RESUMEN
BACKGROUND: Hypertension and proteinuria are medical complications associated with the multisystemic effects of long-term hypercortisolism in dogs with hyperadrenocorticism (HAC). METHODS: This study investigated the relationships among adrenocorticotropic hormone (ACTH)-stimulation test results, systemic blood pressure, and microalbuminuria in clinically-healthy dogs (n = 100), in dogs affected with naturally occurring pituitary-dependent (PDH; n = 40), or adrenal-dependent hyperadrenocorticism (ADH; n = 30). RESULTS: Mean systemic blood pressure was similar between clinically healthy dogs and dogs with HAC (p = 0.803). However the incidence of hypertension was highest in dogs with ADH (p = 0.017), followed by dogs with PDH, with the lowest levels in clinically healthy dogs (p = 0.019). Presence of microalbuminuria and albuminuria in clinically healthy dogs and dogs affected with HAC was significantly different (p < 0.001); incidences of albuminuria followed the same pattern of hypertension; highest incidence in dogs with ADH, and lowest level in clinically healthy dogs; but microalbuminuria showed a different pattern: clinically healthy dogs had highest incidences and dogs with ADH had lowest incidence. The presence of albuminuria was not associated with blood pressure values, regardless of whether dogs were clinically healthy or affected with ADH or PDH (p = 0.306). CONCLUSIONS: Higher incidence of hypertension and albuminuria, not microalbuminuria was seen in dogs affected with HAC compared to clinically healthy dogs; incidence of hypertension and albuminuria was significantly higher in dogs affected with ADH compared to PDH. However, presence of albuminuria was not correlated with systemic blood pressure.
Asunto(s)
Enfermedades de las Glándulas Suprarrenales/veterinaria , Hiperfunción de las Glándulas Suprarrenales/veterinaria , Enfermedades de los Perros/fisiopatología , Enfermedades de la Hipófisis/veterinaria , Enfermedades de las Glándulas Suprarrenales/sangre , Enfermedades de las Glándulas Suprarrenales/fisiopatología , Enfermedades de las Glándulas Suprarrenales/orina , Hiperfunción de las Glándulas Suprarrenales/sangre , Hiperfunción de las Glándulas Suprarrenales/fisiopatología , Hiperfunción de las Glándulas Suprarrenales/orina , Hormona Adrenocorticotrópica/farmacología , Albuminuria/veterinaria , Animales , Enfermedades de los Perros/sangre , Enfermedades de los Perros/orina , Perros , Femenino , Hidrocortisona/sangre , Hipertensión/veterinaria , Masculino , Enfermedades de la Hipófisis/sangre , Enfermedades de la Hipófisis/fisiopatología , Enfermedades de la Hipófisis/orina , Estudios Retrospectivos , TaiwánRESUMEN
OBJECTIVE: This study aimed to evaluate the performance of screening tests (serum cortisol and 24-h urinary free cortisol) and the human-corticotrophin releasing hormone (h-CRH) test in the assessment of adrenal function in patients with hypothalamic-pituitary disorders. DESIGN: Summary receiver operating characteristics (SROC) curve analysis was applied with the insulin tolerance test (ITT) as reference test. A peak serum cortisol response to ITT > or = 500 nmol/l indicated adrenal sufficiency. The sensitivity at the intersect of the diagonal between sensitivity = 1 and (1-specificity) = 1 with the SROC curve, where sensitivity and specificity are equal, and the corresponding weighted kappa, an estimate of agreement with the ITT, served as parameters of test performance. The diagnostic yield, representing the proportion of tests obviating the need for an ITT, was also calculated. MEASUREMENTS: Serum cortisol at 0800 h (n = 122), at 1600 h (n = 116), 24-h urinary free cortisol (n = 115) and the peak serum cortisol to h-CRH (n = 129) were compared with the peak serum cortisol to ITT. PATIENTS: Eighty patients with hypothalamic-pituitary disorders in whom 75 ITT's were performed pre- and 57 post-operatively. RESULTS: Sensitivity at the intersect and weighted kappa were higher for 0800 h serum cortisol (0.873 and 0.763 respectively) than for 1600 h serum cortisol (0.769 and 0.561) and 24-h urinary free cortisol (0.777 and 0.576). These parameters were 0.868 and 0.756 for the h-CRH test. The diagnostic yield was 63.9% for 0800 h serum cortisol compared to 25.9% for 1600 h serum cortisol (P < 10(-8)), 23.5% for 24-h urinary free cortisol (P < 10(-8)) and 60.5% for the h-CRH test (NS). CONCLUSIONS: Serum cortisol measurement at 0800 h is better than 1600 h and 24-h urinary free cortisol to evaluate adrenal function in this patient category. The diagnostic applicability of the h-CRH test is not superior to 0800 h serum cortisol measurement.
