Vol 75, No 1 (2024)
Clinical vignette
Published online: 2023-12-23

open access

Page views 545
Article views/downloads 218
Get Citation

Connect on Social Media

Connect on Social Media

Ectopic ACTH syndrome in the course of ACTH-secreting pancreatic neuroendocrine tumour in a patient with a pituitary lesion — diagnostic challenges and individual approach

Joanna Sobolewska1, Łukasz Działach1, Wioleta Respondek2, Agnieszka Wojciechowska-Luźniak1, Przemysław Witek1
Pubmed: 38497399
Endokrynol Pol 2024;75(1):113-114.

Abstract

Not required for Clinical Vignette

Clinical vignette

Endokrynologia Polska

DOI: 10.5603/ep.97357

ISSN 0423–104X, e-ISSN 2299–8306

Volume/Tom 75; Number/Numer 1/2024

Submitted: 10.09.2023

Accepted: 14.10.2023

Early publication date: 23.12.2023

Ectopic ACTH syndrome in the course of ACTH-secreting pancreatic neuroendocrine tumour in a patient with a pituitary lesion — diagnostic challenges and individual approach

Joanna Sobolewska1Łukasz Działach1Wioleta Respondek2Agnieszka Wojciechowska-Luźniak1Przemysław Witek1
1Department of Internal Medicine, Endocrinology, and Diabetes, Medical University of Warsaw, Warsaw, Poland
2Department of Internal Medicine, Endocrinology, and Diabetes, Mazovian Brodnowski Hospital, Warsaw, Poland

Joanna Sobolewska, MD, Department of Internal Medicine, Endocrinology, and Diabetes, Medical University of Warsaw, Warsaw, Poland, tel. +48 22 326 57 27, fax: +48 22 326 55 30; e-mail: joanna.sobolewska@wum.edu.pl

This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially

Key words: pancreatic neuroendocrine tumours; ectopic adrenocorticotropin syndrome

Ectopic adrenocorticotropin (ACTH) syndrome (EAS) is a severe endocrine disorder resulting from the nonregulated expression and secretion of ACTH by neuroendocrine tumours (NETs) of varying localization, aggressiveness, and degree of histological differentiation [1]. Pancreatic NETs (PanNETs) represent approximately 4% of all NETs, account for around 1–2% of all pancreatic tumours [2], and comprise up to 15% of all EAS cases [1]. Although non-functional PanNETs occur in most cases (60–90%), functional PanNETs (F-PanNETs) [2], usually create diagnostic and therapeutic challenges [3]. Because the management of patients with EAS demands efficient diagnostics and treatment of hypercortisolaemia, NET, and its complications, it may require an individualized patient approach [1].

A 58-year-old female with arterial hypertension and type 2 diabetes was admitted to the Endocrinology Department due to abdominal pain, muscle weakness, and unintentional weight gain. The hormonal evaluation confirmed ACTH-dependent hypercortisolaemia morning serum cortisol: 29.7 μg/dL, midnight serum cortisol: 30.9 μg/dL, ACTH: 87.6 pg/mL, mean urinary free cortisol (mUFC): 388.5 μg/24 h, serum cortisol after 1 mg of dexamethasone: 22.7 μg/dL. Both the corticotropin-releasing hormone (CRH) stimulation test and the high-dose dexamethasone suppression test results were negative, while the combined dexamethasone-desmopressin test result was positive. Magnetic resonance imaging (MRI) revealed an 8 × 5 mm pituitary lesion infiltrating the right cavernous sinus (Fig. 1). Considering the inconclusive results, chest and abdomen diagnostic imaging was undertaken, but no significant abnormalities were detected. Inferior petrosal sinus sampling was performed twice, with inconclusive results. Exploration of the sella turcica was performed; however, it was beyond resectability. Because of persistent disease, the pharmacological treatment of hypercortisolaemia was introduced.

