Diagnosis of Adrenocortical Carcinoma with Hypercortisolism in a Patient Presenting with Hypokalemic Metabolic Alkalosis

Abstract

Adrenocortical carcinoma (ACC) is a rare malignancy with an estimated annual incidence of 0.7–2 cases per million. Most patients present with steroid hormone excess or abdominal mass effects, but 15% of patients with ACC are diagnosed incidentally. A careful history, physical exam, and pertinent lab investigations are necessary to reach the diagnosis. Surgical resection is the cornerstone of treatment in localized ACC; however, systemic chemotherapy with mitotane is preferred in patients with widespread disease or those who are not ideal candidates for surgery.

Introduction

Physicians often encounter patients with electrolyte derangements and are tasked with understanding why they occur. The ability to form many diagnoses that can play a role in such derangements is necessary to treat patients appropriately. We present the case of a patient with severe hypokalemia secondary to adrenocortical carcinoma (ACC). ACC is a very high-grade malignancy with a poor prognosis (1). Patient’s can present with signs of hormone overproduction. However, most of the time ACC is diagnosed incidentally. Managing ACC can be a challenge. Localized tumors can be surgically resected, whereas chemotherapy is offered to patients with metastatic ACC.

1. Case presentation

57-year-old male with past medical history of schizoaffective disorder and recently diagnosed hypertension who was brought to the emergency department after he had a fall and hit his head. On admission, the patient’s vital signs were normal with a blood pressure of 140/100. Physical exam was unremarkable. The patient had no family history of cancer. His baseline labs showed hypokalemia with a potassium level of 1.8 (3.6–5.2 mmol/L) and metabolic alkalosis with bicarbonate of 41 (22–29 mEq/L). The patient’s home medications included furosemide and antipsychotics. After admission, patient suddenly became hypoxic and was requiring oxygen via nasal cannula. CT scan and MRI abdomen/pelvis showed a large right adrenal mass measuring 15.5 × 9.8 cm in axial dimension and 16.2 cm in cranio-caudal dimension respectively (Figs. 1 and 2).

Fig. 1.

CT scan of the abdomen/pelvis showing large right adrenal mass measuring 15.5 × 9.8 cm in axial dimension. The mass abuts right hepatic lobe.

Fig. 2.

MRI abdomen showing large heterogeneously enhancing mass centered in the region of the right adrenal gland measuring. 16.3 cm cephalocaudal dimension. Mass contains small areas of T1 hyperintense signal suspicious for blood products. Areas of necrosis noted within the mass. Mass inseparable from and compressing posterior right hepatic lobe and caudate lobe. Significant mass effect on the suprarenal IVC as well as extension of the mass into the intrahepatic IVC lumen.

Workup for adrenal mass showed aldosterone 7.7 (<23.2 ng/dl), direct renin 9.1 (<33.2 pg/ml) with a ratio of 0.85, ruling out primary hyperaldosteronism. His cortisol was 47.8 (6.7–27.60 Ug/dl) and the repeat was 48 after dexamethasone suppression test was performed. His ACTH was <1.5 (7.2–63 pg/ml), pointing towards primary hypercortisolism. Other significant labs findings included DHEA sulfate of 520 (70–310 ug/dl), 17-hydroxyprogesterone of 310 (27–199 ng/dl) and androstenedione of 103 (40–150 ng/dl). His HbA1C (<6.5%) also jumped up from 6 to 9 in the last 6 months. Due to the risk of malignancy, interventional radiology was consulted to biopsy the adrenal mass. Pheochromocytoma was ruled out before the biopsy as the plasma metanephrines 28.9 (0–244 pg/dl) and normetanephrine 16.2 (0–88 pg/dl) were within normal limits. Meanwhile, the patient was started on lisinopril and spironolactone, and potassium was repleted as needed. He was started on insulin regimen for the new onset diabetes. Biopsy confirmed the diagnosis of adrenal cortical carcinoma, myxoid variant (Fig. 3). Immunohistochemical staining (Inhibin+, Melan-A+, Calretinin, Synaptophysin+) supported an adrenal cortical phenotype (Fig. 4).

