RESUMEN
Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care. PURPOSE: Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development. METHODS: We conducted a structured comparative analysis of existing CPGs in the AP region using a "5IQ" model (identification, investigation, information, intervention, integration, and quality). One-hundred data elements were extracted from each guideline. We then employed a four-round Delphi consensus process to structure the framework, identify key components of guidance, and develop clinical care standards. RESULTS: Eighteen guidelines were included. The 5IQ analysis demonstrated marked heterogeneity, notably in guidance on risk factors, the use of biochemical markers, self-care information for patients, indications for osteoporosis treatment, use of fracture risk assessment tools, and protocols for monitoring treatment. There was minimal guidance on long-term management plans or on strategies and systems for clinical quality improvement. Twenty-nine APCO members participated in the Delphi process, resulting in consensus on 16 clinical standards, with levels of attainment defined for those on identification and investigation of fragility fractures, vertebral fracture assessment, and inclusion of quality metrics in guidelines. CONCLUSION: The 5IQ analysis confirmed previous anecdotal observations of marked heterogeneity of osteoporosis clinical guidelines in the AP region. The Framework provides practical, clear, and feasible recommendations for osteoporosis care and can be adapted for use in other such vastly diverse regions. Implementation of the standards is expected to significantly lessen the global burden of osteoporosis.
Asunto(s)
Osteoporosis , Fracturas de la Columna Vertebral , Asia/epidemiología , Humanos , Tamizaje Masivo , Osteoporosis/diagnóstico , Osteoporosis/epidemiología , Osteoporosis/terapia , Nivel de AtenciónRESUMEN
Previous studies have found that bromocriptine, cyproheptadine, and valproic acid can reduce ACTH secretion in Nelson's syndrome, but none of these agents has achieved widespread use due to their failure to normalize ACTH in most patients. The current study was undertaken to determine whether these three agents, which act through different mechanisms, decrease plasma ACTH synergistically when administered together. Six adult female patients (mean age, 41 yr) with Nelson's syndrome were studied. ACTH was measured every 20 min for 8 h, 2 h before and 6 h after each of the following six treatments: placebo, bromocriptine (2.5 mg), cyproheptadine (8 mg), valproic acid (1 g), cyproheptadine plus valproic acid, and the combination of all three drugs. The sequence of treatments was determined randomly, and there was an interval of at least 2 days between each treatment. The hourly ACTH values were averaged, and the percent maximal suppression of plasma ACTH, relative to the baseline values before drug administration, was compared among the six treatments. Basal plasma ACTH levels in the six patients ranged from 40-3324 pmol/L (normal range, 1-8). The percent maximal suppression of ACTH after administration of placebo (6 +/- 11%), cyproheptadine (17 +/- 15%), valproic acid (37 +/- 10%) or the combination of cyproheptadine and valproic acid (19 +/- 14%) did not achieve statistical significance. Bromocriptine, on the other hand, caused a significant decrease in plasma ACTH (52 +/- 8%; P < 0.05), as did the combination of bromocriptine, cyproheptadine, and valproic acid (58 +/- 12%; P < 0.05). However, the combined effect of the three drugs did not significantly exceed the effect of bromocriptine alone. We conclude that at the doses studied, bromocriptine had the greatest acute effect in suppressing ACTH secretion in Nelson's syndrome, and that combined administration with valproic acid and cyproheptadine did not further increase this acute ACTH-suppressive effect.
