Transcript Adrenal_and_Pituitary_Incidentaloma

Adrenal Incidentaloma
and Pituitary
Incidentaloma/Tumors
Adrenal Incidentaloma
Objectives
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Definition
Epidemiology/Statistics
Etiology
Biochemical work up
Treatment
Definition
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Adrenal mass > or = 1cm
Discovered incidentally
Asymptomatic
Epidemiology and Statistics
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Prevalence 4-6%
Increases with increasing age
0.2 % between 20-29 years of age
 7% in patients over 70 years of age
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Etiology
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Adrenal adenoma
Adrenocortical carcinoma
Myelolipoma
Pheochromocytoma
Adrenal cyst
Adrenal hemorrhage
Adrenal metastasis
Infection
Infiltrative disease
ACTH-independent MMAD
ACTH-dependent Cushing’s
Congenital adrenal hyperplasia
Question 1
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A 45 y/o healthy woman undergoes emergent abdominal
imaging after an automobile accident and was found to have a
6.3 cm right adrenal mass. The results of basic chemistry and
hematology tests are normal. Which of the following is the
best evaluation plan for this patient?
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A. Chest CT, morning serum cortisol, repeat imaging in 3 months
B. 1 mg dexamethasone suppression test, 24-hour urine
metanephrines and catecholamines, surgical consultation
C. Paired plasma renin and aldosterone, 8 AM serum cortisol, repeat
abdominal imaging in 6 months
D. No hormonal evaluation, surgical consultation
Evaluation
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2 questions:
Is it functioning?
 Is it malignant?
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Evaluation (cont’d)
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Functional status
10 – 15% functional
 Hormonal evaluation
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Subclinical Cushing’s syndrome
 Pheochromocytoma
 Primary aldosteronism
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Evaluation for hormonal function
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Subclinical Cushing’s syndrome
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Low dose 1mg overnight dexamethasone suppression test
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Normal: cortisol suppresses < 5 mcg/dL
Sensitivity 89%, specificity 98%
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Test of choice for adrenal incidentaloma
Autonomy
24-hour urine free cortisol
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Endo Soc. recommended cut point 1.8 mcg/dL – sens 95%, spec 80%
Hypersecretion
24 hr UFC > 4x upper normal limit
May miss subclinical Cushing’s or Cushing’s in renal failure
Midnight salivary cortisol
Midnight serum cortisol
Evaluation for hormonal function
(cont’d)
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Subclinical Cushing’s syndrome (cont’d)
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Pseudo-Cushing’s
Stress
 Morbid obesity
 Psychiatric illness (MDD, anxiety, anorexia/bulimia)
 Alcoholism (rare)
 Glucocorticoid resistance
 Uncontrolled DM
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Elevated cortisol-binding globulin (estrogen, pregnancy,
hyperthyroidism)
 Drugs that increases dexamethasone metabolism (rifampin,
phenytoin, phenobarbital, alcohol)
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Evaluation for hormonal function
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Pheochromocytoma
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Urine metanephrines and catecholamines
Sensitivity 91%, specificity 98%
 Screen cases with low suspicion
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Serum fractionated metanephrines and catecholamines
Sensitivity 96-100%, specificity 85-95%
 High false positive rate
 High suspicion
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Imaging over-rules biochemical testing
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Early, asymptomatic pheo may have negative hormonal testing
Evaluation for hormonal function
(cont’d)
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Pheochromocytoma (cont’d)
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Conditions that may interfere with test results
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Meds – discontinue at least 2 weeks
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Tricyclic antidepressants
Levodopa
Drugs containing adrenergic receptor agonists (decongestants, appetite
suppressants)
Amphetamines
Buspirone and most psychoactive agents
Prochlorperazine
Reserpine
Acetaminophen
Increased endogenous catecholamines: physiologic stress, alcohol
or clonidine withdrawal
Evaluation for hormonal function
(cont’d)
