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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular diagnostic techniques provide an unsurpassed opportunity to understand the pathophysiological basis of endocrine disorders. Diseases have been associated with mutations in almost every gene known to have a role in either the production or secretion of a hormone or the mediators of hormone signalling. Even though most of these mutations are rare and account for only a small fraction of endocrine diseases, molecular diagnostics offers a valuable tool for the clinician in these cases. The most common endocrine disorders such as autoimmune thyroiditis, type 2 diabetes mellitus, osteoporosis, growth disorders, and obesity have all major genetic components, but these are mostly unknown. In this review the clinical implications of molecular diagnostics are illustrated for some endocrine diseases: congenital adrenal hyperplasia, congenital hypothyroidism, thyroid hormone resistance, familial hypocalciuric hypercalcaemia, growth hormone deficiency and resistance, and monogenic obesity. Improved diagnostic specificity has direct implications for treatment and follow up in these syndromes. Molecular diagnostics in endocrine tumours and diabetes are presented in two other articles in this series.
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PMID:[Molecular diagnostics in endocrine diseases]. 1647 3

Adult growth hormone deficiency (GHD) is a multifactorial disorder in which pituitary dysfunction associated with pituitary adenomas or their treatment plays a major role. The introduction of recombinant growth hormone (GH) for the treatment of GHD has opened up new treatment avenues but has also raised concerns about possible untoward long-term metabolic effects of GH, such as the potential effect of GH on insulin sensitivity and a deterioration in glucose tolerance. Research has shown that GH induces insulin resistance by the stimulation of lipolysis and a concomitant switch from oxidation of glucose to oxidation of lipids, during both acute and chronic treatment. However, although this is a consistent effect of GH therapy, it does not mean per se that it leads to abnormal glucose tolerance and diabetes mellitus. This article discusses this and other potential long-term metabolic effects of GH, and raises a number of questions to be addressed by future research.
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PMID:Insulin sensitivity in adults with growth hormone deficiency and effect of growth hormone treatment. 1643 44

Although numerous studies are available in the literature on endocrine complications in thalassaemia, little is known about this subject in developing countries. Therefore, an international multicenter study was conducted in a large series of children and adolescents with beta thalassaemia major in order to obtain more information on the prevalence of short stature and endocrine complications in different areas of the world and to elucidate the problems that must be dealt with in the future. A questionnaire was sent to 29 Centres treating a total of 3817 beta thalassaemia major patients. Thirty-six per cent of patients were over the age of 16 years. Short stature was present in 31.1% of males and 30.5% of females, and the prevalence of growth hormone deficiency was 7.9% in males and 8.8% in females. Lack of pubertal changes was the most common endocrine complication (40.5%) followed by hypoparathyroidism (6.9%), impaired glucose tolerance (6.5%), insulin-dependent diabetes mellitus (3.2%) and primary hypothyroidism (3.2%). The prevalence of endocrine complications differed among centres, particularly for growth hormone deficiency, hypoparathyroidism and hypothyroidism. Compliance to chelation therapy was poor in 51% of patients and serum liver enzymes were high in 65% of patients. Since several endocrine glands may be affected in patients with thalassaemia major, and their life expectancy is now much longer, it is important that physicians be aware of the endocrine abnormalities that may develop. Therefore, periodic evaluation of these problems should be carried out in thalassaemic patients with iron overload, particularly after the age of 11 years. In conclusion, since iron overload and liver damage seem to be the most important factors responsible for endocrine complications, adequate compliance to chelation therapy and rigid precautions against liver infections are imperative.
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PMID:Prevalence of endocrine complications and short stature in patients with thalassaemia major: a multicenter study by the Thalassaemia International Federation (TIF). 1646 5

