A 51-year-old obese woman with a complex medical and
psychiatric history was admitted for evaluation of bilateral adrenal nodules.
She had a history of depression, psychosis and osteoporosis. A recent fall
resulted in a sacral fracture. Computed tomography scan confirmed this fracture
and incidentally revealed large bilateral adrenal nodules. The patient reported
problems with balance, swelling in her legs, nausea, recurrent rashes and easy
bruising. Her psychiatric status made an outpatient evaluation impossible, and
she was admitted for further assessment of her adrenal function.
Stephanie L. Lee
Physical exam revealed a morbidly obese woman with a
blood pressure of 136 mgHg/89 mmHg and a pulse of 89 beats per minute. Her face
appeared Cushingoid with periorbital swelling and rubor. Her thyroid was
palpable without nodularity. Her abdominal exam revealed visible superficial
veins but no striae. She had large ecchymoses on her extremities and an
erythematous, scaly, and papular rash in her inframam-mary creases and groin.
Random lab tests revealed a suppressed
adrenocorticotropic hormone (ACTH) <5 pg/mL with an elevated serum cortisol.
A low dose overnight dexamethasone suppression test revealed cortisol excess
after administration of dexamethasone 1 mg at 11 p.m. with the next morning
ACTH level <5 pg/mL, dexamethasone level 40 ng/dL and cortisol level 24.8
mcg/dL. These results suggested adrenal macronodular hyperplasia with Cushing
syndrome. A cosyntropin stimulation test was performed to evaluate ACTH
responsiveness to determine if she had ACTH-dependent or ACTH-independent
macronodular hyperplasia. A vigorous sixfold increase in cortisol from 20.1
mg/dL to 125 mg/dL and 20-fold increase in 17-hydroxyprogesterone from 39 ng/dL
to 931 ng/dL after IV cosyntropin (250 mcg) were consistent with ACTH-dependent
macronodular adrenal hyperplasia. Her thyroid studies, insulin-like growth
factor I level, and 24-hour urinary catecholamines and vanillylmandelic acid
were all within normal limits.
A CT scan with an adrenal protocol was performed (see
figure 1) that showed multiple low attenuation masses within both adrenal
glands consistent with adrenal adenomas. The largest mass in the right adrenal
gland was 5.2 cm × 3.8 cm × 3.2 cm and measured –3 Hounsfield
units in attenuation. The largest mass in the left adrenal gland was 4.7 cm
× 4.2 cm × 3.9 cm with attenuation between –12 and –1
1. Abdominal computed tomography scan of bilateral macronodular adrenal
hyperplasia. A. Axial image. B. Coronal Image. The red arrow indicates the
bilateral macronodular adrenal hyperplasia with multiple large hypodense
nodules. The green arrow indicates the kidney and L indicates the liver.
The patient was diagnosed with adrenal Cushing syndrome
from ACTH-dependent bilateral adrenal macronodular hyperplasia. The patient had
a bilateral adrenalectomy that revealed massive enlargement of both glands with
multiple large cortical nodules consistent with macronodular adrenal
hyperplasia. The left adrenal gland weighed 145.1 g and the right adrenal gland
weighed 88.9 g. She was discharged from the hospital in her usual state of
health on fludricortisone 0.1 mg daily and hydrocortisone 10 mg twice daily in
addition to her regular medications.
Bilateral macronodular adrenal hyperplasia is a rare
cause of Cushing syndrome, accounting for less than 1% of all adrenal Cushing
syndrome. These patients usually present at an older age with long standing
symptoms. The exquisite sensitivity of exogenous ACTH stimulation of cortisol
and 17-hydroxyprogesterone production reflects the increased quantity of
hormone producing cells in ACTH-dependent bilateral macronodular adrenal
hyperplasia. ACTH-independent macronodular adrenal hyperplasia may have
aberrant “illegitimate” or excess eutopic hormone receptors for
gastric inhibitory polypeptide, vasopressin, catecholamines, luteinizing
hormone, human chorionic gonadotropin, follicle-stimulating hormone, serotonin
and angiotensin that stimulate excess cortisol production. If aberrant adrenal
receptors are present, clinically relevant screening tests should be performed,
and a customized medical treatment plan can be designed to block the aberrant
receptors and reduce excessive glucocorticoid production (see table).
As evident in this case, macronodular adrenal
hyperplasia can present dramatically with extreme glucocorticoid excess. It is
important to determine if the cortisol excess is an ACTH-dependent or
ACTH-independent process. If ACTH-independent cortisol production is
determined, the presence of aberrant adrenal receptors should be assessed as
there are medical as well as definitive surgical therapeutic options for
management of the Cushing syndrome.
Lisa Usdan, MD, is a Fellow in Endocrinology at
Boston Medical Center.
Stephanie L. Lee, MD, PhD, is an Associate Professor
of Medicine at Boston University School of Medicine and Director of Endocrine
Clinics at Boston Medical Center.
For more information:
- Bourdeau I, D’Amour P, Hamet P, et al. Aberrant membrane
hormone receptors in incidentally discovered bilateral macronodular adrenal
hyperplasia with subclinical Cushing’s syndrome. J Clin Endocrinol
- Christopoulos S, Bourdeau I, Lacroix A. Clinical and subclinical
ACTH-independent macronodular adrenal hyperplasia and aberrant hormone
receptors. Hormone Research. 2005;64:119-131.
- Doppman JL, Chrousos GP, Papanicolaou DA, et al.
Adrenocortioctropin-independent macronodular adrenal hyperplasia: an uncommon
cause of primary adrenal hypercortisolism. Radiology.
- Lieberman SA, Eccleshall TR, Feldman D. ACTH-independent massive
bilateral adrenal disease (AIMBAD): a subtype of Cushing’s syndrome with
major diagnostic and therapeutic implications. Eur J