Levothyroxine Treatment of Subclinical Hypothyroidism After Non-thyroid Head and Neck Surgery: A Randomized Controlled Trial
Trial Snapshot
- Phase
- Phase 2
- Status
- Withdrawn
- Sponsor
- University of Alberta
- Primary Endpoint
- Number of patients with a post-operative wound complication
Study Overview
Brief Summary
Patients that require treatment for cancers of the head and neck often require a combination of surgery and/or radiation and chemotherapy. Hypothyroidism is one of the most common complications, and has been associated with post-operative complications such as wound healing problems, fistula formation, and decreased quality of life and survival. Several studies have examined hypothyroidism after radiation to the head and neck, but few have examined this after non-thyroid head and neck surgery. Head and neck resection is theorized to devascularize the thyroid, thus resulting in post-operative hypothyroidism.
Synthroid is a synthetic thyroid hormone often used in cases of patients with proven hypothyroidism and after surgical thyroid removal. It's use has been in effect and studied for over fifty years.
Treatment algorithms for hypothyroidism are well published. However, treatment of subclinical hypothyroidism (elevated TSH with normal or near-normal T3/T4) is controversial. The rate of subclinical hypothyroidism after non-thyroid head and neck surgery is high (up to 20%), and is associated with post-operative complications as noted above.
Therefore the investigators propose a double blinded randomized controlled trial comparing outcomes of patients that develop subclinical hypothyroidism after head and neck surgery, who are given a standardized dose of synthroid treatment versus those treated with placebo. The main outcomes to be examined are post-operative complications (wound healing issues, fistula formation), survival, and quality of life measures.
Detailed Description
Background and Scope:
Hypothyroidism is one of the most common complications following multimodality treatment for head and neck cancer, with an incidence of 7-58% depending on the subsite. The causes for this high rate of hypothyroidism following treatment for head and neck cancer are multifactorial. Patients treated for head and neck cancer often require radiation therapy (RT). The negative effects of RT on the thyroid are well published, and the resultant hypothyroidism can have widespread implications on a patient's physical and mental health. Head and neck surgery has also been hypothesized to devascularize and disturb the overall anatomical structure of the thyroid, thus contributing to the high incidence of hypothyroidism after surgery.
Despite the literature demonstrating the connection between head and neck cancer treatment and hypothyroidism, complications from this illness after major head and neck surgery remain common. Decreased survival as well as increased rates of fistulas, infections, and wound breakdown are some of the physical consequences. Other possible issues include decreased functional outcomes and increased mental illness, as these are known consequences of untreated hypothyroidism. While several studies have examined the rate and timing of hypothyroidism after radiation to the head and neck, there is a paucity of literature on the effect of surgery on thyroid function. Specifically, in patients treated with single modality surgery, and in patients treated with primary surgery before the start of RT, when the risk of wound complications is high.
Synthroid is a synthetic thyroid hormone, and is the mainstay of treatment of patients with proven hypothyroidism and after surgical thyroid removal. Its use has been in effect and studied for over fifty years. Side effects of the drug most commonly occur with overdosing and will mimic those of hyperthyroidism, which may include: heart palpitations, abdominal pain, nausea, anxiety, confusion, agitation, insomnia, weight loss, and increased appetite. There is a low chance (< 1%) of allergic reaction to the drug, which may include shortness of breath, swelling of the face and tongue.
Whereas treatment algorithms for clinical hypothyroidism are well established, treatment of subclinical hypothyroidism remains controversial. Subclinical hypothyroidism refers to a state of elevated thyroid stimulating hormone (TSH), with normal or near-normal thyroid hormone levels (T3 and T4), or a lack of symptoms of hypothyroidism. Endocrinologists disagree on whether this disease should be treated, since it is almost always asymptomatic, and the treatment is mainly for relief of symptoms. Head and neck cancer patients, however, represent a special population, in which the effects of subclinical hypothyroidism can result in consequences besides symptoms, such as wound healing issues and fistula development as described above. Studies have shown that the rate of subclinical hypothyroidism during head and neck cancer treatment is high.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Biopsy proven head and neck cancer, as defined by AJCC staging system
- •Treated with surgery in Edmonton, Alberta
- •Treated with curative intent
- •Diagnosis of sub-clinical hypothyroidism after head and neck surgery (TSH 4-10mIU/L, and free T4 10-24pmol/L)
Exclusion Criteria
- •Head and neck cancer of the thyroid gland, or other subsite involving the thyroid gland
- •Underwent previous treatment for a different head and neck cancer
- •History of radiation therapy and or chemotherapy to the head and neck
- •History of thyroid disease as follows:
- •Hypothyroidism
- •Hyperthyroidism
- •Autoimmune thyroid disease including Grave's disease and Hashimoto's thyroiditis
- •History of thyroiditis
- •History of diabetes mellitus
- •History of long term steroid usage
- •History of immunocompromise
- •History of thyroid surgery
- •History of ischemic heart disease
- •Patients taking a medication that may alter the metabolism or interact with levothyroxine, which they cannot safely stop (see Appendix A).
Arms & Interventions
Control
Daily placebo
Intervention: Placebo (Drug)
Treatment
Participants administered daily levothyroxine at 1.6mcg/kg to a target normal TSH, measured at 6 weeks after the initiation of therapy
Intervention: Levothyroxine (Drug)
Outcomes
Primary Outcomes
Number of patients with a post-operative wound complication
Time Frame: 12 weeks post-operatively
* Rate of fistula formation * Rate of wound breakdown * Rate of post-operative infection * Rate of flap failure (dehiscence and/or necrosis requiring salvage)
Secondary Outcomes
- Number of patients with clinical depression(12 weeks post-operatively)
- Number of surviving patients at 6 months(6 months post-operatively)
- Number of patients with G-tube(12 weeks post-operatively)
- Quality of life based on EQ-5D7(12 weeks post-operatively)