scholarly journals Pheochromocytoma as the Etiology of Cushing Syndrome Through Paracrine ACTH Signaling

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A148-A148
Author(s):  
Amruta Jaju ◽  
Vanessa Williams ◽  
Mariam Murtaza Ali ◽  
Anis Rehman ◽  
Sonaina Imtiaz ◽  
...  
Keyword(s):  
Adrenal Cortex ◽  
Cushing Syndrome ◽  
Adrenergic Blockade ◽  
Ectopic Acth ◽  
Unilateral Adrenalectomy ◽  
Ectopic Acth Secretion ◽  
Bilateral Adrenal Hyperplasia ◽  
Plasma Metanephrines ◽  
The Right ◽  
Patient’S History

Abstract Introduction: Pheochromocytomas are rare catecholamine-secreting tumors of the adrenal medulla that may also secrete ACTH. There are approximately 100 cases of ACTH-producing pheochromocytomas reported in the peer reviewed literature, and they typically cause Cushing syndrome by significantly raising circulating ACTH levels. We report a pheochromocytoma causing apparent ACTH-independent Cushing syndrome by paracrine action of locally produced ACTH on ipsilateral adrenal cortex. Case: A 64-year-old female was referred for an incidentally discovered left adrenal mass. The mass was 4 cm and 37 Hounsfield units on non-contrast computed tomography, and the right adrenal gland was unremarkable. The patient’s history was notable for three years of resistant hypertension, and examination revealed stigmata of Cushing syndrome including moon facies, scattered bruises, and wide, pink striae. Three measurements of plasma metanephrines ranged from 3- to 4.5-fold elevated, and 24 h urine metanephrines were 5.2-fold elevated. Urine 24 h epinephrine was 2.7-fold elevated. Three 8 AM cortisol measurements on overnight dexamethasone suppression tests were 16.3–17.4 mcg/dL (< 1.8), and 8 AM dexamethasone on one test was 494 ng/dL (140–295). Two midnight salivary cortisol measurements were 0.348 and 0.416 mcg/dL (< 0.112), and 8 AM ACTH levels on two occasions were 6.8 and 7.9 pg/mL (7.2–63.3). After adrenergic blockade, the patient underwent left adrenalectomy. Her tumor stained for synaptophysin and chromogranin consistent with pheochromocytoma, and focal staining for ACTH was also observed. Hyperplasia of the adjacent adrenal cortex was present. Hypertension resolved after adrenalectomy, and the patient developed secondary adrenal insufficiency (8 AM cortisol and ACTH 1.0 mcg/dL [> 15] and 2.9 pg/mL, respectively). Discussion: There are five published reports of pheochromocytoma and subclinical hypercortisolemia due to paracrine ACTH or IL-6 activity on ipsilateral adrenal cortex, but this case is distinguished by the occurrence of overt Cushing syndrome. Our patient had ACTH < 10 pg/mL on two measurements, her pheochromocytoma showed focal staining for ACTH, and hyperplasia of adjacent adrenal cortex was observed. In contrast, median ACTH level was 5-6x above the upper limit of normal in a recent review of 95 cases of pheochromocytomas with Cushing syndrome due to ectopic ACTH secretion. If Cushing syndrome was due to bilateral adrenal hyperplasia independent of the patient’s pheochromocytoma, cortisol excess would not have resolved after unilateral adrenalectomy. Communication between cortical and medullary circulations through venous radicles provides a mechanism for ACTH produced by the patient’s pheochromocytoma to affect the function of adjacent cortex. This case demonstrates a novel mechanism by which ACTH from a pheochromocytoma can cause Cushing syndrome.

scholarly journals Bowel perforation complicating an ACTH-secreting phaeochromocytoma

2016 ◽  
Vol 2016 ◽  
Author(s):  
Elise Flynn ◽  
Sara Baqar ◽  
Dorothy Liu ◽  
Elif I Ekinci ◽  
Stephen Farrell ◽  
...  
Keyword(s):  
Bowel Perforation ◽  
Diagnostic Workup ◽  
List Type ◽  
Ectopic Acth ◽  
Urinary Catecholamines ◽  
Unilateral Adrenalectomy ◽  
Gastrointestinal Complications ◽  
Ectopic Acth Secretion ◽  
Plasma Metanephrines ◽  
Acth Secreting

