Ectopic Adrenocorticotropic Hormone Production in a Stage IV Neuroendocrine Tumor: A Rare Presentation of Cushing’s Syndrome

Posted on April 25, 2025 by MaryO

Abstract

Neuroendocrine tumors (NETs) are heterogeneous neoplasms that arise from neuroendocrine cells, resulting in endocrine imbalances that impact quality of life and prognosis. Ectopic adrenocorticotropic hormone (ACTH) production by NETs is a rare cause of ACTH-dependent Cushing’s syndrome. While the majority of these cases are associated with intrathoracic tumors, recent reports have indicated an increasing incidence of cases originating from diverse anatomical sites. Furthermore, despite comprehensive imaging efforts, a substantial proportion of cases remain challenging to localize.

In this case, we describe a 54-year-old man with a stage IV NET with metastatic liver and pancreatic lesions, who presented with Cushing’s syndrome due to ectopic ACTH production. The patient exhibited symptoms of severe hypercortisolism, including weight gain, proximal muscle weakness, acute-onset heart failure, and hypertension. Imaging revealed bilateral adrenal hypertrophy. Laboratory tests revealed hypokalemia and hyperglycemia and confirmed elevated cortisol levels and a lack of suppression after dexamethasone administration, consistent with ectopic rather than pituitary ACTH production. The patient was treated with metyrapone because ketoconazole was contraindicated because of liver metastasis and recent upper gastrointestinal bleeding requiring proton pump inhibitor use. This case highlights the rare occurrence of ACTH-producing NETs and emphasizes the importance of considering this diagnosis in cases with similar presentations. Furthermore, medical management of this patient without surgical intervention, owing to multiple contraindications, offers an important perspective for treating complex cases.

Introduction

Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms that can secrete various hormones; however, ectopic adrenocorticotropic hormone (ACTH) production is rare, occurring in only 5-10% of all Cushing’s syndrome cases [1]. Liddle et al. described the first case in 1962 [2]. A recent case series that examined the clinical and diagnostic treatment of ectopic ACTH in a tertiary center included information on only 12 cases collected over a 17-year period [3]. The most common site for ectopic ACTH from malignancy is the intrathoracic region, primarily in small-cell lung carcinomas. Unfortunately, obtaining a single diagnostic image that can detect tumor-producing ACTH remains challenging. According to the literature, ectopic ACTH resulting in Cushing’s syndrome can remain undetected [3,4].

In the present case, a patient with a stage IV NET presented with the classic features of Cushing’s syndrome, leading to the diagnosis of ectopic ACTH production. The complexity of this case, owing to the patient’s metastatic disease, the contraindications for certain therapies, and the requirement for atypical medical management, highlights the challenges of treating advanced NETs, especially metastatic lesions with hormonal overproduction. This report aimed to underscore the importance of early recognition and the effectiveness of metyrapone as a treatment for hypercortisolism in metastatic NET.

Case Presentation

A 54-year-old man with a known history of a World Health Organization (WHO) grade 3, stage IV NET with metastatic lesions in the liver and pancreas presented to the hospital with new-onset acute heart failure. His medical history consisted of papillary thyroid cancer diagnosed in January 2023, for which he underwent total thyroidectomy and left neck dissection. Three months later, the patient was found to have a new liver lesion that was biopsied and was consistent with a WHO grade 3 NET (Figure 1). He was started on capecitabine and temozolomide chemotherapy regimen, which was switched to folinic acid, fluorouracil, and oxaliplatin due to disease progression. He had undergone positron emission tomography (PET)/computed tomography (CT) as part of the follow-up for NET, and the findings were consistent with hypermetabolic pancreatic and liver lesions. However, no uptake was observed in the lungs and/or adrenal glands (Figure 2).

Liver-tissue-section-showing-positive-synaptophysin-immunohistochemical-staining-in-neoplastic-cells,-consistent-with-a-neuroendocrine-neoplasm.
Figure 1: Liver tissue section showing positive synaptophysin immunohistochemical staining in neoplastic cells, consistent with a neuroendocrine neoplasm.
FDG-PET/CT-scan-of-the-whole-body-showing-hypermetabolic-pancreatic-tail-mass-which-measures-up-to-6.5-cm-and-multifocal-liver-hypermetabolic-metastases.-
Figure 2: FDG PET/CT scan of the whole body showing hypermetabolic pancreatic tail mass which measures up to 6.5 cm and multifocal liver hypermetabolic metastases.

