ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Although research into mineral metabolism has exploded in the last 2 decades, resulting in dramatic improvement in the treatment of bone diseases, mineral metabolism in relation to growth has been surprisingly neglected until the last few years. We review here recent advances in our understanding of calcium, magnesium, chromium, iron, and zinc, and their relation to growth using molecular biology and improved stable isotope techniques.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Tall stature in childhood may be intrinsic and the normal expression of familial genetic factors, or it may be the expression of adverse overgrowth syndromes such as cerebral gigantism (Sotos syndrome) or its complementary disorder (Weaver syndrome), the fragile X syndrome associated with macroorchidism, the Beckwith-Wiedemann syndrome caused by overexpression of paternally imprintedIGF2, or several other eponymic syndromes caused by mutation in various genes that influence growth (Simpson-Golabi-Behmel [TPC3], Bannayan-Riley Ruvalcaba [PTEN], Marfan [FBN1]). Tall stature may also be acquired in association with obesity, precocious puberty, thyrotoxicosis, or excess secretion of pituitary growth hormone either as an isolated disorder or as part of the complex of diseases associated with multiple endocrine neoplasia type 1. Evaluation of the tall child comprises the historical review, physical examination, estimation of growth potential (bone age), and selected laboratory studies and gene analyses as indicated by the clinical picture. Treatment of the tall child depends on establishing the correct diagnosis. Constitutionally tall children and their parents are most often reassured and observed; those with sexual precocity are managed by suppression of the sex hormone–secreting process, whereas children with growth hormone–secreting pituitary adenomas are treated neurosurgically. Patients with other causes of tall stature require individualized plans of care.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The evaluation of the child with isosexual precocious puberty involves family history, clinical findings including bone age, specific medical imaging, and hormonal data. Assessments of all these data, as well as follow-up of pubertal development, are required to decide which patients should be proposed for therapy. Central isosexual precocity, a condition much more common in girls than in boys, is currently viewed as a spectrum of disorders from isolated premature thelarche to borderline early puberty. In some countries, there may be a trend toward earlier onset of puberty. Peripheral isosexual precocity has many different causes, some specific to either boys or girls and others involving both sexes. Treatment of central isosexual precocity is usually based on long-acting forms of gonadotrophin-releasing hormone (GnRH) agonists, which may not be indicated in slowly progressive variants or borderline early puberty because they do not affect final height. In peripheral isosexual precocity, it is often possible to treat the underlying cause. In activating mutations of luteinizing hormone (LH) receptors or Gs&agr;-protein, the aim of treatment is to block hormonal synthesis or action. However, the addition of GnRH agonists is required to treat disorders that are evolving toward central isosexual precocity. In isosexual precocity, preservation of height potential is particularly important in precocious puberty started at young ages.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Malnutrition of vitamin D and calcium is still the most common cause of rickets and especially in individuals with dark complexions. The capacity of the two renal enzymes in vitamin D metabolism is rather low. Only approximately 10% of 25-hydroxyvitamin D is 24-hydroxylated and 0.3% is 1&agr;-hydroxylated. The activities of these two enzymes are reciprocally controlled by 1,25-dihydroxyvitamin D itself, and vitamin A antagonizes the action of vitamin D. Mutations in the 25-hydroxyvitamin D-1&agr;-hydroxylase gene cause hereditary vitamin D–dependent rickets type I (VDDRI). The domains that are essential for the enzyme activity were identified and are rather selective. X-linked hypophosphatemic rickets is caused by mutations in thePHEXgene and inactivity of the membrane-bound endopeptidase, resulting in impairment of both Na-dependent P-cotransporter and vitamin D metabolism. Likewise, tumor-induced osteomalacia is related to overproduction by a mesenchymal tumor of the putative phosphatonin with remission after resection of the tumor. These disease mechanisms lead to a rational algorithmic approach to diagnosis of rickets.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The extracellular calcium-sensing receptor (CaR) is a seven transmembrane–spanning G-protein–coupled receptor. It contains a large extracellular domain (ECD), the signature seven transmembrane domains (TMDs), three intracellular loops, and a large carboxy terminal tail. The CaR is expressed in the parathyroid, thyroid C-cells, kidney, brain, pituitary, intestine, bone marrow, skin, and other tissues. CaRs regulate serum calcium homeostasis through changes in parathyroid hormone (PTH) levels and renal calcium excretion. CaRs may also participate in controlling cell growth and differentiation, and in augmenting the actions of other hormones. Autosomal dominant hypocalcemia is caused by gain-of-function mutations that increase the sensitivity of the CaR to Ca2+.Familial benign hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism result from inactivating mutations of the CaR. The locations of the point mutations that are responsible for both increased and decreased sensitivity to extracellular Ca2+are typically in the ECD of the CaR, supporting the idea that the ECD is responsible for both Ca2+binding and sensing changes in Ca2+. Binding of Ca2+to the ECD may cause a conformational change in the ECD that promotes an interaction with critical TMD residues, thus enhancing G-protein–dependent signal transduction. A class of compounds called calcimimetics potentiates the effects of extracellular Ca2+on the CaR.Calcimimetics have been shown to reduce PTH and serum Ca2+in patients with primary (1°) and secondary (2°) hyperparathyroidism (HPT). Studies with rats suggest that calcimimetics may be useful in treating renal osteodystrophy and may also suppress parathyroid growth. Further long-term studies will be needed to address the possible benefit of calcimimetics to patients with 1° and 2° HPT.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Malignant endocrine tumors are relatively rare, but they may cause significant morbidity and mortality. Metastatic disease is not generally amenable to surgery, chemotherapy, or radiotherapy. There is therefore great interest in developing gene therapy as a treatment for metastases and for some primary endocrine tumors. Current gene therapy strategies largely involve the use of gene-directed enzyme pro-drug therapy (GDEPT) and using recombinant adenovirus vectors. In this review the authors examine the basic strategies used in GDEPT, progress in this area, and future directions of this work.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Receptor dimerization, subtype specialization, polymorphisms and disease-linked mutations, pharmacologic “plasticity,” dominant negative effects, new competitive effects, allosteric modulation, and surprising new approaches to pharmacotherapy—these are the themes that appear to be dominating endocrine receptor biology at the cusp of the new millenium. So, can we forecast a new age of receptor-based therapies of endocrine disorders?

