Pandora’s Box: Autoimmune Hypothyroidism Treatment During Pregnancy

There are international protocols for the management of hypothyroidism induced by autoimmune thyroid disease during pregnancy. In this descriptive study, we analyzed the implementation of international protocols regarding these pathologies, in local clinical practice. Analyzing the cases admitted to the Obstetrics and Gynecology department of Bucharest University Emergency Hospital on a period of 55 months, we identified the pregnancies with autoimmune hypothyroidism treated with Levothyroxine (LT4). We determined the prevalence of specific immunological markers for autoimmune hypothyroidism in pregnant women, we analyzed whether they are associated with distinct clinical phenotypes and ultrasound characteristics, and also, we evaluated the treatment of choice. Measurement of thyroglobulin antibodies, thyroid peroxidase antibodies, Thyroid-Stimulating Hormone, free fractions of Triiodothyronine and Thyroxine with substitute treatment instituted early (in the first 2 weeks postnatal) determine the normalization of cognitive development, especially in areas known for iodine deficiency, including Romania.

Development of Graves' Disease After SARS-CoV-2 mRNA Vaccination: A Case Report and Literature Review

Background: Mounting evidence has revealed the interrelationship between thyroid and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to explain the thyroid dysfunction and autoimmune thyroid disorders observed after coronavirus disease 2019 (COVID-19). There are limited reports of thyroid dysfunction after SARS-CoV-2 vaccination.Methods: We report a case of a 40-year-old Chinese woman who developed Graves' disease after BNT162b2 mRNA vaccine. A search of PubMed and Embase databases from 1 September 2019 to 31 August 2021 was performed using the following keywords: “COVID,” “vaccine,” “thyroid,” “thyroiditis,” and “Graves.”Results: A 40-year-old Chinese woman who had 8-year history of hypothyroidism requiring thyroxine replacement. Her anti-thyroid peroxidase and anti-thyroglobulin antibodies were negative at diagnosis. She received her first and second doses of BNT162b2 mRNA vaccine on 6 April and 1 May 2021, respectively. She developed thyrotoxicosis and was diagnosed to have Graves' disease 5 weeks after the second dose of vaccine, with positive thyroid stimulating immunoglobulin level, diffuse goiter with hypervascularity on thyroid ultrasonography and diffusely increased thyroid uptake on technetium thyroid scan. Both anti-thyroid peroxidase and anti-thyroglobulin antibodies became positive. She was treated with carbimazole. Literature search revealed four cases of Graves' disease after SARS-CoV-2 vaccination, all after mRNA vaccines; and nine cases of subacute thyroiditis, after different types of SARS-CoV-2 vaccines.Conclusion: Our case represents the fifth in the literature of Graves' disease after SARS-CoV-2 vaccination, with an unusual presentation on a longstanding history of hypothyroidism. Clinicians should remain vigilant about potential thyroid dysfunction after SARS-CoV-2 vaccination in the current pandemic.

Graves’ disease in a patient with Down syndrome: a shift from hyperthyroidism to hypothyroidism

Down syndrome (DS) is associated with an increased risk of multisystemic dysfunction, namely endocrine abnormalities. Thyroid dysfunction is the most common endocrinological disorder, and it can manifest as either hypothyroidism or hyperthyroidism. A 16-year-old patient with DS developed hyperthyroidism after a lifetime of alternating between subclinical hypothyroidism and euthyroidism. He presented new onset weight loss, agitation and diarrhoea. Laboratory studies were compatible with hyperthyroidism. Thyroid receptor antibodies (TRAbs) were positive, antithyroid peroxidase antibodies and thyroglobulin antibodies were negative. Antithyroid medication (methimazole) was prescribed and, despite therapy adjustments, laboratory evaluation revealed new onset hypothyroidism with persistently positive TRAbs. He experienced weight gain and remained in a hypothyroid state even with withdrawal of methimazole and administration of levothyroxine. This case illustrates an example of Graves’ disease with coexisting stimulating and inhibiting TRAbs that led to a shift from hyperthyroidism to hypothyroidism, a rare condition in patients with DS.

