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Hypothyroidism - Symptoms, Causes, Risks, and Clinical Trials


Hypothyroidism comes with many symptoms

Hypothyroidism is a clinical condition in which the glands present in the front of your neck - called the thyroid gland, are unable to properly function and produce enough thyroid hormone required by the body. It is a key hormone for energy regulation in the body. Its deficiency leads to multiple systemic features.

Subclinical hypothyroidism is a type of hypothyroidism where there are mild to no clinical features, with only a slight increase in thyroid regulatory hormones of the pituitary gland. 

Hypothyroidism is prevalent more so in females than in males. Approximately 10 million people in the United States suffer from some degree of hypothyroidism.

Causes - Hypothyroidism and Clinical Trials

Reduced synthesis of thyroid hormone can be caused by:
Hashimoto's thyroiditis: It is the most common cause of reduced synthesis of thyroid hormones in the United States. It is an auto-immune condition, where the immune cells of your body confuse normal cells for foreign cells and attacks them. In Hashimoto's thyroiditis, your immune cells attack thyroid glands and cause chronic inflammation leading to reduced synthesis of thyroid hormones. It is a condition more prevalent in females and you are at more risk of developing the disorder if other members of your family suffer from it.

Hyperthyroidism treatment: In people with thyroid glands producing an excess of the hormone, various medications and surgery can be done to reduce excess hormone production. However, sometimes these methods may lead to permanently diminished levels of thyroid. Treating hyperthyroidism with radioactive iodine therapy is the major culprit here.

Also, removing excess gland surgically while treating hyperthyroidism can result in depleted levels of the hormone. This occurs when the remaining gland cannot produce enough hormones required by the body which leads to various clinical manifestations.

Medications: The prolonged use of certain medicines can lead to reduced synthesis of the thyroid hormone, drugs implicated are:
  • Lithium: A drug used in the treatment of mania
  • Mitotane: A drug used for cancer treatment
  • Amiodarone: A drug used to treat irregular rhythms of the heart and maintain a steady heartbeat.

Radiation therapy: Radiation therapy of the neck to treat cancer around the neck and head can result in decreased production of thyroid hormone.

Iodine Deficiency: Iodine is crucial for the synthesis of thyroid hormone. Though a rare occurrence in the United States, iodine deficiency in diets is a prime cause of hypothyroidism in developing countries of the world.

Clinical features - Hypothyroidism and Clinical Trials

A patient with hypothyroidism presents with:
  • Loss of energy and fatigue
  • Decreased body metabolism leading to weight gain
  • Reduced appetite
  • Intolerance to cold 
  • Decreased sweating and dry skin
  • Hair loss
  • Increased sleepiness
  • Muscle and joint pain and weakness, especially in the extremities
  • Depression
  • Constipation
  • Impaired concentration and memory
  • Menstrual abnormalities and reduced fertility
  • Blurring of vision
  • Hoarseness of voice
  • Reduced hearing
  • Development of goiter
  • Dull facial expression and slowed movement
  • Puffiness around the eye
  • Decreased heartbeat
  • Delayed and weak body reflexes.

Diagnosis - Hypothyroidism and Clinical Trials

Your doctor will take a detailed medical history and thorough clinical examination to look for the signs of hypothyroidism. If the symptoms are suggestive of hypothyroidism the doctor will order a blood test to check the level of thyroid hormones.

Your blood will be checked for levels of hormone Thyroid Stimulating Hormone (TSH) and Thyroxine (T4). Typically in hypothyroidism, the levels of T4 produced from the thyroid gland are low whereas the levels of TSH are high because the pituitary gland is trying to stimulate thyroid activity for proper thyroid hormone maintenance. In subclinical forms of hypothyroidism, there is a slight compensatory increase in levels of TSH but the levels of T4 remain normal or are only slightly low. In subclinical hypothyroidism, clinical features may or may not be present; it can be diagnosed only through blood tests.

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Management - Hypothyroidism and Clinical Trials

The treatment modalities in hypothyroidism aim at only alleviating symptoms and improving quality of life. There is no cure for hypothyroidism.

The drug commonly used in the treatment of hypothyroidism is levothyroxine. It is a synthetic analog of the Thyroxine hormone produced from the thyroid gland. It has actions similar to thyroid hormone, thus helps alleviate symptoms related to thyroid deficiency. After starting the drug therapy regular monitoring of blood hormone level should be done to assess the efficacy and monitor its progress. You will most probably require to take the medicine lifelong. In case the medicine does not show desired effects its dose may need to be increased.

New Treatments - Hypothyroidism and Clinical Trials

Thyroid function following Iopamidol administration: Iopamidol based products are used as contrast agents in CT scans in the pediatric population. It has been shown to cause hypothyroidism in some cases. A clinical trial is currently undergoing to assess abnormal thyroid function after iv exposure to Iopamidol-based agents in the pediatric population for radiological study. It is currently in Phase 4 of its clinical trial.

Thyroid hormone supplementation in patients on hemodialysis: Hypothyroidism is a common complication in patients with chronic kidney disease. Currently, levothyroxine is used as thyroid replacement therapy in patients with chronic kidney disease on hemodialysis therapy. However, its safety and efficacy in these patients are not fully known. A clinical trial is currently underway which aims at assessing its efficacy in reducing symptoms and improving quality of life in these patients.

Evaluation of the patient with thyroid disorder: An observational study is currently underway which aims at understanding the causes, the natural history, clinical features and assessing the efficacy of standard treatment therapies in the treatment of thyroid disorders including hypo and hyperthyroidism. It also aims at forming clinical data for thyroid researches in the future.

Levothyroxine: Levothyroxine as a sole thyroid replacement therapy in post-operative cases of thyroidectomy is being observed for its adequacy and safety in maintaining thyroid levels and improving the sense of well-being in such patients. Many patients taking levothyroxine after thyroid surgeries had shown to develop brain fog, fatigue, worsening mood, and general quality of life. These changes were attributed to a certain type of enzyme polymorphism. The utility of levothyroxine in such enzyme polymorphism is being studied for improving symptoms.

  1. I.Kostoglou-Athanassiou, K.Ntalles et al. Hypothyroidism - new aspects of an old disease. Hippokratia. 2010 Apr-Jun; 14(2): 82–87.

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