Dr. Valerie Gettings, NMD

 

Subheadline

A case report exploring how low-dose tirzepatide improved insulin resistance, thyroid function, and thyroid autoantibody levels in a patient with Hashimoto’s thyroiditis, highlighting the emerging role of metabolic therapies in autoimmune thyroid disease.

Short Description

This case report describes a 40-year-old woman with Hashimoto’s thyroiditis, hypothyroidism, and worsening insulin resistance who experienced improvements in thyroid function, fasting insulin, and thyroid antibody levels following low-dose tirzepatide therapy. The case highlights the growing recognition of the metabolic-immune axis in autoimmune thyroid disease and suggests a potential role for GLP-1/GIP receptor agonists as adjunctive therapeutic tools.

Keywords
Hashimoto’s thyroiditis, tirzepatide, insulin resistance, thyroid autoimmunity, GLP-1 receptor agonist, hypothyroidism

Introduction

Hashimoto’s thyroiditis (HT) is an autoimmune disease that is characterized by the presence of persistent antibodies (thyroid peroxidase antibodies, known as anti-TPO, and thyroglobulin antibodies, known as anti-TG), that build up, attack the thyroid, and over time decrease the way the thyroid functions and how it produces hormones.1 The standard of care for Hashimoto’s thyroiditis is treatment with synthetic T4 medication – levothyroxine (brand name Synthroid) – with the goal of normalizing thyroid stimulating hormone (TSH) levels; however, it does not block the autoimmune process.2 In fact, research shows that levothyroxine only normalized thyroid antibodies in 16% of participants.3 What is often limited in standard treatment of HT is attention to the viral, immunological, and metabolic factors that drive autoimmunity.

Metabolic syndrome is a key factor in HT that is not fully addressed by monotherapy with levothyroxine. Research shows that while levothyroxine can be helpful to decrease lipid markers, it did not improve insulin resistance based on HOMA-IR and QUICKI.4 Furthermore, research shows that increased TSH and anti-TPO are key predictive markers of insulin resistance and further drive autoimmunity.5 In HT, the proinflammatory state of hyperinsulinemia, high TSH, and increased thyroid antibodies drive specific cytokine pathways including, NF-kb, TLR4, etc. and IL-6, the master switch of Th17 pathways, that play a key role in the pathogenesis of HT and worsen thyroid destruction.6,7 This ongoing inflammatory cycle is not interrupted by conventional treatment.

Tirzepatide has a dual role of being a Glucagon Like Peptide-1 (GLP-1) and a Glucose-dependent Insulinotropic Polypeptide (GIP) receptor agonist and is effective for patients with type 2 diabetes and lowering body weight, fat mass, hemoglobin A1C (HbA1c), and insulin resistance in obese or overweight adults without type 2 diabetes.8 Furthermore, tirzepatide works on the same cytokine pathways involved in the pathogenesis of HT, such as IL-6 and Th17, among others, and suggests favorable results in decreasing the pathogenesis of HT, while decreasing insulin resistance and improving metabolic health.6

This case report is notable since it demonstrates the effective use of tirzepatide at low dose in an HT patient who had post-surgical worsening of insulin resistance and thyroid medication resistance that improved thyroid function and insulin resistance while decreasing thyroid antibodies. This case adds to cutting edge research exploring metabolic interventions in the treatment of autoimmune thyroid conditions.

Case Presentation

Patient Information

A 40-year-old female with established diagnoses of HT and hypothyroidism on levothyroxine and liothyronine without symptom improvement. She had increasing insulin resistance, hyperlipidemia, and persistent inflammatory markers.

Presenting Concern

The patient’s symptoms included body pain (specifically both shoulders), fatigue, anxiety, low libido, bloating, gas, depression, menstrual migraines, and weight gain. She also experienced severe iron deficiency anemia with pica. She also had post-elective liposuction of the abdomen and bilateral arms performed by a plastic surgeon. She had persistent constipation since childhood. She experienced insulin resistance and gestational diabetes during pregnancy. Despite strength training and a consistent nutrition schedule, she had difficulty with weight loss.

Clinical History and Context

The patient had HT and hypothyroidism diagnoses since 2020 and was prescribed Levothyroxine 50mcg and Liothyronine 2.5mg daily, monitored by primary care and endocrinologist. Post-elective liposuction and tummy tuck, she had increasing metabolic markers (including fasting insulin and pre-diabetic HbA1c) and thyroid antibodies over the next two years warranting intervention. She also had secondary adrenal insufficiency starting Oct. 2025. She has been gluten and dairy free since 2020. Case and labs monitored across 19 appointments since Feb. 2024.

Clinical Findings

Physical exam findings over time included brittle nails, scars from surgery on abdomen and arms, post-surgical swelling, central adiposity prior to surgery, and dry hair. Key negatives that influenced clinical reasoning: no organomegaly, no masses on palpation, no hoarseness, no personal or family history of thyroid cancer, and no anxiety according to GAD-7 prior to initiation of hydrocortisone or tirzepatide.

