The Parathyroid Peeps host a patient support community on Inspire and a question was recently raised regarding the effectiveness of ethanol ablation and when it might be used as an intervention for hyperparathyroidism. We asked parathyroid expert Dr. Deva Boone, our medical advisor on Inspire, to respond and help educate us on this topic.
Dr. Deva Boone founder and surgeon at Southwest Parathyroid Center hosts a Parathyroid Question and Answer website: where you can review answers to many common questions asked about primary hyperparathyroid disease and also have your personal questions answered. We encourage you to take advantage of this excellent source of information!
Deva Boone, MD, FACS, FACE
A few years ago an endocrinologist called me about a very difficult parathyroid case. His patient had recurrent primary hyperparathyroidism and had already had several operations in an attempt to treat it. During his first parathyroid operation, a single large parathyroid tumor was removed, but it was broken apart and a piece was left behind. His second and third operations were aimed at evaluating his other glands and trying to find the problem. Due to thick scar tissue, his surgeons were unable to find the parathyroid tumor remnant, though they believed they could see it on ultrasound. The patient was miserable. His calcium was high, his bones ached, and he was exhausted.
Believing that surgery was no longer an option, his endocrinologist decided to try ethanol ablation. On the ultrasound, he could see what appeared to be a parathyroid tumor. Using a tiny needle to extract a few cells from the mass, he was able to confirm that it was parathyroid. He then injected 96% ethanol into the mass, with the hope of destroying the abnormal parathyroid tissue. The results were immediate. The patient’s calcium normalized and he felt amazing. However, in the end, ethanol ablation was not the solution – let’s learn why.
Ethanol Ablation of Parathyroid Tumors
Many of my patients, upon learning that they have primary hyperparathyroidism (pHPT), ask whether there might be a way to avoid surgery. There are no medications that can cure pHPT, but lately a few people have asked about ethanol ablation. In this procedure, the parathyroid tumor is injected with ethanol in order to damage or kill the gland. It is done under ultrasound guidance, and just involves a needle going into the parathyroid tumor. No skin incision or general anesthesia required. It is also called “chemical parathyroidectomy” because the doctor is using chemicals to essentially remove the parathyroid tumor.
This isn’t a new procedure. Doctors were attempting it in the 1980s, with mixed results. There are still scattered attempts to use it, but in general it is not widely practiced. Standard parathyroidectomy, or surgically removing the diseased parathyroid glands, remains the preferred treatment. It has incredibly high cure rates and is very safe.
But there are people who would prefer a non-surgical approach, so let’s review the medical literature on ethanol ablation.
Medical studies on ethanol ablation of parathyroid adenomas
All of the published studies involve small numbers of patients, usually treated at a single hospital. Most will describe the immediate outcomes of the ethanol injection and then follow the patients for a short period to see whether the calcium level normalized and remained normal.
Overall, the results have been poor. One early study published in 1989[i]looked at 18 patients with primary hyperparathyroidism who received ethanol ablation of their parathyroid tumors. While twelve patients (67%) showed improvement in their calcium and PTH levels, only 8 patients (44%) had normal calcium levels 6 months after injection. In addition, the procedure had a high complication rate: four patients (22%!) had recurrent laryngeal nerve injuries from the injection, causing vocal cord paralysis and difficulty speaking. One of these was permanent! For comparison, the rate of recurrent laryngeal nerve injury for an experienced parathyroid surgeon performing a parathyroidectomy should be well under 1%. While it might seem that injection of the parathyroid would be safer than open surgery, this was not the case.
The same authors published a follow-up study[ii]a few years later. They added another 14 patients, who were given up to three ethanol injections one week apart. They noted lab improvements in 11 (79%). Again, one patient in the group had a permanent vocal cord paralysis. Taken overall, the success rate was still poor, at 59%, and the complication rate was still high, at 6% for permanent nerve injury. In addition, a third of patients still had to have parathyroid surgery, and during surgery it was found that most of them had scarring around the parathyroid. Scarring can make the operation significantly more challenging (I know this from experience) and increases the risks from surgery.
