Adrenal Incidentaloma and Pituitary Incidentaloma/Tumors

Adrenal Adrenal Incidentaloma and Incidentaloma and

Pituitary Pituitary Incidentaloma/TumIncidentaloma/Tum

orsors

Adrenal Adrenal IncidentalomaIncidentaloma

ObjectivesObjectives

DefinitionDefinition Epidemiology/StatisticsEpidemiology/Statistics EtiologyEtiology Biochemical work upBiochemical work up TreatmentTreatment

DefinitionDefinition

Adrenal mass > or = 1cm Adrenal mass > or = 1cm Discovered incidentallyDiscovered incidentally AsymptomaticAsymptomatic

Epidemiology and Epidemiology and StatisticsStatistics

Prevalence 4-6%Prevalence 4-6% Increases with increasing ageIncreases with increasing age

0.2 % between 20-29 years of age0.2 % between 20-29 years of age 7% in patients over 70 years of age7% in patients over 70 years of age

EtiologyEtiology Adrenal adenomaAdrenal adenoma Adrenocortical carcinomaAdrenocortical carcinoma MyelolipomaMyelolipoma PheochromocytomaPheochromocytoma Adrenal cystAdrenal cyst Adrenal hemorrhageAdrenal hemorrhage Adrenal metastasisAdrenal metastasis InfectionInfection Infiltrative diseaseInfiltrative disease ACTH-independent MMADACTH-independent MMAD ACTH-dependent Cushing’sACTH-dependent Cushing’s Congenital adrenal hyperplasiaCongenital adrenal hyperplasia

Question 1Question 1

A 45 y/o healthy woman undergoes emergent A 45 y/o healthy woman undergoes emergent abdominal imaging after an automobile accident and abdominal imaging after an automobile accident and was found to have a 6.3 cm right adrenal mass. The was found to have a 6.3 cm right adrenal mass. The results of basic chemistry and hematology tests are results of basic chemistry and hematology tests are normal. Which of the following is the best evaluation normal. Which of the following is the best evaluation plan for this patient?plan for this patient? A. Chest CT, morning serum cortisol, repeat imaging in 3 A. Chest CT, morning serum cortisol, repeat imaging in 3

monthsmonths B. 1 mg dexamethasone suppression test, 24-hour urine B. 1 mg dexamethasone suppression test, 24-hour urine

metanephrines and catecholamines, surgical consultationmetanephrines and catecholamines, surgical consultation C. Paired plasma renin and aldosterone, 8 AM serum C. Paired plasma renin and aldosterone, 8 AM serum

cortisol, repeat abdominal imaging in 6 monthscortisol, repeat abdominal imaging in 6 months D. No hormonal evaluation, surgical consultation D. No hormonal evaluation, surgical consultation

EvaluationEvaluation

2 questions:2 questions: Is it functioning?Is it functioning? Is it malignant?Is it malignant?

Evaluation (cont’d)Evaluation (cont’d)

Functional status Functional status 10 – 15% functional10 – 15% functional Hormonal evaluationHormonal evaluation

Subclinical Cushing’s syndromeSubclinical Cushing’s syndrome PheochromocytomaPheochromocytoma Primary aldosteronismPrimary aldosteronism

Evaluation for hormonal Evaluation for hormonal functionfunction

Subclinical Cushing’s syndromeSubclinical Cushing’s syndrome Low dose 1mg overnight dexamethasone suppression Low dose 1mg overnight dexamethasone suppression

testtest Normal: cortisol suppresses < 5 mcg/dL Normal: cortisol suppresses < 5 mcg/dL Sensitivity 89%, specificity 98%Sensitivity 89%, specificity 98%

Endo Soc. recommended cut point 1.8 mcg/dL – sens 95%, spec Endo Soc. recommended cut point 1.8 mcg/dL – sens 95%, spec 80%80%

Test of choice for adrenal incidentalomaTest of choice for adrenal incidentaloma AutonomyAutonomy

24-hour urine free cortisol24-hour urine free cortisol HypersecretionHypersecretion 24 hr UFC > 4x upper normal limit24 hr UFC > 4x upper normal limit May miss subclinical Cushing’s or Cushing’s in renal failureMay miss subclinical Cushing’s or Cushing’s in renal failure

Midnight salivary cortisolMidnight salivary cortisol Midnight serum cortisolMidnight serum cortisol

Evaluation for hormonal Evaluation for hormonal function (cont’d)function (cont’d)

Subclinical Cushing’s syndrome (cont’d)Subclinical Cushing’s syndrome (cont’d) Pseudo-Cushing’sPseudo-Cushing’s

StressStress Morbid obesityMorbid obesity Psychiatric illness (MDD, anxiety, anorexia/bulimia)Psychiatric illness (MDD, anxiety, anorexia/bulimia) Alcoholism (rare)Alcoholism (rare) Glucocorticoid resistanceGlucocorticoid resistance Uncontrolled DMUncontrolled DM

Elevated cortisol-binding globulin (estrogen, Elevated cortisol-binding globulin (estrogen, pregnancy, hyperthyroidism) pregnancy, hyperthyroidism)

Drugs that increases dexamethasone Drugs that increases dexamethasone metabolism (rifampin, phenytoin, metabolism (rifampin, phenytoin, phenobarbital, alcohol)phenobarbital, alcohol)

Evaluation for hormonal Evaluation for hormonal functionfunction

PheochromocytomaPheochromocytoma Urine metanephrines and catecholamines Urine metanephrines and catecholamines

Sensitivity 91%, specificity 98%Sensitivity 91%, specificity 98% Screen cases with low suspicionScreen cases with low suspicion

