Skip to content

Human Physiology · Endocrine and reproduction

The Thyroid

Thyroid hormone sets the pace of the body: metabolism, heart rate, muscle function and brain development. This page explains how it is made and controlled, how muscle regulates its own thyroid signal, how to recognise too little or too much, and what the evidence says about treating mild thyroid failure in older adults.

11Sections
5Figures
3Tables
10Questions

Part 8 · Endocrine and Reproduction · Chapter 35 of 47

Learning objectives

By the end of this page you should be able to:

  • Describe the synthesis and control of thyroid hormones.
  • Interpret TSH and T4 in common thyroid disorders.
  • List the actions of thyroid hormone on body systems.
  • Explain local control of thyroid hormone in muscle.
  • Compare the features of hypothyroidism and hyperthyroidism.
  • Apply thyroid physiology to exercise prescription.

Why it matters

Thyroid disorders are common, especially in women and older adults. They cause fatigue, muscle weakness, cramps, heart rhythm problems and carpal tunnel syndrome, all of which physiotherapists see.

Recognising thyroid features helps you refer appropriately and set safe exercise limits, for example in a patient with untreated hyperthyroidism and a fast irregular pulse.

Making thyroid hormone

The thyroid traps iodine from the blood and attaches it to the amino acid tyrosine on a large storage protein, thyroglobulin. It releases mainly thyroxine (T4), which has four iodine atoms, and a little tri-iodothyronine (T3), the more active form.

Most T3 is made outside the thyroid, when tissues remove one iodine from T4. In the blood, almost all thyroid hormone is bound to carrier proteins; only the free fraction acts.

Figure 1 · The thyroid axis

Hypothalamic-pituitary-thyroid axis with conversion of T4 to T3 in tissues The hypothalamus releases TRH, the pituitary TSH, and the thyroid mostly T4 with some T3. Tissues convert T4 to the active T3. Thyroid hormone feeds back to suppress TRH and TSH. A note explains how TSH and T4 together classify thyroid disorders. HypothalamusTRHAnterior pituitaryTSHThyroid glandmostly T4, some T3needs iodineTissues (muscle, liver, brain)deiodinase convertsT4 → active T3negative feedbackBlood test logicHigh TSH, low T4:primary hypothyroidismHigh TSH, normal T4:subclinicalLow TSH, high T4:hyperthyroidism
TSH is the most sensitive test. Because of feedback, TSH moves in the opposite direction to thyroid hormone in primary thyroid disease.
ResultTSHFree T4Meaning
NormalNormalNormalEuthyroid
Primary hypothyroidismHighLowThyroid failing; pituitary pushing harder
Subclinical hypothyroidismHighNormalEarly or mild failure
HyperthyroidismLowHighThyroid overactive; pituitary suppressed

Actions of thyroid hormone

Figure 2 · What thyroid hormone does

Main actions of thyroid hormone on body systems Six boxes: thyroid hormone raises metabolism and heat production, speeds and strengthens the heart, affects muscle contraction and repair, supports bone growth and turnover, supports brain development and alertness, and speeds gut motility. Metabolismraises oxygen use and heatHeartfaster rate, stronger beatMusclecontraction speed, repair, metabolismBonegrowth in children; turnoverBraindevelopment; alertness, moodGutmotilityThyroid hormone sets the pace of almost every tissue
A body-wide accelerator. Too much speeds everything up; too little slows everything down.

Thyroid hormone raises the number of Na/K pumps and mitochondria, increasing oxygen use and heat production. It increases heart rate and contractility, partly by increasing sensitivity to adrenaline. It is essential for brain development in infancy; untreated deficiency at birth causes severe developmental delay, which is why newborns are screened.

Thyroid hormone in muscle

Salvatore and colleagues review how skeletal muscle is a major target of thyroid hormone [1]. Muscle cells contain deiodinase enzymes: DIO2 converts T4 into active T3, and DIO3 inactivates T3 [1].

Figure 3 · Muscle controls its own thyroid signal

Deiodinase enzymes activating and inactivating thyroid hormone inside a muscle cell Inside a muscle cell, the enzyme DIO2 converts T4 from the blood into active T3, which acts on the nucleus, and DIO3 inactivates T3. Balancing these enzymes lets muscle set its own thyroid hormone level. Muscle cellT4 from bloodDIO2activatesT3nucleusDIO3inactivatesLocal controlmuscle sets its own T3level during growthand repair [1]
Thyroid signalling is local as well as systemic. Deiodinases regulate T3 during muscle development and satellite-cell repair [1].

By adjusting these enzymes, muscle sets its own internal T3 level, independent of blood levels. This local control matters during muscle development and in satellite-cell-mediated repair after injury [1].

