Ultrasound, Doppler and other signs during drug-free transition from subclinical hypothyroidism to euthyroidism: a case report
Andrey Valerievich Ushakov
Background: It is known that subclinical hypothyroidism (SCH) often converts to euthyroidism. However, the mechanism of such changes is unclear and can only be speculated. This difficulty is likely due to limitations in diagnostic guidelines and their interpretation. Therefore, in the presented case, important diagnostic criteria that can improve understanding of the essence and pathogenesis of primary hypothyroidism are shown and explained.
Case Description: A 15-year-old female patient experienced a transition from SCH to euthyroidism against the background of highly normal values of thyroid hormones, the full state of the thyroid parenchyma and significantly increased blood flow in the Doppler mode. She did not take medications. Conditions likely to trigger SCH included acute respiratory illness, living in a cold climate, and mental stress due to prolonged preparation for exams. The transition to euthyroidism occurred after sufficient stay in the conditions of a southern resort in the summer and mental comfort.
Conclusions: As a result, it was revealed that the amount of thyroid-stimulating hormone (TSH) depends on the intensity of energy expenditure of the body in accordance with living conditions. The increased intensity of blood flow in the thyroid during SCH and euthyroidism shows the leading role of the autonomic nervous system and the auxiliary importance of TSH. The concentration of thyroid hormones at the maximum limit of normal in SCH, together with the significantly increased Doppler blood flow, suggests common elements of pathogenesis with Graves’ disease through the autonomic nervous system. With many months of thyroid overstrain, ultrasound shows signs of corresponding depletion in the form of hypoechogenicity of the lobules, but the preservation of a sufficient amount of hormone-producing tissue.
Keywords: Thyroid ultrasound; hypothyroidism; Hashimoto’s thyroiditis; Doppler; case report
Received: 17 March 2024; Accepted: 13 December 2024; Published online: 17 January 2025.
doi: 10.21037/acr-24-59
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Key findings
• The basis for the development of subclinical hypothyroidism (SCH) is overstrain of the thyroid gland to replenish the excess consumption of its calorigenic hormones. This overstrain is manifested by an increase in the intensity of blood flow under the control of the autonomic nervous system.
What is known and what is new?
• SCH often converts to euthyroidism, but the mechanism of this transformation is unclear. This circumstance limits the possibilities of recovery and makes it difficult to choose indications for hormonal treatment.
• Thyroid overstrain is confirmed due to increased energy expenditure by the body. Depletion of the thyroid parenchyma in SCH is associated with its overstrain. The magnitude of neural stimulation of the thyroid in SCH can be very strong and indicate common elements with the pathogenesis of Graves’ disease.
What is the implication, and what should change now?
• In studies of the development of SCH and the transition to euthyroidism, it is necessary to take into account the energy expenditure of the body to overcome unfavorable living conditions and diseases. Ultrasound and Doppler will help determine the hormone production potential of the gland and the magnitude of thyroid overstrain in SCH.
Introduction
Subclinical hypothyroidism (SCH) is usually defined as a laboratory symptom: a combination of excess thyroid-stimulating hormone (TSH) with normal levels of thyroid hormones [especially free thyroxine (FT4)]. The term “subclinical” implies the absence of symptoms. However, such a relationship is not observed, which creates one of the reasons for criticizing the concept of “subclinical hypothyroidism” (1,2). There are also doubts and disagreements about the usefulness of determining SCH at different values of thyroid hormones within the normal range, including combinations of laboratory parameters with the same excess of TSH (3).
In addition, practice has repeatedly confirmed that the SCH state often turns into euthyroidism. Such normalization is determined in almost 50–60% of cases in the period from 3 months to 3 years (4,5). One review, including 21 studies with 2,192 participants, found that hormone replacement therapy was futile for SCH and that the basis of SCH as a disease was poorly understood (6). When analyzing the literature on indications for treatment of SCH, the authors identify contradictions, the use of empirical and statistical principles instead of pathogenetic ones (7). Also, evaluation of ultrasound and Doppler signs in SCH is not used.
The presented example of the transition from SCH to euthyroidism contains a combination of signs that make it possible to understand the nature of the processes in SCH. The analysis of this case reveals for the first time the basis of SCH and demonstrates the principles of diagnosis and evaluation of important features of the disease. This case is presented in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-24-59/rc).
