Fascinating new discoveries regarding cytokines and thyroid hormone. More treatment possibilities.
"We report here that TREM2 is a thyroid hormone regulated gene and its expression in macrophages and microglia is stimulated by thyroid hormone. Both endogenous thyroid hormone and sobetirome, a synthetic thyroid hormone agonist drug, suppress pro-inflammatory cytokine production from myeloid cells including macrophages that have been treated with the SARS-CoV-2 spike protein which produces a strong, pro-inflammatory phenotype...Our findings represent the first report of endocrine regulation of TREM2 and provide a unique opportunity to drug the TREM2 signaling pathway with orally active small molecule therapeutic agents."
- Ferrara SJ, Chaudhary P, DeBell MJ, Marracci G, Miller H, Calkins E, Pocius E, Napier BA, Emery B, Bourdette D, Scanlan TS - "TREM2 is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor" bioRxiv [Preprint]. 2021 Jan 27:2021.01.25.428149. doi: 10.1101/2021.01.25.428149. PMID: 33532772; PMCID: PMC7852265.
February 9, 2021
A new paper was published yesterday, summarizing "available studies regarding thyroid function alterations in patients with COVID-19 and to overview the possible physio-pathological explanations." (Croce et al, 2021)
- Croce L, Gangemi D, Ancona G, Liboà F, Bendotti G, Minelli L, Chiovato L - "The cytokine storm and thyroid hormone changes in COVID-19" J Endocrinol Invest (2021) doi: 10.1007/s40618-021-01506-7. Epub ahead of print. PMID: 33559848.
https://link.springer.com/article/10.10 ... 21-01506-7
"Patients with TD [thyroid dysfunction] had a significantly higher fatality rate than did those without TD during hospitalization (20% vs 0%, P = 0.002). Patients with TD were more likely to stay in the hospital for more than 28 days than were those without TD (80% vs 56.52%, P = 0.048)."
- Zhang Y, Lin F, Tu W, Zhang J, Choudhry AA, Ahmed O, Cheng J, Cui Y, Liu B, Dai M, Chen L, Han D, Fan Y, Zeng Y, Li W, Li S, Chen X, Shen M, Pan P; medical team from Xiangya Hospital to support Hubei, China - "Thyroid dysfunction may be associated with poor outcomes in patients with COVID-19" Mol Cell Endocrinol 521:111097 (2021) doi: 10.1016/j.mce.2020.111097. Epub 2020 Dec 2. PMID: 33278491; PMCID: PMC7709789
A letter to the Editor published today in an Austrian journal highlighted the association of hypothyroidism with COVID-19.
"Although our sample size is small and the cause for hypothyroidism has not been assessed, we would still like to point out the increased association of COVID infection and hypothyroidism in our patients."
- Bakshi SS, Kalidoss VK - "Is there an association between hypothyroidism and COVID 19? : A preliminary report" Wien Klin Wochenschr. 2021 Feb 3:1–2. doi: 10.1007/s00508-021-01813-2. Epub ahead of print. PMID: 33537842; PMCID: PMC7857644.
Another review was pre-published today.
"Subacute thyroiditis, autoimmune thyroiditis and an atypical form of thyroiditis are complications of COVID-19. Thyroid hormone dysfunction affects the outcome by increasing mortality in critical illnesses like acute respiratory distress syndrome, which is a leading complication in COVID-19."
- Speer G, Somogyi P - "Thyroid complications of SARS and coronavirus disease 2019 (COVID-19)" Endocr J. 2021 Jan 19. doi: 10.1507/endocrj.EJ20-0443. Epub ahead of print. PMID: 33473054
https://www.jstage.jst.go.jp/article/en ... 3/_article
Today, Chinese researchers have published another review on the interaction of COVID-19 and thyroid (Chen et al., 2021).
"COVID-19 and thyroid disease may mutually aggravate the disease burden. Patients with SARS-CoV-2 infection should not ignore the effect in thyroid function, especially when there are obvious related symptoms."
- Chen W, Tian Y, Li Z, Zhu J, Wei T, Lei J - "Potential interaction between SARS-CoV-2 and thyroid: a review" Endocrinology bqab004 (Jan 11 2021)
https://academic.oup.com/endo/advance-a ... 04/6082366
Kumari et al. just published a review from India where fluoride poisoning is endemic and "hypothyroidism and hyperthyroidism are more common...being 11%, compared to only 2% in the UK and 4.6% in the US" (Kumari al., 2020).
The authors state that "the malfunction of thyroid hormone synthesis may aggravate SARS-CoV-2 infection and thus monitoring the thyroid hormone may help in understanding the pathogenesis of COVID-19."
