肾上腺意外瘤指南课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,肾上腺意外瘤指南,（优选）肾上腺意外瘤指南,Definition,“Mass lesion greater than 1 cm in diameter discovered “accidentally” during a radiographic examination performed for indications other than an evaluation for adrenal disease.”,Management of the clinically inapparent adrenal mass (incidentaloma). NIH State-of-the-Science Conference Statement Feb 4-6, 2002.,Prevalence,Autopsies: 87,065 cases: 6% with adrenal adenomas,Abdominal CT (61,054 CT scans reviewed): 4% with adrenal adenomas,Now approaches the 8.7% incidence reported in autopsy series,Incidence Increases with Age,Endocrine and Metabolism Clinics of North America . 2000; 29(1):159-185,Three Main Questions,Is the adrenal mass hormonally active?,Is the mass benign or malignant?,Does the patient have a history of a previous malignant lesion?,Is it metastatic?,Anatomy,Anatomy,No cortisol suppression after 1 mg overnight dexamethasone suppression test BEST SCREENING TEST!,Mass between 46 cm: Criteria other than size should be used to dictate surgery vs.,Primary Aldosteronism,Urinary total metanephrines,1% of adrenal incidentaloma,JCEM 2005; 90:871,“The first initial test of choice for low risk patients is the 24hour urinary fractionated metanephrines and catecholamines.,monitoring,Probability of malignancy increases with size,Refractory to treatment,Three Main Questions,Subclinical Cushings Syndrome,Literature Search,Buffalo hump,Water= 0 HU,Is the mass benign or malignant?,Sensitivity was highest for fractionated PLASMA free metanephrines (99 percent),Subclinical Cushings syndrome: 9%,Anatomy,Primary Aldosteronism,Cushings Syndrome,DHEA-s,Pheochromocytoma,Frequency of Findings,Multicenter study of 1096 cases,Nonfunctioning adenoma: 85%,Subclinical Cushings syndrome: 9%,Pheochromocytoma: 4%,Aldosteronomas: 2%,Mantero et al. 85 (2): 637. (2000),Frequency of Findings,Allolio, B., Adrenal Incidentalomas.,Adrenal Disorders, ed. C.G. Margioris AN. 2001, Totowa: Humana Press Inc.,A summary of the literature,Nonfunctioning adenoma Approximately 80%,Subclinical Cushing syndrome (SCS), 5%,Pheochromocytoma 5%,Aldosteronoma 1%,adrenocortical carcinoma (ACC) 5 %,Metastatic lesion 2.5%,Ganglioneuromas, myelolipomas,or benign cysts,考虑是否手术治疗之前准确的功能诊断非常必要,嗜铬细胞瘤要进行认真的术前准备以避免术中和术后的发作和死亡。,原发性醛固酮增多症的患者需要明确是否存在肾上腺皮质增生及无功能的肾上腺腺瘤。肾上腺源性Cushing综合征的患者在行切除术后可能发生肾上腺皮质功能不全，激素的替代以及增减治疗需要非常仔细。亚临床Cushing综合征的患者是否需要手术治疗仍存在争议。,肾上腺皮质癌的患者手术前需要外科医师和内分泌科医师或肿瘤科医师共同协商决定切除的方式，因为首次切除的效果是生存率的主要预测因素。,超过4cm的肾上腺无功能瘤可以考虑切除。小的髓脂肪瘤或良性的囊肿一般影像学检查即可确诊，通常不需要治疗，除非有症状可以考虑手术治疗。,Algorithm for the evaluation and management of an adrenal incidentaloma,*,Reimage in 3 to 6 months and annually for 1 to 2 years; repeat functional studies annually for 5 years.If mass grows more than 1cm or becomes hormonally active, then adrenalectomy is recommended.,Hyperfunctioning Hormonal Evaluation,Subclinical Cushings Syndrome,Pheochromocytoma,Primary Aldosteronism,Sex hormonesecreting adrenocortical tumors,Atherosclerosis,Lipid rich mass are benign,2001, Totowa: Humana Press Inc.,Assessment of Malignant Potential,94% specificity; 91% sensitivity in hypertensive population,cystic, calcified mass,肾上腺源性Cushing综合征的患者在行切除术后可能发生肾上腺皮质功能不全，激素的替代以及增减治疗需要非常仔细。,Primary Aldosteronism,Primary Aldosteronism,Pheochromocytoma,JCEM 2005; 90:871,A summary of the literature,Hamrahian, et al.,2000; 29(1):159-185,Sex hormonesecreting adrenocortical tumors,Although elevated levels of fractionated plasma metanephrines have high sensitivity for pheo (99%), the test has a low specificity (85%) and thus should be used when suspicion is high.,Adipose tissue= 20 to 150 HU,Classic triads:,Literature Search,7% incidence reported in autopsy series,Subclinical Cushings Syndrome,Hypercortisolism without clinical manifestations of Cushings syndrome,Most frequent hormonal abnormality in adrenal incidentalomas,Subclinical Cushings Syndrome,Central obesity,Facial rounding,Buffalo hump,Easy bruising,Purple striae,Proximal muscle weakness,Emotional/cognitive changes,Subclinical Cushings Syndrome,Increase risk for:,Hypertension,Dyslipidemia,Impaired glucose tolerance,Type 2 DM,Atherosclerosis,Osteoporosis?,Tauchmanova L, et. al. Patients