Biomedical subjects

M Phillip

Publications and source records attributed to M Phillip.

At least 19 recordsLinked to original sources

PubMed2007

Heat-shock protein peptide DiaPep277 treatment in children with newly diagnosed type 1 diabetes: a randomised, double-blind phase II study.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a T-cell-mediated autoimmune disease that leads to the destruction of insulin-producing beta cells. Treatment with DiaPep277, a peptide derived from heat-shock protein 60 (hsp60), has been found to slow the deterioration of beta-cell function after clinical onset of diabetes in NOD mice and human adults. Our aim was to evaluate the efficacy and safety of DiaPep277 treatment in attenuating beta-cell destruction in children with recent-onset T1DM. METHODS: A prospective, randomized, double-blind, phase II design was used. The sample included 30 children (19 males) aged 7-14 years who had been diagnosed with T1DM from 53 to 116 days previously, and had basal C-peptide concentrations above 0.1 nmol/L. The children were randomized to receive subcutaneous injections of 1 mg DiaPep277 (15 patients) or 40 mg mannitol (placebo) at entry and at 1, 6, and 12 months. The duration of follow-up was 18 months. The groups were compared for stimulated C-peptide level, exogenous insulin dose, and HbA1c concentration. RESULTS: C-peptide levels similarly decreased over time in the DiaPep277- and placebo-treated patients. There was no significant difference in insulin dose or HbA1c concentration between the groups at any time point. No serious drug-related adverse effects were recorded throughout the study period. CONCLUSIONS: One-year treatment with DiaPep277 at a dosage of 1 mg is safe for use and well tolerated in children with recent-onset T1DM. However, it appears to have no beneficial effect in preserving beta-cell function or improving metabolic control.

Adolescent↗

PubMed2006

Endocrine dysfunction and parameters of the metabolic syndrome after bone marrow transplantation during childhood and adolescence.

Endocrine dysfunction and parameters of metabolic syndrome were assessed in 91 patients aged 4.3-32.5 years who underwent allogeneic or autologous BMT in childhood. Final short stature, found in five of the 35 patients who attained final height, was associated with the underlying disease (specifically, Fanconi anemia) (P=0.0013), previous cranial irradiation (P=0.0007), type of conditioning irradiation (P<0.05) and allogeneic BMT (P=0.05). Growth hormone deficiency (n=10) was associated with previous cranial irradiation (P<0.005) and conditioning total body irradiation (P<0.001). Twelve patients had primary hypothyroidism, one had hyperthyroidism and one papillary thyroid carcinoma. Hypothyroidism was associated with neck/mediastinal (P<0.005) and conditioning irradiation (P<0.05). Primary gonadal failure was found in 24 of the mature patients (62.5% females). Hypogonadism was associated with the underlying disease (especially hematological malignancies) (P<0.05), pretransplant treatment (P<0.05), irradiation conditioning (P<0.001), older age (P<0.005) and advanced pubertal stage at BMT (P<0.05). Obesity (body mass index >2 s.d.) was found in 4.4% and type II diabetes and impaired glucose tolerance in 3.3% each. Dyslipidemia was found in 27.9% of the 43 patients tested. These findings emphasize the need for long-term follow-up of endocrine and metabolic parameters in young patients after BMT in order to offer proper treatment and improve quality of life.

Adolescent↗

PubMed2006

A new mutation in the growth hormone-releasing hormone receptor gene in two Israeli Arab families.

