Non-surgical therapies for thyroid nodules and cysts

[Image by Jung Suk Sim with creative commons license.]

Most doctors in North America know of two ways to deal with thyroid nodules. 1) watch them grow and wait, doing nothing, and 2) thyroidectomy, removing part or all of the thyroid gland that is affected.

However, in countries beyond North America, mainly Korea and Italy, endocrinologists and other specialists have developed additional treatments for nodules:

  • Radiofrequency ablation (RFA), and other subtypes of thermal ablation, such as Microwave Ablation (MWA) and High Intensity Focused Ultrasound (HIFU)
  • Ethanol ablation

Unfortunately, it is difficult or impossible to access these treatments in Canada, as of the time of writing this in February 2020.

A patient named Jane Armstrong started a Change.org petition to advocate for this therapy. Please visit her link and sign her petition.

I publicly call on the Canadian Society for Endocrinology and Metabolism (CSEM) to ask for your position statement regarding these therapies. A search of your website for “nodules” and “ablation” gave no results. On behalf of thyroid patients in Canada, we ask you, if these nodule therapy options are not being offered in Canada yet, why not?

There is no controversy surrounding these therapies. These therapies, especially RFA which is most frequently discussed, are not viewed as “new” or “experimental” treatments.

  • The scientific literature on these procedures goes back to 1990.
  • There are now international guidelines and recommendations for these procedures.
  • The reference list (on Page 2 of this article) contains no less than 85 scientific journal articles on one or more of these treatments.

This post provides images and video links, introduces some of the specialized terminology, outlines the reasons for treating thyroid nodules, and then explains these non-surgical procedures in general and their effectiveness safety in particular.

Before & After images

NOTE: Images from scientific publications are reproduced within the terms of Canadian and US copyright “fair dealing” and “fair use” for purposes of education and review: See copyright law info

[Image by Jung Suk Sim with creative commons license]

Image from Sim & Baek (2019):

Image from Singapore National Eye Center:

See links to VIDEOS at the end of this article, below.

Terminology

The word “ablation” simply means “removal or destruction of material,” in this case the offending nodule(s). 

These nodule treatments are sometimes called “Minimally Invasive Therapies,” or MITs, because they usually do not require invasive surgery.

Some therapies such as Ethanol ablation may involve injection, so the term “percutaneous” is used. “In surgery, a percutaneous procedure is any medical procedure or method where access to inner organs or other tissue is done via needle-puncture of the skin, rather than by using an “open” approach where inner organs or tissue are exposed.” (Wikipedia)

The treatments are often guided by ultrasound, which is sometimes abbreviated “US.”

The radiofrequency and laser therapies are sometimes called “thermal” ablation.

Why treat nodules?

The growth of nodules, and “Multinodular goiter,” a swollen thyroid gland with multiple nodules and/or cysts, are conditions that increase in frequency as one ages. Nodules “are discovered by palpation [touching] in 3–7% and by ultrasound (US) in about 50% of the general population” (Hahn et al, 2019). Single, isolated nodules are also found on thyroid glands. They are often benign (that is, not cancerous).

Nowadays, the main focus of thyroid ultrasound and nodule diagnosis tends to be on whether or not they are cancerous. A finding or high likelihood of cancer is the most common reason for getting rid of them by surgery, but confirmation depends on having a biopsy. In some patients, having a biopsy can be risky. If nodules are determined to have a low risk of being cancerous, they are often ignored and left alone.

Nodules can be troublesome for other reasons besides cancer.

Their growth can interfere with nearby anatomy in the throat or chest, putting pressure on the esophagus or windpipe and causing discomfort, vocal disturbance, or sleep disturbances, and they could become visibly noticeable as well, resulting in adverse social and psychological effects on the patient. Sometimes the fear that benign nodules may become cancerous weighs heavily on the mind of the patient.

Some nodules can hypersecrete thyroid hormones, often an excess of thyroid hormone, even without excess TSH stimulation. (In Graves’ disease, TSH-Receptor antibodies will stimulate thyroid tissue and nodules even when there is no TSH due to thyroid hormone feedback.)

Hypersecreting nodules are sometimes called “hot” or “toxic” or “autonomous” nodules even though there is nothing either hot or toxic about the hormones being secreted.

