distinct) age groups could not be identified. Conclusions: The indirect approach reported here is well-suited to create continuous reference intervals from clinical laboratory databases and bypasses the ethical and practical limitations of conventional procedures. The generated continuous reference intervals capture the dynamic nature of pediatric development more accurately than age groups and can therefore improve clinical decision making.
G557 Value of scintigraphy in identifying cause of congenital hypothyroidism
Background Identification of Congenital Hypothyroidism (CHT) with Blood Spot (BS) Thyroid Stimula... more Background Identification of Congenital Hypothyroidism (CHT) with Blood Spot (BS) Thyroid Stimulating Hormone (TSH) is an essential part of Newborn Screening (NBS) in the UK. A screen positive result requires confirmation with plasma free thyroxine (fT4) and TSH. Technetium-99m scintigraphy can be used to define size and location of the thyroid. We investigated the utility of scintigraphy to identify the cause of CHT and impact on clinical management. Methods Newborns who were screen positive for CHT (initial screening BS TSH >20 mU/L or >8 mU/L on initial sample confirmed in the second sample taken 7–10 days later) at an NBS centre between 2007 and 2017 had scintigraphy at diagnostic assessment. Scintigraphy data [normal/large gland (dyshormonogenesis), small/absent (dysplasia) and abnormal position (ectopia)] was tested for correlation with BS TSH, plasma TSH and fT4. Results 418 newborns were referred from 5 34 783 newborns screened by NBS. 303 had confirmed CHT and underwent scintigraphy. The largest group was dyshormonogenesis (n=139, 45.7%) followed by ectopia (n=84, 27.6%) and dysplasia (n=80, 26.3%). Median BS TSH (mU/L) was lower in dyshormonogenesis than in ectopia and dysplasia [23.0 vs 106.0 vs 172.0][p<0.001]. Plasma TSH showed similar differences. fT4 levels (pmol/L) were higher in dyshormonogenesis than in ectopia and dysplasia [12.1 vs 9.6 vs 4.0][p<0.001]. Initial levothyroxine doses (micrograms/day) were 25.0, 37.5 and 37.5 respectively [p<0.001]. Conclusions Thyroid scintigraphy at this NBS centre over a 10 year period demonstrates dyshormonogenesis is by far the most frequent form of CHT and over 3 times more common than the historical frequency of 10%–15%. This is a paradigm shift in our understanding about the causes of CHT and has significant implications for genetic counselling and testing for families. Scintigraphy identifies and locates ectopia which might otherwise be incorrectly classified as dysplasia. Accurate CHT classification is crucial for initial levothyroxine dosage.
OBJECTIVE Acromegaly is associated with reduced life expectancy, while therapeutic 'cure' (define... more OBJECTIVE Acromegaly is associated with reduced life expectancy, while therapeutic 'cure' (defined by achievement of GH levels <5 mU/l) is associated with normalization of life expectancy. Surgery remains the treatment of choice but in those in whom operative 'cure' is not achieved, radiotherapy and/or medical treatment are valuable treatment modalities. The chance of subsequent 'cure' with radiotherapy or somatostatin analogue therapy is increased if the post-operative GH level is reduced below 30 mU/l. Using strict criteria for cure and a single dedicated pituitary surgeon, two large European studies reported 'cure' rates of 42% and 56%. In the Manchester region, surgery for these patients has been performed by a number of neurosurgeons, with no specific designated pituitary surgeon dominating the picture. We wished to examine the impact of this surgical strategy on cure rates and the incidence of a post-operative GH level below 30 mU/l. DESIGN We reviewed the GH results between 1974 and 1997 for every acromegalic who had been referred to the endocrine departments of the two Manchester hospitals responsible for the majority of pituitary disease referrals in Manchester and who had been subsequently referred for pituitary surgery. PATIENTS AND MEASUREMENTS Seventy-three (33 male) patients had had GH status assessed before and after surgery by an OGTT or GH profile. The
instruments, and to population-specific reference intervals created using conventional methods sh... more instruments, and to population-specific reference intervals created using conventional methods showed a high concordance of reference limits and their age-dependent dynamics. Cutoff points which would favor partitioning reference intervals into separate (distinct) age groups could not be identified. Conclusions: The indirect approach reported here is well-suited to create continuous reference intervals from clinical laboratory databases and bypasses the ethical and practical limitations of conventional procedures. The generated continuous reference intervals capture the dynamic nature of pediatric development more accurately than age groups and can therefore improve clinical decision making.