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Primary aldosteronism – performed if pt has HTN
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Plasma aldosterone concentration (PAC) and plasma renin activity
(PRA)
PAC/PRA > 20 and PAC > 15 ng/dL
Confirmation test
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Saline infusion
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Oral salt loading
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PAC > 10 ng/dL
24 hr urine aldosterone > 12 mcg and 24 hr urine Na > 200 mEq
Catopril suppression
Fludrocortisone suppression
Adrenal vein sampling
Evaluation for hormonal function
(cont’d)
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Primary aldosteronism (cont’d)
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Agents that markedly affect ARR – withdraw at least 4
weeks
Spironolactone, eplerenone
 All diuretics
 Liquorice products (chewing tobacco, confectionary licorice)
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If ARR is non-diagnostic off the above agents, consider
withdrawing other anti-HTN meds for 2 weeks and repeat
test
Evaluation for hormonal function
(cont’d)
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Primary aldosteronisim (cont’d)
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Drugs that minimally affect ARR
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Drugs that can falsely suppressed ARR
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Verapamil
Hydralazine
Alpha-adrengeric blockers – prazosin, doxazosin, terazosin
ARB, ACE I, diuretics, aldosterone receptor antagonists - increase PRA
Drugs that can falsely elevated ARR
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Beta blocker, central alpha 2 agonist (clonidine, methyldopa), NSAIDS –
suppresses renin release
Back to Question 1
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A 45 y/o healthy woman undergoes emergent abdominal
imaging after an automobile accident and was found to have a
6.3 cm right adrenal mass. The results of basic chemistry and
hematology tests are normal. Which of the following is the
best evaluation plan for this patient?
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A. Chest CT, morning serum cortisol, repeat imaging in 3 months
B. 1 mg dexamethasone suppression test, 24-hour urine
metanephrines and catecholamines, surgical consultation
C. Paired plasma renin and aldosterone, 8 AM serum cortisol, repeat
abdominal imaging in 6 months
D. No hormonal evaluation, surgical consultation
Question 2
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A 45-year-old man is diagnosed with a 1.5 cm left
adrenal mass on abdominal/pelvic CT to evaluate
abdominal pain. The lesion has attenuation value of 3
HU pre-contrast, 40 HU immediately after contrast
administration, and 15 HU at 10 minutes postcontrast. The adrenal mass is likely
A.
 B.
 C.
 D.
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Pheochromocytoma
Adrenocortical carcinoma
Metastatic lesion
Adrenal adenoma
Question 3
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41 y/o F with h/o HTN, who presented with
abdominal pain and found to have a 3 cm L adrenal
mass on abdominal CT. F/u MRI shown below.
T1W MRI
T2W MRI
Question 3 (cont’d)
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Your differential diagnoses include all of the following
except
A. Pheochromocytoma
B. Adrenocortical carcinoma
C. Metastatic malignancy
D. Adrenal adenoma
Imaging differences between malignant and
benign lesions
Malignant
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Size > 4 cm
Irregular, calcifications
Inhomogenous
High attenuation on non-contrast
studies > 10 HU
Highly enhanced with contrast,
slower washout (< 50% at 10
min)
Isointensity with liver on T1W
and hyperintense on T2W MRI
images
No signal loss on out-of-phase
chemical shift MRI
Benign
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Size < 4cm
Round, smooth contour
Homogeneous
Low attenuation on non-contrast
studies <10 HU
Limited enhancement with
contrast and earlier washout of
contrast
Isointensity with liver on both
T1W and T2W MRI images
Lose signal on out-of-phase
chemical shift MRI
Back to Question 2
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A 45-year-old man is diagnosed with a 1.5 cm left adrenal
mass on abdominal/pelvic CT to evaluate abdominal pain.
The lesion has attenuation value of 3 HU pre-contrast, 40 HU
immediately after contrast administration, and 15 HU at 10
minutes post-contrast. The adrenal mass is likely
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A. Pheochromocytoma
B. Adrenocortical carcinoma
C. Metastatic lesion
D. Adrenal adenoma
Back to Question 3
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41 y/o F with HTN who presented with abdominal
pain and found to have a 3 cm L adrenal mass on
abdominal CT. F/u MRI shown below.