Hypersecreting nodules do not emanate heat, but if a person were to do a radioiodine (RAI) uptake scan to see how much iodine they take up, the nodules would show up as as “hot spots” of increased RAI on the results.

[“Toxic mng” = Toxic (hypersecreting) multinodular goiter. Image from DNB Help, “Pharynx & Larynx – 3: Evaluation of the thyroid nodule” at https://dnbhelp.wordpress.com/pharynx-larynx-3/ ]

Hyperfunctinoal nodules can be toxic to the body if they cause Free T4 and/or T3 levels to elevate above reference range to the degree that they cause thyrotoxicosis–excess thyroid hormone in tissues.

But nodules don’t always cause thyrotoxicosis, especially if the gland as a whole is damaged, in which case, the nodule may not add much hormone to existing blood concentrations.

Therefore, simply calling them “autonomous,” “hypersecreting” or “hyperfunctional nodules” are more objective ways to describe them than the imprecise (and unnecessarily frightening) terms “hot” or “toxic.”

Hormone from hypersecreting nodules can be troublesome if a patient is taking thyroid hormone therapy or anti-thyroid medication for Graves’ disease. Even on a stable dose of thyroid hormone or anti-thyroid medication, hormone levels can fluctuate based on one or more nodules’ activity. Because each individual has a narrow optimal range for thyroid hormone within the population reference range, even minor fluctuations within the reference range can cause relative increase in symptoms of thyrotoxicosis (when they add extra T3 or T4) or of hypothyroidism (when they stop contributing).

Not all thyroid nodules or cysts actively secrete. Hypersecretion from a nodule usually ceases as the nodule tissue fibroses (dies) over time. These inactive nodules and cysts could show as abnormally empty areas that one would expect to have some uptake in a “normal” RAI scan in the image above.

Summary of these treatments

Cesareo et al’s 2017 article provides a good summary in its abstract:

“The majority of benign thyroid nodules are asymptomatic, remain stable in size and do not require treatment. However, a minority of patients with growing nodules may have local symptoms or cosmetic concerns, and thus demand surgical therapy.

The timely use of ultrasound-guided, minimally invasive thermal therapies has changed the natural history of benign, enlarging thyroid nodules (TNs).

These procedures produce persistent shrinkage of TNs and an improvement of local symptoms.

Among the various procedures, percutaneous ethanol injection represents the first-line treatment for thyroid cysts, while in solid cold nodules, laser and radiofrequency ablation (RFA) have proven to be very effective and safe techniques in producing significant volume reduction that remains stable over several years.

In particular, RFA seems to be suited for the management of small and medium nodules, while larger nodules may require repeated RFA treatments, and could be difficult to treat if they extend into the chest.

RFA is performed in outpatient clinics and has a lower risk of complications compared to surgery.

However, to date, there is still no unanimous consensus on the percutaneous treatment of benign nodules using such minimally invasive thermal techniques. In this review, we critically revise [review] the literature to identify patients who are more likely to benefit from RFA treatment as an alternative to surgery.”

Another review article in 2014 (note, this is 6 years ago!) by Papini et al explains:

“Surgery is the long-established therapeutic option for benign thyroid nodules, which steadily grow and become symptomatic.

The cost of thyroid surgery, the risk of temporary or permanent complications, and the effect on quality of life, however, remain relevant concerns.

Therefore, various minimally invasive treatments, directed towards office-based management of symptomatic nodules, without requiring general anaesthesia, and with negligible damage to the skin and cervical tissues, have been proposed during the past two decades.

Today, ultrasound-guided percutaneous ethanol injection and thermal ablation with laser or radiofrequency have been thoroughly evaluated, and are accessible procedures in specialized centres.

In clinical practice, relapsing thyroid cysts are effectively managed with percutaneous ethanol injection treatment, which should be considered therapy of choice.

In solid non-functioning thyroid nodules that grow or become symptomatic, trained operators may safely induce, with a single session of laser ablation treatment or radiofrequency ablation, a 50% volume decrease and, in parallel, improve local symptoms.

In contrast, hyperfunctioning nodules remain best treated with radioactive iodine, which results in a better control of hyperthyroidism, also in the long-term, and fewer side-effects.

