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Biomedical subjects

R Stanhope

Publications and source records attributed to R Stanhope.

At least 37 records · Page 2Linked to original sources
PubMed2001

Multiple pituitary hormone deficiency: management of puberty for optimal auxological results.

The overview in this paper focuses on ways of achieving optimal auxological results in puberty, principally in idiopathic and congenital multiple pituitary hormone deficiency (MPHD), suggested by the co-authors. We agreed that diagnosing gonadotrophin insufficiency/deficiency is difficult in young children and should be repeated in late prepuberty, but a firm diagnosis of MPHD helps avoid endocrine re-testing at the end of growth. The hypothalamic-pituitary axis must be reassessed periodically in evolving endocrinopathies, though current practice varies widely. Optimum age to induce puberty is 11-12 years in girls and 13-14 boys, and sex steroids are the preferred agents. Short-course testosterone to increase micropenis size is advantageous, but inducing early testicular maturation is not known to improve later fertility. There is also little evidence for increasing the dose of GH during puberty, though therapy should continue to final height, and possibly until peak bone mass is achieved. Delaying puberty is an option in septo-optic dysplasia, and minimising the dose of hydrocortisone is crucial in treating ACTH/cortisol insufficiency. Many unresolved questions remain in this difficult area.

Adolescent↗
PubMed2001

The anabolic steroid oxandrolone increases muscle mass in prepubertal boys with constitutional delay of growth.

The aim of this study was to investigate the effect of oxandrolone on body composition in boys with constitutional delay of growth and puberty. In 14 prepubertal boys, height, weight, triceps and subscapular skinfolds and upper arm circumference were measured. Body mass index, the ratio of subscapular to triceps skinfolds and the upper muscle area were also determined. The difference of the various measurements and indices, 3 to 6 months before and after commencement of oxandrolone treatment, were calculated, while the boys remained prepubertal. We observed a marked increase in body mass index, a decrease of triceps and subscapular skinfolds, an increase in the ratio of subscapular to triceps skinfolds and also an increase in upper muscle area after the onset of oxandrolone treatment. These results suggest that low dose oxandrolone administration in prepubertal boys with constitutional growth delay causes a disproportionate increase of weight to height which is largely due to increased body muscle.

Anabolic Agents↗
PubMed2001

An open-label acceptability study of Norditropin SimpleXx--a new liquid growth hormone formulation.

A new liquid formulation of hGH (Norditropin SimpleXx) has been developed to avoid the need for reconstitution before administration. In addition, the liquid GH formulation has been combined with an advanced pen delivery system, either with or without a needle auto-insertion mechanism. This study was designed to assess the acceptability of the new system compared with the patient's previous system. A total of 103 children with GH deficiency received a daily injection of Norditropin liquid GH for 12 weeks with a choice of a pen/auto-insertion system. Acceptability was determined by nurse-supervised questionnaires administered to the patients and parents. Following treatment, 94% of patients preferred the Norditropin liquid GH system. This preference was irrespective of the previous system in use, patient age or length of GH therapy. More patients found it the less painful system (50% vs 13%), 92% of patients found it more convenient, and the formulation was well tolerated. In conclusion, Norditropin liquid GH was very well accepted and preferred by the majority of patients. It avoided reconstitution which had been a major cause of dissatisfaction with the patients' previous systems, and resulted in greater convenience and reduced levels of pain associated with injection.

Adolescent↗
PubMed2000

Hyponatraemia associated with lamotrigine in cranial diabetes insipidus.

We report the cases of two children with cranial diabetes insipidus who were treated with lamotrigine for seizures and who had accompanying changes in desmopressin requirements. Lamotrigine is a new anticonvulsant chemically unrelated to other existing antiepileptic drugs. Studies suggest it acts at voltage-sensitive sodium channels and also decreases calcium conductance. Both of these mechanisms of action are shared by carbamazepine, which can cause hyponatraemia secondary to inappropriate secretion of antidiuretic hormone. It is possible that the effect of lamotrigine on fluid balance in the cases described is also centrally mediated.

Adolescent↗
PubMed2000

Growth and endocrine disorders in multisystem Langerhans' cell histiocytosis.

