Pulmonary adenocarcinoma presenting with symptoms of ectopic adrenocorticotropic hormone production.

Sir,

Paraneoplastic syndromes are disorders seen along with benign or malignant tumors but are not directly related to invasion, mass effect, or metastases. Commonly, paraneoplastic endocrine syndromes are detected in patients after the diagnosis of cancer. In certain cases, they may also be the first sign of an underlying malignancy, and hence, early detection is essential for successful treatment of tumor.[1] Although adenocarcinoma is the most common histological type in lung carcinomas,[2] its presentation with a paraneoplastic syndrome is rare.[3] We report a rare case of a patient with pulmonary adenocarcinoma who presented with symptoms of ectopic adrenocorticotropic hormone (ACTH) production instead of respiratory symptoms.

A 51-year-old male, manual laborer by occupation, presented with complaints of palpitations, dull aching pain in both legs, and blackish discoloration of both hands and feet for 1 year. There was no history of cough, hemoptysis, chest pain, or dyspnea. He was diagnosed with systemic hypertension 8 years back and type 2 diabetes mellitus 4 months back. He has been a chronic smoker for the past 30 years.

The patient had undergone a chest radiograph posteroanterior view for palpitations 6 months back which revealed a well-defined smoothly marginated opacity in the right lower lobe. Contrast-enhanced computed tomography (CT) scan taken elsewhere revealed a mildly enhancing smoothly marginated soft-tissue density lesion in the right lower lobe without calcification, fat density, or mediastinal lymphadenopathy, and a diagnosis of sequestration was made. Histopathological study was done, but the results were inconclusive.

General physical examination revealed clubbing and hyperpigmentation of both hands and feet. There was Grade 5 power in all the limbs. Laboratory investigations revealed hypokalemia (1.3 meq/L), metabolic alkalosis (pH = 7.52, serum bicarbonate = 39.8 mmol/L), hyperglycemia (fasting blood glucose = 308 mg%), elevated serum cortisol levels (75 mg/dl, normal reference range 7–23 mg/dl), and high serum ACTH (496 pg/ml, normal 0–46 pg/ml).

Skull radiograph lateral view taken to rule out pituitary tumor causing raised ACTH values did not show widening or erosion of sella turcica [Figure 1a]. Contrast-enhanced CT scan of the brain was done, but there was no pituitary mass or sellar erosion [Figure 1b-d]. Therefore, ectopic ACTH production was suspected. Dexamethasone suppression also did not cause any fall in the cortisol levels.

Figure 1

X-ray skull lateral view (a) and sagittal reformatted image of computed tomography head (b) showing normal sized sella with no evidence of sellar erosion or ballooning. Contrast-enhanced computed tomography scan of brain coronal (c) and axial (d) images does not reveal pituitary mass lesions

As small cell carcinoma of the lung is the most common source of ectopic ACTH production, a chest radiograph was taken in search of a primary lung malignancy. It revealed a well-defined opacity in the right lower lobe with right paratracheal lymphadenopathy [Figure 2a] and [Figure 2b].

Figure 2

X-ray chest posteroanterior view (a) and lateral view (b) showing a well-defined opacity involving right lower lobe. Transthoracic ultrasonogram (c) showing a well-defined isoechoic lesion involving right lower lobe abutting the liver. Transabdominal ultrasonogram (d) showing enlarged right adrenal gland

Ultrasound scanning of the chest and abdomen was done which showed a well-defined isoechoic lesion measuring 11.3 cm × 8.2 cm in the right lower lobe abutting the liver [Figure 2c]. The right suprarenal gland was enlarged measuring 4.48 cm × 1.87 cm [Figure 2d].

For further characterization, contrast-enhanced CT scan of the chest and abdomen was performed [Figure 3a-e]. A heterogeneously enhancing mass lesion was seen in the right lower lobe with invasion of the right descending pulmonary artery, right paratracheal and subcarinal lymphadenopathy, and a mildly enhancing nodule in the left upper lobe suggesting bronchogenic carcinoma Stage IVa (T4 N3 M1a). Both adrenal glands were diffusely enlarged with preservation of normal shape suggestive of bilateral adrenal hyperplasia. Compared to the previous CT scan, the size of the lesion had increased. Now, there is extensive mediastinal lymphadenopathy and an enhancing nodule in contralateral upper lobe. CT-guided biopsy from the right lower lobe mass and histopathological examination identified tumor to be a poorly differentiated adenocarcinoma.

Figure 3

Contrast-enhanced computed tomography scan of thorax and abdomen coronal (a) and axial (b-d) shows a heterogeneously enhancing mass lesion involving right lower lobe with invasion of the right descending pulmonary artery, right paratracheal and subcarinal lymphadenopathy, and a nodule in the left upper lobe. Diffusely enlarged bilateral adrenal glands with preservation of normal shape are seen in the coronal image (a) of contrast-enhanced computed tomography scan of the thorax and abdomen and in axial computed tomography image of the abdomen (e)

Ectopic Cushing's Syndrome (ECS) is a paraneoplastic endocrine syndrome manifesting with hypercortisolism, usually seen with carcinoids and small cell lung carcinoma and rarely with nonsmall cell lung carcinoma.[4] Typical cushingoid features include moon face, acne, purple striae, proximal myopathy, peripheral edema, hypertension, hyperglycemia, hypokalemia, and metabolic alkalosis. This classical presentation may be absent in cases of ectopic ACTH production by tumors other than carcinoids because of the sudden onset and aggressive nature. The preferred treatment for ECS includes treatment of the underlying malignancy with inhibition of cortisol secretion. Patients with ECS have poor prognosis and survival rate which is determined by the tumor histology, presence of metastases, and severity of hypercortisolemia.[5]

Our patient was started on ketoconazole 200 mg once daily following which he had improvement of symptoms. He also underwent chemotherapy for the primary lung malignancy. While on chemotherapy, he died due to cardiac arrest.

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Conflicts of interest

There are no conflicts of interest.