Graves' Ophthalmopathy in a Paediatric Population.

Background Graves' disease is an autoimmune disorder leading to hyperthyroidism. It is often associated with ophthalmic manifestations. Graves' disease is reported to be rare in the paediatric population. Patients and Methods We performed a retrospective analysis on all patients diagnosed with ophthalmopathy related to Graves' disease at a paediatric age (less than 18 years old) in our institution between 2004 and 2015. Results Eight patients were identified: 6 females and 2 males. The median age at diagnosis was 11.5 years (range 3-16). Ophthalmic signs were: proptosis (6/8), superficial punctate keratitis (5/8), eyelid retraction (4/8), lagophthalmos (2/8), and oculomotor dysfunction (2/8). No patients showed signs of complication such as ocular hypertension or compressive optic neuropathy. Orbital decompression was performed in one patient in a non-emergency setting. Conclusion Ophthalmic involvement in Graves' disease is rarely encountered in paediatric patients. Ophthalmologists should be aware of this entity to ensure that patients with thyroid dysfunction are identified at an early point in time.

[Short stature]. / La petite taille.

Careful clinical assessment and a limited number of laboratory investigations usually allow distinguishing pathologic short stature from a great number of children presenting with constitutional or familial short stature. Chronic digestive and renal problems have to be ruled out. Growth hormone deficiency may be difficult to diagnose. Turner syndrome has to be ruled out in any girl with so far unexplained short stature. More difficult is the clinical diagnostic orientation to rare genetic disorders, such as skeletal dysplasias, genetic syndromes and inborn errors of metabolism. Medical history, clinical assessment and oriented investigations allow to isolate difficult cases and to refer them to specialists for specific therapy and/or genetic counselling.

[From obesity to type 2 diabetes in children and adolescents]. / De l'obésité au diabète de type 2 chez l'enfant et l'adolescent.

Obesity has a prevalence of 15-16% among subjects aged 6-17 yr. in United States as well as in Europe. Another 10 to 15% of children and adolescents appear to be at risk of obesity. The presence of type 2 diabetes among adolescents in our country represents a challenge from both a screening and a therapeutic point of view. In addition to obesity, a positive familial history, puberty, ethnic susceptibility as well as conditions known to exhibit insulin resistance (acanthosis nigricans, dislipidemia, polycystic ovary syndrome) represent majors risk factors. Detecting subjects at risk among a large number of obese children appear to be a critical step. Therapy of type 2 diabetes requires as important means as those set for type I diabetes, taking into account the fact that both types of diabetes share the same vascular complications.

Evaluation of hepatic and whole body glycogen metabolism in humans during repeated administrations of small loads of 13C glucose.

BACKGROUND: Postprandial suppression of endogenous glucose production and regulation of glucose homeostasis involve alterations of whole body and hepatic glycogenolysis and glycogen breakdown. These parameters can be estimated by the simultaneous measurement of net total and exogenous, (13)C-labeled, glucose oxidation. METHODS: Eight subjects were studied on 3 occasions, while receiving oral loads of 60 mg, 120 or 180 mg (13)C glucose/kg every hour for 4 consecutive hours. Net glucose oxidation was calculated from indirect calorimetry, and exogenous glucose oxidation from (13)CO(2) production. These parameters were evaluated during the hour following the fourth glucose load. Whole body endogenous glycogen breakdown was calculated as (net glucose oxidation) - (exogenous glucose oxidation). Total glycogen synthesis was calculated as (glucose load) - (exogenous glucose oxidation). Whole body glucose turnover was measured with 6.6 (2)H(2) glucose. The systemic appearance of oral, (13)C labeled glucose was monitored, and the suppression of endogenous glucose production was calculated. RESULTS: Plasma glucose tracers had reached near steady state during the hour following the fourth glucose load. Glucose ingestion dose-dependently suppressed endogenous glycogen breakdown and stimulated total glycogen synthesis. Endogenous glycogen breakdown was completely inhibited with 180 mg oral glucose/kg. Endogenous glucose production was suppressed in a dose-dependent way, but remained positive with all 3 doses. The first pass splanchnic glucose uptake averaged 25-35%. CONCLUSION: Repeated administration of small doses of (13)C labeled glucose allow to reach near steady state conditions after four hours, and to non-invasively evaluate whole body glycogen turnover and hepatic glucose metabolism.

