TSH-Secreting Pituitary Adenoma (Thyrotropinoma)

How a thyrotropinoma causes hyperthyroidism

Normally, the pituitary gland releases TSH, which tells the thyroid to make T4 and T3. When thyroid hormone levels rise, the pituitary reduces TSH (negative feedback). In most hyperthyroidism, such as Graves' disease, the thyroid overproduces on its own and TSH is very low.

In a thyrotropinoma, the tumor makes TSH regardless of feedback. The thyroid is continually stimulated, so thyroid hormone levels rise while TSH stays normal or high. This is called central or secondary hyperthyroidism, and it is easily missed if only TSH is measured.

Some thyrotropinomas also produce growth hormone or prolactin, causing features of acromegaly or milk discharge and menstrual changes.

Symptoms

From excess thyroid hormone

• palpitations, fast heartbeat or atrial fibrillation
• weight loss despite good appetite
• heat intolerance and sweating
• tremor, anxiety and irritability
• frequent bowel movements
• fatigue, muscle weakness and poor sleep
• goiter, an enlarged thyroid

Symptoms are often milder than expected for the hormone levels. Eye bulging and the skin changes of Graves' disease are absent.

From the tumor

Most thyrotropinomas are macroadenomas (1 cm or larger) when found and can press on nearby structures:

• headaches
• loss of peripheral vision (bitemporal hemianopia) from pressure on the optic chiasm
• reduced function of other pituitary hormones (hypopituitarism): fatigue, low libido, irregular periods

Diagnosis

1. Thyroid blood tests: high free T4 and/or free T3 with a TSH that is normal or raised.
2. Exclude lab interference: antibodies in some people's blood can distort test results. Repeating tests with a different method helps.
3. Distinguish from resistance to thyroid hormone (RTH): an inherited condition with the same blood pattern but no tumor. Clues for a tumor include a raised alpha-subunit level, high SHBG, lack of TSH response to TRH stimulation, a family history (more typical of RTH) and MRI findings. Genetic testing for THRB variants helps.
4. Pituitary MRI to locate and measure the tumor.
5. Other pituitary hormone tests and visual field testing.

Some people with thyrotropinoma have been mistakenly treated with thyroid surgery or radioactive iodine, which can make the tumor grow. Accurate diagnosis first is important.

Treatment

Surgery

Transsphenoidal surgery, through the nose and sphenoid sinus, is first-line. Before surgery, thyroid levels are usually normalized with somatostatin analogs or antithyroid drugs, and beta-blockers for symptoms. Surgery cures many patients with smaller tumors.

Medicines

• somatostatin analogs (octreotide, lanreotide): lower TSH production in most patients and shrink the tumor in some. Used before surgery, when surgery is not curative, or when surgery is not possible
• beta-blockers to control heart rate and tremor
• antithyroid drugs are used only short-term, because lowering thyroid hormone can increase TSH and tumor growth

Radiotherapy

Stereotactic radiosurgery or conventional radiotherapy for residual or recurrent tumor.

Treat thyroid only as part of a plan

Thyroid surgery or radioactive iodine is not used as the primary treatment.

Outlook

With modern surgery and medicines, most people achieve normal thyroid hormone levels. Larger, invasive tumors are harder to cure and may need long-term medicine. Lifelong follow-up with thyroid tests and MRI is recommended because recurrence is possible.

Frequently asked questions

What is a TSH-secreting adenoma?

It is a rare, usually benign pituitary tumor that makes too much thyroid-stimulating hormone. The excess TSH overstimulates the thyroid, causing hyperthyroidism with high thyroid hormones and a TSH that is normal or high rather than low.

Why is TSH normal or high in a thyrotropinoma?

The tumor produces TSH independently of the body's feedback system, so it keeps releasing TSH even when thyroid hormone levels are high. In most other causes of hyperthyroidism, high thyroid hormone suppresses TSH to very low levels.

What are the symptoms of a TSH-secreting pituitary tumor?

Symptoms include those of an overactive thyroid, such as palpitations, weight loss, sweating, tremor and anxiety, plus a goiter. Larger tumors can cause headaches, loss of side vision and reduced production of other pituitary hormones.

How is a thyrotropinoma treated?

The main treatment is transsphenoidal surgery to remove the tumor. Somatostatin analogs such as octreotide or lanreotide control hormone levels before surgery or when surgery is not curative. Radiotherapy is used for remaining or recurrent tumor.

What else causes high T4 with normal TSH?

Resistance to thyroid hormone, an inherited condition, can produce the same pattern without a tumor. Laboratory interference from antibodies, certain medicines, and recent changes in thyroid medication can also cause it. Specialized tests help tell these apart.