INTRODUCTION: Langerhans' cell histiocytosis is a rare disorder, with diabetes insipidus occurring in up to half of patients. Causes of growth failure include the illness itself, treatments used and growth hormone insufficiency. PATIENTS AND METHODS: We identified all patients with an endocrinopathy secondary to Langerhans' cell histiocytosis (LCH). Growth data were analysed from all patients with multisystem involvement. RESULTS: Of 144 patients with multisystem LCH, 50 had an endocrinopathy, 49 of whom had diabetes insipidus. Growth hormone insufficiency (GHI) was present in 21 patients, seven of whom had other anterior pituitary deficiencies as well (gonadotrophin deficiency + GHI n = 2, gonadotrophin deficiency + TSH deficiency + GHI n = 2, panhypopituitarism n = 3). GH insufficiency, the development of which appeared to be independent of pituitary radiation, occurred at a median age of 8.3 years (4.7-18 years) and at a median interval of 3.5 years (0-11.8 years) after diagnosis of LCH. The median height SDS at diagnosis of growth hormone insufficiency was -2.9. Thirteen of the patients with growth hormone insufficiency attained final height with a median height SDS of -1.2. The final height SDS of 15 patients without GH insufficiency was closer to target height SDS, but not statistically different from that of the GH insufficient group. CONCLUSIONS: GH therapy significantly improves growth in GH insufficient patients with Langerhans' cell histiocytosis. Early institution of GH therapy may further improve height outcome. However, most children with Langerhans' cell histiocytosis regardless of endocrine function, failed to reach target height.

Adolescent↗
PubMed2000

Premature thelarche: clinical follow-up and indication for treatment.

Not only is the diagnosis of isolated premature thelarche difficult to distinguish from other variants of premature sexual maturation, but within the subgroups of isolated premature thelarche, there are probably at least two subgroups: "classical" and "atypical". We do not appreciate how potential treatment could affect each group, although it seems likely that those in the "classical" group would not have an indication for treatment. The longer-term follow-up of large numbers of patients is essential if we are to understand the long-term sequelae of this condition.

Aging↗
PubMed1999

Pituitary dysfunction, morbidity and mortality with congenital midline malformation of the cerebrum.

UNLABELLED: The purpose of this study was to review systematically a series of patients with congenital midline brain defects and pituitary dysfunction in early childhood and to quantitate the degree of dysfunction and clinical outcome. This study was a retrospective analysis of case notes of patients with pituitary dysfunction associated with either a midline cerebral anomaly and/or optic nerve hypoplasia. Forty patients were studied: 2 with semilobar holoprosencephaly, 2 with lobar holoprosencephaly, 18 with septo-optic dysplasia with an intact septum pellucidum, 7 with septo-optic dysplasia with an absent septum pellucidum, 7 with agenesis of the corpus callosum and 4 patients with isolated pituitary hypoplasia. An early age of diagnosis, feeding difficulties, neurodevelopmental disability, visual impairment and seizures were common occurrences. Despite disordered neuro-anatomy, most seizure disorders were caused by hypoglycaemia or hypernatraemia. Hypotensive/hypoglycaemic crises accounted for two out of three deaths within the study population. Most of patients had multiple pituitary hormone deficiency with growth hormone and adrenocorticotrophic hormone deficiency occurring most commonly. Unequivocal isolated hypothalamic dysfunction was an uncommon finding. In congenital midline brain malformation there is a spectrum of disordered neuro-anatomy associated with variable pituitary dysfunction. Clinical manifestations such as convulsions and developmental delay may be due to disordered metabolism and/or neuro-anatomy. CONCLUSION: Children with congenital midline brain defects frequently manifest convulsions, neurodevelopmental disability and poor growth due to disordered metabolism and/or neuro-anatomy. Treating clinicians must be aware of the complex, dynamic neurological and metabolic nature of these patients and their potential for early demise.

Abnormalities, Multiple↗
PubMed1999

Lipid profile, glucose tolerance and insulin sensitivity after more than four years of growth hormone therapy in non-growth hormone deficient adolescents.

