Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a 12-7/12 year-old male with obesity, eunuchoid proportions, genetic stigmata of Turner's syndrome and mild developmental delay. We investigated whether cytogenetic alterations could be responsible for his phenotype. Conventional karyotype in 70 peripheral blood cells was 45,X(15%)/46,XYqh-(85%). Dual FISH on 1,000 nuclei revealed 8% of X0 cells (DXZ1 X-centromeric probe) and 92% of XY cells (DYZ3 Y-centromeric probe). We studied Y chromosome microdeletions by PCR. The patient showed a terminal Yq deletion from the 5I interval including the AZFb and AZFc regions. FSH, LH and testosterone (468 ng/dl) were within the normal range for his age. At Tanner IV pubertal development the spermiogram showed azoospermia and the testicular aspirate spermatic arrest. The present report suggests that Y chromosome deletions including AZFb and AZFc regions may cause spermatogenic arrest in early puberty.
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PMID:YqTER deletion causes arrest of spermatogenesis in early puberty. 1564 3

Obesity, predominantly centrally distributed, is common in women with Turner syndrome (TS) and is thought to contribute to the increased risk of atherosclerosis; however, insulin concentrations are unexpectedly low. To explore this discrepancy, we assessed fat content and distribution by magnetic resonance imaging (MRI) and bioelectrical impedance (BI). Six nondiabetic, estrogen-treated women with TS were compared with six age-matched normal controls of similar body mass index. Clinical history, anthropometric measurements, biochemical markers, and MRI and BI measures of adiposity were assessed. TS women had increased intrahepatocellular lipids (IHCL) on MRI. After height adjustment, they also had an excess of total and visceral compared with sc adipose tissue (AT) than controls, without elevated insulin concentrations. BI and MRI measures correlated strongly for total and sc, but not visceral, AT in TS. IHCL was associated with cumulative estrogen-deficient years (r = 0.928; P = 0.008). Women with TS depart from the classical picture of metabolic syndrome despite an excess of total and visceral AT on MRI. Elevated IHCL in TS is associated with estrogen deficiency. BI may be useful to estimate total body fat, but does not reliably localize fat depots in TS.
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PMID:Excess visceral and hepatic adipose tissue in Turner syndrome determined by magnetic resonance imaging: estrogen deficiency associated with hepatic adipose content. 1571 13

Women with Turner syndrome (TS) have increased risks of atherosclerosis, diabetes mellitus, and obesity. We hypothesized that women with TS have adverse metabolic or inflammatory markers for cardiovascular disease compared with normal women and estrogen-deficient controls. This was a cross-sectional study conducted at University College London Hospitals, UK. One hundred seventeen estrogen-treated women with TS and normal fasting blood glucose were compared with 30 age-matched normal controls and 31 estrogen-treated women with 46,XX premature ovarian failure (POF). The main outcome measures were markers of the metabolic syndrome, including the adipokines IL-6 and leptin, and C-reactive protein (CRP). TS women were more obese than controls (waist circumference, 79.9 +/- 12.4, 73.5 +/- 6.9, and 74.7 +/- 8.6 cm in TS, normal subjects, and POF controls, respectively; P = 0.005; body mass index, 26.8 +/- 5.8, 23.7 +/- 3.2, and 22.9 +/- 3.4 kg/m2; P < 0.001). This obesity was associated with increased CRP (2.9 +/- 1.5, 0.8 +/- 1.0, and 1.2 +/- 0.9 mg/liter; P < 0.001) and IL-6 concentrations (1.5 +/- 0.7, 1.0 +/- 1.5, and 1.2 +/- 0.5 pg/ml; P = 0.014), but lower fasting serum insulin (4.7 +/- 2.3, 6.3 +/- 3.0, and 6.9 +/- 2.9 mIU/ml; P = 0.004), glucose (83 +/- 11, 90 +/- 7, and 90 +/- 7 mg/dl; P < 0.001), and leptin (10.2 +/- 6.3, 14.4 +/- 7.6, and 14.8 +/- 8.1 ng/ml; P = 0.048). Triglyceride concentrations were similar in TS and POF women and were greater than in normal controls (97 +/- 53, 97 +/- 53, and 71 +/- 27 mg/dl; P = 0.024). We conclude that women with TS have various physical and biochemical features suggestive of the metabolic/insulin resistance syndrome, but there is a discrepancy among CRP, IL-6, and leptin, with leptin and fasting insulin concentrations being lower than expected for the degree of obesity. Obesity and estrogen therapy do not fully explain these findings. Women with TS may have specific metabolic defects contributing to cardiovascular risk.
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PMID:Adipokine dysregulation in turner syndrome: comparison of circulating interleukin-6 and leptin concentrations with measures of adiposity and C-reactive protein. 1572 8

