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13 pages, 3776 KiB

Open AccessArticle

Elastographic Evaluation of Thyroid Nodules in Children and Adolescents with Hashimoto’s Thyroiditis and Nodular Goiter with Reference to Cytological and/or Histopathological Diagnosis

by Hanna Borysewicz-Sańczyk, Beata Sawicka, Filip Bossowski, Janusz Dzięcioł and Artur Bossowski

J. Clin. Med. 2022, 11(21), 6339; https://doi.org/10.3390/jcm11216339 - 27 Oct 2022

Cited by 2 | Viewed by 1238

Abstract

There are data indicating the coexistence of papillary thyroid carcinoma and autoimmune thyroiditis (AIT) in children. The aim of the study was elastographic evaluation of thyroid nodules in children and adolescents with AIT and nodular goiter in relation to cytological and/or histopathological diagnosis. [...] Read more.

There are data indicating the coexistence of papillary thyroid carcinoma and autoimmune thyroiditis (AIT) in children. The aim of the study was elastographic evaluation of thyroid nodules in children and adolescents with AIT and nodular goiter in relation to cytological and/or histopathological diagnosis. We examined 215 children (57 boys and 158 girls) with 261 thyroid nodules (143 non-AIT and 118 AIT). All study participants underwent a conventional ultrasound examination with elastography followed by fine needle aspiration biopsy (FNAB). Abnormal Strain Ratio (SR ≥ 5) was observed in 36 non-AIT nodules and 15 AIT nodules. Papillary thyroid carcinoma was diagnosed in 5 patients (2% of all investigated nodules). SR of malignant thyroid nodules was statistically higher in comparison to SR of benign nodules both in the group of non-AIT (6 ± 4 vs. 3.67 ± 2.62, p = 0.024) and AIT nodules (6.3 ± 0.01 vs. 2.92 ± 1.89, p = 0.047). Comparison of non-AIT and AIT benign nodules revealed that SR was higher in non-AIT nodules (3.67 ± 2.62 vs. 2.92 ± 1.89, p = 0.01). We observed a strong positive correlation (R = 1) between TSH concentration and SR ratio in the group of all malignant thyroid nodules. Autoimmune inflammatory process of the thyroid gland does not limit the use of elastography in the diagnosis of thyroid nodules in children. Full article

(This article belongs to the Special Issue Hypothyroidism: Causes, Effects and Current Treatments)

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9 pages, 266 KiB

Open AccessArticle

Long-Term Adherence to Levothyroxine Replacement Therapy in Thyroidectomized Patients

by Raffaella Bocale, Giovambattista Desideri, Angelina Barini, Annamaria D’Amore, Mauro Boscherini, Stefano Necozione and Celestino Pio Lombardi

J. Clin. Med. 2022, 11(15), 4296; https://doi.org/10.3390/jcm11154296 - 24 Jul 2022

Cited by 1 | Viewed by 1298

Abstract

(1) Background: We evaluated the long term adherence to two distinct formulations of levothyroxine (L-T4), liquid or solid, which are differently influenced by concomitant food ingestion. (2) Methods: A total of 106 thyroidectomized patients (82 female, mean age 58.2 ± 13.3 years) on [...] Read more.

(1) Background: We evaluated the long term adherence to two distinct formulations of levothyroxine (L-T4), liquid or solid, which are differently influenced by concomitant food ingestion. (2) Methods: A total of 106 thyroidectomized patients (82 female, mean age 58.2 ± 13.3 years) on L-T4 replacement therapy in either liquid (n = 52) or solid formulation (n = 54) were administered the four-item Medication Adherence Questionnaire (MAQ). (3) Results: The study population had 59.4% adherers and 40.6% non-adherers. The global MAQ score was significantly better in patients under liquid L-T4 in comparison to those under solid L-T4 (0.42 ± 0.82 vs. 0.83 ± 0.95, respectively, p = 0.0085). The patients on tablet L-T4 forgot to take their medication more frequently than those on liquid LT4 treatment (p = 0.0159) and were more often careless at times about taking their medication (p = 0.007), whilst about one in two thyroidectomized patients preferred tablets for lifetime medication therapy. The global MAQ score was directly correlated with the circulating TSH levels in the whole study population (0.700, p < 0.0001) and inversely correlated with both the FT3 (−0.220, p = 0.0232) and FT4 (−0.327, p = 0.0006) serum concentrations. (4) Conclusions: Long-term adherence to L-T4 treatment was globally satisfactory although it was better for the liquid formulation, which appears to represent an easier-to-manage L-T4 replacement therapy for most thyroidectomized patients, particularly for those with difficulties in taking L-T4 while fasting. Full article