Serum fractionated metanephrines and Serum fractionated metanephrines and catecholaminescatecholamines

Sensitivity 96-100%, specificity 85-95%Sensitivity 96-100%, specificity 85-95% High false positive rate High false positive rate High suspicionHigh suspicion

Imaging over-rules biochemical testingImaging over-rules biochemical testing Early, asymptomatic pheo may have negative hormonal Early, asymptomatic pheo may have negative hormonal

testingtesting


Pheochromocytoma (cont’d)Pheochromocytoma (cont’d) Conditions that may interfere with test results Conditions that may interfere with test results

Meds – discontinue at least 2 weeksMeds – discontinue at least 2 weeks Tricyclic antidepressantsTricyclic antidepressants LevodopaLevodopa Drugs containing adrenergic receptor agonists Drugs containing adrenergic receptor agonists

(decongestants, appetite suppressants)(decongestants, appetite suppressants) AmphetaminesAmphetamines Buspirone and most psychoactive agentsBuspirone and most psychoactive agents ProchlorperazineProchlorperazine ReserpineReserpine AcetaminophenAcetaminophen

Increased endogenous catecholamines: physiologic Increased endogenous catecholamines: physiologic stress, alcohol or clonidine withdrawalstress, alcohol or clonidine withdrawal


Primary aldosteronism – performed if pt has HTN Primary aldosteronism – performed if pt has HTN Plasma aldosterone concentration (PAC) and plasma Plasma aldosterone concentration (PAC) and plasma

renin activity (PRA)renin activity (PRA) PAC/PRA > 20 and PAC > 15 ng/dLPAC/PRA > 20 and PAC > 15 ng/dL Confirmation testConfirmation test

Saline infusionSaline infusion PAC > 10 ng/dLPAC > 10 ng/dL

Oral salt loadingOral salt loading 24 hr urine aldosterone > 12 mcg and 24 hr urine Na > 200 mEq24 hr urine aldosterone > 12 mcg and 24 hr urine Na > 200 mEq

Catopril suppression Catopril suppression Fludrocortisone suppressionFludrocortisone suppression

Adrenal vein samplingAdrenal vein sampling


Primary aldosteronism (cont’d)Primary aldosteronism (cont’d) Agents that markedly affect ARR – withdraw Agents that markedly affect ARR – withdraw

at least 4 weeksat least 4 weeks Spironolactone, eplerenoneSpironolactone, eplerenone All diureticsAll diuretics Liquorice products (chewing tobacco, Liquorice products (chewing tobacco,

confectionary licorice)confectionary licorice) If ARR is non-diagnostic off the above If ARR is non-diagnostic off the above

agents, consider withdrawing other anti-agents, consider withdrawing other anti-HTN meds for 2 weeks and repeat testHTN meds for 2 weeks and repeat test


Primary aldosteronisim (cont’d)Primary aldosteronisim (cont’d) Drugs that minimally affect ARRDrugs that minimally affect ARR

Verapamil Verapamil HydralazineHydralazine Alpha-adrengeric blockers – prazosin, doxazosin, terazosinAlpha-adrengeric blockers – prazosin, doxazosin, terazosin

Drugs that can falsely suppressed ARRDrugs that can falsely suppressed ARR ARB, ACE I, diuretics, aldosterone receptor antagonists - ARB, ACE I, diuretics, aldosterone receptor antagonists -

increase PRAincrease PRA Drugs that can falsely elevated ARRDrugs that can falsely elevated ARR

Beta blocker, central alpha 2 agonist (clonidine, Beta blocker, central alpha 2 agonist (clonidine, methyldopa), NSAIDS – suppresses renin releasemethyldopa), NSAIDS – suppresses renin release

Back to Question 1Back to Question 1

A 45 y/o healthy woman undergoes emergent A 45 y/o healthy woman undergoes emergent abdominal imaging after an automobile accident and abdominal imaging after an automobile accident and was found to have a 6.3 cm right adrenal mass. The was found to have a 6.3 cm right adrenal mass. The results of basic chemistry and hematology tests are results of basic chemistry and hematology tests are normal. Which of the following is the best evaluation normal. Which of the following is the best evaluation plan for this patient?plan for this patient? A. Chest CT, morning serum cortisol, repeat imaging in 3 A. Chest CT, morning serum cortisol, repeat imaging in 3

monthsmonths B. 1 mg dexamethasone suppression test, 24-hour B. 1 mg dexamethasone suppression test, 24-hour

urine metanephrines and catecholamines, surgical urine metanephrines and catecholamines, surgical consultationconsultation

C. Paired plasma renin and aldosterone, 8 AM serum C. Paired plasma renin and aldosterone, 8 AM serum cortisol, repeat abdominal imaging in 6 monthscortisol, repeat abdominal imaging in 6 months

D. No hormonal evaluation, surgical consultation D. No hormonal evaluation, surgical consultation


A 45-year-old man is diagnosed with a 1.5 A 45-year-old man is diagnosed with a 1.5 cm left adrenal mass on abdominal/pelvic cm left adrenal mass on abdominal/pelvic CT to evaluate abdominal pain. The lesion CT to evaluate abdominal pain. The lesion has attenuation value of 3 HU pre-has attenuation value of 3 HU pre-contrast, 40 HU immediately after contrast contrast, 40 HU immediately after contrast administration, and 15 HU at 10 minutes administration, and 15 HU at 10 minutes post-contrast. The adrenal mass is likely post-contrast. The adrenal mass is likely A. PheochromocytomaA. Pheochromocytoma B. Adrenocortical carcinomaB. Adrenocortical carcinoma C. Metastatic lesionC. Metastatic lesion D. Adrenal adenomaD. Adrenal adenoma


41 y/o F with h/o HTN, who presented 41 y/o F with h/o HTN, who presented with abdominal pain and found to have a 3 with abdominal pain and found to have a 3 cm L adrenal mass on abdominal CT. F/u cm L adrenal mass on abdominal CT. F/u MRI shown below.MRI shown below.

