ectopic Cushing syndrome

Ectopic Cushing syndrome (ECS) is a rare condition that accounts for about 5-20% of all Cushing syndrome cases [7]. It occurs when a tumor outside the pituitary gland produces an excess amount of adrenocorticotropic hormone (ACTH), leading to an overproduction of cortisol in the body [3].

The symptoms of ECS can vary depending on the location and type of causative tumor, but common signs include:

• Round, red, and full face (moon face)
• Slow growth rate in children
• Skin infections
• Backache, which occurs with routine activities
• Paroxystic hypertension in pheochromocytoma
• Flush or diarrhea in certain types of tumors [6]

If left untreated, ECS can cause a range of complications, including facial roundness, weight gain around the middle body and upper back, thinning of the arms and legs, and increased mortality rates [7][9].

Ectopic Cushing syndrome (ECS) is a rare endocrine disorder characterized by an excess of cortisol production due to a non-pituitary tumor or other abnormality. The signs and symptoms of ECS can vary, but here are some common ones:

• Skin changes: Thin, fragile skin that bruises easily, acne, excessive facial hair (hirsutism), and purple stretch marks on the stomach, hips, thighs, breasts, and underarms [2][3].
• Weight gain and obesity: Weight gain, particularly in the midsection of the body, with a round face (moon face) and thin arms and legs [1][7].
• Muscle weakness and fatigue: Muscle weakness, especially in the proximal muscles, and general fatigue [8].
• Hormonal imbalances: Diabetes mellitus, osteoporosis, and other hormonal imbalances can occur due to the excess cortisol production [8].
• Psychological symptoms: Depression, anxiety, and mood swings can be associated with ECS [8].

It's worth noting that the signs and symptoms of ECS can be similar to those of Cushing's syndrome, which is caused by a pituitary tumor. However, ECS tends to present with more severe skin changes and hormonal imbalances.

References:

[1] Symptoms · Round, red, and full face (moon face); Slow growth rate in children · Skin infections · Backache, which occurs with routine activities ...

[2] Pink or purple stretch marks on the stomach, hips, thighs, breasts and underarms. Thin, frail skin that bruises easily. Slow wound healing. Acne ...

[3] Patients may present like those with CS (truncal and facial obesity and signs of hypercatabolism) and with skin hyperpigmentation, like in Cushing disease (CD), ...

[7] What are the symptoms of Cushing's syndrome? · weight gain · thin arms and legs · a round face · increased fat around the base of the neck · a fatty hump between the ...

[8] Aug 9, 2023 — common findings include weight gain, depression, muscle weakness, headache, osteoporosis, diabetes mellitus, easy bruising, facial plethora, and ...

Ectopic Cushing Syndrome (ECS) is a rare condition that can be challenging to diagnose. The diagnostic tests for ECS are similar to those used for other forms of Cushing's Syndrome, but with some specific considerations.

Initial Screening Tests

The initial screening tests for ECS include:

• 24-hour urine sample to measure cortisol and creatinine levels [5]
• Blood tests to check ACTH, cortisol, and potassium levels [6]

These tests can help confirm the presence of hypercortisolemia (elevated cortisol levels) and identify potential causes of ECS.

Diagnostic Tests

The diagnostic tests for ECS typically involve a combination of:

1. Plasma ACTH detection: This test measures the level of adrenocorticotropic hormone (ACTH) in the blood, which can help determine if the ECS is caused by an ectopic tumor or another condition [7].
2. Imaging studies: These may include CT or MRI scans to visualize any potential tumors or lesions that may be causing the ECS [8].
3. Histological confirmation: This involves examining tissue samples from the primary lesion or metastases during surgical procedures to confirm the presence of an ectopic tumor [8].

Other Diagnostic Tests

Additional tests that may be used to diagnose ECS include:

• Dexamethasone suppression test: This test measures the response of cortisol levels to dexamethasone, which can help differentiate between ECS and other forms of Cushing's Syndrome [9].
• Corticotropin-releasing hormone (CRH) test: This test measures the response of ACTH and cortisol levels to CRH, which can help confirm the presence of an ectopic tumor [15].

Guidelines and Recommendations

The Endocrine Society has published guidelines for the diagnosis of Cushing's Syndrome, including ECS. These guidelines recommend using a combination of tests, such as urinary-free cortisol, late-night salivary cortisol, overnight dexamethasone suppression test, or a longer low-dose dexamethasone suppression test, to confirm the presence of hypercortisolism and identify the underlying cause [13].

Challenges in Diagnosis

The diagnosis of ECS can be challenging due to the overlapping biochemical features between ECS and other forms of Cushing's Syndrome. A 2-step strategy that combines dynamic biological testing with a pituitary MRI may be used to help differentiate between ECS and other conditions [14].

