Paraneoplastic Endocrine Syndromes- An Overview

Introduction

Endocrine paraneoplastic syndromes are clinical conditions caused by tumors (which do not produce any hormones) that produce hormones or cytokines. These syndromes can help with early diagnosis of cancer, monitor cancer progression, or avoid diagnostic errors. Symptoms of paraneoplastic endocrine syndrome occur in eight percent to 20 percent of individuals with cancer. Although paraneoplastic endocrine syndrome can occur at any age, it is more common among older individuals and is not specific to any race or sex.

What Are Paraneoplastic Endocrine Syndromes?

Normally, endocrine glands in the body produce hormones that regulate various bodily functions. However, in paraneoplastic endocrine syndromes, cancer cells produce hormones or hormone-like substances that cause abnormal levels of hormones in the body, leading to various symptoms. The specific hormone or substance produced by cancer cells depends on the type of cancer involved. In some cases, the immune system may also play a role by attacking normal cells (autoimmune response) in the body in response to the presence of cancer cells, leading to the development of paraneoplastic syndromes.

While the incidence of these are relatively rare, paraneoplastic endocrine syndrome can have a significant impact on individual outcomes and are important to consider in the diagnosis and management of cancer. The nervous system, bones, hormones, and other systems and organs are affected by paraneoplastic endocrine syndromes.

What Are the Types of Paraneoplastic Endocrine Syndromes?

The most common types of endocrine paraneoplastic syndromes include:

• Inappropriate Secretion of the Antidiuretic Hormone (SIADH)- This occurs when the tumor produces a hormone that affects the kidneys, leading to water retention and low levels of sodium in the blood.

• Malignancy-Related Hypercalcemia- It is caused by the tumor producing a substance that increases calcium levels in the blood. Consequently, this can lead to a range of symptoms, including fatigue, nausea, and confusion. Malignancy-related hypercalcemia is the most common type of paraneoplastic endocrine syndrome.

• Hypoglycemia- Hypoglycemia can occur when the tumor produces insulin-like substances that cause low blood sugar levels, which can result in weakness, dizziness, and confusion.

• Cushing Syndrome- Cushing syndrome is caused by the production of cortisol-like substances by the tumor, leading to a range of symptoms such as high blood pressure, weight gain, and an increased risk of infections.

• Acromegaly- Acromegaly is caused by the production of growth hormone-like substances, leading to an overgrowth of bones and soft tissues in the body.

Which Types of Cancer Are Linked to Paraneoplastic Syndromes?

While paraneoplastic syndrome symptoms can occur in people with any type of cancer, the most commonly associated cancers are that of the stomach, breast, lung, kidney, pancreas, ovary, testicle, blood cells, and lymph nodes.

What Causes Paraneoplastic Endocrine Syndrome?

The exact cause of paraneoplastic endocrine syndromes is not completely understood. Moreover, the probable cause may vary depending on the specific syndrome and underlying cancer. Cancer present in the body produces certain substances to which the human body reacts (autoimmune response) and attacks the healthy tissues as well in the process. This causes symptoms in the body that may not be present in the absence of cancer.

What Are the Symptoms of Paraneoplastic Endocrine Syndrome?

Symptoms can occur before or after the cancer is diagnosed and may be the first indication that cancer is present. Symptoms of the paraneoplastic endocrine syndrome are diverse and depend on the specific hormone or protein that is produced by a specific tumor.

• Urge to urinate more often.

• Excessive thirst.

• Nausea and vomiting.

• Constipation.

• Change in appetite.

• Weight loss.

• Muscle weakness.

• Individuals may also experience changes in their menstrual cycles, blood sugar levels, and electrolyte balance.

• Women may also experience changes in their menstrual cycles.

• Neurological symptoms such as difficulty walking, memory loss, confusion, and seizures may also occur.

• Skin rashes and nail changes are also possible symptoms.

How to Diagnose Paraneoplastic Endocrine Syndrome?

The diagnosis of paraneoplastic endocrine syndrome can be challenging, and a team of specialists, including oncologists, endocrinologists, and neurologists, may be involved in the diagnostic process. Some of the diagnostic criteria are as follows:

• Evidence of endocrine abnormality due to neoplastic disease and not from any other endocrine disorder.

• Elevated hormone levels.

• Normal or suppressed endogenous hormone production.

• Increased hormone gradients across the tumor.

• Symptom improvement after tumor treatment.

• The detection of relevant tumor mRNA (messenger ribonucleic acid) for hormone production.

• Blood tests can detect hormones and the presence of antibodies that are associated with paraneoplastic endocrine disorders.

• A biopsy may be done to confirm the presence of cancer and to determine the type of cancer that is causing the disorder.

• Imaging tests like X-rays, CT (computed tomography) scans, and MRIs (magnetic resonance imaging) can help detect tumors and any damage to the affected organs.

How to Treat Paraneoplastic Endocrine Syndrome?

The primary focus of treatment is to address the underlying tumor that is causing the syndrome. Adjunctive therapies may also be used to manage symptoms and improve the individual's quality of life.

• The following treatments are used to manage hypercalcemia associated with paraneoplastic endocrine syndrome:

  • Intravenous Fluids: To increase urine output and flush excess calcium out of the body.

  • Bisphosphonates: To prevent bone loss and reduce calcium levels in the blood.

  • Denosumab: To prevent bone destruction and reduce calcium levels in the blood.

  • Glucocorticoids: To reduce inflammation and lower calcium levels in the blood.

  • Calcimimetics: To block the effects of parathyroid hormone and lower calcium levels in the blood.

  • Calcitonin: To reduce bone breakdown and lower calcium levels in the blood.

• Treatment for other endocrine abnormalities associated with the syndrome will depend on the specific hormone involved and may include medications or surgery.

• Treatment may also involve supportive care, such as pain management, nutritional support, and physical therapy.

• Chemotherapy and radiation therapy are directed to treat the underlying cancer.

• Surgical excision of cancer.

What Is the Prognosis of Paraneoplastic Endocrine Syndrome?

The prognosis of paraneoplastic endocrine disorders depends on the type and stage of cancer that is causing the disorder. In some cases, the disorder may resolve after the cancer is treated. However, in other cases, the disorder may persist even after the cancer is treated. The prognosis is generally poorer in cases where the disorder is caused by advanced cancer.

Conclusion

The early detection and prompt treatment of paraneoplastic endocrine syndromes are crucial for improving the quality of life and survival of the one with the condition. Paraneoplastic endocrine syndromes are rare and complex disorders that can lead to significant suffering and mortality in cancer patients. With continued research and early intervention, it is possible to improve outcomes for those with this challenging condition.