RESUMEN
PURPOSE: Some adrenal incidentalomas produce cortisol in mild excess ('subclinical' Cushing's adenomas) and can potentially induce osteopenia. Their diagnosis is usually based on exclusive tumour uptake on adrenal scintigraphy using 131I-6 beta-methyl-iodo-19-norcholesterol and on inadequate cortisol response to dexamethasone (DXM) suppression tests. The aims of the present study were to evaluate bone mineral density (BMD) and metabolic markers of bone turnover in patients with incidentalomas and to test the effect of mild hypercortisolism on bone parameters. METHODS: Thirty-five patients (13 men, 22 postmenopausal women, 49-76 years) with unilateral incidentaloma were studied. BMD was measured by dual X-ray absorptiometry. Two biochemical markers of bone formation, serum osteocalcin (BGP) and bone alkaline phosphatase (bALP), and two markers of bone resorption, urinary free deoxypyridinoline (D-Pyr) and urinary carboxy-telopeptide of bone type 1 collagen (CTX), were measured by radioimmunoassay. D-Pyr and CTX were corrected for creatinine excretion. RESULTS: Median values of lumbar and femoral T-score were -1.125 and -0.920, respectively, whereas corresponding Z-score values where normal (0.105 and 0.120, respectively). Thirty-nine percent of patients had low serum BGP values and 3% had low bALP values; 16% showed elevated D-Pyr/creatinine values and 23% increased CTX/creatinine values. Patients both with suppression of the contralateral adrenal on scintigraphy and with an inadequate cortisol response to 1 mg DXM (> 50 nmol/L) (n = 14) presented a lower femoral T-score (P < 0.02) and, to a lesser extent, a lower femoral Z-score (P = 0.11) than other patients (n = 21). The proportion of increased values of CTX/creatinine (42% versus 11%, P = 0.08) also tended to be higher in the first than in the second group of patients. These two groups of patients were similar in terms of age, but tumour size was larger (P < 0.04) and plasma ACTH value was lower (P < 0.02) in patients with scintigraphic and endocrine abnormalities. CONCLUSION: Subclinical hypercortisolism defined on the basis of scintigraphic and hormonal criteria seems to contribute to bone loss in patients with adrenal incidentaloma. As other possible side effects of mild hypercortisolism, these findings have to be taken into account in the therapeutic management of these patients.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/complicaciones , Biomarcadores de Tumor/análisis , Densidad Ósea , Enfermedades Óseas Metabólicas/etiología , Regeneración Ósea , Resorción Ósea , Hidrocortisona/metabolismo , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/patología , Dexametasona , Femenino , Glucocorticoides , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , CintigrafíaRESUMEN
OBJECTIVE: Biochemistry and I-6beta-iodomethyl norcholesterol scintigraphy (IMS) have both been used to assess cortisol secretion by adrenocortical incidentalomas. However, which biochemical abnormalities indicate subclinical corticoid excess is still debatable whilst IMS is expensive and cumbersome. The aim of the study was to evaluate prospectively patients with adrenal incidentalomas using both IMS and biochemical methods to examine whether the IMS pattern is associated with biochemical abnormalities and, if this is so, to find a biochemical parameter that could be used as a screening test to identify a subset of patients on whom IMS could subsequently be performed. METHODS: Thirty-one patients with benign cortical adenomas were recruited from 43 consecutive patients with adrenal incidentalomas. All 31 patients underwent IMS and measurement of (i) 0800 h serum cortisol, ACTH, dehydroepiandrosterone and 17-hydroxyprogesterone; (ii) midnight serum cortisol; (iii) 2400 h excretion of urinary free cortisol; (iv) cortisol after the overnight 1 mg dexamethasone (DEX) suppression test; (v) cortisol after an i.v. 4 mg DEX test; (vi) determination of the diurnal variation in serum cortisol. RESULTS: Sixty-one per cent of patients displayed unilateral uptake during IMS and 39% showed bilateral uptake. Patients with unilateral uptake exhibited significantly lower ACTH concentrations (P=0.0005), higher midnight cortisol concentrations (P=0.02), disrupted diurnal variation of serum cortisol (P=0.02) and higher cortisol concentrations after DEX suppression tests (P=0.01). Cortisol concentrations following the two DEX suppression tests correlated closely (r=0.80, P=0.0001). The i.v. 4 mg DEX test was clearly more sensitive for the diagnosis of unilateral uptake than the overnight 1 mg DEX test (76 vs 52%). Using various thresholds of cortisol concentration following the overnight 1 mg DEX test, it was found that the sensitivity of the test could be improved to 100% if the threshold was set at 60 nmol/l rather than the classical value of 138 nmol/l. All patients but one with post-test serum cortisol concentrations above 60 nmol/l as against none of patients with cortisol below 60 nmol/l exhibited at least one associated biochemical abnormality indicating subclinical glucocorticoid excess. CONCLUSION: In adrenocortical incidentalomas, unilateral uptake during IMS suggests subclinically excessive and/or autonomous cortisol secretion. A cortisol concentration above 60 nmol/l following the overnight 1 mg DEX test is highly correlated with unilateral uptake and is associated with biochemical abnormalities indicating subclinical glucocorticoid excess. Our results favour the use of the 1 mg overnight DEX test with revised criteria of interpretation as a screening test for subclinical hypercortisolism among patients with adrenocortical incidentalomas.