OBJECTIVE: To study the effects of long-term (> 4 years) growth hormone (GH) therapy on insulin sensitivity, glucose tolerance and lipid profile in non-GH deficient adolescents at completion of their growth. SUBJECTS: Thirty non-GH deficient (15 'idiopathic' short stature, 8 intrauterine growth retardation, 7 partial GH deficiency in childhood but normal on retesting) were recruited, median (range) age 16.9 years (15-20.3) prior to ceasing their GH therapy. Their median (range) duration of GH treatment was 7.9 years (4-11). Insulin sensitivity was also recorded in 10 normal controls with a median (range) age of 20.5 years (18.4-22.3). METHODS: Insulin sensitivity was assessed by a short insulin tolerance test in 18 patients on GH therapy and controls. It was repeated in 14 patients six months after stopping their GH therapy. A 3-h standard oral glucose tolerance test (OGTT) was performed in 19 patients on GH therapy, and repeated after 6 months off GH in 10 patients. Fasting lipids were also measured. RESULTS: Insulin sensitivity index was significantly lower in the patients on GH therapy than in the controls, (median (range)) 3.7%/min (1.2-5.3) and 5.3%/min (3.8-6.2), respectively. Six months after termination of GH therapy, insulin sensitivity increased significantly from 3.6%/min (1.2-5) to 4. 8%/min (2.8-5.6). Fasting plasma insulin decreased significantly off GH therapy from 10.1 to 3.6 mU/l. The area under the insulin curve during the OGTT was also significantly higher on GH therapy. Apart from one patient with impaired glucose tolerance on GH treatment, plasma glucose concentrations remained within the normal range. No lipid abnormalities were recorded. CONCLUSIONS: These data suggest that long-term GH therapy may cause insulin resistance in non GH deficient adolescents, but usually with neither impaired glucose tolerance nor hyperlipidaemia.

Adolescent↗
PubMed1999

Multiple neonatal endocrinopathies in McCune-Albright syndrome.

Two cases of McCune-Albright syndrome (MAS) are reported who presented in the neonatal period with profound failure to thrive, cardio-respiratory distress, precocious puberty and Cushing's syndrome for which both underwent bilateral adrenalectomy. Both girls had also bilateral nephrocalcinosis; in one case that may have been attributed to Cushing's syndrome, but in the second case the cause remained obscure with no obvious abnormality of calcium metabolism. The first girl had hydrocephalus which is uncommon in this condition and the second girl still failed to thrive at the age of 6 years, despite adequate caloric intake and hormonal manipulation. A constellation of other abnormal features are described. These cases illustrate the complexity of MAS which can become a life-threatening or a debilitating disorder.

Age of Onset↗
PubMed1999

Growth failure and pituitary function in CHARGE and VATER associations.

Growth failure and anterior pituitary dysfunction are clinical features of the CHARGE and VATER associations. This study investigated pituitary dysfunction as a potential cause of poor growth in a series of four and three patients with the CHARGE and VATER associations, respectively, who had height standard deviation scores (SDS) less than-2. Five of the seven patients had associated subnormal growth velocity SDS. Patients were investigated with a combination of dynamic and basal endocrine tests. All patients were found to be normonatraemic and to have normal basal thyrotroph and stimulated corticotroph function. The one peripubertal patient had evidence of biochemical gonadotroph dysfunction. Although two patients had marginally low stimulated serum growth hormone responses to glucagon stimulation testing, this was associated with either normal growth velocity or normal serum insulin-like growth factor binding protein 3 (IGFBP-3) concentrations. Thus, somatotroph dysfunction could not be demonstrated unequivocally in any patient. Poor childhood linear growth in the CHARGE and VATER associations does not appear to be associated with pituitary dysfunction.

Abnormalities, Multiple↗
PubMed1999

Sexually dimorphic and radiation dose dependent effect of cranial irradiation on body mass index.

OBJECTIVES: To investigate the relation between cranial irradiation received during treatment for childhood leukaemia and obesity at final height. DESIGN: Retrospective cross sectional study. SETTING: Paediatric oncology centres at Great Ormond Street Hospital for Children and the Royal Marsden Hospital. SUBJECTS: Survivors of childhood leukaemia who received cranial irradiation, were in continuous first remission, and had reached final height. An unirradiated group of patients from the United Kingdom acute lymphoblastic leukaemia XI trial was also included; these patients were in continuous first remission and had been followed for at least four years from diagnosis. MAIN OUTCOME MEASURES: Body mass index standard deviation score (BMI z score) at final height for irradiated patients and at most recent follow up for unirradiated patients. Regression analysis was used to examine the effect on BMI z score of sex, age at diagnosis, and the dose of radiation received. RESULTS: For cranially irradiated patients, an increase in the BMI z score at final height was associated with female sex and lower radiation dose, but not with age at diagnosis. Severe obesity, defined as a BMI z score of > 3 at final height, was only present in girls who received 18-20 Gy irradiation and had a prevalence of 8%. Both male and female unirradiated patients had raised BMI z scores at latest follow up and there was no association with age at diagnosis. CONCLUSIONS: These data are further evidence for a sexually dimorphic and dose dependent effect of radiation on the human brain.

