adrenal incidentaloma by brandi jones salomone

Adrenal IncidentalomaAdrenal Incidentaloma

By Brandi Jones SalomoneBy Brandi Jones Salomone

Case presentationCase presentation

47 year old female presents to your 47 year old female presents to your office for follow up of an “abnormal office for follow up of an “abnormal CT scan”. Patient just seen in ED CT scan”. Patient just seen in ED and underwent stone study CT to and underwent stone study CT to assess for nephrolithiasis. Patient assess for nephrolithiasis. Patient passes stone but radiologist passes stone but radiologist comments on a 3.5 cm right adrenal comments on a 3.5 cm right adrenal mass and recommends that she mass and recommends that she follow-up with you.follow-up with you.

Background on Adrenal Background on Adrenal IncidentalomaIncidentaloma

Now a common problemNow a common problem Advances in CT scan and MRIAdvances in CT scan and MRI Adrenal gland made up of central Adrenal gland made up of central

medulla and exterior cortexmedulla and exterior cortex Produces cholesterol-based steroidsProduces cholesterol-based steroids Medullary catecholamine productionMedullary catecholamine production

Figure 1 Steroid Pathway from Figure 1 Steroid Pathway from Harrison’s textHarrison’s text

Questions to answer about the Questions to answer about the Adrenal IncidentalomaAdrenal Incidentaloma

““Is it hormonally active?”Is it hormonally active?” ““Is it benign or malignant?”Is it benign or malignant?”

Table 1 Differential diagnosis of an Table 1 Differential diagnosis of an Adrenal IncidentalomaAdrenal Incidentaloma

AdenomaAdenoma HyperplasiaHyperplasia CarcinomaCarcinoma PheoPheo MyelolipomaMyelolipoma HematomaHematoma CystCyst MetastasisMetastasis

GanglioneuromaGanglioneuroma NeurofibromaNeurofibroma HamartomaHamartoma Infiltrative diseaseInfiltrative disease

Herrera et al, Herrera et al, SurgerySurgery

Retrospective cohort studyRetrospective cohort study Guidelines for the investigation and Guidelines for the investigation and

management of an adrenal management of an adrenal incidentaloma (AI)incidentaloma (AI)

Sought to answer three questions: Sought to answer three questions: (1) do AI need routine endocrine (1) do AI need routine endocrine evaluation, (2) is there a size below evaluation, (2) is there a size below which an AI may be safely observed, which an AI may be safely observed, (3) need for follow-up evaluation (3) need for follow-up evaluation


Methods: collected 61,054 CT scansMethods: collected 61,054 CT scans 2066 (3.4%) had an adrenal mass2066 (3.4%) had an adrenal mass Strict exclusion criteria: previous Strict exclusion criteria: previous

malignancy, biochemical documentation of malignancy, biochemical documentation of disease, adrenal nodules > 1cm, disease, adrenal nodules > 1cm, constitutional or localizing symptoms, &/or constitutional or localizing symptoms, &/or evidence of local invasionevidence of local invasion

259 patients qualified for study + 89 259 patients qualified for study + 89 othersothers

Figure 2 Distribution of 2066 adrenal Figure 2 Distribution of 2066 adrenal abnormalities based on clinical factors. abnormalities based on clinical factors.



342 cases, 136 men and 206 women342 cases, 136 men and 206 women Reasons for CT scan: nonspecific Reasons for CT scan: nonspecific

abdominal pain, known abdominal or abdominal pain, known abdominal or thoracic disease, renal problems, thoracic disease, renal problems, musculoskeletal painmusculoskeletal pain


170 patients underwent endocrine 170 patients underwent endocrine testing: urinary testing: urinary metanephrines,VMA,urinary metanephrines,VMA,urinary excretion of 17-(OHCS), serum excretion of 17-(OHCS), serum cortisol,1 mg dexamethasone cortisol,1 mg dexamethasone suppression test,serum potassiumsuppression test,serum potassium

no androgen testingno androgen testing


Results of hormone analysis: 5 Results of hormone analysis: 5 pheochromocytomas and 2 cortisol pheochromocytomas and 2 cortisol producing adenomasproducing adenomas

4.1% of those tested had evidence of 4.1% of those tested had evidence of hyper-functionhyper-function

