Introduction
Cushing’s syndrome is a syndrome that manifests with signs and symptoms
of hypercortisolism and usually affects multiple systems. Depending on
the level and duration of exposure to high cortisol levels the
presentation varies with the most commonly observed findings being
obesity, round (moon) facies with acne, high blood pressure, and high
blood sugar with multiple electrolytes derangements [1]. Moreover,
the presentation might differ between men and women, where men can
present at a younger age as compared to females who can present at a
later age with symptoms of gonadal dysfunction such as amenorrhea and
other menstrual abnormalities being more common
[2]. Diagnosis usually is divided into two phases.
The first is to establish the diagnosis which requires a high clinical
suspicion along with confirmatory laboratory studies, such as high
cortisol levels, and in-suppressible cortisol with the administration of
low dose dexamethasone (1 mg). The second phase is to identify the
etiology, which is done by administering high dose dexamethasone (8 mg);
failure to suppress cortisol indicates an ectopic source of ACTH
secretion [3] The treatment choice depends on the underlying
etiology. One of the secondary causes of Cushing’s syndrome is
neuroendocrine tumors of the thymus. These tumors may secrete ACTH
leading to the rapid development of hypercortisolism and ultimately
Cushing’s syndrome [4]. Thymic malignancies are a rare group of
diseases composing around 1% of all malignancies. Of these
malignancies, thymic neuroendocrine tumors comprise 2-5% and are
considered the least common [4]. They inherently
occur more in males with a median age of diagnosis around the 5th decade
of life [5]. These are usually aggressive and malignant with the
potential to metastasize. Hence treatment should be prompt to remove the
thymus gland. The response is variable depending on the prognostic
factors[5]Case presentation:We report A 24 years old Filipina lady, who was recently diagnosed with
hypertension and hypothyroidism and presented to our hospital with
generalized fatigue and weakness that had been going on for three months
before presentation. She had increased abdominal girth along with acne
and occasional difficulty while getting up from chairs or walking. On
examination, she was thinly built with a slightly rounded face
containing numerous acnes. A slight hump on her back was noted. She also
had proximal bilateral weakness mainly in the lower limbs. Her Blood
pressure was found to be 163/67 mmHg. Labs showed her 8 AM cortisol
level to be high (2636nmol/l, Reference range [133-537 nmol/L]) with
a high ACTH (114pg/ml, Reference range [7.2-63.3 pg/ml]). A low dose
dexamethasone suppression. test failed to suppress cortisol with a
reading of (3572nmol/l ), but then high dose dexamethasone suppression
test showed a cortisol level of (2959 nmol/l, Reference range [133-537
nmol/L]), which meant failure to suppress Cortisol suggesting the
cause to be an ectopic source. A chest, abdomen and pelvic CT scan were
done which showed findings of a small thymic neuroendocrine tumorFigure 1.(axial contrast-enhanced CT Study at the level of
mid-thoracic regions shows a small peripherally enhancing solid
abnormality within the thymus (Circle)) )associated with bilateral
adrenal hypertrophy figure 2.(Axial contrast-enhanced CT study
at the level of the upper abdomen shows a smooth enlargement of both
adrenal glands in keeping with hypertrophy ( arrows). This further
confirmed the suspected diagnosis of Cushing’s syndrome secondary to a
thymic neuroendocrine tumor. She underwent surgical excision of the
tumor by right Video-assisted thoracoscopic surgery (VATS) with en-block
excision of the mediastinal mass and total removal of anterior
mediastinal fat. Samples were sent to pathology which was consistent
with a typical carcinoid tumor (ACTH expressing). The tumor expressed CK
AE1/AE3 and Synaptophysin that was confined to the thymus. Following the
surgery, her ACTH dropped to 6.1 pg/m and cortisol to 399 nmol/l, along
with improvement in her symptoms and blood pressure with titration down
on her antihypertensives with no postoperative complications.
Discussion:We present a rare case of Cushing’s syndrome encountered. The initial
presentation was suggestive of an endocrinopathy, which was confirmed by
biochemical tests revealing hypercortisolism secondary to an ectopic
source. CT scan revealed a very small tumor confined to the thymus.
After resecting the tumor, the symptoms and laboratory findings related
to Cushing’s syndrome improved with no postoperative complications.
There is very little evidence in the literature describing the
relationship of Cushing’s syndrome with a thymic Neuroendocrine tumor
[ 6]. Thymic NET’s are usually rare and account for a small
percentage of malignancies, occurring more in males at a the ratio of
3:1 [7].Functional Thymic tumors tend to have a more complicated
course, and rapid onset of the development of clinical symptoms when
associated with an endocrinopathy. Suspicion of such tumors should be
raised and sought when diagnosing an ectopic Cushing’s syndrome. They
are detected by imaging studies, such as CT scan of the chest, FDG PET,
or Dotatate PET CT which are also useful to detect any synchronous
metastasis[8] Surgical excision remains the mainstay of treatment
and prognosis depends on the presence of metastasis and histopathologic
parameters such as mitotic activity[8]
Conclusion: While investigating the causes of Cushing’s syndrome, ectopic sources
should always be considered
There is limited data available on the association between Cushing’s
syndrome and thymic neuroendocrine tumors currently. Thymic
neuroendocrine tumors are considered malignant, and the mainstay of
treatment is surgical excision. Prognosis depends on several factors
most crucial being that of early diagnosis and absence of distant
metastasis.
Author’s contribution:Ahmad S matarneh: manuscript write up, Data collection and clinical
care.
Adbelrahman O hamad: clinical care, study planning and design
Mohammad Khair: clinical care
Elhadi ouzi: clinical care
Mousa S Hussein: Clinical care.
Nabil sherif mahmood: clinical care
Mohammad yassin: Mentor
Conflict of interest:None declared.Ethical approval: approved by Hamad medical corporation, MRC number MRC-04-20-451
Acknowledgments: We thank the internal medicine department at Hamad Medical Corporation
for giving us the chance and support to conduct this
work.Funding information:Qatar national library