1. Adrenal Incidentaloma and Pituitary Incidentaloma/Tumors

2. Adrenal Incidentaloma

3. Objectives Definition Epidemiology/Statistics Etiology
Biochemical work up
Treatment

4. Definition Adrenal mass > or = 1cm Discovered incidentally
Asymptomatic

5. Epidemiology and Statistics
Prevalence 4-6%
Increases with increasing age
0.2 % between years of age
7% in patients over 70 years of age

6. Etiology 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

7. Question 1
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?
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

8. Evaluation
2 questions:
Is it functioning?
Is it malignant?

9. Evaluation (cont’d) Functional status 10 – 15% functional
Hormonal evaluation
Subclinical Cushing’s syndrome
Pheochromocytoma
Primary aldosteronism

10. Evaluation for hormonal function
Subclinical Cushing’s syndrome
Low dose 1mg overnight dexamethasone suppression test
Normal: cortisol suppresses < 5 mcg/dL
Sensitivity 89%, specificity 98%
Endo Soc. recommended cut point 1.8 mcg/dL – sens 95%, spec 80%
Test of choice for adrenal incidentaloma
Autonomy
24-hour urine free cortisol
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

11. Evaluation for hormonal function (cont’d)
Subclinical Cushing’s syndrome (cont’d)
Pseudo-Cushing’s
Stress
Morbid obesity
Psychiatric illness (MDD, anxiety, anorexia/bulimia)
Alcoholism (rare)
Glucocorticoid resistance
Uncontrolled DM
Elevated cortisol-binding globulin (estrogen, pregnancy, hyperthyroidism)
Drugs that increases dexamethasone metabolism (rifampin, phenytoin, phenobarbital, alcohol)

12. Evaluation for hormonal function
Pheochromocytoma
Urine metanephrines and catecholamines
Sensitivity 91%, specificity 98%
Screen cases with low suspicion
Serum fractionated metanephrines and catecholamines
Sensitivity %, specificity 85-95%
High false positive rate
High suspicion
Imaging over-rules biochemical testing
Early, asymptomatic pheo may have negative hormonal testing

13. Evaluation for hormonal function (cont’d)
Pheochromocytoma (cont’d)
Conditions that may interfere with test results
Meds – discontinue at least 2 weeks
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

14. Evaluation for hormonal function (cont’d)
Primary aldosteronism – performed if pt has HTN
Plasma aldosterone concentration (PAC) and plasma renin activity (PRA)
PAC/PRA > 20 and PAC > 15 ng/dL
Confirmation test
Saline infusion
PAC > 10 ng/dL
Oral salt loading
24 hr urine aldosterone > 12 mcg and 24 hr urine Na > 200 mEq
Catopril suppression
Fludrocortisone suppression
Adrenal vein sampling

15. Evaluation for hormonal function (cont’d)
Primary aldosteronism (cont’d)
Agents that markedly affect ARR – withdraw at least 4 weeks
Spironolactone, eplerenone
All diuretics
Liquorice products (chewing tobacco, confectionary licorice)
If ARR is non-diagnostic off the above agents, consider withdrawing other anti-HTN meds for 2 weeks and repeat test

16. Evaluation for hormonal function (cont’d)
Primary aldosteronisim (cont’d)
Drugs that minimally affect ARR
Verapamil
Hydralazine
Alpha-adrengeric blockers – prazosin, doxazosin, terazosin
Drugs that can falsely suppressed ARR
ARB, ACE I, diuretics, aldosterone receptor antagonists - increase PRA
Drugs that can falsely elevated ARR
Beta blocker, central alpha 2 agonist (clonidine, methyldopa), NSAIDS – suppresses renin release

17. Back to Question 1
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?
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

18. Question 2
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
A. Pheochromocytoma
B. Adrenocortical carcinoma
C. Metastatic lesion
D. Adrenal adenoma

19. Question 3
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

20. Question 3 (cont’d)
Your differential diagnoses include all of the following except
A. Pheochromocytoma
B. Adrenocortical carcinoma
C. Metastatic malignancy
D. Adrenal adenoma

21. Imaging differences between malignant and benign lesions
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
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

22. Back to Question 2
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
A. Pheochromocytoma
B. Adrenocortical carcinoma
C. Metastatic lesion
D. Adrenal adenoma