Thyroid disorders

Figure 4 · Too little versus too much

Comparison of features of hypothyroidism and hyperthyroidism A comparison table. Hypothyroidism causes tiredness, cold intolerance, slow pulse, weight gain, muscle aches with slow reflex relaxation, carpal tunnel syndrome and dry skin. Hyperthyroidism causes restlessness, heat intolerance, fast pulse or atrial fibrillation, weight loss, proximal weakness and tremor, bone loss and warm moist skin. HypothyroidismHyperthyroidismEnergytired, slowrestless, anxiousHeatfeels coldheat intolerance, sweatingHeartslow pulsefast pulse, atrial fibrillationWeightgainlossMuscleaches, cramps, slow reflex relaxationproximal weakness, wasting, tremorNerves and jointscarpal tunnel syndromebone loss over timeSkin and hairdry, coarsewarm, moist
Musculoskeletal signs are common. Both states can cause muscle weakness; thyroid tests belong in the work-up of unexplained myopathy.
DisorderCommon causes
HypothyroidismAutoimmune (Hashimoto) thyroiditis, iodine deficiency, after thyroid surgery or radioiodine, some drugs
HyperthyroidismGraves disease, toxic nodules, thyroiditis, excess thyroid tablets

Red flags

Hyperthyroidism with a fast irregular pulse, breathlessness or chest pain needs medical review before exercise. In hypothyroidism, very slow pulse, confusion or marked swelling can signal severe disease.

Mild thyroid failure in older adults

Subclinical hypothyroidism, with raised TSH but normal T4, is common in older people. It is tempting to treat it as a cause of tiredness. Stott and colleagues tested levothyroxine in 737 adults aged 65 or over [2].

Figure 5 · Treating mild thyroid failure in older adults

Effects of levothyroxine in older adults with subclinical hypothyroidism Three results. Levothyroxine lowered TSH to 3.63 versus 5.48 with placebo, but hypothyroid symptom scores changed by 0.2 in both groups and tiredness scores by 3.8 versus 3.2, with no difference. TSH after 1 year3.63 vs 5.48 mIU/LHypothyroid symptom score change0.2 vs 0.2 (no difference)Tiredness score change3.8 vs 3.2 (no difference)Levothyroxine versus placebo; 737 adults aged 65 or over with subclinical hypothyroidism [2]
Normalising a blood test did not improve how people felt. In older adults with subclinical hypothyroidism, tiredness needs another explanation, and deconditioning is a common one [2].

Levothyroxine lowered TSH, but after a year hypothyroid symptoms and tiredness were no better than with placebo [2]. For physiotherapists, this means tiredness in such patients needs a broader explanation, and deconditioning is often a treatable part of it.

Practical skill · exercise and thyroid disease

Ask about thyroid diagnosis and treatment. In treated hypothyroidism, exercise as usual; expect slower progress until levels are stable. In untreated hyperthyroidism, defer vigorous exercise, monitor heart rate and rhythm, and protect bone with gradual loading once controlled.

Clinical relevance for the physiotherapist

  • Unexplained weakness or cramps. Thyroid tests are part of the medical work-up.
  • Carpal tunnel syndrome. Consider hypothyroidism, especially if bilateral.
  • Older adults with tiredness. Thyroid tablets did not help in subclinical disease [2]; address activity and strength.
  • Hyperthyroidism. Watch for atrial fibrillation and bone loss.
  • Muscle repair. Local thyroid signalling supports regeneration [1].

Assessment and application

SituationInterpretationAction
Weight loss, tremor, pulse 130 irregularPossible hyperthyroidism with AFDefer exercise; urgent medical review
Bilateral carpal tunnel, weight gain, cold intolerancePossible hypothyroidismSuggest GP thyroid tests
Older adult, TSH 6.5, tired and inactiveSubclinical; thyroxine unlikely to help [2]Graded activity and strength programme
Slow ankle reflex relaxationClassic hypothyroid signReport alongside other features

Common mistakes

  • Assuming any tiredness with a slightly raised TSH is thyroid-related [2].
  • Exercising a patient with untreated hyperthyroidism and AF.
  • Forgetting that TSH moves opposite to T4 in primary disease.
  • Thinking blood T3 alone controls muscle thyroid signalling [1].
  • Missing thyroid disease as a cause of myopathy.

Exam preparation

Long answer

Describe the synthesis, regulation and actions of thyroid hormones.

  • Iodine trapping, thyroglobulin, T4 and T3.
  • Hypothalamic–pituitary–thyroid axis (Figure 1).
  • Actions on body systems (Figure 2).
  • Peripheral conversion and deiodinases [1] (Figure 3).
  • Hypo- and hyperthyroidism (Figure 4).

Short notes

  • TSH.
  • Thyroid hormone and muscle [1].
  • Hypothyroidism.
  • Subclinical hypothyroidism in older adults [2].

