adrenal cushing`s syndrome in a female patient with ovarian cancer

Archives of the Balkan Medical Union
Copyright © 2016 CELSIUS
vol. 51, no. 3, pp. 410-412
September 2016
CASE REPORT
ADRENAL CUSHING’S SYNDROME IN A FEMALE
PATIENT WITH OVARIAN CANCER
DAN NICOLAE PÃDURARU1, SIMONA ELENA ALBU1, MARA CARSOTE2*, ANA VALEA3
1
Carol Davila University of Medicine and Pharmacy, University Emergency Hospital, Bucharest, Romania
Carol Davila University of Medicine and Pharmacy, C.I. Parhon National Institute of Endocrinology, Bucharest,
Romania
3
Iuliu Hatieganu University of Medicine and Pharmacy, Clinical County Hospital, Cluj-Napoca, Romania
2
S UMMARY
Introduction: Cushing's syndrome (CS) is an important cause
of secondary osteoporosis. Association of ovarian cancer and
surgically induced menopause leads to further bone loss.
Case report: A 59-year old female patient, known with left breast
fibroadenoma, ovarian adeno-carcinoma, and early surgical
menopause consequence of bilateral oophorectomy, was admitted
for CS features including lumbar pain, muscle weakness, etc.
Hormonal specific tests and abdominal computed tomography
scan confirmed CS related to a left adrenal adenoma. Secondary
osteoporosis was highlighted at Dual-Energy X-Ray Absorptiometry (DXA) without anomalies at whole body bone scintigraphy
and profile X-ray. Vitamin D deficiency without secondary hyperparathyroidism and normal thyroid function tests were founded.
Laparoscopic left adrenalectomy was performed and weekly oral
alendronic acid together with daily vitamin D and calcium
supplements were offered to the patient. Close endocrine,
oncologic and imagery check-up is recommended.
Conclusion: Surgical menopause for ovarian cancer in association
with anti-estrogen therapy in young females is a contributor to
later diagnosis of osteoporosis. A second tumor, though benign,
may accelerate the bone loss due to endocrine anomalies as
adrenal tumor related hypercorticism. The CS confirmation of a
patient with ovarian cancer may indicate an ectopic source of
ACTH which was not the case here.
Abbreviations: mg = milligram, cm = centimeter, ACTH =
Adrenocorticotropic Hormone, BMD = bone mineral density,
CS = Cushing’s syndrome, DXM = dexamethasone, FT4 =
Free Thyroxine, iPTH = intact Parathormone
Key words: ovarian cancer, menopause, osteoporosis, Cushing’s
syndrome
Correspondence address:
R ÉSUMÉ
Le syndrome de Cushing surrénal chez une femme avec un
cancer de l'ovaire
Introduction: Le syndrome de Cushing (CS) est une cause
importante d'ostéoporose secondaire. L’association entre le cancer
de l'ovaire et la ménopause induite chirurgicalement conduit à
une perte osseuse.
Présentation de cas: Une femme âgée de 59 ans, connue avec un
fibroadénome du sein gauche, adéno-carcinome ovarien et une
ménopause précoce suite à une ovariectomie bilatérale a été
admise pour des caractéristiques du syndrome de Cushing, y
compris la douleur lombaire, la faiblesse musculaire, etc. Les tests
spécifiques hormonaux et la tomographie computérisée ont
confirmé le syndrome de Cushing lié à un adénome surrénalien
gauche. L'ostéoporose secondaire a été mise en évidence à
l’absorptiométrie (DEXA) sans anomalies dans tout le corps à la
scintigraphie osseuse et le profil X-ray. La carence en vitamine D
sans hyper-parathyroïdie secondaire et les tests de la fonction
thyroïdienne normale ont été trouvés. On a effectué la surrénalectomie laparoscopique gauche et on a offert au patient de
l'acide alendronique à voie orale hebdomadairement avec de la
vitamine D et des suppléments de calcium. On recommande un
suivi endocrinien étroit, oncologique et imagistique.