T1W MRI
T2W MRI
Back to Question 3
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Your differential diagnoses include all of the following
except
A. Pheochromocytoma
B. Adrenocortical carcinoma
C. Metastatic malignancy
D. Adrenal adenoma
CT-guided adrenal biopsy
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Rarely indicated
Can’t distinguish benign from malignant cortical
tissues
Helpful if metastasis or infection
Rule out pheochromocytoma prior to biopsy
Treatment
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Lesion > 6 cm or functioning and no evidence of
metastases  surgical resection
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Lesion < 4 cm and non-functioning
Repeat scans in 3-6, 12, and 24 months
 Repeat hormonal testing annually for 4 years
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If lesion is 4-6 cm or is enlarging by 1cm or more 
consider removal
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Question 4
36 y/o woman was found incidentally to have a 3-cm right
adrenal mass. The left adrenal gland is very small.
Gained approximately 22 lb over the past 18 months
Diagnosed with impaired glucose tolerance
P/E showed central obesity, proximal muscle weakness, and
wide violaceous striae
1mg DST – plasma cortisol 12 mcg/dL
24-hr urine free cortisol - 3x the normal upper limit for daily
excretion
Serum ACTH is < 5 pg/mL
The patient undergoes laparoscopic right adrenalectomy
During the first 24 hours after surgery experiences
hypotension and nausea.
Question 4 (cont’d)
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Which of the following is the most appropriate
management at this time?
A. Surgery to explore for retroperitoneal bleeding
 B. Emergent CT scan of abdomen and retroperitoneum
 C. Evaluation to insure that the correct adrenal gland was
resected
 D. Administer hydrocortisone, 100mg IV q8 hrs
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NEJM 2007; 356:601-610
Pituitary
Incidentaloma/Tumors
Objectives
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Definition and classification of pituitary incidentaloma
Causes of pituitary incidentaloma
Review of anterior and posterior pituitary hormones
Biochemical evaluation
Treatment and follow-up
Pituitary incidentaloma
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Previously unrecognized lesion in the pituitary
Prevalence up to 10%
Classification
Microadenoma < 10 mm
 Macroadenoma > 10 mm
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More likely to cause visual and hormonal abnormalities
Etiology of incidentaloma
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Pituitary adenoma
Pituitary hyperplasia
Pituitary carcinoma
Craniopharyngioma
Meningioma
Lymphocytic hypophysitis
Rathke’s cleft cyst
Germinoma
Primary CNS lymphoma
Metastasis
AVM
Pituitary incidentaloma (cont’d)
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Functional status
Hyposecretion
 Hypersecretion
 Non-functioning
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Mass effect
Headache
 Visual field deficits (bitemporal hemianopsia)
 Cranial nerve III, IV, VI palsy - diplopia
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Hypopituitarism
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Decreased secretion of one or more anterior pituitary
hormones (ACTH, GH, FSH, LH, TSH, prolactin)
Panhypopituitarism – deficiency of all pit hormones
 Partial – deficiency of some pit hormones
 Isolated – deficiency of only one pit hormone
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Diagnosis can’t be make by measuring pituitary
hormones
Overlap between normal and hypopituitary ranges
 Hormone present not bioactive
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Hypopituitarism
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Central adrenal insufficiency
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Abnormality in CRH or ACTH production  decreased cortisol
Fatigue, weakness, anorexia, weight loss, lightheadedness, orthostatic
hypotension, nausea/vomiting, hyponatremia
Different from primary AI –
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ACTH not elevated - no hyperpigmentation
Aldosterone secretion normal - no hyperkalemia
Dx - morning fasting serum cortisol
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< 3 mcg/dL – highly suggestive of AI
> 15 mcg/dL – normal
> 3 < 15 mcg/dL  further testing
Hypopituitarism
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Central AI (cont’d)
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Cosyntropin stimulation test –
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Not useful in acute setting (normal until adrenals atropy – weeks
to months)
Insulin tolerance test – gold standard
Hypoglycemia stimulates entire HPA axis
 Contraindicated in elderly, CV disease, seizures
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Medic alert bracelet
 Glucocorticoid replacement
 Sick day coverage
 Stress dose coverage
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Question 5
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A 50 y/o man who presented with new onset headache and
was subsequently diagnosed with a 1.5 cm pituitary mass.