Oligo-amenorrheic long-distance runners may lose more bone in spine than in femur.

PURPOSE: Strenuous training can be associated with amenorrhea leading to amenorrhea-related accelerated bone loss. Insufficient calorie energy, calcium, and/or protein intakes can also be frequently encountered in women with intense training, possibly contributing to bone loss. Long-distance runners with or without regular menses (age range 19-37 yr) were prospectively studied. METHODS: Changes in areal bone mineral density (BMD) were measured at 1-yr interval. RESULTS: Among 10 eumenorrheic, 11 oligo-amenorrheic, and 9 oral contraceptive users, there was no difference in energy, calcium, or protein intakes. Baseline BMD values were significantly lower in the oligo-amenorrheic group than in the two others at the level of lumbar spine (anteroposterior view: 0.941+/-0.039 in oligo-amenorrheic vs 1.077+/-0.029 or 1.051 +/-0.017 g x cm(-2), P < 0.005, in the eumenorrheic and contraceptive user groups, respectively) but not in weight-bearing bone such as proximal and midshaft femur. Over a 1-yr interval, during which the three groups did not differ in terms of running distances and dietary intakes, oligo-amenorrheic women displayed a significant decrease in lumbar spine BMD in lateral view (-0.049+/-0.012 in oligo-amenorrheic vs -0.001+/-0.013 and 0.014+/-0.012 g x cm(-2), p < 0.005, in the eumenorrheic and contraceptive user groups, respectively). We did not detect any significant change in femoral neck, trochanter, or midshaft BMD. CONCLUSIONS: Oligo-amenorrhea in long-distance runners, with adequate dietary intakes, was associated with a decrease in BMD affecting more the lumbar spine than the proximal and midshaft femur during a 1-yr follow-up.

Human insulin induces a higher glucagon response to induced hypoglycemia in short normal children, compared to porcine insulin.

After transfer of diabetic patients from porcine to human insulin, many reports emerged supporting an increased hypoglycemia unawareness. Several studies were then undertaken in both diabetic and healthy adults to investigate counterregulatory hormone responses to both porcine and human insulin-induced hypoglycemia as a possible underlying cause for this different hypoglycemia awareness. Most studies demonstrated similar neuroendocrine responses to both insulin species in adults. However, no such studies have ever been performed in healthy children. We undertook a double-blinded study of counterregulatory hormone responses to both porcine and human insulin-induced hypoglycemia in 17 short normal children randomly assigned to two groups, one receiving human and the other porcine insulin. We found similar responses of growth hormone, cortisol, epinephrine, norepinephrine and dopamine to both porcine insulin- and human insulin- induced hypoglycemia. Interestingly, we observed a significantly higher glucagon secretion when hypoglycemia was induced by human insulin. In conclusion, human insulin induces a higher glucagon secretion in healthy children than porcine insulin. Evidently, this observation cannot be extrapolated to diabetic patients. This study, however, further underlines the importance of performing investigations in children, since results found in adults differ from those observed in children.

Calcium-enriched foods and bone mass growth in prepubertal girls: a randomized, double-blind, placebo-controlled trial.

