ISSN:1051-2144    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Ectopic adrenocorticotropic (ACTH) syndrome is a relatively rare cause of Cushing’s syndrome. Sometimes the tumor cannot be found. Unfortunately, medical treatment is sometimes ineffective and bilateral adrenalectomy becomes necessary. We report a case of Cushing’s syndrome with the clinical and biochemical characteristics of ectopic ACTH syndrome, but the source of the ACTH could not be found. Somatostatin receptor scintigraphy was negative. Somatostatin analog was tried after a positive Sandostatin test. Cushing’s syndrome improved. Six months later this treatment failed.

ISSN:1051-2144    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Acromegaly is caused by a primary growth hormone-secreting pituitary adenoma in more than 95% of the cases. In a small number of patients, it is the result of hypersecretion of growth hormone-releasing hormone (GHRH). Clinical and laboratory findings are similar in both conditions, and the diagnosis of a GHRH-secreting tumor is possible only by identification of GHRH in the tumor or circulation. We report the case of a 61-year-old woman referred to the Hospital Naval Marcílio Dias to investigate a pulmonary mass. The mass was large and calcified, suggesting a hamartoma. The patient also had acromegalic features, elevated serum insulin-like growth factor-1 (IGF-1) levels, and no GH suppression after an oral glucose tolerance test. Magnetic resonance imaging (MRI) showed a diffusely enlarged pituitary gland, suggestive of hyperplasia. The hypothesis of acromegaly secondary to ectopic GHRH secretion by the pulmonary mass was made. A left pneumectomy was performed and histopathologic analysis revealed a carcinoid tumor. A fragment of the tumor was sent for special stains and GHRH was identified by immunohistochemistry. The clinical and biochemical aspects of acromegaly improved 2 weeks after surgery. One year later, serum GH and IGF-1 levels were normal and MRI revealed a partial empty sella. The differential diagnosis of somatotroph adenoma and ectopic GHRH hypersecretion is difficult but is essential to appropriate therapy.

ISSN:1051-2144    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Science encompasses the art of describing events with numbers and words, then applying those descriptions to the understanding of measurable phenomena. Validating the understanding requires that the phenomena of interest not only be predictable, but also coherent with the whole of scientific thought. Validation of the successful integration of evolutionary narrative, comparative endocrinology, and explanation of the mechanisms accounting for the variance in human body composition, especially skeletal mineralization studied in the context of medicine, is the purpose of this work. Evaluation of mineral metabolism and medical interventions in individual patients permitted the development of physiological models depicting relationships describing a discipline termed structural ecology. A central assumption of structural ecology is that heterogeneity within both populations and individuals is adaptive to environmental change and results in a physiology based not on homeostasis, but adaptive heterostasis directed toward the maintenance of adequate energy. The signaling system for structural ecology is phosphate-based, with skeletal mineralization assuring adequate phosphate to the organism. Validation of the models, termed structural influence models, has been accomplished through the successful prediction of a statistical correlation between variance in bone mineral content at the trochanter and the environmental influence of acute gravitational change on urinary Na+excretion (r = 0.44,P= 0.004) as accomplished with head-out immersion in water with a group of postmenopausal women (n = 33). Further analysis of the data identifies the presence of antipolar heterogeneity in which subgroups, one increasing and the other decreasing urinary Na+excretion with immersion, the latter without apparent confounding factors. Coherence criteria are used to provide a highly plausible explanation for this finding, based on both the evolutionary narrative and the originally proposed structural influence models. It is then possible to explore the relative merits of investigative strategies using statistics versus coherence, and descriptive methods, numbers versus words, in the application of data to the understanding of medicine. The structural influence models depicting structural ecologic relationships appear to be useful in clarifying the difficulties arising when attempting to apply the mean values from heterogeneous groups to the individuals, as well as the problem of validating anecdotal evidence with group studies.

