# Ectopic Cushing Syndrome due to Metastatic Medullary Thyroid Cancer

**Authors:** Majd Oweidat, Anas Abu Rumilah

PMC · DOI: 10.1016/j.aed.2025.03.003 · AACE Endocrinology and Diabetes · 2025-04-10

## TL;DR

A rare case of Cushing syndrome caused by metastatic medullary thyroid cancer is reported, emphasizing the need for early diagnosis.

## Contribution

Highlights medullary thyroid cancer as a rare cause of ectopic ACTH secretion leading to Cushing syndrome.

## Key findings

- Metastatic medullary thyroid cancer can cause ectopic ACTH secretion resulting in Cushing syndrome.
- Delayed diagnosis of ACTH-dependent hypercortisolism increases morbidity and worsens outcomes.
- Systematic evaluation using biochemical markers, imaging, and cytology is crucial for rare hypercortisolism cases.

## Abstract

Cushing syndrome (CS) is a life-threatening condition that occurs due to hypercortisolism. The most common cause of endogenous CS is adrenocorticotropic hormone (ACTH)–dependent CS caused by a pituitary adenoma (Cushing disease). Ectopic production of ACTH from tumors elsewhere in the body is rare and is most often associated with small cell lung cancer. This report describes a patient with ACTH-dependent CS secondary to metastatic medullary thyroid cancer (MTC), a rare cause of ectopic CS.

A 52-year-old man presented with progressive diarrhea, fatigue, muscle weakness, and hypokalemia. Initial investigations revealed metabolic alkalosis, elevated urinary potassium excretion, and fasting hyperglycemia. Evaluations confirmed ACTH-dependent hypercortisolism with elevated serum ACTH and urinary free cortisol levels. Imaging and fine needle aspiration confirmed MTC with metastatic lymph node involvement, supported by elevated serum calcitonin and carcinoembryonic antigen levels. Surgical intervention revealed extensive tumor invasion but was complicated by vascular injuries, resulting in postoperative hypoxic brain injury and fatality.

This case highlights the importance of early recognition and investigation of unexplained ACTH-dependent hypercortisolism. Delayed diagnosis complicates management, increases morbidity, and worsens outcomes. A systematic diagnostic approach—including biochemical markers, imaging, and cytology—is crucial in identifying rare causes of hypercortisolism.

Early evaluation of persistent hypokalemia and hypercortisolism is essential to prevent delayed diagnosis of CS. This case highlights MTC as a rare source of ectopic ACTH secretion.

## Linked entities

- **Diseases:** Cushing syndrome (MONDO:0018912), small cell lung cancer (MONDO:0008433)

## Full-text entities

- **Genes:** CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796] {aka CALC1, CGRP, CGRP-I, CGRP-alpha, CGRP1, CT}, POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}
- **Diseases:** CS (MESH:D003480), hypokalemia (MESH:D007008), small cell lung cancer (MESH:D055752), diarrhea (MESH:D003967), MTC (MESH:C536914), vascular injuries (MESH:D057772), Cushing disease (MESH:D047748), muscle weakness (MESH:D018908), tumor (MESH:D009369), fatigue (MESH:D005221), metabolic alkalosis (MESH:D000471), pituitary adenoma (MESH:D010911), hypoxic brain injury (MESH:D002534), hyperglycemia (MESH:D006943)
- **Chemicals:** potassium (MESH:D011188), cortisol (MESH:D006854)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

16 references — full list in the complete paper: https://tomesphere.com/paper/PMC12268540/full.md

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Source: https://tomesphere.com/paper/PMC12268540