FDG: fluorodeoxyglucose; PET: positron emission tomography; CT: computed tomography

The patient was admitted first with gastrointestinal (GI) bleeding secondary to duodenal ulcers that were managed with a proton pump inhibitor (PPI), pantoprazole 40 mg, oral, BID (Figure 3). Ten days later, he presented with worsening dyspnea and shortness of breath, and clinical examination was consistent with volume overload and 4+ pitting edema in the lower extremities. Additionally, he was found to have a significantly low potassium level (2.6 mmol/L) and worsening serum blood glucose (341 mg/dL). The constellation of symptoms in the patient, including significant weight gain, obesity, easy bruising, proximal muscle weakness, acute-onset heart failure, hypertension, hypokalemia, and worsening hyperglycemia with new insulin requirements, raised concerns about hypercortisolism and prompted testing. The serum ACTH levels were markedly elevated (488 pg/mL; reference range: 10-60 pg/mL). CT of the abdomen and pelvis revealed bilateral adrenal gland hypertrophy (Figure 4).

Upper-endoscopy-images-showing-four-cratered,-non-bleeding-duodenal-ulcers-with-a-clean-ulcer-base-(Forrest-Class-III).
Figure 3: Upper endoscopy images showing four cratered, non-bleeding duodenal ulcers with a clean ulcer base (Forrest Class III).
CT-of-the-abdomen-and-pelvis-demonstrating-bilateral-adrenal-gland-hypertrophy.
Figure 4: CT of the abdomen and pelvis demonstrating bilateral adrenal gland hypertrophy.

CT: computed tomography

Morning cortisol levels were significantly increased (42.2 µg/dL), and the 8-mg dexamethasone suppression test showed no suppression, with a post-dexamethasone cortisol level of 44.2 µg/dL. The 24-hour urinary-free cortisol level was elevated (2259 µg/24 hour; reference range: 3.5-45 µg/24 hour). At this time, the differential diagnoses included but were not limited to Cushing’s disease or ectopic ACTH production secondary to metastatic NET. However, given that the patient had bilateral adrenal gland hypertrophy that was noted on imaging and his cortisol did not suppress with a high-dose dexamethasone suppression test, these findings support ectopic ACTH secretion secondary to metastatic NET over Cushing’s disease from a pituitary source. 

After confirming the diagnosis, the patient was started on metyrapone 500 mg, administered two times per day; his serum cortisol began to decrease (from 42 to 38 µg/dL) and continued to decline until it reached the lowest level (8.9 µg/dL) with metyrapone 500 mg, administered four times per day. Unfortunately, because of cost-related issues, the patient was switched to octreotide; however, subsequently, his serum cortisol level increased (from 8.9 to 49 µg/dL). Ketoconazole was not a viable option because of drug-drug interactions with PPI. Alternative suppressive medications were considered and included osilodrostat and mifepristone. However, given the patient’s QTc prolongation and previous history of arrhythmia, it was felt that the use of these medications was too high risk for fatal arrhythmia. Given the limited medical options, the patient was evaluated for surgery, and, given the multiple comorbidities as well as metastatic disease without an apparent culprit lesion, he was not initially deemed to be a suitable surgical candidate. Therefore, metyrapone was reinitiated to control hypercortisolemia while the patient was admitted, and it effectively lowered his total serum cortisol levels. However, given that metyrapone was not a long-term option and medical management had failed (octreotide was ineffective in controlling serum cortisol levels, and ketoconazole could not be used due to drug-to-drug interactions with PPI), surgery was considered as an option. Despite the high risk associated with the procedures owing to the patient’s condition, bilateral adrenalectomy was performed, considering the lack of medical options and the patient’s goals of care. The patient was discharged home on oral hydrocortisone, 15 mg in the morning and 10 mg in the evening, in addition to fludrocortisone 0.1 mg daily. The patient’s body surface area is 2.5 m². The pathology of his adrenal glands was consistent with that of a metastatic NET (Figure 5). The patient was seen in the endocrinology clinic after bilateral adrenalectomy for a follow-up almost one month after the procedure. He reported feeling tired and falling asleep quite often. He used to be able to walk; however, now, he could only make it a quarter of the way due to muscle weakness. Unfortunately, further follow-up and outcome could not be evaluated as the patient died three months after his bilateral adrenalectomy surgery, and the cause of death was unknown.