Case presentation
A 15-year-old female patient (175 cm, 50 kg) underwent an initial examination in Ushakov Thyroid Clinic at the end of July 2023 and a follow-up diagnosis in January 2024. The reason for the visit was a SCH, identified a month earlier in another clinic. There is also a significant excess of antibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TGAb).
Her appearance is normal; feels good. The only complaints are periodic fatigue and coldness of the feet. At rest, blood pressure is 117/76 mmHg, pulse is 67 per minute. A blood test showed: (I) signs of euthyroidism with the maximum normal value of free triiodothyronine (FT3); (II) signs of grade 1 anemia (Table 1).
Table 1
| Sign | Examination 1: June 13, 2023 | Examination 2: July 23, 2023 | Examination 3: January 28, 2024 |
|---|---|---|---|
| TSH, mU/mL | 8.8 (0.27–4.26) | 3.05 (0.35–5.10) | 4.08 (0.35–5.10) |
| FT4, pmol/L | 20.1 (10.3–24.5) | 10.3 (6.43–18.02) | 12.6 (6.43–18.02) |
| FT3, pmol/L | – | 6.14 (2.76–6.40) | 4.70 (2.76–6.40) |
| Total T4, nmol/L | – | 92.37 (64.35–186.61) | 106.95 (64.35–186.61) |
| TPOAb, IU/mL | >1,000 (0.0–30.0) | >1,000 (0.0–9.0) | >1,000 (0.0–9.0) |
| TGAb, IU/mL | >2,000 (0.0–100.0) | 299 (0.0–4.0) | 87 (0.0–4.0) |
| RBC, mln/µL | 4.2 | 4.02 (117–153) | 4.59 (117–153) |
| Hemoglobin, g/dL | 132 | 102.00 | 138.00 |
| Complaints | Fatigue, cold feet | Fatigue, cold feet | Fatigue, cold feet |
| Thyroid volume (right lobe; left lobe), mL | 13.9 (6.5; 7.4) | 11.7 (6.1; 5.6) | 14.6 (7.9; 6.7) |
| Echogenicity of two lobes of parenchyma | Slight hypoechogenic | Slight hypoechogenic | Moderate hypoechogenic |
| PSV in the system of the superior thyroid artery (right; left), cm/s | No; No | 52.3; 47.6 | 32.2; 39.9 |
| PSV of the common carotid artery (right; left), cm/s | No; No | 63.5; 56.4 | 68.2; 62.3 |
| Blood flow intensity in parenchyma of thyroid lobes | Significantly increased | Significantly increased | Slightly increased |
| Use of thyroid hormone replacement | No, never | No, never | No, never |
*, for blood parameters, laboratory standards are indicated in parentheses. TSH, thyroid-stimulating hormone; FT4, free thyroxine; FT3, free triiodothyronine; Total T4, total thyroxine; TPOAb, antibodies to thyroid peroxidase; TGAb, antibodies to thyroglobulin; RBC, red blood cells; PSV, peak systolic velocity.
In July 2023, ultrasound revealed a slight increase in thyroid volume, signs of minor stromal swelling (low hypoechogenicity of the parenchyma), the presence of about 99% complete hormone-producing tissue (8), significantly increased blood flow intensity in two lobes, moderate increase in peak systolic velocity (PSV) in the superior thyroid arteries (STA) (Figure 1, Table 1). Nodules were missing. A gradient-percentage method for assessing hypoechogenicity and a quantitative method for determining blood intensity were used (8). The settings for gray scale and Doppler modes are shown in the images (Figure 1).
Almost 6 months later (January, 2024), a control examination was carried out (Table 1, Figure 2). The state of euthyroidism was preserved, FT3 was optimized. Ultrasound revealed a similar volume of the thyroid, increased stromal swelling (moderate hypoechogenicity of the parenchyma) (8), a small number of hypoechoic lobules, the presence of about 98% of complete hormone-producing tissue, slightly increased intensity of blood flow in two lobes, and low enhancement of PSV STA (Figure 2).
The patient was born and lived all her life in a cold and little sunny region with a sufficient concentration of iodine. For many years as a child, she was bothered by periodic pain in her knee joints. Non-steroidal anti-inflammatory drugs helped.
