Corticoids Research Articles

Adrenocortical suppression and recovery after continuous hypnotic infusion: etomidate versus its soft analogue cyclopropyl-methoxycarbonyl metomidate

IntroductionEtomidate is no longer administered as a continuous infusion for anesthetic maintenance or sedation, because it results in profound and persistent suppression of adrenocortical steroid synthesis with potentially lethal consequences in critically ill patients. We hypothesized that rapidly metabolized soft analogues of etomidate could be developed that do not produce persistent adrenocortical dysfunction even after prolonged continuous infusion. We hope that such agents might also provide more rapid and predictable anesthetic emergence. We have developed the soft etomidate analogue cyclopropyl-methoxycarbonyl etomidate (CPMM). Upon termination of 120-minute continuous infusions, hypnotic and encephalographic recoveries occur in four minutes. The aims of this study were to assess adrenocortical function during and following 120-minute continuous infusion of CPMM and to compare the results with those obtained using etomidate.MethodsDexamethasone-suppressed rats were randomized into an etomidate group, CPMM group, or control group. Rats in the etomidate and CPMM groups received 120-minute continuous infusions of etomidate and CPMM, respectively. Rats in the control group received neither hypnotic. In the first study, adrenocortical function during hypnotic infusion was assessed by administering adrenocorticotropic hormone (ACTH) 90 minutes after the start of the hypnotic infusion and measuring plasma corticosterone concentrations at the end of the infusion 30 minutes later. In the second study, adrenocortical recovery following hypnotic infusion was assessed by administering ACTH every 30 minutes after infusion termination and measuring plasma corticosterone concentrations 30 minutes after each ACTH dose.ResultsDuring hypnotic infusion, ACTH-stimulated serum corticosterone concentrations were significantly lower in the CPMM and etomidate groups than in the control group (100 ± 64 ng/ml and 33 ± 32 ng/ml versus 615 ± 265 ng/ml, respectively). After hypnotic infusion, ACTH-stimulated serum corticosterone concentrations recovered to control values within 30 minutes in the CPMM group but remained suppressed relative to those in the control group for more than 3 hours in the etomidate group.ConclusionsBoth CPMM and etomidate suppress adrenocortical function during continuous infusion. However, recovery occurs significantly more rapidly following infusion of CPMM.

Adrenocortical steroid response to ACTH in different phenotypes of non-obese polycystic ovary syndrome

BackgroundAdrenal androgen excess is frequently observed in PCOS. The aim of the study was to determine whether adrenal gland function varies among PCOS phenotypes, women with hyperandrogenism (H) only and healthy women.MethodsThe study included 119 non-obese patients with PCOS (age: 22.2 ± 4.1y, BMI:22.5 ± 3.1 kg/m2), 24 women with H only and 39 age and BMI- matched controls. Among women with PCOS, 50 had H, oligo-anovulation (O), and polycystic ovaries (P) (PHO), 32 had O and H (OH), 23 had P and H (PH), and 14 had P and O (PO). Total testosterone (T), SHBG and DHEAS levels at basal and serum 17-hydroxprogesterone (17-OHP), androstenedione (A4), DHEA and cortisol levels after ACTH stimulation were measured.ResultsT, FAI and DHEAS, and basal and AUC values for 17-OHP and A4 were significantly and similarly higher in PCOS and H groups than controls (p < 0.05 for all) whereas three groups did not differ for basal or AUC values of DHEA and cortisol. Three hyperandrogenic subphenotypes (PHO, OH, and PH) compared to non-hyperandrogenic subphenotype (PO) had significantly and similarly higher T, FAI, DHEAS and AUC values for 17-OHP, A4 and DHEA (p < 0.05). All subphenotypes had similar basal and AUC values for cortisol.ConclusionPCOS patients and women with H only have similar and higher basal and stimulated adrenal androgen levels than controls. All three hyperandrogenic subphenotypes of PCOS exhibit similar and higher basal and stimulated adrenal androgen secretion patterns compared to non-hyperandrogenic subphenotype.