Adolescent↗
PubMed1999

Absence of catch-down growth in Russell-Silver syndrome after short-term growth hormone treatment.

We describe 3 children with Russell-Silver syndrome without growth hormone insufficiency who were treated with growth hormone for 2, 3. 7 and 6 years, showing a rapid growth acceleration. After cessation of growth hormone treatment, they grew at a normal rate without 'catch-down' growth. It may be possible that short intra-uterine growth retardation (IUGR) children with dysmorphic features respond to growth hormone therapy differently from non-dysmorphic IUGR short children. Short-term growth hormone treatment for children with Russell-Silver syndrome may avoid side effects and diminish costs.

Age Determination by Skeleton↗
PubMed1999

Why is the retention of gonadotrophin secretion common in children with panhypopituitarism due to septo-optic dysplasia?

Septo-optic dysplasia (De Morsier syndrome) is a developmental anomaly of mid-line brain structures and includes optic nerve hypoplasia, absence of the septum pellucidum and hypothalamo-pituitary abnormalities. We describe seven patients (four female, three male) who had at least two out of the three features necessary for the diagnosis of septo-optic dysplasia. Four patients had hypopituitarism and yet normal gonadotrophin secretion: one of these also had anti-diuretic hormone insufficiency; three had isolated GH deficiency and yet had premature puberty, with the onset of puberty at least a year earlier than would have been expected for their bone age. In any progressive and evolving anterior pituitary lesion it is extremely unusual to lose corticotrophin-releasing hormone/ACTH and TRH/TSH secretion and yet to retain gonadotrophin secretion. GnRH neurons develop in the nasal mucosa and migrate to the hypothalamus in early fetal life. We hypothesise that the arrival of GnRH neurons in the hypothalamus after the development of a midline hypothalamic defect may explain these phenomena. Progress in spontaneous/premature puberty in children with De Morsier syndrome may have important implications for management. The combination of GH deficiency and premature puberty may allow an apparently normal growth rate but with an inappropriately advanced bone age resulting in impaired final stature. GnRH analogues may be a therapeutic option. In conclusion, some patients with De Morsier syndrome appear to retain the ability to secrete gonadotrophins in the face of loss of other hypothalamic releasing factors. The migration of GnRH neurons after the development of the midline defect may be an explanation.

Child↗
PubMed1999

The spectrum of Silver-Russell syndrome: a clinical and molecular genetic study and new diagnostic criteria.

The Silver-Russell syndrome (SRS) is characterised by severe intrauterine growth retardation, with a preserved head circumference, leading to a lean body habitus and short stature. Facial dysmorphism and asymmetry are considered typical features of the syndrome, although the range of phenotypic variance is unknown. Fifty seven subjects varying in age from 0.84 to 35.01 years, in whom the diagnosis of SRS had been considered definite or likely, were re-evaluated in a combined clinical and molecular study by a single observer (SMP). In 50 patients the clinical findings complied with a very broad definition of SRS. Notable additional findings included generalised camptodactyly seen in 11 (22%), many with distal arthrogryposis. Thirteen of the 25 males required genital surgery for conditions including hypospadias and inguinal hernia. Fourteen (36.8%) subjects above school age have received a statement of special educational needs. Molecular genetic analysis was performed in 42 subjects and has identified maternal uniparental disomy of chromosome 7 in four. The phenotype was generally milder with birth weights for one patient above and three below -2 SD from the mean. Two children had classical facial dysmorphic features, and two had a milder facial phenotype. Of relevance to the possible molecular mechanism underlying this condition, none of the four disomic patients had significant asymmetry.

Abnormalities, Multiple↗
PubMed1998

Frontonasal dysplasia with optic disc anomalies and other midline craniofacial defects: a report of six cases.

The association of optic disc abnormalities with basal encephaloceles, specifically of the sphenoethmoidal type, and midline facial clefts has rarely been reported, although the association of midline facial clefts with encephaloceles is well described. We now report six cases of children, three males and three females, presenting with a sphenoethmoidal encephalocele, optic disc anomalies, midline facial clefting, hypertelorism, complete or partial agenesis of the corpus callosum, and endocrinological disturbances, including diabetes insipidus and pituitary dysfunction. This report underlines the importance of careful ophthalmic and endocrinological investigation of children with midline clefts associated with basal encephaloceles. These cases may represent a distinct entity within the spectrum of frontonasal dysplasia.

Abnormalities, Multiple↗