Asunto(s)
Hormona Adrenocorticotrópica/sangre , Bromocriptina/uso terapéutico , Ciproheptadina/uso terapéutico , Síndrome de Nelson/sangre , Síndrome de Nelson/tratamiento farmacológico , Ácido Valproico/uso terapéutico , Adulto , Bromocriptina/efectos adversos , Ciproheptadina/efectos adversos , Combinación de Medicamentos , Sinergismo Farmacológico , Femenino , Humanos , Persona de Mediana Edad , Factores de Tiempo , Ácido Valproico/efectos adversosRESUMEN
As endogenous Cushing's syndrome (CS) in children occurs during a critical developmental period, when the majority of peak bone mass is acquired, we hypothesized that children with CS might be at an increased risk of osteoporosis. To determine the effects of CS on bone density, bone metabolism, and growth, we studied a 15-yr-old female identical twin pair, one of whom had CS (twin A), and the other of whom was healthy (twin B). Before therapy for CS, twin A showed a severe loss of bone mineral density [BMD; -3.2SD at the lumbar spine (LS)] compared to twin B (-0.1 SD), which in twin A was associated with low serum osteocalcin levels and urinary pyridinium cross-link excretion. Cure of CS in twin A led to a marked increase in these bone markers, suggesting a state of active bone remodeling. After 27 months of follow-up, even though twin A's BMD improved significantly, it still remained abnormal [-1.9 SD at LS compared with that of twin B (0 SD)], suggesting that twin A continued to be at increased long term risk of osteoporosis. In addition, as a consequence of CS, twin A's final height was 21 cm less than that of her identical twin. We recommend that all children with CS should have BMD monitored after treatment to determine the long term risk of osteoporosis.
Asunto(s)
Composición Corporal , Densidad Ósea , Síndrome de Cushing/fisiopatología , Enfermedades en Gemelos , Crecimiento , Pubertad , Gemelos Monocigóticos , Adolescente , Estatura , Síndrome de Cushing/cirugía , Femenino , Hormona Folículo Estimulante/sangre , Hormona del Crecimiento/sangre , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hormona Luteinizante/sangre , Osteocalcina/sangre , Compuestos de Piridinio/orinaAsunto(s)
Adenoma/complicaciones , Síndrome de Cushing/etiología , Hemorragia/complicaciones , Enfermedades de la Hipófisis/complicaciones , Neoplasias Hipofisarias/complicaciones , Adenoma/metabolismo , Hormona Adrenocorticotrópica/metabolismo , Adulto , Femenino , Humanos , Neoplasias Hipofisarias/metabolismoRESUMEN
Subtotal adrenalectomy was given to 10 adult patients with Cushing's disease, concurrently with or following therapeutic regimen by long term reserpine administration and pituitary irradiation. In the present study, we describe long term follow-up results. Two patients died after the operation due to acute adrenal crisis and pneumonia, respectively. The other 8 patients achieved clinical and biochemical remissions and were followed for long term. Three patients relapsed 9, 14 or 17 years after achieving remission, two patients developed hypopituitarism 12 or 20 years after and one died of cerebral vascular accident at 64 years, 5 years after the remission. The remaining 2 patients maintained remission for 10 or 18 years, respectively. During the remission periods of 0.5 to 20 years with a mean of 10.1 +/- 6.7 years, 6 of 7 patients examined by 1 mg overnight dexamethasone test showed normal suppressibility of plasma cortisol. Provocative tests of plasma GH by l-arginine infusion and/or insulin-induced hypoglycemia were performed in 6 patients in the early remission period. All of 5 patients in the arginine infusion test and 3 of 5 in the insulin-induced hypoglycemia test showed normal responses. Furthermore, to facilitate prediction of long term response or failure to our therapeutic regimen, long term reserpine administration and pituitary irradiation, pretreatment clinical and biochemical characteristics were analyzed retrospectively in 3 divided groups; the present 10 patients treated with reserpine and pituitary irradiation followed by subtotal adrenalectomy, 11 patients achieving long term remission treated by our regimen alone, and 7 patients failed with our regimen alone. There were no significant factors predictive of response to our regimen. These findings suggest that subtotal adrenalectomy does not lead favorable outcome, however, reserpine administration shows usefulness to improve pituitary functions in treating Cushing's disease.
