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P C Hindmarsh

Publications and source records attributed to P C Hindmarsh.

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

Joint growth hormone and cortisol spontaneous secretion is more asynchronous in older females than in their male counterparts.

In humans, cortisol and GH are secreted in a pulsatile manner, and an interaction between GH and the hypothalamic-pituitary-adrenal axis has been established. In view of the sexually dimorphic pattern in GH secretion, we investigated the GH-cortisol bihormonal secretory dynamics in male and female healthy older individuals. We studied the GH and cortisol secretory patterns in 83 healthy subjects (45 men and 38 women; age range, 59.4-73.0 yr) by determining serum GH and cortisol concentrations at 20-min intervals for 24 h. The irregularity of GH and cortisol secretion was assessed using approximate entropy (ApEn), a scale- and model-independent statistic. The synchrony of joint GH-cortisol spontaneous secretion was quantified using the cross-ApEn statistic. Cross-correlation analysis of GH and cortisol patterns was computed at various time lags covering the 24-h period. Mean 24-h serum GH concentrations were significantly higher in females (mean, 1.31 mU/L; SD, 0.87) than in males (mean, 0.88 mU/L; SD, 0.42; P = 0.009), whereas mean 24-h serum total cortisol concentrations were higher in males (mean, 9.0 microg/dL; SD, 1.4) than in females (mean, 7.3 microg/dL; SD, 1.4; P = 0.0001). GH secretion was more irregular in females (mean ApEn, 0.81; SD, 0.23) than in males (mean ApEn, 0.60; SD, 0.20; P < 0.001). No significant difference in the regularity of cortisol secretion was noted between sexes. Cross-ApEn values of paired GH-cortisol were higher in females (mean, 1.15; SD, 0.18) than in males (mean, 1.01; SD, 0.16; P = 0.0003). Stepwise multiple linear regression analysis indicated that estradiol and insulin-like growth factor-binding protein-3 concentrations were independently related to GH ApEn values (r(2) = 0.14; P = 0.01), whereas cross-ApEn values of paired GH-cortisol were best predicted by FSH concentrations (r(2) = 0.37; P = 0.003). Cross-correlation analysis revealed a significant positive correlation between GH and cortisol, peaking at lag time of 4.7 h in males (r = 0.30; P < 0.0001) and 4.3 h in females (r = 0.14; P < 0.0001), with GH leading cortisol by these time intervals. In addition, a significant negative correlation between the two hormones was noted over time, peaking at 4.7 h in males (r = -0.21; P < 0.0001) and 6.3 h in females (r = -0.25; P < 0.0001), with cortisol leading GH by these time intervals. The above results indicate that in the elderly, females have a more disordered GH secretory pattern and a more asynchronous joint GH-cortisol secretion than their male counterparts. These observations most likely reflect bidirectional interactions between the GH and hypothalamic-pituitary-adrenal axis in humans as well as diminution of subsystem integrity and synchronous control of interconnected hormonal systems with advancing age.

Aged↗
PubMed2001

Bioavailability of oral hydrocortisone in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

