肾上腺区巨大肿瘤的影像学定位诊断和介入治疗评价

①目的　探讨不同影像学检查方法对肾上腺区巨大肿瘤的定位诊断及介入治疗的价值。②方法　收集经手术和病理证实、肿瘤直径＞ １０ｃｍ 的肾上腺区巨大肿瘤病人１７ 例,对其诊断和治疗进行总结分析。③结果１７例中ＣＴ定位诊断正确１１ 例,占６４．７％ ;Ｂ超诊断正确７ 例,占４１．２％ ．５ 例行ＤＳＡ 检查,定位诊断正确率达１００％ ,均行肾上腺动脉栓塞治疗后手术切除。④结论　各种影像学检查方法,对肾上腺区巨大肿瘤的定位诊断正确率由高到低依次为ＤＳＡ,ＣＴ和Ｂ超。介入治疗既可作为手术前栓塞治疗,也可作为不能手术切除肿瘤的姑息性治疗。     

Value of direct measurement of active renin concentrations in congenital adrenal hyperplasia due to 21-hydroxylase deficiency

In congenital adrenal hyperplasia (CAR) due to 21-hydroxylase deficiency, measurement of plasma renin activity (PRA) has been the method of choice in diagnosing salt loss and in monitoring adequacy of mineralocorticoid replacement therapy. Due to methodological problems in PRA determinations, direct immunoradiometric assays for the measurement of active renin concentration have been developed. We measured PRA and active renin concentrations simultaneously in 39 patients with CAH (30 salt-wasting, 9 simple virilizing) to evaluate the potential role of this new method in the management of this disease. PRA was determined with an enzymatic assay (sample volume: 2 × 1000 l plasma), active renin concentration with a direct immunoradiometric assay (sample volume: 2 × 200 l plasma or serum). We found a highly significant correlation between active renin and PRA in our patients (P < 0.001), as previously shown in healthy subjects. Active renin was as reliable as PRA to assess the quality of mineralocorticoid replacement.     

Family studies of the steroid 21-hydroxylase and coplement C4 genes define 11 haplotypes in classical congenital adrenal hyperplasia in The Netherlands

Two steroid 21-hydroxylase genes are normally present within the human major histocompatibility complex near the genes encoding the fourth component of complement (C4A and C4B). Steroid 21-hydroxylase is encoded by the CYP21 gene, while the highly homologous CYP21P gene is a pseudogene. We studied steroid 21-hydroxylase and complement C4 haplotypes in 33 Dutch patients (29 families) suffering form classical congenital adrenal hyperplasia (CAH) and in their 80 family members, and also in 55 unrelated healthy controls, using 21-hydroxylase and complement C4 cDNA probes. Eleven different haplotypes, defined in terms of gene deletions, gene duplications, conversions of CYP21 to CYP21P, and long and short C4 genes, were found. In 23% of the patients' haplotypes, the CYP21 gene was deleted; in 12%, it was converted into a CYP21P pseudogene. In the remaining 65%, the defect was apparently caused by a mutation not detectable by this method. The most common haplotype (with one CYP21 and one CYP21P gene) was significantly more often observed in patients with simple virilizing CAH than in those with salt-losing CAH. Comparison of the 21-hydroxylase haplotypes found in CAH patients from several countries shows evidence for considerable genetic variation between the groups studied.     

Endocrine effects of dehydroepiandrosterone and its fluorinated analog,fluasterone, in rats

