Kaohsiung Journal of Medical Sciences (2018) 34, 705e706
Available online at www.sciencedirect.com
ScienceDirect
journal homepage: http://www.kjms-online.com
Letter to the Editor
The coexistence of Cushing syndrome and
gynecomastia as the manifestations of
adrenocortical carcinoma
Dear editor,
A 43-year-old man presented with gynecomastia for 4
months. He also complained about loss of libido and 3-kg
weight gain. Bilateral gynecomastia with testicular atro-
phy was noted as well as his Cushingoid appearance on
the physical exam. Computed tomography scan showed a
huge heterogeneous hypoechoic left suprarenal mass
(Fig. 1A) corresponding to the palpable abdominal mass.
Multiple metastatic lung nodules were also detected
(Fig. 1B). The diagnosis of feminizing adrenocortical
carcinoma (ACC) with Cushing syndrome was proposed by
elevated UFC (606.02 mg/24 h, 21e143) with low ACTH
level, and hyperestrogenemia (1221 pmol/L, 0e130). Left
adrenalectomy, nephrectomy with splenectomy and IVC
thrombectomy were performed. The pathological study
showed a tumor size of 12  13  15 cm with extensive
necrosis and capsular invasion, Ki-67 was 10% positive.
Postoperatively, mitotane was commenced to control
his advanced tumor. His gynecomastia subsequently
regressed as well as his estradiol levels decreased. Un-
fortunately, he died six months later due to the uncon-
trolled infection.
Gynecomastia, an enlargement of male breast, is a
common disorder in clinical practice. It represents a femi-
nizing condition due to either absolute or relative estrogen
excess. Causes of hyperestrogenemia include exogenous
administration and endogenous overproduction from
secreting tumors or increased peripheral aromatization;
whereas relative estrogen excess refers to a decrease in
androgen levels or its actions. An initial step in making the
diagnosis is to differentiate from lipomastia and breast
cancer. True gynecomastia is characterized by a rubbery
mass concentric within the nipple-areolar complex [1].
Conflicts of interest: All authors declare no conflicts of
interests.
https://doi.org/10.1016/j.kjms.2018.06.004
1607-551X/Copyright ª 2018, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Most cases have a benign etiology from physiologic changes
or medications; however, few cases can be a result of un-
derlying endocrine disorders or tumors. Feminizing tumors
can be categorized into estrogen-producing testicular or
adrenal tumors and hCG-producing testicular or non-
testicular tumors. Several possible causes can be uncov-
ered with an extensive history and physical examination:
onset/duration, tenderness, medications, family history of
gynecomastia or neurological diseases, systemic diseases
(liver or renal failure), and endocrine disorders (hyper-
estrogenemia, hypogonadism, thyrotoxicosis). Initial in-
vestigations should include a liver/renal function, hormonal
profiles (testosterone, estradiol, LH, TSH, prolactin) and
tumor markers (hCG, a-fetoprotein); nonetheless, about
one-fourth would be classified as idiopathic.
ACC is a rare tumor with dismal prognosis. Adjacent
organ invasion or metastasis is crucial to distinguish from
the benign lesions. Larger size (>4 cm), sex hormone
excess (virilization/feminization), high mitotic figures or
capsular/vascular invasion are also characteristics of
ACC [2]. Nearly 60% of ACC is functional, predominantly
with a cortisol excess, a whereas feminizing tumor is
found in only 2e6% [2,3]. Hyperestrogenemia in ACC has
been attributed to an increased tumoral aromatase ac-
tivity. Another possible mechanism is the peripheral
conversion of weaker androgens from the tumor [4].
Feminizing tumor is manifested mainly by symptoms of
hyperestrogenism (e.g. gynecomastia, testicular atro-
phy, and erectile dysfunction), mass symptoms or dete-
rioration of the general conditions (fatigue, weight loss).
As described in our patient, multiple hormonal secretions
represent its de-differentiated tumorigenesis and ste-
roidogenic dysregulations. Therefore, complete hor-
monal evaluation is requisite in ACC patients even if
clinical symptoms are absent to prevent adrenal insuffi-
ciency postoperatively and provide as a marker of tumor
706
Figure 1. (A) Computed tomography scan showed a huge
heterogeneous hypoechoic left suprarenal mass, (B) multiple
metastatic lung nodules were demonstrated.
recurrence [5]. Complete surgical removal is the only
curative treatment. Mitotane and chemotherapy are
adjunctive modalities to control an advanced disease.
In conclusion, gynecomastia is common and self-limited
but few cases can be from a malignant cause. Further
investigation is required when it occurs in an unusual age
group or is progressive.
Appendix A. Supplementary data
Supplementary data related to this article can be found at
https://doi.org/10.1016/j.kjms.2018.06.004.
Letter to the Editor
References
[1] Narula H, Carlson HE. Gynaecomastia-pathophysiology, diag-
nosis and treatment. Nat Rev Endocrinol 2014;10:684e98.
[2] Kidd MT, Karlin NJ, Cook CB. Feminizing adrenal neoplasms:
case presentations and review of the literature. J Clin Oncol
2011;29:e127e30.
[3] Else T, Kim AC, Sabolch A, Raymond VM, Kandathil A, Caoili EM,
et al. Adrenocortical carcinoma. Endocr Rev 2014;35:282e326.
[4] Hatano M, Takenaka Y, Inoue I, Homma K, Hasegawa T,
Sasano H, et al. Feminizing adrenocortical carcinoma with
distinct histopathological findings. Intern Med 2016;55:
3301e7.
[5] Fassnacht M, Kroiss M, Allolio B. Update in adrenocortical
carcinoma 2013;98:4551e64.
Mongkontida Umphonsathien
Endocrinology Unit, Department of Medicine, Police
General Hospital, Bangkok, Thailand
Division of Endocrinology and Metabolism, Department of
Medicine, Faculty of Medicine, Chulalongkorn University,
Bangkok, Thailand
Panudda Srichomkwun
Division of Endocrinology and Metabolism, Department of
Medicine, Faculty of Medicine, Chulalongkorn University,
Bangkok, Thailand
Excellence Center in Diabetes, Hormones and Metabolism,
King Chulalongkorn Memorial Hospital, Bangkok, Thailand
Patinut Buranasupkajorn
Division of Endocrinology and Metabolism, Department of
Medicine, Faculty of Medicine, Chulalongkorn University,
Bangkok, Thailand
Excellence Center in Diabetes, Hormones and Metabolism,
King Chulalongkorn Memorial Hospital, Bangkok, Thailand
Division of Hospital and Ambulatory Medicine, Department
of Medicine, Faculty of Medicine, Chulalongkorn
University, Bangkok, Thailand
Thiti Snabboon*
Division of Endocrinology and Metabolism, Department of
Medicine, Faculty of Medicine, Chulalongkorn University,
Bangkok, Thailand
Excellence Center in Diabetes, Hormones and Metabolism,
King Chulalongkorn Memorial Hospital, Bangkok, Thailand
*Corresponding author. Excellence Center in Diabetes and
Metabolism, BhumiSirimangalanusorn Bldg, 4C fl., King
Chulalongkorn Memorial Hospital, Rama IV Road, Patum-
wan, Bangkok, 10330, Thailand.
E-mail address: Thiti.S@chula.ac.th
27 March 2018