T1W MRIT1W MRI T2W MRIT2W MRI

Question 3 (cont’d)Question 3 (cont’d)

Your differential diagnoses include all of Your differential diagnoses include all of the following exceptthe following except

A. PheochromocytomaA. Pheochromocytoma

B. Adrenocortical carcinomaB. Adrenocortical carcinoma

C. Metastatic malignancyC. Metastatic malignancy

D. Adrenal adenomaD. Adrenal adenoma

Imaging differences between Imaging differences between malignant and benign lesionsmalignant and benign lesions

Size > 4 cm Size > 4 cm Irregular, calcificationsIrregular, calcifications InhomogenousInhomogenous High attenuation on non-High attenuation on non-

contrast studies > 10 HUcontrast studies > 10 HU Highly enhanced with Highly enhanced with

contrast, slower washout contrast, slower washout (< 50% at 10 min)(< 50% at 10 min)

Isointensity with liver on Isointensity with liver on T1W and hyperintense on T1W and hyperintense on T2W MRI imagesT2W MRI images

No signal loss on out-of-No signal loss on out-of-phase chemical shift MRIphase chemical shift MRI

Size < 4cmSize < 4cm Round, smooth contourRound, smooth contour HomogeneousHomogeneous Low attenuation on non-Low attenuation on non-

contrast studies <10 HUcontrast studies <10 HU Limited enhancement Limited enhancement

with contrast and earlier with contrast and earlier washout of contrastwashout of contrast

Isointensity with liver on Isointensity with liver on both T1W and T2W MRI both T1W and T2W MRI imagesimages

Lose signal on out-of-Lose signal on out-of-phase chemical shift MRIphase chemical shift MRI

MalignaMalignantnt

BenignBenign


A 45-year-old man is diagnosed with a 1.5 cm left A 45-year-old man is diagnosed with a 1.5 cm left adrenal mass on abdominal/pelvic CT to evaluate adrenal mass on abdominal/pelvic CT to evaluate abdominal pain. The lesion has attenuation abdominal pain. The lesion has attenuation value of 3 HU pre-contrast, 40 HU immediately value of 3 HU pre-contrast, 40 HU immediately after contrast administration, and 15 HU at 10 after contrast administration, and 15 HU at 10 minutes post-contrast. The adrenal mass is minutes post-contrast. The adrenal mass is likely likely A. PheochromocytomaA. Pheochromocytoma B. Adrenocortical carcinomaB. Adrenocortical carcinoma C. Metastatic lesionC. Metastatic lesion D. Adrenal adenomaD. Adrenal adenoma


41 y/o F with HTN who presented with 41 y/o F with HTN who presented with abdominal pain and found to have a 3 abdominal pain and found to have a 3 cm L adrenal mass on abdominal CT. cm L adrenal mass on abdominal CT. F/u MRI shown below. F/u MRI shown below.

T1W MRIT1W MRIT2W MRIT2W MRI


Your differential diagnoses include all of Your differential diagnoses include all of the following exceptthe following except

A. PheochromocytomaA. Pheochromocytoma

B. Adrenocortical carcinomaB. Adrenocortical carcinoma

C. Metastatic malignancyC. Metastatic malignancy

D. Adrenal adenomaD. Adrenal adenoma

CT-guided adrenal biopsyCT-guided adrenal biopsy

Rarely indicatedRarely indicated Can’t distinguish benign from Can’t distinguish benign from

malignant cortical tissuesmalignant cortical tissues Helpful if metastasis or infectionHelpful if metastasis or infection Rule out pheochromocytoma prior to Rule out pheochromocytoma prior to

biopsybiopsy

TreatmentTreatment

Lesion > 6 cm or functioning and no Lesion > 6 cm or functioning and no evidence of metastases evidence of metastases surgical surgical resectionresection

Lesion < 4 cm and non-functioning Lesion < 4 cm and non-functioning Repeat scans in 3-6, 12, and 24 monthsRepeat scans in 3-6, 12, and 24 months Repeat hormonal testing annually for 4 years Repeat hormonal testing annually for 4 years

If lesion is 4-6 cm or is enlarging by 1cm If lesion is 4-6 cm or is enlarging by 1cm or more or more consider removal consider removal

Question 4Question 4 36 y/o woman was found incidentally to have a 3-36 y/o woman was found incidentally to have a 3-

cm right adrenal mass. The left adrenal gland is cm right adrenal mass. The left adrenal gland is very small. very small.

Gained approximately 22 lb over the past 18 Gained approximately 22 lb over the past 18 months months

Diagnosed with impaired glucose toleranceDiagnosed with impaired glucose tolerance P/E showed central obesity, proximal muscle P/E showed central obesity, proximal muscle

weakness, and wide violaceous striaeweakness, and wide violaceous striae 1mg DST – plasma cortisol 12 mcg/dL1mg DST – plasma cortisol 12 mcg/dL 24-hr urine free cortisol - 3x the normal upper 24-hr urine free cortisol - 3x the normal upper

limit for daily excretionlimit for daily excretion Serum ACTH is < 5 pg/mLSerum ACTH is < 5 pg/mL The patient undergoes laparoscopic right The patient undergoes laparoscopic right

adrenalectomy adrenalectomy During the first 24 hours after surgery During the first 24 hours after surgery

experiences hypotension and nausea.experiences hypotension and nausea.