Asunto(s)
Adrenalectomía , Síndrome de Cushing/terapia , Irradiación Hipofisaria , Reserpina/uso terapéutico , Adolescente , Adulto , Terapia Combinada , Síndrome de Cushing/fisiopatología , Femenino , Estudios de Seguimiento , Hormonas/sangre , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Hipófisis/fisiología , Sistema Hipófiso-Suprarrenal/fisiología , Resultado del TratamientoRESUMEN
We present the characteristic features of mineralocorticoid receptor regulation in human mononuclear leukocytes in patients with diabetes mellitus. Eighteen diabetic patients (3M and 15F, aged from 28 to 77 years with a mean of 53 +/- 14 (mean +/- SD) years) and 7 normal subjects (6M and 1F, aged from 29 to 59 years with a mean of 41 +/- 13 years) were studied. The mean plasma aldosterone concentration in the diabetic patients was significantly lower than that in the normal subjects (137 +/- 62 vs 189 +/- 36 pmol/l, p < 0.05). Seven of the 18 diabetic patients were hypoaldosteronemic. These 7 patients, however, showed normokalemia, except one with mild hyperpotassemia. The number of binding sites of [3H]aldosterone to mineralocorticoid receptor in the diabetic patients was significantly higher than that in the normal subjects (853 +/- 281 vs 488 +/- 109 sites/cell, p < 0.05), but there was no significant difference in Kd of [3H]aldosterone binding to mineralocorticoid receptor between the diabetic patients and normal subjects (1.34 +/- 0.37 vs 0.99 +/- 0.61 nmol/l). In the diabetic patients, a significant negative correlation was observed (r = 0.70, p < 0.01) between plasma aldosterone concentration and the binding sites, but not between plasma aldosterone concentration and Kd. In the total subjects, including normal subjects and diabetic patients, a significant negative correlation was also found between plasma aldosterone concentration and binding sites (r = 0.72, p < 0.001). These results suggest that increased binding sites of mineralocorticoid receptor may help to prevent diabetic patients from being hyperkalemic.
Asunto(s)
Aldosterona/metabolismo , Diabetes Mellitus/metabolismo , Leucocitos Mononucleares/metabolismo , Mineralocorticoides/metabolismo , Receptores de Esteroides/metabolismo , Adulto , Anciano , Aldosterona/sangre , Sitios de Unión , Corticosterona/sangre , Desoxicorticosterona/sangre , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Potasio/sangre , Receptores de Mineralocorticoides , Renina/análisis , Regulación hacia ArribaRESUMEN
To evaluate the secretory regulation of 19-hydroxyandrostenedione (19-OH-AD), its plasma concentration was measured before and after stimulation and inhibition tests for the ACTH-adrenal axis and the renin-angiotensin system in 50 normal subjects. Basal levels of plasma 19-OH-AD did not correlate with either those of plasma renin activity (PRA) or the plasma aldosterone concentration (PAC), but positively correlated with those of plasma cortisol. Plasma 19-OH-AD was stimulated by 0.25 mg ACTH-(1-24) and was suppressed by 1 mg dexamethasone (DEX) as were plasma cortisol and PAC. On the other hand, with 2-h standing alone or iv 40 mg furosemide plus 2-h standing, plasma 19-OH-AD and cortisol did not increase but PRA and PAC did. With iv furosemide plus 2-h standing with 3 mg DEX pretreatment, plasma 19-OH-AD and cortisol did not respond either, but PRA and PAC increased. With 25 mg oral captopril following 1-h standing with 3 mg DEX pretreatment, plasma 19-OH-AD and cortisol did not change but PAC decreased. These results indicate that the secretion of 19-OH-AD is mainly under the control of the ACTH-adrenal axis rather than the renin-angiotensin system.