The management of congenital adrenal hyperplasia due to 21-hydroxylase (CYP21) deficiency requires glucocorticoid substitution with oral hydrocortisone given twice or thrice daily. In paediatric practice little is known of the bioavailability of oral hydrocortisone tablets used in these patients. The aim of this study was to assess the bioavailability of oral hydrocortisone and to evaluate current replacement therapy in the light of cortisol pharmacokinetic properties. We determined the bioavailability of hydrocortisone following oral and intravenous administration in sixteen (median age: 10.9 years, range: 6.0-18.4 years) adequately controlled CYP21 deficient patients. Serum total cortisol concentrations were measured at 20-min intervals for 24 h while patients were on oral substitution therapy, and at 10-min intervals for 6 h following an intravenous bolus of hydrocortisone in a dose of 15 mg/m(2) body surface area. The area under the serum total cortisol concentration versus time curve (AUC) following oral and intravenous administration of hydrocortisone was calculated using the trapezoid method. The bioavailability was estimated by dividing the corrected for dose AUC after oral hydrocortisone administration by the corrected for dose AUC after the intravenous hydrocortisone administration and was exemplified as a percentage. After oral administration of hydrocortisone in the morning, median serum total cortisol concentrations reached a peak of 729.5 nmol/l (range: 492-2520 nmol/l) at 1.2 h (range: 0.3-3.3 h) and declined monoexponentially thereafter to reach undetectable concentrations 7 h (range: 5-12 h) after administration. Following administration of the evening hydrocortisone dose, median peak cortisol concentration of 499 nmol/l (range: 333-736 nmol/l) was attained also at 1.2 h (range: 0.3-3.0 h) and subsequently declined gradually, reaching undetectable concentrations at 9 h (5-12 h) after administration of the oral dose. After the intravenous hydrocortisone bolus a median peak serum total cortisol concentration of 1930 nmol/l (range: 1124-2700 nmol/l) was observed at 10 min (range: 10-20 min). Serum cortisol concentrations fell rapidly and reached undetectable levels 6 h after the hydrocortisone bolus. The absolute bioavailability of oral hydrocortisone in the morning was 94.2% (90% confidence interval (CI): 82.8-105.5%) whereas the apparent bioavailability in the evening was estimated to be 128.0% (90% CI: 119.0-138.0%). We conclude that the bioavailability of oral hydrocortisone is high and may result in supraphysiological cortisol concentrations within 1-2 h after administration of high doses. The even higher bioavailability in the evening, estimated using as reference the data derived from the intravenous administration of hydrocortisone bolus in the morning, is likely to reflect a decrease in the hydrocortisone clearance in the evening. Decisions on the schedule and frequency of administration in patients with congenital adrenal hyperplasia should be based on the knowledge of the bioavailability and other pharmacokinetic parameters of the hydrocortisone formulations currently available.

Administration, Oral↗
PubMed2000

Effect of early maternal iron stores on placental weight and structure.

BACKGROUND: Large placental size and low birthweight have been implicated as factors predicting high blood pressure in adulthood. Maternal anaemia has been suggested as a link. We investigated the interaction between maternal iron status and other factors known to influence birthweight and placental size. METHODS: In a prospective study of 1650 low-risk, singleton, caucasian pregnancies, we related placental size and birthweight to maternal iron status, socioeconomic status, and parity. Placental morphology was assessed in 17 randomly chosen primigravid pregnancies. FINDINGS: Parity was an important determinant of birthweight (mean standard deviation score -0.13 [SD 0.90] para 0; -0.24 [0.90] para 1; 0.32 [1.1] para 2; 0.21 [1.1] para > or = 3; p<0.0001) and placental weight (mean 655 g [SD 130]; 679 g [122]; 675 g [139]; 694 g [157], respectively; p=0.01). Cigarette smoking influenced birthweight only. Socioeconomic status had little effect after correction for parity. In addition to parity, the factors influencing placental weight were maternal height, weight, and serum ferritin concentration at booking, but not haemoglobin concentration. Serum ferritin concentrations were associated with folate intake and parity. In the placental morphology subset, serum ferritin concentration was inversely related to overall measures of peripheral villous capillarization. Haemoglobin concentration showed no such association. INTERPRETATION: These findings show a relation between maternal anaemia and placental size and birthweight across the normal range for these measures. Low ferritin concentrations in early pregnancy were associated with increased placental vascularisation at term. The association between ferritin concentration and folate supplementation emphasises the importance of preconceptional health, particularly in women at high risk of iron deficiency.

Adult↗
PubMed2000

Blood pressure and Turner syndrome.