Other studies published in the 1990s had similarly disappointing results. One study[iii]followed 27 patients who received ethanol ablation for parathyroid adenomas. Fifteen patients showed an initial cure after ablation. On following these patients, though, 4 out of those 15 developed recurrent disease within 2 years, for an overall cure rate of 41%. The Mayo Clinic published their results from 36 patients in 1998[iv]. Initial results were satisfactory, but at 16 months out, only a third of patients were still cured. Two thirds still had primary hyperparathyroidism despite ablation.
Better results came from a more recent study released in 2020[v]. The authors looked at tumor size in 45 patients followed for a year after ethanol ablation. After one month, less than half of patients had successful ablations, defined as a decrease in size of the tumor and improvement in calcium and PTH levels. The patients who did not see improvement had subsequent monthly injections (up to 4). By the end of the year they noted a cure rate of 85%, but this excluded the 6 patients were lost to follow up or did not complete the study, suggesting they may have sought care elsewhere. In addition, they did not follow anyone after a year, and prior studies would suggest that a significant number of those patients would develop recurrent disease.
Though this more recent study is somewhat encouraging, the procedure cannot compare to the results of parathyroid surgery. For the majority of patients, a single operation will cure them for life (no monthly repeats necessary). The operation also works for patients who were excluded from the studies of ethanol ablation, such as those with tumors that could not be seen on ultrasound and those suspected of having multigland disease. For ethanol ablation to work, the parathyroid tumor needs to be visible on ultrasound, which is not the case for many patients. Parathyroid surgery is also very safe, with minimal complications when performed by experienced surgeons. For these reasons, few physicians would advocate the routine use of ethanol ablation in primary hyperparathyroidism.
Is ethanol ablation ever useful?
Despite the poor results of “chemical parathyroidectomy” it may still be helpful in select situations. Advocates of the procedure argue that it can be used for patients who are “not surgical candidates,” meaning they are not healthy enough to undergo the operation. In my experience, there are very few patients who are in such bad shape that they cannot have parathyroid surgery. It is a quick (around 30 minutes on average) and safe outpatient procedure that I’ve done on many elderly people with heart disease, lung disease, kidney failure, and other serious medical conditions. I have never had a patient who truly could not get parathyroid surgery because of their other medical conditions, though theoretically it could happen.
Ethanol ablation may be useful in one small group: those rare individuals with multiple endocrine neoplasia (MEN) who have already had a subtotal parathyroidectomy (three of four parathyroids have already been removed) and have recurrent disease in the last parathyroid remnant. Patients with MEN1 develop parathyroid hyperplasia, or overgrowth of all four parathyroids, and this is a lifetime condition. The treatment is surgical; removing three parathyroid glands and part of the fourth, leaving behind a piece of the last gland. The remnant is left there to prevent permanent hypOparathyroidism, characterized by a lack of parathyroid hormone and an inability to keep calcium levels from dropping too low. Recurrent hypERparathyroidism can occur when the remnant grows large again. Treatment for that usually involves another operation, to trim back the gland. Repeat operations are more difficult, since the gland is surrounded by scar tissue, and have higher rates of complications. For patients with MEN1, hyperparathyroidism is usually a chronic disease, which is controlled and managed but never entirely cured.
A study from 2008[vi]looked at this population: 22 patients with MEN1 who had already had a subtotal parathyroidectomy (3.5 glands removed) and had developed recurrent disease. For some of these patients, ethanol ablation was successful, in that it helped to lower their calcium levels. Half of the patients required multiple injections. Unsurprisingly, recurrence was common. Within 3 years of the initial injection, 90% again had high calcium levels. But, the authors noted, repeat injections were usually just as successful as the first. For patients who have a lifelong parathyroid condition, these repeated injections are a viable method of long-term management.
