肾上腺意外瘤指南Adrenal Incidentaloma guidelines[材料参考]

1、Adrenal Incidentaloma guidelines,AACE/AAES,1,参考档案,Outline,Definition Prevalence Anatomy and Physiology Review Diagnostic Workups Conclusions,2,参考档案,Definition,“Mass lesion greater than 1 cm in diameter discovered “accidentally” during a radiographic examination performed for indications other than a

2、n evaluation for adrenal disease.”,Management of the clinically inapparent adrenal mass (incidentaloma). NIH State-of-the-Science Conference Statement Feb 4-6, 2002.,3,参考档案,Prevalence,Autopsies: 87,065 cases: 6% with adrenal adenomas Abdominal CT (61,054 CT scans reviewed): 4% with adrenal adenomas

3、Now approaches the 8.7% incidence reported in autopsy series,4,参考档案,Incidence Increases with Age,Endocrine and Metabolism Clinics of North America . 2000; 29(1):159-185,5,参考档案,Three Main Questions,Is the adrenal mass hormonally active? Is the mass benign or malignant? Does the patient have a history

4、 of a previous malignant lesion? Is it metastatic?,6,参考档案,Anatomy,/sealion/view_photo.php?set_albumName=album265 repeat functional studies annually for 5 years.If mass grows more than 1cm or becomes hormonally active, then adrenalectomy is recommended.,14,参考档案,Hyperfunctioni

5、ng Hormonal Evaluation,Subclinical Cushings Syndrome Pheochromocytoma Primary Aldosteronism Sex hormone-secreting adrenocortical tumors,15,参考档案,Subclinical Cushings Syndrome,Hypercortisolism without clinical manifestations of Cushings syndrome Most frequent hormonal abnormality in adrenal incidental

6、omas,16,参考档案,Subclinical Cushings Syndrome,Central obesity Facial rounding Buffalo hump Easy bruising Purple striae Proximal muscle weakness Emotional/cognitive changes,17,参考档案,Subclinical Cushings Syndrome,Increase risk for: Hypertension Dyslipidemia Impaired glucose tolerance Type 2 DM Atheroscler

7、osis Osteoporosis?,Tauchmanova L, et. al. Patients with subclinical Cushings syndrome due to adrenal adenoma have increase cardiovascular risk. JCEM 2000; 85:1440.,18,参考档案,Subclinical Cushings Syndrome,Biochemical abnormalities Elevated urine free cortisol Low or suppressed ACTH Blunted diurnal vari

8、ation 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; 59:2296,19,参考档案,Dexamethasone Supp

9、ression 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 72-82% (100%) Sensitivity 75-100% (58%) Severe bipolar depression and severe alcoholism can give false positive results If the DST 8AM serum cortisol is abnormal,

10、 then baseline ACTH, serum and 24-hour urinary cortisol should be obtained and midnight salivary cortisol, or a 2-day low-dose dexamethasone suppression test is needed to confirm autonomy,20,参考档案,Hyperfunctioning Hormonal Evaluation,Subclinical Cushings Syndrome Pheochromocytoma Primary Aldosteronis

11、m Sex hormone-secreting adrenocortical tumors,21,参考档案,Pheochromocytoma,Rare but fatal catecholamines producing tumor Incidence: 2-8/million people/year Account for 5% of adrenal incidentaloma Rule of 10s: 10% extra-adrenal, 10% bilateral, 10% familial, 10% malignant Aside from catecholamines, it can

12、 also secrete dopamine, ACTH, PTH, calcitonin, VIP,22,参考档案,Pheochromocytoma,Classic triads: Sudden severe headache Diaphoresis Palpitations 94% specificity; 91% sensitivity in hypertensive population,23,参考档案,Pheochromocytoma,19-76% of pheo are undiagnosed until after death 80% of patient with unsusp

13、ected 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,24,参考档案,Imaging,Silent 8 cm pheo,25,参考档案,Pheochromocytoma,Available

14、Tests: Plasma fractionated free metanephrines 24-hour urinary fractionated metanephrines and catecholamines Plasma catecholamines Urinary total metanephrines Urinary vanillylmandelic acid Which test is best?,26,参考档案,Literature Supports,Sensitivity was highest for fractionated PLASMA free metanephrin

15、es (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

16、of first choice.”,JAMA 2002,27,参考档案,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 Diseas

17、e, 2002 Braz J Med Biol Res 33(10) 2000,When the test is negative, no other tests are needed.,28,参考档案,NIH State-of-the Science Conference Statement,Final Statement 7/16/2002 “Plasma free metanephrines are recommended as the test of choice for excluding or confirming the diagnosis of pheochromocytoma