High calcium intake during childhood has been suggested to increase bone mass accrual, potentially resulting in a greater peak bone mass. Whether the effects of calcium supplementation on bone mass accrual vary from one skeletal region to another, and to what extent the level of spontaneous calcium intake may affect the magnitude of the response has, however, not yet been clearly established. In a double-blind, placebo-controlled study, 149 healthy prepubertal girls aged 7.9+/-0.1 yr (mean+/-SEM) were either allocated two food products containing 850 mg of calcium (Ca-suppl.) or not (placebo) on a daily basis for 1 yr. Areal bone mineral density (BMD), bone mineral content (BMC), and bone size were determined at six sites by dual-energy x-ray absorptiometry. The difference in BMD gain between calcium-supplemented (Ca-suppl.) and placebo was greater at radial (metaphysis and diaphysis) and femoral (neck, trochanter, and diaphyses) sites (7-12 mg/cm2 per yr) than in the lumbar spine (2 mg/cm2 per yr). The difference in BMD gains between Ca-suppl. and placebo was greatest in girls with a spontaneous calcium intake below the median of 880 mg/d. The increase in mean BMD of the 6 sites in the low-calcium consumers was accompanied by increased gains in mean BMC, bone size, and statural height. These results suggest a possible positive effect of calcium supplementation on skeletal growth at that age. In conclusion, calcium-enriched foods significantly increased bone mass accrual in prepubertal girls, with a preferential effect in the appendicular skeleton, and greater benefit at lower spontaneous calcium intake.

Asynchrony between the rates of standing height gain and bone mass accumulation during puberty.

During puberty, the marked increased in both standing height and bone mass appear to be dissociated in time, the former occurring earlier than the latter. However, the age or pubertal stage at which this dissociation is maximal in girls as opposed to boys, and whether this dissociation is similar at all parts of the skeleton, are not clearly established. Standing height and bone mineral mass, as assessed by measuring areal bone mineral density (BMD), at the levels of the lumbar spine, femoral neck and midfemoral shaft, were measured in 98 females and 100 males between the ages of 9 and 19 years twice at a 1-year interval. In males, the greatest difference between height and BMD gains occurred in the 13-14 year age group and was more pronounced for the lumbar spine and femoral neck than for the midfemoral shaft. In females, the greatest difference was detectable at a younger age (11-12 year age group) and appeared to be of a lower magnitude than in males. In both genders, the maximal difference occurred during the period of peak height velocity, which corresponded to the pubertal stages P2-P3. Such a dissociation between the rates of statural growth and mineral mass accrual could define a state of relatively low bone mass and contribute to the higher incidence of fracture known to occur at the age and/or pubertal stage when this dissociation is maximal.

Does puberty alter dietary habits in adolescents living in a western society?

PURPOSE: Puberty is considered to be a period with major behavioral changes and alterations in lifestyle. It is also assumed that important modifications in food habits would occur during pubertal maturation, particularly in affluent societies. To test this hypothesis, we conducted a prospective survey in 193 adolescents (95 females and 98 males) aged 9-19 years. METHODS: Food intake was assessed using a 5-day dietary diary method with weighing of most food intakes. Diaries were analyzed for macronutrient consumption with a nutrition determination software integrating food composition tables and 103 local food items. The stage of puberty or sexual maturity was clinically assessed and rated from stage P1 (prepubertal) to P5 (adult). RESULTS: The total energy intake which was within the recommended dietary allowances (RDA) was significantly influenced by both pubertal maturation and sex when expressed in absolute terms, but by pubertal stages only when adjusted per kilogram of body weight. Compared with RDA, the macronutrient distribution of the total energy intake showed an excessive quantity of fat (especially saturated fatty acids) and an insufficient amount of carbohydrate-rich fibers. The intakes of proteins, of which two out of three came from animal sources, were above RDA. Overall, these inadequacies in the macronutrient intake distribution were constant throughout pubertal maturation. CONCLUSION: This study indicates that the type of diet which has been linked with several chronic diseases in adults living in developed countries already prevails before pubertal maturation. This dietary pattern changes marginally during pubertal development. Therefore, our investigation does not support the notion that "bad" food habits become particularly worse during the years of pubertal maturation.

Cushing's disease due to a giant pituitary adenoma in early infancy: CT and MRI features.

We report the case of a 12-month-old girl presenting with diabetes insipidus and Cushing s disease. Brain magnetic resonance imaging (MRI) demonstrated a large tumour arising from the sella turcica, extending up to the foramen of Monro and invading the cavernous sinuses. Surgery was performed to remove the suprasellar part of the tumour, and histology revealed an adrenocorticotrophin (ACTH) secreting pituitary adenoma. This entity is very rare in this age group and the MRI features have not previously been described.