BACKGROUND: Mutations in the GHRH receptor gene (GHRH-R) are emerging as a common cause of familial isolated GH deficiency (IGHD). DESIGN: We searched for GHRH-R mutations in 10 patients with IGHD of Israeli-Arab origin, belonging to two highly consanguineous families. METHODS: Analysis of the 13 coding exons, the intron-exon boundaries, and the proximal promoter of the GHRH-R was performed by denaturing gradient gel electrophoresis. Abnormally migrating bands were sequenced. The newly found mutation was inserted into GHRH-R cDNA. Wild type and mutant receptor were expressed in Chinese hamster ovary (CHO) cells, and the cAMP response to GHRH was measured. RESULTS: All patients were homozygous for a novel GHRH-R missense mutation in exon 11 that replaces arginine with cysteine (R357C). Functional assay demonstrated complete inactivity of the mutant receptor in vitro. The prevalence of the mutant allele in the Israeli-Arab population was found to be 2%. All the patients had low but detectable GH reserve, proportionate short stature, and growth retardation since early childhood, with good growth response to GH treatment. Magnetic resonance imaging, performed in 3 patients, revealed a normal sized anterior pituitary in one patient evaluated at early childhood, and a borderline hypoplastic gland in the 2 patients evaluated at puberty. CONCLUSIONS: We describe a novel missense mutation in the GHRH-R. The high incidence of the mutant allele in Israeli Arabs suggests that the mutation may be a common cause of familial IGHD in this population.

Adolescent↗

PubMed2005

Effect of sex hormone administration on circulating ghrelin levels in peripubertal children.

BACKGROUND: Ghrelin levels gradually decrease throughout childhood and with advancing pubertal stage. The change during puberty is more pronounced in boys than girls. OBJECTIVE: The objective of the study was to investigate whether the pubertal drop in ghrelin secretion is modified by the increase in sex hormones. PATIENTS AND METHODS: Ghrelin levels were measured in 34 short peripubertal children (17 boys and 17 girls) aged 8-12.5 yr before and after sex hormone priming for GH stimulation testing. RESULTS: In boys, priming with testosterone increased testosterone to pubertal levels (23.7 +/- 7.1 nmol/liter), which in turn induced a marked decrease in ghrelin (from 1615.8 +/- 418.6 to 1390.0 +/- 352.0 pg/ml) and leptin (from 8.0 +/- 4.5 to 5.8 +/- 3.2 ng/ml) and an increase in IGF-I (from 162.7 +/- 52.8 to 291.1 +/- 101.6 ng/ml) (P < 0.001 for all parameters). In girls, priming with estrogen led to a supraphysiological increase in estradiol levels (1313.8 +/- 438.0 pmol/liter), which had no effect on ghrelin, leptin, or IGF-I. There was no correlation between ghrelin levels and levels of sex hormones, leptin, or body mass index in either boys or girls. CONCLUSIONS: A pharmacological increase in sex hormones is associated with a marked decline in circulating levels of ghrelin in boys but not girls. Additional longitudinal studies through puberty are needed to elucidate the physiological interaction between sex hormones and ghrelin.

Body Height↗

PubMed2005

Insulin resistance and impaired glucose tolerance in obese children and adolescents referred to a tertiary-care center in Israel.

OBJECTIVE: To establish the prevalence of insulin resistance and impaired glucose tolerance (IGT) and their determinants in a cohort of obese children and adolescents. METHODS: A retrospective design was used. The study group included 234 patients with a body mass index (BMI) greater than the 95th percentile for age and gender and 22 patients with a BMI between the 85th and 95th percentile for age and gender referred for evaluation to a major tertiary-care center in Israel. Ages ranged from 5 to 22 y. Estimates of insulin resistance (homeostatic model assessment (HOMA-IR)); insulin sensitivity (ratio of fasting glucose (GF) to fasting insulin (IF) (GF/IF), the quantitative insulin sensitivity check index (QUICKI)), and pancreatic beta-cell function (HOMA-derived beta-cell function (HOMA %B)) were derived from fasting measurements. An oral glucose tolerance test (OGTT) was performed in 192 patients to determine the presence of IGT. RESULTS: Insulin resistance was detected in 81.2% of the patients, IGT in 13.5%, and silent diabetes in one adolescent girl. Only two patients with IGT also had impaired fasting glucose (IFG). The prevalence of IGT was higher in adolescents than prepubertal children (14.7 vs 8.6%). GF/IF and QUICKI decreased significantly during puberty (P<0.005), whereas HOMA-IR and HOMA %B did not. Insulin resistance and insulin sensitivity indexes were not associated with ethnicity, presence of acanthosis nigricans or family history of type 2 diabetes. Patients with obesity complications had lower insulin sensitivity indexes than those without (P=0.05). Compared with subjects with normal glucose tolerance (NGT), patients with IGT had significantly higher fasting blood glucose (85.9+/-6.5 vs 89.2+/-10.6 mg/dl, P<0.05), higher 2-h post-OGGT insulin levels (101.2+/-74.0 vs 207.6+/-129.7 microU/ml, P<0.001), a lower QUICKI (0.323+/-0.031 vs 0.309+/-0.022, P<0.05), and higher fasting triglyceride levels (117.4+/-53.1 vs 156.9+/-68.9, P=0.002). However, several of the fasting indexes except QUICKI failed to predict IGT. There was no difference between the group with IGT and the group with NGT in fasting insulin, HOMA-IR, HOMA %B or the male-to-female ratio, age, BMI-SDS, presence of acanthosis nigricans, ethnicity, and family history of type 2 diabetes. CONCLUSIONS: Insulin resistance is highly prevalent in obese children and adolescents. The onset of IGT is associated with the development of severe hyperinsulinemia as there are no predictive cutpoint values of insulin resistance or insulin sensitivity indexes for IGT, and neither fasting blood glucose nor insulin levels nor HOMA-IR or HOMA %B are effective screening tools; an OGTT is required in all subjects at high risk. Longitudinal studies are needed to identify the metabolic precursors and the natural history of the development of type 2 diabetes in these patients.