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Despite feeding, lean tissue is wasted during critical illness, a problem that often persists even after the underlying disease has resolved and that perpetuates intensive care dependency. A neuroendocrine dysfunction in the chronic phase of illness was recently found to play a role.The acute phase of critical illness consists primarily of an activated anterior pituitary function, whereas peripheral anabolic pathways are inactivated. It provides the metabolic substrates and host defense required for survival and thus has been considered adaptive and beneficial. Persistence of this acute stress response throughout the course of critical illness was hitherto assumed. This assumption has now been invalidated. Indeed, a uniformly reduced pulsatile secretion of several anterior pituitary hormones is present in protracted critical illness, causing impaired function of target organs. A hypothalamic rather than pituitary dysfunction explains why administration of relevant releasing factors evokes immediate and pronounced pituitary hormone release followed by increases of target organ hormone levels and peripheral tissue responses. Recognizing the differences between acute and prolonged critical illness offers a frame in which to interpret recent “unexpected” adverse outcomes of studies using high doses of either thyroxine or growth hormone in long-stay intensive care unit patients. Also, the new concept of reduced stimulation of pituitary function in protracted critical illness opens new therapeutic perspectives to reverse the paradoxical ‘wasting syndrome’ and intensive care dependency. Treatment with releasing factors, as opposed to peripherally active hormones such as thyroid hormone, growth hormone, insulin-like growth factor-I, or anabolic steroids, enables the body to adjust peripheral hormonal metabolism and activity according to the needs determined by the disease process. This is an important safety aspect for an endocrine treatment at a time when it is virtually impossible to determine ‘normal’ or ‘optimal’ circulating levels of different peripherally active hormones. Whether this novel endocrine strategy will also enhance clinical recovery from critical illness remains to be explored.

ISSN:1068-3097    

出版商:OVID    

年代:2001

数据来源: OVID