2.8% of total 3422.8% of total 342

Table 2 Characteristics of patients with functioning Table 2 Characteristics of patients with functioning and malignant tumors. Herrera et al, and malignant tumors. Herrera et al, SurgerySurgery


52 patients underwent adrenalectomy52 patients underwent adrenalectomy 5 patients had malignancy: 4 5 patients had malignancy: 4

adrenocortical carcinomas and one adrenocortical carcinomas and one metastasismetastasis

1.2% of 342 had cancer1.2% of 342 had cancer No malignancy < 5 cm in diameterNo malignancy < 5 cm in diameter 287 of 342 had follow-up; 90% at one 287 of 342 had follow-up; 90% at one

yearyear None had extension of tumor or hormonal None had extension of tumor or hormonal

excessexcess


Conclusions: (1) Hormonal Conclusions: (1) Hormonal screening on patients with an AI > 1 screening on patients with an AI > 1 cm, (2) any patient with a hyper-cm, (2) any patient with a hyper-secretory state should undergo secretory state should undergo adrenalectomy, (3) advise adrenalectomy, (3) advise adrenalectomy on AIs > 4 cm and adrenalectomy on AIs > 4 cm and (4) comparison CT scans at 3 month (4) comparison CT scans at 3 month intervals for those choosing intervals for those choosing observation only of their AI < 4 cmobservation only of their AI < 4 cm


Weaknesses: (1) No clarification on Weaknesses: (1) No clarification on their own criteria for testing patients their own criteria for testing patients for hormonal over-production, (2) for hormonal over-production, (2) Unclear why patients underwent Unclear why patients underwent adrenalectomy, (3) 55 patients lost adrenalectomy, (3) 55 patients lost to follow-up, (4) 90% of those that to follow-up, (4) 90% of those that followed up seen at 1 year mark, (5) followed up seen at 1 year mark, (5) no patients at follow-up underwent no patients at follow-up underwent hormonal testing and only 55% had hormonal testing and only 55% had repeat CT scansrepeat CT scans

Kasperlik-Zaluska, Kasperlik-Zaluska, Clinical Clinical EndocrinologyEndocrinology

Retrospective study of 208 patients Retrospective study of 208 patients referred for AIreferred for AI

Adrenal masses found by US for Adrenal masses found by US for following reasons and confirmed by following reasons and confirmed by CT scan: abdominal or lumbar pain, CT scan: abdominal or lumbar pain, nephrolithiasis, UTI, hematuria or nephrolithiasis, UTI, hematuria or erythrocytosiserythrocytosis

148 women and 60 men148 women and 60 men


Researchers attempted to exclude Researchers attempted to exclude patients with a malignancypatients with a malignancy

All patients had a CXR, DRE, CBE, All patients had a CXR, DRE, CBE, pap smear, CDP and an ESR.pap smear, CDP and an ESR.

No patients with positive screening No patients with positive screening testtest


Methods for endocrine testingMethods for endocrine testing 24 hour 17-OHCS in patients with 24 hour 17-OHCS in patients with

HTN or an arrythmiaHTN or an arrythmia 107 patients underwent am cortisol 107 patients underwent am cortisol

and ACTH levels; 89 had pm levels and ACTH levels; 89 had pm levels as wellas well

48 patients with findings suspicious 48 patients with findings suspicious for Cushing’s syndrome underwent for Cushing’s syndrome underwent low dose dexamethasone testinglow dose dexamethasone testing


Results of endocrine testingResults of endocrine testing Increased 17-OHCS in 2 with Increased 17-OHCS in 2 with

adenomas, 3 with ACC, 5 othersadenomas, 3 with ACC, 5 others 9 patients with increased urinary 9 patients with increased urinary

catecholaminescatecholamines All patients with hyper-secretion All patients with hyper-secretion

underwent adrenalectomyunderwent adrenalectomy Total of 19 patients with laboratory Total of 19 patients with laboratory

evidence of hyper-secretionevidence of hyper-secretion


Total of 85 patients underwent Total of 85 patients underwent adrenalectomy either because of an adrenalectomy either because of an AI > 4 cm and/or hormone over- AI > 4 cm and/or hormone over-productionproduction