- Kumari K, Chainy GBN, Subudhi U - "Prospective role of thyroid disorders in monitoring COVID-19 pandemic" Heliyon 6(12):e05712 (2020)
"Our literature search provided greater evidence that the thyroid gland and the entire hypothalamic–pituitary–thyroid (HPT) axis could be relevant targets of damage by SARS-CoV-2. Specifically, COVID-19-related thyroid disorders include thyrotoxicosis, hypothyroidism, as well as nonthyroidal illness syndrome."
- Scappaticcio L, Pitoia F, Esposito K, Piccardo A, Trimboli P - "Impact of COVID-19 on the thyroid gland: an update" Rev Endocr Metab Disord. 2020 Nov 25:1–13 doi: 10.1007/s11154-020-09615-z. Epub ahead of print. PMID: 33241508; PMCID: PMC7688298.
A new study from China shows that FT3 levels were significantly lower in patients with severe COVID-19 than in non-severely ill patients. Reduced FT3 independently predicted all-cause mortality of patients with severe COVID-19 (Gao et al., 2020).
- Gao W, Guo W, Guo Y, Shi M, Dong G, Wang G, Ge Q, Zhu J, Zhou X - "Thyroid hormone concentrations in severely or critically ill patients with COVID-19" J Endocrinol Invest. 2020 Nov 2:1–10 (2020)
Another study from China was published today, investigating TSH, FT4, FT3 and anti-thyroid antibodies in 191 patients (Lui et al., 2020).
"Ten patients had isolated low TSH, suggestive of subclinical thyrotoxicosis due to thyroiditis, although the contribution of autoimmunity was likely in two of them. Autoimmune thyroiditis probably also contributed to subclinical hypothyroidism in another patient. Ten patients had isolated low fT3, likely representing non-thyroidal illness syndrome. Lower SARS-Cov-2 PCR cycle threshold values and elevated C-reactive protein were independently associated with occurrence of low TSH (p=0.030) and low fT3 (p=0.007) respectively. A decreasing trend of fT3 with increasing COVID-19 severity (p=0.032) was found. Patients with low fT3 had more adverse COVID-19-related outcomes."
- Lui DTW, Lee CH, Chow WS, Lee ACH, Tam AR, Fong CHY, Law CY, Leung EKH, To KKW, Tan KCB, Woo YC, Lam CW, Hung IFN, Lam KSL- "Thyroid Dysfunction in Relation to Immune Profile, Disease Status and Outcome in 191 Patients with COVID-19" J Clin Endocrinol Metab Nov 3:dgaa813 (2020)
https://academic.oup.com/jcem/advance-a ... 13/5952837
"Experimental hormone therapy may speed recovery for COVID patients."
Duluth patients (USA) were among the first to get T3 as an experimental treatment to mitigate lung failure.
- Read more:
"Symptoms of thyrotoxicosis such as sore throat, fatigue, chills, anorexia, and weight loss can be easily confused for COVID-19 symptoms.2 Therefore, a high clinical suspicion is required to rule out both diseases simultaneously."
- Chong WH, Shkolnik B, Saha B, Beegle S - "Subacute Thyroiditis in the Setting of Coronavirus Disease 2019" Am J Med Sci S0002-9629(20)30416-X (Sept. 2020)
An overview from France was published this month, highlighting the abnormal thyroid function tests observed so far in COVID-19.
- Caron P - "Thyroid disorders and SARS-CoV-2 infection: From pathophysiological mechanism to patient management" Ann Endocrinol (Paris) 81(5):507-510 (Oct. 2020) 10.1016/j.ando.2020.09.001. Epub 2020 Sep 18. PMID: 32950466; PMCID: PMC7498405
October 14, 2020
It appears that thyroid dysfunction is being reported more and more, particularly thyrotoxicosis/thyroiditis. Hopefully this will initiate more research.
"This study provides first evidence that COVID-19 may be associated with high risk of thyrotoxicosis in relationship with systemic immune activation induced by the SARS-CoV-2 infection."
- Lania A, Sandri MT, Cellini M, Mirani M, Lavezzi E, Mazziotti G - "Thyrotoxicosis in patients with COVID-19: the THYRCOV study" Eur J Endocrinol 183(4):381-387 (Oct. 2020) doi: 10.1530/EJE-20-0335. PMID: 32698147
https://eje.bioscientifica.com/view/jou ... 0-0335.xml
We were alerted to a study from China today, from July of this year.
"The levels of TSH and serum total triiodothyronine (TT3) of the patients with COVID-19 were significantly lower than those of the healthy control group and non-COVID-19 pneumonia patients. The more severe the COVID-19, the lower the TSH and TT3 levels were, with statistical significance (p < 0.001)."
