Incidentalomas Adrenal Pituitary Renal and Thyroid Elyssa Del Valle MD October 14 2016 Vice President amp Medical Director Terminology Nodule Lesion Mass Tumor Nodule is a radiographic finding of a ID: 779699
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What in the World To Make of IncidentalomasAdrenal, Pituitary, Renal and Thyroid
Elyssa Del Valle, M.D.
October 14, 2016
Vice President & Medical Director
Slide2Slide3Terminology: Nodule, Lesion, Mass, TumorNodule 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
Slide4Anatomy of Adrenal Glands
Adrenal glands are known as suprarenal glands
Slide5Adrenal Incidentaloma: DefintionAn 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
Slide6Prevalence of Adrenal IncidentalomasIncidentalomas have become widespread since use of CT, MRI, resulting in the dilemma regarding their significancePrevalence is 4.4% on CT and MRI
Prevalence increases with increasing ageIn those between 20-29 yrs
old, prevalence is 0.2%In those over 70 yrs of age, prevalence is 7%
Slide7Underwriting Risks of Adrenal IncidentalomasMalignancy Risk Factors - Nodule > 4 cm
- Multiple - Imaging characteristics
- Growth on surveillance - Hormone ProducingSurgical Risks
Slide8What Next In Its EvaluationMust ask 3 specific questions:Is the nodule/mass/lesion functioning or nonfunctioning?
Does it have radiographic features to suggest malignancy?Does the person have a history of a previous malignancy?
These questions are similarly raised for most glandular Incidentalomas
Slide9Why Ask These Questions Re: Adrenal Incidentaloma?80% are nonfunctioning adenomas
5% have associated subclinical Cushing’s Syndrome5% pheochromocytoma
1% hyperaldosteronism< 5% are adrenocortical carcinoma
2.5% have metastatic diseaseRemaining are benign cysts, ganglioneuromas, lipoma
or myelolipomas
Slide10Question 1: Functioning or NonfunctioningAdrenal glands produce a variety of hormonesMedulla 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
Slide11Functioning or Nonfunctioning: Hormone EvaluationSubclinical 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
Slide12Conditions Associated with Functional Adrenal NodulesCortisol secreting adenoma- obesity, IFG, DM, HLD, HTNPheochromocytoma
– HTN, CVA -* (10% are malignant) Aldosterone
secreting adenoma- *HTN, HypokalemiaAndrogen 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
Slide13Question 2: Malignant Characteristic on Imaging Size > 4 cmShape: irregular, unclear margins,
Texture: heterogeneous with mixed densitiesAttenuation (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 minutesAppearance on MRI: Hyperintense in relation to liver
Necrosis, hemorrhage or calcifications: commonGrowth rate: usually rapid (>2 cm per year in adenocarcinoma; slow to rapid in metastatic lesions) Marker of higher grade
tumor
Slide14Question 3: Any History of Prior MalignancyMetastasis is the cause in 50% who have history of malignancyCancers associated with metastasis to adrenals include:
LungKidneyColonBreast
EsophagusPancreasLiver
StomachMelanoma
Slide15Guidelines for Evaluation of Adrenal IncidentalomaHormonal evaluation with dexamethasone suppression test, 24 hour cortisol, metanephrine
and catecholamine, plasma aldosterone and plasma renin activityIf results consistent with autonomous hormone secretion, consider unilateral laparoscopic adrenalectomy
If imaging suggests infection or metastasis, consider CT guided FNAIf 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
Slide16AACE/AAES Adrenal Incidentaloma Guidelines
Slide17Mortality and Morbidity of Adrenal IncidentalomaMortality related to local and metastatic spread if malignantMortality
concerns for functional adenomas include DM, HTN, MI, CVA, Arrhythmia, CHF and Surgical ComplicationsMorbidity concerns for functional adenomas include DM, HTN, Post MI, CVA, Obesity, Osteoporosis, Arrhythmia,
Virilization
Slide18Pituitary GlandCancerinfo.tri-kobe.org
Slide19Pituitary Incidentalomas: DefinitionAn unsuspected lesion detected on imaging performed for reasons other than pituitary symptoms or diseaseCan also include asymptomatic
prolactinomaPituitary microadenoma
is defined as less than 1 cmMacroadenoma is defined as 1 cm or larger
Slide20Etiologies of Sellar LesionsCongenital
Rathke’s
cleft cystArachnoid cyst
Neoplasms
Pituitary adenoma (most common)
Meningioma
Craniopharyngioma
Germ cell tumor
Schwannoma
/neuroma
Hypothalmic
hamartomas
Metastasis (lung, breast)
Aneurysm
Cavernous sinus thrombosis
Infarction/Hemorrhage
Vascular
Sarcoidosis
Lymphocytic
hypophysitis
Granulomatous
hypophysitis
Pituitary
abcess
Dermoid
and
epidermoid
tumors
Inflammatory/Infectious
Slide21Prevalence 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
Slide22Classification of Pituitary AdenomaSize: Micro < 1 cm or Macro > 1 cm
Functional or NonfunctionalFunctional 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%)
Slide23Clinical Course in Prospective StudiesNon-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
Slide24Symptoms Associated with Pituitary AdenomasMass effect: If large, can invade and compress structures outside
sella and cause HA, double vision/diminished visual field and acuity and hydrocephalusHormonal 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
Slide25Pictorials of AcromegalyCarel
Struycken
André René Roussimoff