23. Back to Question 3
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.
T2W MRI
T1W MRI

24. Back to Question 3
Your differential diagnoses include all of the following except
A. Pheochromocytoma
B. Adrenocortical carcinoma
C. Metastatic malignancy
D. Adrenal adenoma

25. CT-guided adrenal biopsy
Rarely indicated
Can’t distinguish benign from malignant cortical tissues
Helpful if metastasis or infection
Rule out pheochromocytoma prior to biopsy

26. Treatment
Lesion > 6 cm or functioning and no evidence of metastases  surgical resection
Lesion < 4 cm and non-functioning
Repeat scans in 3-6, 12, and 24 months
Repeat hormonal testing annually for 4 years
If lesion is 4-6 cm or is enlarging by 1cm or more  consider removal

27. 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.

28. Question 4 (cont’d)
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

29. NEJM 2007; 356:

30. Pituitary Incidentaloma/Tumors

31. Objectives Definition and classification of pituitary incidentaloma
Causes of pituitary incidentaloma
Review of anterior and posterior pituitary hormones
Biochemical evaluation
Treatment and follow-up

32. Pituitary incidentaloma
Previously unrecognized lesion in the pituitary
Prevalence up to 10%
Classification
Microadenoma < 10 mm
Macroadenoma > 10 mm
More likely to cause visual and hormonal abnormalities

33. Etiology of incidentaloma
Pituitary adenoma
Pituitary hyperplasia
Pituitary carcinoma
Craniopharyngioma
Meningioma
Lymphocytic hypophysitis
Rathke’s cleft cyst
Germinoma
Primary CNS lymphoma
Metastasis
AVM

35. Pituitary incidentaloma (cont’d)
Functional status
Hyposecretion
Hypersecretion
Non-functioning
Mass effect
Headache
Visual field deficits (bitemporal hemianopsia)
Cranial nerve III, IV, VI palsy - diplopia

36. Hypopituitarism
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
Diagnosis can’t be make by measuring pituitary hormones
Overlap between normal and hypopituitary ranges
Hormone present not bioactive

37. Hypopituitarism Central adrenal insufficiency
Abnormality in CRH or ACTH production  decreased cortisol
Fatigue, weakness, anorexia, weight loss, lightheadedness, orthostatic hypotension, nausea/vomiting, hyponatremia
Different from primary AI –
ACTH not elevated - no hyperpigmentation
Aldosterone secretion normal - no hyperkalemia
Dx - morning fasting serum cortisol
< 3 mcg/dL – highly suggestive of AI
> 15 mcg/dL – normal
> 3 < 15 mcg/dL  further testing

38. Hypopituitarism Central AI (cont’d) Cosyntropin stimulation test –
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
Medic alert bracelet
Glucocorticoid replacement
Sick day coverage
Stress dose coverage

39. Question 5
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
A. Start levothyroxine replacement
B. Start testosterone replacement
C. Perform Cosyntropin stimulation test
D. Start human growth hormone replacement

40. Hypopituitarism Central hypothyroidism
Symptoms and signs – same as primary hypothyroidism except goiter
Dx - low FT4 and low or inappropriately normal TSH
LT4 replacement
Treat AI before starting LT4 as LT4 increases cortisol metabolism  adrenal crisis
Follow FT4 level, goal FT4 mid normal range

41. Back to question 5
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
A. Start levothyroxine replacement
B. Start testosterone replacement
C. Perform Cosyntropin stimulation test
D. Start human growth hormone replacement

42. Hypopituitarism (cont’d)
Hypogonadotropic hypogonadism
Men
Decreased libido, infertility
Low total testosterone and low or inappropriately normal FSH/LH
Testosterone replacement (gonadotropins if desire fertililty)
Women
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

43. Hypopituitarism (cont’d)
Growth hormone deficiency
Dx - Low IGF-1
Low IGF-1 caveats
Fasting, anorexia, malnourishment
Poorly controlled DM
Exogenous estrogen
Liver disease
Confirmation tests
Insulin tolerance test
Arginine-GHRH stimulation test (GHRH no longer available in the U.S.)
Glucagon stimulation test
HGH replacement
Improves BMD and body composition; does not decrease weight
Contraindicated – active cancer
Follow IGF-1 level

44. Hormonal hypersecretion
Lactotroph (prolactinoma) – 50-60%
Gonadotroph (nonfunctioning) – 15-45%
Somatotroph (acromegaly) – 10-20%
Corticotroph (Cushing’s disease) – 10-15%
Thyrotroph (Hyperthyroidism) – 1%

