Surreal illustration representing the diagnostic journey of Cushing's syndrome.

The Case of the Cyclical Cushing's: A Diagnostic Odyssey

Rhea Morgan in Health & Wellness August 2025 • 4 min read.

"Unraveling the complexities of a rare Cushing's syndrome case involving a cyclic pattern and an unusual tumor location."

Cushing's syndrome (CS), a condition resulting from prolonged exposure to elevated levels of cortisol, presents a diagnostic puzzle when it stems from ectopic ACTH production. In these instances, tumors outside the pituitary gland secrete ACTH, the hormone that stimulates cortisol release. Identifying the source of this ectopic ACTH can be a lengthy and challenging process.

Adding another layer of complexity, some individuals with ectopic ACTH-dependent CS experience cyclical symptoms, where periods of cortisol excess alternate with periods of normal cortisol production. This cyclical pattern further complicates diagnosis and management.

This article delves into a fascinating case study of a patient with ACTH-dependent CS exhibiting a cyclical pattern and caused by an exceedingly rare tumor: a carotid glomus tumor, also known as a chemodectoma. We will explore the diagnostic hurdles, the impact of the cyclical nature of the disease, and the treatment approaches employed in this unique case.

The Diagnostic Labyrinth: Unmasking the Source of ACTH

Surreal illustration representing the diagnostic journey of Cushing's syndrome.

A 49-year-old Brazilian male presented with a constellation of symptoms including severe hypertension, mood swings, muscle weakness, skin darkening, and increased abdominal fat. Initial investigations pointed towards ACTH-dependent Cushing's syndrome, but the source of the excess ACTH remained elusive.

Adding to the diagnostic challenge, the patient's symptoms exhibited a cyclical pattern, with periods of severe hypercortisolism interspersed with periods of relative normalcy. These cycles were often exacerbated by episodes of diverticulitis, an intestinal infection, initially misleading the medical team to focus on the intestinal tract as the primary issue.

Extensive Imaging: Chest X-rays, CT scans, and MRI of the pituitary and abdomen were initially unremarkable, except for bilateral adrenal enlargement.
Petrosal Sinus Sampling: Bilateral simultaneous inferior petrosal sinus sampling (BIPSS) after desmopressin stimulation suggested ectopic ACTH production.
Colonoscopies: Multiple colonoscopies were performed, revealing intestinal polyps, but no malignancy or evidence of ACTH production.
Octreoscan: After four years of investigation, an Octreoscan finally pointed towards a neuroendocrine cervical tumor.

Ultimately, surgery revealed a neuroendocrine tumor of the carotid glomus, a chemodectoma, invading local lymph nodes. This tumor was confirmed to be producing ACTH, finally explaining the patient's Cushing's syndrome. This case marks the first reported instance of a carotid glomus tumor causing ACTH-dependent Cushing's syndrome in a cyclic fashion.

Lessons Learned: Navigating the Complexities of Ectopic ACTH Syndrome

This case underscores the diagnostic challenges posed by ectopic ACTH-dependent Cushing's syndrome, particularly when complicated by cyclical patterns. The rarity of chemodectomas as a cause of ectopic ACTH production further emphasizes the need for vigilance and comprehensive investigation.

Clinicians should consider the possibility of cyclical Cushing's syndrome in patients with fluctuating symptoms and be aware that infections or other co-morbidities can exacerbate these cycles, potentially masking the underlying cause.

The successful identification and treatment of this patient's chemodectoma highlights the importance of persistent investigation, even when initial imaging is inconclusive. Emerging techniques like genetic profiling for SDH mutations may aid in the diagnosis and risk stratification of such tumors in the future. Ketoconazole can be used for managing the symptoms

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1590/s0004-27302012000500008, Alternate LINK

Title: A Rare Case Of Cushing Syndrome By Cyclic Ectopic-Acth

Subject: General Medicine

Journal: Arquivos Brasileiros de Endocrinologia & Metabologia

Publisher: FapUNIFESP (SciELO)

Authors: Mariana Farage, Mario Alberto Da Dantas Loures Costa, Amélio Fernando Godoy-Matos

Published: 2012-07-01

Everything You Need To Know

Why is Cushing's syndrome resulting from ectopic ACTH production so challenging to diagnose?

Cushing's syndrome, in the context of ectopic ACTH production, is difficult to diagnose because tumors outside the pituitary gland secrete ACTH, leading to excess cortisol. Identifying the specific source of this ectopic ACTH can be challenging and time-consuming. This contrasts with Cushing's disease, where the excess ACTH comes from a pituitary adenoma, which is often easier to locate.

What makes cyclical Cushing's syndrome particularly difficult to identify?

Cyclical Cushing's syndrome, as seen in this case, involves alternating periods of cortisol excess and normal cortisol production. This pattern complicates diagnosis because hormone levels fluctuate, making it difficult to confirm the presence of Cushing's syndrome through standard testing. The intermittent nature of the symptoms can mislead clinicians and delay proper diagnosis, requiring a more extensive and repeated evaluation.

How did diverticulitis complicate the diagnosis in this specific Cushing's syndrome case?

In this case, the patient's symptoms were initially misleading due to exacerbations caused by episodes of diverticulitis, an intestinal infection. These episodes mimicked or worsened the symptoms of Cushing's syndrome, leading the medical team to initially focus on the intestinal tract as the primary source of the problem. This misdirection delayed the discovery of the actual cause, which was the ACTH-producing carotid glomus tumor.

What key diagnostic procedures were employed to identify the source of ACTH in this Cushing's syndrome case?

The diagnostic process involved extensive imaging, including chest X-rays, CT scans, and MRI, along with bilateral inferior petrosal sinus sampling (BIPSS). Colonoscopies were performed due to the initial suspicion of intestinal involvement. The key investigation that ultimately led to the diagnosis was the Octreoscan, which pointed towards a neuroendocrine cervical tumor. BIPSS after desmopressin stimulation suggested ectopic ACTH production, helping to differentiate the cause from a pituitary source.

What is a carotid glomus tumor (chemodectoma) and why is it significant in the context of Cushing's syndrome?

A carotid glomus tumor, also known as a chemodectoma, is a rare neuroendocrine tumor located in the carotid body. Its presence caused ACTH-dependent Cushing's syndrome in a cyclic fashion. The tumor's location near major blood vessels and nerves made surgical removal complex, but it was necessary to resolve the patient's condition. This case represents the first reported instance of a carotid glomus tumor causing ACTH-dependent Cushing's syndrome with a cyclical pattern, underscoring the importance of considering rare tumor locations in Cushing's syndrome diagnosis.