(This article belongs to the Special Issue Hypothyroidism: Causes, Effects and Current Treatments)

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18 pages, 5060 KiB

Open AccessArticle

Alteration of Serum Proteome in Levo-Thyroxine-Euthyroid Thyroidectomized Patients

by Claudia Landi, Silvia Cantara, Enxhi Shaba, Lorenza Vantaggiato, Carlotta Marzocchi, Fabio Maino, Alessio Bombardieri, Alfonso Carleo, Fabrizio Di Giuseppe, Stefania Angelucci, Luca Bini and Maria Grazia Castagna

J. Clin. Med. 2022, 11(6), 1676; https://doi.org/10.3390/jcm11061676 - 17 Mar 2022

Cited by 1 | Viewed by 1856

Abstract

The monotherapy with levo-thyroxine (LT4) is the treatment of choice for patients with hypothyroidism after thyroidectomy. However, many athyreotic LT4-treated patients with thyroid hormones in the physiological range experience hypothyroid-like symptoms, showing post-operative, statistically significant lower FT3 levels with respect to that before [...] Read more.

The monotherapy with levo-thyroxine (LT4) is the treatment of choice for patients with hypothyroidism after thyroidectomy. However, many athyreotic LT4-treated patients with thyroid hormones in the physiological range experience hypothyroid-like symptoms, showing post-operative, statistically significant lower FT3 levels with respect to that before total thyroidectomy. Since we hypothesized that the lower plasmatic FT3 levels observed in this subgroup could be associated with tissue hypothyroidism, here we compared, by a preliminary proteomic analysis, eight sera of patients with reduced post-surgical FT3 to eight sera from patients with FT3 levels similar to pre-surgery levels, and six healthy controls. Proteomic analysis highlights a different serum protein profile among the considered conditions. By enrichment analysis, differential proteins are involved in coagulation processes (PLMN-1.61, -1.98 in reduced vs. stable FT3, p < 0.02; A1AT fragmentation), complement system activation (CFAH + 1.83, CFAB + 1.5, C1Qb + 1.6, C1S + 7.79 in reduced vs. stable FT3, p < 0.01) and in lipoprotein particles remodeling (APOAI fragmentation; APOAIV + 2.13, p < 0.003), potentially leading to a pro-inflammatory response. This study suggests that LT4 replacement therapy might restore biochemical euthyroid conditions in thyroidectomized patients, but in some cases without re-establishing body tissue euthyroidism. Since our results, this condition is reflected by the serum protein profile. Full article

(This article belongs to the Special Issue Hypothyroidism: Causes, Effects and Current Treatments)

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9 pages, 611 KiB

Open AccessArticle

Diagnostic Re-Evaluation and Potential Predictor Factors of Transient and Permanent Congenital Hypothyroidism in Eutopic Thyroid Gland

by Gerdi Tuli, Jessica Munarin and Luisa De Sanctis

J. Clin. Med. 2021, 10(23), 5583; https://doi.org/10.3390/jcm10235583 - 27 Nov 2021

Cited by 2 | Viewed by 1584

Abstract

Background: The incidence of congenital hypothyroidism (CH) has increased over the years, and many predictors for detecting newborns with transient forms (TCH) as early as possible have been considered. Methods: All newborns diagnosed with primary CH and eutopic gland in the Piedmont region [...] Read more.