Reproductive endocrinology of zoo-housed aardwolves

Knowledge regarding the relationship between endocrine parameters and reproductive activity can offer important insights into how social and environmental factors influence the reproductive success of mammals. Although components of both the physical and social environment affect endocrine regulation of reproduction, less is understood about the potential role of interactions between different endocrine axes on reproductive activity. We evaluated temporal patterns of reproductive and adrenocortical steroids in two male and three female aardwolves (Proteles cristata) housed in captivity at Brookfield Zoo, Chicago, IL, USA. We found seasonal variation in faecal androgens, estrogens, and progestagens, which provide support for previous observations of the aardwolf as a seasonal breeder. However, the timing of peak endocrine activity did not correspond to observations from wild populations. Our interpretation is that this discrepancy is caused by photoperiodic regulation of reproductive activity. We found a positive relationship between faecal androgens and faecal glucocorticoid metabolites in males and a positive relationship between faecal estrogens and faecal glucocorticoid metabolites in females when housed with conspecifics but not when housed alone. We also found a positive but asymptotic relationship between faecal progestagens and faecal glucocorticoid metabolites. We argue that these observations indicate a potential effect of reproductive endocrine activity on the hypothalamic–pituitary–adrenal axis, which could result in interesting physiological trade-offs in male reproductive tactics and female pre-partum maternal investment because of the negative effects of long-term glucocorticoid elevation on reproductive performance. Finally, our results suggest that social and environmental factors interact in regulating many aspects of endocrine fluctuations in this mostly solitary species.

The information provided by the adrenal cortical steroids: A hypothesis

We present the hypothesis that in vertebrates their closed blood circulation facilitated the evolution of the adrenal cortex as a central processing unit that provides the rest of the body with information on the effect of changes in the blood glucose and sodium levels on the functioning of the mitochondria, and of sodium transporters in the adrenal cortex.When cells in the glomerulosa can no longer increase the synthesis of aldosterone, the message to the body is that a higher level of sodium in the blood may damage the cells. When the fasiculata cells cannot increase the synthesis of glucorticoids, the message to the body is that their mitochondria cannot produce more ATP, and that higher levels of glucose in the blood may harm the organism.

Melanocortin 2 Receptor-Associated Protein (MRAP) and MRAP2 in Human Adrenocortical Tissues: Regulation of Expression and Association with ACTH Responsiveness

ACTH stimulates adrenocortical steroid production through the melanocortin 2 receptor (MC2R). MC2R trafficking and signaling are dependent on the MC2R accessory protein (MRAP). The MRAP homolog MRAP2 also transports the MC2R to the cell surface but might prevent activation. The objective of the investigation was to study the regulatory pathways of MRAP and MRAP2 and their contributions to ACTH responsiveness in human adrenal tissues. MRAP, MRAP2, and MC2R expression levels were studied in 32 human adrenocortical samples. Regulation of these mRNAs was investigated in 43 primary adrenal cultures, stimulated with ACTH, forskolin, angiotensin II (AngII), phorbol-12-myristate-13-acetate (PMA), or dexamethasone. The induction of cortisol, cAMP, and ACTH-responsive genes after treatment with ACTH was related to MRAP, MRAP2, and MC2R expression levels. MRAP and MRAP2 levels were lower in adrenocortical carcinomas (ACC) than in other adrenal tissues (P < 0.001). Patient ACTH and cortisol levels were associated with adrenal levels of MRAP and MC2R in adrenal hyperplasia samples (P < 0.05) but not in tumors. ACTH induced the expression of MRAP 11 ± 2.1-fold and MC2R 20 ± 3.8-fold in all adrenal tissue types (mean ± SEM, both P < 0.0001), whereas AngII augmented these mRNAs 4.0 ± 1.2-fold and 12.6 ± 3.2-fold (P < 0.0001) in all but the ACC. MRAP2 expression was suppressed by forskolin (-24 ± 15%, P = 0.013) and PMA (-22 ± 7%, P = 0.0007). MRAP, MRAP2, or MC2R levels were not associated with the induction of cortisol, cAMP, or gene expression by ACTH in vitro. MRAP and MC2R expression is induced by ACTH and AngII, which would facilitate cell surface receptor availability. Physiological expression levels of MRAP, MRAP2, and MC2R were not limiting for ACTH sensitivity.