Imaging Algorithm-Based Real-Time Shear Wave Elastography Combined with Thyroglobulin Antibodies in Diagnosis of Thyroid Cancer

To analyze the effect of real-time shear wave elastography (SWE) optimized by mathematical algorithms combined with thyroglobulin antibodies (TGAb) on the clinical diagnosis of differentiated thyroid carcinoma (DTC), a hybrid displacement estimation algorithm based on weighted phase separation and two-dimensional cross correlation was proposed. 102 patients with DTC were divided into a test group (TGAb-positive) and a control group (TGAb-negative). Real-time SWE based on hybrid displacement estimation algorithm was performed. Receiver operating characteristic (ROC) curve was adopted to analyze the characteristics of real-time SWE and its combination with TGAb to detect the sensitivity, specificity, and area under the curve (AUC) of the malignant degree of thyroid cancer. The results showed that the preoperative thyroid-stimulating hormone (TSH), thyroglobulin autoantibodies (TGAb), and thyroid peroxidase antibody (TPOAb) of TGAb-positive patients were higher than those of the TGAb-negative group ( P < 0.05 ). The preoperative tumors of TGAb-positive patients were multifocal, and the tumor size was larger than that of the TGAb-negative patients ( P < 0.05 ). The maximum Young’s modulus Emax of TGAb-positive patients was greater than that of TGAb-negative group ( P < 0.05 ). In addition, there was a very significant positive correlation between the patient’s TGAb level and Emax of Young’s modulus ( P < 0.001 ). The sensitivity, specificity, and AUC of the joint detection of real-time SWE Emax and TGAb for the malignant degree of thyroid cancer were significantly greater than those of the single real-time SWE and TGAb, and the difference was substantial ( P < 0.05 ). In short, joint detection of real-time SWE based on hybrid displacement estimation algorithm combined with TGAb had high sensitivity, specificity, and AUC for the diagnosis of DTC, which was suitable for clinical application.

Cardiac autonomic modulation and anti-TPO antibodies in Subclinical Hypothyroidism – Does any correlation exit?

Background Heart rate variability (HRV) reflects the balance of activities of sympathetic and parasympathetic components of the autonomic nervous system. Anti-thyroid antibodies have long been associated with thyroid dysfunction and influence thyroid profile testing, the most common being anti-Thyroid Peroxidase (TPO) and anti-Thyroglobulin antibodies. Subclinical hypothyroidism (SCHypo) is characterized by elevated TSH with normal thyroid hormones.We hypothesized that autonomic function may be deranged in anti-TPO positive sub-clinical hypothyroid cases even before the onset of overt hypothyroidism. Objectives To investigate the association between anti-TPO antibodies (anti-TPOAb) positive SCHypo and sympathovagal imbalance (SVI). Methodology: The study was conducted on age and BMI matched subclinical hypothyroid patients (n = 52) and healthy controls (n = 20). Cardiac autonomic activity was assessed by short term HRV in the time (SDNN, RMSSD, pNN50) and frequency domain (LFms2, HFms2, LFnu, HFnu, TP and LF/HF ratio). Nonlinear geometric measures (SD1, SD2, SD1/SD2, TINN, HRV triangular index) were also evaluated. Biochemical evaluation of serum thyroid profile, anti-TPOAb was done in all the subjects. Results Decreased HRV was observed in anti-TPOAb positive group when compared to negative and control groups. Significant positive correlation of anti-TPOAb with TSH, LF nu, LF/HF and negative correlation with SDNN, RMSSD, pNN50, SD1, SD1/SD2, HFnu and TP of HRV was observed. Conclusion Anti-TPOAb positive SCHypo group exhibited modifications in HRV characterized by decreased parasympathetic modulation, as compared to controls. The findings were also suggestive of increased risk of autonomic dysfunction in TPOAb- positive patients than negative. Anti-TPO antibody was significantly correlated with TSH and SVI in SCHypo patients.

What Are the Common Characteristics of Pediatric Patients With Antibody Negative Primary Hypothyroidism?

