TSH-Secreting Adenomas- Causes, Symptoms, Diagnosis, and Treatment

Introduction:

TSH-secreting adenomas (thyroid-stimulating hormone) are rare pituitary gland tumors that are benign (non-cancerous). The exact cause of their occurrence is unknown, and these tumors lead to excessive production of thyroid hormones leading to a condition known as hyperthyroidism. TSH-secreting adenoma that is less than 1 cm in diameter is known as microadenoma. At the same time, tumors bigger than 1 cm in diameter are called macroadenoma. Around 75 % of the TSH-secreting adenomas are macroadenomas when they are diagnosed.

The symptoms of TSH-secreting adenomas may be due to excess thyroid hormone in the body (hyperthyroidism) or the large size of the tumor that may be compressing the surrounding structures. In addition, some TSH-secreting adenomas are also characterized by associated overproduction of other pituitary hormones like prolactin, growth hormone, etc.

What Are Adenomas?

Adenomas are non-cancerous tumors that can originate in glands, organs, or other parts of the body lined by epithelial tissues. They commonly develop in the pituitary gland, thyroid gland, and adrenal glands. However, they can grow in other glands and organs as well. Although adenomas are non-cancerous (benign), they are considered precancerous, and in rare cases, they can turn cancerous (benign). Since adenomas are prevalent in hormone-producing glandular organs, they can disrupt hormone production and secretion as they grow in size. When the tumor cells of these adenomas start producing hormones, they are called functional adenomas—for example, prolactinoma, thyroid-stimulating hormone-secreting adenomas, etc.

What Is Thyroid-Stimulating Hormone (TSH)?

Thyroid-stimulating hormones (TSH) or thyrotropin is a glycoprotein hormone secreted by the pituitary gland. TSH is produced by the anterior part of the pituitary gland. As the name suggests, TSH is responsible for stimulating the thyroid gland to produce thyroid hormones; triiodothyronine (T3) and thyroxine (T4). Thyroid hormones are responsible for growth and metabolism in all body parts. Therefore, TSH is essential for the normal functioning of the thyroid gland. According to the American Thyroid Association, the normal level of TSH in the body should be between 0.4 mU/L to 4.0 mU/L (milliunits per liter).

What Are TSH-Secreting Adenomas?

• TSH-secreting adenomas are rare and non-cancerous tumors of the pituitary gland that cause overproduction of thyroid hormones and subsequently lead to enlargement of the thyroid gland and hyperthyroidism (overactive thyroid gland).

• TSH-secreting adenomas are rare and constitute less than one percent of all pituitary adenomas.

• TSH-secreting adenomas are most commonly diagnosed in people in their fifth to sixth decades of life, and they affect both men and women equally.

• TSH-secreting adenomas can also secrete various other pituitary hormones like growth hormone, prolactin, and gonadotropins, and they tend to invade surrounding structures.

• Failure to detect TSH-secreting adenomas can have serious repercussions, such as loss of thyroid tissues or its proper functioning, which can cause the pituitary adenoma volume to become even larger.

• TSH-secreting adenomas are a cause of central hyperthyroidism, but they are frequently misdiagnosed and treated as primary hyperthyroidism.

What Are the Other Names of TSH-Secreting Adenomas?

Other names of TSH-secreting adenoma are:

• TSH-oma.

• Thyrotropin-secreting adenoma.

• TSH-secreting pituitary adenomas.

• Thyrotropin-secreting pituitary adenomas.

What Causes TSH-Secreting Adenomas?

• The exact cause of TSH-secreting adenomas is unknown. However, DNA (deoxyribonucleic acid) mutations can cause the pituitary gland's cells to grow and divide uncontrollably. But what causes these genetic changes is unknown.

• Pituitary adenomas may run in families in a small percentage of cases, but there is no obvious hereditary factor in most cases.

What Are the Symptoms of TSH-Secreting Adenomas?

The size of the tumor and the hormone secretory profile of a TSH-secreting adenoma are two key parameters that influence its signs and symptoms. Patients with adenomas less than 1 cm (microadenomas) may present with no signs and symptoms and appear euthyroid (normal thyroid functioning). However, the common symptoms of TSH-secreting adenomas due to hyperthyroidism are:

• Anxiety.

• Fatigue.

• Tremors.

• Palpitations.

• Unusual weight loss.

• Loss of sleep.

• Excessive sweating.

• Restlessness.

• Heat intolerance.

• Irritability.

• Hair loss.

• Diarrhea.

Symptoms due to the large size of the adenoma:

• Headaches.