Our understanding of the IGF-I system has increased dramatically in recent yr due in part to the advances in molecular and cellular biology. Not only can we now measure circulating levels of the members of this axis in order to address the possibly pathophysiological changes, but genetic alterations can now be identified as the underlying cause of specific clinical situations. In normal children, circulating levels of IGF-I and the IGF binding proteins (IGFBPs) change throughout development and in some cases are gender dependent. Children and adolescents with a variety of illnesses and metabolic disorders have altered circulating IGF-I and IGFBP levels. Hence, in children or adolescents with exogenous obesity, anorexia nervosa, coeliac disease, leukaemia and other types of cancer, as well as in cases of GH deficiency, this axis can be altered. These data may help us to understand the physiology and pathophysiology of this system, but the clinical or diagnostic utility of these measurements is still largely debated. Indeed, in most of the above mentioned illnesses, circulating IGF and IGFBP levels overlap with normal values. Furthermore, these measurements do not provide data concerning levels of these factors at target tissues or of local synthesis and autocrine-paracrine effects. However, measurements of IGF-I and its binding proteins, as well as GH and its binding proteins, can help us to focus our analysis of patients suspected to have genetic abnormalities on the GH receptor, IGF-I, its receptor, IGFALS, or intracellular signalling proteins such as STAT5b or ERK. Possibly, the most clear clinical utility of circulating IGF-I measurements in children is in cases of GH deficiency or insensitivity or under GH treatment. However, the fact there are cases of children with non-detectable levels of circulating IGF-I that yet normal height and growth velocity, or with non-detectable levels of GH yet normal growth and IGF-I levels, raises many questions. Furthermore, circulating IGF-I levels may be within the normal control levels and the child may have a pathological growth pattern. Hence, just how useful are these measurements? Another clinically important question pertains to GH treatment in patients, such as in the Turner Syndrome, where supraphysiological levels of serum IGF-I are reached in order to induce growth. The interpretation and clinical utility of measurements of circulating IGF-I and its BPs are currently being widely discussed. As our knowledge of this system increases, with the identification of new members of this family and its intracellular mechanisms of action, as well as new genetic alterations in patients, the interpretation of laboratory results will also improve and help to better our diagnostic capability.
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PMID:The IGF system in childhood: physiology and clinical implications. 1611 74

Elevated liver enzymes can be seen relatively frequently in patients with Turner syndrome (TS), while the pathogenesis of this remains unclear. Our epidemiological and prospective study aimed to investigate: a) the natural 2-yr course of liver disease in a selected cohort of young patients with TS, who had been preliminarily recruited on the basis of persistently elevated liver enzymes; b) the role of prolonged hormonal therapies in the etiology of liver dysfunction. From an overall population of 214 TS patients younger than 20 yr, only 19 (8.9%) were recruited, according to the following inclusion criteria: increased serum concentrations of one or more liver enzymes, exceeding the uppermost limit of the respective normal ranges, and persistence of these liver alterations for 6 months after the preliminary assessment. On the basis of the results of this prospective study, we can conclude that: a) the prevalence of liver abnormalities in girls and adolescents with TS is much lower and more strictly related to hormonal therapies than in TS adults; b) both autoimmunity and obesity are not frequently involved in the etiology of TS liver dysfunction; c) liver damage is either mild or moderate and its severity is not conditioned by karyotype; d) its course may be self-limiting; e) its natural history may be characterized in some cases by a slight deterioration of intrahepatic cholestasis, with no negative repercussions on liver synthetic function.
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PMID:Increased liver enzymes and hormonal therapies in girls and adolescents with Turner syndrome. 1627 68

Turner syndrome occurs in 1:5000 live births (1:2,500 females) and is caused not only by X-chromosome monosomy, but also in a large degree, by the presence of a mosaicism (45,X) and/or an abnormal X or Y chromosome (deletion, isochromosome X, dicentric chromosome). Clinical features are heterogeneous and typical physical anomalies are often mild or absent. In all cases, patients are short but final height has been improved by growth hormone therapy. Ovarian failure, with variable onset depending on the chromosomal anomalies, is frequent. Others visceral diseases (bone anomalies, lymphedema, deafness, and cardiovascular, thyroid, gastrointestinal diseases) are less common and need a screening at diagnosis, then a survey during adolescence and adulthood. During gestation, typical forms can be diagnosed by ultrasound examination, but mild forms are discovered incidentally during amniocentesis for unrelated reasons (advanced maternal age) and prenatal advice is difficult. The quality of life and social life is better when puberty is not induced too late, and in absence of cardiac disease or deafness. Deafness can lead to learning difficulties and, during adulthood, sterility can have a negative effect on quality of life. The prognosis depends on heart diseases, obesity, arterial hypertension and osteoporosis. Therefore, a long-term follow-up is necessary.
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PMID:[Turner syndrome]. 1732 33