with subclinical Cushings syndrome due to,adrenal adenoma have increase cardiovascular risk. JCEM 2000; 85:1440.,Subclinical Cushings Syndrome,Biochemical abnormalities,Elevated urine free cortisol,Low or suppressed ACTH,Blunted diurnal variation,No cortisol suppression after 1 mg overnight dexamethasone suppression test BEST SCREENING TEST!,1. Mantero F, et al.,Hormone Res,47:284289, 1997,2. Montwill J, et al. The O/N DST is the procedure of choice for screening for Cushings syndrome.,Steroids,1994; 59:2296,Dexamethasone Suppression Test,1 mg dexamethasone at 11PM,Measure cortisol at 8 AM the next morning,Normal: cortisol 1.8g/dL (5ug/dl),Specificity of DST is 7282% (100%) Sensitivity 75100% (58%),Severe bipolar depression and severe alcoholism can give false positive results,If the DST 8AM serum cortisol is abnormal, then baseline ACTH, serum and 24hour urinary cortisol should be obtained and midnight salivary cortisol, or a 2day lowdose dexamethasone suppression test is needed to confirm autonomy,Hyperfunctioning Hormonal Evaluation,Subclinical Cushings Syndrome,Pheochromocytoma,Primary Aldosteronism,Sex hormonesecreting adrenocortical tumors,Pheochromocytoma,Rare but fatal catecholamines producing tumor,Incidence: 28/million people/year,Account for 5% of adrenal incidentaloma,Rule of 10s:,10% extraadrenal, 10% bilateral, 10% familial, 10% malignant,Aside from catecholamines, it can also secrete dopamine, ACTH, PTH, calcitonin, VIP,Pheochromocytoma,Classic triads:,Sudden severe headache,Diaphoresis,Palpitations,94% specificity; 91% sensitivity in hypertensive population,Pheochromocytoma,1976% of pheo are undiagnosed until after death,80% of patient with unsuspected pheo who underwent surgery or anesthesia will die,Although radiographic characteristics can give some clues:,Enhancement with IV on CT,High signal intensity on T2 weighted MRI,Prominent vascularity,Thus the need for screening,Imaging,Silent 8 cm pheo,Pheochromocytoma,Available Tests:,Plasma fractionated free metanephrines,24hour urinary fractionated metanephrines and catecholamines,Plasma catecholamines,Urinary total metanephrines,Urinary vanillylmandelic acid,Which test is best?,Literature Supports,Sensitivity was highest for fractionated PLASMA free metanephrines (99 percent),Using receiver operating characteristic curves, sensitivity values at different upper reference limits were highest for fractionated plasma free metanephrines.,“Fractionated plasma free metanephrines were the best test for excluding pheochromocytoma and should be the diagnostic test of first choice.”,JAMA 2002,Literature Supports,PLASMA free metanephrines BEST screening test,When the test is negative practically rules out pheo,Cost $100 per test,URINARY metanephrines less sensitive,Urinary VMA is outdated,Presented at the First International meeting on Adrenal Disease, 2002,Braz J Med Biol Res 33(10) 2000,When the test is negative, no other tests are needed.,Hamrahian, et al.,Atherosclerosis,suppressed renin activity,Cost $100 per test,Ganglioneuromas, myelolipomas,or benign cysts,Atherosclerosis,Is the mass benign or malignant?,3 hormonal tests necessary for workup of adrenal incidentaloma:,Surgery 1991 Dec;110(6):101421,If the DST 8AM serum cortisol is abnormal, then baseline ACTH, serum and 24hour urinary cortisol should be obtained and midnight salivary cortisol, or a 2day lowdose dexamethasone suppression test is needed to confirm autonomy,On contrastenhanced CT, adenomas exhibit rapid washout compared to nonadenomas (metastases, angiosarcoma, pheo, carcinoma),Although elevated levels of fractionated plasma metanephrines have high sensitivity for pheo (99%), the test has a low specificity (85%) and thus should be used when suspicion is high.,Easy bruising,“Plasma free metanephrines are recommended as the test of choice for excluding or confirming the diagnosis of pheochromocytoma.,Wash out 30 and PAC 20 ng/dL,90% spec and sensitivity for PA,If screening test is positive need to confirm with saline suppression test, adrenal venous sampling and imaging,midnight salivary cortisol, or a 2-,day low-dose dexamethasone suppression test,midnight salivary cortisol, or a 2-,day