肾上腺意外瘤指南Adrenal Incidentaloma guidelines.ppt

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

2、or 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.

3、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

4、 it metastatic?,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.,Hyperfunctioning Hormonal Evaluation,Subclinical Cushings Syndro

5、me Pheochromocytoma Primary Aldosteronism Sex hormone-secreting adrenocortical tumors,Subclinical Cushings Syndrome,Hypercortisolism without clinical manifestations of Cushings syndrome Most frequent hormonal abnormality in adrenal incidentalomas,Subclinical Cushings Syndrome,Central obesity Facial

6、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 Cushin

7、gs 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-

8、 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:

9、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, then baseline ACTH, serum and 24-hour urinary cortisol should be obtained and midnight sa

10、livary cortisol, or a 2-day low-dose dexamethasone suppression test is needed to confirm autonomy,Hyperfunctioning Hormonal Evaluation,Subclinical Cushings Syndrome Pheochromocytoma Primary Aldosteronism Sex hormone-secreting adrenocortical tumors,Pheochromocytoma,Rare but fatal catecholamines produ

11、cing 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 also secrete dopamine, ACTH, PTH, calcitonin, VIP,Pheochromocytoma,Classic triads: Sudden severe headache

12、 Diaphoresis Palpitations 94% specificity; 91% sensitivity in hypertensive population,Pheochromocytoma,19-76% 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: Enhance

13、ment 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 24-hour urinary fractionated metanephrines and catecholamines Plasma catecholamines Urinary

14、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 fractionat

15、ed 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 ph

16、eo 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.,NIH State-of-the Science Conference Statement,Final Statemen

17、t 7/16/2002 “Plasma free metanephrines are recommended as the test of choice for excluding or confirming the diagnosis of pheochromocytoma.”,Management of the clinically inapparent adrenal mass (incidentaloma). NIH State-of-the-Science Conference Statement Feb 4-6, 2002,Disagreement!,Literature Sear

18、ch,“The first initial test of choice for low risk patients is the 24-hour urinary fractionated metanephrines and catecholamines.” 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 susp

19、icion is high.,What to do?,Plasma fractionated metanephrines Sens: 97-100%, Spec 85-89% Urinary fractionated metanephrines and catecholamines Sens: 91%, Spec 98%,Hyperfunctioning Hormonal Evaluation,Subclinical Cushings Syndrome Pheochromocytoma Primary Aldosteronism Sex hormone-secreting adrenocort

20、ical tumors,Primary Aldosteronism,1% of adrenal incidentaloma characterized by: high blood pressure Refractory to treatment hypokalemia Weakness, cramps suppressed renin activity metabolic alkalosis,Primary Aldosteronism,Patients with primary aldosteronism has increased risk for cardiovascular disea

21、se Thus necessary to screen all patients with adrenal incidentaloma for PA Screening test 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,midnight sa

22、livary 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 hormone-secreting adrenocortical tumors,S

23、ex hormone-secreting Adrenocortical Tumors,Rare Typically occur in the presence of clinical manifestations (hirsutism or virilization),Hirsutism,Sex hormone-secreting Adrenocortical Tumors,Rare Typically occur in the presence of clinical manifestations (hirsutism or virilization) Routine screening f

24、or 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/pl

25、asma 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 t

26、he 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% Localize

27、d disease (stage I and II): 42% Metastases: 5.3%,Imaging,complex solid and cystic, calcified mass,Patient with Known Malignancy,10-40% of patients with known malignancy have adrenal metastases at autopsy Most common primary Breast Lung Kidney Melanoma Lymphoma,Assessment of Malignant Potential,Size

28、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 wi

29、th 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):1014-21,Size,Consensus Stat

30、ement 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 Statement Feb 4-6, 2002.,Assessment of

31、 Malignant Potential,Size Imaging Phenotype,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 benign HU10 on unenhanced CT= benign adenoma 100%,Image

32、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,Image Phenotype- CT Scan,Contrast washout On contrast-enhanced CT, adenomas exhibit rapid

33、 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,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 adren