ISSN:1051-2144    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The concern for early cardiovascular morbidity and mortality is becoming increasingly more common in the pediatric arena due to the continually increasing incidence of type 1 and type 2 diabetes mellitus, as well as the rise in obesity in this population. Currently the only treatment recommendations are derived from adult guidelines, due to a lack of evidence-based data in children. Independent risk factors for cardiovascular disease are similar in children and adults: obesity, presence of diabetes, hyperglycemia, insulin resistance, hypertension, and hyperlipidemia. Postmortem studies in children have shown that atherosclerotic plaques begin in childhood, and coronary artery lesions can be seen as early as 10 years of age. The development of atherosclerotic plaques appears to be due to endothelial dysfunction as a result of inflammatory changes from the above listed cardiovascular risk factors. Currently there are several serum markers of inflammation that are predictive of cardiovascular disease in adults, but the significance of changes in the levels of these markers in children is currently unknown. Additionally, there are several noninvasive techniques to measure endothelial dysfunction, including brachial artery reactivity and ECHO Doppler carotid intima-medial thickness, which may ultimately prove to be predictive for cardiovascular disease in children. The management of hypertension in adult patients has been a critical aspect of prevention of cardiovascular disease, but treatment of hypertension in pediatric patients is difficult due to the lack of trials of safety and efficacy in children, as well as lack of universally accepted standards for the appropriate age and blood pressure level for starting treatment. However, data from adult studies of cardiovascular risk suggest that there would be benefit to early, aggressive control of elevated blood pressure in children. Future studies will be needed to determine which antihypertensive medications will be safe and effective in children, as well as to determine starting points for treatment of hypertension in this population. The treatment of dyslipidemia in adults has resulted in significant risk reduction for cardiovascular morbidity and mortality, but there is a paucity of information available about the long-term safety of using lipid-lowering medications in growing children. Currently, bile acid sequestrants are the only lipid-lowering medication approved for children of all ages, while other lipid-lowering medications are only approved for use in children age 10 and above, and for use in familial hypercholesterolemia. Short-term studies of the statin medications in small groups of male children have shown excellent compliance with no adverse effects on growth, sexual maturation, or hormone levels, but longer-term, more comprehensive studies are needed in the pediatric population. Both the statins and the thiazolidinediones have been shown to have pleotropic effects on the endithelium, which may confer a cardioprotective environment. Treatment of cardiovascular risk factors in childhood consists of a step-wise approach, including lifestyle modification and pharmacologic therapy. Therapy must be individualized based on number of risk factors, family history, and existing complications. Although further longitudinal studies of medications are needed in children, there may be benefit to following adult guidelines, especially in high-risk adolescents, and instituting early, aggressive treatment for modifiable risk factors.

ISSN:1051-2144    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The development of a growth hormone (GH) receptor antagonist was driven by the appreciation of the need for additional treatment in the significant minority of patients with acromegaly inadequately controlled by conventional therapies, as well as by the recognition of the therapeutic potential of manipulation of the GH/Insulin-like growth factor 1 (IGF-1) axis in diseases such as breast cancer and the small vessel complications of diabetes. The “design” of pegvisomant has exploited the rapid advances in the last decade of our understanding of cytokines and their receptors. GH is a 191 amino acids peptide that contains 2 disulfide bonds and 4 &agr; helices, and has a molecular mass of approximately 22,000 d. A glycine at position 120 in the 3rd &agr;-helix of human GH (hGH) is crucial to its biologic activity and, if replaced with a variety of amino acids, the GH analog acts not as an agonist, but as a growth suppressor. Pegvisomant (Somavert) is a 191 amino acid GH analog that contains a position 120 amino acid substitution that generates the antagonist, as well as additional amino acid substitutions to optimize site 1 binding. The antagonist is further modified by addition of polyethylene glycol moieties, which increase its half-life and reduce immunogenicity. In an era when the need for tight control of the GH/IGF-I axis has been convincingly demonstrated, but when pituitary surgery and the combined use of dopamine agonists and somatostatin (SMS) analogs leave significant numbers of patients inadequately controlled, the availability of pegvisomant is a welcome addition to the existing treatment modalities for acromegaly. Early clinical studies indicate pegvisomant to be the most potent medical treatment of acromegaly to date as serum IGF-I is normalized into the age-related reference range in 97% of patients treated with doses of up to 40 mg per day. Although a great deal more information is needed on the long-term effects of pegvisomant on both the metabolic consequences of acromegaly and pituitary adenoma tumor growth, it represents the most exciting development in the medical management of acromegaly for many years.