Adrenalectomy stimulates the formation of initial atherosclerotic lesions: Reversal by adrenal transplantation

Long-term changes in the secretion of immunosuppressive adrenal-derived glucocorticoid hormones influence cardiovascular disease risk. Here we determined the consequences of changes in adrenal steroid metabolism for the development of atherosclerotic lesions in mice.Atherosclerosis-susceptible low-density-lipoprotein (LDL) receptor knockout mice were subjected to adrenalectomy (ADX) or a control (SHAM) operation and subsequently fed an atherogenic diet for 4 weeks. Atherogenic diet feeding raised plasma corticosterone levels in SHAM mice, but not adrenalectomized mice, resulting in an 83% lower (P<0.01) corticosterone level in adrenalectomized mice. Adrenalectomy was associated with a respectively 22% and 29% lower plasma level of cholesterol and triglycerides. In contrast, white blood cell counts were increased 2-fold (P<0.01) in adrenalectomized mice, which could be attributed to a significant 2.1- to 2.6-fold rise in lymphocyte (P<0.05) and monocyte (P<0.05) numbers. Probably as a result of the enhanced systemic inflammatory status, adrenalectomy was associated with a higher susceptibility for diet-induced atherosclerosis (321±18×103μm2 for ADX vs 240±31×103μm2 for SHAM; P<0.05) not withstanding the lowered cholesterol levels. Restoring adrenocortical steroid secretion – but not adrenal medulla function – and the associated downstream glucocorticoid receptor signaling in adrenalectomized mice through adrenal transplantation induced a reversal of the adrenalectomy-associated rise in white blood cell numbers, plasma monocyte chemoattractant protein 1 (MCP-1) levels, and atherosclerotic lesion development (lesion size in transplanted mice: 258±34×103μm2; P<0.05 vs ADX).In conclusion, our studies show that adrenal-derived steroids protect against the development of initial atherosclerotic lesions in LDL receptor knockout mice.

Stimulatory Adrenocortical Effects of a Selective Estrogen Receptor Modulator in Ovariectomized Female Macaques

Here, we report the effects of estrogen and the selective estrogen receptor modulator (SERM) levormeloxifene on adrenocortical measures in ovariectomized female cynomolgus monkeys (Macaca fascicularis). Animals were randomized into one of five treatment groups, each containing 23 to 26 animals: (1) placebo, (2) 0.016 mg/kg 17β-estradiol (E(2)), (3) 0.5 mg/kg levormeloxifene (L(1)), (4) 1.0 mg/kg levormeloxifene (L(2)), and (5) 5.0 mg/kg levormeloxifene (L(3)). Treatments were administered orally each day for 18 mo. All doses of levormeloxifene resulted in adrenal weights at least 50% greater than placebo (p < .0001 for all). The target dose of levormeloxifene (L(2)) resulted in higher serum concentrations of cortisol (+63%), dehydroepiandrosterone-sulfate (+73%), and androstenedione (+37%) compared with the placebo group (p < .05 for all). In contrast, E(2) resulted in no significant differences in adrenal weight or adrenocortical steroids. Oral E(2) and all SERM doses resulted in similar reductions in serum gonadotropins and at least threefold greater uterine weight versus placebo (p < .0001 for all). Results indicate that the SERM levormeloxifene, in contrast to E(2), may have robust stimulatory effects on adrenocortical hormones in a postmenopausal model. These findings warrant further investigation into long-term SERM effects on adrenocortical function.

子宮腟部びらんに対する電気焼灼術の応用と術後使用薬剤の効果(第2報)細胞呼吸促進剤(Solcoseryl-Jelly)および局所副腎皮質ホルモン剤(Kenalog)の併用について

子宮腟部びらんに対する電気焼灼術の応用と術後使用薬剤の効果(第2報)細胞呼吸促進剤(Solcoseryl-Jelly)および局所副腎皮質ホルモン剤(Kenalog)の併用について

Bronquiolite obliterante pós-infecciosa em crianças

OBJETIVOS: Revisar os trabalhos publicados sobre os principais aspectos da bronquiolite obliterante pos-infecciosa, relacionados com sua historia, etiologia, epidemiologia, fatores de risco, patogenia, alteracoes histologicas, manifestacoes clinicas, exames complementares, criterios diagnosticos, diagnostico diferencial, tratamento e prognostico. FONTES DOS DADOS: Realizou-se uma revisao nao sistematica nas bases de dados MEDLINE e LILACS, selecionando-se 66 referencias mais relevantes. SINTESE DOS DADOS: Na bronquiolite obliterante pos-infecciosa ocorre lesao do epitelio respiratorio, e a gravidade clinica esta relacionada aos diferentes graus de lesao e ao processo inflamatorio. O diagnostico baseia-se no quadro clinico, na exclusao dos principais diagnosticos diferenciais e no auxilio dos exames complementares. A tomografia computadorizada de alta resolucao, principalmente com imagens em inspiracao e expiracao, possibilta a avaliacao das pequenas vias aereas. As provas de funcao pulmonar caracterizam-se por padrao obstrutivo fixo com reducao acentuada do FEF25-75%. O tratamento nao esta bem estabelecido, e o uso de corticoides tem sido preconizado em forma de pulsoterapia ou por via inalatoria em elevadas doses, no entanto, os dados da literatura a respeito de sua eficacia ainda sao escassos. O prognostico a longo prazo e variavel, podendo haver melhora clinica ou evolucao para insuficiencia respiratoria cronica e obito. CONCLUSAO: A bronquiolite obliterante pos-infecciosa e uma doenca que cursa com elevada morbidade e deve ser abordada por equipe multidisciplinar com acompanhamento em longo prazo.