Conclusion: La ménopause chirurgicale pour le cancer de l'ovaire
en association avec un traitement anti-œstrogénique chez les
femmes jeunes contribue plus tard au diagnostic de l'ostéoporose.
Un seconde tumeur, bien que bénigne, peut accélérer la perte
osseuse due aux anomalies endocriniennes comme la tumeur
surrénalienne liée à l’hypercorticisme. La confirmation du SC chez
une patiente avec cancer de l'ovaire peut indiquer une source
ectopique d'ACTH, ce qui n'est pas ici le cas.
Mots clefs: cancer, ménopause, ostéoporose, syndrome de
Cushing ovarien
Mara Carsote, MD
Carol Davila University of Medicine and Pharmacy & C.I. Parhon National Institute of Endocrinology
Aviatorilor Ave 34-38, Bucharest, Romania
e-mail: [email protected]
Archives of the Balkan Medical Union
I NTRODUCTION
enopausal osteoporosis may have a dual
etiology, for instance, secondary causes as
hypercorticism or non-metastatic cancer
related bone loss may be found in association with primary
form due to estrogen lack. (1,2) Anti-cancer management
for different gynecological malignancies may interfere with
bone status and increases the speed of bone mineral density
(BMD) deterioration. (3) Ovarian cancer is associated with
indication of surgical menopause in pre-menopausal women,
pelvic radiotherapy and these may elevate the osteoporosis
risk. (3,4,5) Osteoporosis in such circumstances needs to be
assessed from a multi-factorial point of view. (6,7) We aim to
introduce the case of a woman with treated ovarian cancer
and adrenal Cushing syndrome (CS) as supplementary
causes of osteoporosis. This is a case report type of
manuscript. The informed consent was signed by the subject
who agreed to use the scan below.
M
C ASE
REPORT
Medical history – ovarian cancer
This is a 60-year old non-smoking female, known with
multiple co-morbidities including surgery for left breast
fibroadenoma at the age of 36 years, ovarian carcinoma
followed by surgical menopause at age of 41 years. The
oncologic condition was followed for the next years and
considered remitted. Consecutively, she was offered vitamin D and calcium supplements which she intermittently
took. She also had high blood pressure and dyslipidemia.
The medical family history includes: a sister with breast
cancer and brother with high blood pressure.
CS diagnosis
At age of 58 years, she was admitted to an endocrine
check-up for asthenia, proximal muscle weakness, mood and
sleep disturbances, weight gain and persistent lumbar pain,
moon face, red striae. She had a body mass index of 33 kg/m2,
Figure 1 - Lumbar DXA report on a 58year old female with adrenal Cushing’s
syndrome, surgical menopause at age
of 41 years in the context of ovarian
cancer management
September 2016, 411
blood pressure of 150/85 mmHg, heart beat rate of 76 per
minute. Laboratory test showed high morning baseline
plasma cortisol with loss of circadian rhythm, and
suppressed ACTH (Adrenocorticotropic Hormone) levels.
Non suppression at 2 days of 2 mg (milligram) Dexamethasone (DXM) test confirmed CS. (table 1) Inadequate suppression at 2 days of 8 mg DXM test pointed an adrenal
source. (table 1) Abdominal computed tomography scan
showed a left adrenal tumor of 2.9 cm as cause of adrenal
CS. Left laparoscopic adrenalectomy was performed within
five months without any complications. An adrenocortical
adenoma was confirmed at pathological report. Postoperatively replacement glucocorticoid therapy was given for a
period of four months for preventing adrenal insufficiency.
Osteoporosis management
Bone profile included vitamin D deficiency with normal
parathormone levels. (table 1) Central DXA (DualEnergy X-Ray Absorptiometry) assays confirmed osteoporosis. No thyroid cause of bone loss was revealed since
thyroid function was normal. Whole body bone scintigram
and profile X-Ray were negative for anomalies. Ovarian
tumor marker CA 125 was in the normal reference range
(of 24.6 U/mL, normal above 35 U/mL) confirming
ovarian cancer remission. Therapy with weekly oral
alendronate was recommended together with daily vitamin
D and calcium supplements. The patient was further
followed-up by a multidisciplinary team including
endocrine, oncologic, and gynecologic surveillance.