Which of the following is the most Which of the following is the most appropriate management at this time?appropriate management at this time? A. Surgery to explore for retroperitoneal A. Surgery to explore for retroperitoneal

bleedingbleeding B. Emergent CT scan of abdomen and B. Emergent CT scan of abdomen and

retroperitoneumretroperitoneum C. Evaluation to insure that the correct adrenal C. Evaluation to insure that the correct adrenal

gland was resectedgland was resected D. Administer hydrocortisone, 100mg IV q8 hrsD. Administer hydrocortisone, 100mg IV q8 hrs

NEJM 2007; 356:601-610NEJM 2007; 356:601-610

Pituitary Pituitary Incidentaloma/TumIncidentaloma/Tum

orsors

ObjectivesObjectives

Definition and classification of pituitary Definition and classification of pituitary incidentalomaincidentaloma

Causes of pituitary incidentalomaCauses of pituitary incidentaloma Review of anterior and posterior Review of anterior and posterior

pituitary hormonespituitary hormones Biochemical evaluationBiochemical evaluation Treatment and follow-upTreatment and follow-up

Pituitary incidentalomaPituitary incidentaloma

Previously unrecognized lesion in the Previously unrecognized lesion in the pituitarypituitary

Prevalence up to 10%Prevalence up to 10% ClassificationClassification

Microadenoma < 10 mm Microadenoma < 10 mm Macroadenoma > 10 mmMacroadenoma > 10 mm

More likely to cause visual and hormonal More likely to cause visual and hormonal abnormalitiesabnormalities

Etiology of Etiology of incidentalomaincidentaloma

Pituitary adenomaPituitary adenoma Pituitary hyperplasiaPituitary hyperplasia Pituitary carcinomaPituitary carcinoma CraniopharyngiomaCraniopharyngioma MeningiomaMeningioma Lymphocytic hypophysitisLymphocytic hypophysitis Rathke’s cleft cystRathke’s cleft cyst GerminomaGerminoma Primary CNS lymphomaPrimary CNS lymphoma MetastasisMetastasis AVMAVM

Pituitary incidentaloma Pituitary incidentaloma (cont’d)(cont’d)

Functional statusFunctional status HyposecretionHyposecretion HypersecretionHypersecretion Non-functioningNon-functioning

Mass effect Mass effect HeadacheHeadache Visual field deficits (bitemporal Visual field deficits (bitemporal

hemianopsia)hemianopsia) Cranial nerve III, IV, VI palsy - diplopiaCranial nerve III, IV, VI palsy - diplopia

HypopituitarismHypopituitarism

Decreased secretion of one or more anterior Decreased secretion of one or more anterior pituitary hormones (ACTH, GH, FSH, LH, pituitary hormones (ACTH, GH, FSH, LH, TSH, prolactin)TSH, prolactin) Panhypopituitarism – deficiency of all pit hormonesPanhypopituitarism – deficiency of all pit hormones Partial – deficiency of some pit hormonesPartial – deficiency of some pit hormones Isolated – deficiency of only one pit hormoneIsolated – deficiency of only one pit hormone

Diagnosis can’t be make by measuring Diagnosis can’t be make by measuring pituitary hormonespituitary hormones Overlap between normal and hypopituitary rangesOverlap between normal and hypopituitary ranges Hormone present not bioactiveHormone present not bioactive


Central adrenal insufficiency Central adrenal insufficiency Abnormality in CRH or ACTH production Abnormality in CRH or ACTH production decreased decreased

cortisolcortisol Fatigue, weakness, anorexia, weight loss, Fatigue, weakness, anorexia, weight loss,

lightheadedness, orthostatic hypotension, lightheadedness, orthostatic hypotension, nausea/vomiting, hyponatremianausea/vomiting, hyponatremia

Different from primary AI – Different from primary AI – ACTH not elevated - no hyperpigmentation ACTH not elevated - no hyperpigmentation Aldosterone secretion normal - no hyperkalemiaAldosterone secretion normal - no hyperkalemia

Dx - morning fasting serum cortisolDx - morning fasting serum cortisol < 3 mcg/dL – highly suggestive of AI< 3 mcg/dL – highly suggestive of AI > 15 mcg/dL – normal> 15 mcg/dL – normal > 3 < 15 mcg/dL > 3 < 15 mcg/dL further testing further testing


Central AI (cont’d)Central AI (cont’d) Cosyntropin stimulation test – Cosyntropin stimulation test –

Not useful in acute setting (normal until adrenals Not useful in acute setting (normal until adrenals atropy – weeks to months)atropy – weeks to months)

Insulin tolerance test – gold standardInsulin tolerance test – gold standard Hypoglycemia stimulates entire HPA axisHypoglycemia stimulates entire HPA axis Contraindicated in elderly, CV disease, seizuresContraindicated in elderly, CV disease, seizures

Medic alert braceletMedic alert bracelet Glucocorticoid replacementGlucocorticoid replacement Sick day coverageSick day coverage Stress dose coverageStress dose coverage

Question 5Question 5 A 50 y/o man who presented with new onset A 50 y/o man who presented with new onset

headache and was subsequently diagnosed with headache and was subsequently diagnosed with a 1.5 cm pituitary mass. Fasting morning serum a 1.5 cm pituitary mass. Fasting morning serum cortisol is 5 mcg/dL, FT4 0.6 ng/dL (cortisol is 5 mcg/dL, FT4 0.6 ng/dL (0.79 to 2.35), TSH 1.2 mIU/L (, TSH 1.2 mIU/L (0.47 to 4.68), total , total testosterone 120 ng/dL (testosterone 120 ng/dL (132 to 813), FSH 2 , FSH 2 mIU/ml, LH 3 mIU/ml, IGF-1 70 ng/mL (mIU/ml, LH 3 mIU/ml, IGF-1 70 ng/mL (109 to 284), prolactin 15 ng/mL (, prolactin 15 ng/mL (3.7 to 17.9). The best . The best next step isnext step is A. Start levothyroxine replacementA. Start levothyroxine replacement B. Start testosterone replacementB. Start testosterone replacement C. Perform Cosyntropin stimulation testC. Perform Cosyntropin stimulation test D. Start human growth hormone replacementD. Start human growth hormone replacement


