Endocrine Abstracts

Introduction: Cushing’s syndrome in childhood usually results from exogenous steroids, which can potentially cause adrenal suppression and leave the patient at risk of adrenal crisis. Classically this occurs secondary to oral glucocorticoid medication, but there are also frequent reports resulting from high dose topical steroids. Prolonged intranasal or inhaled steroids have also been implicated, however cases resulting from the prolonged use of ocular steroids are extrem...

Salt-losing conditions can be challenging to manage well in infancy and early childhood. We describe a child with both salt-wasting 21-hydroxylase deficiency (SW21OHD) and cystic fibrosis (CF).A male infant, JW, birth weight 3.5 kg, presented with a salt-wasting crisis on day 9 of life with hyponatraemia, hyperkalaemia, and weight loss of 415 g. Serum 17-hydroxyprogesterone (17OHP) was >1000 nmol/l and a diagnosis of SW21OHD was made. Neonatal screen...

Background: CYP11B2 encodes a steroid 11/18-β-hydroxylase that functions in mitochondria in the zonaglomerulosa of the adrenal cortex to synthesize the mineralocorticoid aldosterone. The enzyme catalyzes three necessary reactions: 11-β-hydroxylation of 11-deoxycorticosterone (11-DOC) to corticosterone, 18-hydroxylation of corticosterone to 18-hydroxycorticosterone (18-OHB); and 18-oxidation of 18-hydroxycorticosterone to aldosterone. Aldosterone synthase (<e...

Aberrant pseudoexon inclusion is rarely recognised as a cause of human disease. Here we report two novel, compound heterozygous mutations in nicotinamide nucleotide transhydrogenase (NNT), one of which activates a pseudoexon, as the cause of familial glucocorticoid deficiency in two siblings. Whole-exome sequencing identified a single novel, heterozygous variant (R71X) in both affected individuals. Follow-up cDNA analysis identified the pseudoexon inclusion (p.P998_D9...

Introduction: Cerebral oedema has rarely been reported in adrenal insufficiency. We report a case of decompensated cerebral oedema due to autoimmune adrenalitis.Case report: A 12-year-old boy presented to hospital with a 1 day history of headache, fever up to 39.9 °C, confusion, diarrhoea, and vomiting. He had a left-sided ptosis, reduced conscious level (Glasgow coma scale 8/15) and was hypertensive (blood pressure 134/90 mmHg). He required intubat...

Introduction: Congenital adrenal hyperplasia (CAH) is a rare condition affecting steroid-hormone synthesis. We reviewed the investigation and management of children with CAH against current international guidelines and explored variation by region and specialty of responsible clinician.Methods: Active national surveillance of new diagnoses of CAH in children under age 16 years and resident in Great Britain, undertaken prospectively from 2007 to 2009....

Congenital adrenal hyperplasia (CAH) has an estimated prevalence of one in 10 000–20 000 live births. Patients are described as salt wasting (SW), simple virilising (SV), or non-classical (NC). The CAH genotype is usually compound heterozygous.Aims: To characterise the cohort of CAH patients presenting to a regional centre 1994–2014, to quantify the allelic frequency of CYP21A2 mutations and to examine genotype–phenotype associations.<...

Background: Limited evidence exists regarding the effect of antenatal prednisolone (ANP) on neonatal adrenal function. Our regional neonatal unit screens these babies by measuring three random serum cortisol levels 8 h apart on day 3 of life. Adrenal function is considered adequate if two cortisol levels are >100 nmol/l. Those with inadequate random cortisol levels undergo a low-dose Synacthen test (LDST). Our survey of UK tertiary Paediatric Endocrinology centres revealed...

Introduction: Childhood adrenocortical tumours (ACT) are extremely rare (worldwide incidence: 0.3/million per year). Most affected are young girls – female:male 2:1, peak age at diagnosis −3.5 years.Case report: A 2.5-year-old-girl presented with a 4-month history of greasy hair, acne, weight gain, especially around face and upper shoulders. She had irritability, daytime lethargy and night-time sleep disturbance. She later developed pubic hair...

Introduction: Atopic dermatitis can cause significant exudative fluid loss from a large body surface area in an infant leading to severe hyponatraemia.Case report: A 5-month-old boy was referred to the paediatric team from dermatology with severe cradle cap, eczema and fever. He also had faltering growth (weight: 4.95 kg, well below 0.4th centile) and moderate developmental delay. On examination, he had severe infected eczema over a large area of the sca...