18、.”,Management of the clinically inapparent adrenal mass (incidentaloma). NIH State-of-the-Science Conference Statement Feb 4-6, 2002,29,参考档案,Disagreement!,30,参考档案,Literature Search,“The first initial test of choice for low risk patients is the 24-hour urinary fractionated metanephrines and catechola

19、mines.” 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.,31,参考档案,What to do?,Plasma fractionated metanephrines Sens: 97-100%, Spec 85-89% Urinary fractionated metan

20、ephrines and catecholamines Sens: 91%, Spec 98%,32,参考档案,Hyperfunctioning Hormonal Evaluation,Subclinical Cushings Syndrome Pheochromocytoma Primary Aldosteronism Sex hormone-secreting adrenocortical tumors,33,参考档案,Primary Aldosteronism,1% of adrenal incidentaloma characterized by: high blood pressur

21、e Refractory to treatment hypokalemia Weakness, cramps suppressed renin activity metabolic alkalosis,34,参考档案,Primary Aldosteronism,Patients with primary aldosteronism has increased risk for cardiovascular disease Thus necessary to screen all patients with adrenal incidentaloma for PA Screening test

22、is: PAC and PAC/PRA ratio PAC/PRA 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,35,参考档案,midnight salivary cortisol, or a 2- day low-dose dexamethasone suppression test,midnight sali

23、vary cortisol, or a 2- day low-dose dexamethasone suppression test,36,参考档案,37,参考档案,Hyperfunctioning Hormonal Evaluation,Subclinical Cushings Syndrome Pheochromocytoma Primary Aldosteronism Sex hormone-secreting adrenocortical tumors,38,参考档案,Sex hormone-secreting Adrenocortical Tumors,Rare Typically

24、occur in the presence of clinical manifestations (hirsutism or virilization),39,参考档案,Hirsutism,40,参考档案,Sex hormone-secreting Adrenocortical Tumors,Rare Typically occur in the presence of clinical manifestations (hirsutism or virilization) Routine screening for excess androgens and estrogens is not w

25、arranted,41,参考档案,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

26、).,42,参考档案,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,43,参考档案,Three Main Questions,Is the adrenal mass ho

27、rmonally active? Is the mass benign or malignant? Does the patient have a history of a previous malignant lesion? Is it metastatic?,44,参考档案,Primary Adrenal Carcinoma,Very rare: 5 cases per 1 million population Small size corresponds to better prognosis 5 year survival Overall: 16% Localized disease

28、(stage I and II): 42% Metastases: 5.3%,45,参考档案,Imaging,complex solid and cystic, calcified mass,46,参考档案,Patient with Known Malignancy,10-40% of patients with known malignancy have adrenal metastases at autopsy Most common primary Breast Lung Kidney Melanoma Lymphoma,47,参考档案,Assessment of Malignant P

29、otential,Size Imaging Phenotype (features),48,参考档案,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),49,参考档案,Size,May

30、o 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(

31、6):1014-21,50,参考档案,Size,Consensus Statement Mass 6 cm should be removed Mass 4 cm can be monitored Mass between 4-6 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

32、Statement Feb 4-6, 2002.,51,参考档案,Assessment of Malignant Potential,Size Imaging Phenotype,52,参考档案,Image Phenotype- CT Scan,Hounsfield unit (HU)- semiquantitative method for measuring x-ray attenuation Water= 0 HU Adipose tissue= -20 to -150 HU Kidney= 20 to 50 HU Bone= 1000 HU Lipid rich mass are be

33、nign HU10 on unenhanced CT= benign adenoma 100%,53,参考档案,Image Phenotype- CT Scan,Retrospective analysis of 151 patients with adrenal masses HU10 or a combination of tumor size 4cm and HU 20= excluded non-adenomas in 100 percent of cases,Hamrahian, et al. JCEM 2005; 90:871,54,参考档案,Image Phenotype- CT

34、 Scan,Contrast washout On contrast-enhanced CT, adenomas exhibit rapid washout compared to non-adenomas (metastases, angiosarcoma, pheo, carcinoma) Wash out of 60% at 10 min= no cancer Wash out 60% at 10 min= high risk for malignant lesion,55,参考档案,Imaging- metastases,56,参考档案,MRI,Equally effective as

35、 CT Adenomas are isointense with the liver on T2 weighted images Carcinomas are hyperintense compared to the liver on T2 weighted images,57,参考档案,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 fr