Adolescent↗

PubMed2005

Three novel mutations in POU1F1 in Israeli patients with combined pituitary hormone deficiency.

BACKGROUND: POU1F1, a pituitary-specific transcription factor of the class 1 POU family, is crucial for the development and differentiation of the anterior pituitary gland. Mutations in the POU1F1 gene have been shown to be responsible for a syndrome of combined pituitary hormone deficiency (CPHD), including prolactin, growth hormone and thyroid-stimulating hormone deficiencies. METHODS: Five patients with CPHD from three families were evaluated. The clinical and biochemical data were taken from the medical records. DNA was analyzed by polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE), and sequencing. RESULTS: Molecular analysis yielded three novel mutations in POU1F1: W193X, Q242R (-2 bp), and F262L. CONCLUSIONS: Three novel POU1F1 mutations were detected in Israeli patients with CPHD. Two of them, a W193X missense mutation and a deletion of two adenine bases at position 242Q, may lead to the production of a truncated protein that lacks the entire POU homeodomain or part of it, respectively. The third mutation, F262L, resides in the POU homeodomain and hence might change the activity of the protein.

Arginine↗

PubMed2004

Type 1 diabetes in Jewish Ethiopian immigrants in Israel: HLA class II immunogenetics and contribution of new environment.

The interrelationship between human leukocyte antigen immunogenetics and environmental factors and their contribution to the emergence of type 1 diabetes (T1D) were studied in Jewish immigrants from Ethiopia in Israel. This community displays high incidence of T1D, and is unique both by its ethnic segregation and its rapid exposure to a new environment after the immigration. The study population consisted of 152 Ethiopian Jews living in Israel, 33 with T1D and 119 unrelated controls. Human leukocyte antigen class II susceptible and protective alleles in the Jewish Ethiopian patients were similar to those in patients of other ethnic groups in Israel and in non-Jewish Ethiopian patients, with a few exceptions. Three haplotypes were markedly associated with diabetes in Jewish Ethiopian patients: DRB1*0301 DQA1*05 DQB1*02 (OR 4.4, p < 0.001); DRB1*0404 DQA1 03 DQB1*0302 (OR 19.2, p = 0.006), and DRB1*0405 DQA1*03 DQB1*0302 (OR 87.8, p < 0.001). The highly susceptible allele DRB1*0301 was more common in the general Ethiopian population (25.2%) than in all other ethnic groups in Israel, which may render this community prone to the disease. The age at onset of disease in patients with two susceptible haplotypes was negatively correlated with the duration of living in Israel (r = -0.621, p = 0.04). We concluded that ongoing exposure of genetically predisposed immigrants from Ethiopia to diabetogenic environmental factors eventually leads to a high incidence of overt diabetes in this ethnic group.

Adolescent↗

PubMed2004

Prepubertal gynaecomastia: aetiology, course and outcome.

