Thyroid-stimulating hormone

Thyroid-stimulating hormone
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Abbreviation	TSH
Molecular formula	Glycoprotein (~28 kDa); two subunits (α and β) with complex carbohydrate chains
Type	Pituitary glycoprotein hormone
Administration	Endogenous only
Bioavailability	N/A, regulated by hypothalamic TRH and feedback from T3/T4
Synonyms	Thyrotropin, Thyrotropic hormone
Source	Anterior pituitary gland (thyrotrope cells)
Ray's verdict	Strongly negative, TSH itself is harmful, not just a marker, inflammatory and tissue-damaging

Introduction

Thyroid-stimulating hormone (TSH), also known as thyrotropin, is a glycoprotein hormone produced by the anterior pituitary gland. It serves as the primary regulator of thyroid gland activity, stimulating the thyroid to produce thyroxine (T4) and triiodothyronine (T3). TSH is commonly measured in clinical settings as a marker of thyroid function, though its interpretation and the appropriateness of current reference ranges remain subjects of significant debate.

History/Etymology

The TSH test became widely adopted as the "gold standard" for evaluating thyroid function after replacing the protein-bound iodine (PBI) test, which was abandoned in the 1960s when it was proven to be irrelevant to thyroid function (Ray Peat, "Thyroid: Therapies, Confusion, and Fraud"). Prior to the 1940s, hypothyroidism was diagnosed on the basis of basal metabolic rate (BMR) and clinical signs and symptoms, with approximately 40% of the American population meeting the diagnostic criteria (Ray Peat, "Hypothyroidism").

The PBI test, introduced in the late 1940s, suggested that only 5% of the population was hypothyroid (Ray Peat, "Thyroid"). This dramatic reduction from 40% to 5% shaped the statistical norms for subsequent tests. When TSH measurement became available, its "normal" ranges were established using these already artificially narrowed expectations, resulting in what some researchers consider pathologically high TSH levels being defined as normal (Ray Peat, "Hypothyroidism").

The reference ranges for TSH have undergone numerous revisions: while 7.0 microIU/mL was once considered normal, the cutoff was later lowered to 6.4, then 5.5, and then 4.2 (Danny Roddy, "The Male Pattern Baldness Myth"). In 2003, the American Association of Clinical Endocrinologists changed their guidelines for the normal range to 0.3 to 3.0 microIU/mL (Ray Peat, "Hypothyroidism").

Structure/Chemical properties

TSH is a glycoprotein hormone consisting of two non-covalently linked subunits: an alpha subunit common to other pituitary hormones (FSH, LH, hCG) and a beta subunit unique to TSH that confers its biological specificity. The hormone is synthesized in the thyrotroph cells of the anterior pituitary gland under the control of hypothalamic thyrotropin-releasing hormone (TRH) (PubMed, "Central regulation of hypothalamic-pituitary-thyroid axis").

The molecular structure enables TSH to bind to TSH receptors on thyroid follicular cells, initiating a cascade of intracellular signaling that promotes thyroid hormone synthesis and release.

Function/Mechanism of Action

TSH operates within the hypothalamic-pituitary-thyroid (HPT) axis through a negative feedback loop. The hypothalamus secretes TRH, which stimulates TSH release from the pituitary. TSH then acts on the thyroid gland to promote the synthesis and release of T4 and T3. When circulating thyroid hormone levels rise, they suppress further TSH secretion; when they fall, TSH increases (Danny Roddy, "Q&A with Georgi Dinkov").

Approximately 90% of TSH suppression occurs through circulating T4, which is converted to T3 within the cells of the pituitary. This intrapituitary conversion is what primarily signals to the pituitary that the thyroid has done its job (Danny Roddy, "If free T3 looks good, why is TSH still a little high?").

Beyond its effects on the thyroid, TSH has direct actions on many cell types including fibroblasts, fat cells, pigment cells in the skin, mast cells, and bone marrow cells (Ray Peat, "Hypothyroidism"; Whetsell et al., 1999). This widespread action suggests TSH functions as more than simply a thyroid-regulating hormone.

"TSH has direct actions on many cell types other than the thyroid, and probably contributes directly to edema, fibrosis, and mastocytosis." (Ray Peat, "Hypothyroidism")

TSH is increased by stress hormones and serotonin. Low thyroid individuals often exhibit elevated serotonin, which in turn raises both TSH and prolactin. This creates a self-perpetuating pattern of high TSH, high prolactin, and high serotonin that suppresses mitochondrial respiration and carbon dioxide production (Ray Peat, "Serotonin and Endotoxin" interview).

Medical uses/Effects

Pro-inflammatory actions

TSH itself is considered pro-inflammatory, with direct tissue-irritating effects wherever it has been studied. It promotes inflammation in blood vessels and bone marrow, and contributes to hypertension and circulatory problems (Ray Peat, "One Radio Network," 2020). The TSH molecule creates inflammation in the blood vessels, working alongside parathyroid hormone to calcify blood vessels and shift calcium out of bones (Ray Peat, "Super Health Researcher," 2019).