Central hypothyroidismCentral hypothyroidism Symptoms and signs – same as primary Symptoms and signs – same as primary

hypothyroidism except goiterhypothyroidism except goiter Dx - low FT4 and low or inappropriately Dx - low FT4 and low or inappropriately

normal TSHnormal TSH LT4 replacementLT4 replacement

Treat AI before starting LT4 as LT4 increases Treat AI before starting LT4 as LT4 increases cortisol metabolism cortisol metabolism adrenal crisis adrenal crisis

Follow FT4 level, goal FT4 mid normal rangeFollow FT4 level, goal FT4 mid normal range

Back to question 5Back to question 5 A 50 y/o man who presented with new onset A 50 y/o man who presented with new onset

headache and was subsequently diagnosed with headache and was subsequently diagnosed with a 1.5 cm pituitary mass. Fasting morning serum a 1.5 cm pituitary mass. Fasting morning serum cortisol is 5 mcg/dL, FT4 0.6 ng/dL (cortisol is 5 mcg/dL, FT4 0.6 ng/dL (0.79 to 2.35), TSH 1.2 mIU/L (, TSH 1.2 mIU/L (0.47 to 4.68), total , total testosterone 120 ng/dL (testosterone 120 ng/dL (132 to 813), FSH 2 , FSH 2 mIU/ml, LH 3 mIU/ml, IGF-1 70 ng/mL (mIU/ml, LH 3 mIU/ml, IGF-1 70 ng/mL (109 to 284), prolactin 15 ng/mL (, prolactin 15 ng/mL (3.7 to 17.9). The best . The best next step isnext step is A. Start levothyroxine replacementA. Start levothyroxine replacement B. Start testosterone replacementB. Start testosterone replacement C. Perform Cosyntropin stimulation testC. Perform Cosyntropin stimulation test D. Start human growth hormone replacementD. Start human growth hormone replacement

Hypopituitarism (cont’d)Hypopituitarism (cont’d) Hypogonadotropic hypogonadismHypogonadotropic hypogonadism

MenMen Decreased libido, infertilityDecreased libido, infertility Low total testosterone and low or inappropriately normal Low total testosterone and low or inappropriately normal

FSH/LH FSH/LH Testosterone replacement (gonadotropins if desire Testosterone replacement (gonadotropins if desire

fertililty)fertililty) WomenWomen

Amenorrhea, infertilityAmenorrhea, infertility Low estradiol and low or inappropriately normal FSH/LHLow estradiol and low or inappropriately normal FSH/LH No data on estrogen/progestin replacement in No data on estrogen/progestin replacement in

reproductive-age women – recommend to replacereproductive-age women – recommend to replace Gonadotropins if desire fertilityGonadotropins if desire fertility

Hypopituitarism (cont’d)Hypopituitarism (cont’d) Growth hormone deficiencyGrowth hormone deficiency

Dx - Low IGF-1Dx - Low IGF-1 Low IGF-1 caveatsLow IGF-1 caveats

Fasting, anorexia, malnourishmentFasting, anorexia, malnourishment Poorly controlled DMPoorly controlled DM Exogenous estrogenExogenous estrogen Liver diseaseLiver disease

Confirmation testsConfirmation tests Insulin tolerance testInsulin tolerance test Arginine-GHRH stimulation test (GHRH no longer available Arginine-GHRH stimulation test (GHRH no longer available

in the U.S.)in the U.S.) Glucagon stimulation testGlucagon stimulation test

HGH replacementHGH replacement Improves BMD and body composition; does not decrease Improves BMD and body composition; does not decrease

weightweight Contraindicated – active cancerContraindicated – active cancer

Follow IGF-1 levelFollow IGF-1 level

Hormonal hypersecretionHormonal hypersecretion

Lactotroph (prolactinoma) – 50-60%Lactotroph (prolactinoma) – 50-60% Gonadotroph (nonfunctioning) – 15-45%Gonadotroph (nonfunctioning) – 15-45% Somatotroph (acromegaly) – 10-20%Somatotroph (acromegaly) – 10-20% Corticotroph (Cushing’s disease) – 10-Corticotroph (Cushing’s disease) – 10-

15%15% Thyrotroph (Hyperthyroidism) – 1%Thyrotroph (Hyperthyroidism) – 1%

Question 6Question 6 32 y/o M who presented with several weeks of 32 y/o M who presented with several weeks of

visual field deficits. Work up revealed 2.5 cm visual field deficits. Work up revealed 2.5 cm prolactin secreting pituitary adenoma, which prolactin secreting pituitary adenoma, which extends into the suprasellar space, extends into the suprasellar space, compressing the optic chiasm. The best compressing the optic chiasm. The best treatment option after a complete treatment option after a complete ophthalmologic evaluation isophthalmologic evaluation is

A. Starting cabergoline or bromocriptine A. Starting cabergoline or bromocriptine treatmenttreatment

B. Start octreotide LAR 30mg SQ monthlyB. Start octreotide LAR 30mg SQ monthly C. Refer for radiosurgeryC. Refer for radiosurgery D. Refer for transphenoidal surgeryD. Refer for transphenoidal surgery