BACKGROUND: Palpable and measurable glandular breast tissue is a rare finding in prepubertal boys and warrants thorough evaluation to rule out an underlying pathology. OBJECTIVE: To characterize the course and outcome of prepubertal gynaecomastia, examine its effect on puberty, and try to identify its underlying cause. PATIENTS AND METHODS: Twenty-nine out of 581 (5%) boys referred to our clinic for evaluation of gynaecomastia between 1980 and 2000 were prepubertal at diagnosis. Data on age at appearance of gynaecomastia, general and endocrine evaluation, course of growth and puberty, and treatment were collected from the medical files. RESULTS: Prepubertal gynaecomastia was diagnosed at mean age of 8.9 +/- 2.2 years. In 27 of the 29 boys (93.2%) no underlying cause was identified. The remaining two boys (6.8%) had hyperaromatase syndrome. Nine boys (31%) were obese. Spontaneous resolution was recorded in six boys (20.5%), no change in 15 (52%), and further breast enlargement in eight (including the two with hyperaromatase syndrome) (27.5%). Accelerated growth and bone maturation rates were noted only in the two boys with hyperaromatase syndrome. Pubertal onset was documented in 13 boys at 11.8 +/- 1.1 years. CONCLUSIONS: According to our large single tertiary care centre experience, 5% of boys referred for evaluation of gynaecomastia were prepubertal. The development of gynaecomastia was the only abnormality and was not associated with other pubertal signs or accelerated growth rate. In most cases, the gynaecomastia was idiopathic. Further prospective studies are needed to evaluate the pathophysiological mechanisms responsible for this phenomenon.

Aromatase↗

PubMed2004

The aromatase inhibitor letrozole increases epiphyseal growth plate height and tibial length in peripubertal male mice.

Sex hormones may influence longitudinal growth, either indirectly, by affecting the growth-hormone-insulin-like growth factor I (IGF-I) axis, or directly, by affecting changes within the epiphyseal growth plate (EGP). The aim of the present study was to investigate the effects of letrozole, an aromatase inhibitor, on longitudinal growth and changes in the EGP in vivo. Eighteen peripubertal male mice were divided into three groups. The first group was killed at baseline, the second was injected with letrozole (Femara) s.c., 2 mg/kg body weight/day, for 10 days, and the third was injected with the vehicle alone. Serum testosterone levels were found to be significantly higher in the treated group than in the controls. Letrozole induced a significant increase in body weight, tail length and serum growth hormone level, but had no significant effect on the level of serum IGF-I. On histomorphometric study, there was a significant increase (12%) in EGP height in the treated animals compared with controls. Immunohistochemistry showed a 3.4-fold letrozole-induced increase in the proliferation of the EGP chondrocytes, as estimated by the number of proliferation cell nuclear antigen-stained cells, and a decrease in the differentiation of the EGP chondrocytes, as estimated by type X collagen staining. Letrozole did not interfere with type II collagen levels. The study group also showed a twofold increase in the number of IGF-I receptor-positive cells compared with controls. In conclusion, the aromatase inhibitor, letrozole, appears to increase the linear growth potential of the EGP in mice.

Animals↗

PubMed2003

Leptin reverses the inhibitory effect of caloric restriction on longitudinal growth.

Caloric imbalance, particularly in critical periods of growth and development, is often the underlying cause of growth abnormalities. Serum levels of leptin are elevated in obesity and are low in malnutrition and malabsorption. The aim of the present study was to determine whether leptin integrates energy levels and growth in vivo, as shown previously in our ex vivo experiments, even in the presence of caloric restriction. In the first part of the study, mice were divided into three groups. Two groups were fed ad libitum and received leptin or vehicle only, and the third group was pair-fed with the group injected with leptin to dissociate leptin's effect on growth from its effect on food consumption. Mice given leptin had a significantly greater tibial length than untreated pair-fed animals and a similar tibial length as control mice fed ad libitum despite their lower weight. In addition, leptin significantly increased the overall size of the epiphyseal growth plate by 11%. On immunohistochemistry and in situ hybridization studies, leptin stimulated both the proliferation and differentiation of tibial growth plate chondrocytes without affecting the overall organization of the plate. There was also a marked increase in the expression and level of IGF-IR. In the second part of the study, two groups of mice were fed only 60% of their normal chow; one was injected with leptin, and the other was injected with vehicle alone. Caloric deprivation by itself reduced serum levels of IGF-I by 70% and the length of the tibia by 5%. Leptin treatment corrected the fasting-induced growth deficiency, but further reduced the level of serum IGF-I. These results indicate that leptin stimulates growth even in the presence of caloric restriction independently of peripheral IGF-I.

