NEWS - Updates

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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NEWS - Updates

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February 26, 2021

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.
    https://pubmed.ncbi.nlm.nih.gov/33532772/

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
February 5, 2021
"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
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709789/
February 3, 2021

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.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857644/
January 19, 2021

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."
January 11, 2021

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."
December 25, 2020

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."
November 25, 2021
"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.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688298/
November 4, 2020

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).
November 3, 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
November 2, 2020

"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.
October 27, 2020

"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."

October 27, 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
    https://www.ncbi.nlm.nih.gov/pmc/articles/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."
October 1, 2020

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)."
September 20, 2020

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)
    https://pubmed.ncbi.nlm.nih.gov/32780854/

    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
    https://pubmed.ncbi.nlm.nih.gov/32436948/

    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
    https://pubmed.ncbi.nlm.nih.gov/32488726/

    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.
    https://pubmed.ncbi.nlm.nih.gov/32843467/

    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
    https://pubmed.ncbi.nlm.nih.gov/32504458/
September 18, 2020

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/
September 11, 2020

Interesting editorial review published today, on COVID-19 and thyroid observations.
September 1, 2020

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)
    https://pubmed.ncbi.nlm.nih.gov/32738929/
June 6, 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
    https://www.ncbi.nlm.nih.gov/pmc/articles/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
    https://pubmed.ncbi.nlm.nih.gov/32361826/
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T3 Treatment

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Experimental hormone therapy may speed recovery for COVID patients

Duluth patients were among the first to get an experimental treatment that uses a thyroid hormone to mitigate lung failure. It's now part of a Phase 2 FDA study.

Star Tribune - November 2, 2020

By Katie Galioto and Jeremy Olson

DULUTH — Every time the phone rang, it seemed to Kristine Smoley like more bad news about her husband, who contracted COVID-19 and was in a hospital intensive care unit on a ventilator because he couldn’t breathe on his own.

Smoley was prepared for the worst when a nurse from Duluth’s Essentia Health called with hope — albeit with risks and no solid evidence it would save her husband.

“They asked if I wanted to consider signing off on an experimental treatment for him,” Smoley said. “A treatment that had never been done before.”

Essentia’s Dr. Tim Rich and the University of Minnesota Medical School’s Dr. David Ingbar had studied for years whether a common thyroid hormone could be repurposed for the treatment of acute respiratory distress syndrome (ARDS), an often fatal type of lung failure. The doctors received federal approval late last year to test the therapy, so when COVID-19 caused a sudden surge in ARDS, they were ready for their first patient — Smoley’s husband, Bob Schlicht.

“It was scary,” Smoley said. “But I don’t know that I really had an option. Because the other option wasn’t good.”

The turnaround that followed was so remarkable that Rich and Ingbar have advanced their research — unique for a regional medical provider in a world of urban and academic COVID-19 studies — to a phase 2 U.S. Food and Drug Administration (FDA) study. The doctors have optimism about the impact their treatment could have amid the pandemic.

“There has been a lot of highly technical science to understand this biology, but the elegance now is in its simplicity,” said Rich, a pulmonologist. “This is not a designer drug. This is something we know the lung needs and uses.”

New therapies are needed against a pandemic that has caused 150,672 known infections, 10,334 hospitalizations and 2,475 deaths among Minnesotans. Only the antiviral remdesivir has received full FDA approval as a COVID-19 therapy for hospitalized patients, while treatments such as plasma infusions remain experimental and available only under emergency authorization.

Rich and Ingbar made a key discovery during the H1N1 pandemic of 2009, when families of those who died from influenza-related ARDS permitted autopsies. Rich found the victims’ lungs lacked T3, a thyroid hormone that would normally be detectable.

Ingbar said T3 reduces inflammation and coaxes epithelial cells in the lungs to absorb fluids — which is vital for patients with ARDS.

“A part of this acute lung injury with ARDS is the lungs get leaky, and they tend to fill with fluid,” Ingbar said. “That makes it really hard to get oxygen in or carbon dioxide out.”

Schlicht was coughing and congested when Smoley dropped him at an emergency room in Grand Rapids on March 26, a few days after the retired couple cut cross-country travels short due to the spread of the novel coronavirus that causes COVID-19.

Schlicht, 68, was Itasca County’s first known positive case of COVID-19. Smoley watched medical staff garbed in full protective gear take her husband to an isolated room. He was transferred to Duluth within two days.

A few weeks later, Mary Ellen Evangelista found herself in a similar situation. Her brother, Tim White, was a corrections officer at the Moose Lake prison, where inmates and workers tested positive for COVID-19 in early April.

Evangelista, who lives in Georgia, urged White to call an ambulance after he spent a week getting sicker at home. He was placed on a ventilator in Duluth late that night because the virus led to ARDS.

Doctors told Evengelista that her 51-year-old brother might not survive and asked to try the thyroid hormone.

“And every day, I just had a little more glimmer of hope,” she said.