Background: Endogenous Cushing’s syndrome (CS) in children remains a challenge to diagnose and exclude. 24-h urinary free cortisol (UFC) measurements are a convenient, non-invasive test for paediatric patients.Objective: To assess the screening accuracy of 24-h UFC measurements in paediatric patients referred to our centre for evaluation of possible CS.Methods: A retrospective review of children referred to our centre between ...

Mutations in CYP11A1, like those in STAR cause lipoid congenital adrenal hyperplasia manifesting with adrenal and gonadal insufficiencies along with derangements of the renin/angiotensin system. Increased adrenal size is usually a feature of STAR but not of CYP11A1 mutation. Milder forms presenting without all of these features have also been described. We present six patients from four families with CYP11A1 mutations discovered by ...

Introduction/aims: Adrenarche, the gradual increase in adrenal androgen secretion resulting in clinical features of pubic hair, axillary hair, body odour and acne, is independent from gonadotrophin-dependent central puberty. It is important that children presenting with these features are not unnecessarily investigated, whilst ensuring significant pathology is not overlooked.There is variation in practice in management of adrenarche. We identified curren...

Introduction: Severe generalised recessive dystrophic epidermolysis bullosa (RDEB) is a rare disorder resulting from loss of function mutations in the type VII collagen gene (COL7A1). Although RDEB is characterised by severe trauma induced skin blistering and erosions, it is a multisystem disorder with low bone mass as one of the many complications.Objectives: We sought to describe the prevalence of low bone mass, vertebral fractures and scolios...

Introduction: Hyperostosis-hyperphosphataemia syndrome (HHS) is a rare autosomal recessive condition caused by inactivating mutations in the GALNT3 gene, characterised by elevated serum phosphate and 1,25(OH)2 vitamin D, increased urinary tubular reabsorption of phosphate and hyperostosis of long bones.Case report: A 15-year-old boy (weight+1.05 S.D.; height −0.1 S.D.) with consanguineous parents of...

Background: Bone mass is low and fracture risk is higher in obese children. We wished to ascertain the relationships of obesity-related changes in hormones with skeletal microstructure.Method: Children aged 8–15 years matched by gender and pubertal stage were recruited into lean and obese groups (18 pairs). We used high resolution peripheral quantitative computed tomography (HRpQCT – resolution-82 μm) to assess three-dimensional cortical a...

Introduction: Hypocalcaemia is a recognised cause of neonatal seizures most often related to vitamin D deficiency in the mothers of exclusively breast fed infants. There have also been case reports of an underlying diagnosis of hyperparathyroidism in a reportedly well mother becoming apparent after the infant presents with hypocalcaemic seizures. Maternal hypercalcaemia suppresses parathyroid activity in the foetus, which causes transient neonatal hypocalcaemia.<p class="a...

Introduction: Bisphosphonate therapy (BPT) reduces osteoclast activity and may be associated with adynamic bone turnover. The extent of suppression of bone turnover and its determinants are unclear.Methods: Markers of bone metabolism were evaluated in 15 children (9M/6F) receiving cyclical BPT intravenously for osteoporosis. The median age at first biochemical assessment was 10.8 years (0.16, 16.3). Serum type I collagen cross-linked C-telopeptide (CTX),...

Background: Decreased bone mineral density using dual energy absorptiometry (DXA) is reported in mixed cohorts of testosterone treated and testosterone naïve men with Klinefelter syndrome (KS). Bone mass and body composition in men with congenital anorchia (CA) have not been reported.Hypothesis: Men with KS and CA treated with testosterone from adolescence have normal bone mass and body composition.Methods: DXA and pQCT were p...

Introduction: Hypercalcaemia secondary to malignancy is rare in children. PTH-rP secreted by malignant cells increases bone resorption and renal calcium retention causing hypercalcaemia. We report a case of hypercalcaemia refractory to bisphosphonate and corticosteroid therapy, but responsive to treatment with Denosumab.Case report: A 17-year-old boy with epidermolysis bullosa presented with advanced squamous cell carcinoma of the left leg and symptomati...

Background: The 24-hydroxylase enzyme is responsible for the degradation of 1,25-dihydroxyvitamin D3. Loss of function mutations of the gene encoding 24-hydroxylase, CYP24A1, may cause hypercalcaemia, nephrolithiasis and nephrocalcinosis, and are responsible for some cases of idiopathic hypercalcaemia of infancy.Case: The index case presented with faltering growth at 4 months old. She was hypercalcaemic with serum calcium 2.79 mmol/l (normal r...

