Case Presentation: A 74-year-old female presented with a history of chronic diarrhea of 3 years duration, weight loss, blood in the stool, and abdominal cramps. Past medical history was significant for hypertension, metabolic syndrome, and previous episode of perforated diverticulitis. Physical examination identified a nontender 2 cm mass in her left submandibular area with no thyromegaly. The serological exam showed elevated chromogranin A and a carcinoid tumor was suspected. An octreotide scan identified an uptake on the right side of the abdomen and the left side of the neck. Simultaneously, workup for secretory diarrhea revealed a greatly elevated calcitonin level. Ultrasound of the neck identified a highly suspicious thyroid mass, CT scan showed a heterogeneous thyroid nodule, and several enhanced lesions in the liver. The patient had no family history of medullary thyroid cancer (MTC) or MEN syndrome. A liver biopsy offered evidence of MTC. Subsequently, thyroid biopsy confirmed a diagnosis of MTC. The patient underwent a total thyroidectomy followed by chemotherapy. Her regiment included Vandetanib, to which she had an excellent response leading to resolution of diarrhea and normalization of bowel function. However, the drug was poorly tolerated, and the dosage had to be tapered down and eventually stopped completely.2.5 years after the initial diagnosis of MTC, the patient returned to the clinic with symptoms consistent with a Cushing syndrome (CS). Cortisol level was drastically elevated. Further workup was started with high dose dexamethasone suppression test, which failed to affect the elevated cortisol levels, indicating an ectopic ACTH tumor. Brain MRI ruled out pituitary adenoma. It was concluded that the liver lesions were the source of ectopic ACTH. Patient was not a good surgical candidate, and bilateral adrenalectomy was not an option. While still in the hospital, the patient developed altered mental status and bleeding of colovaginal fistula. Her calcitonin level increased. Patient’s family decided in favor of comfort care, and less than 2 weeks later patient passed away.
Discussion: Among the most common presenting signs of MTC are detectable cervical lymph nodes, and upper aerodigestive tract compression. Our patient’s presenting symptom was diarrhea, in which case MTC is not high on a differential. Nonetheless, the work up for patient’s GI disturbances helped to reveal an accurate diagnosis.
Production of ACTH by an MTC metastasis is a rare occurrence. Even with the primary lesion being removed, liver metastasis produced ACTH leading to CS, and overall worsening health superimposed on major pre-existing health issues. Ultimately, late diagnosis due to an unusual presentation of MTC, and other comorbidities lead to poor prognosis.
Conclusions: ECS triggered by ACTH producing MTC liver metastasis is a rare syndrome that signifies progressive disease. MTC should be considered in patients presenting with chronic diarrhea and weakness unexplained by other causes.