Summary ACTH-secreting phaeochromocytoma (ASP) is a rare cause of ACTH-dependent Cushing’s syndrome (CS). We report the case of a 63-year-old female presenting with CS secondary to an ASP complicated by bowel perforation. This case report highlights ASP as an uncommon but important cause of ectopic ACTH secretion (EAS). There have been 29 cases of ASP, all of which were unilateral and benign, but associated with significant complications. Patients presenting with ASP have the potential for cure with unilateral adrenalectomy. Given this promising prognosis if recognised, ASP should be considered in the diagnostic workup of ACTH-dependent CS. As this case demonstrates, gastrointestinal complications can arise from severe hypercortisolaemia associated with CS. Early medical and surgical intervention is imperative as mortality approaches 50% once bowel perforation occurs. Learning points Consider phaeochromocytoma in the diagnostic workup of ACTH-dependent CS; screen with plasma metanephrines or urinary catecholamines. Serial screening may be required if ACTH-secreting phaeochromocytoma is suspected, as absolute levels can be misleading. Early catecholamine receptor blockade and adrenal synthesis blockade may avoid the need for rescue bilateral adrenalectomy in ACTH-secreting phaeochromocytoma. Consider early medical or surgical management when gastrointestinal features are present in patients with CS, as bowel perforation due to severe hypercortisolaemia can occur and is associated with significant mortality.

scholarly journals SUN-938 Rare Case of Ectopic Cushing Syndrome Caused by ACTH Secreting Thymic Neuroendocrine Tumor in a Patient with Multiple Endocrine Neoplasia Type 1

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Yamuna Gorantla ◽  
Jorge Soria Moncada ◽  
Juan Sarmiento ◽  
Ambika Amblee ◽  
Malini Ganesh
Keyword(s):  
Neuroendocrine Tumor ◽  
Poor Prognosis ◽  
Rare Case ◽  
Cushing Syndrome ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Multiple Tumors ◽  
Men 1 ◽  
Acth Secreting

Abstract Introduction Cushing syndrome (CS) represents an uncommon manifestation of MEN1 and can be caused by both ACTH dependent or independent etiologies. Among them, ectopic ACTH secretion from a Thymic neuroendocrine tumor (TNET) in MEN1 is rare, with very few cases reported so far in literature. We report a case of Ectopic Cushing syndrome (ECS) in a MEN1 patient (pt) with multiple tumors, secondary to ACTH-secreting TNET. Case description: A 44 year old male presented to our institution for nausea, vomiting, dizziness. He had initial workup which revealed multiple tumors (papillary thyroid cancer, thymic mass, parathyroid adenomas, bilateral adrenal nodules, macroprolactinoma, peripancreatic nodules). Given concern for MEN 1, genetic testing was performed which was confirmative. Hormonal workup at this time for adrenal nodules was negative including low dose dexamethasone suppression test(DST). The immobile thymic mass was found to be poorly differentiated NET on biopsy with Ki-67 >50% with vascular invasion and adhesions to lung/chest wall on VATS, not amenable to surgery. The pt declined chemotherapy and radiotherapy due to poor social support. Six months later, he presented with complaints of shortness of breath, proximal muscle weakness, anasarca. Evaluation revealed AM cortisol >60 ug/dL(range 6.7-22), high-dose DST Cortisol >60 ug/dL, 24hr urine free cortisol: 8511mcg (range 4-50) and ACTH level: 278pg/mL(range 6-50) confirming ACTH-dependent CS. Special stains from the previous TNET biopsy demonstrated positive staining for ACTH confirming ectopic ACTH secretion. Ketoconazole and chemotherapy with Etoposide and Carboplatin was started, however he clinically deteriorated and expired a few weeks after diagnosed of ECS. Discussion: TNET in MEN 1 is rare, with a prevalence of 3-8%. TNET are unusual neoplasms that account for 2% to 7% of all mediastinal tumors. TNET in MEN1 rarely secrete functional hormones with very few reported Ectopic ACTH secretion. MEN1 associated ECS from TNET is an aggressive disease with local invasion of adjacent mediastinal structures or metastasis being common, resulting in poor prognosis as demonstrated in few case reports including our case. Radical surgery of involved adjacent structures and adjuvant local RT can provide local disease control. Conclusion: Our pt is a rare case of ECS from TNET in MEN1 with poor prognosis. A special feature of this case is that the patient had initial negative evaluation for hypercortisolemia, however 6 months later he presented with signs and symptoms of severe hypercortisolism, with evaluation confirming transformation into ACTH producing TNET. This conversion is very rarely found in literature and adds to the unique presentation of the case.

