Challenging case: A young woman presenting with rapid weight gain

“Challenging Cases in Urology” is a new Urology Times section in which residents from the nation’s leading urology programs present their toughest cases and how they ultimately managed them. Cases inform readers of the problem-solving process and provide a lesson from the authors’ experience.

Douglas Ridyard, MD, is a urology resident at the University of Connecticut School of Medicine, Farmington.

History

An 18-year-old previously healthy collegiate athlete presented to the emergency room with a rapid weight gain of 20 pounds during the previous 2 months. She complained of significant fatigue and irregular menstrual periods.

Examination

On initial examination, the patient was hypertensive with a blood pressure of 170/110. She had a rounded face and a dorsocervical fat pad. Her abdominal exam was unremarkable with no palpable masses. A basic metabolic panel in the emergency room demonstrated hypokalemia and hyperglycemia.

A CT scan, on the following page, was performed (figure).

Next: What further testing would you perform to confirm the diagnosis?

Laboratory testing and treatment

The patient was initially referred to endocrinology for a metabolic evaluation. She underwent extensive testing, which demonstrated a cortisol level of 46 ug/dL (normal, <5 uq/dL) after an overnight 1-mg dexamethasone suppression test. An ACTH level was subsequently measured at <5 pg/mL.

An abdominal CT study with contrast washout was performed that demonstrated an absolute 72% washout within the mass, which favored the diagnosis of a benign adrenal adenoma.

The patient underwent a laparoscopic right adrenalectomy. The final pathology demonstrated a 6.5-cm high-grade adrenocortical carcinoma. After her surgery, the patient received adjuvant treatment with both radiation and mitotane (Lysodren) chemotherapy. The patient continues on close surveillance with regular cross-sectional imaging of the chest, abdomen, and pelvis as well as monitoring of her endocrine markers.

Discussion

This case documents the unfortunate presentation of a young woman with Cushing syndrome, which was ultimately found to be the result of a functional adrenocortical carcinoma. The case demonstrates the importance of a prompt and thorough workup of patients presenting with endocrine derangements.

The patient initially presented with classic features of Cushing syndrome, including weight gain, moon facies, and a buffalo hump. Cushing syndrome, the result of excessive levels of circulating cortisol, can be confirmed by a 24-hour urine-free cortisol, an overnight dexamethasone suppression test, or a late night salivary cortisol level.

Endocrine Society clinical practice guidelines recommend performing two different types of screening tests to establish the diagnosis of Cushing syndrome (J Clin Endocrinol Metab 2008; 93:1526-40). Testing ACTH levels ascertains whether Cushing syndrome reflects a primary pituitary lesion or an adrenal source of cortisol. ACTH levels were low in this patient, indicating a primary adrenal source of her high serum cortisol levels.

A non-contrast CT is the initial imaging study recommended for the evaluation of adrenal lesions. This imaging modality usually confirms the presence of a mass and also helps establish whether the mass is a benign adrenal adenoma or an adrenocortical carcinoma. Adrenal adenomas typically have a high lipid content compared to malignant lesions. An adrenal mass that measures less than 10 HU is generally considered diagnostic of a benign adenoma. Adrenal masses of greater than 10 HU should undergo testing with a CT washout study to further characterize the mass. An absolute percent washout of greater than 60% usually indicates a benign adenoma (J Am Coll Radiol 2017; 14:1038-44). Imaging of the mass presented in this case demonstrated a 5.4-cm mass with 40 HU on non-contrast imaging and an absolute washout of 72%, suggesting the mass was a benign atypical adenoma.

Due to the size of the patient’s mass as well as its functional component, surgical removal of the mass was indicated. The final pathology revealed an adrenocortical carcinoma. Adrenocortical carcinomas are not commonly found in young adults. They usually have a bimodal age distribution with peaks in the first decade of life as well as the fourth and fifth decade (Ann Oncol 2012; 23 [Suppl 7]:vii131-8). Due to the rarity of the disease, defined treatment algorithms have not been established or validated, but there are several accepted management principles that warrant review.

Next: "The primary concern associated with surgical management is rupture of the tumor capsule and tumor spillage into the wound."The primary concern associated with surgical management is rupture of the tumor capsule and tumor spillage into the wound. While there are limited data comparing open versus laparoscopic techniques, some surgeons favor open surgical resection of suspicious masses to reduce the chance of tumor spillage (Ann Oncol 2012; 23 [Suppl 7]:vii131-8). Lymphadenectomy at the time of tumor resection is controversial, but a recent retrospective study of over 100 patients demonstrated a significant survival benefit from lymphadenectomy at 5-year follow-up (Ann Surg Oncol 2016; 23 [Suppl 5]:708-13).

The primary treatment of adrenocortical carcinoma is complete surgical resection. This provides the sole opportunity for disease-free survival (Ann Oncol 2012; 23 [Suppl 7]:vii131-8). Due to the high risk of recurrence, adjuvant treatment is commonly utilized, although its efficacy is poorly understood due to the relative rarity of the disease. Adjuvant radiation is recommended in patients with high-risk disease, as small trials have demonstrated reduced local recurrence of tumor after adjuvant radiation. Long-term survival benefit from adjuvant radiation remains unproven (Int J Radiat Oncol Biol Phys 2015; 92:252-9).

Mitotane is the primary chemotherapeutic agent used in the treatment of adrenocortical carcinoma. It is toxic toward adrenal cortical cells, and steroid replacement therapy is required. Mitotane’s efficacy is supported by case control studies. A prospective randomized trial is currently ongoing (Ann Oncol 2012; 23 [Suppl 7]:vii131-8). Close follow-up is needed in adrenocortical carcinoma because of its high rate of recurrence. Specific surveillance guidelines have not been established, but some authors suggest thoracic and abdominal imaging along with endocrine studies as frequently as every 3 months after surgical resection (Ann Oncol 2012; 23 [Suppl 7]:vii131-8).

Conclusion

Adrenocortical carcinoma is a rare cancer with a high recurrence rate after surgical resection. Due to the rarity of the disease, limited clinical data are available to guide management. Although uncommon in younger patients, this case demonstrates the importance of a vigilant approach toward adrenal lesions.