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Adrenal Incidentaloma and Pituitary Incidentaloma/Tumors

Adrenal Incidentaloma and Pituitary Incidentaloma/Tumors. Adrenal Incidentaloma. Objectives. Definition Epidemiology/Statistics Etiology Biochemical work up Treatment. Definition. Adrenal mass > or = 1cm Discovered incidentally Asymptomatic. Epidemiology and Statistics.

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Adrenal Incidentaloma and Pituitary Incidentaloma/Tumors

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  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 20-29 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 96-100%, 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. 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 Imaging differences between malignant and benign lesions Malignant Benign

  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; 356:601-610

  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

  34. 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

  35. 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

  36. 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

  37. 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

  38. 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

  39. 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

  40. 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

  41. 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

  42. 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

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

  44. 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

  45. 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

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

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

  48. 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

  49. 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

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