White spent more than a month in the Duluth hospital but has been back home since spring and is working to gain enough strength to return to work. Chest X-rays for months have shown healthy lungs.

“This is really a much faster recovery than we see with typical ARDS,” said Ingbar, noting that many survivors have lung scarring that can cause breathing problems for years and the need for supplemental oxygen.

White plans to visit his family in Georgia for the holidays. Evangelista choked up discussing the trip.

“That he’s going to be with us at Christmas was not a foregone conclusion back in April,” she said.

Schlicht said he feels “100% healthy” and has been helping build an event center near home for his son’s upcoming wedding.

“Each visit really puts in perspective how close we were to death,” he said.

While the timing of recovery and abrupt reversal of symptoms suggest that T3 worked, doctors can’t rule out that the men recovered due to other medical care.

The trial was paused for months following the treatment of Schlicht and White for a safety review, but Rich and Ingbar recently received the go-ahead to give the therapy to more patients in Duluth and plan to expand to three Twin Cities-area hospitals.

The next step to prove cause and effect is to recruit 68 patients with ARDS from COVID-19 or other causes for the FDA-approved study, and to compare 50 who receive supplemental T3 with 18 who receive standard care.

ARDS stems from a variety of causes, including heat, physical trauma or inhaled substances. Research showed that any such lung injury produces more of an enzyme that breaks down T3.

“There’s a real local destruction of the hormone that explains why its concentration is so low,” Ingbar said.

Doctors administer the hormone directly to a patient’s lungs through a breathing tube. That is a novel part of this study, as sick people have received thyroid hormones for years, but never straight into their lungs in this manner.

The U’s Center for Translational Medicine is working to produce a patented powder T3 formulation. That inhaled or nebulized form would be cheaper and easier to administer, meaning more patients could receive it if it proves safe and effective.

“Our hope is actually that this therapy should work for some other illnesses in addition to ARDS,” Ingbar said. He and Rich may explore administering the treatment earlier to see if it prevents patients’ lungs from suffering distress.

Success of the ongoing study will be measured by whether supplemental T3 sops up enough lung fluid and allows for healthy blood oxygen levels. Rich said the overriding hope is not only survival but a return to life without chronic breathing problems and disabilities.

“Any survival of ARDS, especially this COVID ARDS, is exciting, but it’s not enough to survive,” Rich said. “It’s to not have the morbidity of a compromised lung for the rest of your life.”

The recoveries of Schlicht and White will be featured in an upcoming medical journal. The two men, the first people in the world to receive this experimental treatment, met after White’s October checkup at the hospital where they spent so many sick days. They exchanged an elbow bump.

“I’m a very lucky man,” White said, “to be sitting here today.”

SOURCE:
https://www.startribune.com/hormone-boo ... esh=true#5
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Other relevant studies

Post by admin »

Harris A, Al Mushref M - "Graves' Thyrotoxicosis Following SARS-CoV-2 Infection" AACE Clin Case Rep 7(1):14–6 (2020) doi: 10.1016/j.aace.2020.12.005. Epub ahead of print. PMID: 33521256; PMCID: PMC7834282
https://pubmed.ncbi.nlm.nih.gov/33521256/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834282/

Khoo B, Tan T, Clarke SA, Mills EG, Patel B, Modi M, Phylactou M, Eng PC, Thurston L, Alexander EC, Meeran K, Comninos AN, Abbara A, Dhillo WS - "Thyroid Function Before, During, and After COVID-19" J Clin Endocrinol Metab 106(2):e803-e811 (2021) doi: 10.1210/clinem/dgaa830. PMID: 33180932; PMCID: PMC7823247
https://pubmed.ncbi.nlm.nih.gov/33180932/

Piticchio T, Le Moli R, Tumino D, Frasca - "Relationship between betacoronaviruses and the endocrine system: a new key to understand the COVID-19 pandemic-A comprehensive review" J Endocrinol Invest. 2021 Feb 13:1–18 (2021) doi: 10.1007/s40618-020-01486-0. Epub ahead of print. PMID: 33583003; PMCID: PMC7882054.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882054/

Rotondi M, Coperchini F, Ricci G, Denegri M, Croce L, Ngnitejeu ST, Villani L, Magri F, Latrofa F, Chiovato L - "Detection of SARS-COV-2 receptor ACE-2 mRNA in thyroid cells: a clue for COVID-19-related subacute thyroiditis" J Endocrinol Invest. 2020 Oct 6:1–6. doi: 10.1007/s40618-020-01436-w. Epub ahead of print. PMID: 33025553; PMCID: PMC7538193.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538193/

van Gerwen M, Alsen M, Little C, Barlow J, Naymagon L, Tremblay D, Sinclair CF, Genden E - "Outcomes of Patients With Hypothyroidism and COVID-19: A Retrospective Cohort Study" Front Endocrinol (Lausanne). 2020 Aug 18;11:565. doi: 10.3389/fendo.2020.00565. PMID: 33013686; PMCID: PMC7461836
https://pubmed.ncbi.nlm.nih.gov/33013686/
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