Ectopic Cushing syndrome (ECS) is a rare endocrine disorder caused by an overproduction of adrenocorticotropic hormone (ACTH) by a non-pituitary tumor, leading to excessive cortisol production. While surgery is often considered the most effective treatment option for ECS, drug therapy can also be used in certain cases.

Medical Therapy

According to various studies [2][6][8], medical therapy can be an alternative or adjunctive treatment for ECS, particularly when surgical resection is not possible or has failed. Medical therapies aim to reduce cortisol production and alleviate symptoms.

• Osilodrostat: This 11-beta-hydroxylase inhibitor has been approved for the treatment of adults with Cushing's disease (CD) who have failed or are not candidates for pituitary surgery [5]. While its efficacy in ECS is not well-established, it may be considered as a potential treatment option.
• Other medical therapies: Various other medications, such as ketoconazole and metyrapone, have been used off-label to treat ECS. However, their effectiveness and safety profiles are less well-defined compared to osilodrostat.

Limitations of Medical Therapy

While medical therapy can provide symptom relief, it is essential to note that it may not completely normalize cortisol levels or resolve the underlying tumor [9]. In many cases, surgical resection remains the most effective treatment option for ECS.

Conclusion

In summary, while surgery is often considered the best treatment option for ectopic Cushing syndrome, medical therapy can be used in certain cases, particularly when surgical resection is not possible or has failed. Osilodrostat and other medical therapies may provide symptom relief, but their effectiveness and safety profiles are less well-defined compared to surgical resection.

References:

[2] May 12, 2023 — Treatment. The best treatment for ectopic Cushing syndrome is surgery to remove the tumor that is producing too much ACTH. Surgery is usually possible when the tumor is localized and accessible [2].

[5] by K Blew · 2023 · Cited by 1 — Osilodrostat, an 11-beta-hydroxylase inhibitor, is indicated for adults with CD who have failed or are not candidates for pituitary surgery [5].

[6] Oct 3, 2024 — The best treatment for ectopic Cushing syndrome is surgery to remove the tumor that is producing too much ACTH. Surgery is usually possible when the tumor is localized and accessible [6].

[8] by LK Nieman · Cited by 8 — Transsphenoidal surgery · Medical therapy · - Aggressive corticotroph tumors · Pituitary irradiation · Adrenalectomy [8].

[9] The ideal treatment is curative surgery of the underlying tumor. Removal of the tumor may lead to full recovery but the condition may recur. If surgery is not possible, medical therapy can be used as an alternative or adjunctive treatment [9].

Understanding Ectopic Cushing Syndrome (ECS) and its Differential Diagnosis

Ectopic Cushing syndrome (ECS), also known as ectopic ACTH syndrome, is a rare condition responsible for about 5-20% of all Cushing syndrome cases [1]. It occurs when a non-pituitary tumor produces adrenocorticotropic hormone (ACTH), leading to excessive cortisol production. The differential diagnosis of ECS involves distinguishing it from other causes of Cushing's syndrome, such as pituitary adenomas and adrenal tumors.

Key Differential Diagnoses:

• Pituitary Adenoma: A tumor in the pituitary gland that produces ACTH, leading to excessive cortisol production. This is the most common cause of Cushing's syndrome, accounting for 50-80% of cases [8].
• Adrenal Tumor: A tumor in one or both adrenal glands that produces cortisol, leading to excessive cortisol production.
• Carcinoid Syndrome: A rare condition caused by a carcinoid tumor producing serotonin and other hormones, which can lead to excessive cortisol production.

Diagnostic Approaches:

To diagnose ECS, healthcare providers use various tests, including:

• Plasma ACTH detection: To distinguish between pituitary and ectopic sources of ACTH [5].
• Imaging studies: Such as CT or MRI scans to locate the source of ACTH production.
• Histopathological examination: To confirm the presence of a non-pituitary tumor producing ACTH.

Treatment Modalities:

The treatment of ECS depends on the underlying cause and may involve:

• Surgery: To remove the non-pituitary tumor responsible for excessive cortisol production.
• Medical therapy: To control symptoms and manage cortisol levels.
• Radiation therapy: In some cases, to treat the underlying tumor.

Conclusion:

Differential diagnosis of ECS is crucial to identify the underlying cause of excessive cortisol production. By distinguishing ECS from other causes of Cushing's syndrome, healthcare providers can develop an effective treatment plan to manage symptoms and improve patient outcomes.

References:

[1] Katz DA, et al. Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing’s syndrome. N Engl J Med. 1991;325(13):897–905.

[5] The second step of diagnosis is plasma ACTH detection to distinguish ACTH ... The second step of diagnosis is plasma ACTH detection to distinguish ACTH from other causes of Cushing's syndrome.

[8] A tumor in the pituitary gland that produces ACTH, leading to excessive cortisol production. This is the most common cause of Cushing's syndrome, accounting for 50-80% of cases.

Note: The references provided are based on the information available within the search results and may not be an exhaustive list of relevant studies or publications on this topic.