Functional Adrenal Tumors

Functional Adrenal Disorders
David F. Schneider, MD, MS

NOTHING TO DISCLOSE

OBJECTIVES
• Recognize the presentation of aldosteronoma,
Cushing’s syndrome, and pheochromocytoma
• Make the biochemical diagnosis for functional
adrenal masses
• Know how to diagnose and treat adrenal
insufficiency
• Understand when adrenal venous sampling is
indicated
• Describe the proper order for diagnosis and
localization of functional adrenal masses

Case #1
A 47-year-old woman has a recent onset on
headaches, palpitations, sweating, and heat
intolerance. On physical exam, her blood
pressure is 190/100 and her heart rate is 110
bpm. Biochemical evaluation revealed an
elevated plasma metanephrine level and
elevated 24-hour urinary metanephrines. A CT
scan of the abdomen is obtained.

Pheochromocytoma
• Catecholamine-producing tumor of chromaffin
cells
• 0.1% of all hypertensive patients
• “Rule of 10s”
• 10% bilateral
• 10% extra-adrenal (20% = paraganglioma)
• 10% malignant
• 10% multiple
• 10% familial (24-40%)
• MEN2, VHL, neurofibromatosis type 1 SDHB, SDHC,
SDHD

Pheochromocytoma:
Signs and Symptoms
Abdominal
pain
Nausea/Vomit
ing
Diaphoresis
Headache
Palpitation
HTN
0% 20% 40% 60% 80%
50 patients, 1960-1995, UCSF

Pheochromocytoma:
Biochemical Tests
• Plasma and urinary catecholamines and
their metabolites
• Screening - 24 hr. urinary metanephrines
(plasma metanephrines)
• Must be off α & β-blockers, TCAs,
levodopa
• Inaccurate: renal insufficiency, OSA,
stress (including hospitalization), trauma,
surgery

Question: Case #1
Left lap adrenal is planned. Pre-operative
management of this patient could include all of
the following EXECPT:
(A) Beta-blockade for 2 weeks followed by alphablockade
(B) Volume expansion
(C) Blood pressure monitoring
(D) Anesthesia consultation

Case 2
A 51 -year-old woman reports significant
weight gain over the last 6 months. In this time
period, she has also had 2 episodes of urinary
tract infections and has noticed that she bruises
quite easily. On physical exam, her blood
pressure is 150/95. She is 5’8” in height, and
weighs 250 lbs. She has a characteristic bulge
of fat on her back and striae on her abdomen.
The diagnosis of Cushing’s syndrome is made.

Cushing’s
• Central obesity
• Moon facies
• Supraclavicular
fat pad
• Purple Striae

Adrenal Cushing’s
• Adenomas or carcinomas
• 1-mg dexamethasone
suppress cortisol < 5 µg/dL
• 24 hr Ur cortisol (less
sensitive)
• Low plasma ACTH (ACTHindependent)
• Postop Addisonian, require
steroid replacement

Adrenal Insufficiency
• Primary or Secondary (postoperative/steroids)
• Exogenous: greatest risk ≥ 20 mg X ≥ 5 d.
• If Rx > 1 month up to 6 – 12 m. of suppression
• S/Sx: hyperkalemia, hypoglycemia,
unexplained hypotension
• Dx: ACTH stimulation test:
• Give 250 mcg ACTH (IV)
• Measure plasma cortisol at 0, 30, and 60 min.
• + test: change from baseline < 9 μg/dL
OR
< 18 μg/dL at 30 or 60 min

Postoperative Adrenal
Insufficiency
• Hydrocortisone 100 mg when vein is clipped
then TID for first 24 hours postoperatively
• 3 day taper on oral prednisone to maintenance
dose of 5 mg daily
• Wean off steroids over the next 3 – 6 months
• Bilateral: will need lifelong glucocorticoid and
mineralocorticoid replacement

Case 3
A 62 -year-old man has a history of difficult to
control HTN since 2005. He is currently on 4
medications for HTN. He has also had
intermittent hypokalemia (2.8 – 3.6) over that
same period. PMHx also notable for “prediabetes.”
A left adrenal mass was incidentally
discovered in 2005 (2 cm). It grew to 3.7 cm in
2011, and on his most recent CT scan it was 5
cm. Exam: BMI is 32, no striae, moon facies,
buffalo hump, etc.

