Some cancers are quiet by nature – slow-growing, often curable, rarely the ones that keep surgeons up at night. Thyroid cancer has largely earned that reputation. But reputations like this can obscure as much as they reveal: incidence is rising sharply in some countries for reasons no one can fully explain, and one rare subtype defies the disease’s usual association with favorable outcomes altogether. These are distinctions that demand a surgeon’s eye as much as an epidemiologist’s, and few have spent as long studying them as Henning Dralle, Professor of Surgery and Chair of the Department of Surgery at the University of Halle-Wittenberg since 1994, whose work has centered on the thyroid, parathyroid, and adrenal glands.
At the 8th Annual International Congress of Clinical Endocrinology in Tbilisi, where Professor Dralle presented on sporadic medullary thyroid carcinoma and the evolving surgical approach to it, we spoke with him more broadly about thyroid cancer – from the epidemiological differences he has observed between Germany and Georgia, to what has changed in surgical strategy for medullary disease, and what patients should understand about their long-term outlook after surgery.
Before we get to the clinical details, could you tell us a little about the congress and why thyroid cancer is an important topic to discuss here?
I’m very pleased, and I’d also like to thank the organizers for inviting me to this very important congress. It is a huge meeting, and I am absolutely astonished by its scale. So many endocrinologists and colleagues from other disciplines are here – I just looked into the auditorium and saw perhaps more than 300 colleagues. It is clearly an important congress, and for that reason, I think it is also important to talk about thyroid cancer.
Thyroid cancer is a fascinating disease, quite apart from the burden it places on patients and everything they have to go through. Overall, it is not uncommon. The most frequent type, papillary thyroid cancer, is especially common in this country. I am surprised by that, and I do not know exactly why it is so frequent here. As you know, I am from Germany.
Indeed, we are seeing a real rise in thyroid cancer cases here, and the exact reasons remain unclear. Screening practices may be part of the explanation, though that is likely not the whole picture. This question of underlying drivers also came up at a meeting on cancer burden at the University of Georgia, where one of the university’s doctoral researchers presented findings on the role of environmental factors in thyroid cancer. Her data pointed to gender and regional disparities as well – incidence was higher along the western regions of Georgia and lower in the east. This suggests that environmental factors warrant closer examination, as there may be underlying drivers contributing to the rising incidence we are unfortunately observing.
Given that, how do you see Georgia’s situation in the broader, global context – alongside countries where papillary thyroid cancer is also notably common?
That is an extremely important point. Of course, I should clarify that this concerns non-medullary thyroid cancer, since medullary thyroid cancer incidence is broadly comparable between Germany, other Western countries, and Georgia. But regarding follicular and, in particular, papillary thyroid cancer, I would say Georgia occupies something of an intermediate position between Europe and Asia – not only culturally, but also, it seems, in terms of cancer epidemiology and geography.
Looking globally – across Japan, South Korea, Western countries, and Russia – there are two principal risk factors associated with follicular and papillary thyroid cancer. I was invited to Minsk in 1993, following the Chernobyl accident, where a great many children presented with thyroid complications, and local physicians sought guidance on performing surgery with fewer complications. That experience gave me direct exposure to radiation-induced thyroid cancer, which represents one major risk factor.
The second major factor, more prominent in Asian countries, relates to dietary intake – certain food patterns appear to be associated with increased papillary thyroid cancer incidence. This was, in part, what prompted South Korea and Japan to introduce population-wide screening programs, which you alluded to earlier. This raises an important question: to what extent is the apparent frequency of papillary thyroid cancer in these countries a reflection of more comprehensive detection through screening, rather than a true increase in incidence relative to countries without such programs?
At least in my experience, most of the patients I have seen report having sought a general health check on their own initiative, rather than through a structured screening pathway. There may be a gap in public awareness – not everyone necessarily has a specific reason to pursue a thyroid ultrasound in the absence of a dedicated screening program.