Pathology confirmed 21 adenomas, Pathology confirmed 21 adenomas, 17 ACCs, 13 pheochromocytomas, 17 ACCs, 13 pheochromocytomas, 12 metastasis, 10 myelolipomas and 12 metastasis, 10 myelolipomas and 12 others12 others

Figure 3 Tumor sizes in the patients with adrenal Figure 3 Tumor sizes in the patients with adrenal adenoma, adrenal carcinoma, pheochromocytoma, others adenoma, adrenal carcinoma, pheochromocytoma, others (operated) and unoperated patients. Kasperlik-Zaluska, (operated) and unoperated patients. Kasperlik-Zaluska, CECE


Malignant tumor range: 3.2-20cmMalignant tumor range: 3.2-20cm Benign tumor range: 1.5-21 cmBenign tumor range: 1.5-21 cm Majority of adenomas < 6 cmMajority of adenomas < 6 cm All but 2 ACCs > 6 cm and all > 3 cmAll but 2 ACCs > 6 cm and all > 3 cm


Conclusions: (1) Size as a predictor of Conclusions: (1) Size as a predictor of malignancy is highly sensitive but poorly malignancy is highly sensitive but poorly specific, (2) ACC is highly prevalent in this specific, (2) ACC is highly prevalent in this study; 21% of patients who underwent study; 21% of patients who underwent adrenalectomy and 8.6% of total group, adrenalectomy and 8.6% of total group, (3) endocrine testing for patients with (3) endocrine testing for patients with clinical evidence of hyper-secretion and/or clinical evidence of hyper-secretion and/or those going to surgery, (4) criteria for those going to surgery, (4) criteria for surgery are: hyper-secretory state and/or surgery are: hyper-secretory state and/or AI > 4 cm, and (5) patients choosing AI > 4 cm, and (5) patients choosing observation only of their AI should observation only of their AI should undergo repeat US at 1, 3 and 6 month undergo repeat US at 1, 3 and 6 month intervalsintervals


Weaknesses: (1) Not clear why Weaknesses: (1) Not clear why patients tested for hormonal excess, patients tested for hormonal excess, (2) High prevalence of ACC not (2) High prevalence of ACC not consistent with overall incidence of consistent with overall incidence of disease nationwide, i.e. population disease nationwide, i.e. population biased because all referred, (3) biased because all referred, (3) adrenal masses initially detected by adrenal masses initially detected by US, and (4) lack of consistent follow-US, and (4) lack of consistent follow-upup

Luton et al, Luton et al, European Journal of European Journal of EndocrinologyEndocrinology

Retrospective cohort studyRetrospective cohort study Outcomes of 92 patients with an AI who Outcomes of 92 patients with an AI who

underwent adrenalectomy, FNA or autopsyunderwent adrenalectomy, FNA or autopsy CT scans performed for various reasonsCT scans performed for various reasons Initial group of 208 decreased to 180 all of Initial group of 208 decreased to 180 all of

whom underwent a complete physical whom underwent a complete physical exam, an abdominal CT scan and multiple exam, an abdominal CT scan and multiple endocrinological studiesendocrinological studies

103 women; 77 men103 women; 77 men

Luton et al, Luton et al, European Journal of European Journal of EndocrinologyEndocrinology

Methods: 88 patients underwent Methods: 88 patients underwent adrenalectomy secondary to a adrenalectomy secondary to a secreting tumor, an AI > 3 cm in secreting tumor, an AI > 3 cm in diameter and/or at risk for not diameter and/or at risk for not following upfollowing up

3 others underwent FNA3 others underwent FNA 1 had an autopsy1 had an autopsy

Table 3 Adrenal Incidentalomas Table 3 Adrenal Incidentalomas etiologies. Luton, etiologies. Luton, EJEEJE

Figure 4 AI size distribution Figure 4 AI size distribution according to diagnosis. Luton, according to diagnosis. Luton, EJEEJE

Luton et al, European Journal of Luton et al, European Journal of EndocrinologyEndocrinology

