Functional Adrenal Tumors
Functional Adrenal Tumors
Functional Adrenal Tumors
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<strong>Functional</strong> <strong>Adrenal</strong> Disorders<br />
David F. Schneider, MD, MS
NOTHING TO DISCLOSE
OBJECTIVES<br />
• Recognize the presentation of aldosteronoma,<br />
Cushing’s syndrome, and pheochromocytoma<br />
• Make the biochemical diagnosis for functional<br />
adrenal masses<br />
• Know how to diagnose and treat adrenal<br />
insufficiency<br />
• Understand when adrenal venous sampling is<br />
indicated<br />
• Describe the proper order for diagnosis and<br />
localization of functional adrenal masses
Case #1<br />
A 47-year-old woman has a recent onset on<br />
headaches, palpitations, sweating, and heat<br />
intolerance. On physical exam, her blood<br />
pressure is 190/100 and her heart rate is 110<br />
bpm. Biochemical evaluation revealed an<br />
elevated plasma metanephrine level and<br />
elevated 24-hour urinary metanephrines. A CT<br />
scan of the abdomen is obtained.
Pheochromocytoma<br />
• Catecholamine-producing tumor of chromaffin<br />
cells<br />
• 0.1% of all hypertensive patients<br />
• “Rule of 10s”<br />
• 10% bilateral<br />
• 10% extra-adrenal (20% = paraganglioma)<br />
• 10% malignant<br />
• 10% multiple<br />
• 10% familial (24-40%)<br />
• MEN2, VHL, neurofibromatosis type 1 SDHB, SDHC,<br />
SDHD
Pheochromocytoma:<br />
Signs and Symptoms<br />
Abdominal<br />
pain<br />
Nausea/Vomit<br />
ing<br />
Diaphoresis<br />
Headache<br />
Palpitation<br />
HTN<br />
0% 20% 40% 60% 80%<br />
50 patients, 1960-1995, UCSF
Pheochromocytoma:<br />
Biochemical Tests<br />
• Plasma and urinary catecholamines and<br />
their metabolites<br />
• Screening - 24 hr. urinary metanephrines<br />
(plasma metanephrines)<br />
• Must be off α & β-blockers, TCAs,<br />
levodopa<br />
• Inaccurate: renal insufficiency, OSA,<br />
stress (including hospitalization), trauma,<br />
surgery
Question: Case #1<br />
Left lap adrenal is planned. Pre-operative<br />
management of this patient could include all of<br />
the following EXECPT:<br />
(A) Beta-blockade for 2 weeks followed by alphablockade<br />
(B) Volume expansion<br />
(C) Blood pressure monitoring<br />
(D) Anesthesia consultation
Case 2<br />
A 51 -year-old woman reports significant<br />
weight gain over the last 6 months. In this time<br />
period, she has also had 2 episodes of urinary<br />
tract infections and has noticed that she bruises<br />
quite easily. On physical exam, her blood<br />
pressure is 150/95. She is 5’8” in height, and<br />
weighs 250 lbs. She has a characteristic bulge<br />
of fat on her back and striae on her abdomen.<br />
The diagnosis of Cushing’s syndrome is made.
Cushing’s<br />
• Central obesity<br />
• Moon facies<br />
• Supraclavicular<br />
fat pad<br />
• Purple Striae
<strong>Adrenal</strong> Cushing’s<br />
• Adenomas or carcinomas<br />
• 1-mg dexamethasone<br />
suppress cortisol < 5 µg/dL<br />
• 24 hr Ur cortisol (less<br />
sensitive)<br />
• Low plasma ACTH (ACTHindependent)<br />
• Postop Addisonian, require<br />
steroid replacement
<strong>Adrenal</strong> Insufficiency<br />
• Primary or Secondary (postoperative/steroids)<br />
• Exogenous: greatest risk ≥ 20 mg X ≥ 5 d.<br />
• If Rx > 1 month up to 6 – 12 m. of suppression<br />
• S/Sx: hyperkalemia, hypoglycemia,<br />
unexplained hypotension<br />
• Dx: ACTH stimulation test:<br />
• Give 250 mcg ACTH (IV)<br />
• Measure plasma cortisol at 0, 30, and 60 min.<br />
• + test: change from baseline < 9 μg/dL<br />
OR<br />
< 18 μg/dL at 30 or 60 min
Postoperative <strong>Adrenal</strong><br />
Insufficiency<br />
• Hydrocortisone 100 mg when vein is clipped<br />
then TID for first 24 hours postoperatively<br />
• 3 day taper on oral prednisone to maintenance<br />
dose of 5 mg daily<br />
• Wean off steroids over the next 3 – 6 months<br />
• Bilateral: will need lifelong glucocorticoid and<br />
mineralocorticoid replacement
Case 3<br />
A 62 -year-old man has a history of difficult to<br />
control HTN since 2005. He is currently on 4<br />
medications for HTN. He has also had<br />
intermittent hypokalemia (2.8 – 3.6) over that<br />
same period. PMHx also notable for “prediabetes.”<br />
A left adrenal mass was incidentally<br />
discovered in 2005 (2 cm). It grew to 3.7 cm in<br />
2011, and on his most recent CT scan it was 5<br />
cm. Exam: BMI is 32, no striae, moon facies,<br />
buffalo hump, etc.
