Case Presentation: A 35-year-old female with a history of depression, psychosis, hypertension, and type 2 diabetes presented to the emergency room for severe hypokalemia found on routine labs. She was hospitalized for an episode of psychosis a month prior with a suicide attempt and was being treated at an inpatient mental health clinic since then. On admission, the patient was experiencing signs of psychosis including hallucinations and disordered speech. The patient was also hypertensive with a blood pressure of 150/93. She was recently started on insulin for new onset diabetes and losartan for new onset hypertension. Labs on admission were significant for leukocytosis, hypokalemia, and hyperglycemia. Initial differentials included hyperaldosteronism, hypercortisolism, insulin abuse, or pheochromocytoma. C peptide and serum metanephrines were normal. Aldosterone levels were slightly low. Morning serum cortisol and ACTH levels were significantly elevated, indicating a Cushing syndrome. A whole-body CT scan, MRI brain, and MRI abdomen was ordered to assess for pituitary masses or other ectopic sources of ACTH. A 2.2 x 2.4 x 1.8 cm mass on the inferior anterior mass on the right kidney was found on CT scan and MRI and this was thought to be the source of the ectopic ACTH (Figure 1). Urology performed a right partial nephrectomy. Pathology results of the renal mass confirmed chromophobe renal cell carcinoma. Genetic testing revealed an FLCN mutation, diagnostic for BHDS. The patient had no further episodes of psychosis after the surgery. She was discharged on hydrocortisone 30 mg twice per day.
Discussion: BHDS is an exceedingly rare autosomal dominant disorder caused by mutations in the FLCN tumor suppressor gene, with symptoms of the disease occurring between 30-50 years old. BHDS patients have an increased risk of renal cell carcinoma (RCC), particularly chromophobe or hybrid oncocytic tumors. RCC in BHDS has an excellent prognosis with the treatment of choice being nephron sparing surgery to remove the cancer once the dominant tumor is larger than 3 cm. Most patients only need one renal surgical intervention in their lifetime as the tumors are slow-growing and usually do not metastasize. In this case, our patient with BHDS not only presented with chromophobe RCC but also developed Cushing syndrome because of the tumor’s hormonal activity. Cushing’s syndrome is characterized by excessive levels of cortisol in the blood, which can result from various etiologies, including endogenous overproduction or exogenous administration of corticosteroids. Cushing’s syndrome can also result from ectopic ACTH production and lead to a wide range of clinical manifestations, including weight gain, hypertension, diabetes mellitus, and skin changes. Psychiatric symptoms, including psychosis and depression, can also occur due to the excess cortisol.
Conclusions: In conclusion, this is the first ever recorded case of ectopic ACTH-secreting RCC in a patient with BHDS. The patient was successfully treated with tumor resection with resolution of her diabetes, hypertension, hypokalemia, and psychosis. This case underscores the importance of recognizing the diverse manifestations of BHDS, highlighting the need for vigilant monitoring of associated conditions such as chromophobe RCC and its rare complications like Cushing syndrome.