DIURETIC EFFECT OF SOME ADRENOCORTICAL STEROIDS IN THE RAT.

Abstract Cortisone, hydrocortisone and some of their Δ1- and fluorinated analogues have a pronounced diuretic effect in the rat; this is accompanied by increased urinary excretion of both Na+ and K+. Diuresis is maximal some 4 hr after oral administration, and in acute studies, the diuretic potency of some of the newer corticosteroids exceeds 100 times that of chlorothiazide.

The hypothalamo-pituitary-adrenocortical system

Although it is more than 100 years since Addison first drew attention to the vital importance of the adrenal glands, it was not until 1930 that it became generally accepted that the cortex is their lifemaintaining part. It also became evident that increased activity of the adrenal cortex is an essential part of the body's response to stress and is dependent upon stimulation of the adrenal cortices by an adrenocorticotrophic hormone (ACTH) secreted by the anterior pituitary gland. In the 1930's a remarkable stimulus to interest in the physiology of the adrenal cortex was provided by Selye's claims that various "diseases of adaptation" result from abnormal adrenocortical responses to stress. An even greater impetus to research came almost 20 years later with Hench's demonstrations of the remarkable effectiveness of adrenal cortical steroids (corticosteroids or corticoids) in the treatment of various allergic and inflammatory conditions. The foundations of Neuroendocrinology were laid when Harris showed that the release of ACTH, in addition to that of other anterior pituitary hormones, is controlled by the hypothalamus. In recent years attention has been focused on the numerous polypeptides which affect the functional activity of the pituitary gland, and our understanding of the mechanisms which control their secretion is advancing rapidly. At the same time, the frequent indiscriminate use of the many sophisticated methods, particularly those involving radioimmunoassays, which have been exploited for their investigation has often produced a considerable amount of data which have done nothing but add to our confusion! Chemistry of the corticosteroids Adrenocortical extracts effective in the treatment of Addison's disease were first prepared in 1930. They were believed to contain only one hormone, but chemists soon began to show that a very large number of steroids could be isolated from these extracts. However, some of these steroids were de

The importance of the 19-methyl and the C(20) ketone groups for the thymolytic activity of the adrenocortical steroids.

Abstract Evidence is presented to show that reduction of the ketone grouping at carbon 20 in the α-ketol side chain of the adrenocortical steroid to form either the α- or β-hydroxy derivative, produced a profound, if not complete, loss in the ability of the analogue to involute the thymus gland of the immature albino rat. The 19-nor-derivative of hydrocortisone (cortisol) was unable to produce a significant decrease in the thymus weight at the doses employed, suggesting that the 19-methyl is one of the groups which are essential for the thymolytic activity of the corticosteroids. A 19-norhydrocortisone derivative in which the 4-dehydro-3-keto grouping in ring A was replaced by a phenolic type of structure similar to that found in the oestrogenic steroids had no effect on the thymus gland of the rat.

The Effects of Prolonged Administration of Some Adrenocortical Steroids in the Rat

AbstractAn approximation has been made of the relative potency of some adrenocortical steroids to retard body growth and cause adrenocortical atrophy in chronically treated rats. The site of cortical atrophy and depletion of sudanophilic lipid varies with the nature of the steroid administered. The implications of these findings have been discussed with particular reference to the pituitary control of the zona glomerulosa. Corticosteroid induced adrenocortical atrophy is reversible on cessation of treatment. The effect of prolonged administration of cortisone on the weight of organs and other endocrine glands has also been studied.

