Adrenal function evaluation in critically ill dogs with low doses of synthetic ACTH / Avaliação da função adrenal em cães portadores de doenças críticas com baixa dose de ACTH sintético

The hypothalamus-pituitary-adrenal axis function may be impaired in patients with critical illnesses, especially cases of sepsis, named critical illness-related corticosteroid insufficiency (CIRCI). This study examined the function of the hypothalamic-pituitary-adrenal axis in normal dogs (n = 10) and dogs with critical diseases (n = 16), through determinations of endogenous ACTH (adrenocorticotropic hormone), basal cortisol and cortisol after stimulation in low doses of synthetic ACTH (1.0µg/kg/IV). The stimulation test with ACTH dose tested was verified as effective for evaluation of adrenal function in healthy and sick dogs. Ill dogs differed from healthy dogs by presenting higher basal cortisol values. Eight sick dogs presented a decrease in endogenous ACTH, basal cortisol, or Δ-cortisol. No significant differences were found between the control groups and critically ill dogs for the values of endogenous ACTH, cortisol after stimulation or Δ-cortisol. We concluded that the stimulation test with low-dose ACTH was effective for evaluation of adrenal function, as well as the fact that a considerable portion of critically ill dogs studied here, especially with sepsis, had evidence of inadequate corticosteroid response to stress.(AU)

A função do eixo hipotálamo-hipófise-adrenal pode estar comprometida em pacientes com doenças críticas, em especial casos de sepse, sendo nomeada de Insuficiência Corticosteroide Relacionada à Doença Crítica (ICRDC). O presente trabalho analisou a função do eixo hipotálamo-hipófise-adrenal em cães normais (n=10) e cães portadores de doenças críticas (n=16), por meio de determinações de ACTH (hormônio adrenocorticotrófico) endógeno, de cortisol basal e de cortisol após estímulo com baixa dose de ACTH sintético (1,0µg/kg/IV). Constatou-se que o teste de estimulação com ACTH na dose testada se mostrou eficaz para avaliação da função adrenal em cães sadios e doentes. Os cães doentes diferiram dos sadios ao apresentar valores maiores de cortisol basal. Oito cães doentes apresentaram diminuição do ACTH endógeno, do cortisol basal ou do Δ-cortisol. Não foram encontradas diferenças significativas entre os grupos Controle e Criticamente enfermos para os valores de ACTH endógeno, cortisol após estimulação ou Δ-cortisol. Concluiu-se que o teste de estimulação com baixa dose de ACTH mostrou-se eficaz para avaliação da função adrenal, assim como, uma parcela considerável da população de cães críticos aqui estudados, em especial com sepse, apresentaram evidências de resposta corticosteroide inadequada frente ao estresse.(AU)

Aldosterone secretion in patients with septic shock: a prospective study / Secreção de aldosterona em pacientes com choque séptico: estudo prospectivo

OBJECTIVE: To assess serum levels of the main factors that regulate the activation of the zona glomerulosa and aldosterone production in patients with septic shock, as well as their response to a high-dose (250 µg) adrenocorticotropic hormone (ACTH) stimulation test. SUBJECTS AND METHODS: In 27 patients with septic shock, baseline levels of aldosterone, cortisol, ACTH, renin, sodium, potassium, and lactate were measured, followed by a cortrosyn test. RESULTS: Renin correlated with baseline aldosterone and its variation after cortrosyn stimulation. Baseline cortisol and its variation did not correlate with ACTH. Only three patients had concomitant dysfunction of aldosterone and cortisol secretion. CONCLUSIONS: Activation of the zona glomerulosa and zona fasciculata are independent. Aldosterone secretion is dependent on the integrity of the renin-angiotensin-aldosterone system, whereas cortisol secretion does not appear to depend predominantly on the hypothalamic-pituitary-adrenal axis. These results suggest that activation of the adrenal gland in critically ill patients occurs by multiple mechanisms.

OBJETIVO: Avaliar os níveis séricos dos principais fatores que regulam a ativação da zona glomerulosa e a produção de aldosterona em pacientes com choque séptico, assim como sua resposta ao teste de cortrosina em alta dose (250 µg). SUJEITOS E MÉTODOS: Em 27 portadores de choque séptico, foram aferidos níveis basais de aldosterona, cortisol, ACTH, renina, sódio, potássio e lactato, bem como realizado teste de cortrosina. RESULTADOS: Renina se correlacionou com níveis basais de aldosterona e sua variação após teste de cortrosina. Cortisol basal e sua variação não se correlacionaram com ACTH. Apenas três pacientes apresentaram disfunção concomitante da secreção de aldosterona e cortisol. CONCLUSÕES: Ativação das zonas fasciculada e glomerulosa são independentes. Secreção de aldosterona é dependente da integridade do sistema renina-angiotensina-aldosterona, enquanto secreção de cortisol não parece predominantemente dependente do eixo hipotálamo-hipófise-adrenal. Esses resultados sugerem que a ativação da adrenal em pacientes críticos ocorre por múltiplos mecanismos.