Sobolewska-1.png
Figure 1. Frontal magnetic resonance imaging (MRI) of the pituitary gland

The patient remained in follow-up for almost 10 years, and during this time received various medications (pasireotide s.c., ketoconazole, cabergoline); the features of ACTH-dependent hypercortisolaemia persisted despite pharmacotherapy. Eventually, in 2022, a focal lesion 15 × 14 mm in the pancreatic tail was visualized on a whole-body computed tomography (CT) scan (Fig. 2). Single photon emission computed tomography (SPECT-CT) somatostatin-receptor scintigraphy and Gallium-68 dotatate positron emission tomography/CT (Ga-68-HA-DOTATATE-PET-CT) did not reveal increased tracer accumulation and proliferative process features with high expression of somatostatin receptors. 18F-fluorodeoxyglucose PET/CT (18F-FDG-PET-CT) showed no proliferative hypermetabolic changes. The patient underwent endoscopic ultrasound with tumour biopsy, and histological examination identified neuroendocrine cells with positive ACTH, CD56, and chromogranin staining. The patient did not consent to surgery, and treatment with Lanreotide Autogel was introduced, resulting in normalization of hypercortisolaemia. The dimensions of the pancreatic lesion remained stable. After obtaining the patient’s consent, one year later, a tail resection of the pancreas was performed, obtaining complete normalization of the pituitary-adrenal axis. Since the procedure, the patient has undergone scheduled hormonal assessments and remains in good general condition. The hormonal parameters are summarized in Table 1. An MRI excluded the lesion recurrence.

Sobolewska-2.png
Figure 2. Computed tomography (CT) scan presenting a focal lesion in the pancreatic tail
Table 1. Summarize of hormonal parameters during treatment

Parameter

Baseline results

During ketoconazole treatment

During cabergoline treatment

During Lanreotide Autogel treatment

After the pancreatomy

Reference range

Morning serum cortisol [μg/dL]

29.7

34.4

11.0

9.1

14.3

3.7–19.4

Midnight serum cortisol [μg/dL]

30.9

17.9

10.9

4.4

2.3

< 5.4

ACTH [pg/mL]

87.6

75.1

22.6

19.9

32.7

6–48

mUFC [μg/24 h]

388.5

549.8

185.0

87.40

26.0

4.3–176

The clinical case follow-up and diagnostics of ACTH-dependent Cushing’s syndrome (CS) may last several years. The use of more than one dynamic test, combined with imaging examinations, improves the accuracy of diagnostics and, in most cases, enables successful differentiation of pituitary tumours from NETs secreting ectopic ACTH [4]. However, the high receptor expression of well-differentiated NETs, differences in the NET type, the patient’s age and gender, and concomitant non-functional pituitary lesion, as well as the severity of hypercortisolaemia, could affect the results and make the diagnostic process of CS even more challenging [4]. Well-differentiated NETs may share molecular similarities with corticotrophic pituitary adenomas, clarifying the overlap in biochemical test responses [1]. The desmopressin test, in which the absence of ACTH and cortisol response is a characteristic of EAS, appears to be limited [1]; however, the test has approximately 83% sensitivity in indicating Cushing disease (CD) and 68% specificity in indicating EAS [5]. Indeed, as in the case of the described patient, the false-positive result for CD was probably due to the expression of the vasopressin V3 receptor by the PanNET.

The described case emphasizes that extensive diagnostics, as well as an individual patient approach, are crucial in the management of CS.

Conflict of interest

Authors declare no conflict of interest.

References

  1. Young J, Haissaguerre M, Viera-Pinto O, et al. Management of endocrine disease: Cushing’s syndrome due to ectopic ACTH secretion: an expert operational opinion. Eur J Endocrinol. 2020; 182(4): R29–R58, doi: 10.1530/EJE-19-0877, indexed in Pubmed: 31999619.
  2. Kos-Kudła B, Rosiek V, Borowska M, et al. Pancreatic neuroendocrine neoplasms - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne trzustki - uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polską Sieć Guzów Neuroendokrynych)]. Endokrynol Pol. 2022; 73(3): 491–548, doi: 10.5603/EP.a2022.0050, indexed in Pubmed: 36059173.
  3. Li YL, Cheng ZX, Yu FH, et al. Advances in medical treatment for pancreatic neuroendocrine neoplasms. World J Gastroenterol. 2022; 28(20): 2163–2175, doi: 10.3748/wjg.v28.i20.2163, indexed in Pubmed: 35721885.
  4. Fleseriu M, Auchus R, Bancos I, et al. Consensus on diagnosis and management of Cushing’s disease: a guideline update. Lancet Diabetes Endocrinol. 2021; 9(12): 847–875, doi: 10.1016/S2213-8587(21)00235-7, indexed in Pubmed: 34687601.
  5. Ceccato F, Barbot M, Mondin A, et al. Dynamic Testing for Differential Diagnosis of ACTH-Dependent Cushing Syndrome: A Systematic Review and Meta-analysis. J Clin Endocrinol Metab. 2023; 108(5): e178–e188, doi: 10.1210/clinem/dgac686, indexed in Pubmed: 36453141.