Turner syndrome occurs in one out of every 2,500 to 3,000 live female births. The syndrome is characterized by the partial or complete absence of one X chromosome (45,X karyotype). Patients with Turner syndrome are at risk of congenital heart defects (e.g., coarctation of aorta, bicuspid aortic valve) and may have progressive aortic root dilatation or dissection. These patients also are at risk of congenital lymphedema, renal malformation, sensorineural hearing loss, osteoporosis, obesity, diabetes, and atherogenic lipid profile. Patients usually have normal intelligence but may have problems with nonverbal, social, and psychomotor skills. Physical manifestations may be subtle but can include misshapen ears, a webbed neck, a broad chest with widely spaced nipples, and cubitus valgus. A Turner syndrome diagnosis should be considered in girls with short stature or primary amenorrhea. Patients are treated for short stature in early childhood with growth hormone therapy, and supplemental estrogen is initiated by adolescence for pubertal development and prevention of osteoporosis. Almost all women with Turner syndrome are infertile, although some conceive with assisted reproduction.
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PMID:Turner syndrome: diagnosis and management. 1770 42

Therapy with recombinant growth hormone is currently approved for the indications growth hormone deficiency,Turner syndrome, chronic renal failure, small for gestational age (SGA) and Prader-Willi syndrome. Positive experience from on-going clinical studies (e.g. on obesity, type 2 diabetes, Crohn's disease) support an extended range of applications for recombinant growth hormone. However, growth hormone therapy is very expensive. On the other hand, biosimilars are already available that are significantly lower in price. During the coming years, research must show whether the efficacy and safety of biosimilars (including possible new indications) are equal to that of the established preparations.
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PMID:[Therapy with recombinant growth hormone]. 1806 78

Noninsulindependent diabetes mellitus is 2-4 times more prevalent in Turner subjects as compared to normal females, and tends to develop at a younger age, but it is usually mild and responsive to weight loss or monotherapy. The primary pathogenic event is beta cell dysfunction, but insulin resistance also plays a central role and is worsened by the presence of hypertension, obesity and dyslipidemia which are common in Turner syndrome. We present the case of a 30 year-old female patient with short stature, 141cm (<-- 2.5 SD), overweight 51kg, waist circumference 79cm, triangular facies, downslanting palpebral fissures, low set ears, short neck, secondary amenorrhea, palpitations, a history of polyuria, polydypsia of three months duration and a fasting morning glucose of 260 mg/dL. Cardiac and renal defects were excluded, hormonologic evaluation was consistent with hypergonadotropic hypogonadism (FSH 65 mUI/mL) and primary hypothyroidism (TSH 5.68 microUI/mL) and karyotype was 45,XO. She also had hypercholesterolemia (247 mg/dL), hypocalcemia (8 mg/dL), mild elevation of hepatic enzymes (ALAT 51 U/L) and osteopenia (Tscore--2.22). Glycaemic control was achieved with diet only; therapy consisted of hormone replacement theraphy, thyroxine and beta blockers.
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PMID:Diabetes mellitus and Turner syndrome. 1833 65

With an increasing spectrum of indications for growth hormone (GH), knowledge of the short- and long-term safety of this treatment is essential. In this chapter we review the main adverse effects that have been demonstrated or discussed after long-term GH treatment in children. It is well recognized that plasma insulin concentrations increase during GH treatment. The incidence of type 2 diabetes is raised during GH treatment, especially in subjects with other risk factors. Recommendations include assessing glucose tolerance by measuring plasma glucose and HbA1c before and during treatment. There is no consensus on the indications for insulin measurement and/or oral glucose tolerance tests. Other recognized short-term complications of GH treatment include pseudo-tumour cerebri, otitis media (Turner syndrome), and orthopaedic problems such as worsening of scoliosis and slipped femoral epiphysis. There are reports of sudden death within the first 6 months of treatment in children with Prader-Willi syndrome, mostly associated with severe obesity. Large cohort follow-up studies suggest that children treated with GH following childhood cancer treatment do not have a greater number of relapses, but there may be a higher incidence of second primary tumours in the early years of GH therapy. A cohort treated with human pituitary GH showed a higher incidence of tumours, and a GH effect on tumorigenesis has been seen in follow-up studies of acromegaly raising the question of whether de novo cancer risk may be increased. A new prospective pan-European safety surveillance study (SAGhE) has been launched to address these essential questions. The role of monitoring the IGF-1 response (total or free concentrations) to GH treatment to predict long-term safety is unclear at present. Attempts to target IGF-1 levels within the normal range may result in the use of excessive doses of GH. In general, higher dosage GH regimens may be associated with supraphysiological IGF-1 levels.
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PMID:Safety of recombinant human growth hormone. 2052 16


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