"The TSH goes around irritating or creating inflammation, for example, in the blood vessels... TSH in excess works in that same direction, calcifying the blood vessels, increasing blood pressure." (Ray Peat, "Super Health Researcher," 2019)

TSH contributes to atherosclerosis, increased blood lipids, and increased blood pressure (Ray Peat, "Serotonin Raises TSH" interview). High TSH is associated with increased production of mucopolysaccharides, the accumulation of which is a hallmark of hypothyroidism (myxedema) (Danny Roddy, "The Male Pattern Baldness Myth").

Bone metabolism

TSH reduces bone turnover indicators, which has been misinterpreted as protective against osteoporosis. However, TSH, like estrogen, increases osteoprotegerin, which is closely associated with bone loss, osteoporosis, osteopenia, and calcification of soft tissues (Ray Peat, "The Thyroid" interview). TSH increases the movement of calcium into arteries and heart while depleting it from bones (Ray Peat, "The Thyroid" interview).

Cancer associations

Chronic exposure of the thyroid gland to TSH is carcinogenic, leading to nodule formation and ultimately increased risk of thyroid cancer (Ray Peat, "Q&A: PUFAs, fructose, weight loss"). Populations with TSH below 0.4 show the lowest incidence of thyroid cancer (Danny Roddy, "The Male Pattern Baldness Myth"). Some types of thyroid cancer can be controlled by keeping TSH completely suppressed (Ray Peat, "Hypothyroidism").

TSH's role may extend to other cancers as well. Its action on diverse cell types including pigment cells suggests a potential involvement in melanoma development (Ray Peat, "Hypothyroidism").

Cardiovascular effects

One study found that TSH levels of 1.5 to 3.5 (within the "normal" range) were associated with developing fatal coronary heart disease (Danny Roddy, "The Male Pattern Baldness Myth"). TSH increases fibrinogen in the blood, making it more viscous and harder to circulate (Ray Peat, "Blood Pressure Regulation" interview, KMUD).

Relationship to stress

TSH functions as an indicator of stress as much as it indicates thyroid status. Stress hormones like cortisol and adrenaline can suppress TSH, making a person appear euthyroid on tests while remaining functionally hypothyroid (Ray Peat, "One Radio Network," 2020). Conversely, stress conditions that increase the need for thyroid production tend to increase TSH, while simultaneously producing cortisol and adrenaline that suppress it defensively (Ray Peat, "Super Health Researcher," 2019).

Dosing

Produced endogenously, you wouldn't want to supplement an inflammatory and tissue damaging hormone anyway

Instead look at Supplementing T3/T4

Reference ranges and optimal values

The current accepted range of 0.3 to 3.0 microIU/mL is considered too lenient by some researchers. Ray has observed that over a period of several years, he never saw a person whose TSH was over 2 microIU/mL who was "comfortably healthy," forming the impression that the normal or healthy quantity was probably something less than 1.0 (Ray Peat, "Hypothyroidism").

Thyroid specialists at the University of California Medical Center in San Francisco prefer to see corrected TSH levels around 0.2, slightly below the standard normal range (Danny Roddy, "The Male Pattern Baldness Myth"). A population found to be generally healthy without heart disease or cancer had TSH values of 0.4 or less (Ray Peat, KMUD interview). Many individuals report being healthy with TSH values of 0.1 or even lower (Ray Peat, "One Radio Network," 2021).

"I think it's good to have close to zero on TSH as long as everything else is going smoothly... I look at TSH as one of the pro-inflammatory pituitary hormones that is best when it's minimal." (Ray Peat, "One Radio Network," 2021)

Animals lacking pituitaries (and therefore TSH) in W.D. Denckla's experiments showed remarkable longevity, and naturally pituitary-deficient dwarf mice that lack TSH, prolactin, and growth hormone live about a year longer than normal mice (Ray Peat, "Hypothyroidism"; Heiman et al., 2003).

Side/Adverse effects

Direct effects of elevated TSH

• Edema and tissue swelling (Wheatley and Edwards, 1983)
• Fibrosis and mastocytosis (Ray Peat, "Hypothyroidism")
• Inflammation of blood vessels (Ray Peat, "Super Health Researcher," 2019)
• Increased blood pressure and hypertension (Ray Peat, "One Radio Network," 2020)
• Calcification of soft tissues (Ray Peat, "The Thyroid" interview)
• Bone loss through increased osteoprotegerin (Ray Peat, "The Thyroid" interview)
• Increased risk of thyroid cancer with chronic elevation (Ray Peat, "Q&A: PUFAs, fructose, weight loss")
• Increased blood lipids and atherosclerosis (Ray Peat, "Serotonin Raises TSH" interview)
• Mucopolysaccharide accumulation (Danny Roddy, "The Male Pattern Baldness Myth")

When TSH is very low (suppressed)

The main medical concern regarding suppressed TSH is osteoporosis. However, this argument is based on the same flawed reasoning used to promote estrogen for bone health: reduced bone turnover indicators were equated with bone protection, when in fact the substances that reduce turnover (TSH and estrogen) are associated with calcium being moved from bones into soft tissues (Ray Peat, "The Thyroid" interview).

Until there is evidence that very low TSH is somehow harmful, there is no basis for setting a lower limit to the normal range (Ray Peat, "Hypothyroidism").