Background: The most common cause of acquired primary hypothyroidism is autoimmune thyroiditis which is typically associated with positive anti-thyroid peroxidase and/or anti-thyroglobulin antibodies. However, some children present with primary hypothyroidism and negative antibodies. Whether there are differences between patients with acquired primary hypothyroidism who have positive vs negative anti-thyroid antibodies has not been systematically examined. Aim:To define the characteristics of patients with primary hypothyroidism and negative antibodies. Methods: A retrospective chart review of patients with hypothyroidism seen in the pediatric endocrine clinic at Riley Hospital for Children in Indianapolis, Indiana from August 2016 until December 2019 was performed. Variables examined included age at diagnosis, signs and symptoms at presentation, height, weight, BMI, TSH, FT4, T4, thyroid peroxidase and anti-thyroglobulin antibodies, family history of thyroid disease, physical exam at diagnosis, and associated diseases. Results: Of 173 patients aged 10.6 ± 3.9 years, 128 (74%) had positive antibodies and 44 (26%) had negative antibodies. Of those with positive antibodies, 80 % were female and 20% were male. Of those with negative antibodies, 53% were female and 47% were male. No differences were seen in the incidence of obesity or Down syndrome in patients with positive antibodies compared with those who had negative antibodies. A positive family history of thyroid disease was present in 45% of those with positive antibodies and in 22% of those with negative antibodies, P=0.006 Fifty-eight patients (45%) with positive antibodies reported excessive fatigue and 40 (31%) had a goiter. In contrast, 10 (22.7%) who had negative antibodies reported mild intermittent fatigue, P=0.006 and 7 (15.9 %) had a goiter, P=0.04 The average TSH in the antibody positive group was 129± 230 mcu/ml compared with 48 ± 131 mcu/ml in those with negative antibodies, p=0.04. A trend was also noted for a lower FT4 in those with positive antibodies (0.68±0.37 vs 0.85±0.27, p=0.050) No other differences in baseline characteristics were seen between patients with negative vs positive antibodies. Conclusion: Patients with positive anti-thyroid antibodies had more severe hypothyroidism and were more likely to report extreme fatigue than those with negative antibodies. It is unknown why some children with acquired primary hypothyroidism presumed due to autoimmune thyroid disease have negative antibodies. Long-term follow-up will be needed to determine whether the natural history of thyroid disease in children with primary hypothyroidism is associated with antibody status.

Hashimotothyreoïditis bij kinderen en adolescenten: klinische, hormonale en echografische kenmerken bij de diagnosestelling

Hashimoto’s thyroiditis in children and adolescents: clinical, hormonal and ultrasound features at diagnosis The clinical, biochemical and sonographic features of 51 children and adolescents (45 girls) being diagnosed with hashimotothyroiditis (HT) were studied. HT was diagnosed based on the presence of thyroid peroxidase and/or thyroglobulin antibodies, together with thyroid ultrasound compatible with thyroiditis or manifest hypothyroidism characterized by decreased free T4 and increased TSH levels. The median age of the patients was 12.8 years (range: 5.9 and 16.5 years). At the time of diagnosis, 18 patients (35.3%) were euthyroid, 16 (31.3%) subclinically hypothyroid, 13 (25.5%) hypothyroid, and 4 (7.8%) hyperthyroid. The reasons for referral were an enlargement of the thyroid gland (39.2%), symptoms suggestive of hypothyroidism (35.3%) or an accidental finding on work-up for an unrelated problem (25.4%). The most common clinical manifestations were a goiter (60.8%), fatigue (60.8%), weight gain (25.0%), constipation (11.8%), hair loss (11.8%) and growth retardation (5,9%). A goiter was most common in the euthyroid children. Growth retardation was only observed in three hypothyroid children. On ultrasound an enlarged thyroid gland was diagnosed in 80.0% of the patients. Associated coeliac disease was diagnosed in four patients; one patient developed type 1 diabetes mellitus during the follow-up period and one patient developed Hashimoto’s encephalopathy.

Relationship Between Thyroid Hormonal Status in Patients with a Hypothyroid Form of Hashimoto’s Thyroiditis and Iodine Concentrations in Drinking Water

The current study aimed to identify correlative and regressive dependencies between the water iodine concentration and the levels of TSH (thyroid-stimulating hormone), thyroglobulin antibodies (TgAbs), and thyroid peroxidase (TPOAb) in the serum of 168 in patients (34 men and 134 women) with a hypothyroid form of Hashimoto’s thyroiditis who use water from the supply network and individual wells. Based on the water iodine concentration, low and moderate degrees of iodine endemia in the location of the patients were determined. In the groups of men and women using water from different water supply sources, there were direct correlations between the water iodine concentrations and the TgAbs and TPOAb titers as well as an inverse dependence between iodine and TSH levels. Multivariate regressive analysis indicated that TgAb and TSH in the group of women using water from a supply network and TPOAb titers in the group of women using well water were independent factors associated with water iodine concentrations. Statistically significant correlations and regressive dependencies between the water iodine concentrations and the biomarkers of the thyroid status of the patients indicate the risk of Hashimoto’s thyroiditis progression, especially among women with additional iodine intake.