Diagnostic Assessment

Prior to starting tirzepatide Feb. 2026, laboratory evaluation included:

• Jan 2026: Fasting insulin 12 μIU/mL (Reference Range. 2.6−24.9 μIU/mL), Anti-TPO at 239 IU/mL (Reference Range Less than 34 IU/mL) and Anti-TG 16.7 IU/mL (Reference range less than ≤ 3.9 IU/mL)
• June 2026: Fasting insulin at 9 μIU/mL, Anti-TPO 194 IU/mL and Anti-TG 6.4 IU/mL.

Fasted Insulin optimal range is less than 5 μIU/mL. HbA1c within normal limits (5.1 %) since Oct. 2025.

Clinical Assessment

Working diagnosis: HT and hypothyroidism with increasing thyroid antibodies, insulin resistance, and secondary adrenal insufficiency, contributing to worsening metabolic dysfunction.

Differential diagnoses considered:

Polymyalgia rheumatica: Patient is less than 50. CRP levels have normalized with treatment. Pain has resolved with antibody support, trigger point injections, and chiropractic care.

Euthyroid sick syndrome: CRP has normalized, TSH elevated, and diagnosis would not account for low cortisol.

Therapeutic Intervention

Black seed oil, fish oil, and antibody support products to bring down thyroid antibodies with some success but not normalization. Strength training and pilates used to support insulin resistance and weight management. Interventions mentioned have strong evidence for their intent.

Hydrocortisone introduced in Dec. 2025 10mg in the morning, 5mg at noon; after one month 5mg in the AM and 2.5mg at noon. Stopped March 2026 when cortisol normalized. Rationale: secondary adrenal insufficiency was worsening metabolic dysfunction and needed to be addressed for patient’s quality of life and endocrine health.

Tirzepatide compounded with cyanocobalamin started Feb. 2026: Started at 1 mg per injection weekly. Increased to 1.9 mg April 2026 weekly and is current dose. Rationale: to decrease insulin resistance, inflammatory markers, and assess potential for decreasing thyroid antibodies.

Levothyroxine continued at current dose. Liothyronine stopped by patient in April 2026 due to difficulty falling asleep at night.

Follow-up and Outcomes

Following three months on the hydrocortisone for secondary adrenal insufficiency and four months of compounded tirzepatide, repeated lab testing showed a 25% decrease in fasting insulin, 18.83% decrease in anti-TPO antibody, and 61.68% decrease in anti-TG antibody.

The patient has had a 3lb weight loss, increased reported energy, and increase in quality of life with reversal of low cortisol symptoms.

Despite discontinuation of liothyronine by the patient, and the addition of tirzepatide, TSH reduced by 33% and thyroid free T3 and free T4 levels increased 7.69% and 9% increase respectively.

Safety and Tolerability

Patient has intermittent constipation, tolerating low dose of tirzepatide well. Patient monitored monthly. Discontinuation of liothyronine by patient since it was creating difficulty in falling asleep at night. Discontinuation and taper of hydrocortisone at three months without adverse event. No serious adverse events were reported.

Timeline

2020: Diagnosed with Hashimoto’s and hypothyroidism. Levothyroxine and liothyronine initiated.
Feb. 2024: Initial presentation. HbA1c 6.3%. Insulin 3.6 μIU/mL. Liposuction surgery and tummy tuck.
Apr. 2024: Severe anemia treated with iron infusions.
Oct. 2025: Insulin at 10 μIU/mL, thyroid WNL, cortisol 7.5, thyroid antibodies anti-TPO 71 and anti-TG 7.8, HbA1c 5.1%
Jan. 2026: Insulin at 12 μIU/mL, thyroid antibodies: anti-TPO 239 IU/mL and anti-TG 16.7 IU/mL.
Dec. 2025: Hydrocortisone initiated for secondary adrenal insufficiency (stopped Mar. 2026).
Feb 2026: Tirzepatide initiated at 10 units (1 mg) weekly.
June 2026: Insulin at 9 μIU/mL, thyroid antibodies: anti-TPO 194 IU/mL and anti-TG 6.4 IU/mL.

Discussion

This case illustrates the critical role of addressing metabolic and autoimmune drivers of HT, especially since TSH and anti-TPO antibodies are key markers of insulin resistance, in addition to levothyroxine.5

In assessing the four-month outcome of the case of improved thyroid function, decreased thyroid antibodies, and improved insulin resistance, there are specific pathways that would have been addressed by tirzepatide alone. While tirzepatide is used to improve insulin resistance and obesity in those without diabetes, it also works on the same proinflammatory cytokine pathways of HT such as NF-κB, TLR4, IL-6 and Th17 cell activation. Th17 cells are also higher in those with HT.6 These overlapping cytokine pathways of tirzepatide and HT may explain the role tirzepatide played in decreasing HT autoimmunity in this case.