Pictorials of Cushing’s Disease
Abdominal Striae and Truncal Obesity
Buffalo Hump and Moon
Facies
Slide27Guideline for Pituitary Macroadenoma > 1 cm
Consider as a symptomatic sellar
massVision evaluation by acuity and fieldsClinical and biochemical evaluation for both hormone hypersecretion
and hypopituitarism, repeating at 6, 12 and 24 monthsHypersecretion 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
)
Slide28Guidelines for Pituitary Microadenoma < 1 cmClinical and biochemical evaluation for hormone
hypersecretionVision 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 yearIf no change, repeat MRI in 2-3
yearsIf abutting
optic chiasm or size is increasing, treat as
macroadenoma
Underwriting Risks for Pituitary IncidentalomasMalignancy Risks
Lymphoma, adenocarcinoma, sarcoma, metastasis (breast and lung)Hormone producing
ProlactinomaACTH secreting causing Cushing’s
diseaseGrowth hormone secreting adenomas causing acromegalyFSH/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
Slide30Underwriting Concerns: Morbidity/MortalityMorbidityFunctional: Cushing’s, Hyperthyroidism, Acromegaly,
GalactorrheaEnlarging: Compress optic chiasm causing visual disturbances, headache, nausea, hypopituitarism, central diabetes insipidus (ADH suppression)
MortalityHormone excess (acromegaly,
hyperthyroidsim, Cushings)Operative complications
MalignancyHydrocephalus: Compression
of third
ventricle
Cardiovascular disease
Slide31Renal Incidentalomas
Slide32Incidental Renal Lesions: Solid
Tumors
Inflammatory Lesions
Malignant Masses
Renal Cell Carcinoma
Lymphomas
Sarcomas
Metastases
Infection
Infarction
Trauma
(Hematoma)
Benign Masses
Renal Adenomas
Angiomyolipomas
Oncocytomas
Others
Slide33Incidental Renal Lesions: Cystic
Slide34Bosniak 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.
Slide35Renal Cysts: Bosniak – Next StepBosniak
1 Cysts: Incidentally foundBosniak 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 removalBosniak
IIF, III and IV cystsSymptomatic/rapidly enlarging cysts
Bleeding/ruptured cysts or acute severe flank
pain
Slide36Risk Factors and Associated ConditionsIncreasing ageDuration of hemodialysisPolycystic Kidney DiseaseVon
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
Slide37Natural Course and Epidemiology of Renal CystsIncidence increases with age: 0.2% age 0-18
20% age 20-40 33% age 41-60Most 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
Slide38Underwriting Concerns for Risk of MalignancySmoking
Age > 60History or suspected history of malignancy elsewhere
Family history of hereditary syndromes such as Tuberous sclerosis or VHLNodule size > 4 cm
Nodule growth on serial imagingMultiple if not disease relatedCT imaging: solid, complex Bosniak
2F, 3, 4, capsular invasion and/or enlarged lymph nodes
Angiomyolipoma
: Bilateral (80-90% tuberous sclerosis) > 4 cm surgery
Slide39Underwriting Risks for Renal IncidentalomasIncidence of Renal Cancer3% of renal incidentalomas
grow and metastasize w/in 3 yrs of surveillanceRenal cell carcinoma with metastasis is incurable
Slide40Thyroid Anatomy
Slide41Thyroid Incidentaloma PrevalenceSeen in 50% of autopsiesScreening thyroid ultrasounds will find thyroid nodules in 50% of those screened
Carotid ultrasounds will typically detect thyroid incidentalomas in 13%
Slide42Underwriting Risk of Malignancy within Thyroid NodulesStrong family history of thyroid cancerPersonal or family history of MEN (Multiple Endocrine Neoplasm) or history of parathyroid tumor or
pheochromocytomaHistory of radiation treatment to neck area
Thyroid nodule described as hard, fixed, firm or causing tracheal deviationThyroid ultrasound shows irregular or micro lobulated border, taller than wide, marked hypoechoicity
, spiculated, increased vascularity, indistinct borders, extension beyond the capsule or into the chestAbnormal neck lymph nodes
Thyroid nodule greater >
2
cm
Slide43Underwriting Risk of Malignancy within Thyroid NoduleGrowth on surveillance imagingPositive on PET scanCold on Thyroid scan
Hot nodules on thyroid scans are almost always benign and would rate as hyperthyroidism
Slide44Case 1Marianne 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 70On 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?
Slide45Case 1 (Continued)Adrenal Nodule: Biochemical (hormonal) testing abnormalFavorable factors:
Benign adrenal unilateral disease
Treated with surgery with no complicationsImproved
glycemic control off medicationUnfavorable factors: noneRisk Assessment Life – Rate for DM only
Disability-Rate as would for DM
Slide46Case 2Stuart 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?
Slide47Case 2 (Continued)Non functioning pituitary microadenoma
Favorable factors:Microadenoma
less than 1 cmNonfunctionalStable
repeat imaging 5 years later Unfavorable factors: NONERisk Assessment Life
– STD/Preferred as qualifies
Disability - Rider
Slide48Case 3Sarah 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 65In 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?
Slide49Case 3 (Continued)Thyroid noduleFavorable factors:
Female genderNo history of head or neck radiation
No abnormal neck lymph nodesNo family history of thyroid cancer or
MENNodule < 2 cmFavorable
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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