Animals↗

PubMed2003

Leptin: obesity, diabetes and other peripheral effects--a review.

There is an increasing epidemic of obesity in the Western and developing world that has not spared children and, hence, is of great concern. Obesity presents numerous physiological and psychosocial problems for the child. Childhood obesity not only increases the risk of obesity in adulthood, it is associated with type 2 diabetes mellitus; is the leading cause of pediatric hypertension; increases the risk of coronary heart disease; and increases stress on the weight-bearing joints. Social and psychological problems are also significant consequences of obesity in children, with lowering of self-esteem and its effects on relationships with peers. Obesity is clearly associated with increased levels of the recently discovered hormone, leptin. Leptin, secreted from adipocytes, is involved in the regulation of food intake, energy expenditure, and energy balance in humans. This review focuses on the hormone, leptin, in an effort to document some of its many local and systemic effects on the body and, specifically, its potential role in obesity-induced diabetes.

Adipose Tissue↗

PubMed2003

Greater prevalence of iron deficiency in overweight and obese children and adolescents.

OBJECTIVE: To assess whether overweight children and adolescents, who often have poor dietary habits, are at increased risk of iron deficiency (ID). METHODS: The study sample included 321 children and adolescents followed in two endocrine centers in Israel between 1999 and 2001. The subjects were divided into three groups on the basis of body mass index (BMI) for age and gender as follows: group 1-BMI below 85th percentile (normal weight); group 2-BMI above 85th, but below 97th percentile (overweight); and group 3-BMI above 97th percentile (obese). ID was defined as iron levels <8 micromol/l (45 mcg/dl), and iron-deficiency anemia (IDA) was defined as ID and hemoglobin level below 2 standard deviation score (SDS) for the mean for age and gender. RESULTS: Iron levels below 8 micromol/l (45 mcg/dl) were noted in 38.8% of the obese children and 12.1% of the overweight children, compared with 4.4% of the normal-weight group (P<0.001). There was a significant negative correlation of low iron levels with BMI SDS (r=-0.44, P<0.001), but not with age or gender. Among the children with ID, 26.6% also had IDA. Groups 1, 2, and 3 accounted for 6.7%, 35%, and 58.3% of the children with IDA, respectively. CONCLUSIONS: ID is common in overweight and obese children. A significantly greater proportion of obese than normal-weight children have IDA. Insufficient dietary intake of iron, whether absolute or relative to body mass, and increased iron needs may be a result of unbalanced nutrition or repeated short-term restrictive diets. Because of potentially harmful effects of ID, obese children should be routinely screened and treated as necessary.

Adolescent↗

PubMed2003

Role of obesity and leptin in the pubertal process and pubertal growth--a review.

The prevalence of obesity is increasing alarmingly to epidemic proportions in children and adolescents, especially in industrialized countries. The finding that overweight children, especially girls, tend to mature earlier than lean children has led to the hypothesis that the degree of body fatness may trigger the neuroendocrine events that lead to the onset of puberty. Obese children have high leptin levels, and these may play a role in their earlier onset of puberty. Leptin receptors have been identified in the hypothalamus, gonadotrope cells of the anterior pituitary, and ovarian follicular cells, as well as Leydig cells. Leptin accelerates gonadotropin-releasing hormone (GnRH) pulsatility in hypothalamic neurons, and it has a direct effect on the anterior pituitary. Leptin administration at low doses may have a permissive, threshold effect on the central networks that regulate gonadotropin secretion. However, at high levels, such as those in obese people, it can have an inhibitory effect on the gonads. Children with obesity also have increased adrenal androgen levels, which may be involved in the accelerated growth of these children before puberty. Recent data indicate that leptin has a specific role in stimulating the activity of enzymes essential for the synthesis of adrenal androgens. Children with exogenous obesity frequently show an increase in height velocity with tall stature for age despite low growth hormone levels. Our group has shown that leptin acts as a skeletal growth factor, with a direct effect on skeletal growth centers, in the mice mandibular condyle, a model of endochondral ossification. In summary, obesity is associated with early puberty. Elevated leptin levels might have a permissive effect on the pubertal process and pubertal growth.