Adrenal-tissue-section-showing-positive-synaptophysin-immunohistochemical-staining-in-neoplastic-cells,-consistent-with-a-neuroendocrine-neoplasm.
Figure 5: Adrenal tissue section showing positive synaptophysin immunohistochemical staining in neoplastic cells, consistent with a neuroendocrine neoplasm.

Discussion

This case of a stage IV NET with ectopic ACTH production leading to Cushing’s syndrome is notable because of its rarity and complexity. Although NETs are known for their diverse hormonal secretions, only a small subset of them are associated with ACTH production, making this case an important addition to the limited literature.

NETs causing ectopic Cushing’s syndrome are most frequently found in the intrathoracic region (40-60%), including bronchial tumors, small-cell lung carcinoma, and thymic carcinomas. Additional sites where these tumors may occur include the pancreas and thyroid gland (particularly medullary thyroid carcinoma). Less common locations include the prostate, rectum, ovaries, and bladder [5].

Our patient’s PET/CT findings were consistent with those of hypermetabolic lesions in the liver and pancreas. However, there was no uptake in the lungs, which is the most common site reported in the literature [5]. Additionally, there was no uptake in the adrenal glands, and the pathology was later found to be consistent with NETs. This posed a challenge to the diagnosis and identification of the culprit lesion. Reportedly, high-resolution cross-sectional CT imaging has a sensitivity of 50-67% in identifying the source of ectopic ACTH production, and when the findings are negative, a variety of nuclear medicine functional imaging techniques (Octreoscan, fluorine-18 fluorodeoxyglucose PET/CT, and gallium-68 somatostatin receptor-targeted PET/CT) can be used [6]. However, despite advances in imaging modalities, up to 20% of ectopic ACTH syndrome cases remain occult after initial imaging [4,7]. 

ACTH-producing pancreatic neuroendocrine (pNE) tumors are rare malignancies characterized by their aggressive nature [8]. Individuals diagnosed with this condition have less favorable outcomes compared with those with insulinoma, gastrinoma, or nonfunctional ACTH-producing pNE tumors [9]. The underlying reasons for the aggressiveness of the tumor and the resulting poor patient outcomes remain elusive. One study proposed that decreased methylation of the proopiomelanocortin promoter may enhance the ability of the tumors to secrete ACTH [10].

A similar presentation was reported by Al-Toubah et al. in a 2023 case series on ACTH-secreting pNE neoplasms. That study highlighted the rarity of ACTH production in these tumors and emphasized that such cases often present with severe hypercortisolemia and Cushing’s syndrome. However, most patients in their series were treated with ketoconazole, which was not an option for our patient because of liver metastasis and recent upper GI bleeding requiring PPI treatment [11].

A systematic review published in February 2021 by Wu et al. investigated ACTH-producing pNE tumors. That study analyzed 210 publications, including data from 336 patients diagnosed with this condition. The results indicated a higher prevalence among female individuals (66.4%), at an average age of 44.7 years. The review reported the following frequencies of clinical symptoms: 69.3% experienced hypokalemia, 63.2% developed diabetes, 60.1% suffered from weakness, 56.4% had hypertension, 41.1% displayed moon face, and 37.4% presented with edema [12].

In the present case, the patient presented with decompensated heart failure, which is consistent with various case reports describing acute decompensated heart failure as the first presentation. Sugihara et al. reported three cases of Cushing’s syndrome characterized by left ventricular failure as the predominant feature associated with gross left ventricular hypertrophy [13]. Similarly, Petramala et al. reported a case of a 28-year-old woman with Cushing’s syndrome secondary to an adrenal adenoma who exhibited congestive heart failure as an initial symptom [14]. In this regard, some studies have examined the relationship between cardiac dysfunction and hypercortisolism and found that cardiac remodeling is independent of hypertension and is probably related to the direct action of cortisol on myocardial tissue via glucocorticoid receptors [15,16]. These cardiac impairments may be reversible with the appropriate treatment of the underlying hypercortisolism, such as the surgical resection of the adrenal adenoma or pituitary adenoma, and the medical management of heart failure [14].

