Transcript File

What in the World To Make of
Incidentalomas
Adrenal, Pituitary, Renal and Thyroid
Elyssa Del Valle, M.D.
Vice President & Medical Director
October 14, 2016
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Terminology: Nodule, Lesion, Mass, Tumor
 Nodule is a radiographic finding of a mass or lesion and does not in and
of itself imply whether benign or malignant
 Tumor is used to imply mass/lesion/nodule that has been removed or
biopsied and confirmed as either benign, malignant or atypical
 Point to this: If nodule has characteristics of a benign process by virtue of
imaging and lab results, often it may not warrant biopsy/removal to assume
a benign entity
 If nodule has malignant characteristics on imaging, then it would
necessitate biopsy to confirm malignant tumor via cytology evaluation
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Anatomy of Adrenal Glands
Adrenal glands are known as suprarenal glands
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Adrenal Incidentaloma: Defintion
 An adrenal mass, generally 1 cm or greater, that is discovered during a
radiologic examination performed for indications other than an evaluation
for adrenal disease
 In other words, detection of an otherwise unsuspected adrenal mass on
imaging
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Prevalence of Adrenal Incidentalomas
 Incidentalomas have become widespread since use of CT, MRI, resulting in
the dilemma regarding their significance
 Prevalence is 4.4% on CT and MRI
 Prevalence increases with increasing age
 In those between 20-29 yrs old, prevalence is 0.2%
 In those over 70 yrs of age, prevalence is 7%
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Underwriting Risks of Adrenal Incidentalomas
 Malignancy Risk Factors
- Nodule > 4 cm
- Multiple
- Imaging characteristics
- Growth on surveillance
- Hormone Producing
 Surgical Risks
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What Next In Its Evaluation
Must ask 3 specific questions:
1) Is the nodule/mass/lesion functioning or nonfunctioning?
2) Does it have radiographic features to suggest malignancy?
3) Does the person have a history of a previous malignancy?
These questions are similarly raised for most glandular Incidentalomas
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Why Ask These Questions Re: Adrenal Incidentaloma?
 80% are nonfunctioning adenomas
 5% have associated subclinical Cushing’s Syndrome
 5% pheochromocytoma
 1% hyperaldosteronism
 < 5% are adrenocortical carcinoma
 2.5% have metastatic disease
 Remaining are benign cysts, ganglioneuromas, lipoma or myelolipomas
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Question 1: Functioning or Nonfunctioning
 Adrenal glands produce a variety of hormones
 Medulla or center produce catecholamines (epinephrine)
 Cortex or outer portion produce steroids( cortisol and androgen) and
mineralocorticoids (aldosterone)
 Thus in order to answer, need to assess for overproduction of these
hormones
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Functioning or Nonfunctioning: Hormone Evaluation
 Subclinical Cushing’s: autonomous cortisol secretion who have no overt
symptoms/signs of hypercortisolism
• overnight dexamethasone suppression test
• 24 hour urine for cortisol
 Silent pheochromocytoma: in hypertensive individuals
• 24 hour urine for metanephrines, catecholamines
 Primary Aldosteronism: in hypertensive individuals
• Potassium level and ratio of morning aldosterone to plasma renin activity
 Sex hormone secreting tumor and congenital adrenal hyperplasia
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Conditions Associated with Functional Adrenal Nodules
 Cortisol secreting adenoma- obesity, IFG, DM, HLD, HTN
 Pheochromocytoma – HTN, CVA -* (10% are malignant)
 Aldosterone secreting adenoma- *HTN, Hypokalemia
 Androgen secreting adenoma – virilization (hirsutism, cliteromegaly,
deepening of voice, amenorrhea) has special concern for malignancy
 Appropriate next step- Surgical removal and classification of tumor as
benign or malignant - removal associated with resolution of conditions
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Question 2: Malignant Characteristic on Imaging
 Size > 4 cm
 Shape: irregular, unclear margins,
 Texture: heterogeneous with mixed densities
 Attenuation (density) on noncontrast CT: > 10 Hounsfield (usually>25)
 Vascularity on contrast CT: vascular as opposed to avascular
 Rapidity of washout of contrast: < 50% at 10 minutes
 Appearance on MRI: Hyperintense in relation to liver
 Necrosis, hemorrhage or calcifications: common
 Growth rate: usually rapid (>2 cm per year in adenocarcinoma; slow to rapid in metastatic
lesions) Marker of higher grade tumor
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Question 3: Any History of Prior Malignancy
 Metastasis is the cause in 50% who have history of malignancy
 Cancers associated with metastasis to adrenals include:
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Lung
Kidney
Colon
Breast
Esophagus
Pancreas
Liver
Stomach
Melanoma
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Guidelines for Evaluation of Adrenal Incidentaloma