Background: The incidence of congenital hypothyroidism (CH) has increased over the years, and many predictors for detecting newborns with transient forms (TCH) as early as possible have been considered. Methods: All newborns diagnosed with primary CH and eutopic gland in the Piedmont region of Italy in the period of January 2014–June 2019 were enrolled and re-evaluated at the age of 2 years. Results: 105 newborns were diagnosed with CH during the study period. Dyshormonogenesis was observed in 55/105. At re-evaluation, we found that 52.7% had permanent CH (PCH), while 47.3% had TCH. Male/female rate, TSH levels at diagnosis, levothyroxine requirement at withdrawal and extra-thyroid congenital malformations rate were higher in the PCH group (p = 0.02, p = 0.009, p = 0.02 and p = 0.01), while fT4 levels at diagnosis were lower (p = 0.03). Sensitivity of 72.4% and specificity of 80.7% for serum TSH above 60 mcUI/mL, sensitivity of 73% and specificity of 72.4% for serum fT4 level below 7.2 pg/mL and sensitivity of 66% and specificity of 68% for drug requirement above 2.25 mcg/kg/day were observed in PCH. Conclusions: Demographic, clinical and hormonal data at diagnosis and levothyroxine requirement during the first two years should be adequately monitored to identify infants who are most likely to discontinue therapy after the age of 24 months. Full article

(This article belongs to the Special Issue Hypothyroidism: Causes, Effects and Current Treatments)

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11 pages, 2074 KiB

Open AccessArticle

Improvements in Quality of Life and Thyroid Parameters in Hypothyroid Patients on Ethanol-Free Formula of Liquid Levothyroxine Therapy in Comparison to Tablet LT4 Form: An Observational Study

by Katarzyna Bornikowska, Małgorzata Gietka-Czernel, Dorota Raczkiewicz, Piotr Glinicki and Wojciech Zgliczyński

J. Clin. Med. 2021, 10(22), 5233; https://doi.org/10.3390/jcm10225233 - 10 Nov 2021

Cited by 6 | Viewed by 2367

Abstract

Levothyroxine (LT4) is a standard therapy in hypothyroidism; however, its bioavailability and therapeutic effects might be affected by many factors. Data shows that therapy with liquid LT4 characterized by quicker pharmacokinetics provides better thyroid hormones control than tablet LT4. We addressed the quality [...] Read more.

Levothyroxine (LT4) is a standard therapy in hypothyroidism; however, its bioavailability and therapeutic effects might be affected by many factors. Data shows that therapy with liquid LT4 characterized by quicker pharmacokinetics provides better thyroid hormones control than tablet LT4. We addressed the quality of life (QoL) and efficacy of the new ethanol-free formula of liquid LT4 (Tirosint^®SOL) treatment in 76 euthyroid patients with primary (PH, n = 46) and central hypothyroidism (CH, n = 30), and compared the results to retrospective data on equivalent doses of tablet L-T4 therapy. After 8 weeks of liquid LT4 therapy, we found a significant improvement in QoL in both PH and CH patients. TSH levels were unaltered in PH patients. Free hormone levels (fT4 and fT3) increased in all the patients, with the exception of fT3 in the CH group. SHBG and low-density lipoprotein (LDL) also improved. Liquid LT4 therapy provided a better thyroid hormone profile and improvement in patients’ QoL than the tablet form, which was possibly due to the more favorable pharmacokinetics profile resulting in better absorption, as suggested by the increased free thyroid hormone levels. In summary, this is the first study addressing the QoL in hypothyroid patients, including primary and central hypothyroidism, treated with liquid LT4 formula in everyday practice. Full article

(This article belongs to the Special Issue Hypothyroidism: Causes, Effects and Current Treatments)

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9 pages, 555 KiB

Open AccessFeature PaperArticle

Decreased Thyroxine Levels during rhGH Therapy in Children with Growth Hormone Deficiency

by Ewelina Witkowska-Sędek, Anna Małgorzata Kucharska, Małgorzata Rumińska, Monika Paluchowska and Beata Pyrżak

J. Clin. Med. 2021, 10(21), 5100; https://doi.org/10.3390/jcm10215100 - 30 Oct 2021

Cited by 6 | Viewed by 1539

Abstract

Background: Hypothyroidism in children leads to growth retardation. However, there is some evidence that recombinant human growth hormone (rhGH) therapy could suppress thyroid function. The most common observation in rhGH-treated patients is a decrease in thyroxine levels, which is reported as transient, but [...] Read more.

