Male hypogonadism due to a mutation in the gene for the beta-subunit of follicle-stimulating hormone.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
M Phillip
Publications and source records attributed to M Phillip.
Increase of serum lipoprotein (a) levels during growth hormone therapy in normal short children.
UNLABELLED: We studied the effect of growth hormone (GH) therapy on serum lipoprotein levels and the atherogenic index in short children without GH deficiency. Fasting blood samples were collected from ten (eight males) normal, short, prepubertal children, aged 6-12 years, before, during a 1-year course of GH therapy (0.1 IU/Kg/day), and 3 months after the cessation of GH administration. An increase in serum lipoprotein(a) [Lp(a)] levels of (mean% +/- SEM) 43 +/- 14, 58 +/- 18, 61 +/- 17 above the baseline levels was noted at 3 months (P < 0.05), 6 months (P < 0.01), and 1-year (P < 0.01) respectively after the beginning of GH administration. (ANOVA, P < 0.01). An inverse relationship between baseline serum Lp(a) concentrations and the percentage increment in Lp(a) after 9 months of GH therapy (r = -0.65, P < 0.05) was observed. GH therapy over a period of 1 year had no effect on plasma cholesterol, triglycerides, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein cholesterol [HDL-C] concentrations and the atherogenic index. Three months after the cessation of GH therapy, serum Lp(a) levels were not significantly different from the pre-treatment values. CONCLUSIONS: Serum Lp(a) concentrations remained above pretreatment values during a 1-year period of GH treatment in short children without GH deficiency and declined shortly after cessation of therapy. Since GH therapy for short children without GH deficiency usually continues for several years, we suggest that serum Lp(a) levels should be determined and followed regularly in such children under prolonged GH therapy.
Analysis of Variance↗
Once versus twice daily injections of growth hormone in children with idiopathic short stature.
The aim of this study was to compare the growth response of 22 short pre-pubertal children without growth hormone deficiency, treated with a single daily growth hormone injection (group A), to the growth response of 27 similar children, treated with the same daily dose divided into 2 subcutaneous injections per day (group B), for 1 y, in a randomized study. GH treatment significantly promoted growth parameters, height standard deviation score and height velocity standard deviation score in both groups. Serum insulin-like growth factor I was also increased. There were no significant differences in growth response, serum IGF-I levels, or the advance in bone age between the two study groups after 1 y of GH therapy. We conclude that twice daily s.c. growth hormone injections provide no advantages over once daily injection of the same dose in promoting the linear growth of short children without growth hormone deficiency.
Age Determination by Skeleton↗
Clinical presentation and outcome in primary familial hypomagnesaemia.
The clinical presentation and long term outcome (mean follow up eight years, range 0.25 to 21) of 15 patients with autosomal recessive primary familial hypomagnesaemia is described. The most common (67%) presenting events were generalised hypocalcaemic-hypomagnesaemic seizures at a mean (SD) age of 4.9 (2.5) weeks. Thirteen infants, treated soon after diagnosis with high dose enteral magnesium developed normally. Their serum calcium returned to normal concentrations but serum magnesium could not be maintained at normal concentrations (0.53 (0.12 SD) mmol/l; normal > 0.62). Delay in establishing a diagnosis led to a convulsive disorder with permanent neurological impairment in two infants. Reported complications of prolonged hypomagnesaemia such as renal stones, hypertension, arrhythmias, sudden death, or dyslipidaemia were not observed.
Consanguinity↗
Serum insulin-like growth factors I and II are not affected by undernutrition in children with nonorganic failure to thrive.
The aim of our study was to determine the serum levels of IGF-I, IGF-II, and their binding proteins IGFBP-1 and IGFBP-3 in young children 3 months to 2 years of age with nonorganic failure to thrive (NOFTT). 29 children with NOFTT and 32 normal controls were recruited and studied for auxologic and hormonal parameters. The NOFTT group had significantly higher serum concentrations of IGFBP-1 than the control group: 57.7+/-18 vs. 48+/-19 microg/l (p < 0.05). IGF-I and IGF-II serum levels were highly correlated to serum IGFBP-3 but there were no differences in the serum IGF-I, IGF-II and IGFBP-3 levels between the groups. We conclude that IGF-I, IGF-II, and IGFBP-3 are not useful for the evaluation of nutritional status in children, under the age of 2 years, with NOFTT.