Apolipoprotein E polymorphism and lipoproteins in insulin-treated diabetes mellitus
Atherosclerosis, 1989
... PHW and MI received financial assistance from the North West Regional Health Authority, Eli L... more ... PHW and MI received financial assistance from the North West Regional Health Authority, Eli Lilly and Co. ... 27 Curtiss, LJ and Witztum, JL, Plasma apolipoproteins AI, All, B, CI and E are glucosylated in hyperglycaemic diabetic subjects, Diabetes, 34 (1985) 452. References. ...
In cancer models, thrombospondin-1 (TSP-1) has been shown to inhibit angiogenesis or promote meta... more In cancer models, thrombospondin-1 (TSP-1) has been shown to inhibit angiogenesis or promote metastasis by increasing adhesion of malignant cells to endothelium. To determine the role of TSP-1 in breast cancer and breast cancer angiogenesis, we have measured TSP-1 in plasma and tumour cytosols and compared levels to established clinicopathological prognostic parameters and intratumoural microvessel density. TSP-1 was measured, by radioimmunoassay, in plasma (pTSP-1) and tumour cytosols (cTSP-1) of women with early breast cancer (EBC) (n=71). pTSP-1 in EBC was compared to pTSP-1 levels in women with advanced breast cancer (ABC) (n=66), normal controls (n=77) and was correlated with prognostic features and microvessel density (MVD) (measured by CD31 immunostaining). cTSP-1 levels were compared to prognostic features and microvessel density. pTSP-1 in women with EBC (median 484, IQR 344-877 ng/ml) and ABC (median 588, IQR 430-952 ng/ml) were elevated when compared to normal controls (median 21, IQR 175-247) (p<0.001). Women with lymph node metastases (n=35) had higher levels of TSP-1 (median 799 ng/ml, IQR 455-943) than women who were node negative (median 343 ng/ml, IQR 267-514) (n=36) (p<0.05). Levels of pTSP-1 in EBC correlated with MVD (R=0.39, p<0.05). Levels of TSP-1 in tumour cytosols of women with EBC (median 1714, IQR 893-5283 ng/ml) correlated with microvessel density (R=0.46, p<0.01). Circulating levels of TSP-1 appear to be a marker of breast cancer aggressiveness and in breast cancer may have a pro-angiogenic rather than anti-angiogenic role.
to the needs of children and their parents. Further research is required to explore the views of ... more to the needs of children and their parents. Further research is required to explore the views of children and bereaved parents who have experienced deferred consent.
An audit to assess the impact of increasing the borderline blood spot TSH cut-off on the detection of cases of congenital hypothyroidism (CHT) identified via newborn screening
Context: Active surveillance of primary congenital hypothyroidism (CH) in a multiethnic populatio... more Context: Active surveillance of primary congenital hypothyroidism (CH) in a multiethnic population with established newborn bloodspot screening. Objective: To estimate performance of newborn screening for CH at different test thresholds and calculate incidence of primary CH.
IMPORTANCE Endogenous cortisol levels in children and adolescents during acute illnesses can cont... more 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.
P021 An evaluation of the cystic fibrosis newborn screening service at Royal Manchester Children's Hospital - experience from a tertiary service provider in Northwest United Kingdom
Thyrotoxicosis due to hyperthyroidism is a serious disorder in childhood often presenting to gene... more 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 longterm management.
