Diffuse papillary hyperplasia of the thyroid gland

by Jason Wasserman MD PhD FRCPC
July 3, 2025

Diffuse papillary hyperplasia of the thyroid gland is a non-cancerous condition characterized by an enlargement of the thyroid gland due to an increase in both the size and number of thyroid cells. The word “diffuse” means that the changes are seen throughout the entire gland, rather than being limited to one area. The term “papillary” refers to the small finger-like projections of tissue (called papillae) that are often seen when the gland is examined under the microscope.

This condition is most commonly associated with Graves’ disease, an autoimmune disorder that causes the thyroid to become overactive (a condition known as hyperthyroidism). Although it may cause noticeable symptoms, diffuse papillary hyperplasia itself is not cancer and does not increase the risk of thyroid cancer.

What causes diffuse papillary hyperplasia?

The most common cause of diffuse papillary hyperplasia is Graves’ disease, an autoimmune disorder. In Graves’ disease, the immune system produces abnormal proteins called autoantibodies. These autoantibodies target and activate a receptor on thyroid cells called the thyroid-stimulating hormone receptor (TSHR).

When TSHR is activated, it sends a signal to the thyroid follicular cells, prompting them to grow and produce thyroid hormone. In Graves’ disease, this stimulation occurs continuously, even when the body does not require additional hormone. As a result:

  • The thyroid gland becomes enlarged (a condition called goiter).

  • The number and size of thyroid cells increase.

  • The gland starts producing too much thyroid hormone, leading to hyperthyroidism.

This constant stimulation also causes the gland to exhibit a distinctive appearance under the microscope, characterized by the formation of papillary projections, which are a hallmark of diffuse papillary hyperplasia.

What are the symptoms of diffuse papillary hyperplasia?

The symptoms of diffuse papillary hyperplasia are caused by hyperthyroidism, or an overproduction of thyroid hormone. Common symptoms include:

  • Nervousness or anxiety.

  • Fatigue or muscle weakness.

  • Shaking or hand tremors.

  • Weight loss despite normal or increased appetite.

  • Rapid or irregular heartbeat (palpitations).

  • Increased sweating and heat intolerance.

  • Difficulty sleeping.

  • Enlarged thyroid (goiter), which may be visible as a swelling in the front of the neck.

Not everyone experiences all of these symptoms, and some people may have mild or nonspecific signs that develop gradually.

How is this condition diagnosed?

Diffuse papillary hyperplasia is most commonly diagnosed after thyroid surgery, when the entire thyroid gland is removed and examined under a microscope by a pathologist.

Before surgery, doctors may suspect the diagnosis based on:

  • Blood tests, which often show elevated thyroid hormone levels and the presence of TSH receptor antibodies (TSHR-Ab)

  • Imaging, such as a thyroid ultrasound or a nuclear medicine thyroid scan, which may show a diffusely enlarged gland with increased activity

However, the definitive diagnosis is usually made by a pathologist after reviewing the thyroid tissue.

What does diffuse papillary hyperplasia look like under the microscope?

When the thyroid gland is examined under the microscope, diffuse papillary hyperplasia shows the following features:

  • The thyroid follicles (round structures that store thyroid hormone) are smaller and more numerous than usual.

  • The follicular cells, which line the follicles and produce thyroid hormone, appear tall and crowded, a result of increased activity and cell growth.

  • Many papillary projections—small finger-like extensions of tissue lined by follicular cells—can be seen within the follicles. These are not a sign of cancer in this setting.

  • The tissue may also exhibit scalloping of the colloid, characterized by a wavy appearance at the edges of the pink-staining fluid within the follicles. This is another common feature of hyperactive thyroid tissue.

These features reflect the gland’s constant stimulation by TSHR antibodies in Graves’ disease, helping to distinguish diffuse papillary hyperplasia from other thyroid conditions.

What does it mean if “representative sections” were examined?

The term “representative sections” means that only selected samples from different areas of the thyroid gland were placed on glass slides and examined under the microscope. This is a standard practice, especially when the thyroid has been removed for Graves’ disease.

Because the gland is often very large in this condition, examining the entire thyroid would be impractical and is unlikely to provide additional information. In most cases, a few representative sections are enough to confirm the diagnosis of diffuse papillary hyperplasia.

Questions to ask your doctor

  • Is my thyroid overactive due to Graves’ disease?

  • What do my blood test results show?

  • What are the treatment options for hyperthyroidism?

  • Do I need surgery to remove my thyroid gland?

  • What did the pathology report show after surgery?

  • Will I need thyroid hormone replacement after surgery?

  • How will my condition be monitored over time?

Other helpful resources

American Thyroid Association
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