[Peak bone mass: facts and uncertainties]. / Le pic de masse osseuse: réalités et incertitudes.

Peak bone mass, which can be defined as the amount of bony tissue present at the end of the skeletal maturation, is an important determinant of osteoporotic fracture risk in adulthood. The techniques of single or dual energy absorptiometry measure the so-called "areal" or "surface" bone mineral density (BMD), a variable which has been shown to be directly related to bone strength. During puberty the gender difference in bone mass becomes expressed. This difference appears to be essentially due to a more prolonged bone maturation period in males than in females, with a larger increase in bone size and cortical thickness, as there is no significant sex difference in the volumetric trabecular density at the end of pubertal maturation. At the beginning of the 3rd decade, there is a large variability in the normal values of areal BMD in axial and appendicular skeleton. This large variance, which is observed at sites particularly susceptible to osteoporotic fractures in adulthood, such as lumbar spine and femoral neck, is barely reduced after correction for statural height, and does not appear to substantially increase during adult life. It is generally accepted that peak bone mass at any skeletal site is attained in both sexes during the mid-thirties. However, recent studies indicate that in healthy caucasian females, bone mass accumulation can virtually be completed before the end of the second decade, for both lumbar spine and femoral neck. Several variables are supposed to influence bone mass accumulation during growth: heredity, sex, diet components, endocrine factors, mechanical forces, and exposure to risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Prospective study of psychological development of adolescent female athletes: initial assessment.

PURPOSE: This study aimed at assessing the impact of physical training on psychological functioning at the onset of a prospective study of psychological and somatic maturation of adolescent female athletes. METHODS: Twenty-seven highly trained gymnasts aged 12.7 +/- 1.1 year (mean +/- SD, training load = 18-26 hr/week) and 16 age-matched but moderately trained swimmers (13.0 +/- 0.9 yr, training load 4-15 hr/wk) were submitted to standardized somatic and psychiatric examinations during training camps. RESULTS: Gymnasts were significantly shorter, lighter and thinner (p < 0.001) than swimmers. Their bone age was moderately but significantly retarded (-1.42 +/- 0.99 yr, p < 0.001) in contrast with swimmers in whom it was adequate for chronological age (+0.28 +/- 0.94 year, ns). Only 7.4% of gymnasts had already had menarche in contrast with 50% of age-matched swimmers (p = 0.003). Psychological functioning was considered as normal in all subjects. However, seven athletes including 3/27 gymnasts and 4/16 swimmers (p = 0.394) were considered as subjects "at risk" to develop a manifest mental disorder over time. Ten gymnasts (41.7%) presented with a global delay in psychological maturation, whereas no such case was observed among swimmers (p = 0.015). No correlation could be established between psychological delay and pubertal retardation (p = 0.210). CONCLUSION: Strenuous training in gymnastics for more than 1 yr has so far no detectable interference with the normal maturational events of adolescence. The outcome of athletes at risk to develop psychopathology as well as those with a global delay in psychological maturation who presented as if they were still in the latency period, remains uncertain.

Peak bone mass.

Peak bone mass, which can be defined as the amount of bony tissue present at the end of the skeletal maturation, is an important determinant of osteoporotic fracture risk. Measurement of bone mass development. The bone mass of a given part of the skeleton is directly dependent upon both its volume or size and the density of the mineralized tissue contained within the periosteal envelope. The techniques of single-1 and dural-energy photon or X-ray absorptiometry measure the so-called 'areal' or 'surface' bone mineral density (BMD), a variable which has been shown to be directly related to bone strength. Bone mass gain during puberty. During puberty the gender difference in bone mass becomes expressed. This difference appears to be essentially due to a more prolonged bone maturation period in males than in females, with a larger increase in bone size and cortical thickness. Puberty affects bone size much more than the volumetric mineral density. There is no significant sex difference in the volumetric trabecular density at the end of pubertal maturation. During puberty, the accumulation rate in areal BMD at both the lumbar spine and femoral neck levels increases to four- to sixfold over a 3- and 4-year period in females and males, respectively. Change in bone mass accumulation rate is less marked in long bone diaphyses. There is an asynchrony between the gain in statural height and bone mass growth. This phenomenon may be responsible for the occurrence of a transient period of a relative increase in bone fragility that may account for the pattern of fracture incidence during adolescence.(ABSTRACT TRUNCATED AT 250 WORDS)

