malignant ACTH producing neoplasm of pituitary gland

A malignant ACTH-producing neoplasm of the pituitary gland, also known as a pituitary carcinoma, is a rare and aggressive form of cancer that arises from the corticotrophic cells of the anterior pituitary gland. This type of tumor produces excess adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce excessive cortisol, leading to Cushing's syndrome.

Characteristics:

• Rarity: Pituitary carcinomas are extremely rare, accounting for only a small percentage of all pituitary tumors.
• Aggressiveness: These tumors are highly aggressive and can metastasize early, making them challenging to manage.
• Symptoms: Patients with pituitary carcinoma may experience symptoms similar to those with Cushing's syndrome, such as weight gain, high blood pressure, and glucose intolerance.

Causes:

• Genetic mutations: Pituitary carcinomas are often associated with genetic mutations that disrupt normal cell growth and division.
• Environmental factors: Exposure to certain environmental toxins or radiation may contribute to the development of pituitary carcinoma.

Treatment options:

• Surgery: Surgical removal of the tumor is often the first line of treatment, but complete resection can be challenging due to the tumor's aggressive nature.
• Radiation therapy: Radiation therapy may be used in conjunction with surgery or as a standalone treatment option.
• Chemotherapy: Chemotherapy may be considered for patients with metastatic disease.

Prognosis:

• Poor prognosis: Pituitary carcinomas have a poor prognosis, with a 5-year survival rate of less than 20% (4).

References:

(1) - These malignant behaving tumors are called pituitary carcinomas (PC). PC is challenging to manage as they metastasize early and have a poor response to treatment. [4]

(11) Adrenocorticotropic hormone (ACTH)-producing tumors. ACTH stimulates the adrenal gland to make glucocorticoids (or steroids, which influence metabolism and act as anti-inflammatory and immunosuppressive agents). An oversupply of ACTH, such as that produced by this type of tumor, can cause Cushing's disease (one type of Cushing's syndrome). [11]

(7) Pituitary carcinoma is a cancerous (malignant) tumour of the pituitary gland. [7]

Symptoms of Malignant ACTH Producing Neoplasm of Pituitary Gland

A malignant ACTH (Adrenocorticotropic Hormone) producing neoplasm of the pituitary gland can cause a range of symptoms, primarily due to excessive production of cortisol by the adrenal glands. Some common signs and symptoms include:

• Weight gain: Particularly around the neck and midsection, as well as thinning of the arms and legs [3][5]
• Unexplained weight gain: Reflected in the face, neck, and trunk of the body, but with thin arms [5]
• Headache: Due to pressure on the brain or nearby structures [2][8]
• Vision problems: Such as blurred vision or loss of side vision (peripheral vision) due to pressure on the optic nerves [6][13]
• Dizziness: Caused by pressure on the brain or nearby structures [6]
• Numbness or pain in the face, neck, and trunk: Due to excessive cortisol production [7]

Other Possible Symptoms

In addition to these symptoms, a malignant ACTH producing neoplasm of the pituitary gland may also cause:

• Menstrual disorders: In women, due to hormonal imbalances [7]
• Cold intolerance: Caused by decreased levels of thyroid hormones [7]
• Excessive hair growth: On the face and body, due to hormonal imbalances [12]

Important Note

It's essential to seek medical attention if you experience any of these symptoms. A doctor will perform a physical examination, ask questions about your health, and order blood and urine tests to check hormone levels. If signs point to a pituitary tumor, further tests may be necessary to confirm the diagnosis.

References:

[3] Cushing's Disease Signs & Symptoms [5] Dec 21, 2021 — Adrenocorticotropic Hormone (ACTH) [6] Symptoms of growing tumours [7] All pituitary tumors and craniopharyngiomas [8] When the tumor is big enough, it may cause headaches and vision problems. [12] For example, benign pituitary gland tumors can make high levels of another hormone called adrenocorticotropic hormone (ACTH).