45. Question 6
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

46. Question 7
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

47. Hormonal hypersecretion
Men
Gynecomastia ED
Infertility
Osteopenia/osteoporosis
Mass effect
Prolactinoma
Women :
Hirsutism
Galactorrhea
Menstrual irregularity
Infertility
Osteopenia/osteoporosis
Mass effect
Prolactin > 200 ng/mL - prolactin-secreting tumors
Stalk effect
Hook effect

48. Hormonal hypersecretion
Prolactinoma (cont’d)
Conditions that can cause hyperprolactinemia
Pregnancy
Stress
Exercise
Food
Nipple stimulation
Intercourse
Postpartum
Estrogen therapy

49. Hormonal hypersecretion
Prolactinoma (cont’d)
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
Indications for surgery
Unable to tolerate or unresponsive to medical treatment
Pituitary apoplexy

50. Back to question 6
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

51. Back to question 7
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

52. Hormonal hypersecretion
Cushing’s disease
Increased ACTH production  increased cortisol
Most common cause of endogenous Cushing’s syndrome
Specific symptoms and signs of Cushing’s syndrome
Central obesity
Proximal muscle weakness
Wide (>1 cm), purple striae
Spontaneous ecchymosis
Hypokalemia
Osteopenia/osteoporosis

53. Hormonal hypersecretion
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
8 mg DST
CRH stimulation test
Inferior petrosal sinus sampling (IPSS)

54. Hormonal hypersecretion
Cushing’s disease (cont’d)
Treatment
Transphenoidal surgery (TSS) is primary treatment
Better outcome with high volume surgeons/hospitals
Radiotherapy or radiosurgery
Ketoconazole, mitotane, octreotide, etomidate, metyrapone, aminoglutethemide, pasreotide, cabergoline, and mifepristone

55. Hormonal hypersecretion
TSH-Secreting Adenoma
Rarest, 0.5 – 1%
Symptoms of hyperthyroidism
Elevated FT4 and inappropriately normal or elevated TSH
Treatment
TSS is primary treatment
Octreotide, lanreotide, dopamine agonist
Radiotherapy or radiosurgery

56. Question 8 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

57. 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 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.

58. Question 9 (cont’d) The next best treatment is A. Bromocriptine
B. Cabergoline
C. Octreotide
D. Pegvisomant
E. Neurosurgery referral for transphenoidal surgery

59. Hormonal hypersecretion
Acromegaly
Increased GH production  increased IGF-1
Clemmons DR et al, JCEM 2003

60. Hormonal hypersecretion
Acromegaly (cont’d)
Best screening test is serum IGF-1
Confirmed with OGTT
Failure of GH suppression to < 1 ng/mL
Pitfalls in IGF-1 levels
Low –
Fasting, anorexia, malnourishment
Poorly controlled DM
Exogenous estrogen
Liver disease
High
Pregnancy, adolescent/puberty, hyperthyroidism

61. Hormonal hypersecretion
Acromegaly (cont’d)
Screening for co-morbidities
Colonoscopy, fasting glucose and A1c, EKG
Sleep test if symptoms/signs of OSA present
Treatment
Transphenoidal sinus surgery is primary treatment
Octreotide, lanreotide, pegvisomant, dopamine agonist
Radiotherapy or radiosurgery

62. Back to question 8 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

63. 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 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.

64. Back to question 9 (cont’d)
The next best treatment is
A. Bromocriptine
B. Cabergoline
C. Octreotide
D. Pegvisomant
E. Neurosurgery referral for transphenoidal surgery

65. 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 Ophthalmologic evaluation confirmed visual field defects. The next best step is
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

66. Nonfunctioning pituitary adenoma
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.

67. 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 Ophthalmologic evaluation confirmed visual field defects. The next best step is
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

68. Summary
Adapted from Uptodate

69. 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

70. References
1. Young, WF “The Incidentally discovered adrenal mass.” NEJM 2007; 356:
2. The diagnosis of Cushing’s syndrome: An Endocrine society clinical practice guideline, JCEM 2008; 93:
3. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an Endocrine society clinical practice guideline, JCEM 2008; 93:
4. Guidelines for acromegaly management: an update. JCEM 2009;94:
5. Clemmons DR et al, JCEM 2003; 88:
6. MKSAP 12 and 14
7. Up to date