Fig. 3.

D cells in myxoid stroma consistent with Adrenocortical carcinoma.

Fig. 4.

Immunohistochemical staining: A-Inhibin+; B- Calretinin; C-Synaptophysin+; D- Ki 67.

Urology was consulted for surgery but due to the locally advanced adrenocortical carcinoma with liver invasion and extension into the inferior vena cava, the decision was made not to proceed due to the high risk of morbidity and mortality. The patient was planned for chemotherapy with mitotane and was transferred to an adrenal facility for better care. Patient was eventually lost to follow up.

2. Discussion

Adrenocortical carcinoma (ACC) is a very rare and aggressive endocrine tumor,witha reported-incidence of 0.5–2 cases per million, occurring more commonly in women.1 Majority of the cases have already metastasized at the time of diagnosis, most commonly involving the lymph nodes, lungs, liver and bone. Due to its aggressive nature, detection at initial stages is associated with better surgical outcomes. About 60% of the patients present with symptoms of hormone excess, which may manifest in the form of Cushing syndrome, electrolyte abnormalities or virilization, whereas non-specific symptoms like abdominal fullness and flank pain may be seen in the rest of the patients having non-functioning tumors. Hypercortisolism is the most common manifestation of a functional ACC, which was seen in our patient. Most patients will have suppressed ACTH and increased cortisol when checked at 08:00 am. Hypercortisolism is confirmed by a 1 mg dexamethasone suppressiontest, midnight salivary cortisol or elevated 24-h free cortisol in urine.2 Other supportive lab findings include elevated serum glucose and adrenal androgens. High urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) are also indicative of ACC. There are various distinct histological morphologies of this tumor, and among these the myxoid variant is a very rare and aggressive subtype, which was seen in our patient. The differential diagnoses in adults include Cushing syndrome, renal cell carcinoma, hyperaldosteronism and hyperandrogenism,3 whereas those in children include nephroblastoma, neuroblastoma, and metastatic adrenal deposits. Our patient had an elevated cortisol level with a biopsy proven adrenocortical carcinoma. Normal plasma aldosterone to renin ratio (ARR) and normal androgen levels ruled out primary hyperaldosteronism and hyperandrogenism, respectively. Approximately 30% of the ACCs are diagnosed incidentally while scanning for other medical issues.4 Diagnostic modalities include biochemical and hormonal tests, imaging (such as CT, MRI, and FDG-PET scan), and confirmation of diagnosis via histopathology after biopsy.5 Complete surgical excision is the premier treatment option. Other treatment options entail a multi-disciplinary approach and include mitotane systemic therapy, cytotoxic chemotherapy, radiation therapy, radiofrequency ablation, and immunotherapy. Mitotane, by virtue of its adrenolytic activity, reduces local recurrence and can be used in advanced ACC when surgery isn’t a viable option, and thus was used in the treatment of our patient.6 The prognosis for ACC is poor, with 5-year survival rates hovering around 15–44%.7 Older age, functioning tumor, advanced stage at diagnosis, and incomplete resection are the main clinical factors associated with poor survival. Recurrence is frequently seen following a complete resection. Median time of recurrence is 1 year. Surveillance includes CT of the chest and abdomen every 3 months along with monitoring of steroid hormones.8 Ultrasound has shown clinical significance during follow up of selected patients.9

3. Conclusion

We encountered a rare case of Cushingoid adrenocortical carcinoma. It is very crucial to diagnose it early, as its poor prognosis and overall survival can largely be attributed to its aggressive nature and diagnosis at advanced stages. Complete surgical resection remains the mainstay of treatment offering the best chance for long term survival; however, adjuvant chemotherapy and radiotherapy can be offered to high-risk patients. Regular follow up plans should be established due to the high recurrence rate of such tumors.