- Chen M, Zhou W, Xu W - "Thyroid Function Analysis in 50 Patients with COVID-19: A Retrospective Study" Thyroid (2020) doi: 10.1089/thy.2020.0363. Epub ahead of print. PMID: 32600165.
https://www.liebertpub.com/doi/10.1089/ ... %200pubmed
More studies are coming in, reporting on thyroid dysfunction in COVID-19. Subacute thyroiditis (deQuervain's) is increasingly observed (Brancatella et al., 2020; Ippolito et al., 2020; Mattar et al., 2020; Asfuroglu Kalkan & Ates, 2020).
- Brancatella A, Ricci D, Cappellani D, Viola N, Sgrò D, Santini F, Latrofa F - "Is Subacute Thyroiditis an Underestimated Manifestation of SARS-CoV-2 Infection? Insights From a Case Series" J Clin Endocrinol Metab 105(10):dgaa537 (2020)
Brancatella A, Ricci D, Viola N, Sgrò D, Santini F, Latrofa F - "Subacute Thyroiditis After Sars-COV-2 Infection" J Clin Endocrinol Metab 105(7):dgaa276 (2020) doi: 10.1210/clinem/dgaa276. PMID: 32436948; PMCID: PMC7314004
Ippolito S, Dentali F, Tanda ML - "SARS-CoV-2: a potential trigger for subacute thyroiditis? Insights from a case report" J Endocrinol Invest 43(8):1171-1172 (2020) doi: 10.1007/s40618-020-01312-7. Epub 2020 Jun 2. PMID: 32488726; PMCID: PMC7266411
Mattar SAM, Koh SJQ, Rama Chandran S, Cherng BPZ - "Subacute thyroiditis associated with COVID-19" BMJ Case Rep 13(8):e237336 (2020) doi: 10.1136/bcr-2020-237336. PMID: 32843467; PMCID: PMC7449350.
Asfuroglu Kalkan E, Ates I - "A case of subacute thyroiditis associated with Covid-19 infection" J Endocrinol Invest 43(8):1173-1174 (2020) doi: 10.1007/s40618-020-01316-3. Epub 2020 Jun 5. PMID: 32504458; PMCID: PMC7273820
A study from Greece was brought to our attention, reporting on subacute thyroiditis in a person with COVID-19 (Ruggeri et al., 2020).
- Ruggeri RM, Campennì A, Siracusa M, Frazzetto G, Gullo D - "Subacute thyroiditis in a patient infected with SARS-COV-2: an endocrine complication linked to the COVID-19 pandemic" Hormones (Athens) 16:1–3 (2020) doi: 10.1007/s42000-020-00230-w. Epub ahead of print. PMID: 32676935; PMCID: PMC7365600.
https://www.ncbi.nlm.nih.gov/pmc/articl ... /32676935/
Interesting editorial review published today, on COVID-19 and thyroid observations.
- Gorini F, Bianchi F, Iervasi G - "COVID-19 and Thyroid: Progress and Prospects" Int J Environ Res Public Health 17(18):E6630 (2020) doi: 10.3390/ijerph17186630. PMID: 32932954.
https://www.mdpi.com/1660-4601/17/18/66 ... h-17-06630
Today (Epub July 30, 2020) the first description of thyroid alterations in hospitalised patients with COVID-19 was published (Muller et al., 2020).
- Muller I, Cannavaro D, Dazzi D, Covelli D, Mantovani G, Muscatello A, Ferrante E, Orsi E, Resi V, Longari V, Cuzzocrea M, Bandera A, Lazzaroni E, Dolci A, Ceriotti F, Re TE, Gori A, Arosio M, Salvi M - "SARS-CoV-2-related atypical thyroiditis" Lancet Diabetes Endocrinol 8(9):739-741 (2020)
Today we read the first two articles on COVID-19 and possible thyroid involvement. Bellastella et al. offer a very concise summary of the knowledge so far, while Pal & Banerjee's work describe the knowledge - and lack thereof - regarding the endocrine system overall.
We are still waiting for the first study reporting on COVID-19 effects/interactions with TSH and thryoid hormones (serum and tissue levels), and status of the thyroid.
- Bellastella G, Maiorino MI, Esposito K - "Endocrine complications of COVID-19: what happens to the thyroid and adrenal glands?" J Endocrinol Invest 1–2 (2020).doi: 10.1007/s40618-020-01311-8. Epub ahead of print. PMID: 32488724; PMCID: PMC7265876
Pal R, Banerjee M - "COVID-19 and the endocrine system: exploring the unexplored" J Endocrinol Invest May 2:1–5 ( (2020) doi: 10.1007/s40618-020-01276-8. Epub ahead of print. PMID: 32361826; PMCID: PMC7195612