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 Table of Contents  
Year : 2016  |  Volume : 3  |  Issue : 4  |  Page : 291-294

Cushing's syndrome due to adrenocorticotropic hormone-secreting pheochromocytoma

1 NIMS, Kukatpally, Hyderabad, Telangana, India
2 Department of Endocrinology, DNB Resident, KIMS, Secunderabad, Telangana, India
3 Consultant Endocrinologist, KIMS, Kondapur, Hyderabad, Telangana, India

Date of Web Publication14-Sep-2016

Correspondence Address:
Dr. Manoj Mengade
C/O, Ajay Kumar, House No. 1-8-109, Macleod Guda, PG Road, Sindhi Colony, Secunderabad - 500 003, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2348-3334.190578

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Adrenocorticotropic hormone (ACTH) producing pheochromocytoma is the rare cause of Cushing's syndrome (CS). Herein, we present a 53-year-old female patient with ectopic ACTH-dependent Cushing's syndrome due to pheochromocytoma. ACTH secreting pheochromocytoma is a rare but important source of ectopic ACTH secretion. Early diagnosis of pheochromocytoma with CS needs a high index of suspicion. The scenario provides clues for a detailed discussion about the pitfalls and diagnostic difficulties in establishing the underlying cause of ACTH-dependent CS. It demonstrates relative contributions of clinical, biochemical, and radiological clues in arriving at the correct underlying cause of CS.

Keywords: Adrenocorticotropic hormone, Cushing's syndrome, pheochromocytoma

How to cite this article:
Chanukya G V, Mengade M, Reddy B. Cushing's syndrome due to adrenocorticotropic hormone-secreting pheochromocytoma. CHRISMED J Health Res 2016;3:291-4

How to cite this URL:
Chanukya G V, Mengade M, Reddy B. Cushing's syndrome due to adrenocorticotropic hormone-secreting pheochromocytoma. CHRISMED J Health Res [serial online] 2016 [cited 2022 Aug 11];3:291-4. Available from: https://www.cjhr.org/text.asp?2016/3/4/291/190578

  Introduction Top

Cushing syndrome may be due to ectopic secretion of adrenocorticotropic hormone (ACTH) from bronchial carcinoid, islet cell tumor, small cell lung carcinoma, medullary carcinoma of the thyroid, thymic carcinoid, disseminated neuroendocrine tumor and disseminated gastrointestinal carcinoid. Cushing syndrome due to ACTH-secreting pheochromocytomas have sporadically been reported in the literature and accounts for 3% of ectopic ACTH-dependent Cushing syndrome.[1] We are reporting a case of ACTH-secreting pheochromocytoma presenting as Cushing's syndrome (CS).

The case provides clues for a detailed discussion on the pitfalls and diagnostic difficulties in establishing the correct underlying cause of ACTH-dependent CS. In addition, we review the literature concerning ACTH-producing pheochromocytomas.

  Case Report Top

A 53-year-old female known diabetic and hypertensive for 7 years presented to casualty with recurrent hypoglycemic attacks, hypokalemia, metabolic alkalosis, and labile hypertension with incidental ultrasonography finding of the right adrenal mass which was confirmed with contrast-enhanced computed tomography with dimensions of 4 cm × 3.8 cm × 3.3 cm mass associated with calcifications. On further evaluation in our hospital renal Doppler was normal, aldosterone-renin ratio - 17.1 (n < 30), 24 h urinary cortisol was 22153.92 μg/24 h (28.50–213.70), overnight dexamethasone suppression test was 146.50 μg/dl (n < 1.8), CS confirmed with low dose dexamethasone suppression test 188.71 μg/dl (n < 1.8), serum ACTH 375 pg/mL (10–60 pg/mL) indicating ACTH-dependent CS, 24 h urinary metanephrine was 3737.23 μg/g (27–155), and 24 h urinary normetanephrine was 1169.62 μg/g (46–256). Other relevant investigations were within normal range. In view of these investigations diagnosis of ACTH-dependent CS and pheochromocytoma was made and further evaluated for its etiology.

To detect the source of ACTH, magnetic resonance imaging brain [Figure 3] with pituitary-specific dynamic contrast enhanced study was done which was normal. To evaluate further inferior petrosal sinus sampling (IPSS) done with ACTH central to peripheral ratio, right side 1:1.5 and left side 1:1.2 indicating no lateralization and no pituitary source of ACTH. To detect the ectopic source of ACTH, 68 Ga-DOTATOC positron emission tomography (PET) computed tomography [Figure 4], [Figure 5], [Figure 6] was performed (octreotide somatostatin receptor PET scan) which was showing positive for right adrenal tumor and mild uptake noted in the left adrenal medially [Figure 1] and [Figure 2], rest of the scan normal.
Figure 1: 68 Ga-DOTATOC positron emission tomography computed tomography (octreotide somatostatin receptor positron emission tomography scan) showing positive for right adrenal tumor and mild uptake noted in left adrenal medially

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Figure 2: Coronal section of 68 Ga-DOTATOC positron emission tomography computed tomography (octreotide somatostatin receptor positron emission tomography scan) showing positive for right adrenal tumor and mild uptake noted in left adrenal medially

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Figure 3: Magnetic resonance imaging Brain with contrast showing no abnormality

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Figure 4: Computed tomography abdomen - heterogeneous mass in right adrenal with left adrenal hyperplasia

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Figure 5: Inferior petrosal sinus sampling with arginine vasopressin (IV) - adrenocorticotropic hormone ratio central to peripheral right side - 1:1.5 and left side - 1:1.2, showing no lateralization

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Figure 6: F-18 fluorodeoxyglucose positron emission tomography computed tomography-Showing well defined heterogeneously enhancing hypermetabolic right adrenal lesion with bilateral bulky adrenal gland

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In view of above scenario, it was decided to proceed for laparoscopic right adrenalectomy, but unfortunately, the patient deteriorated and succumbed with progressive sepsis. Postmortem biopsy of adrenal could not get for histopathology and immunohistochemical (IHC) analysis.