Asunto(s)
Androstenodiona/análogos & derivados , Adolescente , Adulto , Aldosterona/sangre , Androstenodiona/metabolismo , Captopril/farmacología , Cosintropina/farmacología , Dexametasona/farmacología , Femenino , Furosemida/farmacología , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/metabolismo , Radioinmunoensayo , Renina/sangre , Sistema Renina-Angiotensina/efectos de los fármacosRESUMEN
Twenty adult patients with Cushing's disease treated with long term reserpine administration in combination with a single course of external pituitary irradiation were followed. Eleven patients experienced long term remissions of 15.5 +/- 8.9 (mean +/- SD) yr (55%) after a mean irradiation dose of 53.9 +/- 11.4 Gy and a mean duration of reserpine administration of 24.3 +/- 9.3 months. The long term remission rates of the patients irradiated with 50 Gy or less (n = 9; 45.0 +/- 7.1 Gy) and those with more than 50 Gy (n = 10; 61.3 +/- 3.3 Gy; excluding 1 irradiated with 66 Gy who developed brain necrosis) were 56% (5 of 9) and 60% (6 of 10), respectively, and did not differ significantly. There were no significant differences between the 2 groups with regard to the duration of reserpine administration or pretreatment clinical features. At the latest examination, regardless of the irradiation dose, all 9 patients with long term remission showed a higher level of plasma cortisol or 11-hydroxycorticosteroids in the morning than in the evening, normal suppressibility of plasma cortisol with overnight 1 mg dexamethasone (9 of 10), and well preserved responses of other pituitary hormones to various loading tests: normal responses of plasma ACTH to CRH (6 of 9), TSH (7 of 8), and PRL (5 of 8) to TRH and age-related normal responses of GH to GRH (4 of 8), LH (6 of 8), and FSH (6 of 8) to GnRH. These findings suggest that long term reserpine administration in combination with a conventional dose of pituitary irradiation is useful in the treatment of Cushing's disease.
Asunto(s)
Síndrome de Cushing/tratamiento farmacológico , Irradiación Hipofisaria , Reserpina/uso terapéutico , Adolescente , Glándulas Suprarrenales/fisiopatología , Adulto , Síndrome de Cushing/fisiopatología , Síndrome de Cushing/radioterapia , Relación Dosis-Respuesta en la Radiación , Femenino , Estudios de Seguimiento , Gónadas/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función Hipofisaria , Hipófisis/fisiopatología , Reserpina/efectos adversos , Factores de TiempoRESUMEN
Treatment with a high daily dose bromocriptine was evaluated in 6 Cushing's disease patients (4 females and 2 males; aged 23 to 56 years). The highest doses administered were 40 mg to patient 1, 55 mg to patient 2, 35 mg to patient 3, 25 mg to patient 4, 25 mg to patient 5, and 17.5 mg to patient 6. The former 3 cases, 2 (patients 1 and 2) of whom were previously reported and further followed up, showed clinical and biochemical improvement with the regimen. Patient 1 who obtained remission with 40 mg/day has been on remission for further 14 months with a total of 36 months. Patient 2, who had a reduction in pituitary tumor size with 35 mg daily, relapsed thereafter. The therapy, however, resolved the paradoxical responses of plasma ACTH and cortisol to arginine. Readministration of bromocriptine resulted into another clinical and biochemical improvement with 45 to 55 mg/day. Patient 3, a relapsed case after a remission with reserpine plus pituitary irradiation, showed an improvement in the 24-h urinary free cortisol excretion with 35 mg/day. Patient 4 was the only case who had a marked decrease in plasma cortisol (basal; 16.3, nadir; 1.9 micrograms/dl) after a single-dose bromocriptine test among the 5 cases tested. The patient had favorable response with 25 mg/day for 2 months but the dose was not increased after an escape. Patient 5 received the drug in 4 occasions, 7.5 to 25 mg/day, in combination with several agents, which failed to induce clinical remission. The last patient did not respond to a maximum dose of 17.5 mg/day. These observations suggest that, regardless of the result of a single-dose bromocriptine test, treatment with a high daily dose of bromocriptine, 35 mg or more, may be necessary to obtain a favorable clinical response and normal cortisol secretion.