scholarly journals MON-LB035 Adrenal Venous Sampling in the Lateralization of Acth-Independent Cushing Syndrome With Bilateral Adrenal Masses: A Case With a 5-Year Follow-Up

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Yu Mi Kang ◽  
Sachin Majumdar
Keyword(s):  
Cushing Syndrome ◽  
Urine Volume ◽  
Adrenal Vein ◽  
Adrenal Venous Sampling ◽  
Venous Sampling ◽  
Unilateral Adrenalectomy ◽  
Free Cortisol ◽  
Adrenal Masses ◽  
The Common ◽  
The Right

Abstract Background Nearly 25% of adrenal Cushing syndrome (CS) patients with bilateral adrenal masses have unilateral hypercortisolism, making localization crucial for surgical planning. Since there is no standardized protocol for adrenal venous sampling (AVS) in lateralizing adrenal hypercortisolism, we share our experience with a case of CS with bilateral adrenal masses in which lateralization via AVS permitted unilateral adrenalectomy. Clinical Case A 59-year-old woman with hypertension, hyperlipidemia, and prediabetes was hospitalized for worsening back pain and hypertension. Her BMI was 26.5 kg/m2, BP 173/93 mmHg, HR 73/min, she was anxious, diaphoretic, and hirsute. Glucose was 118 mg/dL and HbA1c 6.6%. Abdominal computed tomography revealed a type B aortic dissection with both right (6.1 x 3.1cm and 3.6 x 2.4cm), and left (largest 1.7 cm) sided adrenal masses. Plasma and 24 hour-urine metanephrine, normetanephrine and catecholamines, as well as plasma renin and aldosterone levels, were normal. AM cortisol on three different occasions was 21.30, 20.70, and 21.30 mcg/dL. Midnight cortisol was 17.8 mcg/dL, and 24-hour urine free cortisol on two occasions was 163 mcg (urine volume 3.4L with creatinine 1.14) and 99.2 mcg (urine volume 1.15L). After 1mg dexamethasone her AM ACTH and cortisol were <5 and 18.70 mcg/dL, respectively. Preoperative AVS was performed and 8mg of dexamethasone was administered the night prior to ensure ACTH suppression during the procedure, and epinephrine was measured to ascertain adequate adrenal vein cannulation. Cortisol levels (in mcg/dL) from the common iliac, right and left adrenal veins were 14.7, 61.5, and 23.5 at 0 minute and 15.2, 61.0, and 22.7 at 2 minutes, respectively. Epinephrine levels (in pg/dL) from the common iliac, right and left adrenal veins were 42, 577, and 3225 at 0 minutes, and 46, 718, and 2989 at 2 minutes. Despite higher epinephrine levels from the left adrenal, the cortisol ratio of the right adrenal vein to peripheral vein was 4.18 with the right-to-left ratio of 2.59 and 2.68 at 0 and 2 minutes, suggesting hypersecretion of cortisol from the right adrenal gland. Unilateral right adrenalectomy revealed a 5.6 cm adrenal adenoma arising in a background of adrenal cortical hyperplasia. Morning postoperative cortisol was 2.2 mcg/dL. She was placed on hydrocortisone and tapered over a 10-month period with remission maintained for more than 3.5 years post-operatively. Conclusion This case demonstrates the safety, usefulness, and necessity, of AVS in localizing cortisol production when bilateral adrenal masses are present. In addition, this case suggests that the use of high dose dexamethasone and measurement of catecholamines may be helpful for more accurate interpretation. More data on AVS in CS patients with bilateral adrenal masses is needed so a well-validated and standardized CS-specific ACS protocol can be developed.

scholarly journals Ectopic ACTH syndrome in a dog with a mesenteric neuroendocrine tumour: a case report

2014 ◽  
Vol 59 (No. 7) ◽  
pp. 352-358 ◽  
Author(s):  
VA Castillo ◽  
PP Pessina ◽  
JD Garcia ◽  
P. Hall ◽  
MF Gallelli ◽  
...  
Keyword(s):  
Cushing Syndrome ◽  
Neuroendocrine Tumour ◽  
Clinical Signs ◽  
Ectopic Acth Syndrome ◽  
Histopathological Diagnosis ◽  
Left Adrenal Gland ◽  
Plasma Acth ◽  
Hormone Activity ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion

