CLINICAL IMAGE

Complete remission of hypercortisolemia

in a patient with severe ectopic Cushing
syndrome caused by small-cell lung cancer
Aleksandra Gamrat1*, Ewelina Rzepka1*, Karol Ciszek1, Piotr J. Wysocki2 ,
Alicja Hubalewska­‑Dydejczyk1, Aleksandra Gilis­‑Januszewska1
1 Department of Endocrinology, Jagiellonian University Medical College, Kraków, Poland
2 Department of Oncology, University Hospital, Kraków, Poland

Ectopic Cushing syndrome (ECS) accounts cortisol (UFC) values (Figure 1C and 1D). Shortly af‑
for 10%–20% of all CS cases. The second most ter decreasing the dose of osilodrostat to 1 mg
common cause of ECS is small-cell lung cancer per day, dexamethasone was introduced due to
(SCLC).1,2 However, recent reports indicate that immunotherapy­‑related autoimmune hepatitis
CS in the course of SCLC might be underestimat‑ (Figure 1C and 1D). During treatment, apart from
ed as hypercortisolemia and often remains undi‑ biochemical improvement (based on UFC level
agnosed.2,3 ECS in SCLC is often associated with [Figure 1C] and normal circadian cortisol rhythm
severe hypercortisolemia and poor prognosis.3 with midnight cortisol levels of 3.32 µg/dl), im‑
We report for the first time a case of complete aging showed a partial response of SCLC (regres‑
remission of hypercortisolemia in ECS caused sion of the tumor mass on control CT [Figure 1E]).
by SCLC. Furthermore, a significant clinical improvement
A 65­‑year­‑old man was admitted to a hospi‑ was noted, manifested as regression of peripher‑
tal due to hypertension (220/120 mm Hg), lower al edema, plethora, and moon face, better control
limb edema, and severe hypokalemia (2.16 mmol/l; of hypertension and hypokalemia, and reduction
reference range [RR], 3.5–5.1 mmol/l), lasting for of potassium supplementation and antihyperten‑
about a month. Physical examination showed sub‑ sive drugs. According to the Response Evaluation
tle body changes, such as moon face, redistribu‑ Criteria In Solid Tumors 1.1 guidelines,4 partial re‑
tion of fat tissue, and plethora. Hormonal assess‑ sponse was observed. After treatment, the main
ment suggested ECS—no inhibition in the low-
and high­‑dose dexamethasone test, high adre‑
a
nocorticotropic hormone levels (222 pg/ml; RR,
6–56 pg/ml). Computed tomography (CT) showed
2 polycyclic lesions in the inferior lobe of the left
lung and metastatic mediastinal and abdominal
lymph nodes (Figure 1A). Histopathologic exam‑
Correspondence to: ination of the bronchoscopic biopsy specimen
Aleksandra Gilis­‑Januszewska, MD,
PhD, Department of Endocrinology,
showed SCLC. Treatment with metyrapone was
Jagiellonian University Medical implemented with an increasing dose of up to
College, ul. Jakubowskiego 2, 3250 mg per day. In the sixth week of hypercor‑
52
mm

30-688 Kraków, Poland, tisolemia treatment, a palliative chemoimmuno‑

phone: +48 12 400 23 00,
email: myjanusz@cyf­‑kr.edu.pl
therapy with a carboplatin, etoposide, and atezoli‑
Received: April 9, 2024. zumab combination was initiated, followed by pro‑
Revision accepted: May 28, 2024. phylactic cranial radiotherapy. The chemoimmu‑
Published online: May 29, 2024.
Pol Arch Intern Med. 2024;
notherapy regimen underwent only minor chang‑
134 (7-8): 16768 es during the treatment period (Figure 1B). After 2
doi:10.20452/pamw.16768 months of treatment (following the second cy‑ Figure 1 A – pretreatment chest computed
Copyright by the Author(s), 2024
cle of chemoimmunotherapy), metyrapone was tomography scan showing polycyclic expanding masses
*AG and ER contributed equally to changed to osilodrostat with a starting dose of of small-cell lung cancer in the lower lobe of the left lung
this work. 4 mg per day, later titrated based on urine free (arrow)