Currently, minimally invasive treatment is also investigated for achieving local control of small size neck recurrences of papillary thyroid carcinoma in patients who are poor candidates for repeat cervical lymph node dissection. This particular use [tratment of papilliary thyroid cancer] should still be considered experimental.”

Radiofrequency ablation (RFA)

As explained by Park et al, 2017,

“Radiofrequency ablation (RFA) is a well-known, effective, and safe method for treating benign thyroid nodules and recurrent thyroid cancers. Thyroid-dedicated devices and basic techniques for thyroid RFA were introduced by the Korean Society of Thyroid Radiology (KSThR) in 2012.

Thyroid RFA has now been adopted worldwide, with subsequent advances in devices and techniques.”

Radzina et al, 2017 adds,

“US guided Radiofrequency ablation has been proved to be effective and safe in cases of benign thyroid nodules and a promising treatment method alternative to surgery for patients with recurrent papillary thyroid cancer.

Its major role lies in significant reduction of thyroid nodule mean volume and improvement of the patient symptoms.”

How safe is RFA?

Chung et al, 2017 published an article titled “Safety of radiofrequency ablation of benign thyroid nodules and recurrent thyroid cancers: a systematic review and meta-analysis.”

Here are the results and conclusions summarized in their abstract:

“RESULTS: A total of 24 eligible studies were included, giving a sample size of 2421 patients and 2786 thyroid nodules.

41 major complications and 48 minor complications of RFA were reported, giving a pooled proportion of 2.38% for overall RFA complications [95% confidence interval (CI): 1.42%-3.34%] and 1.35% for major RFA complications (95% CI: 0.89%-1.81%). There were no heterogeneities in either overall or major complications (I2 = 1.24%-21.79%).

On subgroup analysis, the overall and major complication rates were significantly higher for malignant thyroid nodules than for benign thyroid nodules (p = 0.0011 and 0.0038, respectively).”

“CONCLUSIONS: RFA was found to be safe for the treatment of benign thyroid nodules and recurrent thyroid cancers.”

RFA, MWA and HIFU

How do Radiofrequency ablation (RA), Microwave ablation (MWA), and High Intensity Focused Ultrasound (HIFU) therapies compare?

A study by Korkusuz et al in 2018 found that

“RFA showed a significant volume reduction of nodules of 50 % (p<0.05), MWA of 44 % (p<0.05) and HIFU of 48 % (p<0.05) three months after ablation. None of the examined ablation techniques caused serious or permanent complications. RFA, MWA and HIFU showed comparable results considering volume reduction. All methods are safe and effective treatments of benign thyroid nodules.”

Ethanol Ablation

Ethanol is a common chemical found in alcohols (ethyl alcohol, grain alcohol, drinking alcohol).

Hahn et al, 2019, write,

“Ethanol ablation (EA) of thyroid cystic nodules has been performed since the 1990s.”

“EA is widely used as a nonsurgical treatment usually for cystic (i.e., pure cyst) or predominantly cystic benign thyroid nodules (i.e., cystic portion > 50%).

Direct injection of ethanol through a needle or a catheter for the purpose of atrophy of a mass in a solid organ is called EA, ethanol injection, or ethanol sclerotherapy. “

“In recent years, EA has also been used to treat recurrent thyroid cancer. For the treatment of local recurrence of thyroid cancer, surgery should be considered as the first-line treatment option if the recurrence site is confirmed by an imaging technique. However, even if recurrent cancer is confirmed, reoperation may be technically difficult if the normal tissue plane is distorted by the previous surgery and the recurrent cancer occurs in an area where scarring with fibrosis has developed, … [and] external radiation may increase morbidity due to complications.

Therefore, image-guided nonsurgical procedures such as EA or radiofrequency ablation (RFA) have been proposed as alternative therapies for patients who are concerned about the complications of external radiation, refuse external irradiation, may have serious complications following surgery, or who may be at high risk for surgery.”

“In a completely cystic nodule, EA can achieve a volume reduction of 85–95%. However, in a predominantly cystic nodule, the rate of volume reduction varies from 60% to 90%. Results for predominantly cystic nodules with a solid portion less than 20% are satisfactory.