Ectopic ACTH secretion is provoked by extra-pituitary tumours that secrete ACTH, constituting an infrequent type of Cushing Syndrome in the dog. Neuroendocrine tumours (NET) are characterised by the synthesis of peptides with hormone activity. A dog with clinical diagnosis of Cushing&rsquo;s syndrome and presenting an abdominal tumour located in the area of the left adrenal gland was sent to the hospital. Cortisol was not inhibited at four and eight hours after the application of low-dose dexamethasone and the cortisol/creatinine ratio was elevated (93 &times; 10<sup>-6</sup>, referencevalues &lt; 10 &times; 10<sup>&ndash;6</sup>). Plasma ACTH measurements were high (28.6 pmol/l, reference values 5.5&ndash;14.3 pmol/l). On computed tomography, the tumour was found in the meso-epigastrium, with both adrenal glands hyperplasic and no alteration of the pituitary image. The tumour was located between the two layers of the meso-colon and was removed using laparoscopy. After surgery, ACTH concentrations became normal and clinical signs remitted. The histopathological diagnosis was NET, with positive ACTH immunostaining.

scholarly journals MANAGEMENT OF ENDOCRINE DISEASE: Differential diagnosis, investigation and therapy of bilateral adrenal incidentalomas

2018 ◽  
Vol 179 (2) ◽  
pp. R57-R67 ◽  
Author(s):  
Isabelle Bourdeau ◽  
Nada El Ghorayeb ◽  
Nadia Gagnon ◽  
André Lacroix
Keyword(s):  
Differential Diagnosis ◽  
Hormone Secretion ◽  
Adrenal Incidentalomas ◽  
Adrenal Hyperplasia ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Endocrine Disease ◽  
Bilateral Adrenal Hyperplasia ◽  
Hormonal Evaluation

The investigation and management of unilateral adrenal incidentalomas have been extensively considered in the last decades. While bilateral adrenal incidentalomas represent about 15% of adrenal incidentalomas (AIs), they have been less frequently discussed. The differential diagnosis of bilateral incidentalomas includes metastasis, primary bilateral macronodular adrenal hyperplasia and bilateral cortical adenomas. Less frequent etiologies are bilateral pheochromocytomas, congenital adrenal hyperplasia (CAH), Cushing’s disease or ectopic ACTH secretion with secondary bilateral adrenal hyperplasia, primary malignancies, myelolipomas, infections or hemorrhage. The investigation of bilateral incidentalomas includes the same hormonal evaluation to exclude excess hormone secretion as recommended in unilateral AI, but diagnosis of CAH and adrenal insufficiency should also be excluded. This review is focused on the differential diagnosis, investigation and treatment of bilateral AIs.

scholarly journals Ectopic ACTH-Producing Pheochromocytoma as a Rare Cause for Rapid Progressing Cushing Syndrome: A Case Report

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A128-A128
Author(s):  
Daniela Salazar ◽  
Cláudia Fernandes Costa ◽  
Joana Oliveira ◽  
Liliana Violante ◽  
Ana Luísa Cunha ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Cushing Syndrome ◽  
Somatostatin Receptors ◽  
Osteoporotic Fractures ◽  
Urinary Free Cortisol ◽  
Hand Tremor ◽  
Ectopic Acth ◽  
Late Night ◽  
Free Cortisol ◽  
The Right