Malignant Adrenal Rest Tumor of the Retroperitoneum Producing Adrenocortical Steroids

We present a case of a malignant adrenal rest tumor arising from the retroperitoneum with Cushing's syndrome in a 31-year-old female. Her serum cortisol and dehydroepiandrosterone sulfate levels were elevated, while adrenocorticotropic hormone levels were low. Computed tomography scans and magnetic resonance imaging revealed a retroperitoneal tumor with no visible lesions in the adrenal glands and ovaries. From those results and the histopathologic findings following biopsy of an enlarged supraclavicular lymph node, the patient was diagnosed as a malignant adrenal rest tumor of the retroperitoneum. Despite chemotherapy, the patient died of rapid development of multiple metastases. Autopsy revealed a large tumor that extended around the abdominal aorta from the levels of the left kidney to the aortic bifurcation with generalized metastases. Tumor cells were characterized by clear and eosinophilic cytoplasm and atypical nuclei that exhibited frequent and atypical mitoses. Immunohistochemistry regarding steroidogenesis was performed and revealed that the tumor cells were immunopositive for adrenal 4 binding protein/steroidogenic factor-1, cholesterol side-chain cleavage enzyme, 17α-hydroxylase, and 21-hydroxylase. We thus elucidated the adrenocortical steroid production in the tumor cells causing Cushing's syndrome. This case report first demonstrates the steroidogenic capacity in a malignant adrenal rest tumor.

Adiponectin (15–36) stimulates steroidogenic acute regulatory (StAR) protein expression and cortisol production in human adrenocortical cells: Role of AMPK and MAPK kinase pathways

Adiponectin is an abundantly circulating adipokine, orchestrating its effects through two 7-transmembrane receptors (AdipoR1 and AdipoR2). Steroidogenesis is regulated by a variety of neuropeptides and adipokines. Earlier studies have reported adipokine mediated steroid production. A key rate-limiting step in steroidogenesis is cholesterol transportation across the mitochondrial membrane by steroidogenic acute regulatory protein (StAR). Several signalling pathways regulate StAR expression. The actions of adiponectin and its role in human adrenocortical steroid biosynthesis are not fully understood. The aim of this study was to investigate the effects of adiponectin on StAR protein expression, steroidogenic genes, and cortisol production and to dissect the signalling cascades involved in the activation of StAR expression. Using qRT-PCR, Western blot analysis and ELISA, we have demonstrated that stimulation of human adrenocortical H295R cells with adiponectin results in increased cortisol secretion. This effect is accompanied by increased expression of key steroidogenic pathway genes including StAR protein expression via ERK1/2 and AMPK-dependent pathways. This has implications for our understanding of adiponectin receptor activation and peripheral steroidogenesis. Finally, our study aims to emphasise the key role of adipokines in the integration of metabolic activity and energy balance partly via the regulation of adrenal steroid production.

Endocrine Therapy of Breast Cancer

Breast cancer remains one of the first leading causes of death in women, and currently endocrine treatment is of major therapeutic value in patients with estrogen-receptor positive tumors. Selective estrogen-receptor modulators (SERMs), such as tamoxifen and raloxifene, aromatase inhibitors, and GnRH agonists are the drugs of choice. Tamoxifen, a partial nonsteroidal estrogen agonist, is a type II competitive inhibitor of estradiol at its receptor, and the prototype of SERMs. Aromatase inhibitors significantly lower serum estradiol concentration in postmenopausal patients, having no detectable effects on adrenocortical steroids formation, while GnRH agonists suppress ovarian function, inducing a menopause-like condition in premenopausal women. Endocrine therapy has generally a relatively low morbidity, leading to a significant reduction of mortality for breast cancer. The aim of chemoprevention is to interfere early with the process of carcinogenesis, reducing the risk of cancer development. As preventive agents, raloxifene and tamoxifene are equivalent, while raloxifene has more potent antiresorptive effects in postmenopausal osteoporosis. Endocrine treatment is usually considered a standard choice for patients with estrogen-receptor positive cancers and non-life-threatening advanced disease, or for older patients unfit for aggressive chemotherapy regimens. Several therapeutic protocols used in patients with breast cancer are associated with bone loss, which may lead to an increased risk of fracture. Bisphosphonates are the drugs of choice to treat such a drug-induced bone disease. The aim of this review is to outline current understanding on endocrine therapy of breast cancer.