Simple aspiration is the first treatment option for symptomatic benign pure cysts and predominantly cystic nodules. However, simple aspiration has been shown to have a high recurrence rate of ≤ 58%. Therefore, EA is a reasonable approach in patients with recurrent cystic fluid accumulation after initial aspiration.”

Ethanol ablation combined with radiofrequency ablation

As Ha and Baek 2014 explain,

“Ethanol ablation has traditionally been used for treatment of cystic thyroid nodules. Laser ablation and radiofrequency ablation were introduced later and used for treatment of solid thyroid nodules.

To control the bleeding, 99% ethanol was injected. The efficacy of ethanol in controlling bleeding, final nodule volume and complications were assessed. Control of the bleeding by ethanol ablation and subsequent radiofrequency ablation was feasible in all patients.

Ninety-one percent (10/11) could be treated in 1 session. The mean nodule volume dropped from 17.1 to 4.3 mL (P < .018). There were no major complications.

Ethanol ablation and radiofrequency ablation combination therapy is a feasible and safe technique for treating predominantly cystic thyroid nodules that exhibit internal bleeding during preparatory aspiration.”

The current international opinion as of 2019

In 2019, Papini et al published an article providing “a Delphi-based consensus statement from the Italian minimally-invasive treatments of the thyroid (MITT) group.”

In their abstract, “LoE” means “level of evidence.” The numeric grade is based on a chart outlining the strength and quality of evidence in the literature, developed by the Oxford Center of Evidence-Based Medicine, in which 1 = higher quality and 5 = lower quality of evidence.

Their abstract also mentions “EU-TIRADS” which is the European Union’s grading system for the risk of cancer in a nodule.

Abstract:

“Benign thyroid nodules are a common clinical occurrence and usually do not require treatment unless symptomatic. During the last years, ultrasound-guided minimally invasive treatments (MIT) gained an increasing role in the management of nodules causing local symptoms.

In February 2018, the Italian MIT Thyroid Group was founded to create a permanent cooperation between Italian and international physicians dedicated to clinical research and assistance on MIT for thyroid nodules.

The group drafted this list of statements based on literature review and consensus opinion of interdisciplinary experts to facilitate the diffusion and the appropriate use of MIT of thyroid nodules in clinical practice.

(#1) Predominantly cystic/cystic symptomatic nodules should first undergo US-guided aspiration; ethanol injection should be performed if relapsing (level of evidence [LoE]: ethanol is superior to simple aspiration = 2);

(#2) In symptomatic cystic nodules, thermal ablation is an option when symptoms persist after ethanol ablation (LoE = 4);

(#3) Double cytological benignity confirmation is needed before thermal ablation (LoE = 2);

(#4) Single cytological sample is adequate in ultrasound low risk (EU-TIRADS ≤3) and in autonomously functioning nodules (LoE = 2);

(#5) Thermal ablation may be proposed as first-line treatment for solid, symptomatic, nonfunctioning, benign nodules (LoE = 2);

(#6) Thermal ablation may be used for dominant lesions in nonfunctioning multinodular goiter in patients refusing/not eligible for surgery (LoE = 5);

(#7) Clinical and ultrasound follow-up is appropriate after thermal ablation (LoE = 2); (#8) Nodule re-treatment can be considered when symptoms relapse or partially resolve (LoE = 2);

(#9) In case of nodule regrowth, a new cytological assessment is suggested before second ablation (LoE = 5);

(#10) Thermal ablation is an option for autonomously functioning nodules in patients refusing/not eligible for radioiodine or surgery (LoE = 2);

(#11) Small autonomously functioning nodules can be treated with thermal ablation when thyroid tissue sparing is a priority and ≥80% nodule volume ablation is expected (LoE = 3).

Video links

Video link https://www.youtube.com/watch?v=ZqS5iw64xC0
  • Case Presentation: Use of Radiofrequency Ablation (RFA) for Benign Thyroid Nodules: Hopkins Medicine Video
  • Radiofrequency Ablation Therapy for Large Benign Thyroid Nodule: Mayo Proceedings video.
  • Principle and technique for radiofrequency ablation of benign thyroid nodules. Prof Kwang Hwi Lee – Sheikh Khalifa Specialty Hospital, Ras Al Khaimah, United Arab Emirates. IGILUC 2019 conference video.

References are on Page 2


Pages: 1 2


Categories: Nodules

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