Biochemical Evaluation<br />
• Plasma metanephrines: 46 pg/mL<br />
• Plasma normatanephrines: 97 pg/mL<br />
• Total metanephrines: 143 pg/mL<br />
• Aldosterone: 4.0 ng/dL<br />
• Renin: 0.8 ng/mL/hr<br />
Aldo:Renin N/A<br />
• Midnight salivary cortisol: 0.477 and 0.181 μg/dL<br />
(normal < 0.112)<br />
• Dexamethasone Suppression Test:<br />
• Random cortisol = 15.1 μg/dL ACTH = 7 pg/mL<br />
• AM cortisol = 4.0 μg/dL ACTH = 1.5 pg/mL
Dexamethasone Suppression Test<br />
• Measure baseline cortisol and ACTH<br />
• 1 mg Dexamethasone @ 11 pm<br />
• Cortisol and ACTH @ 8 am the next morning<br />
• Interpreting Results:<br />
• < 5 μg/dL “normal”<br />
• < 1.5 μg/dL truly normal (No Cushing’s)<br />
• 1.5 – 5 μg/dL borderline or Subclinical Cushing’s<br />
• > 5 μg/dL abnormal high dose testing (pituitary<br />
vs. adrenal vs. ectopic source)
Subclinical Hypercortisolism (SH)<br />
• Estimated to be present in 5 – 30% of patients<br />
with adrenal incidentaloma<br />
• Incidentaloma present in 4 – 7% of adults<br />
• Therefore, prevalence of SH in adult<br />
population is estimated at 0.2 – 2%<br />
• Data lacking on outcomes
Subclinical Hypercortisolism (SH)<br />
• Only one prospective randomized trial of<br />
surgical vs. follow-up management (Toniato<br />
2009)<br />
• 2/3 patients showed improvement in BP,<br />
possible improvement in FBS and no<br />
improvement in bone density<br />
• Follow-up: 24 – 204 months
Laparoscopic <strong>Adrenal</strong>ectomy<br />
• Control vein early<br />
• Coordination with<br />
Anesthesia –<br />
intraoperative<br />
medications<br />
• 3 (L) or 4 (R) small<br />
incisions<br />
• 23 hr hospital stay
Case 4<br />
During a routine GYN visit, a 33-year-old<br />
woman with a history of headaches was noted<br />
to have a blood pressure of 160/100. Her<br />
laboratory work revealed a K+ of 2.5 mmol/L.<br />
On further biochemical testing, the patient also<br />
had an elevated plasma aldosterone level and a<br />
suppressed renin level with an aldosterone to<br />
renin ratio of 50. The diagnosis of<br />
hyperaldosteronism is made.
Hyperaldosteronism: Diagnosis<br />
• Low K+ ( 20:1 with PA > 15 ng/dL<br />
• Confirmatory test: saline suppression or oral<br />
sodium loading (failure to suppress Ur Aldo)<br />
• Adenoma vs. hyperplasia<br />
• Postural studies: PA decreases upon standing 4 hrs<br />
• 18-hydrocorticosterone elevated in adenomas<br />
• NP-59 scan vs. CT scan<br />
• adrenal vein sampling = gold standard
Hyperaldosteronism: Diagnosis
• Etiology<br />
Hyperaldosteronism<br />
• Adenoma 50% (Conn’s Syndrome)<br />
• Bilateral hyperplasia<br />
• 8 - 12% of all hypertensive patients<br />
• Clinical presentation<br />
• Hypokalemia, HTN, muscle weakness<br />
• Treatment<br />
• Adenoma - lap adrenal<br />
• Hyperplasia - medical (spironolactone)<br />
non-functioning<br />
cortical adenomas<br />
increase with age<br />
need to<br />
distinguish for<br />
proper treatment
Selective <strong>Adrenal</strong> Vein Sampling<br />
> 3-4:1<br />
> 4:1
Diagnostic Algorithm:<br />
Hyperaldosteronism<br />
< 45 y/o
Aldosteronoma: Outcomes<br />
• Hypokalemia resolves 100% of the<br />
time (within 24-48 hours)<br />
• HTN: 15 – 60% normotensive<br />
without medications (3-6 months)<br />
• Predictors of cure (no need for<br />
Rx)younger patients, shorter clinical<br />
course, greater # pre-op Rx, lack of<br />
family history (HTN), good response to<br />
spironolactone<br />
• Median reduction in medications = 2<br />
• Continues to improve over 4 years<br />
Murashima et al. 2009;11:316.
QUESTIONS