Within the first two years after adrenal surgery, a good
outcome was registered.
D ISCUSSION
The particular aspects of this case are: the challenging of
confirming the etiology of osteoporosis in a patient with
multiple potential causes; the rarity of adrenal CS in
menopause on cancer survival patient; the association with
vitamin D deficiency, and the asynchronous diagnosis of
ovarian adenocarcinoma, breast fibroadenoma and adreno-
ADRENAL CUSHING’S SYNDROME IN A FEMALE PATIENT WITH OVARIAN CANCER - PÃDURARU et al
vol. 51, no. 3, 412
Table 1 - Biochemical and hormonal profile of a 58-year ovarian cancer survival female with adrenal Cushing’s syndrome
Parameter
plasma cortisol (6 a.m.)
plasma cortisol (11 p.m.)
plasma morning ACTH
plasma morning cortisol*
plasma morning cortisol**
iPTH
25-OHD
TSH
FT4
FSH
Total serum calcium
Ionic serum calcium
serum sodium
serum potassium
Total cholesterol
Triglycerides
Patient’s value
800
523
6.08
638
532
58.6
24.2
1.86
17.2
85.2
9.1
1.08
139
3.6
254
165
Normal Limits
172-497
71.1-286
<46
<50
#
15-66
30-100
0.4-4
10.6-22.7
25.8-134-8
8.8-12.2
1.06-1.2
136-145
3.7-5.4
<200
<150
Units
nmol/L
nmol/L
pg/mL
nmol/L
nmol/L
pg/mL
ng/mL
μUI/mL
pmol/L
mUI/mL
mg/mL
mmol/L
mmol/L
mmo/L
mg/dL
mg/dL
*after DXM 2 day 2 mg suppression test; ** after DXM 2 day 8 mg suppression test; # <50% of baseline plasma morning cortisol reduction
is consistent with the diagnosis of Cushing’s syndrome; ACTH = Adrenocorticotropic Hormone; PTH = parathormone;
25-OHD = 25 hydroxyvitamin D; TSH = Thyroid Stimulating Hormone; FT4 = Free Levothyroxine; FSH = Follicle Stimulant Hormone
cortical adenoma. In this particular case, the osteoporosis
was caused by estrogen lack considering an early surgical
menopause at age of 41 which was indicated for ovarian
cancer. (8,9) However, knowing prior diagnosis, bone metastasis needed to be ruled out so a whole body bone scintigram
was done and found negative. (8,9) Another element
is glucocorticoid osteoporosis. (1) Non-ectopic CS is exceptionally correlated with ovarian cancer, probably on
common genetic background also this remained unknown
in our case (the patient had a sister diagnosed with another
gynecological cancer). (10) Obviously, co-incidental finding
must be taken into consideration. Actually, CS was a
differential diagnosis in this female case, part from an oncologic basis, but due to multiple cardio-metabolic risk factors
as high blood pressure, high total cholesterol and triglycerides, and obesity as well as their association with osteoporosis. (1) Generally, CS rate is of 1% among subjects with
arterial hypertension and 5% among those with osteoporosis. (11) The woman we introduced had hypovitaminosis
D which may be related to her endocrine and oncologic
records but a general high prevalence is registered in
menopause, including for Romanian area. (12)
C ONCLUSION
Surgical menopause for ovarian cancer in association
with anti-estrogen therapy in young females is a contributor
to later diagnosis of osteoporosis. A second tumor, though
benign, may accelerate the bone loss due to endocrine
anomalies as adrenal tumor related hypercorticism. The CS
confirmation of a patient with ovarian cancer may indicate
an ectopic source of ACTH which was not the case here.
Acknowledgement
We thank each member of the medical team and the
patient.
Conflict of interest: nothing to declare
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