Background: Hypothyroidism in children leads to growth retardation. However, there is some evidence that recombinant human growth hormone (rhGH) therapy could suppress thyroid function. The most common observation in rhGH-treated patients is a decrease in thyroxine levels, which is reported as transient, but the studies in the field are inconsistent. We aimed to evaluate thyroid function in initially euthyroid children with idiopathic isolated GH deficiency during long-term rhGH therapy and to determine who is at a higher risk of thyroid function alterations during the therapy. Methods: The study group consisted of 101 children treated with rhGH for at least three years. Serum TSH and fT4 levels were determined at baseline, after the first six months and after each full year of therapy. The associations between changes in thyroid hormone levels during rhGH therapy and GH deficit, insulin-like growth factor-1 levels and growth response were investigated. Results: A significant decrease in fT4 levels (p = 0.01) was found as early as after the first six months of rhGH therapy. This effect persisted in the subsequent years of treatment without any significant changes in TSH values and tended to be rhGH dose related. Children with a greater fT4 decrease after the initiation of rhGH therapy were older, had higher bone age and responded to that therapy worse than children with lower fT4 changes. Conclusions: Our study revealed a long-term decrease in fT4 levels during rhGH therapy in initially euthyroid GHD children. The decrease in fT4 levels was associated with a lower growth response to rhGH therapy. Full article

(This article belongs to the Special Issue Hypothyroidism: Causes, Effects and Current Treatments)

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9 pages, 382 KiB

Open AccessArticle

Long-Term Outcome of Patients with TPO Mutations

by Leraz Tobias, Ghadir Elias-Assad, Morad Khayat, Osnat Admoni, Shlomo Almashanu and Yardena Tenenbaum-Rakover

J. Clin. Med. 2021, 10(17), 3898; https://doi.org/10.3390/jcm10173898 - 30 Aug 2021

Cited by 3 | Viewed by 1628

Abstract

Introduction: Thyroid peroxidase (TPO) deficiency is the most common enzymatic defect causing congenital hypothyroidism (CH). We aimed to characterize the long-term outcome of patients with TPO deficiency. Methods: Clinical and genetic data were collected retrospectively. Results: Thirty-three patients with primary CH caused by [...] Read more.

Introduction: Thyroid peroxidase (TPO) deficiency is the most common enzymatic defect causing congenital hypothyroidism (CH). We aimed to characterize the long-term outcome of patients with TPO deficiency. Methods: Clinical and genetic data were collected retrospectively. Results: Thirty-three patients with primary CH caused by TPO deficiency were enrolled. The follow-up period was up to 43 years. Over time, 20 patients (61%) developed MNG. Eight patients (24%) underwent thyroidectomy: one of them had minimal invasive follicular thyroid carcinoma. No association was found between elevated lifetime TSH levels and the development of goiter over the years. Conclusions: This cohort represents the largest long-term follow up of patients with TPO deficiency. Our results indicate that elevated TSH alone cannot explain the high rate of goiter occurrence in patients with TPO deficiency, suggesting additional factors in goiter development. The high rate of MNG development and the risk for thyroid carcinoma indicate a need for long-term follow up with annual ultrasound scans. Full article

(This article belongs to the Special Issue Hypothyroidism: Causes, Effects and Current Treatments)

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Review

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9 pages, 271 KiB

Open AccessReview

Pharmacokinetics and Clinical Implications of Two Non-Tablet Oral Formulations of L-Thyroxine in Patients with Hypothyroidism

by Pierpaolo Trimboli and Stéphane Mouly

J. Clin. Med. 2022, 11(12), 3479; https://doi.org/10.3390/jcm11123479 - 16 Jun 2022

Cited by 4 | Viewed by 1979

Abstract

Background: Increased knowledge of the pharmacokinetic characteristics of orally administered levothyroxine (L-T₄) has improved individualization of dosing regimens. However, up to 40–45% of patients, depending on the leading cause of hypothyroidism, are still over- or, more often, undertreated. Unintentional non-adherence to [...] Read more.