Asunto(s)
Bromocriptina/administración & dosificación , Síndrome de Cushing/tratamiento farmacológico , Hormona Adrenocorticotrópica/sangre , Adulto , Bromocriptina/efectos adversos , Ritmo Circadiano/efectos de los fármacos , Hormona Liberadora de Corticotropina , Dexametasona , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Hidrocortisona/sangre , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Masculino , Persona de Mediana Edad , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Inducción de Remisión/métodosRESUMEN
We report the effectiveness of bromocriptine therapy in resolving the abnormal responses of plasma FSH and LH to TRH in a 70-year-old male with FSH-secreting pituitary macroadenoma who had unsuccessful transsphenoidal pituitary surgery. In the pre-treatment and post-operative periods, respectively, basal plasma levels of FSH were increased to 88.7 and 65.6 mIU/ml (normal range; 8.5-32.4) but those of plasma LH were normal being 7.0 and 4.1 mIU/ml; (normal range; 4.1 to 14.0). The responses of plasma FSH and LH to LHRH were exaggerated and their paradoxical responses to TRH were highly suggested. During the bromocriptine therapy, the basal level of plasma FSH was normalized and that of plasma LH remained normal. The magnitude of FSH and LH responses to LHRH decreased and their paradoxical responses to TRH were completely resolved.
Asunto(s)
Adenoma/tratamiento farmacológico , Bromocriptina/uso terapéutico , Hormona Folículo Estimulante/metabolismo , Gonadotropinas/sangre , Neoplasias Hipofisarias/tratamiento farmacológico , Hormona Liberadora de Tirotropina/uso terapéutico , Adenoma/sangre , Adenoma/metabolismo , Anciano , Hormona Folículo Estimulante/sangre , Hormona Liberadora de Gonadotropina , Humanos , Hormona Luteinizante/sangre , Masculino , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/metabolismo , Inducción de Remisión/métodosRESUMEN
We report a rare case of a 57-year-old female patient with Cushing's disease who had clinically and biochemically proven cyclicity. There were periodic increases in plasma ACTH and cortisol and urinary free cortisol and 17-OHCS. Plasma CRH was undetectable and plasma ACTH responded to exogenous CRH when basal plasma cortisol was relatively low. Neither plasma ACTH nor cortisol responded to dexamethasone (oral and intravenous) but plasma ACTH was clearly suppressed by cortisol infusion. With 40 mg/day bromocriptine, the periodic hypercortisolemia disappeared and the patient was maintained on remission. The response of plasma cortisol to dexamethasone suppression test was also normalized.
Asunto(s)
Bromocriptina/uso terapéutico , Síndrome de Cushing/tratamiento farmacológico , Dexametasona , Hidrocortisona , Periodicidad , 17-Hidroxicorticoesteroides/orina , Hormona Adrenocorticotrópica/sangre , Hormona Liberadora de Corticotropina/sangre , Síndrome de Cushing/sangre , Síndrome de Cushing/orina , Retroalimentación , Femenino , Humanos , Hidrocortisona/sangre , Hidrocortisona/orina , Persona de Mediana Edad , Piridinas , Radioinmunoensayo , Inducción de Remisión/métodosRESUMEN