歯肉異常出血を初発症状として発見された免疫性血小板減少症を伴う マントル細胞リンパ腫の1例

Mantle cell lymphoma （MCL） is a rare lymphoma of B-cell origin. We report a case of MCL with immune thrombocytopenia detected by abnormal gingival bleeding as a primary symptom. A 76-year-old man was referred to our hospital because of gingival bleeding. Gingival bleeding of the anterior maxillary region and purpura of the lower extremity was detected. Because the platelet count was 0.0 × 104/μl ,we suspected blood disorders such as ITP. We referred the patient to a hematologist, and he was hospitalized immediately. He received adrenocortical steroid therapy, and the platelet count returned to the normal range.Because bone marrow puncture showed infiltration of malignant lymphoma cells （MCL）, MCL （Stage IV A） with thrombocytopenia was diagnosed. He received chemotherapy with rituximab-2CdA. After treatment, remission was achieved, and there has been no evidence of recurrence. Immediate examination and accurate diagnosis are essential in patients who are referred because of oral hemorrhage with a primary symptom of blood disorders.

Distribution of stomatin expressing in the central nervous system and its up-regulation in cerebral cortex of rat by hypoxia

Stomatin is an important membrane raft protein which can combine skeleton protein, some ion channel, and transporter to regulate their functions. However, until now no data on its expression and function in CNS are available. In this study, we examined distribution of stomatin in CNS of rat, and investigated the effects of hypoxia exposure and glucocorticoid on stomatin expression in cerebral cortex of rat. Immunofluorescence staining revealed a broad expression of stomatin protein in many areas of adult rat brain and spinal cord, including the ventral horn of spinal cord, causal magnocellular nucleus of hypothalamus, the V layer of the cerebral cortex, solitary nucleus, 10 and 12 nuclei, and so on. Hypoxia or ischemic hypoxia significantly up-regulated stomatin expression in cerebral cortex, and the up-regulation was independent on adrenocortical steroids since it also occurred in adrenalectomized (ADX) rats. Moreover, treatment of ADX or sham-operated rats with dexamethasone, a synthetic glucocorticoid alone could significantly stimulate expression of stomatin in lung and heart, but not in cerebral cortex. However, dexamethasone could enhance the hypoxia-stimulated expression of stomatin in cerebral cortex of ADX rats. These findings suggested that stomatin might be involved in various physiological functions and cellular events of neurons in CNS under physiological conditions and play a potential protective role under hypoxic conditions.

Trends of adverse drug reactions related-hospitalizations in Spain (2001-2006)

BackgroundAdverse drug reactions (ADR) are a substantial cause of hospital admissions. We conducted a nationwide study to estimate the burden of hospital admissions for ADRs in Spain during a six-year period (2001-2006) along with the associated total health cost.MethodsData were obtained from the national surveillance system for hospital data (Minimum Basic Data Set) maintained by the Ministry of Health and Consumer Affairs, and covering more than 95% of Spanish hospitals. From these admissions we selected all hospitalization that were code as drug-related (ICD-9-CM codes E), but intended forms of overdoses, errors in administration and therapeutics failure were excluded. The average number of hospitalizations per year, annual incidence of hospital admissions, average length of stay in the hospital, and case-fatality rate, were calculated.ResultsDuring the 2001-2006 periods, the total number of hospitalized patients with ADR diagnosis was 350,835 subjects, 1.69% of all acute hospital admissions in Spain. The estimated incidence of admissions due to ADR decreased during the period 2001-2006 (p < 0.05). More than five percent of patients (n = 19,734) died during an ADR-related hospitalization. The drugs most commonly associated with ADR-related hospitalization were antineoplastic and immunosuppressive drugs (n = 75,760), adrenal cortical steroids (n = 47,539), anticoagulants (n = 26,546) and antibiotics (n = 22,144). The costs generated by patients in our study increased by 19.05% between 2001 and 2006.ConclusionsApproximately 1.69% of all acute hospital admissions were associated with ADRs. The rates were much higher for elderly patients. The total cost of ADR-related hospitalization to the Spanish health system is high and has increased between 2001 and 2006. ADRs are an important cause of admission, resulting in considerable use of national health system beds and a significant number of deaths.

SIADH and other hyponatremic disorders: diagnosis and therapeutic problems.

Hyponatremia is more frequently observed in elderly patients associated with exaggerated response of ADH release and attenuated response of renin-aldosterone system. Differentiation of SIADH and hyponatremia other than SIADH is essential in anticipating the therapeutic effect of water restriction to correct hyponatremia. Serum concentration of uric acid and urinary excretion of kallikrein are significant parameters in biochemical discrimination index to differentiate these two types of hyponatremia. In addition to sodium replacement, water restriction and mineral corticoid, newly developed non-peptide ADH V2 receptor antagonist, OPC-31260, seems to be a useful tool to correct hyponatremia.