Asunto(s)
Glándulas Suprarrenales/fisiopatología , Hidrocortisona/sangre , Enfermedades Hipotalámicas/fisiopatología , Enfermedades de la Hipófisis/fisiopatología , Adenoma/fisiopatología , Adolescente , Adulto , Anciano , Hormona Liberadora de Corticotropina , Craneofaringioma/fisiopatología , Femenino , Hormona del Crecimiento/metabolismo , Hormonas , Humanos , Hidrocortisona/orina , Enfermedades Hipotalámicas/sangre , Enfermedades Hipotalámicas/orina , Insulina , Masculino , Neoplasias Meníngeas/fisiopatología , Meningioma/fisiopatología , Persona de Mediana Edad , Enfermedades de la Hipófisis/sangre , Enfermedades de la Hipófisis/orina , Neoplasias Hipofisarias/fisiopatología , Valor Predictivo de las Pruebas , Prolactinoma/fisiopatología , Sensibilidad y EspecificidadRESUMEN
The optimal method for assessing the hypothalamic-pituitary-adrenal axis (HPA) remains controversial. The insulin tolerance test (ITT) is considered the gold standard, but is invasive and potentially dangerous. The short Synacthen test (SST) is the most commonly used alternative, but its concordance with the ITT is poor. Using sleep as a reliable stimulus to ACTH release, we proposed that the increment in urinary cortisol levels between midnight and waking could provide a noninvasive, physiological means for the assessment of the HPA axis. Double voided urine samples were collected at home at midnight and waking in 40 patients with pituitary disease and 40 controls. Cortisol and creatinine levels were measured, and the cortisol/creatinine (Cort/Cr) ratio was calculated. The Cort/Cr increment was defined as the morning Cort/Cr ratio minus the midnight Cort/Cr ratio. The Cort/Cr increment of the patients was compared to the results of their ITT or SST. Using the results from the 40 controls, a normal Cort/Cr increment was defined as greater then 9. The positive predictive value of a Cort/Cr increment for the diagnosis of HPA insufficiency was 95%. These findings suggest that the midnight to morning Cort/Cr increment is a reliable, noninvasive alternative to the ITT/SST for assessment of the HPA.
Asunto(s)
Glándulas Suprarrenales/fisiopatología , Hidrocortisona/orina , Hipotálamo/fisiopatología , Enfermedades de la Hipófisis/fisiopatología , Hipófisis/fisiopatología , Adulto , Ritmo Circadiano , Creatinina/orina , Femenino , Humanos , Insulina , Masculino , Persona de Mediana Edad , Enfermedades de la Hipófisis/orina , Neoplasias Hipofisarias/fisiopatología , Neoplasias Hipofisarias/terapia , Neoplasias Hipofisarias/orina , Valores de ReferenciaRESUMEN
OBJECTIVE: To determine whether the urine cortisol-to-creatinine ratio (UCCR) could replace the ACTH stimulation test in monitoring effectiveness of mitotane induction treatment in dogs with pituitary-dependent hyperadrenocorticism (PDH). ANIMALS: 15 dogs with PDH. PROCEDURE: All 15 dogs were given an induction dose of mitotane (o,p'-DDD: 35 to 50 mg/kg of body weight/d) for 3 to 14 days. During the induction period, free-catch morning urine samples were collected for determination of UCCR, followed by ACTH stimulation testing, every other day. Treatment response was divided into 3 categories: well-controlled PDH (post-ACTH serum cortisol concentration > or = 28 nmol/L but < or = 138 nmol/L), deficient cortisol secretion (post-ACTH serum cortisol concentration < 28 nmol/L), and excess cortisol secretion (post-ACTH serum cortisol concentration > 138 nmol/L). RESULTS: The linear relation between UCCR and post-ACTH serum cortisol concentration was significant (P < 0.001); however, the prediction intervals surrounding the line were too broad to be clinically useful. The UCCR overlapped among the 3 categories of treatment response. Nevertheless, dogs with PDH receiving mitotane induction treatment and with UCCR > 79 x 10(-6) were always classified as having excess cortisol secretion. CONCLUSION AND CLINICAL RELEVANCE: The UCCR failed to predict post-ACTH cortisol concentration during mitotane induction treatment sufficiently close to be a clinically reliable indicator of treatment control. Seemingly, however, UCCR > 79 x 10(-6) obtained from a dog with PDH during mitotane induction would indicate inadequate adrenal cortex destruction and the need for continued mitotane induction; UCCR < or = 79 x 10(-6) would be inconclusive.