To verify the aldosterone amplifying action of 19-hydroxyandrostenedione (19-OH-AD), we investigated [3H]aldosterone and [3H]19-OH-AD binding to type I (mineralocorticoid) receptor in the renal cytosol of adrenalectomized and ovariectomized rat, and human mononuclear leucocytes (MNL). In the [3H]aldosterone binding study, the cytosol was incubated with [3H]aldosterone and 200-fold RU28362 (11 beta,17 beta-dihydroxy-6-methyl,17 alpha-(1-propynyl)-androsta-1,4,6- trien-3-one), a pure glucocorticoid, with or without 19-OH-AD. Scatchard plots of [3H]aldosterone binding to cytosol with 0.2 or 20 nM 19-OH-AD or without 19-OH-AD were linear. Dissociation constants (Kd) and maximum bindings (Bmax) without 19-OH-AD, and with 0.2 and 20 nM 19-OH-AD were: 0.71 +/- 0.03 nM and 23.0 +/- 3.4 fmol/mg protein (mean +/- SD, n = 3), 0.72 +/- 0.05 nM and 23.1 +/- 2.3 fmol/mg protein (n = 3), and 0.77 +/- 0.04 nM and 22.9 +/- 4.8 fmol/mg protein (n = 3), respectively. 19-OH-AD did not significantly change the Kd and Bmax of [3H]aldosterone binding. A high concentration of 19-OH-AD slightly displaced 0.2 or 5 nM [3H]aldosterone bound to cytosol. In human MNL, Scatchard plots of [3H]aldosterone binding with both 0.2 and 20 nM 19-OH-AD and without 19-OH-AD were linear. Kd and Bmax were, respectively, 1.00 nM and 780 sites/cell in the absence of 19-OH-AD, and 1.07 nM and 774 sites/cell in the presence of 0.2 nM 19-OH-AD. Without 19-OH-AD they were, respectively, 0.95 nM and 551 sites/cell, and 1.10 nM and 560 sites/cell with 20 nM 19-OH-AD. A high concentration of 19-OH-AD slightly displaced 0.2 or 5 nM of [3H]aldosterone bound to MNL. In both tissues, there was no obvious specific binding of [3H]19-OH-AD within the range of 1-60 nM. The above results suggest that the amplifying effect of 19-OH-AD on aldosterone mineralocorticoid action may not occur at the binding site of aldosterone to type I receptor, and that 19-OH-AD itself may not have any direct or indirect mineralocorticoid actions on the steroid receptor-mediated process in the rat kidney and human MNL.
Asunto(s)
Aldosterona/metabolismo , Androstenodiona/análogos & derivados , Riñón/metabolismo , Leucocitos Mononucleares/metabolismo , Adrenalectomía , Androstenodiona/metabolismo , Animales , Sitios de Unión , Citosol/metabolismo , Femenino , Humanos , Ovariectomía , Ratas , Ratas EndogámicasRESUMEN
We report a 37-year old Japanese female patient with Cushing's disease who was treated with a large daily dose of bromocriptine, which resulted in the reduction of the pituitary tumor size with clinical and biochemical improvements. On admission, the pituitary tumor size detected by magnetic resonance imaging (MRI) was 12.4 x 11.1 x 6.2 mm. Both the basal plasma prolactin level and its response to TRH test were normal. The patient was treated with bromocriptine at 5 to 35 mg/day. With 35 mg daily, 24-h urinary free cortisol started to decrease and eventually became normal. Four months after initiation of treatment with the drug, there was clinical remission with normalization of suppressibility of plasma cortisol with 1 mg dexamethasone. Repeated examination of the pituitary fossa by MRI showed a marked reduction in the tumor size (6.3 x 6.2 x 2.4 mm). This is a very rare case in which treatment with bromocriptine resulted in a reduction of the pituitary tumor size as well as clinical and biochemical improvements in a patient with normoprolactinemic Cushing's disease.