Child, Preschool↗
Normal melatonin levels in patients with fibromyalgia syndrome.
OBJECTIVE: To assess urine levels of melatonin measured by 6-sulphatoxymelatonin (aMT6s) in patients with fibromyalgia (FM). METHODS: Nocturnal aMT6s urine levels were measured by ELISA, in a sample of urine collected from 10 PM to 7 AM from 39 female patients with FM and 39 age matched healthy female controls. All subjects were interviewed and assessed for nonarticular tenderness, FM symptoms, quality of life, and physical functioning. RESULTS: Nocturnal aMT6s levels of patients with FM were not statistically different from those of controls: 16.7+/-9.2 vs 16.0+/-11.3 microg, respectively. No association was observed between aMT6s levels of patients with FM and disease duration, reproductive status, sleep and mood disturbances. CONCLUSION: Nocturnal urine aMT6s levels were similar in patients with FM and controls. Studies are needed to elucidate the possible role of melatonin in FM and should include larger samples of newly diagnosed untreated patients with FM.
Adult↗
An 8-year-old girl with an abdominal mass.Pica.
Explore the source record for details and available documents.
Abdominal Neoplasms↗
Case of the month: a 10-year-old boy with Down syndrome and ichthyosiform changes.
Explore the source record for details and available documents.
Child↗
Renal hypertrophy in hyperglycemic non-obese diabetic mice is associated with persistent renal accumulation of insulin-like growth factor I.
The non-obese diabetic mouse is a model of spontaneous insulin-dependent diabetes as a result of autoimmune destruction of pancreatic beta cells, similar to the disease seen in human Type I diabetes. This mouse strain develops glomerular lesions reminiscent of those seen in human disease. The study presented here investigated the changes in renal insulin-like growth factor (IGF) system in hyperglycemic non-obese diabetic mice. Female non-obese diabetic mice and their age- and sex-matched controls were euthanized 4 days, 2 wk, and 4 wk after the onset of glycosuria. Kidney weight increased in diabetic mice, beginning at 2 wk after the onset of glycosuria. This renal hypertrophy was associated with an increase in renal extractable IGF-I protein. However, a decrease in IGF-I mRNA was observed at the same time. Serum IGF-I levels remained stable after 2 wk of diabetes and decreased at 1 month. No change was detected in renal IGF-I receptor mRNA levels. Renal cortical IGF binding protein (IGFBP)-1 mRNA levels were increased. Ligand blot analysis revealed a significant increase in serum and renal 30-kd IGFBP and a decrease in serum and kidney IGFBP-3 and IGFBP-4 at 30 days of diabetes. Insulin therapy prevented the increases in kidney weight, renal IGF-I, and 30-kd IGFBP, but did not reverse the decreased serum IGF-I levels observed at 1 month of diabetes. In summary, renal hypertrophy in non-obese diabetic mice is associated with a persistent accumulation of renal IGF-I and, IGFBP-1. These changes were partially reversed with insulin therapy, which did not correct the hyperglycemia, suggesting an important role for insulin deficiency in mediating these changes in the IGF system. These findings suggest that the IGF system may play a potential role in the development of diabetic nephropathy.
Animals↗
The effect of 2,3 dimercaptosuccinic acid in the treatment of lead poisoning in adults.
Four patients, aged 22-60, belonging to a single family that had been exposed to lead-contaminated food for an unknown period, and nine workers, aged 20-65, who had been exposed to air-borne lead for 6-8 years, were evaluated for lead poisoning in our centres. Blood lead levels were 3.57 +/- 0.39 micromol/L (mean +/- SD) in the family members and 3.46 +/- 0.43 micromol/L (mean +/- SD) in the group of workers. 2,3 dimercaptosuccinic acid (DMSA) therapy was instituted in the four family members while the nine workers were closely monitored after being removed from the contaminated environment without receiving any chelation therapy. DMSA therapy given for the duration of 19 days reduced the blood lead levels to 0.63 +/- 0.44 micromol/L (mean +/- SD), P<0.01, in the four family members. No significant change was observed in the untreated group. The exposure time in the untreated group was probably longer than that in the treated group. Following long-term exposure most of the lead in the body is found in the bones and therefore not easily removed by chelation therapy. No side-effects were reported in the treated group and no rebound elevation of blood lead levels was observed during the therapy period or during the 12-week follow-up period following cessation of therapy. We conclude that 19 days of chelation therapy with DMSA in adults with moderate to severe lead poisoning is effective and safe.