Conclusions: (1) All patients with an Conclusions: (1) All patients with an AI should undergo hormonal AI should undergo hormonal screening tests, (2) All patients with screening tests, (2) All patients with an AI > 3 cm should undergo an AI > 3 cm should undergo adrenalectomy, (3) Adrenalectomy adrenalectomy, (3) Adrenalectomy poses risk, and (4) The greater the poses risk, and (4) The greater the size of the AI the greater the size of the AI the greater the likelihood of malignancylikelihood of malignancy

Luton et al, European Journal of Luton et al, European Journal of EndocrinologyEndocrinology

Weaknesses: (1) 28 patients Weaknesses: (1) 28 patients excluded from study without excluded from study without explanation, (2) No clear statement explanation, (2) No clear statement on whether or not every patient on whether or not every patient underwent every endocrine study, underwent every endocrine study, (3) No specification on which (3) No specification on which endocrine studies to utilize, and (4) endocrine studies to utilize, and (4) No long-term follow-upNo long-term follow-up

Mantero, Mantero, JCEMJCEM

National survey on AINational survey on AI Purpose: To evaluate AI based on Purpose: To evaluate AI based on

imaging size aloneimaging size alone Strict exclusion criteriaStrict exclusion criteria 1004 enrolled; 584 women and 420 1004 enrolled; 584 women and 420

menmen All patients underwent CT scan or All patients underwent CT scan or

MRIMRI

Mantero, JCEMMantero, JCEM

85% underwent hormonal evaluation85% underwent hormonal evaluation Results: 9.2% had SCS, 1.6% had Results: 9.2% had SCS, 1.6% had

an aldosteronoma and 4.2% had an aldosteronoma and 4.2% had pheochromocytomaspheochromocytomas

All these patients underwent All these patients underwent adrenalectomyadrenalectomy

A total of 380 patients underwent A total of 380 patients underwent adrenalectomy. adrenalectomy.

Table 4 Histological picture in relation with Table 4 Histological picture in relation with gender, age, and mass size (CT measurement). gender, age, and mass size (CT measurement).

Mantero, Mantero, JCEMJCEM

Figure 5 Comparison of the mass size of Figure 5 Comparison of the mass size of histologically proven cortical adenomas and histologically proven cortical adenomas and

carcinomas. Mantero, carcinomas. Mantero, JCEMJCEM


Conclusions: (1) An AI > 4 cm is Conclusions: (1) An AI > 4 cm is 93% sensitive for detecting all 93% sensitive for detecting all malignancies and (2) Pain at malignancies and (2) Pain at presentation may be associated with presentation may be associated with a malignant outcomea malignant outcome


Weaknesses: (1) Unclear why Weaknesses: (1) Unclear why patients underwent hormonal patients underwent hormonal testing, (2)Hyper-secretory state testing, (2)Hyper-secretory state numbers may be falsely lowered numbers may be falsely lowered because of exclusion criteria (3) No because of exclusion criteria (3) No long term follow-up, and (4) No long term follow-up, and (4) No information on the 664 patients who information on the 664 patients who opted for observation only of their AIopted for observation only of their AI

Barzon et al, JCEMBarzon et al, JCEM

Retrospective study of 246 patients with an AIRetrospective study of 246 patients with an AI Purpose: to determine if certain characteristics of Purpose: to determine if certain characteristics of

an AI at initial diagnosis make it at risk for an AI at initial diagnosis make it at risk for malignant transformation and/or future hyper-malignant transformation and/or future hyper-secretionsecretion

155 chose observation-only of their AI; 155 chose observation-only of their AI; however,only 50% of group remained in studyhowever,only 50% of group remained in study

All patients seen in interval follow-up; mean All patients seen in interval follow-up; mean duration = 4.6 years and each time underwent duration = 4.6 years and each time underwent hormonal determinations and CT scanhormonal determinations and CT scan


Results: No patients had malignant Results: No patients had malignant transformation of their AItransformation of their AI