INTRODUCTION: Elevated blood pressure (BP) is an important predictor of morbidity and mortality from cardiovascular disease. Patients with Turner syndrome (TS) have a higher morbidity and mortality in middle age than the normal population. As BP in childhood or early adulthood is predictive of BP later in adult life, we assessed manual and 24 h ambulatory BP in patients with TS to determine whether the BP pattern is altered at an early stage in these patients who are known to be at risk of cardiovascular disease. PATIENTS AND METHODS: We studied manual and 24 h ambulatory BP profiles in 75 girls with Turner syndrome, age range 5.4-22.4 years. A monitor with an oscillometric device (SpaceLabs model 90207) and an appropriate sized cuff was used. BP was measured during the day-time (0800-2000 h) and the night-time periods (2200-0800 h). The BP measured were compared with population standards. The effect of different growth promoting agents on BP was also evaluated. RESULTS: Mean manual and 24 h ambulatory BP measurements were 118/77 mmHg (range 95/60-140/102) and 115/70 mmHg (range 93/57-154/99), respectively. There was minimal difference between the two methods with a positive bias of 2.4 mmHg for diastolic BP and a negative bias of 2.1 mmHg for systolic BP. The mean standard deviation scores (SDS) corresponding to the mean BP recordings were 24 h systolic + 0. 81 (range - 1.26 to + 4.45), 24 h diastolic + 0.43 (range - 0.85 to + 3.42), day-time systolic + 1.08 (range - 0.95 to + 4.72), day-time diastolic + 0.70 (range - 0.94 to + 3.71), night-time systolic + 0. 22 (range -2.2 to + 3.64) and night-time diastolic - 0.18 (range -2. 0 to + 2.43). The SDS for both the mean 24 h and day-time systolic and diastolic BP were shifted to the right of the normal distribution. 57% of the girls had less than the normal 10% reduction in nocturnal systolic blood pressure. 17% had diastolic and 21% had systolic blood pressure above the 95th percentile for age and sex. There was no significant difference in the BP SDS between girls on no treatment and those receiving treatment. CONCLUSION: Over 50% of girls with Turner syndrome have an abnormal BP circadian rhythm, which is similar to adult patients with secondary hypertension. Patients with Turner syndrome have higher blood pressure measurements compared to published population standards, as evidenced by the shift to the right of both the systolic and diastolic BP SDS. These findings suggest that girls with Turner syndrome should be carefully monitored in childhood and adulthood for blood pressure and other cardiovascular risk factors.

Adolescent↗
PubMed2000

The influence of renal and cardiovascular abnormalities on blood pressure in Turner syndrome.

INTRODUCTION: Patients with Turner syndrome (TS) are at an increased risk of morbidity and mortality from cardiovascular disease. This study was undertaken to establish the prevalence of hypertension in patients with TS and to establish to what extent cardiovascular or renal abnormalities contribute to the measured blood pressure. PATIENTS AND METHODS: 62 patients with TS, age 5.4-22.4 years, had 24 h-ABPM (ambulatory blood pressure monitoring), echocardiography, renal imaging and measurement of recumbent plasma renin activity (PRA). Blood pressure was compared with population standards. RESULTS: 21% of the TS study population had mean systolic and 17% mean diastolic 24 h-ABPM measurements above the 95th percentile for age and sex (i.e. mild hypertension). Borderline blood pressure (i.e. 90th to 95th percentile) was found in another 17% of the patients. 57% of the patients had a blunted (i.e. less than 10%) fall in the night-time blood pressure. 24% of the patients had a detectable cardiac abnormality, 42% a detectable renal abnormality and 52% were found to have raised plasma renin activity. The presence of a cardiac or renal abnormality had no significant effect on blood pressure. Blood pressure of patients on growth and/or pubertal therapy was not different from those patients on no such treatment. CONCLUSION: Over 30% of patients with Turner syndrome were found to be mildly hypertensive and over 50% had an abnormal diurnal blood pressure profile. In this study we were unable to demonstrate that the presence of renal or cardiac abnormalities had an effect on recorded blood pressure. The use of growth hormone and oestrogen to manage growth failure and pubertal delay did not seem to affect blood pressure. This study suggests that there is a high prevalence of raised blood pressure in Turner syndrome patients. The 24 h-ambulatory blood pressure monitoring profile suggests that this may be secondary in origin, but we were unable to demonstrate an underlying mechanism with the renal and cardiac investigations performed.

Adolescent↗
PubMed2000

Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy?