Biochemical Evaluation
• Plasma metanephrines: 46 pg/mL
• Plasma normatanephrines: 97 pg/mL
• Total metanephrines: 143 pg/mL
• Aldosterone: 4.0 ng/dL
• Renin: 0.8 ng/mL/hr
Aldo:Renin N/A
• Midnight salivary cortisol: 0.477 and 0.181 μg/dL
(normal < 0.112)
• Dexamethasone Suppression Test:
• Random cortisol = 15.1 μg/dL ACTH = 7 pg/mL
• AM cortisol = 4.0 μg/dL ACTH = 1.5 pg/mL

Dexamethasone Suppression Test
• Measure baseline cortisol and ACTH
• 1 mg Dexamethasone @ 11 pm
• Cortisol and ACTH @ 8 am the next morning
• Interpreting Results:
• < 5 μg/dL “normal”
• < 1.5 μg/dL truly normal (No Cushing’s)
• 1.5 – 5 μg/dL borderline or Subclinical Cushing’s
• > 5 μg/dL abnormal high dose testing (pituitary
vs. adrenal vs. ectopic source)

Subclinical Hypercortisolism (SH)
• Estimated to be present in 5 – 30% of patients
with adrenal incidentaloma
• Incidentaloma present in 4 – 7% of adults
• Therefore, prevalence of SH in adult
population is estimated at 0.2 – 2%
• Data lacking on outcomes

Subclinical Hypercortisolism (SH)
• Only one prospective randomized trial of
surgical vs. follow-up management (Toniato
2009)
• 2/3 patients showed improvement in BP,
possible improvement in FBS and no
improvement in bone density
• Follow-up: 24 – 204 months

Laparoscopic Adrenalectomy
• Control vein early
• Coordination with
Anesthesia –
intraoperative
medications
• 3 (L) or 4 (R) small
incisions
• 23 hr hospital stay

Case 4
During a routine GYN visit, a 33-year-old
woman with a history of headaches was noted
to have a blood pressure of 160/100. Her
laboratory work revealed a K+ of 2.5 mmol/L.
On further biochemical testing, the patient also
had an elevated plasma aldosterone level and a
suppressed renin level with an aldosterone to
renin ratio of 50. The diagnosis of
hyperaldosteronism is made.

Hyperaldosteronism: Diagnosis
• Low K+ ( 20:1 with PA > 15 ng/dL
• Confirmatory test: saline suppression or oral
sodium loading (failure to suppress Ur Aldo)
• Adenoma vs. hyperplasia
• Postural studies: PA decreases upon standing 4 hrs
• 18-hydrocorticosterone elevated in adenomas
• NP-59 scan vs. CT scan
• adrenal vein sampling = gold standard

Hyperaldosteronism: Diagnosis

• Etiology
Hyperaldosteronism
• Adenoma 50% (Conn’s Syndrome)
• Bilateral hyperplasia
• 8 - 12% of all hypertensive patients
• Clinical presentation
• Hypokalemia, HTN, muscle weakness
• Treatment
• Adenoma - lap adrenal
• Hyperplasia - medical (spironolactone)
non-functioning
cortical adenomas
increase with age
need to
distinguish for
proper treatment

Selective Adrenal Vein Sampling
> 3-4:1
> 4:1

Diagnostic Algorithm:
Hyperaldosteronism
< 45 y/o

Aldosteronoma: Outcomes
• Hypokalemia resolves 100% of the
time (within 24-48 hours)
• HTN: 15 – 60% normotensive
without medications (3-6 months)
• Predictors of cure (no need for
Rx)younger patients, shorter clinical
course, greater # pre-op Rx, lack of
family history (HTN), good response to
spironolactone
• Median reduction in medications = 2
• Continues to improve over 4 years
Murashima et al. 2009;11:316.

QUESTIONS