Papillary thyroid microcarcinoma is a widely debated topic in modern medicine. Endocrinologists are discussing the best approach: surgical removal, non-intervention and active surveillance of the patient, or conservative, minimally invasive techniques (MIT). Today’s medical experts believe that sometimes the best treatment is not intervention, but rather monitoring the course of the process.
How do we treat benign thyroid nodules (BTND)? What are the treatment options based on nodule size, and what has changed in the new guidelines? What role do thyroid hormones play in pregnancy and infant development? How do we differentiate postpartum thyroid problems from postpartum depression? And finally, hyperprolactinemia, one of the most common endocrine disorders—how do we diagnose it?
Professor Juan-Carlos Gallofre Ferrater answers all these questions. In an interview with “Medscriptum,” he explains in detail the importance of the role of conservative therapies in medicine.
Professor Galofré is an internationally recognized expert in thyroidology. He is a leading endocrinologist at the University Clinic of Navarra and is actively involved in endocrine research. Professor Galofré conducts research on thyroid cancers, other thyroid-related diseases, and especially the connection between the thyroid gland and pregnancy in the body. His area of interest also includes neuroendocrine research, specifically the pituitary gland.
In the interview with “Medscriptum,” Professor Galofré discussed not only new trends in medicine but also shared practical advice. For example, how to determine thyroid dysfunction and what to do when these symptoms are discovered.
Thyroid Nodules and Papillary Thyroid Carcinoma (PTC)
Ekaterine Chitishvili: Professor Galofré, you are actively working in the field of thyroid cancer research. What do you think is the most significant change in the management of benign nodular thyroid diseases (BNTD) today? And what are the modern clinical approaches to managing patients with papillary thyroid microcarcinoma?
Juan Carlos Galofré: Previously, only the doctor made decisions about the patient’s course of action; today, the approach has changed. We now know that there are many open questions for which there is no single best management approach. In cases where multiple options exist- each with its own advantages and drawbacks- it is only logical that the patient should choose the one that best aligns with their preferences. We view everything from the patient’s perspective. The patient makes the choice. We only offer them several treatment tactics.
In the past, when we found a large thyroid nodule, we would resect it. Today, however, the patient decides whether or not to undergo surgery. We offer several alternatives, such as minimally invasive techniques (MIT) for thyroid nodule ablation. This procedure is performed by inserting a in the thyroid nodule and heating its tip- the nodule locally shrinks in size and may even completely shrivel. Regarding thyroid cancer management, according to new trends, if an infracentimetric malignant nodule is found during regular check-ups by fine needle aspiration biopsy and severe malignancy is ruled out, we simply monitor it regularly
Also, new studies conducted in Japan, analyzing data from over 7,000 patients with thyroid papillary microcarcinoma, revealed that the risk of mortality and recurrence is almost the same regardless of whether the patient chooses surgery or active surveillance. Furthermore, patients who underwent surgical intervention complain of fatigue and other additional symptoms. However, in patients managed with active surveillance, the quality of life is maintained. This reflects the current reality.
Minimally Invasive Procedures (MITs)
Ekaterine Chitishvili: Minimally invasive procedures (MIP) are becoming increasingly popular. What is their real potential?
Juan Carlos Galofré: This is a less aggressive direction in medicine. It’s a kind of bridge between simple monitoring and an aggressive intervention(surgery). Currently, we should avoid treatment because there is a clear thyroid cancer over-diagnosing. With minimally invasive intervention, we can treat both benign and malignant forms of nodular thyroid disease. For example, if you have a small cancerous growth, one option is to use minimally invasive techniques. If papillary microcarcinoma is confirmed by fine-needle aspiration (FNA) results Bethesda V or VI classification result, we offer patients two options: a minimally invasive procedure or active surveillance.
However, you might ask, where is the boundary for this classification? Various studies have shown different boundaries. For example, Japanese researchers started active surveillance on 1 cm nodules, while in a New York study, patients with nodules up to 2 cm chose surveillance instead of surgery. Studies conducted in Japan, Korea, and China showed that after thermal ablation, the cancer completely disappeared more than 80% of cases.
My advice is that if the nodule size is less than 1.3 cm, active surveillance can be started. In some cases, the nodule is not perfectly round; therefore, during active surveillance, its growth by more than 3 mm is considered cancer progression. If there is suspicion of extrathyroidal invasion, the patient is under 18 years of age, or has a family history of thyroid cancer, it is better to refer the patient to a surgeon for complete resection
Indeterminate Thyroid Nodules
Ekaterine Chitishvili: What is your approach when the morphological result of fine-needle aspiration (FNA) yields a BETHESDA IV classification?
Juan Carlos Galofré Ferrater: This means that it could be either follicular adenoma or carcinoma. The reason is that in this case, it is not possible to differentiate malignant from benign by cytological examination, because malignancy is detected on the basis of capsule or vascular invasion, which cannot be detected by cytology. Follicular thyroid cancer cells invade the capsule, blood vessels, and lymphatic system.
If an indeterminate response is received on fine-needle aspiration (FNA) such as Bethesda III or IV, guidelines recommend performing lobectomy. However, in recent years, especially in the US and now in Europe as well, the clinical approach has changed. We can now perform molecular studies, which help us to rule out malignancy or rule in benign. Therefore, when we have both the BETHESDA classification and the molecular profile, we can decide with high accuracy and advise the patient whether to undergo surgical operation or follow the path of active surveillance.
Postpartum Thyroiditis and Thyroid Dysfunction in Women
Ekaterine Chitishvili: What do you recommend regarding other thyroid diseases, for example, postpartum thyroiditis, symptoms are often confused with depression. How can new mothers differentiate between thyroid problems and mental health problems, or how common are cases of postpartum thyroiditis?