Dysfunction of the Wilms' Tumour gene (WT1), a transcription factor critical for normal development and function of the urogenital tract, can result in both tumourigenesis [corrected] and urogenital abnormalities. The association of WT1 gene mutations with most cases of Denys-Drash syndrome is well described. More recently WT1 mutations have also been described in a related condition, Frasier syndrome. We report a case where genetic analysis showed a WT1 mutation typically associated with Frasier syndrome: a 1228 + 5 guanine to adenine substitution at the 3' alternative splice donor site in intron 9. The case provides a focus for the discussion of recent evidence that Denys Drash and Frasier syndrome form two ends of a spectrum of disorders. In addition, it illustrates the increasing significance of genetic investigation within clinical practice for diagnostic, prognostic and therapeutic purposes and the importance of karyotype analysis in phenotypically normal girls with renal disease.

Adolescent↗
PubMed2000

Urinary GH and IGF-I excretion in nine year-old children: relation to sex, current size and size at birth.

OBJECTIVES: To study the relationship of 24-hour urinary growth hormone (GH) and IGF-I excretion in childhood to sex and body size. To test the hypothesis that small size at birth followed by postnatal catch-up growth is associated with elevated IGF-I production. DESIGN AND SUBJECTS: Follow-up study of a cohort of 183 healthy children born in Salisbury, UK. MEASUREMENTS: Weight and height, 24-h urinary growth hormone (uGH) and IGF-I (uIGF-I) excretion, and systolic and diastolic blood pressures. RESULTS: At 9 years of age, 24-h uIGF-I excretion, but not uGH excretion, was strongly related to current weight (P < 0.001) and height (P < 0. 001). Urinary GH and IGF-I excretion were positively correlated (r = 0.15, P = 0.05). Boys excreted more uIGF-I per unit uGH than girls (uIGF-I/uGH molar ratio 32.1 compared to 21.0; P for difference = 0. 002). There were no significant relationships of uGH, uIGF-I or uIGF-I/uGH molar ratio with birthweight, birthlength or head circumference at birth, nor with blood pressure at 9 years. 'Catch-up' growth, indicated by an increase in height SD scores between birth and 9 years, was associated with higher IGF-I excretion (P = 0.01) and occurred in children with taller parents (P < 0.001). CONCLUSIONS: Boys appear to be more sensitive to GH than girls, generating more uIGF-I in relation to uGH. Urinary IGF-I excretion at 9 years is related to both absolute height and to the degree of catch-up in height from birth. Our results suggest that IGF-I production is strongly influenced by genetic factors, but also by either the degree to which intrauterine growth falls short of genetic growth potential, or the process of postnatal catch-up growth that follows.

Anthropometry↗
PubMed2000

Molecular genetics of septo-optic dysplasia.

Septo-optic dysplasia (SOD) is a highly variable condition characterized by midline neurological abnormalities associated with pituitary hypoplasia and optic nerve hypoplasia. The aetiology is unknown. Mutant mice, in which a novel homeobox gene, Hesx1, has been disrupted, exhibit a phenotype that resembles the phenotype of SOD. We therefore wished to explore the possibility that this gene is implicated in SOD. We cloned and sequenced the human homologue HESX1 and screened for mutations in affected individuals using single-stranded conformational polymorphism analysis, followed by cloning and sequencing of any exons which showed a band shift. Two siblings with SOD were homozygous for an Arg53Cys missense mutation within the HESX1 homeodomain, leading to a loss of in vitro DNA binding. Subsequently, we have identified heterozygous mutations in HESX1 that are associated with milder pituitary phenotypes. Our studies indicate a vital role for Hesx1/HESX1 in forebrain and pituitary development in mouse and man, and hence in some cases of SOD.

Animals↗
PubMed2000

Growth hormone treatment of children with brain tumors and risk of tumor recurrence.

GH is increasingly used for treatment of children and adults. It is mitogenic, however, and there is therefore concern about its safety, especially when used to treat cancer patients who have become GH deficient after cranial radiotherapy. We followed 180 children with brain tumors attending three large hospitals in the United Kingdom and treated with GH during 1965-1996, and 891 children with brain tumors at these hospitals who received radiotherapy but not GH. Thirty-five first recurrences occurred in the GH-treated children and 434 in the untreated children. The relative risk of first recurrence in GH-treated compared with untreated patients, adjusted for potentially confounding prognostic variables, was decreased (0. 6; 95% confidence interval, 0.4-0.9) as was the relative risk of mortality (0.5; 95% confidence interval, 0.3-0.8). There was no significant trend in relative risk of recurrence with cumulative time for which GH treatment had been given or with time elapsed since this treatment started. The relative risk of mortality increased significantly with time since first GH treatment. The results, based on much larger numbers than previous studies, suggest that GH does not increase the risk of recurrence of childhood brain tumors, although the rising trend in mortality relative risks with longer follow-up indicates the need for continued surveillance.