Asunto(s)
Bromocriptina/uso terapéutico , Síndrome de Cushing/tratamiento farmacológico , Neoplasias Hipofisarias/tratamiento farmacológico , Prolactina/sangre , Hormona Adrenocorticotrópica/sangre , Adulto , Síndrome de Cushing/sangre , Síndrome de Cushing/patología , Dexametasona/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Hidrocortisona/metabolismo , Imagen por Resonancia Magnética , Neoplasias Hipofisarias/patología , Reserpina/uso terapéuticoRESUMEN
To clarify the indication of surgery in incidentally discovered asymptomatic adrenal masses, we analyzed 386 Japanese cases, 379 cases reported in Japan during the past 25 years (from 1964 to 1988) and 7 cases from our own experience. From a total of 460 patients, we carefully selected 379 patients satisfying our criterion of the absence of symptoms and signs suggestive of active hormone over-secretion as described in each case report. From the Japanese series, there was a high incidence of pheochromocytoma patients (20 of 37 patients) who had no symptoms and signs but had high plasma or urine catecholamines. Scintigraphy with 131I-meta-iodo-benzyl-guanidine was useful in the diagnosis of pheochromocytoma. For the other asymptomatic adrenal tumors, except for myelolipoma and adrenal cyst, differential diagnosis between malignant and benign adrenal lesions by imaging procedures such as whole body computed tomography (CT), ultrasonography (US), adrenocortical scintigraphy, and angiography was not always possible. In addition, among the 109 patients with cortical tumors whose hormonal data were reported, no clear-cut differentiation of malignant tumor from benign by means of these data could be obtained. Since 1980 whole body CT scanner and high resolution US scanner have become widely available, and there have been 283 cases of asymptomatic adrenal tumors who satisfied our criterion. Cortical carcinomas smaller than 3 cm and 6 cm in diameter account for 3.8% and 6.6%, respectively, of the total of 101 cases of cortical carcinoma, cortical adenoma, ganglioneuroma, and hemangioma during this period. The size of the smallest cortical carcinoma with metastasis was 2 cm in diameter in this series. Pre-operatively, an adrenocortical carcinoma 2.8 cm in diameter in our patient could not be diagnosed as such by imaging techniques and measurement of plasma hormones. These findings suggest that an adrenal mass larger than 3 cm should be removed and a patient with a smaller cortical tumor should be carefully followed up.
Asunto(s)
Adenoma/terapia , Neoplasias de las Glándulas Suprarrenales/diagnóstico , 17-Hidroxicorticoesteroides/metabolismo , 17-Cetosteroides/metabolismo , Adenoma/diagnóstico , Adenoma/metabolismo , Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/cirugía , Adulto , Anciano , Aldosterona/sangre , Androstenodiona/metabolismo , Corticosterona/metabolismo , Deshidroepiandrosterona/metabolismo , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Renina/sangre , Tomografía Computarizada por Rayos X , Ultrasonografía , Ácido Vanilmandélico/metabolismoRESUMEN
A study of the pathophysiology in our previously reported case of glucocorticoid-responsive hyperaldosteronism (Case E.H., 17 yrs old, female; JCEM, 28: 1807, 1968), who had undergone a long-term successful treatment for 21 yrs of daily 0.5 mg dexamethasone (Dex), suggested again that the patient had 17 alpha-hydroxylase deficiency (17-OH-D) in the adrenal with minimum enzyme deficiency in the ovary. When Case E.H. was injected with zinc-ACTH for 3 days with daily 0.5 mg Dex administration, plasma levels of 17-deoxy-steroids were moderately or dramatically increased, but those of 17 alpha-hydroxy-steroids (17-OH-steroids) responded poorly or not at all. Plasma level of estradiol and urine estrogens were found to be normal in repeated measurements. Plasma basal levels of LH and FSH were normal, and their responses to LH-RH were high normal or slightly exaggerated. Her menstruation was almost regular, and the basal body temperature was at least biphasic with daily 0.5 mg Dex treatment. However, she did not become pregnant during the 17 yrs of her married life. Then, we surveyed 31 Japanese cases of 17-OH-D with suppressed plasma renin activity (PRA) to ascertain whether similar patients to our case, 17-OH-D with suppressed PRA and with hyperaldosteronism, has been reported or not. In this survey work, 9 such cases were found to have high plasma aldosterone (Ald) concentration (PAC) (group I). The other 21 cases had normal or low normal PAC, and the one remaining case had low urine Ald (group II). 