Further, new 2025 research shows that recent studies have indicated that Th17 cells and IL-17 are crucial inflammatory cells and inflammatory mediators involved in the occurrence and development of HT.9 Through the NOTCH pathway mechanism inhibition, research shows that tirzepatide decreases Th17 differentiation which may make it a promising autoimmune modulator.10 While there have not been any specific human studies on the use of tirzepatide to decrease thyroid antibodies, this is an area of emerging research.

Limitations of the case include single patient design and the use of two overlapping interventions. The use of tirzepatide does not establish direct causality in decreasing HT antibodies.

Conclusion

This case shows improved insulin resistance from compounded tirzepatide in an HT patient along with decreased antibodies and improved thyroid function. These outcomes demonstrate the importance of targeting the metabolic-immune axis for clinical and patient benefit beyond standard of care HT treatment. This case supports continued investigation for GLP-1 medications in the use of autoimmune thyroid diseases.

References:
1. Wang L, Zhu X, Xu S, et al. Hashimoto’s thyroiditis: from pathogenesis to clinical management. Front Endocrinol (Lausanne). 2026;17:1729316. doi:10.3389/fendo.2026.1729316
2. Chaker L, Papaleontiou M. Hypothyroidism: a review. JAMA. 2025;334(19):1750-1760. doi:10.1001/jama.2025.13559
3. Schmidt M, Voell M, Rahlff I, et al. Long-term follow-up of antithyroid peroxidase antibodies in patients with chronic autoimmune thyroiditis (Hashimoto’s thyroiditis) treated with levothyroxine. Thyroid. 2008;18(7):755-760. doi:10.1089/thy.2008.0008
4. Ostadrahimi A, Manzari T, Gohari-Lasaki S, et al. Effects of levothyroxine replacement therapy on insulin resistance in patients with untreated primary hypothyroidism. BMC Res Notes. 2023;16(1):237. doi:10.1186/s13104-023-06516-7
5. Zhou YC, Fang WH, Kao TW, et al. Exploring the association between thyroid-stimulating hormone and metabolic syndrome: a large population-based study. PLoS One. 2018;13(6):e0199209. doi:10.1371/journal.pone.0199209
6. Figueroa-Vega N, Alfonso-Pérez M, Benedicto I, Sánchez-Madrid F, González-Amaro R, Marazuela M. Increased circulating pro-inflammatory cytokines and Th17 lymphocytes in Hashimoto’s thyroiditis. J Clin Endocrinol Metab. 2010;95(2):953-962. doi:10.1210/jc.2009-1719
7. Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance. Eur J Immunol. 2010;40(7):1830-1835. doi:10.1002/eji.201040391
8. Corrao S, Pollicino C, Maggio D, Torres A, Argano C. Tirzepatide against obesity and insulin-resistance: pathophysiological aspects and clinical evidence. Front Endocrinol (Lausanne). 2024;15:1402583. doi:10.3389/fendo.2024.1402583
9. He H, Jiang Y, Qiu J, Shen F, Qian D, Meng L. Role of interleukin 17 and T helper cells 17 cells as a new immune target and signalling in the pathogenesis and treatment of autoimmune thyroid diseases. Ann Med. 2025;57(1):2586216. doi:10.1080/07853890.2025.2586216
10. Sun L, Yao SY, Zuo ZF, et al. Tirzepatide improves neutrophilic inflammation in obese asthmatic mice by downregulating Th17 cell differentiation. Mol Biol Rep. 2025;53(1):197. doi:10.1007/s11033-025-11366-6

Conflicts of Interest
None declared.

Funding and Support
None.

Author Bio:
Valerie Gettings, NMD, CISSN is a licensed naturopathic physician, Certified Sports Nutritionist, and founder of Dr. Valerie Gettings, NMD, PLLC in Scottsdale, Arizona. A graduate of the Canadian College of Naturopathic Medicine, she completed additional clinical training in sports medicine and holds a bachelor’s degree in public communications and international relations from American University. Prior to entering clinical practice, Dr. Gettings served as an award-winning public affairs specialist, journalist, and program analyst for the U.S. Navy Bureau of Medicine and Surgery.

Dr. Gettings specializes in thyroid disorders, autoimmune conditions, digestive health, metabolic dysfunction, and hormone-related concerns, with a particular focus on helping high-performing women overcome fatigue, brain fog, weight challenges, and hypothyroid symptoms. Her clinical approach integrates evidence-informed naturopathic medicine, advanced functional testing, nutrition, lifestyle medicine, and root-cause investigation to identify the underlying drivers of chronic illness.

Corresponding Author
Dr. Valerie Gettings, NMD, Dr. Valerie Gettings, NMD, PLLC, 9700 N. 91st St. Ste. A-115, Scottsdale, AZ, 85258, drgettings@drvaleriegettings.com, 480-327-6020