• Visual field disturbance due to compression of the optic nerve by the tumor.

• Presence of a thyroid lump (goiter).

• Bulging or protrusion of the eyes if the tumor has invaded the orbital cavity.

• Partial or complete loss of pituitary function.

Symptoms of pituitary hormone co-secretion (particularly growth hormone and prolactin) include:

• Oligomenorrhea (menstrual cycles longer than 35 days) and amenorrhea (absence of menstrual cycles) in women, and decreased sex drive in men are common symptoms due to associated increased prolactin secretion.

• Headaches, fatigue, excessive sweating, damage to peripheral nerves, sexual dysfunction, pain in the joints, and excess growth of the limbs and bones are common symptoms due to associated excess growth hormone secretion.

Are TSH-Secreting Adenomas Common?

• TSH-secreting adenomas are rare, and they account for only 0.5 % to 2 % of all pituitary adenomas.

• Approximately the rate of occurrence is only one to two cases per million population.

• Certain hereditary conditions like multiple endocrine-neoplasia type 1 syndrome and isolated familial pituitary adenomas increase the risk of developing TSH-secreting adenomas.

How Are TSH-Secreting Adenomas Diagnosed?

TSH-secreting adenomas are diagnosed with the help of the following laboratory examinations and imaging tests:

• Blood Examinations: Levels of thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormones are evaluated with the help of blood samples. Along with these hormones, other hormones secreted by the pituitary gland are evaluated. Levels of growth hormone, prolactin, etc., are also checked.

• Thyroid Hormone Suppression Test: Thyroid hormone suppression is beneficial in diagnosing TSH-secreting adenomas. During this test, exogenous thyroid hormones are given to the patient. T3 (triiodothyronine) is given 80 mcg/day to 100 mcg/day divided into three administrations in ten days. Blood samples are collected on day 0, day 5, and day 10. There will be failed TSH suppression in the case of TSH-secreting adenomas.

• Magnetic Resonance Imaging (MRI): A thin-cut MRI of the pituitary gland is the diagnostic modality for identifying TSH-secreting adenomas. MRI is useful in studying the tumor's size, nature, and proximity to its surrounding structures.

• Computed Tomography Scan (CT): A contrast-mediated CT scan is done in patients with contraindications of MRI.

In addition, a detailed medical and family history should be taken.

How Are TSH-Secreting Adenomas Treated?

TSH-secreting adenomas are erroneously treated for Graves' disease or hyperthyroidism with radioiodine ablation or surgery in about 30 % of cases. Unfortunately, this delays the accurate diagnosis and raises the TSH level, stimulates tumor growth, and is more invasive.

Treatment of these tumors is done with the help of tumor-directed therapies. This tumor-specific treatment of TSH-secreting adenomas includes surgery or surgical resection, medical treatment, and radiation therapy.

• Surgical Therapy: A transsphenoidal approach is the choice of surgical resectioning in the case of TSH-secreting adenomas. This treatment has the benefit of providing relief from symptoms of compression from the tumor mass, restoration of normal pituitary gland function, and increased responsiveness to medical and radiation therapy.

• Medical Therapies: The second line of treatment after surgical therapy is the use of somatostatin analogs. This treatment is given to patients who do not respond to surgical therapy. Somatostatin analogs are also commonly given prior to surgery to restore thyroid hormone levels and shrink tumors. TSH-secreting adenomas have an excellent response in both short-term and long-acting somatostatin analogs.

• Radiation Therapy: After insufficient surgical and medicinal responses, radiation therapy is usually the third-line treatment for TSH-secreting adenomas. Modern radiation treatments have been shown to be effective in controlling tumor growth.

What Are the Complications of TSH-Secreting Adenomas?

If left untreated, TSH-secreting adenomas can lead to the following complications:

• Visual field defects.

• Hypopituitarism (a condition when the pituitary gland does not produce hormones properly).

• Acromegaly (endocrine disorder occurring due to excess growth hormone production by the pituitary gland).

• Galactorrhea (milk discharge that is not related to pregnancy or lactation).

• Heart diseases.

• Stroke.

Conclusion:

The number of cases of TSH-secreting adenomas has significantly increased over the past decade due to the development of more advanced diagnostic methods used for measuring TSH levels, like ultrasensitive immunometric assays. The treatment of TSH-secreting adenomas by surgery or by medical aid (somatostatin) is also very effective. 90 % of the cases of TSH-secreting adenomas improve, and the levels of T3 and T4 are restored after prompt and effective treatment.