34 y/o female who was found to have a 1 34 y/o female who was found to have a 1 cm prolactinoma during infertility work cm prolactinoma during infertility work up. She wishes to conceive soon. The up. She wishes to conceive soon. The best next step isbest next step is A. Start bromocriptine 2.5 mg dailyA. Start bromocriptine 2.5 mg daily B. Start cabergoline 0.25 mg weeklyB. Start cabergoline 0.25 mg weekly C. Start octreotide LAR 30mg SQ monthlyC. Start octreotide LAR 30mg SQ monthly D. Referral to neurosurgery for pituitary D. Referral to neurosurgery for pituitary

mass resectionmass resection


ProlactinomaProlactinoma Women :Women :

HirsutismHirsutism GalactorrheaGalactorrhea Menstrual irregularityMenstrual irregularity InfertilityInfertility Osteopenia/osteoporosisOsteopenia/osteoporosis Mass effectMass effect

Prolactin > 200 ng/mL - prolactin-secreting tumorsProlactin > 200 ng/mL - prolactin-secreting tumors Stalk effect Stalk effect Hook effectHook effect

MenMen GynecomastiaGynecomastia EDED InfertilityInfertility Osteopenia/Osteopenia/

osteoporosisosteoporosis Mass effectMass effect


Prolactinoma (cont’d)Prolactinoma (cont’d) Conditions that can cause Conditions that can cause

hyperprolactinemiahyperprolactinemia PregnancyPregnancy StressStress ExerciseExercise FoodFood Nipple stimulationNipple stimulation IntercourseIntercourse PostpartumPostpartum Estrogen therapyEstrogen therapy


Prolactinoma (cont’d)Prolactinoma (cont’d) TreatmentTreatment

Dopamine agonist – bromocriptine or cabergolineDopamine agonist – bromocriptine or cabergoline Bromocriptine - drug of choice in women desiring Bromocriptine - drug of choice in women desiring

pregnancy pregnancy Cabergoline - better tolerated and better efficacyCabergoline - better tolerated and better efficacy Start low and titrate slowly to avoid side effectsStart low and titrate slowly to avoid side effects

Indications for surgery Indications for surgery Unable to tolerate or unresponsive to medical Unable to tolerate or unresponsive to medical

treatmenttreatment Pituitary apoplexyPituitary apoplexy

Back to question 6Back to question 6

32 y/o M who presented with several weeks of 32 y/o M who presented with several weeks of visual field deficits. Work up revealed 2.5 cm visual field deficits. Work up revealed 2.5 cm prolactin secreting pituitary adenoma, which prolactin secreting pituitary adenoma, which extends into the suprasellar space, compressing the extends into the suprasellar space, compressing the optic chiasm. The best treatment option after a optic chiasm. The best treatment option after a complete ophthalmologic evaluation iscomplete ophthalmologic evaluation is

A. Starting cabergoline or bromocriptine A. Starting cabergoline or bromocriptine treatmenttreatment

B. Start octreotide 30mg LAR SQ monthlyB. Start octreotide 30mg LAR SQ monthly C. Refer for radiosurgeryC. Refer for radiosurgery D. Refer for transphenoidal surgeryD. Refer for transphenoidal surgery


34 y/o female who was found to have a 1 34 y/o female who was found to have a 1 cm prolactinoma during infertility work cm prolactinoma during infertility work up. She wishes to conceive soon. The up. She wishes to conceive soon. The best next step isbest next step is A. Start bromocriptine 2.5 mg dailyA. Start bromocriptine 2.5 mg daily B. Start cabergoline 0.25 mg weeklyB. Start cabergoline 0.25 mg weekly C. Start octreotide LAR 30mg SQ monthlyC. Start octreotide LAR 30mg SQ monthly D. Referral to neurosurgery for pituitary D. Referral to neurosurgery for pituitary

mass resectionmass resection


Cushing’s diseaseCushing’s disease Increased ACTH production Increased ACTH production increased cortisol increased cortisol Most common cause of endogenous Cushing’s Most common cause of endogenous Cushing’s

syndromesyndrome Specific symptoms and signs of Cushing’s Specific symptoms and signs of Cushing’s

syndromesyndrome Central obesityCentral obesity Proximal muscle weaknessProximal muscle weakness Wide (>1 cm), purple striaeWide (>1 cm), purple striae Spontaneous ecchymosisSpontaneous ecchymosis HypokalemiaHypokalemia Osteopenia/osteoporosisOsteopenia/osteoporosis


Cushing’s disease (cont’d)Cushing’s disease (cont’d) 24 hr UFC, 1mg DST, salivary cortisol, MN 24 hr UFC, 1mg DST, salivary cortisol, MN

serum cortisolserum cortisol Confirmation testConfirmation test Conditions that can cause pseudoCushing’sConditions that can cause pseudoCushing’s ACTH > 15 mcg/dlACTH > 15 mcg/dl Differentiate from ectopic Cushing’s syndromeDifferentiate from ectopic Cushing’s syndrome

8 mg DST8 mg DST CRH stimulation testCRH stimulation test Inferior petrosal sinus sampling (IPSS)Inferior petrosal sinus sampling (IPSS)


Cushing’s disease (cont’d)Cushing’s disease (cont’d) Treatment Treatment

Transphenoidal surgery (TSS) is primary Transphenoidal surgery (TSS) is primary treatmenttreatment

Better outcome with high volume surgeons/hospitalsBetter outcome with high volume surgeons/hospitals Radiotherapy or radiosurgeryRadiotherapy or radiosurgery Ketoconazole, mitotane, octreotide, etomidate, Ketoconazole, mitotane, octreotide, etomidate,

metyrapone, aminoglutethemide, pasreotide, metyrapone, aminoglutethemide, pasreotide, cabergoline, and mifepristonecabergoline, and mifepristone