From October 2022 to May 2023 there was a daily headache. It was weak, involved different parts of the head, and lasted for hours. During this period, the patient had intense mental activity associated with preparing for exams. Including, during the cold season 2022–2023, several times she had a cold with low-grade body temperature. In June 2023, an ultrasound examination of the vessels of the neck accidentally revealed changes in the thyroid gland and then SCH and excess TPOAb and TGAb (Table 1). At the end of June and July, she rested for 25 days on the coast in Turkey in more favorable conditions (warmth, sunbathing, lack of mental stress, swimming). Then, together with her parents, she turned to our clinic for help for the first time.
The patient never took hormonal medications or iodine preparations. Magnetic resonance imaging of the brain showed a normal state of the hypothalamic-pituitary zone and other structures. An additional blood test showed a slight iron deficiency.
During the cold season of 2023–2024 there were no colds, but the patient continued to live in the same conditions, including mental stress due to study. At the beginning of autumn 2023, she took a minimum dose of iron with vitamin C (Sorbifer Durules, 1 tablet) for 1.5 months. The patient, her parents and the doctor confirmed the role of unfavorable conditions on the state of the body and hormonal metabolism. The prognosis for the state of hormonal metabolism is favorable with an adequate reduction in mental stress and improvement in temperature living conditions.
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient and her parents for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
Discussion
The only reliable criterion for hypothyroidism is an excess of TSH, which indicates an increase in the body’s need for calorigenic thyroid hormones [triiodothyronine (T3) and thyroxine (T4)] and corresponding stimulation of the thyroid (minor or major). In SCH, regardless of the magnitude of the increase in TSH, thyroid hormones are normal, which can be understood as the ability of the gland to maintain the desired concentration of hormones in the blood under the influence of additional stimulation.
However, it is widely believed that primary hypothyroidism most often occurs due to insufficient hormone-producing capacity of the thyroid gland. Including due to autoimmune influence. Other causes of hypothyroidism are usually rare (primary iodine deficiency) or very rare (impaired deiodination, etc.). Unfortunately, experts lose sight of the most important cause of primary hypothyroidism—an increase in the body’s energy expenditure, which is associated with excess consumption of calorigenic thyroid hormones. After all, the main function of the thyroid is to ensure the absorption of energy by all cells of the body (9,10).
Our patient lived for a long time in a cold climate, which is a condition for strengthening the basal metabolism and activating the thyroid. Studies have confirmed that, for example, residents of cold regions usually have an excess of TSH (11). We do not know about the state of the patient’s thyroid hormonal metabolism in previous years. Nevertheless, based on her living conditions, one can think that energy consumption was increased to some extent.
In the last cold period of the year [2022–2023], preceding SCH, the additional energy consumption of our patient’s body was further increased due to overcoming colds and significant mental stress (12). Presumably, all these circumstances together increased the body’s energy expenditure, and therefore increased the rate of consumption of thyroid hormones. Therefore, the stimulation of the thyroid has increased compensatorily to adequately activate the rate of hormone formation.
As you can see, the increase in TSH in the patient at the beginning of summer 2023 was small (<10 µIU/mL), which corresponds to a slight excessive stimulation of the thyroid, that is, minor hypothyroidism. Since, according to ultrasound data, there was enough hormone-producing tissue in her gland (almost 99%), the overstrain of the thyroid ensured even highly normal levels of FT4 and FT3. All these signs refute the idea of hypothyroidism as an underactive thyroid and its inability to produce sufficient hormones. The FT3 value above the normal limit presumably indicates a pathogenetic process similar to Graves’ disease.
In addition, the intensity of thyroid blood flow was significantly enhanced (Figure 1E,1F). This increase in blood flow is common in diffuse hyperthyroidism (Graves’ disease) and probably corresponds to the magnitude of nerve stimulation of the gland (8,13). An additional reference point for such enhanced stimulation, aimed specifically at the thyroid, is an increase in the PSV of the thyroid artery, with a normal level of PSV in the common carotid arteries (Table 1). Therefore, one can think of common mechanisms of thyroid stimulation in primary hypothyroidism and Graves’ disease (14).
One might think that a decrease in energy-consuming influences when living for about a month in a warm and sunny climate reduced the consumption of calorigenic hormones (T3 and T4). Therefore, almost immediately after the southern holiday, TSH returned to normal. However, this reduction in energy expenditure was still insufficient, since Doppler showed significantly intense thyroid blood flow, as a sign of excessive increase in the functional tension of the gland.
