Leena Patel

Symptomatic adrenal insufficiency during inhaled corticosteroid treatment

Symptomatic adrenal insufficiency, presenting as hypoglycaemia or poor weight gain, may occur on withdrawal of corticosteroid treatment but has not previously been reported during inhaled corticosteroid treatment. This case series illustrates the occurence of clinically significant adrenal insufficiency in asthmatic children while patients were on inhaled corticosteroid treatment and the unexpected modes of presentation. General practitioners and paediatricians need to be aware that this unusual but acute serious complication may occur in patients treated with inhaled corticosteroids.

Linear growth in prepubertal children with atopic dermatitis

OBJECTIVE To define the evolution of prepubertal growth in atopic dermatitis and the factors influencing that growth pattern. METHODS Height and height velocity over two years, weight, triceps and subscapular skin fold thickness, and bone age were assessed in 80 prepubertal patients with atopic dermatitis and a control group of 71 healthy prepubertal school children. RESULTS Height standard deviation scores (SDS) and height velocity SDS did not differ between patients and controls, and were not influenced by body surface area affected by atopic dermatitis, topical glucocorticoid potency, or coexisting asthma. However, height SDS (ru2009=u2009−0.37) and height velocity SDS (ru2009=u2009−0.31) correlated inversely to age in patients but not in controls. A greater proportion (zu2009=u20092.84) of patients than controls had year 2 height velocity SDS less than −1.96. Patients had a mean delay in bone age of 0.22 years and 0.41 years at the beginning of year 1 and year 2 of the study, respectively. The delay in bone age correlated positively with age (ru2009=u20090.39) and duration of atopic dermatitis (ru2009=u20090.39), and negatively with height SDS (ru2009=u2009−0.51) and height velocity SDS (ru2009=u2009−0.38). CONCLUSIONS Prepubertal children with atopic dermatitis are not short compared with controls. However, as they approach the teenage years their height velocity decreases, the proportion of children with extremely low height velocity increases, and the delay in bone age increases. These features are consistent with the pattern of growth seen in people with constitutional growth delay.

Associations with multiple pituitary hormone deficiency in patients with an ectopic posterior pituitary gland

Introductionu2002 The presence of an ectopic posterior pituitary gland (EPP) on magnetic resonance imaging (MRI) is associated with hypopituitarism with one or more hormone deficiencies. We aimed to identify risk factors for having multiple pituitary hormone deficiency (MPHD) compared to isolated growth hormone deficiency (IGHD) in patients with an EPP.

Serum leptin and leptin binding activity in children and adolescents with hypothalamic dysfunction

Marked disturbance in eating behaviour and obesity are common sequelae of hypothalamic damage. To investigate whether these were associated with dysfunctional leptin central feedback, we evaluated serum leptin and leptin binding activity in 37 patients (age 3.5-21 yr) with tumour or trauma involving the hypothalamic-pituitary axis compared with 138 healthy children (age 5.0-18.2 yr). Patients were subdivided by BMI <2 SDS or > or = 2 SDS and healthy children and children with simple obesity of comparable age and pubertal status served as controls. Patients had higher BMI (mean 1.9 vs 0.2 SDS; p <0.001), a greater proportion had BMI > or = 2 SDS (54% vs 8%; p <0.001) and higher serum leptin (mean 2.1 vs 0.04 SDS; p <0.001) than healthy children. Serum leptin (mean 1.1 vs -0.1 SDS; p = 0.004) and values adjusted for BMI (median 0.42 vs 0.23 microg/l:kg/m2; p = 0.02) were higher in patients with BMI <2 SDS. However, serum leptin adjusted for BMI was similar in patients with BMI > or = 2 SDS compared to corresponding controls (1.08 vs 0.95; p = 0.6). Log serum leptin correlated with BMI SDS in all subject groups but the relationship in patients with BMI <2 SDS was of higher magnitude (r = 0.65, slope = 0.29, p =0.05 for difference between slopes) than in healthy controls (r = 0.42, slope = 0.19). Serum leptin binding activity (median 7.5 vs 9.3%; p = 0.02) and values adjusted for BMI (median 0.28 vs 0.48 % x m2/kg; p <0.001) were lower in patients than in healthy children. The markedly elevated leptin levels with increasing BMI in non-obese patients with hypothalamic-pituitary damage are suggestive of an unrestrained pattern of leptin secretion. This along with low leptin binding activity and hence higher free leptin levels would be consistent with central leptin insensitivity.

Likelihood of persistent GH deficiency into late adolescence: relationship to the presence of an ectopic or normally sited posterior pituitary gland

Objectivesu2002 The presence of an ectopic posterior pituitary gland (EPP) in childhood is associated with isolated GH deficiency (IGHD) and multiple pituitary hormone deficiency. GHD in late adolescence has been defined as a peak GH level <5u2003μg/l. The aim of this study was to identify the likelihood of persistent GHD in late adolescence in patients with an EPP compared with those with a normally sited posterior pituitary (NPP).

Insights into the pathophysiology of catch-up compared with non-catch-up growth in children born small for gestational age: an integrated analysis of metabolic and transcriptomic data.