Adolescent↗
PubMed2000

Evidence-based growth hormone therapy prediction models.

Prediction models describing the response of various pathophysiological states to intervention can be of value in confirming a diagnosis, determining the prognosis and promoting compliance with treatment. The rigorous evaluation process of evidence-based medicine, used to assess any diagnostic test or therapeutic intervention, should be applied to studies reporting the development, validation and application of these prediction models. The models can provide only an estimate of the average effect to be expected, so the failure of an individual to exhibit an 'average' response does not necessarily imply a problem with that patient. Further development of the models is required to overcome inherent statistical problems and to allow greater applicability to the individual patient.

Body Height↗
PubMed2000

The GH response to low-dose bolus growth hormone-releasing hormone (GHRH(1-29)NH2) is attenuated in patients with longstanding post-irradiation GH insufficiency.

OBJECTIVE: Previous studies have suggested that post-irradiation GH insufficiency results from a loss of GHRH secretion, since many patients were able to release GH following exogenous GHRH stimulation. However, supramaximal doses of GHRH were used and the response may decline with time after radiotherapy. We re-evaluated the GHRH dose-response curve in patients post cranial irradiation and in controls. DESIGN: Randomized controlled study. METHODS: Five adult male long-term survivors of childhood brain tumours (median age 21.8 years (18.4-26.7); 13.7 years (11.4-15.7) post-radiotherapy, >30Gy) and five matched controls were studied. An intravenous bolus of GHRH(1-29)NH(2) was administered in doses at the lower (0.05 microg/kg) and upper (0.15 microg/kg) range of the dose-response curves for young males, as well as the standard supramaximal dose (1. 0 microg/kg). GH was measured before stimulation, every 2min for the first hour and every 5min for the second hour. All studies were conducted in a random fashion. RESULTS: Significantly lower peak and area under the curve (AUC) GH concentrations occurred in the irradiated group using 0.15 microg/kg (median peak Irradiated, 4. 5mU/l vs median Controls, 37.4mU/l; P<0.01) and 1.0 microg/kg (median peak Irradiated, 4.8mU/l vs median Controls, 15.2mU/l; P<0. 05) GHRH(1-29)NH(2). In irradiated subjects there was an incremental rise in GH output with increasing doses of GHRH(1-29)NH(2 )(median AUC: 122mU/l.min vs 179mU/l.min vs 268mU/l.min; P=0.007) reflecting altered pituitary sensitivity and reduced responsiveness. CONCLUSION: The GH response to bolus GHRH(1-29)NH(2) is attenuated in adult long-term survivors of childhood brain tumours. This may reflect direct pituitary damage and/or the loss of the tropic effects of chronic GHRH deficiency.

Adolescent↗
PubMed1999

Ontogeny of serum leptin concentrations in the human.

OBJECTIVE: Serum leptin concentrations reflect the fat mass of an individual. Fetal growth is rapid and it might be expected that major changes in circulating leptin concentrations in the fetus and neonate take place. We have studied the ontogeny of serum leptin concentrations in cord blood samples obtained by cordocentesis between 14 and 32 weeks of gestation and in samples obtained at term. PATIENTS: Cordocentesis samples from 10 appropriately grown for gestational age (AGA) and 10 intrauterine growth restricted (IUGR) fetuses. The results were compared with cord serum leptin concentrations obtained in 39 term healthy pregnancies. RESULTS: In the AGA and term pregnancies serum leptin concentrations changed little up until 38 weeks of gestation when there was an increase in concentration (Pre 38 weeks 3.5 microg/l (SEM 0.3); Post 38 weeks 5. 6 microg/l (SEM 0.7): Mann Whitney P = 0.03). Serum leptin concentrations were similar in the AGA and IUGR fetuses (AGA 5.9 microg/l (SEM 3.0); IUGR 4.2 microg/l (SEM 1.5): Mann-Whitney P = ns). Serum leptin was strongly related to birth weight (r = 0.58; P < 0.001) and birth length (r = 0.32; P = 0.05) in the term babies but not in the AGA or IUGR groups. CONCLUSION: Serum leptin concentrations in the fetus appear to be independent of gestational age and only rise towards the end of gestation. This late change probably reflects the changes in the accretion of body fat. There appears to be little difference in serum leptin concentrations between AGA and IUGR fetuses.

