Hyperthyroidism and Joint Pain

History and Epidemiology

Produced by the thyroid gland, the thyroid hormone keeps the body regulated. Hypothyroidism occurs when this hormone is in short supply, which causes body processes to slow down, resulting in a constellation of symptoms, including joint pain.

This joint pain may stem from how the thyroid hormone affects the proliferation and differentiation of bone and cartilage at the cellular level. As such, hypothyroidism may lead to musculoskeletal conditions, including:1

  • Epiphyseal dysgenesis
  • Septic necrosis
  • Arthritis, crystal-induced arthritis, and erosive osteoarthritis
  • Arthralgias
  • Muscle weakness
  • Myalgias (with or without elevations in creatinine phosphokinase)
  • Carpal tunnel syndrome
  • Highly viscous, noninflammatory joint effusions in the knees, wrists, and hands

Neuropathic and myopathic symptoms accompanying hypothyroidism can also manifest as joint abnormalities.

Hypothyroid arthropathy, a joint disease that includes arthritis, most commonly strikes the knees and hands in adults and the hip and the epiphysis of the femoral head in children.2

Etiology of Hypothyroidism and Joint Pain

Hypothyroidism may be caused by treatments for other conditions, such as medications or therapies, and as a response to physical conditions, such as a tumor or autoimmune condition, as listed in the table below.3

Table 1. Hypothyroidism Causes and Conditions

Drugs, Treatments, and TherapiesPhysical Conditions
Certain medications, including the newer class of cancer drugs (anti-CTLA-4 and anti-PD-L1/PD-1 therapy), dopamine, prednisone, or opioids
Radioactive iodine therapy
Thyroid surgery
Radiation therapy to the head, neck, or brain
Pituitary or hypothalamus disorders
Pituitary tumors
Tumors that compress the hypothalamus
Sheehan syndrome
Thyroid-releasing hormone resistance or deficiency
Lymphocytic hypophysitis

Risk Factors for Joint Pain from Hypothyroidism

The link between hypothyroidism and joint pain appears to be bi-directional. For example, people with rheumatoid arthritis (RA) are more likely to develop a thyroid condition such as hypothyroidism, and people with hypothyroidism are also at risk for joint pain and joint-related diseases. Moreover, autoimmune disorders tend to cluster in individuals, making it possible to have both Hashimoto’s disease and RA.3

Specifically, people with autoimmune hypothyroid disease are at risk for:2

  • Chronic, widespread pain
  • Fibromyalgia
  • Degenerative joint disease
  • Osteoarthritis 
  • Seronegative inflammatory arthritis

Prognosis

With treatment, most patients with hypothyroidism and joint pain have a good prognosis, and symptoms usually resolve in a few weeks or months. Without treatment, patients may face a high risk of morbidity and mortality. Untreated hypothyroidism may result in severe mental disability among children and heart failure among adults.

Screening for Hypothyroidism and Joint Pain

The American Thyroid Association recommends that screening for hypothyroidism begin at age 35 and continue every five years.

Individuals at high risk for hypothyroidism include:3

  • Women over the age of 60
  • Pregnant people
  • People with histories of head and neck irradiation
  • People with autoimmune disorders and/or type 1 diabetes
  • People with positive thyroid peroxidase antibodies
  • People with family histories of hypothyroidism

Hypothyroidism and Joint Pain Diagnosis & Presentation

Symptoms of hypothyroidism may vary from patient to patient, and they may be very subtle. Patients with hypothyroidism may present with the following signs and symptoms:4,5

  • Fatigue
  • Constipation
  • Weight gain
  • Carpal tunnel syndrome
  • Slow speech or movement
  • Intolerance to cold
  • Menorrhagia or irregular menstrual cycles
  • Muscle stiffness or cramps
  • Sleep apnea/snoring
  • Dry skin
  • Pallor and jaundice
  • Coarse, brittle hair or hair loss
  • Hoarseness
  • Mental health symptoms, such as depression, anxiety, psychosis, memory loss, or other cognitive deficits
  • Enlarged thyroid gland
  • Joint pain
  • Macroglossia
  • Heart-related symptoms, such as bradycardia, pericardial effusion, congestive heart failure, prolonged QT interval
  • Blood-related symptoms, such as hyponatremia, hypercholesterolemia
  • Prolonged ankle reflex relaxation
  • Galactorrhea

Severe hypothyroidism may present as myxedema coma, which is an endocrine emergency, and early diagnosis and intensive care treatment are essential. Consider myxedema in the presence of:4

  • Encephalopathy
  • Hypothermia
  • Seizures
  • Hyponatremia
  • Hypoglycemia
  • Arrhythmias
  • Cardiogenic shock
  • Respiratory failure
  • Fluid retention

Hashimoto’s disease can cause hypothyroidism and can be difficult to tease out from other causes of an underactive thyroid. Some potentially differentiating symptoms of Hashimoto’s disease include:4

  • Throat fullness
  • Fatigue
  • Painless thyroid enlargement
  • Episodic neck pains
  • Episodic sore throat

Diagnostic Workup/Physical Examination Findings

Diagnosis is based on symptoms and thyroid hormone levels in the blood. Since the signs and symptoms may be vague and vary among patients, physicians should:

  • Ask about the symptoms listed in the previous section
  • Obtain complete medical, surgical, medication, and family histories, including any adverse pregnancy and neonatal outcomes

During physical exam, patients with hypothyroid-related joint pain may present with:4

  • Tenderness
  • Synovial thickening — Diagnostic lab tests may include synovial fluid analysis. The synovial fluid may be non-inflammatory, with normal protein and cell counts but increased hyaluronic acid concentration, which produces the highly viscous synovium.
  • Joint effusions — These may be large and lack erythema unless secondary disease processes are at play.