Anti-oestrogen therapy is being used in an attempt to prevent breast cancer but no intermediate e... more Anti-oestrogen therapy is being used in an attempt to prevent breast cancer but no intermediate end points of the effect of tamoxifen on the normal breast are available. Therefore, the purpose of this study was to develop a physiological measure of oestrogen action on the breast. We measured oestrogen-stimulated and -inhibited proteins in breast secretions from women on and off anti-oestrogen therapy. Two oestrogen-stimulated proteins (pS2 and cathepsin D) and oestrogen-inhibited proteins (CP15, gross cystic disease fluid protein 15; Apo ,: apolipoprotein D) were measured. Premenopausal women had significantly higher pS2 and cathepsin D in association with lower Apo D and CP15 secretion levels compared to post-menopausal women. Sequential nipple aspirates from women treated with the luteinizing hormone releasing hormone agonist goserelin (n = 9), tamoxifen (n = 9) and hormone replacement therapy (HRT) (n = 26) were measured. Following treatment with goserelin, median nipple secretion levels of pS2 fell (P < 0.02) and Apo D and CP15 rose significantly (P < 0.03 and P < 0.05 respectively). Similar changes were seen on tamoxifen therapy but not in untreated control women. Treatment with HRT resulted in a rise of pS2 (P < 0.001) and a fall in Apo D (P < 0.05). Measurement of pS2 and Apo D in nipple aspirates may prove useful intermediate end point of breast responsiveness to anti-oestrogens.
40th Meeting of the British Society for Paediatric Endocrinology and Diabetes, Mar 1, 2012
Context: Childhood obesity is increasingly associated with type 2 diabetes (T2D). Metformin reduc... more Context: Childhood obesity is increasingly associated with type 2 diabetes (T2D). Metformin reduces the risk for T2D in adult obese nondiabetic patients, but the evidence in obese children and young people is inconclusive. Objective: The objective of the study was to assess the effect of metformin on body mass index SD score (BMI-SDS), metabolic risk factors, and adipokines. Design: This was a prospective, randomized, double-blind, placebo-controlled trial. Setting: The study was conducted at six pediatric endocrine centers in the United Kingdom. Participants: One hundred fifty-one obese children and young people with hyperinsulinemia and/or impaired fasting glucose or impaired glucose tolerance (metformin: 74, placebo: 77). The study was comprised of 67.5% females, 65.6% postpubertal individuals, and 23.8% British Asian or Afro-Caribbean participants. The age range was 8-18 yr, the mean age was 13.7 (SD 2.3) yr, and the mean BMI-SDS was ϩ3.4 (SD 0.5). Interventions: The intervention included metformin 1 g in the morning and 500 mg in the evening vs. placebo for 6 months. Main Outcome Measure: The main outcome measure was a reduction in BMI-SDS at 6 months. Secondary outcomes included insulin and glucose levels from oral glucose tolerance tests, alanine aminotransferase (ALT), and adiponectin to leptin ratio (ALR) at 3 and 6 months. Results: Metformin was associated with a significant reduction in BMI-SDS compared with placebo at 6 months [mean difference Ϫ0.1 SD (95% confidence interval Ϫ0.18 to Ϫ0.02), P ϭ 0.02]. Significant improvements at 3 months were found in the metformin group: fasting glucose, Ϫ0.16 mmol/liter (Ϫ0.31 to Ϫ0.00), P ϭ 0.047; ALT, 19% (5-36%), P ϭ 0.008; and ALR, 32% (4-67%), P ϭ 0.02. Conclusions: Metformin therapy has a beneficial treatment effect over placebo for BMI-SDS, fasting glucose, ALT, and ALR ratio at 3 months, with changes in BMI-SDS sustained at 6 months.
instruments, and to population-specific reference intervals created using conventional methods sh... more instruments, and to population-specific reference intervals created using conventional methods showed a high concordance of reference limits and their age-dependent dynamics. Cutoff points which would favor partitioning reference intervals into separate (distinct) age groups could not be identified. Conclusions: The indirect approach reported here is well-suited to create continuous reference intervals from clinical laboratory databases and bypasses the ethical and practical limitations of conventional procedures. The generated continuous reference intervals capture the dynamic nature of pediatric development more accurately than age groups and can therefore improve clinical decision making.