TSH-Secreting AdenomaTSH-Secreting Adenoma Rarest, 0.5 – 1% Rarest, 0.5 – 1% Symptoms of hyperthyroidismSymptoms of hyperthyroidism Elevated FT4 and inappropriately normal Elevated FT4 and inappropriately normal

or elevated TSHor elevated TSH TreatmentTreatment

TSS is primary treatmentTSS is primary treatment Octreotide, lanreotide, dopamine agonistOctreotide, lanreotide, dopamine agonist Radiotherapy or radiosurgeryRadiotherapy or radiosurgery


The best screening test for acromegaly The best screening test for acromegaly isis A. Insulin-like growth factor 1A. Insulin-like growth factor 1 B. Human growth hormoneB. Human growth hormone C. Oral glucose tolerance test with C. Oral glucose tolerance test with

measurement of human growth hormonemeasurement of human growth hormone D. Insulin tolerance test with measurement D. Insulin tolerance test with measurement

of human growth hormoneof human growth hormone

Question 9Question 9 42 y/o man is evaluated for a 12 month 42 y/o man is evaluated for a 12 month

history of decreased libido, increased history of decreased libido, increased sweating, arthritis, and occasional sweating, arthritis, and occasional headaches. Initial hormonal evaluation headaches. Initial hormonal evaluation showed normal TSH, FT4, cbc, and showed normal TSH, FT4, cbc, and comprehensive metabolic panel. comprehensive metabolic panel. Testosterone 120 ng/dL. Further testing Testosterone 120 ng/dL. Further testing revealed FSH 3, LH 3, prolactin 30, IGF-1 revealed FSH 3, LH 3, prolactin 30, IGF-1 500 ng/mL, GH 8 ng/mL. GH was 3, 5, and 5 500 ng/mL, GH 8 ng/mL. GH was 3, 5, and 5 ng/ml at 30, 60, and 90 minutes during a 75 ng/ml at 30, 60, and 90 minutes during a 75 gm oral glucose tolerance test, suggesting gm oral glucose tolerance test, suggesting acromegaly. Pituitary MRI showed a 1.5 cm acromegaly. Pituitary MRI showed a 1.5 cm pituitary mass within the sella turcica. pituitary mass within the sella turcica.


The next best treatment isThe next best treatment is A. BromocriptineA. Bromocriptine B. CabergolineB. Cabergoline C. OctreotideC. Octreotide D. PegvisomantD. Pegvisomant E. Neurosurgery referral for transphenoidal E. Neurosurgery referral for transphenoidal

surgery surgery

Clemmons DR et al, JCEM 2003Clemmons DR et al, JCEM 2003

AcromegalyAcromegaly Increased GH production Increased GH production increased increased

IGF-1IGF-1

Hormonal Hormonal hypersecretionhypersecretion


Acromegaly (cont’d)Acromegaly (cont’d) Best screening test is serum IGF-1Best screening test is serum IGF-1 Confirmed with OGTTConfirmed with OGTT

Failure of GH suppression to < 1 ng/mLFailure of GH suppression to < 1 ng/mL Pitfalls in IGF-1 levels Pitfalls in IGF-1 levels

Low – Low – Fasting, anorexia, malnourishmentFasting, anorexia, malnourishment Poorly controlled DMPoorly controlled DM Exogenous estrogenExogenous estrogen Liver diseaseLiver disease

HighHigh Pregnancy, adolescent/puberty, hyperthyroidismPregnancy, adolescent/puberty, hyperthyroidism


Acromegaly (cont’d)Acromegaly (cont’d) Screening for co-morbiditiesScreening for co-morbidities

Colonoscopy, fasting glucose and A1c, EKGColonoscopy, fasting glucose and A1c, EKG Sleep test if symptoms/signs of OSA presentSleep test if symptoms/signs of OSA present

TreatmentTreatment Transphenoidal sinus surgery is primary Transphenoidal sinus surgery is primary

treatmenttreatment Octreotide, lanreotide, pegvisomant, dopamine Octreotide, lanreotide, pegvisomant, dopamine

agonistagonist Radiotherapy or radiosurgeryRadiotherapy or radiosurgery


The best screening test for acromegaly The best screening test for acromegaly isis A. Insulin-like growth factor 1A. Insulin-like growth factor 1 B. Human growth hormoneB. Human growth hormone C. Oral glucose tolerance test with C. Oral glucose tolerance test with

measurement of human growth hormonemeasurement of human growth hormone D. Insulin tolerance test with measurement D. Insulin tolerance test with measurement

of human growth hormoneof human growth hormone


42 y/o man is evaluated for a 12 month history 42 y/o man is evaluated for a 12 month history of decreased libido, increased sweating, of decreased libido, increased sweating, arthritis, and occasional headaches. Initial arthritis, and occasional headaches. Initial hormonal evaluation showed normal TSH, FT4, hormonal evaluation showed normal TSH, FT4, cbc, and comprehensive metabolic panel. cbc, and comprehensive metabolic panel. Testosterone 120 ng/dL. Further testing Testosterone 120 ng/dL. Further testing revealed FSH 3, LH 3, prolactin 30, IGF-1 500 revealed FSH 3, LH 3, prolactin 30, IGF-1 500 ng/mL, GH 8 ng/mL. GH was 3, 5, and 5 ng/ml ng/mL, GH 8 ng/mL. GH was 3, 5, and 5 ng/ml at 30, 60, and 90 minutes during a 75 gm oral at 30, 60, and 90 minutes during a 75 gm oral glucose tolerance test, suggesting acromegaly. glucose tolerance test, suggesting acromegaly. Pituitary MRI showed a 1.5 cm pituitary mass Pituitary MRI showed a 1.5 cm pituitary mass within the sella turcica. within the sella turcica.