Background: We present a teenager with type 1 diabetes who sustained a substantial weight loss of 20 kg over 15 months. He had minimal insulin requirements with an extraordinarily low HbA1c.Presentation: During his presentation with excessive weight loss, he had blood tests which revealed pre-renal failure, following which he was admitted for rehydration and assessment. Apparently he was consuming fluid in excess of 2 l/day. Ultrasound of kidneys was nor...

Introduction: The initial insulin doses for children with newly diagnosed type 1 diabetes mellitus (T1DM) are dependent on the degree of ketosis at presentation, reflecting the presence of insulin resistance. The concept of metabolic memory has heightened the importance of improving glycaemic control following diagnosis.Aim: To determine whether current local prescribing guidelines accurately predict insulin requirement at initiation of treatment followi...

A small for gestational age baby boy (weighing 2.3 kg) was delivered at term by emergency section for foetal bradycardia, to a 35-year-old mother with type 1 diabetes.He was admitted with suspected sepsis because of maternal colonization with group B streptococcus. He had hyperglycaemia (6–12 mmol/l), initially attributed to sepsis and was treated as such. Hyperglycaemia persisted, despite treatment and being clinically well.F...

Background: Care of patients with diabetes should include an assessment of bone health. It is now clear that patients with type I DM have lower bone mineral density which may be manifested as osteopenia in growing skeleton and higher risk of fractures.Objective: To assess bone modelling through the measurement of bone formation and resorption indexes in diabetic children and their correlations with metabolic parameters.Methods: We ...

Background: Children with HbA1cs in target within the first year of diagnosis of diabetes show tracking of future results1 and experience fewer long term complications.2 This phenomenon is called ‘metabolic memory.3 HbA1C depends on a combination of patient factors and quality of care offered by the team (intensive insulin, communication, and support). We hypothesized that well managed, supported, patients should achieve target HbA1cs at l...

Introduction: The prevalence of coeliac disease (CD) in type 1 diabetes (T1DM) is 4.4–11.1 vs 0.5% in the general population. The compliance to gluten free diet (GFD) in symptomatic patients vs those diagnosed on screening is significantly higher as expected. The impact of untreated CD on patients with T1DM ranges from malabsorption and frequent unexplained hypoglycaemia to no symptoms.Aims: i) To describe the demographics of our children with CD.</...

Introduction: Daytime support from the diabetes-team reduces pressure on acute services however out-of-hours less support exists and diabetes related attendances to A&E are a potentially avoidable burden on resources. With the introduction of paediatric diabetes best-practice-tariff, recommendations included 24 h access to trained diabetes professionals for patients with known diabetes. In 2013 our three institutions created a consultant led out-of-hours paediatric diabete...

Background: Type 1 diabetes mellitus is an autoimmune condition resulting in insulin deficiency, causing both long and short term complications. The Diabetes Control and Complications Trial (DCCT) demonstrated that tight glycaemic control and consequent lower HbA1c values reduced the risk of long-term complications. This can be achieved using multiple daily injections (MDI) or newer continuous subcutaneous insulin infusion (CSII) therapy. This is recommended by NICE for those ...

Introduction: Nearly all patients with type 1 diabetes mellitus develop diabetic retinopathy (DR) within 20 years of diagnosis. It is the second largest cause of blindness in those of working age in the UK. Several risk factors have been accepted by the Royal College of Ophthalmologists, including gender, duration of diabetes, glycaemic control, blood lipid profile, blood pressure, and renal impairment.Aim: To study the epidemiology of DR and its associa...

Introduction: Dyslipidaemia and diabetes mellitus have a complex relationship. Uncontrolled diabetes can result in hypertriglyceridaemia through decreased adipose tissue and muscle lipoprotein lipase activity. Conversely, insulin resistance and diabetes can occur in association with primary familial hyperlipidaemia. Eruptive xanthomas can be a presenting feature of the severe hypertriglyceridaemia found in familial hyperlipidaemia.Although there are repo...

Up to 25% of children and young people present in diabetic ketoacidosis (DKA) at diagnosis with type 1 diabetes (T1D). The ‘4 T’s’ campaign, a national Education awareness programme, was led by Diabetes UK in 2013. Our aim was to assess the effectiveness of this campaign locally, after our team also raised local awareness by promotion to primary care.This was a retrospective audit of referrals of children newly presenting with T1D from pri...