There is now conclusive evidence that gene therapy can lead to real clinical benefit. Initial enthusiasm has been muted by set-backs related to viral vectors including retroviral oncogenesis and adenoviral inflammatory response. Plasmid-mediated muscle-targeted gene transfer offers the potential of a cost-effective pharmaceutical grade therapy delivered by simple intramuscular injection without the need for anaesthetic, cell culture, transplantation or immunosuppression. This approach is particularly appropriate for long-term circulating therapeutic protein replacement currently requiring repeated injection therapy. Wide-ranging clinical applications include haemophilia, chronic anaemia, growth hormone deficiency and diabetes. Inadequate transgene expression, unregulated protein delivery and immune response have been major limiting factors. Recent innovations including in situ electroporation enabling sustained systemic protein delivery within the therapeutic range are reviewed. Pharmacological and physiological approaches to regulation are discussed in addition to the role of innate and humoral immunity. Translation of advances in all of these areas to clinical success will enable muscle-targeted gene therapy to capitalise on its inherent strengths and realise its long-standing promise.
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PMID:Plasmid-mediated muscle-targeted gene therapy for circulating therapeutic protein replacement: a tale of the tortoise and the hare? 1647 48

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.
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PMID:Endocrine dysfunction and parameters of the metabolic syndrome after bone marrow transplantation during childhood and adolescence. 1669 34

Patients with beta-thalassemia (thal) major are subject to peroxidative tissue injury by iron overload. Glutathione S-transferases work as antioxidants, and their activity is determined genetically. In this study, we used multiplex polymerase chain reaction (m-PCR) to analyze polymorphisms of two endogenous antioxidant agents, glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1), and to determine their roles in 41 patients with beta-thal major. Our results showed that the GSTM1 and GSTT1 null genotypes were not associated with any incidence of endocrine dysfunction (including diabetes mellitus, hypogonadism, hypothyroidism, and growth hormone deficiency), liver function, or impaired left ventricular ejection fraction (LVEF). The GSTM1 null genotype, but not the GSTT1 null genotype, was associated with a decreased signal intensity ratio on cardiac magnetic resonance imaging (MRI). Our results suggest that genetic variations of the GSTM1 enzyme are associated with cardiac iron deposition in patients with beta-thal major.
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PMID:Glutathione S-transferase M1 gene polymorphisms are associated with cardiac iron deposition in patients with beta-thalassemia major. 1679 50

The purpose of this study carried out at a single institute in Japan was to investigate the clinical characteristics and complications of patients with adult growth hormone deficiency (GHD). Clinical and biochemical data of 110 patients (50 males, 60 females; mean age 42 +/- 17 yr) with adult GHD who attended Tokyo Women's Medical University between 1990 and 1999 were analyzed retrospectively from medical records. This retrospective analysis demonstrated that 109 patients had multiple pituitary hormone deficiencies, with 98 patients having a deficiency of more than three hormones. Sixty-one patients had childhood onset GHD (COGHD) while the remaining 49 patients had adulthood onset GHD (AOGHD). Body mass index (BMI) ranged from 16.9 to 35.9 with a mean of 23.9 +/- 4.1 (kg/m2), with BMI being > or = 25 kg/m2 in 38 patients (31% of COGHD and 38% of AOGHD). Forty-one percent of the patients had hypercholesterolemia, 41% had hypertriglyceridemia, 47% had decreased levels of HDL cholesterol and 48% had increased levels of LDL cholesterol. Intima-media thickness (IMT) of the carotid arteries was investigated in 33 patients, with abnormal findings including increased IMT or plaque being observed in 4 of 18 COGHD patients and 4 of 15 AOGHD patients. Diabetes mellitus and impaired glucose tolerance was found in 4 COGHD patients and 16 AOGHD patients. Insulin resistance was assessed in 36 patients by the homeostasis model insulin resistance index (HOMA-R) and ranged from 0.65 to 10.58 with a mean of 2.80 +/- 0.37. This mean value of HOMA-R was significantly greater than that measured in normal subjects (1.58 +/- 0.05: P < 0.05). These data suggest that abnormal lipid and glucose metabolism, and atherosclerotic changes occur frequently in adult patients with GHD. Insulin resistance may play a role in glucose and lipid metabolism disorders associated with GHD.
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PMID:Metabolic disorders in adult growth hormone deficiency: A study of 110 patients at a single institute in Japan. 1682 2