Female↗
PubMed1999

The relative roles of continuous growth hormone-releasing hormone (GHRH(1-29)NH2) and intermittent somatostatin(1-14)(SS) in growth hormone (GH) pulse generation: studies in normal and post cranial irradiated individuals.

OBJECTIVES: Pulsatile GH release in humans is thought to involve the coordinated interaction of growth hormone-releasing hormone (GHRH) and somatostatin (SS). Disordered GH secretion is seen in most patients following high dose (> 30 Gy) cranial irradiation in childhood and could result from dysregulation of these hypothalamic hormones or reflect direct pituitary damage. We have used a peptide 'clamp' to assess the relative roles of continuous GHRH and intermittent SS in GH pulse generation in healthy volunteers and short-and long-term survivors of childhood brain tumours. DESIGN: Randomized controlled study. PATIENTS: 12 adult male long-term survivors of childhood brain tumours (median age 17.0 years (15.2-19. 7); 12.2 years (5.8-14.0) postradiotherapy, > 30Gy whole brain irradiation) with 9 matched control volunteers and 6 short-term survivors of childhood brain tumours (median age 6.4 years (5.9-7. 7); 2.5 years (1.7-3.6) post radiotherapy, > 30Gy whole brain irradiation) with 6 matched controls (studies of spontaneous GH release alone). MEASUREMENTS: Serum GH concentrations in 24 h spontaneous GH profiles and during three 'clamp' studies: continuous GHRH(1-29)NH2 (60 ng/kg/minutes, subcutaneous infusion, 24 h); intermittent SS(1-14) withdrawal (20microg/m2/hour, intravenous infusion, 3 h on/1 h off, 2-3 cycles over 8-12 h); intermittent SS and continuous GHRH combined (2-3 cycles over 8-12 h). Data were analysed by spectral analysis, 'peak' and 'trough' determination and serial array averaging. RESULTS: In normal adults, discrete pulsatility was seen in all profiles of spontaneous GH secretion. Continuous GHRH amplified peak GH concentrations (median basal peak 21.1 mU/l vs. GHRH 62.0 mU/l, P = 0.008) whilst pulse timing remained unaffected. Rebound GH release following SS withdrawal alone was variable. Combining continuous GHRH with intermittent SS produced regular GH responses upon SS withdrawal (20.3 mU/l; range 2. 3-105.4). Heterogeneous patterns of spontaneous GH release were seen in the irradiated subjects. Spontaneous peak GH release was reduced in the children following irradiation (Irradiation 14.9 mU/l vs. Control 25.1 mU/l, P = 0.007). Peak GH concentrations were significantly amplified by GHRH in half of them. Adult long-term survivors had lower spontaneous GH concentrations and continuous GHRH amplified GH release in most subjects (Spontaneous 4.2 mU/l vs. GHRH 6.5 mU/l, P = 0.008) but peak concentrations remained far less than those of controls. Combining intermittent SS with continuous GHRH regularized GH release in many patients but the GH responses remained attenuated (4.6 mU/l; 2.5-17.5). CONCLUSION: GH pulsatility can be generated in normal volunteers by the combination of continuous GHRH and intermittent SS and provides indirect evidence for a role for GHRH in GH synthesis and replenishment of stored GH pools at times of high SS tone. Patterns of GH release in short-and long-term survivors of childhood brain tumours are heterogeneous suggesting that combined hypothalamic deficiencies of GHRH and SS occur following high dose radiotherapy. The attenuated GH release seen in long-term survivors compared to controls suggests that GH secretory dysfunction does not simply reflect reduced GHRH and SS secretion, and that trophic effects or pituitary damage may be important with time.