Background: Diabetic retinopathy is a frequent cause of vision loss in young adults. NICE guidelines require services to offer annual retinal screening to all diabetic children aged ≥12 years. A local 2009–2010 audit identified 57% underwent screening but only 16% had results documented with the paediatric diabetes service, both areas requiring improvement. In 2011, the paediatric diabetes service formulated a standard operating procedure with the eye-screening prog...

Introduction: An important part of diabetes management is maintaining high standards of in-patient care. A previous audit in the south of England demonstrated difficulties consistently achieving standards identified as good practice. This audit aimed to identify current standards of in-patient care provided to children with type 1 diabetes across the Yorkshire and Humber region.Methods: The audit was conducted against in-patient care standards identified...

Diabetes mellitus is life threatening endocrine disorder with high morbidity and mortality, which is featured by persistent high blood glucose levels due to defect in the insulin secretion, insulin action or both. Extreme high blood glucose levels associated with diabetes leads to various organ dysfunction particularly nervous system, eye, cardiovascular system, and kidney. Kaempferol is a dietary bioflavonoid that is common in plant-derived foods and used in traditional medic...

Aims: We aimed to assess the effectiveness of an insulin pump service for children, describe the demographics of the pump population and to review the change in glycaemic control following initiation of pump therapy. We also assessed patient and staff perceptions of the service.Method: Patients commenced on CSII from July 2013 to July 2014.Data collected included demographics, deprivation scores, HbA1c before and during pump therap...

Introduction: Diabetic ketoacidosis (DKA) is a medical emergency, requiring careful fluid management and insulin administration. The guidelines published by the British Society for Paediatric Endocrinology and Diabetes (BSPED) in 2009 aim to standardise the approach to the management of paediatric DKA across NHS hospitals. Our aim was to report our experience in managing DKA in children in a district general hospital setting.Method: Retrospective case re...

Introduction: The diabetes education program for schools and nurseries at an inner city hospital was introduced in 2010. The team offers 3 h sessions ~5–6×/year with the diabetes CNS and specialist diabetes dietician.Aims: To assess the uptake of the sessions; to look at how sessions were offered and delivered; to analyse the evaluation forms filled out by the participants with particular focus on good points and suggestions for improvement; an...

Introduction: Following the introduction of best practice tariffs for paediatric diabetes, there are now clear guidelines that paediatric units should be able to provide 24 h medical cover and advice for diabetes children. This is a challenge most paediatric diabetes units are struggling to meet with mainly due to limited availability of consultant and diabetic nurse cover. Currently in most hospitals this responsibility lies with the on call registrars. Previous studies in th...

Background: Neonatal diabetes can present from birth to 6 months of age. This can often be confused with sepsis as there is considerable overlap of symptoms in this age group as illustrated below. We recommend an initial check of blood glucose concentrations in all sick infants who present to accident and emergency.Case report: A 7-week-old, born to nonconsanguineous parents presented with a temperature of 38.6 °C and a 1 day history of poor feedin...

Background: Celiac disease is frequently associated with type 1 diabetes mellitus, but is usually ill-defined and not usually suspected until the disease become advance.Aim: To study the prevalence, clinical profile and glycemic variability and the effect of gluten free diet on growth and diabetic control in celiac type 1 diabetes patients in a tertiary care referral centre in north India.Materials and method: Total of 256 patients...

Background: Diabetic ketoacidosis is characterized by biochemical tired of hyperglycemia, acidosis, and ketonemia. It remains a life threatening condition despite improvement in diabetic care, timely identification and intervention remains the backbone of treatment.Aim and objectives: i) To evaluate the clinical and biochemical prognostic markers in diabetic ketoacidosis. ii) To correlate the various prognostic markers with mortality in diabetic ketoacid...

Objectives: The Department of Health introduced a Best Practice Tariff (BPT) to finance Paediatric Diabetes Services in England, in response to variation in service provision and outcome. The tariff became mandatory in April 2013 and depends on achievement of 13 quality standards (QS). The West Midlands (WM) Region covers an area of 5020 square miles, where 2700 Children with Diabetes receive care from 15 Hospital Trusts who are members of the Regional Paediatric Diabetes Netw...

Introduction: Achieving optimum glycaemic control in young adults is challenging. Furthermore, transfer of care to adult services has been associated with deterioration in glycaemic control. We aimed to establish glycaemic control and rate of microvascular complications in young adults with childhood onset type 1 diabetes (T1D) and looked specifically at a subset of patients before and after transfer to adult care.Methods: A retrospective study of patien...