That said, I don’t think this fully answers your question. I am not in a position to provide a definitive explanation here, as it would require a dedicated research program analyzing the full range of contributing factors – not only environmental exposure and dietary intake, but also pathological characteristics. When papillary thyroid cancer has a radiation-related etiology, for instance, there are specific histopathological markers that can help identify this, markers that were well characterized following the post-Chernobyl increase in papillary thyroid cancer in Belarus and parts of Ukraine. These radiation-associated markers are well documented, and a similar analysis would be valuable here as well.
It is interesting to see that here in Georgia, there are many young women with normal thyroids and small papillary thyroid cancers – but not all of them are “good” cancers. This is perhaps the key point in answering your question, and it marks a meaningful difference from Japan and South Korea, where the majority of these micro-cancers genuinely are low-risk.
That is not the case here. I have seen many patients with small cancers that nonetheless came with accompanying lymph node metastases, and a small cancer with lymph node metastases cannot be considered a good cancer. For that reason, I do not think it is a bad thing to continue these ultrasound investigations in young people, as part of routine check-ups.
You’ve touched on epidemiology – but I’m curious how this translates at the bedside. How does the clinical presentation here differ from what you typically see in Germany, and what does that mean for diagnosis in practice?
The clinical presentation is also quite different from what we see in Germany. There, we mostly see patients with nodular goiter, and then, during follow-up, papillary thyroid cancer may be detected. Here, I see many young people – in particular young women – with a completely normal thyroid and a small lesion that, on biopsy, is identified as papillary thyroid cancer. That is a major difference compared with other Western countries.
It is very important for physicians to distinguish between these “good” micro-papillary thyroid cancers and the “bad” ones, because both exist. That distinction matters for everyone involved – endocrinologists, pathologists, surgeons, and of course nuclear medicine specialists – because many patients are afraid of receiving radioiodine treatment after surgery. Diagnostic and therapeutic approaches have changed a great deal over the past 20 years, if you look back.
It sounds like risk stratification is critical even within papillary thyroid cancer itself. I want to shift to a type of thyroid cancer where that risk profile looks completely different from the outset – medullary thyroid carcinoma. What makes it so distinct, and so challenging to diagnose and treat?
The so-called follicular-derived thyroid cancers – meaning papillary thyroid cancer, follicular thyroid cancer, poorly differentiated cancer, and undifferentiated cancer – all arise from the typical thyroid follicular cell. These cells take up iodine in order to produce thyroid hormones, and they make up more than 99% of the thyroid parenchyma.
Medullary thyroid cells are completely different. They are dispersed throughout the thyroid, mainly in the middle, lateral, and posterior parts. There is an old saying that God did not know where to place these medullary thyroid cells, so He dispersed them throughout the thyroid. That illustrates very well that, unlike follicular cells, which are organized in a very specific microenvironment, medullary thyroid cells are scattered throughout the gland.
The second difference is their function. As I mentioned, thyroid follicular cells produce thyroid hormones and take up iodine because iodine is needed for thyroid hormone synthesis. Medullary thyroid cells produce calcitonin and some other biogenic amines, but calcitonin is the most important. Another important substance is carcinoembryonic antigen, or CEA, which is also useful for diagnosis and follow-up in patients with medullary thyroid cancer.
Medullary thyroid cancer is a rare disease, accounting for less than 2% to 3% of all thyroid cancers. That is another major difference. And because calcitonin and CEA production do not require iodine, medullary thyroid cells do not have iodine metabolism. That means medullary thyroid cancer, including metastases, cannot be treated with radioiodine.
So what is the treatment of choice?
Surgery. That is where I come in. The diagnosis is made on laboratory testing, especially calcitonin measurement, and when calcitonin is elevated above a certain range, there is a strong suspicion of medullary thyroid cancer. Another way to diagnose it is, of course, biopsy of the lesion. But it is better to start by measuring calcitonin, because biopsy can sometimes alter the morphology in medullary thyroid cancer.
