Transcript Case Report: Cortisol Secreting Pheochromocytoma

A Case Of Cushing’s
Syndrome associated with
Pheochromocytoma
Dr. Sanam Shorey
PGY5 Endocrinology Fellow
University of Western Ontario
Outline
1.
Case Report
2.
Ectopic ACTH Syndrome
3.
4.
Case Reports of Cushing’s Syndrome
associated with Pheochromocytoma.
Patient Follow-Up
History

43 yr old healthy female

PMHX: Depression

Med’ns: Elavil

Nov 18th/02 admitted Markdale Hospital:
One week hx LUQ pain, Fever, N/V
Intermittent palpitations, headaches, diaphoresis
past yr
History (Cont’d)
2-3 month preceding hx:
•
•
•
•
•
•
facial fullness
facial hirsutism
alopecia
irregular periods
wt gain noted primarily in the abdomenal
area
Physical Examination

Bp 205mmHg/105mmHg, HR: 100 regular, RR 14
and afebrile

General exam revealed obese lady

Head and neck: moon like facies, acanthosis
nigricans, and hirsutism of the upper lip and chin.
Her hair was moist and quite thin. The thyroid exam
was unremarkable.

Cardiac exam was normal outside of sinus
tachycardia.

Respiratory exam revealed bronchial breath sounds
in the left lower base.
Physical Examination (Con’td)

The abdomen was protuberant with striae,
however they were not violaceous in
appearance. There was generalized
tenderness in all quadrants with no evidence
of hepatosplenomegaly.

Neurological exam was normal except for mild
proximal muscle weakness.

The remainder of the examination was normal.
LABS

Normal Electrolytes

Normal Creatinine

Liver enzymes normal

Mild elevation in WBC count (11)
LABS (CONT’D)

AM cortisol 2644 (am170-660 nmol/L)

Cortisol PM 1312 (½ am range)

Urinary 24 hr free cortisol 400 (l50-220 nmol/d)

Plasma DHEA 5.3 (<6.5 umol/L)

Plasma total testosterone 3.2 (1.0-2.5 nmol/L)

Free testosterone 2.3 (1.0-17.5 pmol/L)

Plasma aldosterone 547 (110-860pmol/L standing28444pmol/L supine)
LABS (CONT’D)

Urinary 24 h VMA 366
(10-35 µmol/d)

Urinary 24 h E:
5078.7
(< 60 nmol/d)

Urinary 24 h NE:
5645
(< 600 nmol/d)

Urinary 24 h M
107.3
(< 5.5 µmol/d)

Urinary 24 hr Dop:
445
(< 2500)
Investigations (Cont’d)






Chest X-ray : LLL Consolidation.
CT Abdomen:
11.6 cm AP by 9.9 cm transverse left
suprarenal mass
left sided pleural effusion
left lower lobe consolidation
no enlarged lymph nodes detected.
Treatment

IV fluids for rehydration

IV Cefuroxime and oral Azithromycin

Atenolol 100mg pood for hypertension!!!!

subsequently discharged a few days
later on oral Ceftin and Atenolol.
HISTORY (CONT’D)

November 25th ( a few days post discharge) readmitted
to Markdale hospital

woke up with a terrible headache

in Hospital had a seizure and was sent to their ICU

her family mentioned she had worsening episodic
headaches, diaphoresis and palpitations since being
discharged

polyuria and polydipsia as well over this time
PHYSICAL EXAM

BP 210mmhg/110mmhg with a mild orthostatic drop., P:
96, Afebrile

she was confused with decreased LOC but still able to
protect her airway

PERLA and there was no evidence of papilledema

no nuchal rigidity was noted

no focal neurological signs were detected
LABS

creatinine 730 (120 prior admission)

K: 5.1, Na 137

mild AG acidosis

BG: 26

CK :81800

AST: 3893.

Urine myoglobin was greater than 10,000 with
urinalysis showing granular casts.
INVESTIGATIONS(CONT’D)

CT Head Normal

Lumbar puncture Normal

ECG showed Left anterior hemiblock with twave inversion.

Echocardiogram: hypokinesis of septum ,
apex and distal inferior wall of left ventricle EF:
35%.
Management

started on IV labetolol infusion, nitropatch
0.6mg/hr

insulin drip

Dilantin

Subsequently transferred to a tertiary ICU
center with progressive renal failure and multiorgan dysfunction for potential need for dialysis
MANAGEMENT

IV nitroprusside, phentolamine and labetolol, as well
as oral phenoxybenzamine were initially required for
BP.

Therapy with the the catechol-O-methyl transferase
inhibitor metyrosine was also instituted early, given
the refractory nature of the hypertension and ongoing
crisis.

Medications on discharge from the Intensive care unit
were phenoxybenzamine, metoprolol, amlodipine,
doxazosin, and metyrosine.
FURTHER IMAGING

An MRI was performed as well revealing
the 10X12X12cm left adrenal mass
which was displacing the left kidney
inferiorly.
SURGICAL REMOVAL

After ensuring control of blood pressure ,
surgery was performed to remove the
left adrenal tumor.

