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Year : 2016  |  Volume : 4  |  Issue : 1  |  Page : 24-26

Ectopic adrenocorticotropic hormone syndrome presenting as hypokalemic metabolic alkalosis and hypertension

Department of General Medicine, MES Medical College, Perinthalmanna, Kerala, India

Date of Web Publication23-Dec-2015

Correspondence Address:
Mansoor C Abdulla
Department of General Medicine, MES Medical College, Perinthalmanna - 679 338, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2320-8775.172478

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The ectopic adrenocorticotropic hormone (ACTH) syndrome is an uncommon cause of hypercortisolism, which should be considered in patients with hypokalemic metabolic alkalosis and hypertension in the context of lung neoplasm. We report a 60-year-old male patient with severe hypertension, metabolic alkalosis, and hypokalemia as the initial manifestations of an ACTH-secreting small cell lung carcinoma. Ectopic Cushing's syndrome should always be ruled out in patients with severe hypertension and hypokalemia.

Keywords: Ectopic adrenocorticotropic hormone syndrome, hypertension, hypokalemia, lung cancer, metabolic alkalosis

How to cite this article:
Abdulla MC, Alungal J. Ectopic adrenocorticotropic hormone syndrome presenting as hypokalemic metabolic alkalosis and hypertension. J Assoc Chest Physicians 2016;4:24-6

How to cite this URL:
Abdulla MC, Alungal J. Ectopic adrenocorticotropic hormone syndrome presenting as hypokalemic metabolic alkalosis and hypertension. J Assoc Chest Physicians [serial online] 2016 [cited 2023 Mar 25];4:24-6. Available from: https://www.jacpjournal.org/text.asp?2016/4/1/24/172478

  Introduction Top

Ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) is a rare cause of Cushing's syndrome accounting for about 10% of cases.[1],[2] EAS can be either associated with overt malignancies like small-cell lung cancer (SCLC) or with occult neoplasms like bronchial carcinoid tumors. Patients with EAS and SCLC may have atypical manifestations such as muscle wasting and weight. Early and more pronounced metabolic alterations are seen in EAS by SCLC and other malignant neoplasms.

  Case Report Top

A 60-year-old male was admitted with breathlessness, bilateral pedal edema, facial puffiness and hoarseness of voice for 1 month. He had hypertension since 8 years but not on regular medication. He was a 7 pack year smoker for 35 years. He had pallor, palpable single left supraclavicular lymph node which was 3 cm × 1 cm nontender, firm and mobile. His blood pressure was 170/100 mmHg, heart rate 58 beats/min, respiratory rate of 35 per min, and the temperature was 37.6°C.

Hemoglobin was 11.1 g/dl, total leukocyte count 10,200/μl, platelet count 1.0× 109/L, erythrocyte sedimentation rate 7 mm in 1 h. Peripheral smear showed leukoerythroblastic blood picture with adequate platelets. Urinalysis showed trace albumin with 1–2 leukocytes/high power fields. Biochemical parameters showed remote remote blob storage should be corrected as random blood sugar storage 88 mg%, urea 31 mg/dl, creatinine 1.0 mg/dl, sodium 137 mmol/L, potassium 2.2 mmol/L, magnesium 2.5 mg/dl and calcium 7.5 mg/dl, aspartate aminotransferase 90 IU/l, alanine aminotransferase 45 IU/L, alkaline phosphatase 85 IU/L, total bilirubin 0.8 mg/dl, direct bilirubin 0.2 mg/dl, total protein 4.9 g/dl, albumin 2.5 g/dl, and globulin 2.4 g/dl. Arterial blood gas analysis had severe metabolic alkalosis. The trans-tubular potassium gradient was seven. Chest X-ray and electrocardiogram were normal. Ultrasonography abdomen showed bulky right adrenal, small hepatic cyst and cholelithiasis. Echocardiogram showed concentric left ventricular hypertrophy. Contrast enhanced computed tomography thorax showed right hilar mass lesion with mediastinal invasion [Figure 1]a and [Figure 1]b. An endobronchial biopsy showed small-cell carcinoma of the lung [Figure 1]c and [Figure 1]d. Her 8:00 am plasma cortisol was 1400 nmol/L (reference: 180–800 nmol/L) and plasma ACTH 196 pg/mL (normal values are less than 46 pg/mL). The 24 h free cortisol urinary levels were 990 μg (normal values 4–100 μg) using the immunoenzymatic method. His plasma cortisol failed to suppress after overnight 1mg dexamethasone and after 8mg dexamethasone. A diagnosis of ectopic ACTH syndrome due to lung malignancy was considered. The patient had hypokalemia and hypertension, both of which were difficult to manage. He received high doses of intravenous potassium and four antihypertensives. He was started on chemotherapy (carboplatin and etoposide) with which his metabolic abnormalities were corrected.
Figure 1: Contrast enhanced CT thorax showing right hilar mass lesion with mediastinal invasion (upper panel a and b). Endobronchial biopsy specimen showing small cell carcinoma (lower panel c and d)

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  Discussion Top

EAS refers to endogenous hypercortisolism due to an ACTH-secreting nonpituitary tumor. EAS causes 10% of all cases of endogenous Cushing's syndrome.[1],[2] Various benign and malignant tumors of nonpituitary tissues can be associated with EAS. SCLC and bronchial carcinoids account for about half of the cases. 1–5% of SCLC is associated with Cushing's syndrome. EAS by SCLC and other malignant neoplasms typically leads to early appearance and more pronounced metabolic alterations.