Adolescent↗

PubMed2003

Continuous glucose monitoring for treatment adjustment in diabetic pregnancies--a pilot study.

AIMS: To examine the efficacy of a continuous glucose monitoring (CGM) system for treatment adjustment in patients with diabetic pregnancy treated with insulin. METHODS: The study sample consisted of eight women with diabetic pregnancy, six with pre-pregnancy Type 1 diabetes mellitus and two with gestational diabetes (GDM), all being treated with multiple daily insulin injections. Gestational age ranged from 24 to 32 weeks. Data derived from the Continuous Glucose Monitoring System (MiniMed) for 72 h were compared with fingerstick glucose measurements (six to eight times a day), and treatment was adjusted on the basis of the findings. Two to four weeks later, the patients were re-evaluated with CGM. RESULTS: In the first part of the study, an average of 744+/-33 glucose measurements was recorded for each patient with CGM. The mean total time of hyperglycaemia (glucose level >7.7 mmol/l) undetected by the fingerstick method was 152+/-33 min/day. Nocturnal hypoglycaemic events (glucose level <2.7 mmol/l) were recorded in seven patients. Based on the additional information obtained by continuous monitoring, the insulin regimen was changed in all patients. CGM re-evaluation after treatment adjustment showed a reduction in undetected hyperglycaemia to 89+/-17 min/day and in nocturnal hypoglycaemic events, which were recorded in only one patient. CONCLUSIONS: Continuous glucose monitoring may diagnose high blood glucose levels and nocturnal hypoglycaemic events that are unrecognized by intermittent blood glucose monitoring and could serve as a useful tool for the long-term management of diabetic pregnancies. A large prospective study is needed to determine the clinical implications of this new monitoring technique.

Adult↗

PubMed2003

Continuous glucose monitoring for the evaluation and improved control of gestational diabetes mellitus.

OBJECTIVES: To compare the daily glycemic profile reflected by continuous versus self-monitoring of blood glucose in women with gestational diabetes mellitus (GDM), and to evaluate possible differences in treatment strategy based on the two monitoring methods. MATERIALS AND METHODS: The study sample consisted of 57 women with gestational diabetes, 47 in Israel and ten in California. Gestational age ranged from 24 to 32 weeks in the Israeli women, and 32 to 36 weeks in the American women. Data derived from the Continuous Glucose Monitoring (CGM) System (MiniMed) for 72 h were compared to fingerstick glucose measurements (6-8 times a day). During continuous monitoring, patients documented the timing of food intake, insulin injections and hypoglycemic events. RESULTS: In the Israeli group, 23 women were treated by diet alone, and 24 by diet plus insulin. An average of 763 +/- 62 glucose measurements was recorded for each patient with continuous glucose monitoring. The mean total time of hyperglycemia (glucose level > 140 mg/dl) undetected by the fingerstick method was 132 +/- 31 min/day in the insulin-treated group and 94 +/- 23 min/day in the diet-treated group. Nocturnal hypoglycemic events (glucose levels < 50 mg/dl) were recorded in 14 patients, all insulin-treated. On the basis of the additional information provided by continuous monitoring, the therapeutic regimen (insulin therapy, diet adjustment, or both) was changed in 36 of the 47 patients. All ten American women were treated with insulin. The mean time of undetected hyperglycemia for a total group monitoring time of 30 days was 78 +/- 13 min/day. Eight women had nocturnal hypoglycemia on at least one of the three nights of monitoring for a total of 12 nights. A change in insulin dosage was made in all women on the basis of the data provided by continuous glucose monitoring. CONCLUSION: Continuous glucose monitoring is helpful for monitoring women with GDM and for adjusting diabetes therapy. It can accurately detect high postprandial blood glucose levels and nocturnal hypoglycemic events that may go unrecognized by intermittent blood glucose monitoring. A large prospective study on maternal and neonatal outcome is needed to determine the clinical implications of this new monitoring technique.