 Hormonal evaluation with dexamethasone suppression test, 24 hour cortisol,
metanephrine and catecholamine, plasma aldosterone and plasma renin activity
 If results consistent with autonomous hormone secretion, consider unilateral
laparoscopic adrenalectomy
 If imaging suggests infection or metastasis, consider CT guided FNA
 If hormone testing normal and imaging suggests benign, repeat imaging at 6, 12
and 24 months with annual hormone evaluation for 4 years
 FNA or adrenalectomy for mass > 4cm or if enlarging by 1 cm during period of
observation
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AACE/AAES Adrenal Incidentaloma Guidelines
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Mortality and Morbidity of Adrenal Incidentaloma
 Mortality related to local and metastatic spread if malignant
 Mortality concerns for functional adenomas include DM, HTN, MI, CVA,
Arrhythmia, CHF and Surgical Complications
 Morbidity concerns for functional adenomas include DM, HTN, Post MI,
CVA, Obesity, Osteoporosis, Arrhythmia, Virilization
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Pituitary Gland
Cancerinfo.tri-kobe.org
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Pituitary Incidentalomas: Definition
 An unsuspected lesion detected on imaging performed for reasons other
than pituitary symptoms or disease
 Can also include asymptomatic prolactinoma
 Pituitary microadenoma is defined as less than 1 cm
 Macroadenoma is defined as 1 cm or larger
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Etiologies of Sellar Lesions
Congenital
Vascular
 Rathke’s cleft cyst
 Aneurysm
 Arachnoid cyst
 Cavernous sinus thrombosis
 Infarction/Hemorrhage
Neoplasms
Inflammatory/Infectious
 Pituitary adenoma (most common)
 Sarcoidosis
 Meningioma
 Lymphocytic hypophysitis
 Craniopharyngioma
 Granulomatous hypophysitis
 Germ cell tumor
 Schwannoma/neuroma
 Hypothalmic hamartomas
 Pituitary abcess
 Dermoid and epidermoid tumors
 Metastasis (lung, breast)
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Prevalence of Pituitary Incidentalomas
 Prevalence of <1 cm lesions on CT is 4-20%
 Prevalence of <1 cm on MRI is 10-38%
 In autopsy studies: 27% incidence: nearly all were microadenomas (<1 cm)
 No difference between men/women and across age groups
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Classification of Pituitary Adenoma
 Size: Micro < 1 cm or Macro > 1 cm
 Functional or Nonfunctional
• Functional adenomas usually present early as microadenomas due to expression of
hormone abnormalities
• Non-functional adenomas typically present late as macroadenoma due to mass effects
• Non-functional adenoma (30%)
• Prolactinomas (30%)
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Clinical Course in Prospective Studies
 Non-functioning sellar masses > 1 cm were 4 x likely to experience growth
during follow up than those < 1 cm (incidence 12.5 versus 3.3 per 100
person-years, respectively)
 This illustrates why there is less concern for non-functioning pituitary
incidentalomas less than 0.5 cm
 This also illustrates why we may decline those that are > 1 cm if not
surgically resected unless they prove stable in size for many years
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Symptoms Associated with Pituitary Adenomas
 Mass effect: If large, can invade and compress structures outside sella and cause
HA, double vision/diminished visual field and acuity and hydrocephalus
 Hormonal effect: If large, can compress pituitary gland causing loss of one or
more hormones ranging from LH/FSH deficiency, growth hormone deficiency,
secondary hypothyroidism, adrenal insufficiency or even panhypopituitarism
 Hormonally active adenomas can secrete one or more hormones resulting in
hyperthyroidism, Cushing’s disease (cortisol excess), or acromegaly (growth
hormone excess) or prolactinemia
 If above symptoms not present when pituitary mass found, this would be deemed
an incidentaloma
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Pictorials of Acromegaly
Carel Struycken
André René Roussimoff
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Pictorials of Cushing’s Disease
Abdominal Striae and Truncal Obesity
Buffalo Hump and Moon Facies
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Guideline for Pituitary Macroadenoma > 1 cm
 Consider as a symptomatic sellar mass
 Vision evaluation by acuity and fields
 Clinical and biochemical evaluation for both hormone hypersecretion and
hypopituitarism, repeating at 6, 12 and 24 months
 Hypersecretion testing: Prolactin, Growth Factor (IGF-1), LH, FSH, TSH and 24
hour free cortisol levels
 If labs confirm a hormone hypersecetion, treatment/management is similar to
others with same condition – separate talk
 If non-functional lesions cause visual or other neurological impairment, treat
surgically (transphenoidal is TX of choice)
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Guidelines for Pituitary Microadenoma < 1 cm
 Clinical and biochemical evaluation for hormone hypersecretion
 Vision and hormonal hyposecretion evaluation is not warranted(as these
