A. M. Wallace

Recent trends and clinical features of childhood vitamin D deficiency presenting to a children's hospital in Glasgow

Background The incidence of vitamin D deficiency is unclear in the context of continuing demographic changes and the introduction of new public health measures. Methods All cases in which vitamin D deficiency was suspected as the primary cause of the clinical presentation were studied. Results Between 2002 and 2008, 160 cases of symptomatic vitamin D deficiency were identified with twice as many cases in 2008 (n, 42) as in the previous years. The median age of the cohort was 24 months (range 2 weeks-14 years).Three cases were recorded in children of European background, whereas the rest were in children of South Asian, Middle Eastern or sub-Saharan ethnic background. Presenting features included bowed legs in 64 (40%) and a fit in 19 (12%). In one infant, concerns were raised following a presentation with cardiac failure and hypocalcaemia. Summary Symptomatic vitamin D deficiency remains prevalent in the West of Scotland. There is a need for effective public health education, action and surveillance.

Short-term effects on linear growth and bone turnover in children randomized to receive prednisolone or dexamethasone.

aim To compare the relative potency of prednisolone (Pred) and dexamethasone (Dex) on short‐term growth and bone turnover.

Short-term effects of prednisolone and dexamethasone on circulating concentrations of leptin and sex hormone-binding globulin in children being treated for acute lymphoblastic leukaemia

objective Disturbances in body weight regulation are often encountered during glucocorticoid treatment and are associated with increased insulin resistance and truncal fat accumulation. Children were investigated who were receiving glucocorticoid treatment for acute lymphoblastic leukaemia (ALL). They were randomized to receive either prednisolone or dexamethasone as part of induction of remission. This randomization process provided a suitable opportunity to compare the effects of these two administered steroid on surrogate markers of adipocyte activity (leptin) and hyperinsulinaemia/insulin resistance (SHBG).

Variability in hydrocortisone plasma and saliva pharmacokinetics following intravenous and oral administration to Patients with adrenal insufficiency

Objective  The best method for determining hydrocortisone replacement therapy is not well defined. This study aimed to assess interindividual variability in cortisol pharmacokinetics and to investigate whether measurement of salivary cortisol provides a useful alternative to plasma concentration measurements.

Hazards of ketoconazole therapy in testotoxicosis

An eight‐year‐old boy with Leydig cell hyperplasia (testotoxicosis) was admitted with a three‐day history of rash, vomiting and diarrhoea, followed by acute onset of breathlessness and confusion. He was shocked, with liver cell and renal failure, erythematous rash and severe interstitial pneumonitis. He had been treated with ketoconazole for four years prior to admission, receiving 1200mg daily during the preceding year. Cessation of ketoconazole therapy was associated with full clinical recovery but relapse of testotoxicosis. Ketoconazole was reintroduced cautiously at a lower dose, with no ill‐effect, and reasonable control of testotoxicosis. We conclude that this boys illness, including the interstitial pneumonitis, represented a reaction to ketoconazole which was dose‐related rather than idiosyncratic.

Effect of variation in CYP11B1 and CYP11B2 on corticosteroid phenotype and hypothalamic–pituitary–adrenal axis activity in hypertensive and normotensive subjects

Background  Aldosterone is important in the development of hypertension. We have shown that a single nucleotide polymorphism (SNP) (–344T) in the 5′ regulatory region (UTR) of the gene encoding aldosterone synthase (CYP11B2) associates with aldosterone excess and hypertension as well as altered adrenal 11‐hydroxylation efficiency (deoxycortisol to cortisol). This conversion is carried out by the enzyme 11β‐hydroxylase, encoded by the adjacent gene, CYP11B1. We proposed that the effects of CYP11B2 are explained by linkage disequilibrium (LD) across the CYP11B locus. We have demonstrated high LD across this locus and identified two SNPs in the 5′ UTR of CYP11B1 (–1859 G/T, –1889 A/G) that associate with reduced transcription in vitro and altered 11‐hydroxylation efficiency in vivo. Accordingly, we hypothesized that the reduced adrenal 11‐hydroxylation may lead to chronic resetting of the pituitary–adrenal axis, with chronically increased ACTH drive resulting in aldosterone excess.

The concordance between serum anti-Mullerian hormone and testosterone concentrations depends on duration of hCG stimulation in boys undergoing investigation of gonadal function

Background  In boys undergoing investigation of gonadal function, the relationship between a single measurement of serum anti‐Mullerian hormone (AMH) and hCG stimulated serum testosterone is unclear.

HILUS CELL PATHOLOGY AND HIRSUTISM

Hilus cell abnormalities are uncommon causes of hirsutism with virilization. Although hilus cell tumours have been well described, hilus cell hyperplasia is rare and is poorly defined clinically. We describe three cases of hilus cell hyperplasia and compare them with a case of hilus cell tumour. Both pathologies were associated with increased testosterone and oestradiol secretion. Suppression of testosterone to the ‘normal range’in response to exogenous oestrogen was seen only in the cases with hyperplasia; only partial responsiveness was seen in the case with hilus cell tumour. Bilateral oophorectomy offers the potential for cure for both hilus cell hyperplasia and tumour.

Exaggerated adrenarche in a cohort of Scottish children: clinical features and biochemistry

Objective  To investigate the reported association between exaggerated adrenarche (EA) and reduced foetal growth and to identify possible risk factors for future morbidity in Scottish children with clinical features of EA.

Short-term growth and bone turnover in children undergoing occlusive steroid ('Wet-Wrap') dressings for treatment of atopic eczema.

To assess the effects of steroid wet‐wrap therapy on short‐term growth and bone turnover, eight prepubertal (M:F,5:3) children with a median age of 5.1years (range 3.3–8.8) were studied over a 2‐week period prior to therapy and at 2‐week intervals during therapy. Short‐term growth was assessed by measuring lower leg length velocity (LLLV) by knemometry and bone and collagen turnover was assessed by urinary deoxypyridinoline crosslink excretion corrected for creatinine excretion (DPD). Median duration of study during occlusive dressings was 12 weeks (range 2–18). Topical beclomethasone dipropionate diluted 1:10 or 1:4 in white soft paraffin was applied under tubular (Tubifast®) bandages in 7/8 children. Median LLLV before and during therapy were 0.43 mm/week (10th,90th centile; 0.0,0.7) and 0.42 mm/week (10th,90th centile; −0.35,1.01), respectively (not significant). Median DPD before and during therapy were 25.9 nmol/l/creatinine (10th,90th centile; 20.8, 33.0) and 26.3 nmol/l/creatinine (10th,90th centile; 21.7, 34.1) respectively (not significant). Non‐invasive assessment of the effects of steroid wet‐wrap therapy can be performed in children with eczema. These preliminary results show no substantial growth promoting or adverse effects of therapy.