CLINICAL IMAGE Remission of hypercortisolemia in ectopic Cushing syndrome 1

 Osilodrostat, mg Dexamethasone, 1 mg

B 1400 2.5

1200

Chemoimmunotherapy dosage, mg
2

Dexamethasone, mg
1000
1.5
800

600 1

400
0.5
200

0 0

Atezolizumab, mg Etoposide, mg
Carboplatin, mg Dexamethasone, mg

C 300 45

40
250
35

UUFC concentration, µg/24h

ACTH concentration, pg/ml

200 30

25
150
20

100 15

10
50
5

0 0

ACTH concentration, pg/ml Dexamethasone, 2 mg

UFC, µg/24h Dexamethasone, 1 mg

D 3500 6

3000 5

2500
4
Osilodrostat, mg
Metopirone, mg

2000
3
1500
2
1000

500 1

0 0

Metopirone, mg Dexamethasone, 2 mg
Osilodrostat, mg Dexamethasone, 1 mg

Figure 1 B – chart illustrating changes in chemoimmunotherapy and dexamethasone dosage during treatment; 2.5C – chart
1400
illustrating changes in urine free cortisol (UFC) and adrenocorticotropic hormone (ACTH) levels during treatment. It shows
1200 the patient received dexamethasone as part of oncological treatment. D – chart illustrating changes in
periods in which
notherapy dosage, mg

2
metopirone and osilodrostat dosage during the treatment. It shows periods in which the patient received dexamethasone
xamethasone, mg

1000
as part of oncological treatment.
1.5
2 800 OF INTERNAL MEDICINE
POLISH ARCHIVES 2024; 134 (7-8)

600 1
 4 Eisenhauer EA, Therasse P, Bogaerts J et al. New response evaluation
E criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Can-
cer. 2009; 45: 228-247. 
5 Dormoy A, Haissaguerre M, Vitellius G, et al. Efficacy and safety of osilo-
drostat in paraneoplastic Cushing syndrome: a real­‑world multicenter study
in France. J Clin Endocrinol Metab. 2023; 108: 1475-1487. 
6 Gilis­‑Januszewska A, Bogusławska A, Rzepka E, et al. Individualized
medical treatment options in Cushing disease. Front Endocrinol (Lausanne).
2022; 13: 106-133. 

15
mm
Figure 1 E – chest computed tomography scan made
during the treatment, showing regression of the lesions in
the lower lobe of the left lung

tumor decreased from 52 mm to 16 mm. Due to

the complete remission of CS (morning cortisol
levels at 6 AM, 77 µg/dl), the osilodrostat treat‑
ment was discontinued after 13 months. Adre‑
nal insufficiency was excluded, as the stimula‑
tion test with 1 μg of tetracosactide yielded nor‑
mal cortisol output. Control biochemical tests per‑
formed 1 month after osilodrostat discontinuation
showed eucortisolemia. Recently, the patient has
received the 27th cycle of maintenance immuno‑
therapy. Nearly 2 years after the diagnosis, he re‑
mains clinically stable with no symptoms of CS.
Our case shows that immediate and effective
treatment of life­‑threatening hypercortisolemia,
leading to a diagnosis and rapid initiation of che‑
moimmunotherapy, improves prognosis and may
result in long­‑term remission. It also confirms
that osilodrostat is an effective and easy­‑to­‑titrate
drug in treating hypercortisolemia in ECS.5,6

Supplementary material
Supplementary material is available at www.mp.pl/paim.

Article information
Acknowledgments None.
Funding None.
Conflict of interest None declared.
Open access This is an Open Access article distributed under the terms
of the Creative Commons Attribution 4.0 International License (CC BY 4.0),
allowing anyone to copy and redistribute the material in any medium or for-
mat and to remix, transform, and build upon the material, including commer-
cial purposes, provided the original work is properly cited.
How to cite Gamrat A, Rzepka E, Ciszek K, et al. Complete remis-
sion of hypercortisolemia in a patient with severe ectopic Cushing syn-
drome caused by small-cell lung cancer. Pol Arch Intern Med. 2024; 134:
16768. doi:10.20452/pamw.16768

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CLINICAL IMAGE Remission of hypercortisolemia in ectopic Cushing syndrome 3