Adolescent↗
PubMed1999

Murphy's Law and the pregnant medical doctor: is pregnancy outcome worse?

The 'Murphy's Law' concept that doctors have a higher incidence of adverse pregnancy outcome is often quoted anecdotally but has never been scientifically tested. A group of medical doctors (n =52) were prospectively matched closely with a group of non-doctors (n =52) and pregnancy outcome was recorded. There were no differences noted in pregnancy outcome between the two groups. Whilst a much larger number of doctors is probably required to show a statistically significant difference, this first small study shows no clinically relevant difference between the two groups. The perception of Murphy's Law and the pregnant medical doctor would appear to be a myth.

Journal Article↗
PubMed1999

Thyrotoxicosis in children: thirty years' experience.

Optimal treatment for thyrotoxicosis remains controversial in adults, but more so in paediatric practice. We have conducted a retrospective review of the records of 76 paediatric patients seen between 1965 and 1995 to determine management practice and outcome of therapeutic interventions. Seventeen are currently on antithyroid drug (ATD) treatment, while four have had their care transferred. Of the remaining 55, 21 (38%) achieved long-term remission with ATD alone following a mean treatment duration of 3.3 y (range 0.5-7 y). Block-replacement (high dose of ATD with thyroxine replacement) was more convenient than the titration regimen (3.4+/-0.3 visits to hospital per year versus 6.1+/-0.4, p<0.001). Surgery (subtotal/total thyroidectomy) was carried out in 27 patients, of whom 24 subsequently became hypothyroid and were treated with thyroxine. I131 was used successfully in six patients, two following surgery. ATD should remain the first-line therapy; a block-replacement regimen is more convenient. Surgery in a specialized centre carries a low risk. Caution should still be exercised in the use of I131 in young children.

Adolescent↗
PubMed1999

Peak and trough growth hormone (GH) concentrations influence growth and serum insulin like growth factor-1 (IGF-1) concentrations in short children.

OBJECTIVE: Growth hormone (GH) is secreted in a pulsatile fashion promoting growth and a number of diverse metabolic actions. The precise components of the pulsatile signal involved in growth regulation are unclear. DESIGN: A retrospective analysis of 24 h serum GH concentration profiles to evaluate the relative contribution of peak and trough serum GH concentrations to growth regulation, GH response to insulin induced hypoglycaemia (ITT) and serum insulin like growth factor-1 (IGF-1) concentration. PATIENTS: Fifty short prepubertal children (age 5.2-11.9 years). MEASUREMENT: Analysis of the hormone profile by a concentration distribution method that determines the concentration at or below which the serum GH concentrations in the 24 hour profile spend a percentage of the total time. The method generates an estimate of the observed concentrations (OC) below which 95% and 5% of the values in the time series lie: OC 95 (peaks) and OC5 (troughs). RESULTS: Twenty six of the children were growing at a normal rate for short children with a height velocity standard deviation score (HVSDS) between +0.4 and -0.8 whereas twenty four were growing more slowly (HVSDS between -0.9 to -3.9). The former group had a mean peak GH response to ITT of 27.3 (11.1) mU/l whereas the latter had a mean value of 8.7 (6.5) mU/l. There was no relationship between (peak and trough GH concentration) and the age of the individual or body mass index. Peak GH levels were positively related to HVSDS and serum IGF-1 values (r = 0.44; P = 0.002 and r = 0.53; P = 0.002, respectively). GH trough levels were inversely related to these measurements (r = -0.29; P = 0.05; and r = -0.46; P = 0.002, respectively). Further analysis showed that individuals with the slowest growth rates and lowest IGF-1 concentrations had the lowest peak and highest trough GH concentrations (ANOVA F = 6.0; P = 0.002). Similarly, the peak GH response to ITT was lowest in those individuals with high troughs and low peaks (ANOVA F = 9.99; P < 0.001). CONCLUSIONS: These results suggest that the peak values of a GH concentration profile influence growth rate and the IGF-1 axis whereas elevated trough values have the greatest influence on growth rate and IGF-1 values when GH peaks are low.

Analysis of Variance↗