An ultrasound of the neck and blood tests are routinely recommended. Blood tests test for TSH and T4 levels:4

  • Subclinical hypothyroidism — TSH levels are elevated and free T4 levels are normal.
  • Overt hypothyroidism — TSH levels are elevated and free T4 levels are low.
  • Central hypothyroidism, which results from a disorder of the pituitary gland or hypothalamus — TSH may be biologically inactive and may affect the levels of bioactive TSH.

Differential Diagnosis

Many conditions may lead to hypothyroidism. The list of differential diagnoses is extensive. It includes:4

  • Euthyroid sick syndrome
  • Goiter
  • Myxedema coma
  • Anemia
  • Riedel thyroiditis
  • Subacute thyroiditis
  • Thyroid lymphoma
  • Iodine deficiency
  • Addison’s disease
  • Chronic fatigue syndrome
  • Depression
  • Dysmenorrhea
  • Erectile dysfunction
  • Familial hypercholesterolemia
  • Infertility

Differential diagnoses are based on symptoms. For example, fatigue may indicate iron-deficiency anemia.4

Treatment of Hyperthyroidism and Joint Pain

Hypothyroidism is typically treated with levothyroxine, a thyroid hormone. Most patients receive 1.6 mcg/kg per day, while elderly and atrial fibrillation patients may require lower doses. Hospitalized patients treated with intravenous (IV) levothyroxine receive about half of the oral dose.3 Levothyroxine should be taken 30 to 45 minutes before breakfast and without ingesting any other oral medications, at least three hours after a meal at bedtime.

Patient therapy should be monitored and titrated based on thyroid-stimulating hormone (TSH) or serum-free T4 measurements for overt or subclinical hypothyroidism and free T4 measurements for central hypothyroidism.4

Labs should be drawn:

  • Every four to eight weeks until target TSH or T4 levels are achieved — If TSH or T4 levels are stable, monitoring intervals can be extended to six months and then 12 months if levels remain stable.
  • After any changes in the dose, formulation, or brand of levothyroxine — Maintaining a consistent formulation or brand of levothyroxine is essential. There are slight variations in the dose of the generic formulations.
  • After starting or stopping any medications that may affect TSH or T4 levels

Common medications and supplements that may affect levothyroxine absorption include:6

  • Proton pump inhibitors
  • Sucralfate
  • Calcium
  • Iron
  • Bile acid sequestrants
  • Aluminum-containing antacids
  • Phosphate binders
  • Raloxifene

Effective treatment should help improve all hypothyroidism symptoms. If a patient’s labs are normal while on thyroid replacement, but joint symptoms do not resolve, they likely are not due to hypothyroidism.

Of note, subclinical hypothyroidism is associated with adrenal insufficiency, which may be exacerbated by thyroid replacement treatment. However, diagnosing and treating adrenal insufficiency may reverse subclinical hypothyroidism.

Additionally, since autoimmune disorders tend to cluster, it is important to diagnose and treat each condition. For example, if the joint pain and tenderness are related to co-occurring RA, the RA should also be addressed.

Patients with co-occurring heart disease should be monitored for any symptoms of angina and atrial fibrillation.

Screening for osteoporosis is warranted if a patient is treated with levothyroxine for an extended period of time.4

References

  1. McLean RM, Podell DN. Bone and joint manifestations of hypothyroidism. Seminars in Arthritis and Rheumatism. 1995;24(4):282-290. doi:10.1016/s0049-0172(95)80038-7
  2. Tagoe CL, Zezon A, Khattri S. Rheumatic manifestations of autoimmune thyroid disease: The other autoimmune disease. The Journal of Rheumatology. 2012;39(6):1125-1129. doi:10.3899/jrheum.120022
  3. Li Q, Wang B, Mu K, et al. Increased risk of thyroid dysfunction among patients with rheumatoid arthritis. Frontiers in Endocrinology. 2019;9:1-8. doi:10.3389/fendo.2018.00799
  4. Patil N, Rehman A, Jialal I. Hypothyroidism. In: StatPearls. NCBI Bookshelf version. StatPearls Publishing: 2022, June 19. Accessed October 7, 2022.
  5. El-Shafie KT. Clinical presentation of hypothyroidism. J Family Community Med. 2003;10(1):55–58.
  6. Surks MI. Drug interactions with thyroid hormones. UpToDate. Updated May 19, 2022. Accessed October 7, 2022.

Author Bio

Denise Mann, MS, is a veteran freelance health writer in New York. Her work has appeared on HealthDay, among other outlets. She was awarded the 2004 and 2011 journalistic Achievement Awards from the American Society for Aesthetic Plastic Surgery. She was also named the 2011 National Newsmaker of the Year by the Community Anti-Drug Coalitions of America. She has also been awarded the Arthritis Foundation’s Northeast Region Prize for Online Journalism, the Excellence in Women’s Health Research Journalism Award, the Gold Award for Best Service Journalism from the Magazine Association of the Southeast, a Bronze Award from The American Society of Healthcare Publication Editors, and an honorable mention in the International Osteoporosis Foundation Journalism Awards. She was part of the writing team awarded a 2008 Sigma Delta Chi award for her part in a WebMD series on autism. Mann has a graduate degree from the Medill School of Journalism at Northwestern University in Evanston, Ill.