It is appropriate to consider grade 1 iron deficiency anemia as one of the reasons for excessive thyroid activity that persisted in July 2023. This condition is associated with erythroid difficulty in providing the body with the oxygen needed for energy production (15). Therefore, one can think that the restoration of erythron due to a course of treatment with iron medication, together with summer natural factors, reduced the rate of consumption of thyroid hormones.
As a result, after 6 months we even detected a decrease in thyroid stimulation: with almost the same level of TSH (mostly normal), the intensity of the thyroid blood flow and PSV of the thyroid gland decreased to some extent (Figure 2E,2F, Table 1). In this case, anemia cannot be considered as the key cause of thyroid overstrain, since TSH returned to normal in the presence of anemia with a significant improvement in living conditions.
The TSH-independent regulation of thyroid hormone production detected in the patient is confirmed by data from previous studies, focusing on the role of the sympathetic nervous system (16,17).
As a result of many months of overstrain of the thyroid, signs of depletion of its parenchyma appeared, which ultrasound showed in the form of hypoechoic lobules (Figure 2A-2D). Their appearance is probably caused by isolated nerve conduction influence on individual lobules or groups of lobules (8). This change in the parenchyma is not provoked by the immune process, but is only accompanied by it. This conclusion is acceptable on the basis of: (I) a significant excess of TPOAb and TGAb in the normal state of the thyroid parenchyma in this and other cases (8) and (II) a decrease in the number of TGAb (incorrect testing in the laboratory of the values of TPOAb did not allow us to see the features for this indicator). It should also be clarified that an increase in general hypoechogenicity is associated with stromal swelling, but not immune activity (8).
Signs that influence the transition from subclinical and manifest hypothyroidism to euthyroidism are also being studied in patients taking hormonal drugs. According to 16 studies involving 1,082 patients of different ages, 37% of cases of transition to euthyroidism after stopping the hormonal drug were identified (18). Our assessment of the methods and results of these studies showed: (I) a lack of information about the energy-intensive living conditions of patients; (II) a lack of data on the state of thyroid hormonal metabolism (FT3 and FT4) immediately before the administration of a hormonal drug; and (III) a lack of understanding by specialists of the use of ultrasound capabilities (5,19). In particular, the researchers did not determine by ultrasound the amount of hormone-producing thyroid parenchyma (approximately in percentage) and the magnitude of its overstrain using Doppler (5,19). Despite the fact that our patient was not prescribed a hormonal drug, the identified pathogenetic guidelines may help in correcting the indications for hormonal therapy.
Despite our efforts to focus on diagnostic accuracy in identifying pathogenetically important signs, it is appropriate to consider significant limitations for interpretation: a relatively short observation period, incomplete data from studies of the patient by other specialists, one case. Of course, the present analysis of this case was led by the author’s study of key features in many hundreds of patients with SCH and other thyropathies over the 16 years that remained outside the scope of the article. Regardless of the limitations, the diagnostic criteria shown can help colleagues improve methods for further research.
Conclusions
Significant energy-consuming living conditions are the leading cause of thyroid overstrain, which occurs primarily under the influence of the autonomic nervous system and additionally from the pituitary gland (TSH). Thyroid overstrain is determined in Doppler mode by an increase in blood flow intensity and PSV STA. With SCH, the thyroid is able to provide the body with a sufficient amount of hormones due to more intense activity. The amount of FT3 can be significantly normal in mild hypothyroidism, which, together with a significant increase in blood flow intensity, indicates common pathogenetic principles of primary hypothyroidism with Graves’ disease. Many months of overstrain of the thyroid leads to its corresponding depletion, determined by ultrasound in the form of small hypoechoic segments (lobules). The widespread hypoechogenicity of the thyroid parenchyma is not an indicator of the hormone-forming ability of the gland. Ultrasound assessment of the percentage of hormone-producing thyroid tissue (in combination with gland volume) is an important guide to the likelihood of transition from SCH to euthyroidism.
Acknowledgments
Funding: None.
Footnote
Reporting Checklist: The author has completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-24-59/rc
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Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-24-59/coif). The author has no conflicts of interest to declare.
Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient and her parents for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
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Cite this article as: Ushakov AV. Ultrasound, Doppler and other signs during drug-free transition from subclinical hypothyroidism to euthyroidism: a case report. AME Case Rep 2025;9:32.