G557 Value of scintigraphy in identifying cause of congenital hypothyroidism
Background Identification of Congenital Hypothyroidism (CHT) with Blood Spot (BS) Thyroid Stimula... more Background Identification of Congenital Hypothyroidism (CHT) with Blood Spot (BS) Thyroid Stimulating Hormone (TSH) is an essential part of Newborn Screening (NBS) in the UK. A screen positive result requires confirmation with plasma free thyroxine (fT4) and TSH. Technetium-99m scintigraphy can be used to define size and location of the thyroid. We investigated the utility of scintigraphy to identify the cause of CHT and impact on clinical management. Methods Newborns who were screen positive for CHT (initial screening BS TSH >20 mU/L or >8 mU/L on initial sample confirmed in the second sample taken 7–10 days later) at an NBS centre between 2007 and 2017 had scintigraphy at diagnostic assessment. Scintigraphy data [normal/large gland (dyshormonogenesis), small/absent (dysplasia) and abnormal position (ectopia)] was tested for correlation with BS TSH, plasma TSH and fT4. Results 418 newborns were referred from 5 34 783 newborns screened by NBS. 303 had confirmed CHT and underwent scintigraphy. The largest group was dyshormonogenesis (n=139, 45.7%) followed by ectopia (n=84, 27.6%) and dysplasia (n=80, 26.3%). Median BS TSH (mU/L) was lower in dyshormonogenesis than in ectopia and dysplasia [23.0 vs 106.0 vs 172.0][p<0.001]. Plasma TSH showed similar differences. fT4 levels (pmol/L) were higher in dyshormonogenesis than in ectopia and dysplasia [12.1 vs 9.6 vs 4.0][p<0.001]. Initial levothyroxine doses (micrograms/day) were 25.0, 37.5 and 37.5 respectively [p<0.001]. Conclusions Thyroid scintigraphy at this NBS centre over a 10 year period demonstrates dyshormonogenesis is by far the most frequent form of CHT and over 3 times more common than the historical frequency of 10%–15%. This is a paradigm shift in our understanding about the causes of CHT and has significant implications for genetic counselling and testing for families. Scintigraphy identifies and locates ectopia which might otherwise be incorrectly classified as dysplasia. Accurate CHT classification is crucial for initial levothyroxine dosage.
OBJECTIVE Acromegaly is associated with reduced life expectancy, while therapeutic 'cure' (define... more OBJECTIVE Acromegaly is associated with reduced life expectancy, while therapeutic 'cure' (defined by achievement of GH levels <5 mU/l) is associated with normalization of life expectancy. Surgery remains the treatment of choice but in those in whom operative 'cure' is not achieved, radiotherapy and/or medical treatment are valuable treatment modalities. The chance of subsequent 'cure' with radiotherapy or somatostatin analogue therapy is increased if the post-operative GH level is reduced below 30 mU/l. Using strict criteria for cure and a single dedicated pituitary surgeon, two large European studies reported 'cure' rates of 42% and 56%. In the Manchester region, surgery for these patients has been performed by a number of neurosurgeons, with no specific designated pituitary surgeon dominating the picture. We wished to examine the impact of this surgical strategy on cure rates and the incidence of a post-operative GH level below 30 mU/l. DESIGN We reviewed the GH results between 1974 and 1997 for every acromegalic who had been referred to the endocrine departments of the two Manchester hospitals responsible for the majority of pituitary disease referrals in Manchester and who had been subsequently referred for pituitary surgery. PATIENTS AND MEASUREMENTS Seventy-three (33 male) patients had had GH status assessed before and after surgery by an OGTT or GH profile. The
instruments, and to population-specific reference intervals created using conventional methods sh... more instruments, and to population-specific reference intervals created using conventional methods showed a high concordance of reference limits and their age-dependent dynamics. Cutoff points which would favor partitioning reference intervals into separate (distinct) age groups could not be identified. Conclusions: The indirect approach reported here is well-suited to create continuous reference intervals from clinical laboratory databases and bypasses the ethical and practical limitations of conventional procedures. The generated continuous reference intervals capture the dynamic nature of pediatric development more accurately than age groups and can therefore improve clinical decision making.