Abstract Background: Cushing syndrome due to ectopic CRH or ACTH secretion can be rarely caused by pheochromocytoma, commonly as part of genetic conditions. Case: A 21 year-old male, previously healthy, with no usual medication, went to the physician assistant for hematuria. The kidney US revealed, besides lithiasis, a highly vascularized mass in the right adrenal gland with 10 cm. In his first evaluation the patient had no complaints or pheochromocitoma/hypercortisolism stigmata, other than hand tremor and slight rounding of the face. Blood pressure was 149/88 mmHg, and heart rate 86 bpm. There was no family history of endocrine disease. He rapidly developed increased appetite, insomnia, and severe myalgias, with filling of supraclavicular fossae, facial plethora, and cervical and truncal acne. Laboratory analysis showed abnormal overnight dexamethasone suppression test (57.4 µg/dL, N &lt; 1.8), elevated ACTH 378 pg/mL (N 9.0–52.0), 24h-urinary free cortisol (UFC) (5334.0 µg/24h, N 4.3–176.0), and late-night salivar cortisol (1.44 µg/dL, N &lt; 0.32), hypokalemia (2.8 mEq/L, N 3.8–5.0), and leukocytosis (22.4*109/L, N 4.0–11.0); DHEA-S 962 µg/dL (N 80–560), 4-androstenedione 380 ng/dL (N 70–360), 17-OH progesterone 4.5 ng/mL (N 0.59–3.44), cromogranine A 6063 ng/mL (N 0–100), and markedly elevated urinary amines (adrenaline 173 nmol/24h, N 0–109; noradrenaline 5033 nmol/24h, N 89–473; normetanephrine 334605 nmol/24h, N 480–2424; metanephrine 15998 nmol/24h, N 264–1729; dopamine 4808 nmol/24h, N 424–2612). Hypercalcemia with hypophosphatemia and supressed PTH level was also detected. 68Ga-DOTANOC PET revealed a mass of the right adrenal gland with overexpression of somatostatin receptors (likely pheochromocytoma), without evidence of other tumor lesions of neuroendocrine origin. Pituitary MRI showed normal pituitary gland. Potassium supplementation, alpha-blockade with phenoxybenzamine, and metyrapone were initiated. Due to severe back pain, a CT scan of the spine was performed detecting compressive osteoporotic fractures in the mid dorsal and low dorsal segments. The patient was submitted to right adrenalectomy. Histology revealed pheochromocytoma with 11.2*9mm, with capsular and vascular invasion, extra-adrenal extension, necrosis, and atypical mitosis, with Ki67 of 9.5% and PASS score of 16. Postoperative analysis showed ACTH 45.6 pg/mL (N 7.2-63,3), late-night salivar cortisol &lt; 0,0544 µg/dL (N &lt; 0,32) and free urinary cortisol 41.4 µg/24h (N 4.3–176.0). Discussion: Ectopic cushing syndrome caused by pheochromocytoma is a rarely described entity. In this young patient, it caused rapid clinical progression of hypercortisolism with important hydroelectrolytic disturbances and compressive vertebral fractures, requiring prompt surgical intervention for clinical remission and improvement.

scholarly journals Case Report: A Challenging Localization of a Pulmonary Ectopic ACTH-Secreting Tumor in a Patient With Severe Cushing’s Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Andreea Liliana Serban ◽  
Lorenzo Rosso ◽  
Paolo Mendogni ◽  
Arianna Cremaschi ◽  
Rita Indirli ◽  
...  
Keyword(s):  
Ct Scan ◽  
Rectal Carcinoma ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Pet Ct ◽  
The Right ◽  
Acth Secreting

BackgroundEctopic adrenocorticotropic syndrome (EAS) is a rare cause of endogenous ACTH-dependent Cushing’s syndrome, usually associated with severe hypercortisolism as well as comorbidities. Tumor detection is still a challenge and often requires several imaging procedures. In this report, we describe a case of an ectopic ACTH secretion with a misleading localization of the responsible tumor due to a concomitant rectal carcinoma.Case presentationA 49-year-old man was referred to our Endocrinology Unit due to suspicion of Cushing’s syndrome. His medical history included metastatic rectal adenocarcinoma, diagnosed 5 years ago and treated with adjuvant chemotherapy, radiotherapy and surgical resection. During follow-up, a thoracic computed tomography scan revealed two pulmonary nodules located in the superior and middle lobes of the right lung with a diameter of 5 and 10 mm, respectively. However, these nodules remained radiologically stable thereafter and were not considered relevant. All biochemical tests were suggestive of EAS (basal ACTH levels: 88.2 ng/L, nv 0–46; basal cortisol levels: 44.2 µg/dl, nv 4.8–19.5; negative response to CRH test and high dose dexamethasone suppression test) and radiological localization of the ectopic ACTH-secreting tumor was scheduled. The CT scan revealed a dimensional increase of the right superior lung nodule (from 5 to 12 mm). [68Ga]-DOTA-TOC PET/CT scan was negative, while [18F]-FDG-PET/CT showed a tracer accumulation in the superior nodule. After a multidisciplinary consultation, the patient underwent thoracic surgery that started with two atypical wedge resections of nodules. Frozen section analyses showed a neuroendocrine tumor on the right middle lobe nodule and a metastatic colorectal adenocarcinoma on the superior lesion. Then, a right superior nodulectomy and a right middle lobectomy with mediastinal lymphadenectomy were performed. The final histopathological examination confirmed a typical carcinoid tumor, strongly positive for ACTH. A post-surgical follow-up showed a persistent remission of Cushing’s syndrome.ConclusionsThe present report describes a case of severe hypercortisolism due to EAS not detected by functional imaging methods, in which the localization of ACTH ectopic origin was puzzled by a concomitant metastatic rectal carcinoma. The multidisciplinary approach was crucial for the management of this rare disease.

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