ISSN:1051-2144    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

In this study, we determined the prevalence of idiopathic hypercalciuria (IH) in patients with renal lithiasis, and measured the bone mineral density (BMD) and biochemical markers of bone metabolism in patients with IH. Among 85 consecutive patients with urolithiasis (40 men, 30 postmenopausal and 15 premenopausal women), hypercalciuria (urinary calcium excretion >4 mg/kg per day) was observed in 22 (11 men, 8 postmenopausal and 3 premenopausal women). These 22 patients were then classified as having absorptive or fasting hypercalciuria. In 19 of the 22 hypercalciuric patients (11 men and 8 postmenopausal women), BMD was measured by dual-energy x-ray absorptiometry and serum levels of calcium, alkaline phosphatase, parathyroid hormone, osteocalcin (OC), and urinary deoxypyridinoline (DPD) were determined. When compared with age- and sex-matched control subjects (volunteers from hospital personnel), OC and urinary DPD levels were significantly higher in the renal lithiasis patients when compared with control subjects. Ward’s triangle BMD in women and lumbar BMD in men were significantly lower when compared with sex- and age-matched control subjects. Lumbar, Ward’s triangle, and femoral neck BMD measurements were inversely correlated with the duration of renal lithiasis in male patients. Males also had a significant negative correlation between lumbar BMD and the urinary DPD. BMD decreases significantly in male and postmenopausal female patients with IH. Patients with renal lithiasis should be evaluated for IH, and those with IH should be screened for osteoporosis. Studies determining the clinical and lifestyle consequences of IH and its related osteoporosis should be performed.

ISSN:1051-2144    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The proliferation of pituitary somatotroph cells and their synthesis and secretion of growth hormone (GH) are under the control of the hypothalamic factor GH-releasing hormone (GHRH), which acts by binding to a specific cell surface receptor (GHRH receptor [GHRHR]). Mutations in the GHRHR gene (GHRHR) are emerging as a relatively common cause of familial isolated GH deficiency (IGHD) type IB, the most prevalent form of familial IGHD, transmitted as an autosomal-recessive trait. Initially,GHRHRmutations have been reported in families in which the homozygously affected subjects had consanguineous parents. More recently, kindreds are being discovered in which affected subjects are compound heterozygotes for differentGHRHRmutations, proving that faultyGHRHRalleles could be rather prevalent in the general population. Patients in whom bothGHRHRalleles are defective have severe IGHD, with frankly low serum insulin-like growth factor-1 level and subnormal serum GH response to a variety of GH stimulation tests. Pituitary function is otherwise normal. They never present with micropenis or neonatal hypoglycemia, but they invariably have anterior pituitary hypoplasia when studied by magnetic resonance imaging. In this review, we describe the heterogeneity of theGHRHRmutations discovered so far, the phenotype of affected individuals, and the clinical characteristics that should cause the endocrinologist to suspect the existence of one of these genetic abnormalities.

ISSN:1051-2144    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Acromegaly is an endocrine disorder that affects multiple organ systems and increases mortality by 2 to 4 times that of the general population. Elevated growth hormone (GH) levels are the hallmark of acromegaly, but GH secretion is pulsatile and not an accurate marker of disease. IGF-I provides a reliable indication of overall GH secretion and is the single most reliable screening test for acromegaly. In addition, many of the somatotrophic effects of GH are mediated by IGF-I. The goals of treatment of acromegaly are to achieve biochemical control, stabilize or reduce tumor size, and maintain or recover pituitary function. Treatment options for acromegaly include surgery, radiation therapy, and drug therapy. Available medical therapies include somatostatin analogs and dopamine agonists. The advantages and limitations of these therapies are reviewed. A novel medical therapy is pegvisomant, a GH receptor antagonist that binds to GH receptors on the cell surface of target cells and blocks GH signal transduction and GH action. Unlike other medical therapies, effectiveness of pegvisomant is independent of receptor expression on pituitary tumors. Pegvisomant has been demonstrated to be highly effective in reducing IGF-I concentrations to normal levels and significantly improving signs and symptoms of acromegaly in up to 97% of treated patients. Therefore, pegvisomant is a promising new agent that offers significant advances in the treatment of acromegaly.

ISSN:1051-2144    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:1051-2144    

出版商:OVID    

年代:2003

数据来源: OVID