Apolipoprotein E polymorphism and lipoproteins in insulin-treated diabetes mellitus
Atherosclerosis, 1989
... PHW and MI received financial assistance from the North West Regional Health Authority, Eli L... more ... PHW and MI received financial assistance from the North West Regional Health Authority, Eli Lilly and Co. ... 27 Curtiss, LJ and Witztum, JL, Plasma apolipoproteins AI, All, B, CI and E are glucosylated in hyperglycaemic diabetic subjects, Diabetes, 34 (1985) 452. References. ...
In cancer models, thrombospondin-1 (TSP-1) has been shown to inhibit angiogenesis or promote meta... more In cancer models, thrombospondin-1 (TSP-1) has been shown to inhibit angiogenesis or promote metastasis by increasing adhesion of malignant cells to endothelium. To determine the role of TSP-1 in breast cancer and breast cancer angiogenesis, we have measured TSP-1 in plasma and tumour cytosols and compared levels to established clinicopathological prognostic parameters and intratumoural microvessel density. TSP-1 was measured, by radioimmunoassay, in plasma (pTSP-1) and tumour cytosols (cTSP-1) of women with early breast cancer (EBC) (n=71). pTSP-1 in EBC was compared to pTSP-1 levels in women with advanced breast cancer (ABC) (n=66), normal controls (n=77) and was correlated with prognostic features and microvessel density (MVD) (measured by CD31 immunostaining). cTSP-1 levels were compared to prognostic features and microvessel density. pTSP-1 in women with EBC (median 484, IQR 344-877 ng/ml) and ABC (median 588, IQR 430-952 ng/ml) were elevated when compared to normal controls (median 21, IQR 175-247) (p<0.001). Women with lymph node metastases (n=35) had higher levels of TSP-1 (median 799 ng/ml, IQR 455-943) than women who were node negative (median 343 ng/ml, IQR 267-514) (n=36) (p<0.05). Levels of pTSP-1 in EBC correlated with MVD (R=0.39, p<0.05). Levels of TSP-1 in tumour cytosols of women with EBC (median 1714, IQR 893-5283 ng/ml) correlated with microvessel density (R=0.46, p<0.01). Circulating levels of TSP-1 appear to be a marker of breast cancer aggressiveness and in breast cancer may have a pro-angiogenic rather than anti-angiogenic role.
to the needs of children and their parents. Further research is required to explore the views of ... more to the needs of children and their parents. Further research is required to explore the views of children and bereaved parents who have experienced deferred consent.
An audit to assess the impact of increasing the borderline blood spot TSH cut-off on the detection of cases of congenital hypothyroidism (CHT) identified via newborn screening
Context: Active surveillance of primary congenital hypothyroidism (CH) in a multiethnic populatio... more Context: Active surveillance of primary congenital hypothyroidism (CH) in a multiethnic population with established newborn bloodspot screening. Objective: To estimate performance of newborn screening for CH at different test thresholds and calculate incidence of primary CH.
IMPORTANCE Endogenous cortisol levels in children and adolescents during acute illnesses can cont... more 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.
P021 An evaluation of the cystic fibrosis newborn screening service at Royal Manchester Children's Hospital - experience from a tertiary service provider in Northwest United Kingdom
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