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.

Depression and Autoimmune Thyroiditis - Their Relationship and the Effects of Treating Psychiatric and Thyroid Disorders on Changes in Clinical and Biochemical Parameters Including BDNF and Other Cytokines

Various autoimmune diseases, including autoimmune hypothyroidism (AHT), are associated with a higher risk of developing mood disorders throughout life. Depression is accompanied by the changes in the levels of inflammatory and trophic factors, including interleukines (IL-1beta, IL-2, IL-6), interferon alpha (IFN-alpha), tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP) and brain derived neurotrophic factor (BDNF). Similar disturbances in the cytokine profile are seen in AHT patients and their relatives. Disclosure of the relationship between the co-existence of depression and autoimmune subclinical thyroiditis indicates that the pathomecha-nism of depression may be related to the changes in the immune system, it is possible that both conditions may be caused by the same immune processes. The above hypothesis is indirectly sup-ported by the observations that the treatment with both antidepressants and levothyroxine leads to a decrease in the levels of proinflammatory cytokines with an increase in BDNF concentrations, simultaneously correlating with an improvement in the clinical parameters. However, so far there are no long-term studies determining the causal relationship between depression, thyroid auto-antibodies, and cytokine profile, which could bring us closer to understanding the interrelation-ships between them and facilitate the use of an adequate pharmacotherapy, not necessarily psy-chiatric. We consider the above issues insufficiently investigated but of great importance. This ar-ticle is an overview of the available literature as well as an introduction to our research project.

Depression and Autoimmune Thyroiditis - Their Relationship and the Effects of Treating Psychiatric and Thyroid Disorders on Changes in Clinical and Biochemical Parameters Including BDNF and Other Cytokines

Various autoimmune diseases, including autoimmune hypothyroidism (AHT), are associated with a higher risk of developing mood disorders throughout life. Depression is accompanied by the changes in the levels of inflammatory and trophic factors, including interleukines (IL-1beta, IL-2, IL-6), interferon alpha (IFN-alpha), tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP) and brain derived neurotrophic factor (BDNF). Similar disturbances in the cytokine profile are seen in AHT patients and their relatives. Disclosure of the relationship between the co-existence of depression and autoimmune subclinical thyroiditis indicates that the pathomecha-nism of depression may be related to the changes in the immune system, it is possible that both conditions may be caused by the same immune processes. The above hypothesis is indirectly sup-ported by the observations that the treatment with both antidepressants and levothyroxine leads to a decrease in the levels of proinflammatory cytokines with an increase in BDNF concentrations, simultaneously correlating with an improvement in the clinical parameters. However, so far there are no long-term studies determining the causal relationship between depression, thyroid auto-antibodies, and cytokine profile, which could bring us closer to understanding the interrelation-ships between them and facilitate the use of an adequate pharmacotherapy, not necessarily psy-chiatric. We consider the above issues insufficiently investigated but of great importance. This ar-ticle is an overview of the available literature as well as an introduction to our research project.

Inflammatory and infectious upper respiratory diseases associate with 59 genomic loci that link to type 2 inflammation genes

Inflammatory and infectious upper respiratory diseases (IURDs; ICD-10: J30-J39), such as diseases of sinonasal tract, pharynx and larynx, are growing health problems yet their genomic similarity is not known. We analyzed genome-wide association to eight IURDs (61,195 cases) among 260,405 FinnGen participants, meta-analyzing diseases in four groups based on an underlying genetic correlation structure. We aimed to understand which genetic loci contribute to susceptibility to IURDs in general and its subtypes. We detected 59 independent genome-wide significant (GWS) loci, distinguishing impact on sinonasal or pharyngeal diseases, or both. Fine-mapping implicated non-synonymous variants in 16 genes, including 10 linked to immune-related diseases. Phenome-wide analysis implicated asthma and atopic dermatitis at sinonasal disease loci and inflammatory bowel diseases, and other immune-mediated disorders at pharyngeal disease loci. IURDs also genetically correlated with autoimmune diseases such as rheumatoid arthritis, autoimmune hypothyroidism, and psoriasis. Finally, we associated separate gene pathways in sinonasal and pharyngeal diseases that both contribute to type 2 immunological reaction. We show shared heritability among IURDs that extends to several immune-mediated diseases with diverse mechanisms, such as type 2 high inflammation.

Hypokalemic paralysis and renal tubular acidosis: Initial presentation of Sjogren’s syndrome

Sjogren’s syndrome is a rare autoimmune disease affecting multiple systems with varying clinical features.We report a case of 37 year old woman who presented with recurrent episodes of quadriparesis which was attributable to hypokalemia and initially labelled as hypokalemic periodic paralysis. Later on she was found to have metabolic acidosis rather than alkalosis which pointed towards the diagnosis of renal tubular acidosis (RTA) in the absence of apparent gastrointestinal tract loss. Once the diagnosis of RTA was established, an attempt to search the aetiology revealed that she was having primary Sjogren’s syndrome (pSS) though she did not have any symptom at the time of diagnosis. She was found positive for anti-SSA. Lip biopsy revealed lymphocytic infiltration in periductal as well as parenchymal region. Schirmer test confirmed presence of severe dry eye. A concomitant existence of autoimmune hypothyroidism was a noteworthy association. She responded well with potassium supplementation and symptomatic treatment. Presentation of this case reminds the importance of vigilance while managing a case of recurrent hypokalemia which might be a rare presenting feature of pSS. Bangladesh J Medicine July 2021; 32(2) : 145-148