Small for gestational age (SGA) children exhibiting catch-up (CU) growth have a greater risk of cardiometabolic diseases in later life compared with non-catch-up (NCU) SGA children. The aim of this study was to establish differences in metabolism and gene expression profiles between CU and NCU at age 4–9 years. CU children (n=22) had greater height, weight and body mass index standard deviation scores along with insulin-like growth factor-I (IGF-I) and fasting glucose levels but lower adiponectin values than NCU children (n=11; all P<0.05). Metabolic profiling demonstrated a fourfold decrease of urine myo-inositol in CU compared with NCU (P<0.05). There were 1558 genes differentially expressed in peripheral blood mononuclear cells between the groups (P<0.05). Integrated analysis of data identified myo-inositol related to gene clusters associated with an increase in insulin, growth factor and IGF-I signalling in CU children (P<0.05). Metabolic and transcriptomic profiles in CU SGA children showed changes that may relate to cardiometabolic risk.

Efficacy of a monthly compared to 3-monthly depot GnRH analogue (Goserelin) in the treatment of children with central precocious puberty

Aims: To compare the efficacy of goserelin 10.8 mg (Zoladex LA – ZLA) administered 9–12 weekly with 3.6 mg (Zoladex – Z) given monthly in suppressing pubertal development, and effect on body mass index (BMI). Methods: Children with central precocious puberty (CPP) treated with Z (n = 34) or ZLA (n = 28) were studied retrospectively. Pubertal scores and BMI SDS during 24 months’ treatment were compared. Results: To attain adequate pubertal suppression, more patients on ZLA than Z required increase in injection frequency (p = 0.02) and this was so for 7/8 patients with a structural aetiology for CPP on ZLA and 2/8 on Z. A greater proportion of patients on ZLA had BMI >+2 SDS before (p = 0.05), and at 18 and 24 months (p = 0.02 and 0.04). BMI SDS transiently increased during the first 6 months on ZLA (p = 0.04). Conclusion: Both Z and ZLA were effective in suppressing puberty. To achieve adequate suppression, increased injection frequency was more likely with ZLA than Z, and particularly in patients with structural defects. Children with CPP had an elevated BMI at the onset of therapy and ZLA had a transient positive influence on BMI.

The association of cardiac ventricular hypertrophy with congenital hyperinsulinism.

OBJECTIVEnVentricular hypertrophy (VH) has been observed in children with congenital hyperinsulinism (CHI), a condition of hypoglycaemia characterised by dysregulated insulin secretion, but the prevalence is not known.nnnPATIENTS AND METHODSnCardiac assessment was performed in children (n=49) with CHI at diagnosis and follow-up. Two dimensional and Doppler echocardiography studies were used to assess cardiac structures, while M-mode study was used to measure left ventricular (LV) dimensions, subsequently converted to Z scores. Where possible, LV hypertrophy was confirmed by LV mass index (g/m(2.7)) >95th centile.nnnRESULTSnCardiac structural lesions were found in 14 (28%) children. At initial echocardiography, VH was present in 31 (65%) children with median (range) LV posterior wall dimension in diastole Z scores of +1.6 (-2.4 to +5.8) and interventricular septal wall dimension in end diastole Z scores of +1.9 (-1.7 to +17.2). At follow-up echocardiography, performed after an interval of 178 (45-390) days, VH persisted in 16 (33%) children. In regression analysis, the presence of VH (odds ratio (95% confidence intervals) 1.1 (1.0-1.2), P=0.04) at initial echocardiography was correlated with maximum glucose requirement at diagnosis, indicating that severity of CHI at presentation may play a role in the pathogenesis of VH.nnnCONCLUSIONSnA significant proportion of children with CHI have cardiac structural lesions. A majority also have VH, which may be associated with the severity of CHI at diagnosis. VH may persist in some children, which requires careful long-term cardiac review.

Growth: Importance and Implications of Variations

Abstract Growth is an important sensor of a child’s general health and well-being. Accurate measurement of height, weight and head circumference requires relatively simple equipment and should be a part of standard assessment into any disease condition. In this chapter, we have discussed common growth problems, such as short stature and stress the need to exclude underlying chronic conditions as a first step. Nevertheless, the possibility of an endocrine condition, such as hypothyroidism and growth hormone deficiency, should also be considered. It would be wise to consider the possibility of a brain tumour as a cause for endocrinopathy, particularly in the case of boys with central precocious puberty.

Organ-Specific Pediatric Endocrine Disorders, Pituitary: Craniopharyngioma

Craniopharyngiomas (CPs) are rare neuroepithelial tumors constituting 5%–13% of pediatric brain tumors. Although classed as benign, they can cause considerable morbidity owing to their location, size, local extension, and predisposition to recur regardless of initial treatment modality. Individualized risk-adapted interventions, favoring conservative rather than radical surgery and using improved precision radiotherapy, are aimed at achieving good disease control, minimizing damage to vital structures, and improving outcomes. Recently, novel insights into the molecular pathogenesis of human adamantinomatous CP have opened up the possibility of testing novel treatments targeting pathogenic pathways.