Diagnosing Malignant ACTH Producing Neoplasms of the Pituitary Gland

The diagnosis of malignant ACTH (Adrenocorticotropic hormone) producing neoplasms of the pituitary gland involves a combination of medical history, physical examination, and various laboratory tests.

• Medical History and Physical Exam: A thorough medical history and physical examination are essential to identify any symptoms or signs that may suggest a pituitary tumor. This includes questions about personal and family medical history, as well as a physical exam to check for any abnormalities [5].
• Hormone Blood Testing: Hormone blood testing is used to diagnose pituitary tumors by measuring the levels of ACTH and cortisol in the blood. Elevated levels of these hormones can indicate an overproduction of cortisol due to a pituitary tumor [7].
• Urine Tests: Urine tests may also be used to help diagnose a pituitary adenoma that's making too much of the hormone ACTH, which leads to Cushing's disease [2].
• Imaging Studies: Imaging studies such as MRI scans are essential for diagnosing pituitary tumors. An MRI scan can detect a pituitary adenoma in about 70 percent of cases [8]. These imaging tests should be performed at a pituitary center with special expertise to ensure accurate diagnosis.
• Lab Tests of Pituitary Tissue Samples: In some cases, lab tests may be performed on tissue samples taken from the pituitary gland to confirm the presence and type of tumor.

It's worth noting that an accurate diagnosis usually involves hormone tests and an MRI scan of the pituitary gland [3]. Additionally, blood, urine, and saliva tests are used to diagnose Cushing's disease, which is caused by an overproduction of cortisol due to a pituitary tumor [4].

References:

[1] Oct 10, 2022 — Medical history and physical exam, lab tests of hormone levels, testing for diabetes insipidus, imaging tests, lab tests of pituitary tissue samples. [2] Jun 29, 2024 — Urine tests. A urine test may be used to help diagnose a pituitary adenoma that's making too much of the hormone ACTH . Too much ACTH leads ... [3] An accurate pituitary tumor diagnosis usually involves hormone tests and an MRI scan of the pituitary gland. Hormone Blood Testing to Diagnose Pituitary Tumors. [4] Cushing's disease is diagnosed using blood, urine, and saliva tests that look for abnormal amounts of the hormone cortisol. You may also need to have an MRI ... [5] Mar 10, 2023 — Imaging studies and tests that examine the blood and urine are used to diagnose a pituitary tumor. In addition to asking about your personal and ... [6] by M Orr · 2022 · Cited by 1 — This report describes a complete resolution of severe Cushing disease due to an ACTH secreting pituitary carcinoma followed by the development of pituitary ... [7] May 12, 2023 — Exams and Tests · 24-hour urine sample to measure cortisol and creatinine levels · Blood tests to check ACTH, cortisol, and potassium levels (the ... [8] MRI detects a pituitary adenoma in about 70 percent of cases. It is important that you undergo these imaging tests at a pituitary center with special expertise ... [9] Oct 1, 2024 — Blood and urine tests are as important as imaging tests in diagnosing adrenal cancer. Doctors might choose which tests to do based on the patient's symptoms.

Treatment Options for Malignant ACTH Producing Neoplasms of the Pituitary Gland

Malignant ACTH (Adrenocorticotropic hormone) producing neoplasms of the pituitary gland are rare and aggressive tumors that can cause Cushing's disease. While surgery, radiation therapy, and chemotherapy may be used to treat these tumors, drug treatment is often a crucial component of their management.

Everolimus and Octreotide Combination Therapy

One potential drug treatment for malignant ACTH producing neoplasms of the pituitary gland is the combination of everolimus and octreotide. Everolimus is an mTOR inhibitor that can help reduce tumor growth, while octreotide is a somatostatin analog that can decrease ACTH production (8). This combination therapy has been reported to be effective in treating ACTH-secreting pituitary carcinomas (8).

Temozolomide and Immunotherapy

Another potential drug treatment for malignant ACTH producing neoplasms of the pituitary gland is temozolomide, a chemotherapy agent that can induce tumor regression. Temozolomide has been reported to be effective in treating hypermutated ACTH-secreting pituitary carcinomas (9). Additionally, immunotherapy with ipilimumab and nivolumab may also be beneficial in treating these tumors (9).