Background: Increased knowledge of the pharmacokinetic characteristics of orally administered levothyroxine (L-T₄) has improved individualization of dosing regimens. However, up to 40–45% of patients, depending on the leading cause of hypothyroidism, are still over- or, more often, undertreated. Unintentional non-adherence to L-T₄ replacement therapy includes all situations of unintended drug–drug and drug–food interactions as well as fasting conditions that are not necessarily respected by patients. Results: In this specific context, the overall information concerning those factors with the potential to affect L-T₄ absorption refers only to tablet formulation. Indeed, this is the reason why new non-tablet formulations of L-T₄ were introduced some years ago. In this regard, the current literature review was designed to summarize pharmacokinetic, drug and food interactions and clinical data focusing on two new oral L-T₄ formulations, i.e., liquid and soft-gel capsule in healthy volunteers and patients with primary hypothyroidism. The non-tablet L-T₄ soft-gel capsules and solution have proven bioequivalence with the usual L-T₄ tablet Princeps and generic formulations. Clinical studies have suggested higher performance of non-tablet formulations than tablet in those patients with suboptimal adherence. The impact of gastrointestinal conditions and variation of gastric pH was lower with either soft gel/solution than with tablets. In addition, the extent of drug–drug and drug–food interactions remains low and of uncertain clinical relevance. Conclusions: Pending further studies allowing one to extend the use of soft-gel/solution preparations in unselected patients, non-tablet L-T₄ formulations should be considered as a first-line choice, especially in those patients with moderate-to-high potential of suboptimal tablet performance. Full article

(This article belongs to the Special Issue Hypothyroidism: Causes, Effects and Current Treatments)

23 pages, 2150 KiB

Open AccessReview

Neuropsychological Alterations in Patients with Congenital Hypothyroidism Treated with Levothyroxine: Linked Factors and Thyroid Hormone Hyposensitivity

by Karla Cristina Razón-Hernández, Norma Osnaya-Brizuela, Armando Valenzuela-Peraza, Esperanza Ontiveros-Mendoza, Luis Miguel Rodríguez-Serrano, Jorge Pacheco-Rosado, Gerardo Barragán-Mejía and Karla Sánchez-Huerta

J. Clin. Med. 2022, 11(12), 3427; https://doi.org/10.3390/jcm11123427 - 15 Jun 2022

Cited by 1 | Viewed by 2274

Abstract

Eighty-five percent of the studies of patients with congenital hypothyroidism (CH) treated with Levothyroxine (L-T₄) report neuropsychological sequelae throughout life. In neonates and infants, there is a deficit in sensorimotor skills (impaired balance). In preschool and elementary school children and adolescents, [...] Read more.

Eighty-five percent of the studies of patients with congenital hypothyroidism (CH) treated with Levothyroxine (L-T₄) report neuropsychological sequelae throughout life. In neonates and infants, there is a deficit in sensorimotor skills (impaired balance). In preschool and elementary school children and adolescents, there are alterations in intellectual quotient (low scores), language (delayed phonological acquisition), memory (visual, verbal, visuospatial, visuoconstructive, autobiographical, and semantic), sensorimotor skills (impaired fine and gross motor control), and visuoconstructive–visuospatial domain (low scores in spatial location, block design, and object assembly). These neuropsychological domains are also affected in young adults, except for language (adequate verbal fluency) and visuoconstructive–visuospatial domain (no data). The onset and severity of neuropsychological sequelae in patients with treated CH depend on several factors: extrinsic, related to L-T₄ treatment and social aspects, and intrinsic, such as severity and etiology of CH, as well as structural and physiological changes in the brain. In this review, we hypothesized that thyroid hormone hyposensitivity (THH) could also contribute to neuropsychological alterations by reducing the effectiveness of L-T₄ treatment in the brain. Thus, further research could approach the THH hypothesis at basic and clinical levels to implement new endocrinological and neuropsychological therapies for CH patients. Full article

(This article belongs to the Special Issue Hypothyroidism: Causes, Effects and Current Treatments)

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10 pages, 260 KiB

Open AccessReview

An Underestimated Toxicity Radiation-Induced Hypothyroidism in Patients Multimodally Treated for Breast Cancer

by Camil Ciprian Mireștean, Roxana Irina Iancu and Dragoș Petru Teodor Iancu

J. Clin. Med. 2021, 10(23), 5503; https://doi.org/10.3390/jcm10235503 - 24 Nov 2021

Cited by 4 | Viewed by 2149

Abstract

Radiation therapy is part of the therapeutic arsenal for breast cancer, whether it is adjuvant treatment after lumpectomy or radical mastectomy, or it is used as a palliative option in the case of metastatic or recurrent disease. Significant advances in diagnostic and therapeutic [...] Read more.