low-dose dexamethasone suppression test,Hyperfunctioning Hormonal Evaluation,Subclinical Cushings Syndrome,Pheochromocytoma,Primary Aldosteronism,Sex hormonesecreting adrenocortical tumors,Sex hormonesecreting Adrenocortical Tumors,Rare,Typically occur in the presence of clinical manifestations (hirsutism or virilization),2001, Totowa: Humana Press Inc.,Subclinical Cushings Syndrome,Aldosteronomas: 2%,Bone= 1000 HU,Adrenal Disorders, ed.,2001, Totowa: Humana Press Inc.,FNA is useful only in distinguishing adrenal tumor from metastasis and infection,Overall: 16%,1976% of pheo are undiagnosed until after death,Atherosclerosis,When the test is negative practically rules out pheo,Incidence: 28/million people/year,day low-dose dexamethasone suppression test,Cost $100 per test,Does the patient have a history of a previous malignant lesion?,Pheochromocytoma 5%,Aldosteronoma 1%,Assessment of Malignant Potential,Hirsutism,Sex hormonesecreting Adrenocortical Tumors,Rare,Typically occur in the presence of clinical manifestations (hirsutism or virilization),Routine screening for excess androgens and estrogens is not warranted,Hormonal Workup Summary,3 hormonal tests necessary for workup of adrenal incidentaloma:,1 mg overnight dexamethasone suppresion test,Plasma or urinary fractionated metaneprines,Plasma aldosterone concentration and plasma aldosterone concentration/plasma renin activity ratio (PAC/PRA).,Treatment,All patients with documented pheochromocytoma and primary aldosteronism should undergo surgery,No prospective, randomized trials for Subclinical Cushings Syndrome but concensus is to proceed with surgery if the patient is young,Three Main Questions,Is the adrenal mass hormonally active?,Is the mass benign or malignant?,Does the patient have a history of a previous malignant lesion?,Is it metastatic?,Primary Adrenal Carcinoma,Very rare: 5 cases per 1 million population,Small size corresponds to better prognosis,5 year survival,Overall: 16%,Localized disease (stage I and II): 42%,Metastases: 5.3%,Imaging,complex solid and,cystic, calcified mass,Patient with Known Malignancy,1040% of patients with known malignancy have adrenal metastases at autopsy,Most common primary,Breast,Lung,Kidney,Melanoma,Lymphoma,Assessment of Malignant Potential,Size,Imaging Phenotype (features),Size,Probability of malignancy increases with size,In a study involving 887 patients with adrenal incidentalomas, 90% of patients with adrenal carcinomas has tumor 4 cm (National Italian Study Group, 1997),adrenal carcinomas 2%(6cm),Size,Mayo Clinic Study,342 Patients with adrenal incidentaloma retrospectively evaluated,Tumor diameter averaged 2.5 cm,Most malignant tumors measured 5 cm,Incidentally discovered adrenal tumors: an institutional perspective. Herrera MF; Grant CS; van Heerden JA; Sheedy PF; Ilstrup DM. Surgery 1991 Dec;110(6):101421,Size,Consensus Statement,Mass 6 cm should be removed,Mass 4 cm can be monitored,Mass between 46 cm: Criteria other than size should be used to dictate surgery vs. monitoring,Management of the clinically inapparent adrenal mass (incidentaloma).,NIH State-of-the-Science Conference Statement Feb 4-6, 2002.,Assessment of Malignant Potential,Size,Imaging Phenotype,Image Phenotype CT Scan,Hounsfield unit (HU) semiquantitative method for measuring xray attenuation,Water= 0 HU,Adipose tissue= 20 to 150 HU,Kidney= 20 to 50 HU,Bone= 1000 HU,Lipid rich mass are benign,HU10 on unenhanced CT= benign adenoma 100%,Image Phenotype CT Scan,Retrospective analysis of 151 patients with adrenal masses,HU10 or a combination of tumor size 4cm and HU 60% at 10 min= no cancer,Wash out 60% at 10 min= high risk for malignant lesion,Imaging metastases,MRI,Equally effective as CT,Adenomas are isointense with the liver on T2 weighted images,Carcinomas are hyperintense compared to the liver on T2 weighted images,FNA,Cytology from FNA cannot distinguish benign adrenal mass vs. malignant,It can distinguish adrenal tissue from metastases,FNA is useful only in distinguishing adrenal tumor from metastasis and infection,Need to rule out pheochromocytoma before FNA,Follow Up,Will the mass become hypersecretory?,Will the mass become malignant?,