Objectives: To assess patient satisfaction with the transitional diabetes clinic service. Our transitional diabetes clinics (for 14–19 year olds) are run monthly by a multi disciplinary team comprising of a consultant, nurse and dietician each, from both adult and paediatric diabetes teams.Methods: An electronic tablet with the pre-programmed survey was handed out to 42 young people while they were waiting to be seen in clinic.<p class="abstext"...

Introduction: We present the contrasting cases of two siblings diagnosed with Wolfram’s syndrome aged 2 and 10 years old. We discuss several family factors which have made management of this rare condition even more complex, emphasising the importance of holistic medicine.Case: The older sibling was diagnosed with diabetes mellitus age 4. Parents struggled to cope with the diagnosis, however, and emotional and psychological support was offered. She ...

Introduction: Ovotesticular disorders of sexual development (DSD) are a rare form of DSD with co-existence of both ovarian and testicular tissue in one or both gonads.Case report: A term infant (weight+1.38 SDS) presented at birth with severe penoscrotal hypospadias, a small phallus and a right hemiscrotum with descended gonad (external masculinization score 1.5). Pelvic ultrasound revealed no mullerian structures, a small right gonad with probable epidi...

Introduction: Disorders of sex development (DSD) may present in the newborn as ambiguous genitalia. Gender determination and diagnosis must occur as quickly as possible to minimise parental distress. Aim: to evaluate the initial care of babies born with DSD, and identify areas for improvement.Methods: Detailed assessment of 14 neonatal presentations at a tertiary centre between 2012 and 2014 was undertaken. Based on local trust guidelines, several parame...

Introduction: Gynaecomastia (GM) is a major contributor to psychological morbidity in adolescent boys, yet there is a lack of evidence for effective treatment. It is known to develop due to the relatively higher diurnal oestradiol–testosterone ratio in early to mid puberty.Aims: We retrospectively looked to identify possible criteria for the selection of patients to predict optimal management of GM. We also examined the effect on the persistence of ...

Introduction: 45XO/46XY karyotype has varied phenotypic spectrum ranging from short stature, ambiguous genitalia (60%), clinical signs of Turner’s syndrome in both males and females and normal male phenotype. We report six phenotypically male cases with a varied clinical presentation.Case 1 and 2: Short stature: Two pre-pubertal, phenotypical males, were referred with concerns regarding short stature (height <0.4th centile, height velocity &#150...

Introduction: Women with Turner syndrome (TS) have a 13-year reduction in life expectancy compared to the general population. Cardiovascular disease (CVD), whether congenital or acquired, is the cause of death in around half of these women. Therefore, early identification of congenital heart defects, aortic abnormalities and risk factors for CVD is extremely important, and may have a significant impact on long-term outcomes of CVD in TS.Aim and methods: ...

Introduction: Craniopharyngiomas are rare, pituitary tumours which, though benign with good survival, carry high neuroendocrine morbidity. Optimum management remains controversial despite a UK consensus strategy (2005).Aim: To study disease- and treatment-related neuroendocrine, visual and cognitive outcomes in our most recent cohort, managed with individualised multidisciplinary decision making to limit hypothalamic morbidity.Pati...

Background: Bone age studies require X-ray of the left hand and wrist to assess skeletal maturity. The Tanner-Whitehouse 3 (TW3) scoring method provides an objective framework for calculating bone age and specifies exact placement of the hand. In our service we have noted a number of poor quality films, caused by difficulty with hand placement, e.g. scrunching of the fingers. This compromises the ability to score accurately and in a proportion necessitates re-X-ray, with time,...

Introduction: I report the case of a premature neonate who developed a transient hyperphosphatemia at 1 month of age with associated hyperuremia, hypercreatininemia and hyperparathyroidism.Case report: This baby girl was born by emergency caesarean section for maternal APH at 27+6 weeks. She had an uneventful neonatal period with minimal ventilation. She was treated with ibuprofen, amilorone and frusemide for a PDA with associated heart failure. Her ente...

We describe the development of a new adolescent gender identity dysphoria (GID) service in Northern Ireland (population 1.8 million). Historically patients with GID <18 years were referred to The London joint Tavistock UCH adolescent GID service on a case by case basis. Following the commissioning of a GID service in Northern Ireland, a team of clinical psychologists, paediatric endocrinology nurse specialists, psychiatrist and paediatric endocrinologists, the first GID cl...