Asunto(s)
Adenoma/diagnóstico por imagen , Adenoma/metabolismo , Adosterol , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/metabolismo , Radiofármacos , Corticoesteroides/sangre , Hormona Adrenocorticotrópica/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , CintigrafíaRESUMEN
OBJECTIVES: The authors present a case report that proposes the use of cabergoline treatment in silent ACTH adenoma, an unusual member of the heterogeneous group of the so-called clinically non-functioning pituitary adenomas. DESIGN: Following the clinical and radiological improvement of a recurrent silent ACTH adenoma in a 77-year-old patient treated with cabergoline (0.5 mg every 2 days for 2 years), in vitro studies of the original tumor were performed. METHODS: The original tumor from the patient was studied by in situ hybridization and dopamine D2 receptor autoradiography. It was compared with four macroprolactinomas and two macroadenomas from patients with Cushing's disease. RESULTS: The D2 receptor mRNA signal of the reported case was intense and of the same order of magnitude as that observed in control prolactinomas. Dopamine D2 receptor autoradiography was twice that of control corticotroph adenomas and was close to that observed in prolactinomas. CONCLUSIONS: This is the first description of an in vivo shrinkage of an ACTH silent adenoma under cabergoline. We demonstrate in vitro, the presence of D2 receptors in the primitive tumor in concentrations similar to those found in control prolactinomas. These results suggest that therapeutic trials with cabergoline might be undertaken in recurring cases of ACTH silent tumors and more generally, non-functioning pituitary adenomas.
Asunto(s)
Adenoma/tratamiento farmacológico , Hormona Adrenocorticotrópica/metabolismo , Antineoplásicos/uso terapéutico , Ergolinas/uso terapéutico , Neoplasias Hipofisarias/tratamiento farmacológico , Adenoma/química , Adenoma/metabolismo , Anciano , Autorradiografía , Cabergolina , Humanos , Hibridación in Situ , Masculino , Recurrencia Local de Neoplasia , Neoplasias Hipofisarias/química , Neoplasias Hipofisarias/metabolismo , Prolactinoma/química , ARN Mensajero/análisis , Receptores de Dopamina D2/análisis , Receptores de Dopamina D2/genéticaRESUMEN
Normotensive primary hyperaldosteronism is exceedingly rare. We report two new cases of this syndrome in two middle-aged women, one of Asian origin. The presenting signs were tetany in one case and an adrenal mass in the other. Neither patient had hypertension, despite repeated measurements with a manual armlet. A typical biological profile of primary hyperaldosteronism was demonstrated in both patients, including hypokalemia with inappropriate kaliuresis, elevated resting plasma aldosterone, and undetectable plasma renin activity. The circadian rhythm of blood pressure was studied by ambulatory monitoring pre- and post-operatively. It confirmed the lack of hypertension, but the circadian rhythm of blood pressure was lost before surgery in one patient. Surgical removal of the histologically typical aldosterone-producing adenomas normalized the kalemia. The main finding in these two patients was spontaneously low blood pressure in the post-operative period. This suggests that excess aldosterone induced relative hypertension in these patients whose blood pressure was spontaneously very low. Genetic screening for dexamethasone-sensitive hyperaldosteronism was negative in both patients.
Asunto(s)
Adenoma/metabolismo , Neoplasias de las Glándulas Suprarrenales/fisiopatología , Aldosterona/metabolismo , Hiperaldosteronismo/fisiopatología , Hipertensión/complicaciones , Adenoma/cirugía , Neoplasias de las Glándulas Suprarrenales/cirugía , Adulto , Aldosterona/sangre , Aldosterona/orina , Factor Natriurético Atrial/sangre , Monitoreo Ambulatorio de la Presión Arterial , Southern Blotting , Cromatografía Líquida de Alta Presión , Dexametasona/farmacología , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Hiperaldosteronismo/genética , Hiperaldosteronismo/cirugía , Hipertensión/fisiopatología , Potasio/sangre , Potasio/orina , Radioinmunoensayo , Renina/sangre , Tetania , Tomografía Computarizada por Rayos XRESUMEN
The follow-up of patients who underwent thyroidectomy for differentiated thyroid carcinoma is based on the combination of serum thyroglobulin (Tg) measurement and radioiodine total-body scan (ITBS). The diagnostic strategy to be used in patients with elevated serum Tg level but negative ITBS remains debatable. Somatostatin receptor scintigraphy (SRS) has been proposed. Our objective was to compare the results of SRS and conventional radiological imaging (CRI) for the diagnosis of recurrent disease and/or metastases in 15 patients who had had thyroidectomy for differentiated carcinoma (14 papillary, 1 Hurthle cell carcinoma) and who displayed elevated Tg levels (10 to 65000 ng/mL) together with negative ITBS performed after 100 mCi. All patients underwent SRS and CRI within 3 months, allowing comparison of the 2 approaches for the identification of thyroid carcinoma metastases. CRI first included a chest x-ray and ultrasonography of the neck. It was followed by computed tomography (CT) scanning and/or magnetic resonance imaging (MRI) of the neck, chest and occasionally abdomen, and 99mTc bone scintigraphy in case of negative results. In 6 patients with Tg levels ranging from 65 to 65000 ng/mL, CRI detected 12 histologically proven metastases among 9 organs. Among these patients, SRS identified only 6 metastases. SRS identified 1 case of mediastinal recurrence that was not detected by CRI. In another patient with a Tg level of 51 ng/mL, a cervical node was identified using both SRS and CRI but proved to be a false-positive (inflammatory cervical node). In the other 8 patients with Tg levels ranging from 10 to 580 ng/mL, SRS and CRI were negative, and the source of Tg secretion remains unknown. The results of SRS did not correlate with serum Tg level. In conclusion, the diagnostic accuracy of SRS in this study was disappointing and clearly lower than that of CRI. Our results do not support the use of SRS as a guide conventional imaging modalities in patients operated on for differentiated thyroid carcinoma who display elevated Tg levels together with negative ITBS.