Although hypopituitarism is a known complication of traumatic head injury, it may be under-recognized due to its subtle clinical manifestations. To address this issue, we determine the prevalence of neuroendocrine abnormalities in patients rehabilitating from severe traumatic brain injury (Glasgow Coma Scale < or = 8). 76 patients (mean age 39 +/- 14 yr; range 18-65; 53 males and 23 females; BMI 25.8 +/- 4.2 kg/m2; mean +/- SD) with a severe traumatic brain injury, an average of 22 +/- 10 months before this study (median, 20 months), underwent a series of standard endocrine tests, including TSH, free T4, T4, T3, prolactin, testosterone (males), estradiol (females), cortisol, ACTH, GH, and IGF-I. All subjects also underwent GH response to GHRH + arginine. Growth hormone deficiency (GHD) was defined as a GH response < 9 microg/L to GHRH + arginine and was confirmed by ITT (< 3 microg/L). Pituitary deficiency was shown in 24% of the patients (18/76). 8% (n = 6) had GHD (GH-peak range [GHRH + arginine]: 2.8-6.3 microg/L; GH-peak range [ITT]: 1.5-2.2 microg/L; IGF-I range: 62-174 microg/L). 17% (n = 13) had hypogonadism (total testosterone < 9.5 nmol/L and low gonadotropins in 12 males; low estradiol, and low gonadotropins in 1 female). Total testosterone levels did not correlate with BMI or age. 2 males with hypogonadism also showed a mild hyperprolactinemia (33 and 41 ng/ml). 3% (n = 2) patients had partial ACTH-deficiency (cortisol-peak [ITT] 392 and 417 nmol/L) and 3% (n = 2) had TSH-deficiency. In summary, we have found hypopituitarism in one-fourth of patients with predominantly secondary hypogonadism and GHD. These findings strongly suggest that patients who suffer head trauma must routinely include neuroendocrine evaluations.
Exp Clin Endocrinol Diabetes 2006 Jun
PMID:Hypopituitarism following severe traumatic brain injury. 1686 91

Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant (MIHF) or syntelencephaly is also reported. In most of the cases, facial anomalies are observed in HPE, like cyclopia, proboscis, median or bilateral cleft lip/palate in severe forms, ocular hypotelorism or solitary median maxillary central incisor in minor forms. These latter midline defects can occur without the cerebral malformations and then are called microforms. Children with HPE have many medical problems: developmental delay and feeding difficulties, epilepsy, instability of temperature, heart rate and respiration. Endocrine disorders like diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia and growth hormone deficiency are frequent. To date, seven genes have been positively implicated in HPE: Sonic hedgehog (SHH), ZIC2, SIX3, TGIF, PTCH, GLI2 and TDGF1. A molecular diagnosis can be performed by gene sequencing and allele quantification for the four main genes SHH, ZIC2, SIX3 and TGIF. Major rearrangements of the subtelomeres can also be identified by multiplex ligation-dependent probe amplification (MLPA). Nevertheless, in about 70% of cases, the molecular basis of the disease remains unknown, suggesting the existence of several other candidate genes or environmental factors. Consequently, a "multiple-hit hypothesis" of genetic and/or environmental factors (like maternal diabetes) has been proposed to account for the extreme clinical variability. In a practical approach, prenatal diagnosis is based on ultrasound and magnetic resonance imaging (MRI) rather than on molecular diagnosis. Treatment is symptomatic and supportive, and requires a multidisciplinary management. Child outcome depends on the HPE severity and the medical and neurological complications associated. Severely affected children have a very poor prognosis. Mildly affected children may exhibit few symptoms and may live a normal life.
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PMID:Holoprosencephaly. 1727 16

Hemolytic anemias can induce various anomalies of the endocrine glands which can already be observed in children. Endocrine dysfunction is also found in the course of therapy for aplastic anemias, usually as undesirable side effects. In Europe, 2-9% of the population belongs to ethnic minorities at risk for developing hemolytic anemia. Pituitary affinity to iron deposition explains the high incidence of hypogonadism, puberty delay and growth retardation although other factors have to be considered. Growth hormone deficiency has to be ruled out as it can occur in a minority of subjects with thalassemia and sickle-cell disease (drepanocytosis). Diabetes mellitus, hypothyroidism and hypoparathyroidism may also develop. Follow-up includes close monitoring of growth and pubertal development in order to guide therapeutic interventions.
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PMID:[Severe chronic anemia and endocrine disorders in children]. 1752 72


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