  Discussion Top

This case represents a very rare cause of ectopic CS caused by an ACTH-producing pheochromocytoma and illustrates the diagnostic challenges of ACTH-dependent CS and pheochromocytoma. CS comprises a large group of signs and symptoms that reflect prolonged and inappropriately high exposure of tissue to glucocorticoids. Endogenous CS is an uncommon disorder with an incidence of 2–3 cases per 1 million inhabitants per year with 10% being ectopic. In rare cases, ACTH-producing phaeochromocytomas (3%) are the cause of Cushing syndrome.[1],[2],[3]

The prevalence of pheochromocytoma in patients with hypertension in the general outpatient clinics varies between 0.2 and 0.6%, and autopsy studies demonstrate undiagnosed tumors in 0.05–0.1% of patients.[4],[5] Pheochromocytoma is a challenging and life-threatening tumor, often associated with very difficult to interpret clinical manifestations. This neoplasm may secrete various substances such as somatostatin, encephalin, calcitonin, vasoactive intestinal peptide, neuropeptide Y, renin, ACTH, parathyroid hormone, erythropoietin, adrenomedullin, and dihydroxyphenylalanine in addition to catecholamines. The symptoms manifested by the patients depend on the prevailing secretory products secreted from the tumor.[6],[7],[8]

Ectopic CS caused by ACTH-producing pheochromocytoma has been reported in only 24 patients and was first described by Meloni in 1966.[9] Remarkably, 21 of these 24 patients were women, and almost all presented with large adrenal tumors (2–6 cm).

ACTH produced by the tumor stimulates the adrenal cortex to hyper-secrete cortisol. Hence, as in our patient, the prevalent clinical manifestation is a CS. Many other tumors, such as small-cell lung carcinoma, bronchial carcinoid, and medullary carcinoma of the thyroid, have been found to be associated with ectopic ACTH secretion. These candidate tumors were ruled out in the present case.

Despite the unusual presentation of pheochromocytoma as Cushing syndrome, the prognosis is similar to the conventional pheochromocytomas. After removal of the ACTH-secreting adrenal tumor, the patient develops transient hypocortisolism. This is explained by the feedback inhibition of the cortisol-secreting tumor on ACTH secretion from the pituitary. After adrenalectomy, the pituitary recovers from the feedback inhibition and normal cortisol level is restored. ACTH secreting pheochromocytomas are the exception to the rule; unilateral adrenalectomy is curative, and the contralateral hyperplastic adrenal can be preserved. This approach results in resolution of both syndromes of hormone excess and preserves long-term adrenal function.[8] Final diagnosis can be confirmed with immunohistochemistry for ACTH and chromogranin.

  Conclusion Top

Cushing syndrome can be a rare presentation of pheochromocytoma as a result of ectopic secretion of ACTH. It is often difficult to diagnose this presentation preoperatively, especially in cases with a predominant secretion of ACTH rather than catecholamines. In such cases, the final diagnosis can be made only by IHC analysis. An ACTH secreting pheochromocytoma should be one of the differential diagnoses in patients with adrenal mass and elevated ACTH levels.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Aniszewski JP, Young WF Jr., Thompson GB, Grant CS, van Heerden JA. Cushing syndrome due to ectopic adrenocorticotropic hormone secretion. World J Surg 2001;25:934-40.  Back to cited text no. 1
Lindholm J, Juul S, Jørgensen JO, Astrup J, Bjerre P, Feldt-Rasmussen U, et al. Incidence and late prognosis of Cushing's syndrome: A population-based study. J Clin Endocrinol Metab 2001;86:117-23.  Back to cited text no. 2
Etxabe J, Vazquez JA. Morbidity and mortality in Cushing's disease: An epidemiological approach. Clin Endocrinol (Oxf) 1994;40:479-84.  Back to cited text no. 3
Sinclair AM, Isles CG, Brown I, Cameron H, Murray GD, Robertson JW. Secondary hypertension in a blood pressure clinic. Arch Intern Med 1987;147:1289-93.  Back to cited text no. 4
Platts JK, Drew PJ, Harvey JN. Death from phaeochromocytoma: Lessons from a post-mortem survey. J R Coll Physicians Lond 1995;29:299-306.  Back to cited text no. 5
Lenders JW, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. Lancet 2005;366:665-75.  Back to cited text no. 6
Kirkby-Bott J, Brunaud L, Mathonet M, Hamoir E, Kraimps JL, Trésallet C, et al . Ectopic hormone-secreting pheochromocytoma: A francophone observational study. World J Surg 2012;36:1382-8.  Back to cited text no. 7
Ballav C, Naziat A, Mihai R, Karavitaki N, Ansorge O, Grossman AB. Mini-review: Pheochromocytomas causing the ectopic ACTH syndrome. Endocrine 2012;42:69-73.  Back to cited text no. 8
Meloni CR, Tucci J, Canary JJ, Kyle LH. Cushing's syndrome due to bilateral adrenocortical hyperplasia caused by a benign adrenal medullary tumor. J Clin Endocrinol Metab 1966;26:1192-200.  Back to cited text no. 9


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

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