A case of severe ectopic ACTH syndrome from an occult primary – diagnostic and management dilemmas

Abstract

SummaryResection of primary tumour is the management of choice in patients with ectopic ACTH syndrome. However, tumours may remain unidentified or occult in spite of extensive efforts at trying to locate them. This can, therefore, pose a major management issue as uncontrolled hypercortisolaemia can lead to life-threatening infections. We present the case of a 66-year-old gentleman with ectopic ACTH syndrome from an occult primary tumour with multiple significant complications from hypercortisolaemia. Ectopic nature of his ACTH-dependent Cushing's syndrome was confirmed by non-suppression with high-dose dexamethasone suppression test and bilateral inferior petrosal sinus sampling. The primary ectopic source remained unidentified in spite of extensive anatomical and functional imaging studies, including CT scans and Dotatate-PET scan. Medical adrenolytic treatment at maximum tolerated doses failed to control his hypercortisolaemia, which led to recurrent intra-abdominal and pelvic abscesses, requiring multiple surgical interventions. Laparoscopic bilateral adrenalectomy was considered but decided against given concerns of technical difficulties due to recurrent intra-abdominal infections and his moribund state. Eventually, alcohol ablation of adrenal glands by retrograde adrenal vein approach was attempted, which resulted in biochemical remission of Cushing's syndrome. Our case emphasizes the importance of aggressive management of hypercortisolaemia in order to reduce the associated morbidity and mortality and also demonstrates that techniques like percutaneous adrenal ablation using a retrograde venous approach may be extremely helpful in patients who are otherwise unable to undergo bilateral adrenalectomy.Learning points Evaluation and management of patients with ectopic ACTH syndrome from an unidentified primary tumour can be very challenging.Persisting hypercortisolaemia in this setting can lead to debilitating and even life-threatening complications and hence needs to be managed aggressively.Bilateral adrenalectomy should be considered when medical treatment is ineffective or poorly tolerated.Percutaneous adrenal ablation may be considered in patients who are otherwise unable to undergo bilateral adrenalectomy.

A rare ectopic ACTH secreting atypical pulmonary carcinoid- case report

“…Advances in medical and surgical treatments have improved the overall survival rate for patients with ectopic ACTH [13]. Prognosis depends on primary tumor histology [14]. Patients with small cell lung carcinoma (SCLC) had the worst prognosis, usually dying within 12 months of diagnosis (median 6-8 months) [15,16,17].…”

Zespół Cushinga w przebiegu ektopowego wydzielania ACTH

“…Further, in many patients the origin of malignancy is unknown (even up to 20%; the most commonly finally diagnosed tumour is a bronchial NEN) [5,12,13]. Causes of EAS are mentioned in Table II [6,7,11,[14][15][16][17].…”

“…Subsiding of hypercortisolism symptoms after tumour removal and positive immunochemical staining for ACTH or precursor (POMC) in excised tissue indicates an EAS diagnosis. Such a diagnosis may not be considered a certainty in the case of a primarily disseminated malignancy (with no chance of cure) and heterogeneity of the population of malignant cells (leading to a false negative ACTH staining) [14]. The available laboratory tests used for CS diagnosis are: 24-hour free urine cortisol excretion, 1 mg overnight dexamethasone suppression test (ONDST), late evening salivary free cortisol, night plasma serum cortisol, verification of the rhythm of circadian cortisol secretion (serum cortisol concentration in the morning and in the evening), low-and high-dose dexamethasone cortisol suppression tests, human CRH and desmopressin test, and finally, bilateral inferior petrosal sinus sampling (BIPS), which is not routinely performed in Poland.…”

“…Dodatkowo dużą grupę stanowią pacjenci z nieznanym punktem wyjścia choroby nowotworowej, których odsetek w zależności od piśmiennictwa ocenia się na 20% przypadków (najczęściej ostateczne rozpoznanie to NEN oskrzeli) [5,12,13]. Wszystkie możliwe przyczyny EAS przedstawiono w tabeli II [6,7,11,[14][15][16][17].…”

“…Za najbardziej pewne rozpoznanie EAS należałoby uznać ustąpienie objawów klinicznych CS po resekcji guza oraz dodatnie barwienia immunohistochemicznego na obecność ACTH lub prekursorów (POMC) w preparatach patomorfologicznych. Ma to również swoje ograniczenia, między innymi guzy nieoperacyjne (brak możliwości wyleczenia) oraz heterogenność populacji komórek nowotworowych (fałszywie ujemne barwienia na ACTH) [14]. Do badań mających znaczenie w diagnostyce CS należy wymienić: dobowe wydalanie wolnego kortyzolu w moczu, test nocny z 1 mg deksametazonu, oznaczenie wieczornego stężenia kortyzolu w ślinie, ocena rytmu wydzielania kortyzolu (stężenie kortyzolu w surowicy w godzinach porannych i wieczornych), test hamowania małą/dużą dawką deksametazonu, test z CRH lub desmopresyną, czy niewykonywane w Polsce oznaczenia próbek krwi z zatok skalistych dolnych (BIPS, bilateral inferior petrosal sinus sampling).…”