Proopiomelanocortin (POMC) is the inactive precursor of ACTH. POMC cleavage by prohormone convertase (PC 1–3) in the anterior pituitary gives rise to ACTH and beta-lipotropin, along with small amounts of beta-endorphin. POMC gene expression in nonpituitary cells differs from that in pituitary cells both qualitatively and quantitatively. POMC gene is transcripted using the P3 promoter in nonpituitary tissues in physiological conditions generating a shorter messenger RNA (mRNA) that is not translated. The nonpituitary ACTH-secreting tumors use the pituitary, P2, promoter or the PI promoter generating a pituitary size mRNA. Malignant tumors causing the EAS show an aberrant processing of the POMC resulting in large under processed molecules, like pro-ACTH, or in the activation of abnormal cleavage sites generating fragments, like beta-melanocyte-stimulating hormone, not usually seen in the anterior pituitary. The serum concentrations of the ACTH precursors, such as POMC or pro-ACTH, may be extremely elevated in patients with SCLC and the EAS while the ACTH levels are less markedly elevated.[3]

EAS by SCLC and other malignant neoplasms have atypical manifestations such as muscle wasting, weight loss, and pronounced metabolic alterations more frequent than the classic signs of hypercortisolism. Biologic behavior of the responsible neoplasm results in the clinical heterogeneity observed with EAS compounded by additional factors like Cosecretion of other hormones along with ACTH by the tumor and intermittent hypercortisolism with long periods of spontaneous remission. Patients with EAS harboring SCLC, medullary thyroid carcinomas, and pancreatic tumors had a poor prognosis when compared with bronchial carcinoids.[4],[5] The poor prognosis in patients with SSLC having EAS was not only due to the biologic characteristics of the tumor but these patients have a much higher rate of life-threatening complications during chemotherapy, mostly related to severe infections and gastrointestinal bleeding or ulceration. The severe and uncontrolled hypercortisolism is directly responsible for these detrimental effects. Once the tumor is obvious, EAS confirmation is straightforward because gross elevations in urinary or serum cortisol and plasma ACTH are readily apparent, and an extensive endocrine workup is unnecessary.

Even though the ideal treatment of the EAS is the removal of the ectopic source of ACTH the malignant ACTH-secreting tumors are usually unresectable. In patients with no identifiable source of ectopic hormone production, bilateral adrenalectomy followed by hormone replacement treatment is effective.[6],[7] Anti-neoplastic therapy has been employed with limited success. Experience with adrenal steroid biosynthesis inhibitors, inhibitors of ACTH-secretion, or glucocorticoid receptor antagonist is limited.

We describe a patient with severe hypertension, metabolic alkalosis and hypokalemia as the initial manifestations of an ACTH-secreting small-cell lung carcinoma and review the pathophysiological mechanisms responsible.

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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
Reimondo G, Paccotti P, Minetto M, Termine A, Stura G, Bergui M, et al. The corticotrophin-releasing hormone test is the most reliable noninvasive method to differentiate pituitary from ectopic ACTH secretion in Cushing's syndrome. Clin Endocrinol (Oxf) 2003;58:718-24.  Back to cited text no. 2
Terzolo M, Reimondo G, Alì A, Bovio S, Daffara F, Paccotti P, et al. Ectopic ACTH syndrome: Molecular bases and clinical heterogeneity. Ann Oncol 2001;12 Suppl 2:S83-7.  Back to cited text no. 3
Isidori AM, Kaltsas GA, Pozza C, Fragese V, Newell-Price J, Reznek RH, et al. The ectopic adrenocorticotropin syndrome: Clinical features, diagnosis, management, and long-term follow-up. J Clin Endocrinol Metab 2006;91:371-7.  Back to cited text no. 4
Salgado LR, Fragoso MC, Knoepfelmacher M, Machado MC, Domenice S, Pereira MA, et al. Ectopic ACTH syndrome: Our experience with 25 cases. Eur J Endocrinol 2006;155:725-33.  Back to cited text no. 5
Li H, Yan W, Mao Q, Lu Z, Zeng Z. Role of adrenalectomy in ectopic ACTH syndrome. Endocr J 2005;52:721-6.  Back to cited text no. 6
Salameh JR, Borman KR, Varkarakis GM. Laparoscopic bilateral adrenalectomy for occult ectopic ACTH syndrome. J Laparoendosc Adv Surg Tech A 2008;18:52-5.  Back to cited text no. 7


  [Figure 1]

This article has been cited by
1 A Case of Pulmonary Carcinoid Tumor with a Superimposed Aspergilloma Presenting As a Covert Ectopic Adrenocorticotropic Hormone Syndrome
Kyoung Jin Kim,Ji Hee Yu,Nan Hee Kim,Young Hye Kim,Young Sik Kim,Ji A Seo
Frontiers in Endocrinology. 2017; 8
[Pubmed] | [DOI]


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