Administration, Oral↗
Effect of six months of growth hormone therapy, followed by treatment withdrawal in short children with normal quantitative indexes of growth hormone secretion.
Eight short patients with normal 24-hour integrated concentration of growth hormone by continuous withdrawal (IC-GH) received 6 months of GH therapy, followed by 6 months off. GH therapy increased growth rate (+2.9 cm/yr), repeated IC-GH (sixfold), and IGF-1 concentration (twofold). Posttreatment growth reverted to the pretreatment rate. Thus increased growth rate and IGF-1 concentration is associated with supraphysiologic IC-GH after injection.
Adolescent↗
The relationship of growth rate, plasma growth hormone (GH) concentration, and GH-binding protein.
Growth hormone (GH)-binding protein (GHBP) and GH secretion are potential mediators of linear growth in children. To study the relationship between these variables, we measured GHBP activity, peak stimulated GH (PKGH), and 24-hour integrated GH concentration (ICGH) in 76 children referred for evaluation of growth. Linear growth was expressed as an age- and sex-specific growth rate standard deviation score (GRSD), which was calculated from sequential height measurements in the 6-month period immediately before GH testing. Using multiple regression models, we found that the relationship between GHBP and growth (GRSD) depended on height (height standard deviation [HGTSD] expressed as an age- and sex-specific z score) controlling for ICGH or PKGH. In further analysis of this relationship, we divided the subjects by HGTSD in subsequent analyses. In 19 children of normal stature (HGTSD > -2), GRSD increased with GH concentration (measured both as PKGH and ICGH: P <.013,R2 = .56) but decreased with higher levels of GHBP (P < .005,R2 = .62). In contrast, for 57 subjects with severe short stature (HGTSD < or = -2), GRSD could not be predicted from GHBP, GH secretion, HGTSD, or interaction involving these variables. These data suggest the hypothesis that under normal conditions, GHBP and GH level may be important predictors of growth rate in children.
Adolescent↗
Short-term growth hormone therapy increases serum lipoprotein (a) levels in normal short children without growth hormone deficiency.
We investigated the short-term effect of GH (0.1 IU/kg/day) on serum lipoprotein (a) [Lp(a)] in 8 normal short children aged 6-12 years. GH increased serum Lp(a) concentrations in all the children studied. An increase to 107 +/- 5, 161.6 +/- 14.7 and 152.5 +/- 18.5% (mean +/- SE) of baseline levels was observed after 2 (p = NS), 6 (p < 0.01) and 12 weeks (p < 0.05), respectively. Our results suggest that GH therapy may pose a significant influence on Lp(a) serum levels in non-GH-deficient short children.
Body Height↗
Adrenal insufficiency after achalasia in the triple-A syndrome.
Explore the source record for details and available documents.
Adrenal Insufficiency↗
Fetal pseudohypoaldosteronism: another cause of hydramnios.
Pseudohypoaldosteronism (PHA) is a rare hereditary salt-wasting syndrome which is caused by decreased renal tubular responsiveness to aldosterone. The syndrome consists of hyponatremia, hyperkalemia, dehydration, failure to thrive and increased urinary salt loss. A case of PHA was previously described where fetal polyuria was the probable cause of hydramnios. We present four new cases of PHA, from two families, who were born after pregnancies complicated by severe hydramnios and premature labor. We suggest that PHA should be included in the differential diagnosis of hydramnios, since appropriate investigations might lead to the early diagnosis and treatment of a life-threatening disease.
Adult↗
Modulation of insulin-like growth factor I (IGF-I) receptors and membrane-associated IGF-binding proteins in endometrial cancer cells by estradiol.