The recommendation is that if an endocrinologist sees even a small thyroid lesion on ultrasound, calcitonin should be measured. If calcitonin is elevated above a certain range, then a surgeon should be consulted to determine the appropriate type of surgery. So if a patient, perhaps 42 years old, comes to my consultation with a thyroid lesion of 6, 7, or 8 millimeters and a calcitonin level above, say, 100 picograms per milliliter, then the diagnosis of medullary thyroid cancer is quite clear.
The next step is deciding the extent of surgery. I always speak with the patient and explain that if there are no other suspicious lesions in the thyroid and no suspicious lymph nodes, then the treatment choice is between total thyroidectomy and hemithyroidectomy. Hemithyroidectomy means removing only the lobe containing the lesion. In the past, total thyroidectomy was performed on everyone. The reason was probably that, unlike papillary or follicular thyroid cancer, total thyroidectomy is a prerequisite for radioiodine treatment. If the entire thyroid has not been removed, radioiodine treatment is not possible. That may be why total thyroidectomy was also done in all patients with medullary thyroid cancer.
So what has changed in the approach to medullary thyroid cancer, and what has made the newer strategy more effective?
Very good question. Some five, six, or seven years ago, we made an important observation: there are two types of medullary thyroid cancer, or rather medullary thyroid tumors. One type shows desmoplasia within the tumor. Desmoplasia is a fibrotic reaction, and nearly all of these patients – about 80% – have lymph node metastases. For this group, the traditional approach in the past was total thyroidectomy, usually combined with lymph node dissection.
But we also found that about one third of patients with medullary thyroid cancer have desmoplasia-negative tumors. These tumors never develop lymph node metastases. That was a fascinating turning point, because it changed the entire surgical approach to medullary thyroid tumors and cancers.
The strategy we use today, and have been using for several years – and which I have published in major international surgical journals – is this: when a patient presents with a medullary thyroid tumor, elevated calcitonin, and a thyroid lesion, we perform a hemithyroidectomy with intraoperative frozen section. We ask the pathologist to determine whether desmoplasia is present. This can be done on frozen section. Of course, the pathologist needs experience, but it is absolutely possible to say whether the tumor shows no desmoplasia, or only very little desmoplasia – less than 5% of the tumor. In those patients, lymph node metastases are not expected, and they do not need a total thyroidectomy.
What should patients understand about the long-term outlook following surgery, and how does this differ between hemithyroidectomy and total thyroidectomy?
I would answer this question in a second step. The first point is why the choice of hemithyroidectomy, rather than total thyroidectomy, is so important. Hemithyroidectomy has two major benefits. The first is very important: the patient retains one thyroid lobe to produce thyroid hormones, so there is no need for lifelong thyroid hormone supplementation. That is a major advantage. Especially for someone who is young – 20, 25, or 30 years old – lifelong thyroid hormone replacement means taking medication every day for decades, along with regular monitoring to ensure proper dose adjustment. I would not want that, and I think many patients would feel the same.
The second benefit is that hemithyroidectomy is much less risky, because the risk of hypoparathyroidism is much higher when the entire thyroid is removed. I recently spoke with an endocrinologist here before our interview, and she told me that she sees many patients with permanent hypoparathyroidism. Hypoparathyroidism means more than just checking calcium and parathyroid hormone levels. Many patients also have symptoms, and the symptoms of hypocalcemia are very unpleasant: seizures, weakness, and, in the long term, complications involving the brain, eyes, and kidneys. It is a serious complication, and not an uncommon one.
I am very pleased that, in my own experience over the past 10 years, I have never seen a patient develop permanent hypoparathyroidism after total thyroidectomy in this setting. Still, it remains an important risk. Those are the two main advantages of hemithyroidectomy, because with hemithyroidectomy the risk of hypoparathyroidism is essentially zero: at least two parathyroid glands are preserved, which is enough to maintain calcium metabolism.
As for the outcome, we have analyzed all of these patients. In desmoplasia-negative medullary thyroid tumors, we performed hemithyroidectomy only, and there were no recurrences. In other words, all of these patients remain alive without any evidence of residual disease.