Our patient received metyrapone and could not be treated using ketoconazole because of liver metastasis and drug-drug interactions with PPI, as previously mentioned. In 2022, Landry et al. studied the management of ACTH-secreting NETs [17]. Their study, including 76 patients, found that most patients had metastatic disease at the time of ectopic Cushing’s syndrome diagnosis, similar to our case. Furthermore, they found that de novo hyperglycemia predicted worse survival outcomes. Therefore, controlling the hypercortisolic phase is crucial. Unfortunately, most patients present with metastatic disease, which makes surgical management, that is, removing the ACTH-producing tumor, not always an option. Additionally, they found that patients with medically resistant ectopic Cushing’s syndrome, subsequently controlled with bilateral adrenalectomy, had significantly better disease-specific survival following ectopic Cushing’s syndrome diagnosis than did patients who did not undergo bilateral adrenalectomy.

In our case, there were limited treatment options given the metastatic burden and limitations in using some of the medications to control hypercortisolism. In their article, Landry et al. stated “We have learned this over time as, unfortunately, most patients in our cohort who were diagnosed with resistant ectopic Cushing syndrome only used one type of suppression therapy by the end of the study” [17]. One medication, peptide receptor radionuclide therapy, was reported in multiple studies [5,18,19]. However, the Food and Drug Administration did not approve this therapy until 2018, and it has not been examined for ectopic Cushing’s disease, especially in the metastatic NET setting.

As surgical resection remains the recommended first-line treatment for the majority of patients with Cushing’s syndrome [20], medical therapy plays a critical role when surgery is not feasible; many studies reviewed the use of agents such as mifepristone [21], levoketoconazole [22], and pasireotide [23,24]. Additionally, a recent review study that focused on the clinical consideration for osilodrostat in the management of patients with ectopic ACTH found that quality of life improved during the use of long-term osilodrostat as a treatment for ectopic Cushing’s syndrome raised from a pNE tumor [25].

Conclusions

This case highlights the complexities involved in the diagnosis and management of ectopic ACTH-producing NETs. Due to the rarity of such presentations, clinicians must maintain a high index of suspicion for ectopic ACTH production in patients with unexplained hypercortisolism, particularly when signs of Cushing’s syndrome are present. Additionally, the management of preoperative hypercortisolism may be challenging, as in our patient. The treatment approach in this case was unconventional, given the patient’s ineligibility for surgery due to difficulties in localizing the exact lesion and the metastatic disease. Medical management with metyrapone was chosen. However, as it was cost-prohibitive, alternative therapy with octreotide was attempted, but it failed to achieve adequate control. Ketoconazole was not an option given the recent GI bleeding, and eventually, our patient underwent bilateral adrenalectomy. Therefore, future studies are required to develop predictive markers to determine which patients will benefit from bilateral adrenalectomy versus long-term pharmacotherapy. An extensive study on perioperative management in cases with ectopic ACTH would have proven to be useful in ensuring the survival of our patient.

