Justin Moore, MD, FACP
Division Chief, Endocrinology and Metabolism
Medical Director, Via Christi Weight Management

TRH: Thyrotropin-releasing hormone
TSH: Thyroid stimulating hormone

Only three things can go wrong with your thyroid
1. Underactive (“hypothyroidism”)
2. Overactive (“hyperthyroidism”)
3. Enlargement (“goiter”)/cancer

1. How do we measure thyroid function?
2. Do overweight or obese persons have different thyroid blood tests than persons of normal body weight?
3. If such persons have low thyroid function, is treatment with thyroid hormone associated with a reduction in their weight?
4. Weight aside, what is the evidence that treatment of mild thyroid dysfunction affects well-being?

TSH (compared to free T4) presents an “amplified” picture of thyroid status

The TSH level rises with age
NHANES III, PMID: 11836274

Heavier people have higher TSH levels than lighter people
Arch Intern Med. 2008;168(6):587-592

As people gain weight, their TSH level rises
Arch Intern Med. 2008;168(6):587-592

But it’s not just heavier people who have weird thyroid labs. They are also different in people with anorexia!

In anorexia and obesity, normalization of weight normalizes thyroid labs

Arch Intern Med 2008;168:568-569.

Mainstream medicine holds medications (or hormones) to a very high standard
Population with disease
(n=100)
Placebo group
(n=50)
Hormone group
(n=50)
Outcome?
Outcome?

Meta-analysis
The results of many randomized, controlled trials combined into one “super-study”

Effects of thyroid hormone therapy on weight loss during caloric deprivation of euthyroid obese subjects
Kaptein E M et al. JCEM 2009;94:3663-3675

Why might you treat someone with mild hypothyroidism?
• Some studies do report improvements in
some outcomes
– Clearness of thought
– Cholesterol
– Heart function
• Thyroid hormone at appropriate doses is reasonably safe
• Thyroid hormone is cheap

Does giving thyroid hormone to people with mild
(“subclinical” hypothyroidism) do any good?
• Villar HC et al. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane
Database 2007, PMID: 17636722
• Overview of methods:
– Meta-analysis
• Funding and support:
– Not stated

Cochrane review (17636722)
• Patients: 12 RCTs (n = 485, > 75% women) in adult outpatients with subclinical hypothyroidism and no severe illness
• Intervention: Triiodothyronine (T
3 both.
), thyroxine (T
4
), or
– Daily LT
4 doses varied from 65 µg (4 trials) to 150 µg (1 trial)
• Comparison: Placebo (11 RCTs) or no treatment (1 RCT)
• Outcome: Symptoms, mood, quality of life, cognitive function, serum lipids, myocardial relaxation, adverse events

Results of Cochrane 2007, PMID 17636722

Results of Cochrane 2007, PMID 17636722
• In 1 trial (n = 66), thyroid hormone replacement improved thought clarity
• Weighted mean difference 2.4, (95% CI 0.3 to 4.5, P = 0.03)
• Groups did not differ in any trial for:
– Quality of life (2 trials)
– Adverse effects (4 trials)
• Persons with a baseline LDL cholesterol level >155 mg/dl had improvement in their cholesterol levels

What about giving thyroid hormone to fatigued patients with normal thyroid studies? (BMJ 2001, PMID
11668132)
Patients: 25 persons with symptoms of hypothyroidism, but normal thyroid function testing, and 19 controls
Intervention: 100 ug levothyroxine once daily for 12 weeks, then
“crossover”
Comparison: Placebo
Outcome: Thyroid function testing, measures of cognitive function, tests of psychological and physical well-being

Results
• Subjects showed a greater response to placebo than to thyroid hormone in 3/15 measures of psychological well-being
• Healthy subjects had significantly lower scores for vitality when taking levothyroxine compared to placebo (60 + 17 vs. 73 + 16, p <0.01)
• Fatigued patients’ scores on psychological testing were no different on thyroid hormone versus placebo
– Worse on visual reproduction testing
BMJ 2001, PMID 11668132

• Controls: no significant change in psychological measures with either thyroid hormone or placebo
• Conclusion: Thyroid hormone does not have a nonspecific effect on wellbeing in persons without thyroid dysfunction
BMJ 2001, PMID 11668132

• Turner MR et al, Levothyroxine dose and risk of fractures in older adults: nested case-control study.
BMJ. 2011 Apr 28;342. PMID: 21527461
• Overview of methods:
– Nested case-control study
• Funding and support:
– Canadian Institutes of Health Research

Turner MR, BMJ, PMID: 21527461
• Patients: Canadian patients 70 to 105 years of age
• Intervention: Thyroid hormone
• Comparison: Controls not on thyroid hormone
• Outcome: Any fracture

Results of BMJ 2011, PMID 21527461
• Levothyroxine use was associated with a higher risk of fracture (adjusted OR=1.88%; 95% CI, 1.71-2.05)
• Higher doses of levothyroxine were associated with higher risk.

Does Thyroid Hormone Replacement Reduce
Mortality?
• Razvi S et al. Levothyroxine Treatment of Subclinical
Hypothyroidism, Fatal and Nonfatal Cardiovascular Events, and Mortality. Arch Intern Med. Published online April 23,
2012. PMID: 22529180
• Overview of methods: Cohort study
• Funding:
– Medical Research Council

PMID: 22529180
• Patients: Persons aged 40-70 or >70 years with subclinical hypothyroidism
• Intervention: Levothyroxine
• Comparison: No treatment
• Outcome: Ischemic heart events

Results of PMID: 22529180
• Younger patients (40-70) treated with thyroid hormone:
– Multivariate-adjusted HR 0.61 (95% CI, 0.39-0.95)
• Older patients (>70) treated with thyroid hormone:
– HR 0.99; 95% CI, 0.59-1.33

Be careful what doctors promise you…

• Your thyroid gland is important, and affects almost every organ system you possess
• Hypothyroidism is common, but not nearly as common as overweight or obesity
• Thyroid function testing is easily obtained, and the
TSH blood test is adequate in more than 99 percent of people

• Overweight or obese persons have different thyroid blood tests than persons of normal body weight, but treating them for these test abnormalities does not typically promote weight loss
• Treatment of mild thyroid testing abnormalities has, at best, very mild effects on well-being, but is worth discussing with your doctor

Questions?
KU-WichitaEndocrinology

Photo Credits
• Chicken and cat: http://community.breastcancer.org/forum/102/topic/765586?page=147
• Pituitary gland: http://en.wikipedia.org/wiki/File:Pituitary_gland.png
• Thyroid gland: http://en.wikipedia.org/wiki/File:Thyroid_gland.jpg
• Butterfly neck: http://www.hannahweptsarahlaughed.com/2010/06/thyroid-update-butterfly-in-my-neck
• Archie Cochrane: Cardiff University Library, Cochrane Archive, University Hospital Llandough
• Iodized salt logo: http://en.wikipedia.org/wiki/File:Global_iodized_salt_logo.jpg
• Goiter belt: http://www4.uwsp.edu/geo/faculty/ozsvath/images/goiter_belt.htm
• John Brinkley: http://en.wikipedia.org/wiki/John_R._Brinkley