Is Levothyroxine Alone Adequate Thyroid Hormone Replacement?

NCT02567877 | Terminated

• 2 other identifiers: 14-2155UL1TR001082
• Study Type: observational
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Patients taking thyroid hormone replacement after thyroid removal surgery often report feeling differently than they did prior to taking thyroid hormone. The symptoms can include fatigue, worsening mood or subjective "brain fog" where the patient feels like their thinking is just not as sharp as it was previously. Multiple studies have found that patients taking thyroid hormone replacement have a diminished quality of life compared to matched controls. Previous studies have suggested that the type of deiodinase (DIO) polymorphism a patient has, which is responsible for converting the thyroid hormone T4 into the more biologically active T3, may contribute to their overall cognition and sense of well-being. The Investigators aim to determine if the type of deiodinase polymorphism a patient has contributes to the patient's cognition and overall sense of well-being after surgery and thyroid hormone replacement. Objective: Determine if patients with the deiodinase type 2 CC polymorphism have objective differences in working memory (N-back test is primary endpoint), cognitive function and sense of well-being after thyroidectomy when placed on standard thyroid hormone replacement therapy. Hypotheses: (1) Patients with the deiodinase type 2 CC polymorphism will have worse working memory (N-back test is primary endpoint), cognitive function and sense of well-being on standard thyroid hormone replacement therapy after thyroidectomy compared with before thyroidectomy. (2) Patients with the deiodinase type 2 TT or TC polymorphism will have no differences in working memory, cognitive function or sense of well-being on standard thyroid hormone replacement before and after thyroidectomy.

Conditions

Postsurgical Hypothyroidism; Hypothyroidism

Keywords

hypothyroidism; deiodinase polymorphism; cognitive function; thyroidectomy; levothyroxine

Outcome Measures

Primary Outcomes (1)

• Change in working memory (N-back testing) and correlation with deiodinase type 2 polymorphism

  Change in working memory as assessed by pre- vs post-surgery N-back test scores will be measured and compared between those with the deiodinase type 2 CC polymorphism versus those in the deiodinase type 2 TC and TT polymorphism group

  6-8 months

Secondary Outcomes (8)

• Change in cognitive function (SART testing) and correlation with deiodinase type 2 polymorphism

  6-8 months

• Change in Well-being (SF-36, Billewicz, HADS testing) and correlation with deiodinase type 2 polymorphism

  6-8 months

• Correlation of working memory (N-back testing) and correlation with serum thyronamine levels

  6-8 months

• Change in cognitive function (SART testing) and correlation with serum thyronamine levels

  6-8 months

• Change in Well-being (SF-36, Billewicz, HADS testing) and correlation with serum thyronamine levels

  6-8 months

Study Arms (1)

levothyroxine in thyroidectomy patients

patients undergoing thyroidectomy for nodular thyroid disease

Procedure: thyroidectomy; Drug: levothyroxine in thyroidectomy patients

Interventions

thyroidectomy PROCEDURE

Patients enrolled in the study will undergo a clinically-indicated thyroidectomy performed as standard of care.

Also known as: near-total thyroidectomy, total thyroidectomy

levothyroxine in thyroidectomy patients

levothyroxine in thyroidectomy patients DRUG

Patients will initiate levothyroxine treatment after surgery consistent with standard of care. The drug dosage will be titrated to TSH goal that matches the pre-surgery TSH (+/- 1 mIU/L)

Also known as: Synthroid, Levothyroid, Tirosint

levothyroxine in thyroidectomy patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing thyroidectomy for nodular thyroid disease or low-risk thyroid cancer

You may qualify if:

• TSH in the ideal reference range (0.4-4.0 milli-international units per liter (mIU/L))
• Planned thyroidectomy for nodular thyroid disease or low-risk differentiated thyroid cancer (\<4cm, no ETE, no expected use of RAI or suppressive levothyroxine therapy)

You may not qualify if:

• History of psychiatric illness (major illness as defined by DSM IV: major depression, schizophrenia, mania, etc). Patients prescribed chronic medications for psychiatric illness, those taking benzodiazepines or anti-seizure medication.
• Estrogen therapy that is new within the last 6 weeks or if the dose has been changed within the last 6 weeks
• Positive thyroid antibodies
• Chronic use (\>4 weeks) of concomitant medications that could affect cognition and memory (including sedative hypnotics, selective serotonin reuptake inhibitors, selective serotonin-norepinephrine reuptake inhibitors, Topamax, benzodiazepines, etc.)
• Pregnancy
• Steroid therapy
• Persistent cancer of any type or other major medical illness

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Charite University, Berlin, Germany: collaborator

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Related Publications (4)

• Saravanan P, Chau WF, Roberts N, Vedhara K, Greenwood R, Dayan CM. Psychological well-being in patients on 'adequate' doses of l-thyroxine: results of a large, controlled community-based questionnaire study. Clin Endocrinol (Oxf). 2002 Nov;57(5):577-85. doi: 10.1046/j.1365-2265.2002.01654.x.

  PMID: 12390330 BACKGROUND

• Scanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, Frascarelli S, Crossley DA, Bunzow JR, Ronca-Testoni S, Lin ET, Hatton D, Zucchi R, Grandy DK. 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat Med. 2004 Jun;10(6):638-42. doi: 10.1038/nm1051. Epub 2004 May 16.

  PMID: 15146179 BACKGROUND

• Hoefig CS, Kohrle J, Brabant G, Dixit K, Yap B, Strasburger CJ, Wu Z. Evidence for extrathyroidal formation of 3-iodothyronamine in humans as provided by a novel monoclonal antibody-based chemiluminescent serum immunoassay. J Clin Endocrinol Metab. 2011 Jun;96(6):1864-72. doi: 10.1210/jc.2010-2680. Epub 2011 Apr 13.

  PMID: 21490071 BACKGROUND

• Samuels MH, Schuff KG, Carlson NE, Carello P, Janowsky JS. Health status, mood, and cognition in experimentally induced subclinical hypothyroidism. J Clin Endocrinol Metab. 2007 Jul;92(7):2545-51. doi: 10.1210/jc.2007-0011. Epub 2007 May 1.

  PMID: 17473069 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

blood samples

MeSH Terms

Conditions

Hypothyroidism

Interventions

Thyroidectomy; Thyroxine

Condition Hierarchy (Ancestors)

Thyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Endocrine Surgical Procedures; Surgical Procedures, Operative; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Bryan R Haugen, M.D.

  University of Colorado Denver Anschutz Medical Campus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2015
• First Posted: October 5, 2015
• Study Start: November 1, 2016
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: June 8, 2023

Record last verified: 2023-06

Locations

US (1)