Back to my patient
What about the difficult case I mentioned earlier? The endocrinologist used ethanol ablation, and it worked – for a time. A few months after the injection, the man’s calcium began to rise again, and his symptoms returned. The endocrinologist again injected the tumor with ethanol, and again noted rapid clinical improvement. This time it only lasted a month. After the third injection, which improved matters for just a few weeks, the endocrinologist started looking for other options. Ethanol ablation was not going to be a long-term solution. The man needed another operation, which finally cured him.
Parathyroid ethanol ablation involves chemically damaging a parathyroid tumor with an injection of ethanol. For many patients, it (sort of) works. It can decrease calcium and alleviate symptoms – temporarily. But the gland is rarely destroyed entirely by the injection, so the tumor regrows and the parathyroid disease returns months or years later in up to 70% of patients. And it is not risk-free; patients can have vocal cord paralysis and voice changes after the procedure. For patients with spontaneous primary hyperparathyroidism, who can be cured with an outpatient low-risk operation, ethanol ablation makes little sense. But for those with more complicated disease, such as patients with rare genetic syndromes like MEN1, who have already had one or more operations for their parathyroid condition, ethanol ablation may have a role in managing their disease.
[i]Karstrup S, Transbøl I, Holm HH, Glenthøj A, Hegedüs L. Ultrasound-guided chemical parathyroidectomy in patients with primary hyperparathyroidism: a prospective study. Br J Radiol. 1989;62(744):1037-1042. doi:10.1259/0007-1285-62-744-1037.
[ii]Karstrup S, Hegedüs L, Holm HH. Ultrasonically guided chemical parathyroidectomy in patients with primary hyperparathyroidism: a follow-up study. Clin Endocrinol (Oxf). 1993;38(5):523-530. doi:10.1111/j.1365-2265.1993.tb00349.x
[iii]Cercueil JP, Jacob D, Verges B, Holtzmann P, Lerais JM, Krause D. Percutaneous ethanol injection into parathyroid adenomas: mid- and long-term results. Eur Radiol. 1998;8(9):1565-1569. doi:10.1007/s003300050587
[iv]Harman CR, Grant CS, Hay ID, et al. Indications, technique, and efficacy of alcohol injection of enlarged parathyroid glands in patients with primary hyperparathyroidism. Surgery. 1998;124(6):1011-1020. doi:10.1067/msy.1998.91826
[v]Yazdani AA, Khalili N, Siavash M, et al. Ultrasound-guided ethanol injection for the treatment of parathyroid adenoma: A prospective self-controlled study. J Res Med Sci. 2020;25:93. Published 2020 Oct 28. doi:10.4103/jrms.JRMS_553_19
[vi]Veldman MW, Reading CC, Farrell MA, et al. Percutaneous parathyroid ethanol ablation in patients with multiple endocrine neoplasia type 1. AJR Am J Roentgenol. 2008;191(6):1740-1744. doi:10.2214/AJR.07.3431
ABOUT DR. BOONE – Dr. Boone is the founder of the Southwest Parathyroid Center in Phoenix, Arizona. She has dedicated her career to the understanding and treatment of parathyroid disease, combining compassion, knowledge, and experience to provide world-class care to all patients.
After obtaining her MD at Cornell Medical College, Dr. Boone completed a general surgery residency in New York City and endocrine surgery fellowship in Chicago, IL. She then subspecialized in parathyroid surgery. She joined the Norman Parathyroid Center in 2014, where she performed over 3600 parathyroid operations and consulted with thousands more patients with suspected calcium and parathyroid abnormalities. Very few surgeons worldwide have treated more parathyroid patients than Dr. Boone. At the Norman Center, she also served as the Medical Director from 2017 to 2020, while continuing to operate on 500 to 600 parathyroid patients annually. In 2020 she left to open the Southwest Parathyroid Center.
Dr. Boone is a frequent speaker on parathyroid disease. She enjoys teaching both patients and other physicians about calcium, Vitamin D, and the parathyroids.