References

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  2. Liddle GW, Island DP, Ney RL, Nicholson WE, Shimizu N: Nonpituitary neoplasms and Cushing’s syndrome. Ectopic “adrenocorticotropin” produced by nonpituitary neoplasms as a cause of Cushing’s syndrome. Arch Intern Med. 1963, 111:471-5. 10.1001/archinte.1963.03620280071011
  3. González Fernández L, Maricel Rivas Montenegro A, Brox Torrecilla N, et al.: Ectopic Cushing’s syndrome: clinical, diagnostic, treatment and follow-up outcomes of 12 cases of lung ectopic ACTH. Endocrinol Diabetes Metab Case Rep. 2023, 2023:22-0378. 10.1530/EDM-22-0378
  4. Varlamov E, Hinojosa-Amaya JM, Stack M, Fleseriu M: Diagnostic utility of gallium-68-somatostatin receptor PET/CT in ectopic ACTH-secreting tumors: a systematic literature review and single-center clinical experience. Pituitary. 2019, 22:445-55. 10.1007/s11102-019-00972-w
  5. Davi’ MV, Cosaro E, Piacentini S, et al.: Prognostic factors in ectopic Cushing’s syndrome due to neuroendocrine tumors: a multicenter study. Eur J Endocrinol. 2017, 176:453-61. 10.1530/EJE-16-0809
  6. Frete C, Corcuff JB, Kuhn E, et al.: Non-invasive diagnostic strategy in ACTH-dependent Cushing’s syndrome. J Clin Endocrinol Metab. 2020, 105:3273-84. 10.1210/clinem/dgaa409
  7. Zisser L, Kulterer OC, Itariu B, et al.: Diagnostic role of PET/CT tracers in the detection and localization of tumours responsible for ectopic Cushing’s syndrome. Anticancer Res. 2021, 41:2477-84. 10.21873/anticanres.15024
  8. Falconi M, Eriksson B, Kaltsas G, et al.: ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology. 2016, 103:153-71. 10.1159/000443171
  9. Maragliano R, Vanoli A, Albarello L, et al.: ACTH-secreting pancreatic neoplasms associated with Cushing syndrome: clinicopathologic study of 11 cases and review of the literature. Am J Surg Pathol. 2015, 39:374-82. 10.1097/PAS.0000000000000340
  10. Zhang C, Jin J, Xie J, et al.: The clinical features and molecular mechanisms of ACTH-secreting pancreatic neuroendocrine tumors. J Clin Endocrinol Metab. 2020, 105:3449-58. 10.1210/clinem/dgaa507
  11. Al-Toubah T, Pelle E, Hallanger-Johnson J, Haider M, Strosberg J: ACTH-secreting pancreatic neuroendocrine neoplasms: a case-series. J Neuroendocrinol. 2023, 35:e13336. 10.1111/jne.13336
  12. Wu Y, Xiong G, Zhang H, Wang M, Zhu F, Qin R: Adrenocorticotropic hormone-producing pancreatic neuroendocrine neoplasms: a systematic review. Endocr Pract. 2021, 27:152-7. 10.1016/j.eprac.2020.10.012
  13. Sugihara N, Shimizu M, Shimizu K, Ino H, Miyamori I, Nakabayashi H, Takeda R: Disproportionate hypertrophy of the interventricular septum and its regression in Cushing’s syndrome. Report of three cases. Intern Med. 1992, 31:407-13. 10.2169/internalmedicine.31.407
  14. Petramala L, Battisti P, Lauri G, et al.: Cushing’s syndrome patient who exhibited congestive heart failure. J Endocrinol Invest. 2007, 30:525-8. 10.1007/BF03346339
  15. Fallo F, Budano S, Sonino N, Muiesan ML, Agabiti-Rosei E, Boscaro M: Left ventricular structural characteristics in Cushing’s syndrome. J Hum Hypertens. 1994, 8:509-13.
  16. Yiu KH, Marsan NA, Delgado V, et al.: Increased myocardial fibrosis and left ventricular dysfunction in Cushing’s syndrome. Eur J Endocrinol. 2012, 166:27-34. 10.1530/EJE-11-0601
  17. Landry JP, Clemente-Gutierrez U, Pieterman CR, et al.: Management of adrenocorticotropic hormone-secreting neuroendocrine tumors and the role of bilateral adrenalectomy in ectopic Cushing syndrome. Surgery. 2022, 172:559-66. 10.1016/j.surg.2022.03.014
  18. Cheung NW, Boyages SC: Failure of somatostatin analogue to control Cushing’s syndrome in two cases of ACTH-producing carcinoid tumours. Clin Endocrinol (Oxf). 1992, 36:361-7. 10.1111/j.1365-2265.1992.tb01461.x
  19. De Rosa G, Testa A, Liberale I, Pirronti T, Granone P, Picciocchi A: Successful treatment of ectopic Cushing’s syndrome with the long-acting somatostatin analog octreotide. Exp Clin Endocrinol. 1993, 101:319-25. 10.1055/s-0029-1211252
  20. Gadelha M, Gatto F, Wildemberg LE, Fleseriu M: Cushing’s syndrome. Lancet. 2023, 402:2237-52. 10.1016/S0140-6736(23)01961-X
  21. Fleseriu M, Molitch ME, Gross C, Schteingart DE, Vaughan TB 3rd, Biller BM: A new therapeutic approach in the medical treatment of Cushing’s syndrome: glucocorticoid receptor blockade with mifepristone. Endocr Pract. 2013, 19:313-26. 10.4158/EP12149.RA
  22. Fleseriu M, Auchus RJ, Pivonello R, Salvatori R, Zacharieva S, Biller BM: Levoketoconazole: a novel treatment for endogenous Cushing’s syndrome. Expert Rev Endocrinol Metab. 2021, 16:159-74. 10.1080/17446651.2021.1945440
  23. Colao A, De Block C, Gaztambide MS, Kumar S, Seufert J, Casanueva FF: Managing hyperglycemia in patients with Cushing’s disease treated with pasireotide: medical expert recommendations. Pituitary. 2014, 17:180-6. 10.1007/s11102-013-0483-3
  24. Trementino L, Cardinaletti M, Concettoni C, Marcelli G, Boscaro M, Arnaldi G: Up-to 5-year efficacy of pasireotide in a patient with Cushing’s disease and pre-existing diabetes: literature review and clinical practice considerations. Pituitary. 2015, 18:359-65. 10.1007/s11102-014-0582-9
  25. Fleseriu M, Auchus RJ, Bancos I, Biller BM: Osilodrostat treatment for adrenal and ectopic Cushing syndrome: integration of clinical studies with case presentations. J Endocr Soc. 2025, 9:bvaf027. 10.1210/jendso/bvaf027

