What in the World To Make of - PowerPoint Presentation

What in the World To Make of IncidentalomasAdrenal, Pituitary, Renal and Thyroid Elyssa Del Valle, M.D. October 14, 2016 Vice President & Medical Director

Terminology: 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

Anatomy of Adrenal Glands Adrenal glands are known as suprarenal glands

Adrenal 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

Prevalence 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%

Underwriting Risks of Adrenal IncidentalomasMalignancy Risk Factors - Nodule > 4 cm - Multiple - Imaging characteristics - Growth on surveillance - Hormone ProducingSurgical Risks

What 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

Why 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

Question 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

Functioning 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

Conditions 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

Question 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

Question 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

Guidelines 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

AACE/AAES Adrenal Incidentaloma Guidelines

Mortality 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

Pituitary GlandCancerinfo.tri-kobe.org

Pituitary 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

Etiologies 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

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

Classification 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%)

Clinical 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

Symptoms 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

Pictorials of AcromegalyCarel Struycken André René Roussimoff

Pictorials of Cushing’s Disease Abdominal Striae and Truncal Obesity Buffalo Hump and Moon Facies

Guideline 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 )

Guidelines 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

Underwriting 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

Renal Incidentalomas

Incidental 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

Incidental Renal Lesions: Cystic

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.

Renal 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

Risk 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

Natural 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

Underwriting 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

Underwriting 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

Thyroid Anatomy

Thyroid 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%

Underwriting 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

Underwriting 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

Case 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?

Case 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

Case 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?

Case 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

Case 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?

Case 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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