17-Deoxy-steroids such as corticosterone, 11-deoxycorticosterone and progesterone, which were elevated in this disorder, were added to control plasma, and PAC was measured with Dainabot's "ALDOSTERONE.RIAKIT" used for the measurement of PAC in all group I patients. With the total of large amounts of 600 ng of these 17-deoxy-steroids (200 ng for each), however, the incremental PAC value was much less than the lowest PAC value in patients of group I. PAC of one group I patient was measured directly by "ALDOSTERONE.RIAKIT" and also by RIA after extraction and purification procedure using LH-20 column chromatography. The PAC values obtained by both methods were high and the same (285 pg/ml). In 5 out of 22 group II patients, PAC was also measured with the same RIA kit "ALDOSTERONE.RIAKIT" mentioned above, and yet it was low or low normal.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Hiperplasia Suprarrenal Congénita , Dexametasona/uso terapéutico , Hiperaldosteronismo/tratamiento farmacológico , Esteroide Hidroxilasas/deficiencia , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Humanos , Hiperaldosteronismo/etiología , Japón , Masculino , Factores de TiempoRESUMEN
The clinical and endocrine characteristics of 12 Japanese patients with dexamethasone-suppressible hyperaldosteronism were compared with those in 49 Japanese patients with primary aldosteronism due to aldosteronoma. The results were as follows: 1. Most of the laboratory data in the two groups were almost the same. 2. The grade of vascular damage in both uncontrolled (3) and well-controlled (9) patients with dexamethasone-suppressible hyperaldosteronism did not correlate with blood pressure response. 3. The responsiveness of plasma aldosterone to exogenous ACTH in 6 patients with dexamethasone-suppressible hyperaldosteronism was not different from that in 9 patients with aldosteronoma. Even in 3 well-controlled patients in the former group, the plasma aldosterone response was as low as in all the 3 patients with small aldosteronomas. 4. In 4 patients with small aldosteronomas, plasma aldosterone was continuously suppressed with daily dexamethasone to the same degree as in dexamethasone-suppressible hyperaldosteronism. 5. The blood pressure, however, did not improve even in the patients with small aldosteronomas. The possible indistinguishable mechanism in dexamethasone-suppressible hyperaldosteronism and primary aldosteronism with small adenomas and the role of unknown hypertensinogenic steroid(s) other than aldosterone in inducing hypertension in dexamethasone-suppressible hyperaldosteronism are discussed.
Asunto(s)
Dexametasona/uso terapéutico , Hiperaldosteronismo/sangre , Adenoma/metabolismo , Hormona Adrenocorticotrópica/farmacología , Adulto , Aldosterona/sangre , Aldosterona/metabolismo , Presión Sanguínea/efectos de los fármacos , Humanos , Hiperaldosteronismo/tratamiento farmacológico , Persona de Mediana Edad , Neoplasias Hipofisarias/metabolismo , Potasio/sangreRESUMEN
We reviewed the pathophysiology of our previously reported female patient who had glucocorticoid-responsive hyperaldosteronism and was treated successfully with daily dose of dexamethasone (Dex) for 21 years. In this present study, the possibility that the patient may have 17 alpha-hydroxylase deficiency (17-OH-D) mainly in the adrenal could not be ruled out. We therefore reviewed 31 Japanese patients diagnosed as having 17-OH-D with suppressed plasma renin activity reported in Japan. Among these patients, 9 were found to have a high plasma aldosterone (Ald) concentration (PAC) (group I). Twenty-one patients had either normal or low-normal PAC and the remaining patient had low urine Ald (group II). The slight cross-reactivity of the anti-Ald-antibodies used with 17-deoxy-steroids such as progesterone, 11-deoxycorticosterone and corticosterone which were increased in both groups did not explain the increased PAC in group I. In the patients in group I and group II with high-normal basal PAC, PAC further increased after ACTH and was suppressed by Dex. PAC in 2 group I patients, however, did not respond to angiotensin-II or angiotensin-III infusion. PAC in patients in group II with low or low-normal basal PAC responded equivocally to ACTH and Dex. The basal plasma cortisol in group I was lower than in group II, and plasma cortisol level after ACTH in group I appeared to remain at a lower level than that in group II patients. Among the study subjects, 28 showed a negative correlation between basal PAC and plasma cortisol. A possible discrepancy in the deficiency of 17 alpha-hydroxylase activity in adrenal and gonadal glands was also suggested in three 17-OH-D patients. The pathophysiology of Ald secretion and discrepancy in the deficiency of the enzyme activities in both glands in 17-OH-D patients was discussed.