https://www.cureus.com/articles/351968-ectopic-adrenocorticotropic-hormone-production-in-a-stage-iv-neuroendocrine-tumor-a-rare-presentation-of-cushings-syndrome?score_article=true#!/

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The Role of Endocrinology in Managing Polycystic Ovary Syndrome and Diabetes

Posted on September 28, 2023 by MaryO

Introduction to Endocrinology

Endocrinology is a medical specialty that focuses on the diagnosis and treatment of diseases related to hormones. Endocrinologists are experts in managing and treating diseases related to the endocrine system, which includes the thyroid, pituitary, adrenal glands, and pancreas. Endocrinologists are trained to diagnose and treat conditions such as diabetes, thyroid disorders, pituitary disorders, and other conditions related to hormones. Endocrinologists also specialize in reproductive health and fertility issues, including PCOS.

Endocrinology is a complex field that requires a deep understanding of the endocrine system and its role in regulating the body’s hormones. Endocrinologists must be able to interpret laboratory tests and understand the underlying causes of endocrine disorders. They must also be able to develop individualized treatment plans to address the specific needs of each patient.

Diagnosing PCOS and Diabetes

Endocrinologists are experts in diagnosing and managing PCOS and diabetes. PCOS is a hormonal disorder that affects the ovaries, and it is characterized by irregular menstrual cycles, excess facial and body hair, and infertility. To diagnose PCOS, an endocrinologist will perform a physical exam and order laboratory tests to measure hormone levels. The endocrinologist will also ask the patient about her symptoms and family history to determine if PCOS is the cause.

Diabetes is a chronic condition that affects the body’s ability to process sugar. To diagnose diabetes, an endocrinologist will perform a physical exam and order laboratory tests to measure blood sugar levels. The endocrinologist may also order imaging tests to check for signs of diabetes-related complications.

Treating PCOS and Diabetes

Once the endocrinologist has diagnosed PCOS or diabetes, they will develop an individualized treatment plan to address the patient’s specific needs. For PCOS, the endocrinologist may recommend lifestyle changes such as weight loss, exercise, and dietary changes to help manage symptoms. The endocrinologist may also prescribe medications to regulate hormone levels and improve fertility.

For diabetes, the endocrinologist may recommend lifestyle changes such as weight loss, exercise, and dietary changes to help manage blood sugar levels. The endocrinologist may also prescribe medications to help regulate blood sugar levels. In addition, the endocrinologist may recommend regular check-ups to monitor the patient’s progress and to adjust the treatment plan if needed.

Conclusion

Endocrinology plays an important role in managing PCOS and diabetes. Endocrinologists are experts in diagnosing and treating these conditions, and they are trained to develop individualized treatment plans that address the specific needs of each patient. By working with an endocrinologist, patients can get the help they need to manage their PCOS or diabetes and achieve their health goals.

Endocrinology is a complex field that requires a deep understanding of the endocrine system and its role in regulating the body’s hormones. An endocrinologist can help patients with PCOS and diabetes manage their conditions and achieve their health goals. By working with an endocrinologist, patients can get the help they need to manage their PCOS or diabetes and achieve their health goals.

From https://www.diabetesincontrol.com/the-role-of-endocrinology-in-managing-polycystic-ovary-syndrome-and-diabetes/

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Etomidate Found Effective in Severe Cushing’s Syndrome

Posted on May 18, 2018 by MaryO

Etomidate — a steroid synthesis blocker — is an effective treatment for patients with severe Cushing’s syndrome who do not respond to ketoconazole, according to a new case report from Mexico.

The report, “Etomidate in the control of severe Cushing’s syndrome by neuroendocrine carcinoma,” appeared in the journal Clinical Case Reports.

The investigators reported the case of a 51-year-old woman with ectopic Cushing’s syndrome caused by a pancreatic tumor. Ectopic Cushing’s refers to cases of excess secretion of adrenocorticotropin hormone (ACTH) outside the pituitary or adrenal glands.