Background: Adolescent polycystic ovarian syndrome (PCOS) is being diagnosed more frequently as the prevalence of childhood obesity increases. Adolescent PCOS has been associated with low birth weight (LBW), exaggerated adrenarche (EA) and metabolic syndrome in Mediterranean populations. This study describes the clinical phenotype of a cohort of northern European girls.Methods: A retrospective study of adolescents with PCOS, diagnosed according to the Ro...

Background: There are limited data in paediatric population on the association between vitamin D deficiency/treatment and glucose/insulin metabolism.Objective and hypotheses: This study aimed to investigate the effect of vitamin D therapy on glucose homeostasis, insulin resistance and bone turnover, in children with vitamin D deficiency.Method: 22 children aged 3 months to 10 years (nine males) who were diagnosed with vitamin D def...

Introduction: One third of children in the UK are overweight or obese. The Obesity Services for Children and Adolescents (OSCA) group have agreed upon a guideline for paediatricians on the assessment and management of obese children.Audit aim: To evaluate and improve the care of obese and overweight children.Method: Obese patients seen in secondary care were retrospectively audited from 2008 to 2014.Results: ...

Background: Childhood obesity is a growing problem worldwide, with serious effects on child health. Obese children are at a higher risk of developing metabolic co-morbidities earlier in life (WHO, 2013). Manchester has worse than national average levels of obesity, with an estimated 14 000 obese children (PHE, 2014).Aims and methods: A retrospective case note analysis of 117 obese paediatric patients, seen in our service between March 2012 and 2014, was ...

Recently, rare loss-of-function mutations of melanocortin-2-receptor accessory protein 2 (MRAP2) have been associated with severe, early-onset obesity in humans. In addition, whole body deletion and targeted brain specific deletion of the Mrap2 gene resulted in severe obesity in mice. In vitro data have shown Mrap2 interaction with the melanocortin-4-receptor (MC4R) affecting receptor signalling as a consequence. However, the mechanism by which Mrap2...

Introduction: Congenital hyperinsulinism (CHI) typically presents in the neonate, however a minority of cases (~ 35%) present later in infancy and childhood. We report the challenging case of an older infant presenting with hypoglycaemia, diagnosed with CHI and managed entirely within a secondary care setting.Case report: A 9-month-old macrosomic (99th centile) infant presented to the Children’s Emergency Department with hypoglycaemia and a 1 week h...

Introduction: Congenital hyperinsulinism (CHI) is the commonest cause of recurrent and persistent hypoglycaemia during the newborn period. The management of CHI in patients who are unresponsive or do not tolerate diazoxide includes the use of octreotide therapy which is given as a SUBCUTANEOUS injection, three to four times daily. We report a case of persistent CHI successfully treated with once monthly Lanreotide (a long acting somatostatin analogue).<p cla...

Introduction: Pallister–Hall syndrome (PHS) is characterized by a spectrum of anomalies which includes polydactyly, hypothalamic hamartoma, laryngotracheal cleft, bifid epiglottis, imperforate anus, and renal abnormalities. Hypoplastic cochlea is an infrequently reported association of PHS. The association of PHS with hyperinsulinaemic hypoglycaemia (HH) has not been previously reported in the literature.Case report: A baby girl was born by elective...

Introduction: Focal congenital hyperinsulinism (F-CHI) is caused by dual-hit pathology, comprising a paternally-inherited ABCC8/KCNJ11 mutation and somatic loss of the maternal allele at chromosome 11p15. This leads to dysregulation of insulin secretion and β-cell overgrowth with a focal domain.Objectives: To compare the proliferative index (PI) of the F-CHI lesion and non-lesion pancreatic tissues to age-matched control pancreata and insul...

The index case, born to non-consanguineous British parents, was born with a normal birth weight. He grew along the −2.9 S.D. centile from the age of 2 years. Eczema was diagnosed at the age of 2 weeks. Investigations at 3–4 years of age showed: IGF1<25 ng/ml, IGFBP3 1.29 (N 0.8–3.9), prolactin 265–653 mU/l (N 59–271), GH peak (glucagon test) 17.3 ug/l, normal GH peaks on overnight sampling, and an IGF1<25 ng/ml...

Background: Temple syndrome (TS) is a disorder caused by dysregulation of imprinted genes at chromosome 14q32. It is important to distinguish the growth pattern from other imprinting disorders such as Russell–Silver and Prader–Willi syndromes.Aims: To describe the growth pattern in TS.Methods: 51 cases were identified from 11 countries. Height, weight, birth weight and head circumference were converted to SDS using countr...