58 had no change in any study58 had no change in any study 11 had adrenal mass variations11 had adrenal mass variations 3 had overt hyper-function without mass 3 had overt hyper-function without mass

size changesize change 3 had hyper-function and mass 3 had hyper-function and mass

enlargementenlargement 9 of the 17 underwent an adrenalectomy 9 of the 17 underwent an adrenalectomy

or FNAor FNA

Table 5 Details of patients who developed mass Table 5 Details of patients who developed mass morphology changes and/or adrenal hyper-morphology changes and/or adrenal hyper-

function (n=17). Barzon et al, function (n=17). Barzon et al, JCEMJCEM

Figure 7 Estimated cumulative risk to develop adrenal Figure 7 Estimated cumulative risk to develop adrenal hyper-function in patients with adrenal incidentalomas hyper-function in patients with adrenal incidentalomas

according to mass size (n=75). Barzon et al, according to mass size (n=75). Barzon et al, JCEMJCEM

Figure 8 Estimated cumulative risk of adrenal mass enlargement in Figure 8 Estimated cumulative risk of adrenal mass enlargement in patients with AIs according to endocrine data at diagnosis (n=75). patients with AIs according to endocrine data at diagnosis (n=75).

Barzon et al, Barzon et al, JCEMJCEM

Table 6 Positive predictive value and cumulative risk for development Table 6 Positive predictive value and cumulative risk for development of adrenal hyper-function and mass enlargement in patients with of adrenal hyper-function and mass enlargement in patients with

adrenal incidentalomas. Barzon et al, adrenal incidentalomas. Barzon et al, JCEMJCEM


Conclusions: (1) The major risk factors Conclusions: (1) The major risk factors for malignant transformation are initial for malignant transformation are initial adrenal mass size > 3 cm and/or subtle adrenal mass size > 3 cm and/or subtle endocrine abnormalities at diagnosis, (2) endocrine abnormalities at diagnosis, (2) AI > 3 cm at diagnosis are at risk for AI > 3 cm at diagnosis are at risk for future hyper-function, and (3) Patients future hyper-function, and (3) Patients with AIs > 3 cm at diagnosis and those with AIs > 3 cm at diagnosis and those with subtle hormonal over-production with subtle hormonal over-production should be followed up at regular intervalsshould be followed up at regular intervals


Weaknesses: (1) Failure to Weaknesses: (1) Failure to recommend duration of follow-up recommend duration of follow-up and at what intervals, (2) 50% of the and at what intervals, (2) 50% of the observation only group did not observation only group did not participate and (3) No participate and (3) No recommendations on which patients recommendations on which patients with AI to test for endocrine with AI to test for endocrine abnormalities on initial evaluationabnormalities on initial evaluation

SummarySummary

No randomized, controlled trials No randomized, controlled trials No consensus on appropriate endocrine screening No consensus on appropriate endocrine screening

tests to detect hyper-secretiontests to detect hyper-secretion No optimal radiologic test to distinguish between No optimal radiologic test to distinguish between

benign and malignant tumorsbenign and malignant tumors No consensus on follow-upNo consensus on follow-up Natural history of ACC not entirely clear; Natural history of ACC not entirely clear;

however, appears to hold poor prognosis however, appears to hold poor prognosis Malignant tumors more likely to be > 3 cmMalignant tumors more likely to be > 3 cm

AI <3cm and no clinical evidence of hyper-secretion

AI > 3cmAI with history of malignancy

AI with clinical evidence of hyper-secretion

Consider appropriate search for a primary malignancy

Follow-up CT scans at 6 and 12 months then 1 year intervals for 5 years and endocrine studies if clinically indicated

Offer adrenalectomy

Endocrine studies pre-operatively

Re-offer adrenalectomy and endocrine testing

Stop checking

Endocrine evaluation with low dose dexamethasone suppression test, urine metanephrines, serum K+, serum aldosterone and upright plasma renin activity, serum DHEAS or urine 17-ketosteroids

Proceed with observation vs adrenalectomy based on size criteria and follow algorithm from there

FNANo

Yes

AI with constitutional symptoms

No change

> 1cm increase and/or new clinical suspicion of hyper-secretion

Adrenal incidentaloma on CT scan

Case presentationCase presentation

47 year female with a 3.5 cm adrenal 47 year female with a 3.5 cm adrenal incidentalomaincidentaloma

What to do?What to do?

THANK YOU VERY MUCH!THANK YOU VERY MUCH!

adrenal incidentaloma by brandi jones salomone

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testing patients

adrenal incidentaloma

adrenal nodules

adrenal abnormalities

characteristics of patients

surgery conclusions

surgery methods