Adult↗

PubMed2003

PROP-1 gene mutation (R120C) causing combined pituitary hormone deficiencies with variable clinical course in eight siblings of one Jewish Moroccan family.

BACKGROUND: PROP-1 gene mutations have been described in patients with combined pituitary hormone deficiencies (CPHD). METHODS: Clinical follow-up and molecular analysis of the PROP-1 gene were performed in 4 affected sisters of one consanguineous family, in whom 8 members had CPHD. RESULTS: The 4 sisters were homozygous for the same R120C mutation. Growth hormone and thyroid-stimulating hormone deficiencies were diagnosed concomitantly in all subjects, but at different ages (5.5-10.8 years). All 8 subjects exhibited complete gonadotropin deficiency with failure of spontaneous sexual maturation. Adrenocorticotropic hormone deficiency developed in only 2 sisters in the 3rd and 4th decades of life. CONCLUSIONS: The CPHD in this family, caused by an R120C mutation, was characterized by clinical phenotypic variability in terms of the severity of hormonal deficiencies and the time of their development. Identifying the mutation does not predict the clinical course. Therefore, continuous follow-up with repeated endocrine evaluations is mandatory to provide proper hormone substitution therapy.

Adult↗

PubMed2003

Craniopharyngioma: presentation and endocrine sequelae in 36 children.

We studied the clinical presentation by age of 36 children with craniopharyngioma, and outcome by height and body mass index (BMI). Presenting symptoms included headache (51.4%), vomiting (31%), visual disturbances (22.9%), polyuria and/or polydipsia (17.1%), delayed puberty (19.4%), short stature (13.8%), and precocious puberty (2.7%). Growth deceleration was overlooked, as was diabetes insipidus (actual rate, 52% for both). Delayed puberty was observed in all patients of appropriate age. Mean height standard deviation score (SDS) at admission was significantly lower than mean target height SDS (p = 0.004), while mean final height SDS was similar (p = 0.14). BMI SDS at last follow-up was similar to mean parental BMI SDS. We conclude that although endocrinopathies are present in most patients with craniopharyngioma, they are rarely the reason for referral. While affected prepubertal children have non-endocrine complaints, most adolescents are referred because of delayed puberty. Diabetes insipidus may be more prevalent in craniopharyngioma than previously reported. When patients with hypothalamic obesity are excluded, mean BMI SDS remains within normal range and is influenced mostly by parental BMI SDS.

Adolescent↗

PubMed2002

Involvement of the skeletal GH-IGF system in an experimental model of diabetes-induced growth retardation.

Uncontrolled diabetes is associated with growth retardation. We investigated the effect of insulin-dependent diabetes on animal growth and IGF-I gene expression in the epiphyseal growth plate region of the long bones. We also studied the effect of GH administration on somatic growth in the diabetic state. Streptozotocin (STZ)-injected diabetic rats had a decreased somatic growth rate in comparison to controls. GH administration (2.5 U/kg day) in the diabetic animals (DGH group) prevented this decrease. Serum IGF-I levels were decreased in both diabetic and DGH animals. Within 72 h from diabetes onset, IGF-I mRNA levels in epiphyseal growth plate homogenates decreased whereas IGF-I receptor mRNA levels increased in diabetic animals. The decrease in IGF-I mRNA transcript levels was localized to the metaphyseal region by in situ hybridization. We conclude that in the STZ-induced diabetic state, the reduction in linear growth is associated with a parallel decrease in IGF-I gene expression at the epiphyseal growth plate area. Diabetic growth retardation can be reversed with GH administration, which does not reconstitute serum IGF-I levels. Therefore, we speculate that GH in this model may act locally through the skeletal GH-IGF-I system.

Animals↗