Severe Hypothyroidism Complicated by Myopathy and Neuropathy with Atypical Demyelinating Features

Autoimmune hypothyroidism may result in a wide range of neuromuscular disorders. The frequently observed neurological manifestations of acquired hypothyroidism include mild to moderate myopathy and sensorimotor neuropathy, which usually resolve by clinical and electrophysiological criteria, in adults treated with thyroid hormone replacement. We report a case of a 30-year-old male with severe hypothyroidism secondary to chronic autoimmune thyroiditis who presented with a 2-year history of progressive fatigue, upper and lower limb weakness, myalgia, and intermittent paraesthesia. His neurological exam demonstrated proximal and distal muscle weakness, lower limb areflexia, and relatively intact sensory modalities. The patient’s biochemistry revealed unusually and profoundly raised the thyroid stimulating hormone (TSH) level of 405.5 mIU/L (reference range (RR): 0.27–4.2 mIU/L) and creatine kinase (CK) level of 20,804 U/L (RR: 45–250 U/L), while his nerve conduction studies (NCS) demonstrated severe sensorimotor polyneuropathy with both axonal and demyelinating features. Thyroid hormone replacement therapy over the first 3 months resulted in biochemical normalization of his extremely deranged thyroid function tests (TFTs) and CK levels. At 12 months, despite maintaining euthyroidism and noticeable improvement in strength, his nerve conduction studies (NCS) demonstrated the continued absence of distal motor and sensory responses in his lower limbs with only partial improvement in sensory amplitudes and conduction velocities in his upper limbs. This report highlights the potential for severe neuromuscular consequences from advanced and chronic autoimmune hypothyroidism. The patient’s myopathy has resolved over a period of three months with prompt normalization of CK levels. Concerningly, the patient achieved significant but incomplete recovery from his mixed axonal and demyelinating neuropathy with residual mild distal weakness and areflexia in his lower limbs and persistent motor and sensory impairments on his NCS. The severity and incomplete resolution of our patient’s neurological manifestations emphasize the importance of early diagnosis and the need for prompt therapeutic intervention for hypothyroidism.

A Grave Turn on Hashimoto’s Thyroiditis - A Case Series on Four Patients With Autoimmune Hypothyroidism that Converted to Grave’s Disease

Disclaimer: The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force, or the Department of Defense or the U.S. Government. Introduction: The most common cause of hypothyroidism is Hashimoto’s thyroiditis, a destructive autoimmune injury to the thyroid gland. Rarely, autoimmune hypothyroidism can be caused by thyroid-stimulating hormone (TSH) receptor blocking antibodies (TSHRab), and can be difficult to differentiate clinically from Hashimoto’s. Grave’s disease is the most common etiology of hyperthyroidism, and is typically caused by activation from TSHRab acting as an agonist for the TSH receptor. Patients with autoimmune thyroiditis, whether from TSHRab or Hashimoto’s, have been infrequently reported to convert to Grave’s disease1–3. Presentation: We present four cases whom initially presented with typical symptoms of hypothyroidism, were diagnosed with autoimmune hypothyroidism and started on levothyroxine. All four cases were later found to be hyperthyroid and ultimately diagnosed and treated for Grave’s disease. Conclusion: Primary hypothyroidism can rarely transition to a hyperthyroid state, although these cases may be underreported. The mechanism isn’t well understood, but is hypothesized to be from a switch of a predominance of TSH receptor blocking antibodies (TBAb) to that of thyroid stimulating antibodies (TSAb)1. Assays using competitive binding for TSH receptor antibodies will not differentiate between blocking and stimulating antibodies4. A high index of suspicion is needed to diagnose these individuals. References: 1. McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: Potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid. 2013;23(1). doi:10.1089/thy.2012.03742. Takasu N, Matsushita M. Changes of TSH-stimulation blocking antibody (TSBAb) and thyroid stimulating antibody (TSAb) over 10 years in 34 TSBAb-positive patients with hypothyroidism and in 98 TSAb-positive graves’ patients with hyperthyroidism: Reevaluation of TSBAb and TSAb in TSH-receptor-antibody (TRAb)-positive patients. J Thyroid Res. 2012;2012. doi:10.1155/2012/1821763. Gonzalez-Aguilera B, Betea D, Lutteri L, et al. Conversion to graves disease from hashimoto thyroiditis: A study of 24 patients. Arch Endocrinol Metab. 2018;62(6). doi:10.20945/2359-39970000000864. Li Y, Kim J, Diana T, Klasen R, Olivo PD, Kahaly GJ. A novel bioassay for anti-thyrotrophin receptor autoantibodies detects both thyroid-blocking and stimulating activity. Clin Exp Immunol. 2013;173(3). doi:10.1111/cei.12129