Asunto(s)
Hiperfunción de las Glándulas Suprarrenales/veterinaria , Antineoplásicos Hormonales/uso terapéutico , Creatinina/orina , Enfermedades de los Perros , Hidrocortisona/orina , Mitotano/uso terapéutico , Enfermedades de la Hipófisis/veterinaria , Hiperfunción de las Glándulas Suprarrenales/tratamiento farmacológico , Hiperfunción de las Glándulas Suprarrenales/etiología , Hiperfunción de las Glándulas Suprarrenales/orina , Hormona Adrenocorticotrópica , Animales , Biomarcadores/sangre , Biomarcadores/orina , Perros , Monitoreo de Drogas/métodos , Monitoreo de Drogas/veterinaria , Femenino , Hidrocortisona/sangre , Masculino , Enfermedades de la Hipófisis/tratamiento farmacológico , Enfermedades de la Hipófisis/orina , Pruebas de Función Adreno-Hipofisaria/veterinaria , Factores de TiempoRESUMEN
In 58 patients with a pituitary adenoma or hypothalamic-pituitary disease an insulin-induced hypoglycaemia test and a metyrapone test were performed. The results of these tests were compared with morning plasma cortisol levels and daily urinary cortisol excretion as indicators of insufficiency of the pituitary-adrenal axis. Basal unstressed urinary cortisol excretion was insufficient in 20 cases. These patients, needing life-long glucocorticoid substitution therapy, were excellently detected by both tests and daily urinary cortisol excretion. The predictive value of the morning plasma cortisol level was inferior to these. Five cases with sufficient basal cortisol excretion showed a defective adrenal response to hypoglycaemia. These patients were not discriminated by the metyrapone test, urinary cortisol excretion or plasma cortisol levels. It is concluded that urinary cortisol excretion can safely replace the hypoglycaemia and metyrapone test for the detection of insufficient basal cortisol production in patients with hypothalamic and/or pituitary disorders.
Asunto(s)
Hormona Adrenocorticotrópica/deficiencia , Hidrocortisona , Enfermedades Hipotalámicas/diagnóstico , Enfermedades Hipotalámicas/fisiopatología , Sistema Hipotálamo-Hipofisario/fisiopatología , Insulina , Metirapona , Enfermedades de la Hipófisis/diagnóstico , Enfermedades de la Hipófisis/fisiopatología , Sistema Hipófiso-Suprarrenal/fisiopatología , Adolescente , Adulto , Anciano , Estudios de Evaluación como Asunto , Femenino , Humanos , Hidrocortisona/sangre , Hidrocortisona/orina , Hipoglucemia/inducido químicamente , Enfermedades Hipotalámicas/sangre , Enfermedades Hipotalámicas/orina , Masculino , Persona de Mediana Edad , Enfermedades de la Hipófisis/sangre , Enfermedades de la Hipófisis/orina , Sensibilidad y EspecificidadRESUMEN
We studied the neurohypophyseal function of 20 patients with complete GH deficiency owing to pituitary stalk transection by means of the water deprivation and the hypertonic saline infusion test. In T1-weighted magnetic resonance images, high-signal intensity of the posterior lobe of the hypophysis was missing in all the patients. An ectopic posterior lobe was observed at the proximal stump of the transected stalk in 17 patients, whereas the 3 patients without ectopic posterior lobe had overt diabetes insipidus or intractable nocturnal enuresis. After water deprivation, 3 patients with large ectopic posterior lobes (length along the pituitary stalk axis exceeding 5 mm) showed urinary osmolality and plasma AVP levels as high as those of 13 patients with partial GH deficiency in whom magnetic resonance images revealed no abnormalities. On the other hand, 14 patients with small ectopic posterior lobes (length less than 5 mm) showed significantly lower urinary osmolality and plasma AVP levels than the patients with large ectopic posterior lobes (p less than 0.01 and p less than 0.01, respectively) and the patients with partial GH deficiency (p less than 0.01 and p less than 0.01, respectively). Urinary osmolality in the patients with small ectopic posterior lobes, however, was higher than that in 3 patients without ectopic posterior lobes (p less than 0.01). During the hypertonic saline infusion test, peak plasma AVP levels in the patients with small ectopic posterior lobes were significantly lower than those in the patients with partial GH deficiency (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Hormona del Crecimiento/deficiencia , Sistema Hipotálamo-Hipofisario/fisiología , Enfermedades de la Hipófisis/metabolismo , Neurohipófisis/lesiones , Adolescente , Adulto , Arginina Vasopresina/sangre , Niño , Preescolar , Femenino , Hormona del Crecimiento/uso terapéutico , Humanos , Imagen por Resonancia Magnética , Masculino , Enfermedades de la Hipófisis/sangre , Enfermedades de la Hipófisis/orina , Neurohipófisis/metabolismo , Neurohipófisis/patología , Solución Salina Hipertónica , Privación de AguaRESUMEN
We recently reported (Clin. Chem. 28: 1497-1500, 1982) a liquid-chromatographic method for quantifying free cortisol in urine. We have since evaluated the clinical utility of our method by assaying cortisol in urine from normal subjects, patients, and subjects undergoing endocrine tests. We found that, in contrast with plasma cortisol, urinary cortisol is not bound to protein. It shows some correlation with 17-hydroxycorticosteroids in urine, but is independent of creatinine excretion. The amount of cortisol excreted daily by a particular individual was found to be fairly constant during nine or 10 days. Normal values determined for 203 apparently healthy individuals were 35.8 (SD 18.7) micrograms/day, with no significant sex-related differences but a tendency for a gradual decrease of cortisol excretion with age. We also report urinary cortisol excretion by patients with pituitary-adrenal disorders and some other diseases, and the pattern of response to dexamethasone and metyrapone administration.