Comparison of low dose short synacthen test [1 microgram] with standard dose short synacthen test [250 microgram] in patients of adrenal insufficiency

To determine the diagnostic accuracy of low dose 1 microg short synacthen test taking standard dose 250 microg short synacthen test as gold standard. A descriptive study. Department of Chemical Pathology and Endocrinology Armed Forces Institute of Pathology Rawalpindi from Jan 2006 to Jan 2007. Thirty patients with clinical suspicion of adrenal insufficiency and equal number of age matched healthy males and females as controls were included in the study. Relevant clinical history and physical examination was recorded on designated proforma. Short synacthen test was performed between 0800 - 1000 h by using ACTH doses of 1 microg and 250 microg with interval of 3 days in all patients and controls. Three blood samples were obtained for cortisol [basal, 30 min and 60 min after l/M ACTH injection]. Using 250 microg short synacthen test as a standard test, the 1 microg short synacthen test had sensitivity of 100%, specificity of 72%, positive predictive value of 71% and negative predictive value of 100% and 83% accuracy. The low dose 1 microg short synacthen test is as sensitive as standard dose 250 microg short synacthen test but less specific in the diagnosis of adrenal insufficiency

Prueba de cosintropina en tuberculosis activa grave / Cosyntropin test in severe active tuberculosis

BACKGROUND: Frequency of adrenal insufficiency in patients with tuberculosis varies from 0 to 58%; however, all published series excluded severely ill patients. Our objective was to investigate adrenal insufficiency with the low-dose cosyntropin test in patients with severe active tuberculosis. METHOD: From two large university affiliated hospitals, 18 patients with tuberculosis and criteria of sepsis or severe sepsis according to SCCM/ACCP criteria, defined by the present authors as severe active tuberculosis, participated in the study. A low-dose ACTH test with 10 mg of ACTH was performed. After ACTH test, all patients received a stress dose of hydrocortisone (240 mg/day) during their entire hospitalization along with four antituberculous drugs. Abnormal response was considered when elevation of serum cortisol was <7 microg/dl with respect to basal level, 60 min after ACTH administration. RESULTS: Adrenal insufficiency was found in seven patients (39%); no clinical or laboratory data were associated with the presence of abnormal adrenal response. Except in one patient with HIV infection, all the signs and symptoms improved after antituberculous and hydrocortisone treatment. The increment in serum cortisol value post-ACTH test was lower in patients with hypoalbuminemia. CONCLUSIONS: Adrenal insufficiency is frequent in severe active tuberculosis. The efficacy and security of supplemental steroid treatment in severe active tuberculosis should be established by a randomized clinical trial.

Plasma cortisol response to 1-24 adrenocorticotropin in patients with treated/untreated sellar & suprasellar mass lesions.

BACKGROUND & OBJECTIVES: One microgram short synacthene test is widely recommended as a screening test for evaluation of hypothalamo-pituitary-adrenocortical axis in patients with secondary adrenal insufficiency. Information on adequacy of cortisol response to this dose at different periods of the day in patients with hypothalamic-pituitary disorders is not available. Hence, this study was designed to assess the adequacy of cortisol response to 1 microg 1-24 adrenocorticotropin (ACTH) at 0800 h and 1600 h in patients with sellar and suprasellar mass lesions. METHODS: Thirty five consecutive patients with sellar and suprasellar mass lesions with mean age of 43.0+/-14.4 yr and 36 healthy controls with mean age of 32.3+/-9.0 yr were studied after obtaining informed consent. Maintenance doses of glucocorticoids in these patients were discontinued appropriately. On day 1, prestimulated and stimulated plasma cortisol samples at 0800 h and at 30 and 60 min following i.v. bolus of 1 microg 1-24 ACTH were collected. While on day 3, plasma cortisol samples were similarly collected at 1600 h. Cortisol estimation was done by a sensitive and specific radioimmunoassay. Stimulated plasma cortisol of 500 nmol/l or higher was defined as a normal response. RESULTS: In healthy controls, the prestimulated and peak cortisol levels at 0800 h (377.5+/-93.3 and 729.1+/-183.2 nmol/l) were higher (P<0.001 and P<0.01) than those at 1600 h (230.1+/-75.7 and 665.8+/-138.6 nmol/l). All subjects had a cortisol response of 500 nmol/l or higher in response to 1 microg 1-24 ACTH both at 0800 and 1600 h. In the patients' group, the prestimulated plasma cortisol at 0800 h (250.3+/-169.7 nmol/l) was higher (P<0.001) than that at 1600 h (166.3+/-128.9 nmol/l), while the peak cortisol response was comparable (P>0.05) in the morning as well as in the evening (490.9+/-309.4 vs 464.8+/-318.4). In 27 patients (77%) the morning and evening stimulated cortisol response to 1 microg 1-24 ACTH was consistent (normal in 13 and subnormal in 14) but was discrepant in the remaining 8 (23%). In 7 of these 8 patients, cortisol response was normal at 0800 h but not at 1600 h, while in only one, normal response was seen at 1600 h but not at 0800 h. INTERPRETATION & CONCLUSION: The demonstration of normal peak cortisol response to 1 microg 1-24 ACTH at 0800 h but not at 1600 h in substantial number of patients with sellar and suprasellar mass lesions suggests preference to morning for performing this test.