Introduction: Thyrotroph adenomas are extremely rare accounting for only 0.5–2.8% of paediatric pituitary adenomas. Almost 90% of thyrotropinomas are macroadenomas.Case report: A 9-year-old boy presented with acute onset of a right divergent squint on a background of 6 months of visual disturbance. Opthalmological assessment confirmed reduced visual acuity and visual field defects.MRI revealed a large macroadenoma invading the...

Introduction: Central precocious puberty (CPP) is rarer in boys than girls, therefore evidence is limited for interpreting LHRH testing in boys. Current recommendations also suggest use of basal LH.Objectives: i) Test efficacy of using basal LH and testosterone for predicting CPP in boys. ii) Establish diagnostic cut-offs for LHRH testing in boys.Method: Retrospective data collection of LHRH test results in 67 boys aged 2–10 y...

Background: Childhood-onset GH deficiency (CO-GHD) is perceived to be a cause of low bone density and osteoporosis in adulthood. Data on bone mass and body composition of GH-treated adolescents with CO-GHD at final height are inconsistent.Aims: To compare size/height corrected parameters of bone mass and body composition in adolescents with CO-GHD at final height.Method: Review of CO-GHD treated patients at final height between 200...

Introduction: Current recommendations for diagnosing central precocious puberty (CPP) in girls suggest using basal LH levels >0.3 IU/l to predict progression into CPP and using stimulated LH values >5 IU/l in the LHRH test to diagnose CPP. Our objectives were to test the efficacy of using basal LH values as well as to establish diagnostic cut-offs for LHRH tests.Method: Retrospective data collection of LHRH test results of 173 girls between 2 and...

Introduction: Hartsfield syndrome (#OMIM 615465) describes the rare co-occurrence of holoprosencephaly with ectrodactyly, associated with a spectrum of developmental defects including specific pituitary dysfunction.Case report: Our patient, a male infant, had several congenital abnormalities: bilateral cleft lip and palate, right sided microtia, bilateral ectrodactyly of the hands and feet and semilobar holoprosencephaly. Aged 5 weeks he was noted to be ...

Objectives: 1) When and how to investigate rarer causes of short stature. 2) Evidence for interventions to improve growth in metaphyseal chondrodysplasia, Schmid-type (MCDS).Background: The incidence of skeletal dysplasia is one in 5000, however individually these conditions are rare and prognosis unclear. There is genotypic and phenotypic heterogeneity and no current consensus on classification, which may include clinical, radiographic, molecular or his...

Introduction: Chromosome 18 rearrangements are postulated to be associated with short stature, of uncertain pathophysiology.Methods: Retrospective case review (short stature with chromosome 18 rearrangement), investigation for GH deficiency (peak GH <7 μg/l on glucagon or ITT, unless otherwise indicated) and determining response to GH treatment.Results: In 13 year six such cases were referred from the geneticists, mean ref...

Introduction: 3-M syndrome is associated with mutations in CUL7, OBSL1 and CCDC8 with the three proteins interacting within a novel growth pathway. The impact of this pathway on cellular growth has not been fully defined. We have shown that i) GH and IGF1 signalling are altered; ii) IGF2 expression is reduced and iii) expression of insulin receptor isoforms are altered in 3-M fibroblasts.Aim: To characterise the activa...

Background: IGF1 is the biochemical marker of growth as it is supposed to reflect the activity of the GH axis. The usefulness of IGF1 measurements in children under 3 years has not been verified to date.Aim: We analysed the relationship between serum IGF1 concentration and growth velocity (GV) in children under the age of 3 years.Methods: We compared 300 IGF1 concentrations taken in children younger than 3 years with their GV at ti...

Introduction: Multiple pituitary hormone deficiency (MPHD) and septo-optic dysplasia (SOD) are well known causes of hypopituitarism, but children with optic nerve hypoplasia (ONH) may also be at risk of hormone and neurocognitive disturbances. Clinical and neuroradiological findings of these three related conditions are characterised in this study, aiming to understand their pathophysiology.Design: Data from 140 patients with hypopituitarism (MPHD, SOD) ...

Introduction: Thickened pituitary stalk (TPS) and/or idiopathic central diabetes insipidus (ICDI) are rare in childhood, presenting to different (endocrine, oncology, ophthalmology) specialties. In the absence of other diagnostic features, agreed radiological definitions, biopsy (often too dangerous) or consensus management guidance, subsequent surveillance and treatment are uncertain. Cases may remain undiagnosed or evolve over decades.Aims: i) To longi...

