Investigation and management of adrenal tumours

Disorders of the adrenal gland are rare and complex, with many potential pitfalls in management. An understanding of embryology, anatomy, physiology and biochemistry is crucial. There has been a dramatic increase in the incidental detection of adrenal lesions on cross sectional imaging in recent years. Surgical treatment may be required for syndromes of hormonal excess and/or suspicion of malignancy.     

Adrenocortical function during septic shock

Objective To investigate, in patients with severe septic shock, the adrenocortical function assessed by daily plasma cortisol determinations during the first 72 h and by the short synthetic ACTH stimulation test performed within 24 h of the onset of shock. Design Prospective clinical investigation. Setting Medical intensive care unit in a university teaching hospital. Patients 40 consecutive patients with documented septic shock requiring at least hemodynamic resuscitation and respiratory support. Interventions There were no intervention. Measurements and results Basal cortisol concentrations were increased with a mean value of 36.8 μg/dl (range 7.9–113). Of the overall cortisol determinations 92% were above 15 μg/dl. No statistically significant differences in basal cortisol concentrations were found when survival, type of infection, and positive blood cultures were considered. Patients with hepatic disease had significantly higher cortisol (50.1(±6.2) μ/dl versus 35.9(±3.3) μg/dl,p=0.035) levels compared to other patients. No correlations were found between basal plasma cortisol concentrations and factors such as SAPS, OSF, hemodynamic measurements, duration of shock, and amount of vasopressor and/or inotropic agents. Cortisol concentrations had significant but weak correlation with ACTH levels in survivors (r=0.4;p=0.03;n=28) but not in non-survivors (r=0.03;p=0.85;n=52). Cortisol levels in non-survivors increased significantly from enrollment time to the 72nd hour of the survey (day 1: 38.9(±3.8) μg/dl versus day 3: 66.7(±17.1) μg/dl;p=0.046) and were significantly higher than those recorded in survivors. Responses to the short ACTH stimulation test were not significantly different between survivors and non-survivors. According to the different criteria used to interpret the response to the ACTH stimulation test, incidence of adrenocortical insufficiency was highly variable ranging from 6.25–75% in patients with septic shock. Only one patient had absolute adrenocortical insufficiency (basal cortisol level below 10 μg/dl; response to the ACTH stimulation test below 18 μg/dl. Conclusion Our data suggest that in a selected population of patients with severe septic shock single plasma cortisol determination has no predictive value. The short ACTH stimulation test performed within the first 24 h of onset shock can neither predict outcome nor estimate impairment in adrenocortical function in patients with high basal cortisol level. Adrenal insufficiency is rare in septic shock and should be suspected when cortisol level is below 15 μg/dl and then confirmed by a peak cortisol level lower than 18 μg/dl during the short ACTH stimulation test.     

Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis,neuropathology and glucocorticoid-based therapeutics

Glucocorticoids mediate plethora of actions throughout the human body. Within the brain, they modulate aspects of immune system and neuroinflammatory processes, interfere with cellular metabolism and viability, interact with systems of neurotransmission and regulate neural rhythms. The influence of glucocorticoids on memory and emotional behaviour is well known and there is increasing evidence for their involvement in many neuropsychiatric pathologies. These effects, which at times can be in opposing directions, depend not only on the concentration of glucocorticoids but also the duration of their presence, the temporal relationship between their fluctuations, the co-influence of other stimuli, and the overall state of brain activity. Moreover, they are region- and cell type-specific. The molecular basis of such diversity of effects lies on the orchestration of the spatiotemporal interplay between glucocorticoid- and mineralocorticoid receptors, and is achieved through complex dynamics, mainly mediated via the circadian and ultradian pattern of glucocorticoid secretion. More sophisticated methodologies are therefore required to better approach the study of these hormones and improve the effectiveness of glucocorticoid-based therapeutics.     