are too small to compress optic chiasm or compress pituitary gland and
cause hyposecretion)
 Nonfunctioning microadenoma – repeat MRI and labs in 1 year
• If no change, repeat MRI in 2-3 years
• If abutting optic chiasm or size is increasing, treat as macroadenoma
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Underwriting Risks for Pituitary Incidentalomas
 Malignancy Risks
• Lymphoma, adenocarcinoma, sarcoma, metastasis (breast and lung)
 Hormone producing
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Prolactinoma
ACTH secreting causing Cushing’s disease
Growth hormone secreting adenomas causing acromegaly
FSH/LH secreting adenoma causing hypogonadism
TSH secreting causing hyperthyroidism
 Compression of structures outside sella causing visual changes for
example or hydrocephalus
 Local compression of pituitary gland itself causing hypofunction
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Underwriting Concerns: Morbidity/Mortality
 Morbidity
• Functional: Cushing’s, Hyperthyroidism, Acromegaly, Galactorrhea
• Enlarging: Compress optic chiasm causing visual disturbances, headache, nausea,
hypopituitarism, central diabetes insipidus (ADH suppression)
 Mortality
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Hormone excess (acromegaly, hyperthyroidsim, Cushings)
Operative complications
Malignancy
Hydrocephalus: Compression of third ventricle
Cardiovascular disease
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Renal Incidentalomas
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Incidental Renal Lesions: Solid
Tumors
Malignant Masses
Renal Cell Carcinoma
Lymphomas
Sarcomas
Metastases
Benign Masses
Renal Adenomas
Angiomyolipomas
Oncocytomas
Others
Inflammatory Lesions
Infection
Infarction
Trauma (Hematoma)
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Incidental Renal Lesions: Cystic
Simple
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Usually found as incidental findings on CT/US/MRI
Arise from renal parenchyma
Can be multiple and bilateral
Usually <2cm, however can grow large >10cm
Complex
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Increased fluid density (hyper dense cysts)
Internal thick walled septations
Thick cyst wall, nodular projections into lumen
Calcifications, contract enhancement
The higher the complexity, the greater the malignant risk
Acquired
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Associate with chronic hemodialysis
10-20% after 3 years
40-60% after 5 years
>90% after 10 years of dialysis
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Bosniak Classification: Per Dr. Morton Bosniak
Category I: Benign simple cysts with thin wall w/o septa, calcifications, or solid components.
Do not enhance with contrast and has density equal to water
Category II: Benign cyst with a few thin septa, which may contain fine calcifications or a
small segment of mildly thickened calcification. Includes homogenous high attenuation
lesions less than 3 cm with sharp margins but w/o enhancement
Category IIF: Well marginated cysts with a number of thin septa, with or w/o mild
enhancement or thickening of septa. Calcifications may be present; these may be thick and
nodular. There are no enhancing soft tissue components. This also includes nonenhancing
high-attenuation lesions that are completely contained within the kidney and are 3 cm or
larger.
Category III: Indeterminate cystic masses with thickened irregular septa with enhancement.
Category IV: Malignant cystic masses with all the characteristics of category III lesions but
also with enhancing soft tissue components independent of but adjacent to the septa.
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Renal Cysts: Bosniak – Next Step
 Bosniak 1 Cysts: Incidentally found
 Bosniak II: Option to monitor with US at 6-12 month intervals, periodic
imaging for VHL syndrome, APKD or acquired renal cysts from dialysis
 Referral to urology for surgical removal
• Bosniak IIF, III and IV cysts
• Symptomatic/rapidly enlarging cysts
• Bleeding/ruptured cysts or acute severe flank pain
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Risk Factors and Associated Conditions
 Increasing age
 Duration of hemodialysis
 Polycystic Kidney Disease
 Von Hippel Lindau Syndrome (multiple cysts in kidney, pancreas, liver,
epidydymis, cerebellar hemangioblastoma, pheochromocytomas and
increased risk for RCC (35-40% incidence)
 Tuberous Sclerosis: renal angiomyolipomas and cysts (20-25%),
hemartomas in brain and skin, 2% incidence of RCC
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Natural Course and Epidemiology of Renal Cysts
 Incidence increases with age:
0.2% age 0-18
20% age 20-40
33% age 41-60
 Most cysts grow slowly
3.9 mm per year for age < 50
1.8 mm per year for age > 50
Some involute and disappear over time
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Underwriting Concerns for Risk of Malignancy
Smoking
Age > 60
History or suspected history of malignancy elsewhere
Family history of hereditary syndromes such as Tuberous sclerosis or VHL
Nodule size > 4 cm
Nodule growth on serial imaging
Multiple if not disease related