Background: Childhood tumours of the hypothalamic pituitary axis (HPATs) are very rare and hence any single centre experience is limited. Without evidence-based guidance, treatment is individualised on a case basis. Survival rates are high, but at the expense of significant morbidity. Centralised care or wider multi-professional consultation may improve neuroendocrine and visual outcomes.Objective and hypotheses: 1. To facilitate multi-professional dial...

Background: Previous studies show poor consensus on the use of GH stimulation tests. Sex steroid priming and re-testing in the transition period are areas not previously surveyed. In light of more recent guidance and expert opinion, this survey aims to analyse the diagnostic processes employed in the diagnosis of GH deficiency (GHD) in the UK.Methods: Data were collected from tertiary paediatric endocrinologists, paediatricians with a specialist interest...

Introduction: Xanthogranulomatous hypophysitis (XGH) is a very rare form of pituitary hypophysitis that may present both clinically and radiologically as a tumour. Our case series compares paediatric and adult presentations of XGH.Case series: Patient 1: A 15-year-old female presented with refractory headache, lethargy, short stature, delayed growth (weight (−3.36) SDS, height (−1.73) SDS, BMI 14 kg/m2), and pubertal arres...

Introduction: We present a 5-year-old girl with thyroid hormone resistance, subsequently discovered to be heterozygous for TRβ mutation. This case highlights the necessity to investigate, in detail, all children with persistently high thyroxin with normal TSH levels in order to aid future management and the necessity to follow them up.Case report: SD was born at term by normal delivery weighing 3.34 kg (50th centile). She was referred at 6 months of...

Background: The UK Newborn Screening Programme Centre Clinical Referral Standards and Guidelines for CHT (2013) define TSH cut-offs for screen positive (>20 mU/l) and borderline (>10 and <20 mU/l) results. In Manchester levels >8 and <20 mU/l are classified as borderline. This audit aims to assess whether adopting the national cut-off would result in babies with significant and permanent hypothyroid disease being missed.Patient popula...

Introduction: Biallelic mutations in the TSHB gene are a recognized cause of isolated congenital central hypothyroidism (CH), with autosomal recessive inheritance. In countries where neonatal CH screening relies on detection of an elevated TSH, such cases are missed, with the potential for delayed diagnosis and subsequent developmental impairment.Case: A female infant presented aged 8 weeks with prolonged jaundice, poor weight gain, constipation...

Introduction: Neonatal Grave’s disease is rare, affecting one in 25 000 neonates, and results from transplacental passage of TSH receptor antibodies (TSHR-Ab). Whilst hyperthyroidism occurs in <5% of babies born to mothers with active Grave’s disease; those born to mothers who were previously treated may still be affected. Neonatal Grave’s disease is usually self-limiting, however, complications include craniosynostosis, growth retardation, hyperactivity, de...

Introduction: The commonest pathological cause of goitre in adolescence in the UK is autoimmune thyroid disease. Other thyroid pathologies may occasionally co-exist either linked to the autoimmune process or occurring together by chance.Case report: A previously fit and healthy 15-year-old male presented as an emergency with a 10-day history of painless neck swelling. He had no breathing difficulty, dysphagia or voice change and was also clinically euthy...

Background: About one in 3000 babies born in the UK have congenital hypothyroidism (CHT), which is usually due to an agenesis of the thyroid gland, but some are due to dyshormogenesis, which can be transient or permanent.Method: Retrospective analysis of medical notes of infants referred as ‘suspect’ congenital hypothyroidism from the newborn blood spot screening centre to the paediatric endocrinology service at our hospital from January 2002 t...

Background: Juvenile hypothyroidism is very common problem in developing parts of world, and produces various skeletal manifestations. One of them is short stature and it is the most common reason for referral to endocrinologist.Aim and objectives: To study the prevalence of short stature in juvenile hypothyroidism, to study the various radiological manifestations of juvenile hypothyroidism and to study the impact of treatment on growth velocity and vari...

Hypothyroidism presents diagnostic challenges when occurring in an extremely unwell infant with hepatoblastoma. This case indicates a possible link between Beckwith–Wiedemann syndrome (BWS) and severe hypothyroidism.Antenatally, the baby had polyhydramnios and an abdominal mass. After normal vaginal delivery at 38+4 weeks, examination showed macrosomia (4007 g) small nose, low set ears and inverted V-shaped mouth. Transient hypoglycaemia on day 1 re...