Clinical Picture

Cushings conundrum: an unusual case of primary

pigmented nodular adrenal disease in a 60-year-old woman
Jasna Aleksova, Glenn Ward, Kim Taubman, Jason Tan, Stephen Farrell, Stuart Galloway, Richard J MacIsaac, Nirupa Sachithanandan

Lancet Diabetes Endocrinol 2016;
4: 630
Published Online
October 30, 2015
http://dx.doi.org/10.1016/
S2213-8587(15)00262-4
Departments of Endocrinology
and Diabetes (J Aleksova MBBS,
G Ward, Prof R J Maclsaac FRACP,
N Sachithanandan FRACP),
Nuclear Medicine
(K Taubman FRACP), Surgery
(J Tan FRACS, S Farrell FRACS),
and Pathology
(S Galloway FRACPA),
St Vincents Hospital
Melbourne Fitzroy, Melbourne,
Australia
Correspondence to:
Dr Jasna Aleksova, Department
of Endocrinology and Diabetes,
St Vincents Hospital Melbourne,
Fitzroy, Melbourne, VIC 3065,
Australia
jasnaaleksova@hotmail.com
See Online for appendix
A 60-year-old woman with resistant hypertension,
poorly controlled type 2 diabetes, and chronic obstructive
pulmonary disease requiring inhaled corticosteroids
was referred for investigation of Cushings syndrome.
She had a BMI of 31 kg/m, abdominal obesity, and
proximal muscle wasting. Investigations showed a
normal aldosterone-to-renin ratio, plasma meta-
nephrines, and renal artery Doppler ultrasound
ndings, but increased 24 h urine free cortisol
concentration (454 nmol/L [normal range <350 nmol/L]).
Adrenocorticotropic hormone remained undetectable
on several occasions for 12 months, during the
diagnostic workup (<5 pg/mL). Because of diculty in
ceasing use of inhaled corticosteroids, an overnight
1 mg dexamethasone suppression test was done while
the patient was taking uticasone, showing an 8 am
cortisol concentration of 278 nmol/L (compared with a
normal range of <120 nmol/L). Persistent hyper-
cortisolism was then conrmed with intravenous
dexamethasone suppression testing done after inhaled
uticasone was withheld for several days. An adrenal
CT scan showed an enlarged left adrenal gland, with an
8 mm nodule at the inferior pole (gure A), insucient
to account for the patients hypercortisolism. Functional
imaging with iodocholesterol under dexamethasone
suppression showed bilateral uptake of labelled
cholesterol (gure B). Adrenal vein sampling under
dexamethasone suppression was consistent with
bilateral autonomous cortisol secretion (appendix). The
patient underwent a bilateral adrenalectomy. The
macroscopic and histological appearance was consistent
with primary pigmented nodular adrenal hyperplasia
(also known as primary pigmented nodular adrenal
disease [PPNAD]; gure C, D).
PPNAD is associated with Carneys complex in 90% of
white patients. Carneys complex is an autosomal
dominant multiple neoplasia syndrome, typically pre-
senting with the classic triad of myxomas, spotty skin
pigmentation, and endocrine overactivity. 60% of
Carneys complex in the white population is associated
with germline-inactivating mutations in regulatory
subunit 1 of protein kinase A (PRKAR1A).
To our knowledge, this patient is the oldest reported
person to be diagnosed with PPNADmost patients
are diagnosed before age 40 years. She has no other
manifestations of Carneys complex and is currently
undergoing genetic testing for mutations in the
PRKAR1A gene. This case shows that PPNAD can be
latent for many years and should be considered in
dierential diagnosis of adrenocorticotropic hormone-
independent Cushings syndrome in elderly
individuals.
Contributors
JA searched the literature; collected, analysed, and interpreted data; and
contributed to the writing of the report. GW collected and interpreted
data. KT did the imaging. JT and SF analysed data and did the surgical
procedure. RM and NS collected and interpreted data and contributed to
the writing of the report. SG reviewed the histopathology.
Declaration of interests
We declare no competing interests.

A B C D
x

Figure: Imaging and histopathological ndings

(A) Adrenal CT scan: the arrow shows an 8 mm nodule at the left inferior pole (Hounseeld units <5). (B) Iodocholesterol scan: bilateral uptake of norcholesterol, despite dexamethasone suppression
and non-functioning left adrenal nodule. (C) Macroscopic appearance: bulky adrenals, with multiple pigmented nodules of less than 1 cm. (D) Microscopic appearance: normal cortex (x) and adjacent
pigmented nodule (y), with presence of melanin staining within the cytoplasm of the nodule cells (20 magnication).

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