[The child, growth and high-level sports]. / L'enfant, la croissance et le sport de haut niveau.

The hormonal response to a short but intense session of physical exercise should be distinguished from the endocrine adaptation to systematic physical conditioning. The normal child is perfectly equipped to handle stress situations such as those generated by leisure sport: the transient increase in stress hormones has no deleterious effect on growth and puberty. For highly trained children and adolescents, standardized dynamic testing will provide little information on the state of their endocrine system. In addition, the effects of training should be differentiated from those of various bias of selection. In young elite athletes, as for adult athletes, the alterations of the endocrine system result from an inappropriate physical conditioning programme for the individual level of tolerance. Whereas it has been shown that the gonadal function is predominantly affected (pubertal delay, menstrual dysfunction), alterations of growth hormone and cortisol productions have also been reported. Anomalies of pubertal growth should be searched for among elite adolescent athletes: there are data suggesting that their growth potential should probably not be affected below 15 weekly hours of training. However, children do not respond to stress in a uniform manner and one should be prepared to detect the occasional athlete with inadequate growth at lower training intensities. This seems to be the case when training starts before puberty as well as in physical activities associated with a strict weight control. When growth and/or puberal progression become inappropriate, the only logical therapy consists in reducing markedly or stopping training temporarily: in this situation, there is no medical justification whatsoever to initiate a substitutive therapy.

Evidence for a reduction of growth potential in adolescent female gymnasts.

The goal of this prospective study was to assess whether intensive physical training during puberty could alter the growth potential of adolescent female athletes. Height, sitting height, leg length, weight, body fat, and pubertal stage of 22 gymnasts aged 12.3 +/- 0.2 years (mean +/- SEM), with an average training period of 22 hr/wk, and of 21 swimmers aged 12.3 +/- 0.3 years (average training period 8 hr/wk) were recorded half-yearly for a mean period of 2.35 years (range 2.0 to 3.7 years). Adult height predictions were performed with the methods of Bayley and Pinneau; Roche, Wainer, and Thissen, and Tanner et al. Growth velocity of gymnasts was significantly lower than that of swimmers from 11 to 13 years of bone age (p < 0.05), with a mean peak height velocity of 5.48 +/- 0.32 cm/yr versus 8.0 +/- 0.50 cm/yr for swimmers. Height standard deviation score decreased significantly in gymnasts with time (r = -0.747; p < 0.001). This observation was not associated with a significant alteration of chronologic age/bone age ratio. By contrast, height standard deviation score remained unchanged in swimmers (r = -0.165; p = 0.1). A marked stunting of leg-length growth was observed in gymnasts from 12 years of bone age, resulting in a marked difference in overall sitting-height/leg-length ratio (gymnasts 1.054 +/- 0.005 vs swimmers 1.100 +/- 0.005; p < 0.001). Concomitantly, predicted height of gymnasts decreased significantly with time (Tanner et al.: r = 0.63, p < 0.001; Bayley-Pinneau: r = 0.44, p < 0.001), whereas those of swimmers did not change. We conclude that heavy training in gymnastics (> 18 hr/wk), starting before puberty and maintained throughout puberty, can alter growth rate to such an extent that full adult height will not be reached. The mechanisms underlying these observations are not settled; we suggest that prolonged inhibition of the hypothalamic-pituitary-gonadal axis by exercise, together with or because of the metabolic effects of dieting, is responsible for them.