CT imaging: solid, complex Bosniak 2F, 3, 4, capsular invasion and/or enlarged lymph nodes
Angiomyolipoma: Bilateral (80-90% tuberous sclerosis) > 4 cm surgery
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Underwriting Risks for Renal Incidentalomas
 Incidence of Renal Cancer
 3% of renal incidentalomas grow and metastasize w/in 3 yrs of surveillance
 Renal cell carcinoma with metastasis is incurable
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Thyroid Anatomy
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Thyroid Incidentaloma Prevalence
 Seen in 50% of autopsies
 Screening thyroid ultrasounds will find thyroid nodules in 50% of those
screened
 Carotid ultrasounds will typically detect thyroid incidentalomas in 13%
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Underwriting Risk of Malignancy within Thyroid Nodules
 Strong family history of thyroid cancer
 Personal or family history of MEN (Multiple Endocrine Neoplasm) or history of parathyroid
tumor or pheochromocytoma
 History of radiation treatment to neck area
 Thyroid nodule described as hard, fixed, firm or causing tracheal deviation
 Thyroid ultrasound shows irregular or micro lobulated border, taller than wide, marked
hypoechoicity, spiculated, increased vascularity, indistinct borders, extension beyond the
capsule or into the chest
 Abnormal neck lymph nodes
 Thyroid nodule greater > 2 cm
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Underwriting Risk of Malignancy within Thyroid Nodule
 Growth on surveillance imaging
 Positive on PET scan
 Cold on Thyroid scan
 Hot nodules on thyroid scans are almost always benign and would rate as
hyperthyroidism
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Case 1
 Marianne is a 45 year old accountant applying for $1 million term life insurance
and $3000/month disability policy with a 90 day EP to age 70
 On 5/10, she presented to Emergency room for right flank pain and found to have
right kidney stone, which she eventually passed. The CT also revealed an
incidental left 1.5 cm adrenal nodule characterized as an adrenal adenoma.
 On f/u, her PCP noted no personal or family history for malignancies. She had DM
II controlled on 1000 mg of Metformin and well controlled HTN on HCTZ. 24 hour
urine for cortisol was elevated. Dexamethasone suppression test was abnormal.
Urine for metanephrines were normal as was aldosterone and renin activity. She
underwent left adrenalectomy for functioning adrenal adenoma. Since surgery, DM
is controlled with diet alone.
What is the Risk Assessment?
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Case 1 (Continued)
 Adrenal Nodule: Biochemical (hormonal) testing abnormal
 Favorable factors:
• Benign adrenal unilateral disease
• Treated with surgery with no complications
• Improved glycemic control off medication
 Unfavorable factors: none
 Risk Assessment
Life – Rate for DM only
Disability-Rate as would for DM
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Case 2
 Stuart a 28 year old pharmacist with chronic migraines was previously
evaluated with brain MRI during his senior year in college when age 22.
Brain MRI had revealed a 0.7 cm pituitary mass. His neurologist did not
opine headaches were related to this incidentaloma as visual field testing
was normal as was hormone levels including TSH, prolactin, GH, ACTH,
LH and FSH.
 He was recently seen by his neurologist for follow up of migraines. Repeat
MRI showed stable pituitary lesion when compared to previous study. No
further follow up was recommended regarding the pituitary lesion.
What is the Risk Assessment?
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Case 2 (Continued)
 Non functioning pituitary microadenoma
 Favorable factors:
• Microadenoma less than 1 cm
• Nonfunctional
• Stable repeat imaging 5 years later
 Unfavorable factors: NONE
 Risk Assessment
Life – STD/Preferred as qualifies
Disability - Rider
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Case 3
 Sarah is a 55 year old engineer who is applying for a $2 million whole life policy as
well as $5000/month disability policy/90 EP to age 65
 In January 2014, her PCP noted an asymptomatic right sided bruit and neck exam
was otherwise normal as was remainder of complete physical exam. Carotid
ultrasound was ordered revealing non hemodynamically significant plaque,
however there was a 1.5 cm right thyroid nodule described as isoechoic without
irregular borders or increase in vascularity. Repeat thyroid ultrasound in January
2015 revealed no changes.
 Sarah has no personal history of radiation or cancer and has no family history of
cancer of any types.
What is the Risk Assessment?
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Case 3 (Continued)
 Thyroid nodule
 Favorable factors:
• Female gender
• No history of head or neck radiation
• No abnormal neck lymph nodes
• No family history of thyroid cancer or MEN
• Nodule < 2 cm
• Favorable ultrasound: Not markedly hypoechoic or taller than wide
• 1 year f/u imaging stable
Risk Assessment
- Life-STD/Preferred as qualifies
Disability- Rider
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