Back to question 9 Back to question 9 (cont’d)(cont’d)

The next best treatment isThe next best treatment is A. BromocriptineA. Bromocriptine B. CabergolineB. Cabergoline C. OctreotideC. Octreotide D. PegvisomantD. Pegvisomant E. Neurosurgery referral for E. Neurosurgery referral for

transphenoidal surgerytransphenoidal surgery


40 y/o F with new onset headache and visual field 40 y/o F with new onset headache and visual field deficits who was found to have a 2 cm pituitary deficits who was found to have a 2 cm pituitary mass. Hormonal work up including 1mg mass. Hormonal work up including 1mg dexamethasone suppression test, 24 hr urine free dexamethasone suppression test, 24 hr urine free cortisol, TSH, FT4, IGF1 were normal. 8 am serum cortisol, TSH, FT4, IGF1 were normal. 8 am serum cortisol was 18 mcg/dl. Prolactin level was 35 and cortisol was 18 mcg/dl. Prolactin level was 35 and on repeat was 37, with 1:10 dilution was 4, and 1: on repeat was 37, with 1:10 dilution was 4, and 1: 100 dilution was 0.4. Ophthalmologic evaluation 100 dilution was 0.4. Ophthalmologic evaluation confirmed visual field defects. The next best step isconfirmed visual field defects. The next best step is A. Start bromocriptine 2.5mg dailyA. Start bromocriptine 2.5mg daily B. Start cabergoline 0.25 mg weeklyB. Start cabergoline 0.25 mg weekly C. Observation with repeat pituitary MRI in 3-6 monthsC. Observation with repeat pituitary MRI in 3-6 months D. Neurosurgery referralD. Neurosurgery referral

Nonfunctioning pituitary Nonfunctioning pituitary adenomaadenoma

Gonadotroph adenomaGonadotroph adenoma Mass effectMass effect HypopituitarismHypopituitarism TreatmentTreatment

TSS is primary treatment TSS is primary treatment If no mass effect and no hypopituitarism If no mass effect and no hypopituitarism

observation with repeat MRI q6 months for observation with repeat MRI q6 months for 2 years, then yearly.2 years, then yearly.


40 y/o F with new onset headache and visual field 40 y/o F with new onset headache and visual field deficits who was found to have a 2 cm pituitary deficits who was found to have a 2 cm pituitary mass. Hormonal work up including 1mg mass. Hormonal work up including 1mg dexamethasone suppression test, 24 hr urine free dexamethasone suppression test, 24 hr urine free cortisol, TSH, FT4, IGF1 were normal. 8 am serum cortisol, TSH, FT4, IGF1 were normal. 8 am serum cortisol was 18 mcg/dl. Prolactin level was 35 and cortisol was 18 mcg/dl. Prolactin level was 35 and on repeat was 37, with 1:10 dilution was 4, 1:100 on repeat was 37, with 1:10 dilution was 4, 1:100 dilution was 0.4. Ophthalmologic evaluation dilution was 0.4. Ophthalmologic evaluation confirmed visual field defects. The next best step isconfirmed visual field defects. The next best step is A. Start bromocriptine 2.5mg dailyA. Start bromocriptine 2.5mg daily B. Start cabergoline 0.25 mg weeklyB. Start cabergoline 0.25 mg weekly C. Observation with repeat pituitary MRI in 3-6 monthsC. Observation with repeat pituitary MRI in 3-6 months D. Neurosurgery referralD. Neurosurgery referral

Adapted from UptodateAdapted from Uptodate

SummarSummaryy

SummarySummary Hormonal evaluationHormonal evaluation

1mg DST and/or 24 hr urine free cortisol 1mg DST and/or 24 hr urine free cortisol If suspect adrenal insufficiencyIf suspect adrenal insufficiency

Morning fasting serum cortisol Morning fasting serum cortisol IGF-1IGF-1 TSH, FT4TSH, FT4 ProlactinProlactin FSH/LH panel and estradiol or testosteroneFSH/LH panel and estradiol or testosterone Serum osmolality, urine osmolality, urine Na Serum osmolality, urine osmolality, urine Na

– if suspect DI– if suspect DI

ReferencesReferences 1. Young, WF “The Incidentally discovered adrenal 1. Young, WF “The Incidentally discovered adrenal

mass.” NEJM 2007; 356:601-610mass.” NEJM 2007; 356:601-610 2. The diagnosis of Cushing’s syndrome: An 2. The diagnosis of Cushing’s syndrome: An

Endocrine society clinical practice guideline, JCEM Endocrine society clinical practice guideline, JCEM 2008; 93: 1526-15402008; 93: 1526-1540

3. Case detection, diagnosis, and treatment of 3. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an Endocrine patients with primary aldosteronism: an Endocrine society clinical practice guideline, JCEM 2008; 93: society clinical practice guideline, JCEM 2008; 93: 3266-32813266-3281

4. Guidelines for acromegaly management: an 4. Guidelines for acromegaly management: an update. JCEM 2009;94:1509-1517. update. JCEM 2009;94:1509-1517.

5. Clemmons DR et al, JCEM 2003; 88: 4759-675. Clemmons DR et al, JCEM 2003; 88: 4759-67 6. MKSAP 12 and 146. MKSAP 12 and 14 7. Up to date7. Up to date

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Adrenal Incidentaloma and Pituitary Incidentaloma/Tumors