Cancer chemoprevention is the use of pharmacologic agents to inhibit the development of cancer. The adrenal steroid dehydroepiandrosterone (DHEA) has demonstrated chemopreventive efficacy in animal models of tumorigenesis. However, due to DHEA's undesirable hormonal actions, the fluorinated analog fluasterone (fl‐DHEA), which also has chemopreventive characteristics, was synthesized as a potential alternate agent. It is not known whether fl‐DHEA has hormonal actions. The endocrinologic effects of DHEA and fl‐DHEA in adult male and female Fischer 344 rats were examined following 28 days of daily oral treatment. Initial doses tested were 30 and 300 mg/kg/day for each drug (n=12/sex/group), which are equivalent to 104 and 1,042 µmoles/kg/day DHEA, and 103 and 1,034 µmoles/kg/day fl‐DHEA. However, due to weight loss at the high dose, doses were lowered to 150 mg/kg/day for each drug (521 and 517 µmoles/kg/day DHEA and fl‐DHEA, respectively). Administration of DHEA resulted in dose‐dependent increases in plasma DHEA and DHEA‐S 1 h after dosing in week 4. DHEA produced an estrogenic effect in female rats expressed as decreased plasma FSH and LH, inhibition of ovulation, prolonged estrus, and increased uterine estrogen receptors. DHEA also increased plasma levels of androstenedione in males and females. Administration of fl‐DHEA increased the estrus cycle length due to a prolonged diestrus II phase and decreased the weights of the uterus, prostate, seminal vesicles, and testes. In addition, fl‐DHEA decreased plasma FSH, LH, and tissue estradiol, and increased plasma dihydrotestosterone levels in both sexes. These results indicate that fl‐DHEA is hormonally active and additional studies are warranted to further describe its endocrinologic effects. Drug Dev. Res. 58:169–178, 2003. © 2003 Wiley‐Liss, Inc.     

Outcome of congenital adrenal hyperplasia

In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, affected girls are born with ambiguous genitalia due to increased secretion of androgens in utero by the defective adrenal gland. Even though it is generally accepted that there are differences between male and female brain development, determining factors have been difficult to identify. Girls with CAH have frequently been studied to evaluate the impact of prenatal androgen exposure on psychological, psychosocial, and psychosexual development, and impairments in various areas have been identified. However, there is no comprehensive study available regarding the outcome of this chronic disorder in adult life. We studied the quality of life in women with CAH, with particular emphasis on how they cope with genital malformations, genital operations, and chronic disease as well as lifelong medication. The patients filled out questionnaires covering their physical state, psychological well-being, social relationships, and functional capacity, as well as questionnaires on psychosexual identification and psychosocial integration. The results were evaluated using a computerized statistical program for social studies. Out of a total of 94 patients above 18 years of age, 45 agreed to participate and were compared to 46 healthy, age-matched controls. Age at diagnosis was 2.31 ± 1.55 years and 38% suffered from the simple-virilizing, 45% from the salt-wasting, and 17.0% from the late-onset form of CAH. About one-third of patients had Prader stage 3 or 4 genital virilization. While the overall quality of life did not differ significantly, CAH patients were more often single (47.8% vs. 66.7%) and fewer of them had children (22.2% vs. 38.6%) compared to controls. Significant impairments were found in regard to body image and attitudes toward sexuality, but there was no increased homosexual preference. The women were successful in adjusting to illness and receiving social support. It is speculated that improved psychosocial adaptation is part of a coping mechanism that helps to maintain a high level of well-being despite impairment. Coping mechanisms should be identified and strengthened in order to help patients cope with their chronic illness.     

A patient with congenital lipoid adrenal hyperplasia evaluated by serial abdominal ultrasonography

Adrenal enlargement was followed by serial ultrasonography in an infant with congenital lipoid adrenal hyperplasia (lipoid CAH) from day 12 until 2 years and 4 months of age, when they were no longer detectable. Contrary to other types of CAH in which the configuration changes soon after replacement therapy, this infant with lipoid CAH showed persistent adrenal cortex enlargement due to massive accumulation of lipids and cholesterol resulting in a damaged glandular cyto-architecture. Conclusion ultrasonographically persistent enlargement of the adrenals after replacement therapy is suggestive of the lipoid form of CAH. Received: 3 June 1997 / Accepted in revised form: 19 December 1997     

Abnormalities in the serum insulin-like growth factor-1 axis in women with hyperandrogenism

Objective: To study the insulin-like growth factor-1 (IGF-1) axis in hirsute women.