The patient underwent distal pancreatectomy — the surgical removal of the bottom half of the pancreas — in 2015 due to an ACTH-secreting tumor. Although she had a good initial response, liver metastasis was evident by 2016.

Compared to measurements in 2016, morning blood cortisol, 24-hour urinary-free cortisol, and ACTH levels significantly increased in 2017. The patient also showed low levels of the luteinizing and follicle-stimulating hormones, which the scientists attributed to her severe hypercortisolism (excess cortisol levels).

The woman was being treated with ketoconazole to lower her cortisol values and later received chemoembolization — a method to reduce blood supply and deliver chemotherapy directly to a tumor — for her liver metastasis.

Although ketoconazole is generally the treatment of choice for the control of hormone production in the adrenal glands, its effectiveness is often limited and is associated with side effects, clinicians noted.

In April 2017, the patient arrived at the emergency room with sepsis — a potentially life-threatening complication of an infection — that originated in the gut.

Because ketoconazole had failed to lower cortisol levels, the patient started receiving infused etomidate, an inhibitor of the enzyme 11‐beta‐hydroxylase that prevents cortisol synthesis.

This treatment was stopped one day before the bilateral removal of the adrenal glands as a definitive treatment for the elevated production of cortisol.

While the patient experienced decreased levels of potassium, calcium, and magnesium with an initial dose of 0.04 mg per kg body weight an hour of etomidate, a gradual decrease of etomidate — depending on her cortisol levels — corrected these alterations.

After surgery, the patient showed a significant improvement in her general health, including control of her sepsis. She is currently taking hydrocortisone and fludrocortisone, with treatment for liver metastasis pending.

“Etomidate is a very effective drug in severe Cushing’s syndrome that is refractory to ketoconazole,” the researchers wrote.

“Control of the serum cortisol levels in ectopic Cushing’s syndrome can be obtained with infusion rates much lower than those used in anesthesia, without respiratory side effects,” they added.

The authors recommend an initial dose of etomidate of 0.04 mg/kg per hour, daily monitoring of 24-hour urinary cortisol and cortisol levels, and a gradual decrease of the etomidate dose according to daily measurements of metabolites.

From https://cushingsdiseasenews.com/2018/05/17/severe-cushings-syndrome-case-study-finds-etomidate-effective-therapy/

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ACTH-producing Lung Tumors Hard to Detect, But May Be Cured with Surgery

Posted on December 13, 2017 by MaryO

Ectopic Cushing’s syndrome can be challenging to diagnose, especially when it comes identifying the problem source. But appropriate hormone management protocols, used in combination with advanced imaging methods, may help physicians identify ectopic ACTH-producing tumors.

The findings in a case report of a young man with ectopic Cushing’s syndrome were published in the International Journal of Surgery Case Reports, under the title “Case report: Ectopic Cushing’s syndrome in a young male with hidden lung carcinoid tumor.”

Cushing’s syndrome is caused by high amounts of glucocoticosteroids in the blood. The most common cause is a malfunction of the glands that produce these hormones. In some cases, however, the disease may be caused by tumors elsewhere in the body that have the ability to produce adrenocorticotropic hormone (ACTH).

In half of all Cushing’s patients, ectopic ACTH is produced by small lung cell carcinomas or lung carcinoids (a type of slow-growing lung cancer). But some tumors in the thymus and pancreas also have been found to produce ACTH.

Researchers at Damascus University Hospital in Syria presented the case of a 26-year-old man who had ectopic Cushing’s syndrome due to lung carcinoids.

The patient presented with increased appetite and rapid weight gain for more than a year. These were associated with headache, fatigue, proximal muscle weakness, and easy bruising. He had no family history of hormonal disorder.

Based on the initial physical and symptom evaluation, the clinical team suspected Cushing’s syndrome. Blood analysis revealed high levels of cortisol and ACTH hormones, which supported the diagnosis.

Administration of dexamethasone, a treatment used to inhibit the production of glucocoticosteroids by the pituitary gland, reduced cortisol levels within normal range, but not ACTH levels. This led to the diagnosis of ectopic Cushing’s syndrome.

The next step was to identify the tumor causing the syndrome. The team conducted imaging studies of the brain, chest, and abdomen, but found no tumor.

Because ectopic ACTH is commonly produced by lung cancers, the team then analyzed the patient’s lungs. Again, they failed to detect a tumor.