In addition due to the size of the tumor
the spleen and the left kidney were also
removed.
Adrenal Function
Pre-Operative
Plasma Epinephrine
Plasma
Norepinephrine
< 2800
Plasma Dopamine
< 210
Urinary 24 h
Epinephrine
< 60 nmol/d
Urinary 24 h
Norepinephrine
< 600 nmol/d
Urinary 24 h
Metanephrine
< 5.5umol/d
IntraOp
Post-Operative
(Immediate)
< 50
226000 22800
Post-Operative (approx
2-3 months)
4095
2164
< 150
5078.7
11
< 10
5645
153
254 (March) 317 (May)
107.3
428
3.7
Adrenal Function
Pre-Operative
IntraOp
Post-Operative
(Immediate)
213
227
77
1.91
3.1
Post-Operative (approx
2-3 months)
179
Plasma Cortisol am
170-660 nmol/L
2644
Cortisol PM
½ am range
ACTH
0-18 pmol/L
1313
Urinary 24 hr free
cortisol
50-220 nmol/d
Plasma total
testosterone
1.0-2.5 nmol/L
400
242
3.2
1.0
456
(Dec 19)
4.4
11.4
11.2

Lab values for adrenal function were
taken either immediately preop, intraop
as well as postop and showed an
immediate decline of catecholamines
and cortisol as well as a subtle rise in
ACTH

Glucocorticoid therapy which was started
during surgery was gradually tapered
and discontinued within a few weeks
post-operatively.
Pathological Report




The left adrenal gland mass was 11 X 11.5 X
10.5 cm.
Sectioning revealed a variegated tan-brown
lesion with extensive necrosis, hemorrhage
and cystic degeneration.
Capsule invasion was not identified
extensive confluent necrosis was present as
were prominent mitotic figures.
Immunohistochemistry

Immunomarkers within tumor cells were positive for
chromogranin and synaptophysin

The sustenacular cells around the tumor groups are
positive of S-100 protein.

ACTH markers showed faint granular
intracytoplasmic staining.

Incidental finding in kidney revealed a 3mm renal cell
carcinoma raising the possibility of a Von-HippelLindau syndrome.
Patient Disposition




Following surgery :
blood sugars normalized
Liver and renal function tests also
returned to normal.
Sent home on labetolol.
Ectopic ACTH Syndromes

Comprises approx 10-20% of cases of
Cushing’s Syndrome

Number of tumors that may cause
ectopic ACTH production
Clinically divided into two
categories

1) Malignant tumors: (eg. small cell ca
lung)

2) Indolent cases occurring in pts with
underlying neuroendocrine tumors such
as bronchial carcinoids.
Malignant tumors

Clinically resemble Addison’s disease more than
Cushing’s Syndrome

Duration of symptoms from onset of presentation is
short (< 3months)

Wt loss, hyperpigmentation, myopathy, hirsutism and
acne are prominent

ACTH levels and cortisol levels very high

Hypokalemic alkalosis and peripheral edema should
alert physician to the diagnosis
Indolent Tumors

Symptoms and signs are commonly present for 18
months from from onset to clinical presentation.

Typical features of Cushing’s disease

ACTH levels mildly elevated but may be normal with
high serum cortisol

Hard to differentiate pituitary dependent Cushing’s
disease from the indolent causes of ectopic ACTH
production
Ectopic ACTH syndromes
Pheochromocytoma

Very few reported cases

General consensus:

Relatively benign lesion where surgical intervention
may be curative

Clinical symptoms and signs vary from typical
cushingoid appearance to cases of
hyperpigmentation, wtloss, profound hirsutism and
acne

Majority were female, majority had left adrenal mass,
onset of symptoms were rapidly progressing
Laboratory Testing

Vary:

Majority of cases:

elevated plasma ACTH average 200’s (0-100pg/mol)
Plasma DHEAS 300-400 (60-230ug/dl),
plasma testosterone 95-200 (20-54 ng/dl)







All:
were hypokalemic
elevated cortisol levels,
elevated 24 hr urine cortisol
lack of adrenal suppression with dexamethasone
Pathology
Adrenocortical hyperplasia
Positive Immunostaining for ACTH
Other cases: Pheochromocytoma
with hypercortisolemia

Retrospective study of 6 cases of adrenal
cortical and medullary hyperplasia

pts here presented with features of P. alone
elevated catecholamines and elevated 24 hr
samples of cortisol

Chen M, Lu G et al. 2002 J huazhong Univ Sci Technol Med Sci
22(4):367-368
Other cases

Two reported cases of a mixed adenoma consisting
of adrenomedullary and cortical cells.

presenting with new onset diabetes and
hypertension

pt was not cushingoid

Plasma cortisol and 24 hr urine levels elevated,
Plasma ACTH normal

Dexamethasone Supression test did not supress
cortisol or ACTH
Akai H, Sanoyama K et al. 1993 Nipporn Naibunpi Gakkai Zasshi Aug
20;69(7)659-69
Did our pt have either of these?




Against Ectopic ACTH:
Clinically:
Lab:
not hyperpigmented, no wt loss
ACTH normal, normal DHEAS, normal
testosterone, not hypokalemic on
presentation
Pathology: adrenocortical hyperplasia absent

Against Adrenal tumor:

absence of real corticol histology supporting this.

Was this simply a hypercortisolemic response from the
stress of the pheochromoctyoma?
Current Status:

palpitations, headaches, diaphoresis and weakness
have resolved

periods regularized

she gained a few pounds since discharge but the
weight is more generalized than before and has less
facial fullness

was subsequently switched to diltiazem and is
currently on no antihypertensives with a normal
blood pressure
Current Status

A MIBG scan done post- operatively was
negative.

We are currently following her by clinical
exam and by repeating 24 hour
collections of catecholamines and
cortisol and are requesting a repeat
MIBG in a year’s time