Fasting morning serum cortisol is 5 mcg/dL, FT4 0.6 ng/dL
(0.79 to 2.35), TSH 1.2 mIU/L (0.47 to 4.68), total
testosterone 120 ng/dL (132 to 813), FSH 2 mIU/ml, LH 3
mIU/ml, IGF-1 70 ng/mL (109 to 284), prolactin 15 ng/mL
(3.7 to 17.9). The best next step is
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A.
B.
C.
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Start levothyroxine replacement
Start testosterone replacement
Perform Cosyntropin stimulation test
Start human growth hormone replacement
Hypopituitarism
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Central hypothyroidism
Symptoms and signs – same as primary hypothyroidism
except goiter
 Dx - low FT4 and low or inappropriately normal TSH
 LT4 replacement
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Treat AI before starting LT4 as LT4 increases cortisol
metabolism  adrenal crisis
Follow FT4 level, goal FT4 mid normal range
Back to question 5
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A 50 y/o man who presented with new onset headache and
was subsequently diagnosed with a 1.5 cm pituitary mass.
Fasting morning serum cortisol is 5 mcg/dL, FT4 0.6 ng/dL
(0.79 to 2.35), TSH 1.2 mIU/L (0.47 to 4.68), total
testosterone 120 ng/dL (132 to 813), FSH 2 mIU/ml, LH 3
mIU/ml, IGF-1 70 ng/mL (109 to 284), prolactin 15 ng/mL
(3.7 to 17.9). The best next step is
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A.
B.
C.
D.
Start levothyroxine replacement
Start testosterone replacement
Perform Cosyntropin stimulation test
Start human growth hormone replacement
Hypopituitarism (cont’d)
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Hypogonadotropic hypogonadism
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Men
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Decreased libido, infertility
Low total testosterone and low or inappropriately normal FSH/LH
Testosterone replacement (gonadotropins if desire fertililty)
Women
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Amenorrhea, infertility
Low estradiol and low or inappropriately normal FSH/LH
No data on estrogen/progestin replacement in reproductive-age women –
recommend to replace
Gonadotropins if desire fertility
Hypopituitarism (cont’d)
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Growth hormone deficiency
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Dx - Low IGF-1
Low IGF-1 caveats
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Confirmation tests
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Insulin tolerance test
Arginine-GHRH stimulation test (GHRH no longer available in the U.S.)
Glucagon stimulation test
HGH replacement
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Fasting, anorexia, malnourishment
Poorly controlled DM
Exogenous estrogen
Liver disease
Improves BMD and body composition; does not decrease weight
Contraindicated – active cancer
Follow IGF-1 level
Hormonal hypersecretion
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Lactotroph (prolactinoma) – 50-60%
Gonadotroph (nonfunctioning) – 15-45%
Somatotroph (acromegaly) – 10-20%
Corticotroph (Cushing’s disease) – 10-15%
Thyrotroph (Hyperthyroidism) – 1%
Question 6
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32 y/o M who presented with several weeks of visual
field deficits. Work up revealed 2.5 cm prolactin
secreting pituitary adenoma, which extends into the
suprasellar space, compressing the optic chiasm. The
best treatment option after a complete
ophthalmologic evaluation is
A. Starting cabergoline or bromocriptine treatment
B. Start octreotide LAR 30mg SQ monthly
C. Refer for radiosurgery
D. Refer for transphenoidal surgery
Question 7
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34 y/o female who was found to have a 1 cm
prolactinoma during infertility work up. She wishes to
conceive soon. The best next step is
A. Start bromocriptine 2.5 mg daily
 B. Start cabergoline 0.25 mg weekly
 C. Start octreotide LAR 30mg SQ monthly
 D. Referral to neurosurgery for pituitary mass resection
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Hormonal hypersecretion
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Prolactinoma
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Women :
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Hirsutism
Galactorrhea
Menstrual irregularity
Infertility
Osteopenia/osteoporosis
Mass effect
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Men
Gynecomastia
 ED
 Infertility
 Osteopenia/osteoporosis
 Mass effect
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Prolactin > 200 ng/mL - prolactin-secreting tumors
Stalk effect
Hook effect
Hormonal hypersecretion
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Prolactinoma (cont’d)