Insulin-like growth factor I (IGF-I) receptors and membrane-associated IGF-binding proteins (IGFBPs) were examined in Ishikawa endometrial cancer cells. Our findings suggest that about 95% of [125I]IGF-I is bound to membrane-associated IGFBPs rather than to IGF-I receptors. Specifically, [125I]IGF-I binding to cell membranes could be completely displaced by cold IGF-I or IGF-II, but not by insulin, suggesting that binding was primarily due to IGFBPs. This was confirmed by using [125I]des-(1-3)IGF-I as the ligand. Des-(1-3) IGF-I binds with high affinity to IGF-I receptors, but with markedly lower affinity to IGFBPs. [125I]Des-(1-3)IGF-I bound to Ishikawa cells was displaced by IGF-I, IGF-II, and insulin. These results suggest that measuring IGF-I receptor levels using labeled IGF-I may be misleading. Accordingly, we evaluated the differential binding of [125I]IGF-I and [125I]des-(1-3)IGF-I to study the involvement of the IGF system in the stimulation of Ishikawa cell growth by estradiol. IGF-I stimulates Ishikawa cell proliferation, but at low concentrations, and this stimulation is largely dependent on the presence of estradiol. Estradiol caused a 2.5-fold increase in IGF-I receptor levels. Moreover, estradiol reduced soluble IGFBP levels, presumably increasing the availability of IGFs for their receptors. This elevation in IGF-I receptor levels and the decrease in IGFBP levels were accompanied by a 3.5-fold increase in IGF-I receptor messenger RNA and a 2.5-fold decrease in IGFBP messenger RNAs. These experiments suggest that estradiol sensitizes endometrial cancer cells to the effects of IGFs by simultaneously elevating receptor levels and decreasing (potentially inhibitory) IGFBP levels.
Binding, Competitive↗
Urinary cyclic adenosine 3',5'-monophosphate response in McCune-Albright syndrome: clinical evidence for altered renal adenylate cyclase activity.
The recent finding of an activating mutation in the Gs alpha protein, the protein that couples receptors to stimulation of adenylate cyclase, from endocrine and nonendocrine tissues of patients with McCune-Albright syndrome (MAS) suggests that alterations in adenylate cyclase activity may account for the clinical abnormalities in these patients. Many patients with MAS have hypophosphatemia. This may result from the presence of the activating Gs alpha mutation in proximal renal tubules or the elaboration of a phosphaturic factor from fibrous dysplasia. We, therefore, sought to characterize renal cAMP generation and phosphate handling in MAS patients. Intravenous infusion of PTH is a classic clinical test used to evaluate hormonal responsiveness of renal proximal tubule adenylate cyclase and examine PTH-dependent phosphate clearance. We performed PTH infusion in 6 MAS patients, 10 normal subjects, and 6 patients with pseudohypoparathyroidism (PHP). The basal urinary cAMP (UcAMP) level in the MAS group [5.5 +/- 2.6 nmol/dL glomerular filtration (GF)] was elevated (P < 0.05) compared to those in both normal subjects (3.2 +/- 1.2 nmol/dL GF) and patients with PHP (1.9 +/- 0.6 nmol/dL GF). However, PTH-stimulated peak UcAMP (15.0 +/- 7.0 nmol/dL GF) and the peak/basal UcAMP ratio (3.1 +/- 1.7) in MAS were significantly lower than the respective values in normal subjects (30.8 +/- 16.9 nmol/dL GF and 9.3 +/- 2.9; P < 0.05 for both) and were statistically similar to the blunted levels in PHP (respectively, 3.1 +/- 1.5 nmol/dL GF and 2.0 +/- 1.7). By contrast, the PTH-induced phosphaturic response in MAS patients was similar to that in the normal subjects. Our study provides clinical evidence that MAS patients have altered renal adenylate cyclase activity, manifested by an elevated basal UcAMP, but a blunted UcAMP response to PTH stimulation. These observations are presumably due to a mutation in the Gs alpha protein in the renal tubules. Despite the blunted UcAMP excretion, the phosphaturic response to PTH in MAS patients is intact.
Adenylyl Cyclases↗
High prevalence of thyroxine-binding globulin deficiency among Bedouin infants in southern Israel.
A high prevalence of thyroxine-binding globulin deficiency was found among Bedouin newborns in the Negev area (southern Israel) during a study lasting 2 years. This prevalence is significantly higher than those reported in other populations. Moreover, thyroxine-binding globulin deficiency was found to be more common than congenital hypothyroidism among the Bedouin. The results of thyroxine-binding globulin analysis in four patients may suggest the coexistence of at least two different mutations among the Bedouin population.
Ethnicity↗