Juan Carlos Galofré: You know, it’s very easy to rule out thyroid dysfunction with a simple blood test. If a mother feels palpitations, a rapid heart rate, is constantly tired, it is very simple and inexpensive to perform a serum TSH test, which will reveal whether we are dealing with thyroid dysfunction, and if so, the treatment of postpartum thyroiditis is very simple with monitoring and betablockers in the thyrotoxicosis phase and levothyroxine replacement, therapy when needed.
Most often, postpartum thyroiditis occurs in patients who have Hashimoto’s autoimmune disease, i.e., autoimmune hypothyroidism. This is quite common in today’s medicine. Studies show that more than 30% of women who had Hashimoto’s thyroiditis in the past, the chance of developing postpartum thyroiditis is significantly higher. In the general population, this risk is only about 5%. But if the patient has positive antithyroid antibodies, postpartum thyroiditis is quite common. Especially in women who have already experienced postpartum thyroiditis after a previous delivery. That is why I recommend checking your TSH level for prophylaxis.
How to recognize postpartum thyroiditis?
It usually start with a thyrotoxic period, which manifests as palpitations, hand tremors, constant tension, anxiety, and increased sensitivity to high environmental temperatures, then goes to hypothyroid state. If you are tired, do not go directly to a psychiatrist, but check your thyroid hormone, your TSH.
Thyroid Function and Pregnancy
Ekaterine Chitishvili: Can you explain the role of thyroid hormones in fetal development during the first trimester and why a regulated hormonal state is necessary before planning pregnancy? What risks are associated with thyroid hormone dysfunction during pregnancy?
Juan Carlos Galofré: You must check your thyroid functions in the first trimester of pregnancy. This is the most critical period for fetal development. It is critical because organs develop during this time. This depends on thyroid hormones, especially the central nervous system, to whose development thyroid hormones contribute significantly. If the mother has a thyroid deficiency, a hypothyroid state, and does not receive replacement therapy, this will significantly reduce fetal development or cause a miscarriage. Therefore, it is important to know that what has already developed cannot be changed. Therefore, if you are planning a pregnancy and your TSH is not normal, you must start treatment.
Pituitary Disorders: Hyperprolactinemia
As we have already mentioned, Professor Juan Carlos Galofré actively conducts research on one of the most important parts of the brain, the pituitary gland. That is why “Medscriptum” asked him about hyperprolactinemia. Today, this is a problem for many people. In many cases, hyperprolactinemia proceeds unnoticed. During this time, patients may experience menstrual cycle disturbances, breast swelling or discharge, and also momentary blurring of vision. All these issues fall within Professor Galofre’s competence, which is why we decided to talk to him about pituitary disease- hyperprolactinemia.
Ekaterine Chitishvili: This year Dr. Galofré, actively participated in the metoclopramide stimulation testing process. This method helps patients with cost-effective differential diagnosis of hyperprolactinemia and often prevents expensive Magnetic Resonance Imaging (MRI) of the pituitary. In your opinion, in which clinical cases can we openly refuse imaging studies and rely solely on the metoclopramide test? What are the criteria by which reliability is assessed to exclude a benign pituitary tumor, an adenoma, which may be completely asymptomatic and discovered by chance?
Juan Carlos Galofré: If you undergo a magnetic resonance imaging (MRI) examination, approximately 5% of the population will likely discover a pituitary incidentaloma. This is a pituitary tumor that has no hormone secretion. This is not normal, but it is a fact. We can make a distinction if we have a group of patients with incidentaloma (incidentally discovered pituitary tumor) and patients with hyperprolactinemia due to prolactin secreting adenoma. Not all of them will have an incidentaloma, and excess prolactin will be related to other causes. In some cases of hyperprolactinemia is due to an alteration called macroprolactinemia. There may also be patients who have both an incidentaloma and hyperprolactinemia together, but these two may not be related to each other.
How to distinguish these two patients? Dopamine, which is released from the hypothalamus, inhibits pituitary prolactin secretion. When a patient has a prolactinoma, prolactin levels are excessive and they also have low sensitivity to dopamine. When metoclopramide is used, it will stop the negative effect of dopamine on prolactin. This will happen by reducing dopamine secretion. In patients with hyperprolactinemia who do not have prolactinoma, the metoclopramide test increases prolactin levels by more than 200%. If the cause of hyperprolactinemia is a prolactinoma, then when the negative effects of dopamine are removed, prolactin remains almost stable with a less than 200% increase. Therefore, if a patient has the following clinical signs: milky fluid discharge from the breast (galactorrhea), interrupted menstrual cycle, or subclinical manifestations, we perform the test. Metoclopramide will help us differentiate prolactin excess caused by the pituitary from conditions caused by hyperprolactinemia due to other reasons. With this simple, very cost-effective test, we can avoid pituitary MRI.
Future Directions in Endocrinology
Ekaterine Chitishvili: Please share with us if any promising research or innovative methods are currently underway that, in your expert’s opinion, will have the most significant impact on the diagnosis and personalized treatment of endocrine diseases in the future?
Juan Carlos Galofré : Molecular studies are a great help in both diagnosis and treatment planning. This is especially important in cases of cancer, as it allows us to know what type of treatment will work for a specific patient and what will not. Identifying gene mutations allows us to block them with specific therapies. For example, we have ideal results in the treatment of RET mutations, especially in medullary thyroid cancer. These molecules have very high effectiveness, and these studies are still ongoing in the endocrine field. We also have news in the treatment of hypoparathyroidism, which is often a postoperative complication of thyroid surgery. Recently, a new molecule for parathyroid hormone (PTH) replacement, palopegteriparatide, has been approved both in the USA and Europe. This development finally allows us to treat our patients
