Comparative Analysis of Clinical, Hormonal and Morphological Studies in Patients with Neuroendocrine ACTH-Producing Tumours

Abstract

This paper highlights the problem of neuroendocrine tumours (NETs) with clinical symptoms of hypercorticism caused by hypersecretion of adrenocorticotropic hormone (ACTH) by tumour cells. In most cases (85%), the tumours were localized in the pituitary gland (Cushing's disease); 15% of the patients had an extrapituitary tumour that manifest as an ectopic ACTH secretion (EAS). Comparative analysis of clinical, hormonal, histological, and immunohistochemical characteristics of pituitary and extrapituitary ACTH-secreting NET was performed. It included 46 patients with CD and 38 ones exhibiting ectopic ACTH secretion (EAS). Results of the study suggest differences between CD and EAS in terms of the severity of clinical manifestations and duration of the disease. Hormonal studies showed that EAS unlike CD was associated with high plasma ACTH and cortisol levels, late-evening salivary cortisol and daily urinary free cortisol, the absence of a 60% or greater reduction of cortisol in the HDDST test, and the presence of a low (less than 2) ACTH gradient in response to desmopressin administration with catheterization of cavernous sinuses. The study of morphofunctional characteristics of the removed NET demonstrated the ability of both pituitary and extrapituitary NETs to express ACTH as well as GH, PRL, LH, and FSH. The angiogenic markers (CD31 and VEGF) were detected with equal frequency regardless of the NET localization. The histological structure of all corticotropinomas suggested their benign origin, but extrapituitary NETs were represented by different morphological types with varying malignancy, invasiveness, and metastatic properties. A higher cell proliferation potential (Ki-67) was documented for NET in patients presenting with an ectopic ACTH secretion compared to those having corticotropinomas.

Primary intracranial neuroendocrine tumor with ectopic adrenocorticotropic hormone syndrome: A rare and complicated case report and literature review

“…ii) Ectopic tumors may secrete ACTH or an ACTH analogue and a simple anti-ACTH antibody is insufficient for detecting ectopic secretion. iii) Some lesions may secrete ACTH and corticotropin-releasing hormone (CRH) simultaneously (10). Moreover, Al-Gahtany et al (11) reported three cases of ectopic CRH tumors, with pituitary hyperplasia leading to high corticotrophin hyperlipidemia; they also reported that, postoperatively, the ACTH level immediately returned to normal if the tumor produced ACTH, but it decreased gradually if the tumor produced CRH.…”

“…Patients who receive comprehensive treatment, including completion of chemoradiotherapy, are expected to have longer tumor-free survival, compared with those receiving surgery alone (10). Drugs focusing on the epithelial component may also be selected.…”

Ectopic Cushing syndrome in small cell lung cancer: A case report and literature review

“…This makes early diagnosis much more important. IPSS is the most reliable examination for ECS, but it may not be feasible in many institutes 3, 10. Complete imaging examination, related blood and urine tests, low dose and high dose dexamethasone tests, immunohistochemical characteristics, and cell proliferation potential (Ki‐67) should be considered when suspicious of ECS.…”

Zespół Cushinga w przebiegu ektopowego wydzielania ACTH

“…On the other hand, there are EAS patients in whom the negative feedback after high dose of dexamethasone is preserved (similarly to ACTH-secreting pituitary gland adenoma cases). This is mainly observed in patients with bronchial NENs [7,27]. The ACTH concentration measurement is a significant laboratory problem because this hormone is a thermally unstable protein, and therefore laboratory assessment should be performed immediately after the blood sample was acquired (to limit the possibility of false negative results).…”

“…W grupie chorych z przysadkowym CS szacowanej na 10-20% przypadków, stwierdza się, podobnie jak u pacjentów z EAS brak hamowania po dużej dawce deksametazonu [26]. Z drugiej strony opisano hiperkortyzolemię u chorych z EAS, gdzie zachowane było ujemne sprzężenie zwrotne po zastosowaniu dużej dawki deksametazonu, podobnie jak w postaci przysadkowej CS, głównie u chorych z NEN oskrzeli [7,27]. Problem dotyczy również oznaczenia ACTH.…”