Limitations of Drug Treatment

While drug treatment can be an important component of managing malignant ACTH producing neoplasms of the pituitary gland, it is essential to note that there are limitations to its effectiveness. For example, there is no effective drug that lowers ACTH production and shrinks the pituitary tumor (11). Furthermore, surgery may fail to completely remove the tumor, making it challenging to manage symptoms related to excessive cortisol production (11).

Multidisciplinary Approach

The treatment of malignant ACTH producing neoplasms of the pituitary gland often requires a multidisciplinary approach. This includes a team of experts in neurology, endocrinology, and oncology working together to develop an individualized treatment plan for each patient (12). Standard treatment options include surgery, radiation therapy, drug therapy, and chemotherapy.

References

• [8] Jouanneau et al. reported an ACTH-secreting pituitary carcinoma treated in combination of everolimus and octreotide.
• [9] Temozolomide treatment can improve ... Marked response of a hypermutated acth-secreting pituitary carcinoma to ipilimumab and nivolumab.
• [11] There is no effective drug that lowers ACTH production and shrinks the pituitary tumor.
• [12] Pituitary tumor treatment. Standard treatment for pituitary tumors includes surgery, radiation therapy and drug therapy.

Differential Diagnosis of Malignant ACTH Producing Neoplasm of Pituitary Gland

The differential diagnosis of a malignant ACTH (Adrenocorticotropic hormone) producing neoplasm of the pituitary gland involves distinguishing it from other conditions that may cause similar symptoms. According to various medical sources [3, 6, 10], the following are some important considerations:

• Ectopic Cushing syndrome: This is a condition where a tumor outside the pituitary gland produces ACTH, leading to excessive cortisol production. It can be caused by various types of tumors, including small cell lung carcinoma and neuroendocrine tumors [11].
• Pituitary adenoma: A benign tumor on the pituitary gland that can secrete increased amounts of ACTH, leading to Cushing's disease [8, 9]. However, in some cases, it may be difficult to detect a pituitary adenoma using medical imaging techniques [13].
• Breast carcinoma: Metastases from breast carcinomas, especially HER2-positive subtypes, can also cause Cushing's syndrome by producing ACTH [6].

Key Points

• A malignant ACTH producing neoplasm of the pituitary gland should be considered in the differential diagnosis of Cushing's syndrome.
• Ectopic Cushing syndrome and pituitary adenoma are other important conditions to consider, especially when evaluating patients with excessive cortisol production.
• Accurate diagnosis is crucial for determining the appropriate treatment approach.

References

[3] WS Butt · 2022 · Cited by 2 — Pituitary cancer includes pituitary carcinoma and systemic metastases to the pituitary gland. Some hereditary conditions are also related to an increased risk ...

[6] by P Burman · 2023 · Cited by 31 — Differential Diagnoses—Pituitary Metastases​​ Metastases to the pituitary gland most commonly originate from breast carcinomas, especially HER2-positive subtypes...

[8] Adenomas are benign, or non-cancerous, tumors of the pituitary gland which can secrete increased amounts of ACTH. Women are affected 5 times as often as men ...

[9] Pituitary adenomas are benign tumors on your pituitary gland. They're noncancerous, but they can interfere with normal pituitary function and cause certain...

[10] However, in the differential diagnosis of hypercorticism with an elevated plasma ACTH concentration, the clinician should consider the possibility of an ACTH producing pituitary tumor.

[11] Pituitary adenoma is not detected in up to one-third of cases. Ectopic Cushing syndrome may be associated with either malignant neoplasia (such as small cell lung carcinoma) or less aggressive neuroendocrine tumors, exhibiting only the typical symptoms and signs of CS.

[13] A brief description of approaches to the differential diagnosis of Cushing’s syndrome and subsequent treatment. From a physiological point of view, it would seem fairly simple to distinguish patients with pituitary tumors (Cushing’s disease) from those with ectopic ACTH-secreting tumors using medical imaging techniques.