The patient was discharged with prescription of 200 mg of Nizoral (ketoconazole) once-daily, calcium, and vitamin D. After three months of treatment, he remained stable, with no evidence of symptom improvement.

At this point, the team decided to surgically remove both adrenal glands in an attempt to reduce the hormone levels. Treatment with prednisolone 5 mg and fludrocortisone 0.1 mg once daily was initiated, along with calcium and vitamin D.

Eighteen months later, the patient’s condition worsened and he required hospitalization.

Imaging tests targeting the neck, chest, and abdomen were conducted again. This time, physicians detected a 2 cm mass in the middle lobe of the right lung, which was removed surgically. Detailed analysis of the small tumor confirmed that it was the source of the excessive ACTH.

“ACTH secreting tumors can be very hard to detect,” the researchers stated. “Initial failed localization is common in ectopic ACTH syndrome and it is usually due to carcinoid.”

Cases where the ectopic ACTH production is caused by a carcinoid tumor can be challenging to diagnose because tumors are small and relatively slow-growing. Imaging data is often hard to analyze and the tumors can be confused with pulmonary vessels, the researchers explained.

“In such cases we should first aim to lower blood cortisol medically or through bilateral adrenalectomy to avoid Cushing’s complications,” which should then “be followed up through imaging studies (CT, MRI, scintigraphy or PET) to detect the tumor and resect it, which is the definitive treatment of these patients,” the researchers concluded.

From https://cushingsdiseasenews.com/2017/12/12/case-report-ectopic-acth-producing-lung-tumors-can-hard-detect/

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Interview May 13 with Michelle B (MichelleB), Cyclic Cushing’s Patient

Posted on May 13, 2015 by MaryO

Hello all, I’m Michelle mother of 3 beautiful children, I work part-time, 33yrs young, non-smoker, non-drinker, overall health is good for the most part…..Where do I even begin.

I just recently received the diagnosis of cyclic Cushing’s. I’m not really sure how long I have actually had Cushing’s because I have had a diagnosis of PCOS since I was 17 yrs. old ( I’m now the ripe young age of 33). However looking back through labs with my endocrinologist who I see every 6 months, my ACTH levels have been elevated for a bit over 1 yr. It was not until recently January of 2015- things were going terribly wrong.

Starting in January I started to feel genuinely unwell, on a regular basis. I cant really explain all my symptoms there were so many different sensations and feelings that were seemingly different daily. However the red flag was I was having blood pressure spikes from really high, to very low back to back. I never had any blood pressure issues so this was a concern that led me to see a cardiologist. Upon tons of testing the cardio MD felt that something was telling my otherwise very healthy heart to do this and I should see a endocrinologist. (thank goodness for him) I contacted my endo and let him know…. the testing began.

I did every test: the midnightcortisol saliva test, dex suppression, 24 hr urine test, CRH stimulation testing. And I did them more than once. Each time it was a different response either, inconclusive, normal high, or high. I was then referred to the head of the Cleveland clinics pituitary department Dr. Kennedy. He said he is having a hard time believing when he looks at me that its Cushing’s. However all my labs say it is. I will say I do fit the mold of PCOS to a tee- which symptoms of that do coincide with Cushing’s but he still said we have to be sure its Cushing’s. To add to the mix I did have a normal MRI as well.

Dr. Kennedy started me on a 2 week midnight cortisol saliva test- Upon completion we noted levels of cortisol all over the place, some Normal, normal on high range, high, and really high. He confirmed with all the other tests this is Cushing’s. Now we are trying to figure out what is next…. and where is this damn little tumor at. he feels that it is most likely in the pituitary from my test results, but we still are not ruling out else where. He is thinking that the next step would be exploratory neurosurgery or the IPSS. I’m not sure what to think of all this, except I want to hope for the best like everyone- and just be cured!!

On a side note during all of this I also had episodes of severe pain in my chest and nausea. I went to see a GI who did an upper endo scope. They found I had eosinpphilic esophagitis. I also have never had any GI problems until now; and they came on suddenly. Im also having pain in my pancreas area- not sure if any of the two are related at all to Cushing’s. But once again I was fine until recently with all these issues at once it seems.

wish me luck on further testing, treatment, and ultimately a CURE!!

interview

Michelle was our guest in an interview on BlogTalk Radio  Wednesday, May 13, 2015.

The archived interview is available now through iTunes Podcasts (Cushie Chats) or BlogTalkRadio. There are currently 83 other past interviews for your listening pleasure!

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