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Conditions that can cause hyperprolactinemia
Pregnancy
 Stress
 Exercise
 Food
 Nipple stimulation
 Intercourse
 Postpartum
 Estrogen therapy
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Hormonal hypersecretion
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Prolactinoma (cont’d)
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Treatment
Dopamine agonist – bromocriptine or cabergoline
 Bromocriptine - drug of choice in women desiring pregnancy
 Cabergoline - better tolerated and better efficacy
 Start low and titrate slowly to avoid side effects
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Indications for surgery
Unable to tolerate or unresponsive to medical treatment
 Pituitary apoplexy
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Back to question 6
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32 y/o M who presented with several weeks of visual field
deficits. Work up revealed 2.5 cm prolactin secreting pituitary
adenoma, which extends into the suprasellar space,
compressing the optic chiasm. The best treatment option
after a complete ophthalmologic evaluation is
A. Starting cabergoline or bromocriptine treatment
B. Start octreotide 30mg LAR SQ monthly
C. Refer for radiosurgery
D. Refer for transphenoidal surgery
Back to question 7
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34 y/o female who was found to have a 1 cm
prolactinoma during infertility work up. She wishes to
conceive soon. The best next step is
A. Start bromocriptine 2.5 mg daily
 B. Start cabergoline 0.25 mg weekly
 C. Start octreotide LAR 30mg SQ monthly
 D. Referral to neurosurgery for pituitary mass resection
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Hormonal hypersecretion
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Cushing’s disease
Increased ACTH production  increased cortisol
 Most common cause of endogenous Cushing’s syndrome
 Specific symptoms and signs of Cushing’s syndrome
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Central obesity
 Proximal muscle weakness
 Wide (>1 cm), purple striae
 Spontaneous ecchymosis
 Hypokalemia
 Osteopenia/osteoporosis
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Hormonal hypersecretion
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Cushing’s disease (cont’d)
24 hr UFC, 1mg DST, salivary cortisol, MN serum cortisol
 Confirmation test
 Conditions that can cause pseudoCushing’s
 ACTH > 15 mcg/dl
 Differentiate from ectopic Cushing’s syndrome
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8 mg DST
 CRH stimulation test
 Inferior petrosal sinus sampling (IPSS)
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Hormonal hypersecretion
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Cushing’s disease (cont’d)
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Treatment
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Transphenoidal surgery (TSS) is primary treatment
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Better outcome with high volume surgeons/hospitals
Radiotherapy or radiosurgery
 Ketoconazole, mitotane, octreotide, etomidate, metyrapone,
aminoglutethemide, pasreotide, cabergoline, and mifepristone
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Hormonal hypersecretion
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TSH-Secreting Adenoma
Rarest, 0.5 – 1%
 Symptoms of hyperthyroidism
 Elevated FT4 and inappropriately normal or elevated
TSH
 Treatment
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TSS is primary treatment
 Octreotide, lanreotide, dopamine agonist
 Radiotherapy or radiosurgery
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Question 8
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The best screening test for acromegaly is
A. Insulin-like growth factor 1
 B. Human growth hormone
 C. Oral glucose tolerance test with measurement of
human growth hormone
 D. Insulin tolerance test with measurement of human
growth hormone
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Question 9
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42 y/o man is evaluated for a 12 month history of
decreased libido, increased sweating, arthritis, and
occasional headaches. Initial hormonal evaluation
showed normal TSH, FT4, cbc, and comprehensive
metabolic panel. Testosterone 120 ng/dL. Further
testing revealed FSH 3, LH 3, prolactin 30, IGF-1
500 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
glucose tolerance test, suggesting acromegaly.
Pituitary MRI showed a 1.5 cm pituitary mass within
the sella turcica.
Question 9 (cont’d)
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The next best treatment is
A.
 B.
 C.
 D.
 E.