Radiation therapy is part of the therapeutic arsenal for breast cancer, whether it is adjuvant treatment after lumpectomy or radical mastectomy, or it is used as a palliative option in the case of metastatic or recurrent disease. Significant advances in diagnostic and therapeutic stratification of breast cancers have significantly prolonged survival, even in the metastatic stage. Exposure of patients during the course of the disease in a multidisciplinary therapeutic approach including chemotherapy, hormone therapy, targeted anti-HER therapies or CDK4/6 inhibitors had led to improved survival but with the price of additional toxicity. Among them, hypothyroidism is a well-known consequence of external radiation therapy, especially in the case of cervical region irradiation, including supraclavicular and infra-clavicular nodal levels. In this situation, the thyroid gland is considered as an organ at risk (OAR) and receives a significant dose of radiation. Subclinical hypothyroidism is a common endocrine disorder characterized by elevated TSH levels with normal levels of FT4 (free T4) and FT3 (free T3), and as a late effect, primary hypothyroidism is one of the late effects that significantly affects the quality of life for patients with breast cancer receiving multimodal treatment. Hypothyroidism has a significant impact on quality of life, most often occurring as late clinical toxicity, secondary to thyroid irradiation at doses between 30 and 70 Gy. Dose-volume parameters of irradiation, gland function at the beginning of the treatment and associated systemic therapies may be factors that alter thyroid radio-sensitivity and affect thyroid gland tolerance. In the case of head and neck tumor pathology, in which doses of >50 Gy are routinely used, the thyroid gland is generally considered as an OAR, the rate of radio-induced hypothyroidism being estimated at rates of between 20% and 52%. For breast cancer, the thyroid is often neglected in terms of dosimetry protection, the rate of late dysfunction being 6–21%. Full article

(This article belongs to the Special Issue Hypothyroidism: Causes, Effects and Current Treatments)

10 pages, 399 KiB

Open AccessReview

Thyroid Hormone Changes Related to Growth Hormone Therapy in Growth Hormone Deficient Patients

by Anna Małgorzata Kucharska, Ewelina Witkowska-Sędek, Małgorzata Rumińska and Beata Pyrżak

J. Clin. Med. 2021, 10(22), 5354; https://doi.org/10.3390/jcm10225354 - 17 Nov 2021

Cited by 1 | Viewed by 2283

Abstract

The alterations in thyroid function during recombinant human growth hormone (rhGH) treatment have been reported by many authors since this therapy became widely available for patients with growth hormone deficiency (GHD). Decrease of thyroxine level is the most frequent observation in patients treated [...] Read more.

The alterations in thyroid function during recombinant human growth hormone (rhGH) treatment have been reported by many authors since this therapy became widely available for patients with growth hormone deficiency (GHD). Decrease of thyroxine level is the most frequent observation in patients treated with rhGH. This paper presents literature data describing changes in thyroid function related to rhGH therapy and a current explanation of mechanisms involved in this phenomenon. The effect of GH on the hypothalamic-pituitary-thyroid (HPT) axis is dependent on a multilevel regulation beginning from influence on the central axis, thyroid, and extra-thyroidal deiodinases activity as well as the impact on thyroid hormone receptors on the end. Changes in central and peripheral regulation could overlap during rhGH therapy, resulting in central hypothyroidism or an isolated slight deficiency of thyroxine. The regular monitoring of thyroid function is recommended in patients treated with rhGH and the decision of levothyroxine (L-thyroxine) supplementation should be made in the clinical context, taking into account thyroid hormone levels, as well as the chance for satisfactory growth improvement. Full article

(This article belongs to the Special Issue Hypothyroidism: Causes, Effects and Current Treatments)

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