Hypothyroidism Treatment Policy in the U.S.: Trying to Sort Out the Controversy

Abstract

The problem: how others have stated it

Current medical guidelines for screening for, diagnosis of and treatment of hypothyroidism

The real question: what does the thyroid do and how does it affect us in health and in disease?

Explanation of some basic scientific terms and practices: a crash course

Metabolism

Hormones and neurotransmitters

Iodine, other halogens, and molecules with similar behavior

Water-soluble vs. fat-soluble molecules (or polar vs. nonpolar molecules)

The cell cycle: how the body grows

Transport of substances into the cell

How cellular data are obtained and analyzed in the laboratory

Inflammation and cytokines, and their experimental stimulation

Deep reasoning vs. shallow reasoning: appropriate in different situations

Negative and positive feedback systems and homeostasis

Significant figures

Statistical models

Continuous vs. discrete variables

Dependent vs. independent variables

"Real" vs. surrogate variables

Observational studies, clinical trials, and meta-analyses

Some basic measurement terms

Normal ranges (technically referred to as "reference ranges")

How scientists minimize harm when they don't know everything: type I and II errors, sensitivity and specificity

What does that L- mean? (and those fancy prefixes with the apostrophes?)

Evidence-based medicine

The cast of characters in medical practice: physicians, clinical biochemists, scientific teams, patients, and policy-makers

Thyroid structure and function basics

The hypothalamus-pituitary-thyroid "axis" (where the thyroid gets its orders) and its partnership with its growth hormone counterpart

The thyroid and its hormones

The thyroid's basic unit: the follicle

Other body systems processing thyroid hormones

Relationship to the nervous system, the immune system and to other endocrine glands

Dopamine

Serotonin

Glucocorticoids

The immune system

History: from iodine nutrition management to thyroid hormone replacement

Goiter, myxedema, cretinism, iodine and understanding of how the thyroid gland works: the early European contribution

Contributions from the United States and Japan: from salt iodization to T4 replacement

Iodine deficiency and its treatment with salt iodization

The shift to T4 replacement therapy

Broda Barnes, a hypothyroidism researcher before his time

The Hashimoto paper

Synthroid and thyroid hormone replacement therapy

The invention of the radioimmunoassay (RIA) and of its successor, the enzyme-linked immunosorbent assay (ELISA)

Today: what is settled and decided (and what is not) regarding dietary iodine

Iodine vs. key pollutants

Perchlorate ions

Bromine compounds in dough conditioners, flame retardants and soda

Fluorine compounds and water fluoridation

Hypothyroidism and measurement of thyroid parameters

TSH summary statistics from the Centers for Disease Control (CDC)

The twenty-year follow-up to the Whickham Survey (1995)

The other thyroid diseases: their influence on diagnosis of hypothyroidism

What about hyperthyroidism and thyrotoxicosis? How do views about them influence diagnosis of hypothyroidism?

What about thyroid cancer, "benign" thyroid disease and iodine?

Hypothyroidism (especially "subclinical") and the risk of heart disease

Clinical research findings

The main issue: what questions are we trying to answer?

Studies of the possible causal relationship of "subclinical" hypothyroidism (SCH) and ischemic heart disease (warning: your eyes may glaze over here)

A study of the effects of treatment of subjects with subclinical hypothyroidism (SCH) with T4 on ischemic heart disease (IHD) rates

Possible mechanism linking SCH and "bad" blood lipid levels

The impact of estrogen levels on thyroid health, and implications for pregnancy, infertility and breast cancer

Clinical research: the relationship of estrogen levels on thyroid performance

Estrogen and the hypothalamus: in vitro studies

The impact of non-thyroid diseases on thyroid test results and possible HPT axis hormone treatment

Critical illness, i.e., "low T3 syndrome" and stages on the way

Unresolved questions: differing value systems and problem-solving based on them

Determining the TSH reference range, one of two criteria used for diagnosis: as much art as science

What about the stress of exercise (and staying up late) in healthy subjects?

The chemistry of muscle damage and its relationship to hypothyroidism

Iodine in other parts of the body: how their needs impact thyroid function

Neglected areas of study and other factors

The infection connection

Menopause (and adolescence)

The Alzheimer's dementia connection

Cultural differences

Economic factors

Discussion

Clinical signs and symptoms should count, too!

Problems with relying on TSH levels alone for diagnosis

Mechanisms: what we know about how TSH works

Can we really measure the precision of normal range limits?

To add to the confusion: changing precision of TSH assays, resulting in two normal ranges?

Clinical trials issues: some crucial data may not be available because of ethical rules

Screening: no longer part of the standard annual physical

Stimulants (chemicals raising dopamine levels), exercise and how they complicate hypothyroidism diagnosis

Why do women get hypothyroidism more than men do?

Concomitant disease and its confusing effect on TSH and thyroid hormone levels

Iodine supplementation: how much is needed and the problems associated with determining that

Ideal patient education: the easy and the hard parts

"Normal" range issues: TSH, continuous value variables and precision

Menopause, a neglected factor

Determining threshold levels: the devil in the details

The perfect is now the enemy of the good; what about the patients' needs?

References