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Bromocriptine
Cabergoline
Octreotide
Pegvisomant
Neurosurgery referral for transphenoidal surgery
Hormonal hypersecretion
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Acromegaly
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Increased GH production  increased IGF-1
Clemmons DR et al, JCEM 2003
Hormonal hypersecretion
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Acromegaly (cont’d)
Best screening test is serum IGF-1
 Confirmed with OGTT
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Failure of GH suppression to < 1 ng/mL
Pitfalls in IGF-1 levels
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Low –
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Fasting, anorexia, malnourishment
Poorly controlled DM
Exogenous estrogen
Liver disease
High
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Pregnancy, adolescent/puberty, hyperthyroidism
Hormonal hypersecretion
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Acromegaly (cont’d)
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Screening for co-morbidities
Colonoscopy, fasting glucose and A1c, EKG
 Sleep test if symptoms/signs of OSA present
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Treatment
Transphenoidal sinus surgery is primary treatment
 Octreotide, lanreotide, pegvisomant, dopamine agonist
 Radiotherapy or radiosurgery
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Back to question 8
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The best screening test for acromegaly is
A. Insulin-like growth factor 1
 B. Human growth hormone
 C. Oral glucose tolerance test with measurement of
human growth hormone
 D. Insulin tolerance test with measurement of human
growth hormone
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Back to question 9

42 y/o man is evaluated for a 12 month history of
decreased libido, increased sweating, arthritis, and
occasional headaches. Initial hormonal evaluation
showed normal TSH, FT4, cbc, and comprehensive
metabolic panel. Testosterone 120 ng/dL. Further
testing revealed FSH 3, LH 3, prolactin 30, IGF-1 500
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 glucose
tolerance test, suggesting acromegaly. Pituitary MRI
showed a 1.5 cm pituitary mass within the sella turcica.
Back to question 9 (cont’d)

The next best treatment is
A.
 B.
 C.
 D.
 E.

Bromocriptine
Cabergoline
Octreotide
Pegvisomant
Neurosurgery referral for transphenoidal surgery
Question 10

40 y/o F with new onset headache and visual field deficits
who was found to have a 2 cm pituitary mass. Hormonal
work up including 1mg dexamethasone suppression test, 24 hr
urine free cortisol, TSH, FT4, IGF1 were normal. 8 am
serum cortisol was 18 mcg/dl. Prolactin level was 35 and on
repeat was 37, with 1:10 dilution was 4, and 1: 100 dilution
was 0.4. Ophthalmologic evaluation confirmed visual field
defects. The next best step is




A.
B.
C.
D.
Start bromocriptine 2.5mg daily
Start cabergoline 0.25 mg weekly
Observation with repeat pituitary MRI in 3-6 months
Neurosurgery referral
Nonfunctioning pituitary adenoma
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Gonadotroph adenoma
Mass effect
Hypopituitarism
Treatment
TSS is primary treatment
 If no mass effect and no hypopituitarism  observation
with repeat MRI q6 months for 2 years, then yearly.
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Back to question 10

40 y/o F with new onset headache and visual field deficits
who was found to have a 2 cm pituitary mass. Hormonal
work up including 1mg dexamethasone suppression test, 24 hr
urine free cortisol, TSH, FT4, IGF1 were normal. 8 am
serum cortisol was 18 mcg/dl. Prolactin level was 35 and on
repeat was 37, with 1:10 dilution was 4, 1:100 dilution was 0.4.
Ophthalmologic evaluation confirmed visual field defects.
The next best step is
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A. Start bromocriptine 2.5mg daily
B. Start cabergoline 0.25 mg weekly
C. Observation with repeat pituitary MRI in 3-6 months
D. Neurosurgery referral
Summary
Adapted from Uptodate
Summary

Hormonal evaluation
1mg DST and/or 24 hr urine free cortisol
 If suspect adrenal insufficiency


Morning fasting serum cortisol
IGF-1
 TSH, FT4
 Prolactin
 FSH/LH panel and estradiol or testosterone
 Serum osmolality, urine osmolality, urine Na – if suspect
DI
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References
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1. Young, WF “The Incidentally discovered adrenal mass.”
NEJM 2007; 356:601-610
2. The diagnosis of Cushing’s syndrome: An Endocrine
society clinical practice guideline, JCEM 2008; 93: 1526-1540
3. Case detection, diagnosis, and treatment of patients with
primary aldosteronism: an Endocrine society clinical practice
guideline, JCEM 2008; 93: 3266-3281
4. Guidelines for acromegaly management: an update.
JCEM 2009;94:1509-1517.
5. Clemmons DR et al, JCEM 2003; 88: 4759-67
6. MKSAP 12 and 14
7. Up to date