Design: Controlled clinical study.

Setting: Tertiary care institutional hospital.

Patient(s): Forty hirsute women and 17 women with normal menstrual cycles.

Intervention(s): Basal and ACTH-stimulated samples were obtained, and sampling was repeated 1 (gonadal stimulation) and 21 (gonadal suppression) days after a single 3.75-mg IM dose of triptorelin. Controls did not receive triptorelin for ethical reasons.

Main Outcome Measure(s): Serum GH, IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, glucose, total testosterone, sex hormone-binding globulin, E₂, and gonadotropin levels. Basal and ACTH-stimulated steroid precursors were measured.

Result(s): Patients with idiopathic hirsutism were identified by normal serum androgen levels (n = 17). Those with functional ovarian hyperandrogenism (n = 15) were identified by an increase in the serum testosterone level that normalized during gonadal suppression, whereas those with functional adrenal hyperandrogenism (n = 8) were identified by an initial increase in the testosterone level that persisted during gonadal suppression. The adrenal hyperandrogenism group had increased IGF-1 levels compared with the control, idiopathic hirsutism, and ovarian hyperandrogenism groups. Patients with ovarian hyperandrogenism had normal IGF-1 concentrations, but their IGFBP-3 concentrations were lower than those of controls. No differences were observed in GH levels between any of the groups. These results persisted when the influence of age was corrected for.

Conclusion(s): The IGF-1 axis appears to be involved in the pathogenesis of hyperandrogenism, especially in patients with adrenal hyperandrogenism, who have a clear increase in IGF-1 levels. Moreover, patients with ovarian hirsutism have decreased IGFBP-3 concentrations, which might enhance IGF-1 bioavailability.     

Regional differences in brain monoamine oxidase subtypes in an animal model of geriatric depression: effects of olfactory bulbectomy in young versus aged rats

Geriatric depression is often associated dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, and with poor responsiveness to antidepressants that work through inhibition of monoamine reuptake; accordingly, it has been suggested that MAO inhibitors may represent a therapeutic alternative in this group. In the current study, we evaluated expression of MAO subtypes in brain regions of young and aged rats subjected to olfactory bulbectomy (OBX), a procedure that reproduces many of the biochemical and functional changes associated with human depression. Activities of both MAO A and B were elevated in aged rats as compared to young rats in most regions, but not in the midbrain, and the OBX lesion failed to produce any change in this pattern. These results stand in contrast to the differential effects of glucocorticoids, which reduce brain MAO in young animals but induce activity in aged rats. Our results support the view that the aged brain possesses biochemical characteristics that distinguish its monoamine biochemistry from that of young brain, and that these distinctions may work in conjunction with HPA axis dysregulation to influence the etiology and therapy of geriatric depression. The use of appropriate animal models for depression and for disruption of HPA axis function can allow for the testing of potential human biomarkers (such as platelet MAO) that may serve to predict treatment outcome.     

Agouti related protein in the rat adrenal cortex: implications for novel autocrine mechanisms modulating the actions of pro-opiomelanocortin peptides

Agouti related protein (AgRP) is a recently discovered melanocortin receptors (MCR) antagonist implicated in the control of feeding behaviour. Expression of AgRP has been shown to be localized by in situ hybridization to the arcuate nucleus and median eminence of the brain, where it acts as an antagonist to the MC3 and MC4 receptors, while in the periphery the only significant expression was located in the adrenal medulla. As AgRP is only a weak antagonist of the MC2 and MC5 receptors, which are expressed principally by adipocytes and in the adrenal cortex, the question arizes as to the function of peripheral AgRP. In this study, we investigated the expression of AgRP in the rat adrenal and suggest that it is expressed in the adrenal cortex and not as previously described in the medulla. We also show that AgRP mRNA expression is upregulated in the adrenal during fasting and in the contralateral gland following unilateral adrenalectomy but not during chronic stress. These results indicate an as yet undefined role for AgRP in the periphery and are supportive of the suggestion that a further melanocortin receptor exists.