The response to ACTH is determined early in the treatment of infantile spasms

Although adrenocorticotropic hormone is the most commonly used treatment for infantile spasms in the United States, the optimal regimen for this indication is not known. The purpose of this study was to elucidate the optimal adrenocorticotropic hormone treatment duration. We conducted a retrospective chart review of response to adrenocorticotropic hormone among all patients with infantile spasms managed at our institution from January 2009 to September 2013. Treatment response was defined as clinical remission for greater than or equal to 28 days starting at any point within the adrenocorticotropic hormone course and remission of hypsarrhythmia (or definite EEG improvement if hypsarrhythmia was absent at baseline). For responders, the diagnostic and post‐treatment EEG tracings were reviewed. Electroclinical remission was achieved in 21 of 39 patients (54%) receiving adrenocorticotropic hormone, including 11/25 (44%) receiving a long course (typically 12 weeks) and 10/14 (71%) receiving a short course (typically four weeks). The mean time to clinical remission was 5.8 days (median: 5 days; range: 1–20 days). Only one patient responded beyond two weeks of treatment. This study provides Class IV evidence that among patients with infantile spasms, the response to adrenocorticotropic hormone is most often determined early in the treatment course. Given the importance of rapid remission, clinicians should consider adding or changing treatment if infantile spasms do not resolve within two weeks of adrenocorticotropic hormone initiation. Further study is needed to determine the optimal adrenocorticotropic hormone regimen for infantile spasms.     

肝炎肝硬化患者促肾上腺皮质激素、糖皮质激素水平与中医证候要素的相关性探讨

目的比较代偿期与失代偿期肝炎肝硬化患者血清促肾上腺皮质激素(Adrenocorticotropic hormone,ACTH)、糖皮质激素(Glucocorticoid,GC)的水平,探讨其与中医常见病性类证候要素的相关性。方法研究制定《肝炎肝硬化临床信息采集表》,进行全国多中心的横断面流行病学调查,收集患者的一般情况、症状等信息,采集血液标本并统一检测指标;参照以往制定和发布的肝硬化诊疗共识和原则,结合文献回顾和临床调查结果,并经过专家两轮论证,形成《肝炎肝硬化常见证候要素辨识标准》,根据该标准,判定患者的常见病性类证候要素;分别分析代偿期与失代偿期患者间血清ACTH、GC水平的差异,以及代偿期和失代偿期血瘀、阴虚、湿热、气滞、气虚、阳虚、水停诸病性类证候要素的判定组与非判定组患者间ACTH、GC水平的差异。结果与代偿期比较,失代偿期患者的ACTH和GC水平均升高,其中GC差异有统计学意义(P0.05);在代偿期患者中,只有阳虚判定组患者的ACTH水平显著低于非判定组(P0.05);在失代偿期患者中,只有血瘀判定组患者的ACTH水平显著高于非判定组(P0.05);诸证候要素(除水停)判定组患者的GC水平显著高于非判定组(P0.05)。结论肝炎肝硬化患者的血清ACTH与GC水平反映了疾病的轻重,且初步提示与中医常见病性类证侯要素之间有一定相关性。     

Peripheral nerve regeneration following transection injury to rat sciatic nerve by local application of adrenocorticotropic hormone

The objective of this study was to assess local effect of adrenocorticotropic hormone (ACTH) on the functional recovery of the sciatic nerve in a transection model. Sixty male healthy white Wistar rats were randomized into four experimental groups of 15 animals each: In the sham-operated group (SHAM), the sciatic nerve was exposed and manipulated. In the transected group (TC), the left sciatic nerve was transected and the cut nerve ends were fixed in the adjacent muscle. In the silicone graft group (SIL) a 10-mm defect was made and bridged using a silicone tube. The graft was filled with phosphated-buffer saline alone. In the treatment group a silicone tube (SIL/ACTH) was filled with 10 μL ACTH (0.1 mg/mL). Each group was subdivided into three subgroups of five animals each and regenerated nerve fibres were studied at 4, 8 and 12 weeks post operation. Behavioral testing, functional, gastrocnemius muscle mass and morphometric indices showed earlier regeneration of axons in SIL/ACTH than in SIL group (p < 0.05). Immunohistochemistry clearly showed more positive location of reactions to S-100 in SIL/ACTH than in SIL group. ACTH improved functional recovery and morphometric indices of sciatic nerve. This finding supports role of ACTH after peripheral nerve repair and may have clinical implications for the surgical management of patients after nerve transection.     

Role of hypothalamic corticotropin-releasing factor in mediating alcohol-induced activation of the rat hypothalamic–pituitary–adrenal axis

Alcohol stimulates the hypothalamic–pituitary–adrenal (HPA) axis through brain-based mechanisms in which endogenous corticotropin-releasing factor (CRF) plays a major role. This review first discusses the evidence for this role, as well as the possible importance of intermediates such as vasopressin, nitric oxide and catecholamines. We then illustrate the long-term influence exerted by alcohol on the HPA axis, such as the ability of a first exposure to this drug during adolescence, to permanently blunt neuroendocrine responses to subsequent exposure of the drug. In view of the role played by CRF in addiction, it is likely that a better understanding of the mechanisms through which this drug stimulates the HPA axis may lead to the development of new therapies used in the treatment of alcohol abuse, including clinically relevant CRF antagonists.