Viva and practical

  • “Which is more active, T3 or T4?” — T3.
  • “What does high TSH with low T4 mean?” — primary hypothyroidism.
  • “Does thyroxine help tired older adults with mildly high TSH?” — not in TRUST [2].
  • OSCE: examine for signs of thyroid disease.

Current evidence

Exam and traditional teaching

Thyroid hormone action depends on blood levels; any raised TSH should be treated.

What the evidence adds

Muscle regulates its own T3 through deiodinases [1].

Treating subclinical hypothyroidism in older adults did not improve symptoms or tiredness [2].

What the student should understand

Thyroid hormone sets the body’s pace, but not every tired patient with a high TSH needs tablets. Many need activity.

Check yourself

10 questions on this page. Tap one to see the answer and the reasoning.

Q1. Which enzyme in skeletal muscle converts T4 into active T3?
  1. (A) DIO3
  2. (B) DIO2
  3. (C) Carbonic anhydrase
  4. (D) Lipase

Answer: (B) DIO2 generates active T3 from T4 [1].

Q2. DIO3 in muscle:
  1. (A) Activates T4
  2. (B) Inactivates T3
  3. (C) Makes TSH
  4. (D) Stores iodine

Answer: (B) DIO3 inactivates T3 by removing an inner-ring iodine [1].

Q3. Local control of T3 in muscle is important for:
  1. (A) Bile secretion
  2. (B) Myogenesis and satellite-cell-mediated repair
  3. (C) Urine concentration
  4. (D) Blood clotting

Answer: (B) Deiodinase control is crucial during myogenesis and repair [1].

Q4. The TRUST trial studied levothyroxine in:
  1. (A) Children with goitre
  2. (B) Adults aged 65 or over with subclinical hypothyroidism
  3. (C) Pregnant women
  4. (D) Athletes

Answer: (B) 737 adults aged 65 or over with persisting subclinical hypothyroidism [2].

Q5. After one year, levothyroxine compared with placebo:
  1. (A) Improved symptoms greatly
  2. (B) Lowered TSH but did not improve symptoms or tiredness
  3. (C) Raised TSH
  4. (D) Caused many fractures

Answer: (B) TSH fell, but symptom and tiredness scores did not differ [2].

Q6. The minimum clinically important difference for the TRUST symptom scores was:
  1. (A) 1 point
  2. (B) 9 points
  3. (C) 50 points
  4. (D) 100 points

Answer: (B) A 9-point difference was considered clinically important [2].

Q7. Mean TSH at 1 year in the levothyroxine group was about:
  1. (A) 0.1 mIU/L
  2. (B) 3.63 mIU/L
  3. (C) 6.40 mIU/L
  4. (D) 19.99 mIU/L

Answer: (B) TSH fell to 3.63 mIU/L, versus 5.48 with placebo [2].

Q8. A practical lesson for physiotherapists from TRUST is that tiredness in older adults with mildly raised TSH:
  1. (A) Is always due to the thyroid
  2. (B) Often needs other explanations, such as deconditioning
  3. (C) Cannot be treated
  4. (D) Requires bed rest

Answer: (B) Treating the thyroid did not improve tiredness [2].

Q9. Thyroid hormone signalling in muscle regulates:
  1. (A) Only growth in childhood
  2. (B) Energy expenditure, development and homeostasis
  3. (C) Only bone
  4. (D) Nothing important

Answer: (B) Muscle is a major target of thyroid signalling affecting energy expenditure and homeostasis [1].

Q10. The deiodinase enzymes act as:
  1. (A) A cell-autonomous, pre-receptor control of T3
  2. (B) A kidney filter
  3. (C) A pituitary hormone
  4. (D) A blood buffer

Answer: (A) They provide pre-receptor control of intracellular T3 [1].

Quick review

Key takeaways

  • Thyroid makes mostly T4; tissues convert it to active T3.
  • TRH → TSH → T4/T3 with negative feedback.
  • High TSH + low T4 = primary hypothyroidism.
  • Muscle sets its own T3 via DIO2 and DIO3 [1].
  • Hypo: slow, cold, cramps; hyper: fast, hot, weak, tremor.
  • Levothyroxine did not ease tiredness in subclinical disease in older adults [2].

Further reading

SourceWhy it earns its place
Salvatore D et al. — Nat Rev Endocrinol, 2014Thyroid hormone in muscle [1]
Stott DJ et al. — NEJM, 2017The TRUST trial [2]
Greenspan’s Basic and Clinical EndocrinologyThyroid physiology

References

  1. Salvatore D, Simonides WS, Dentice M, Zavacki AM, Larsen PR. Thyroid hormones and skeletal muscle — new insights and potential implications. Nature Reviews Endocrinology. 2014;10(4):206–214. doi:10.1038/nrendo.2013.238 PMID 24322650 Review
  2. Stott DJ, Rodondi N, Kearney PM, et al. Thyroid hormone therapy for older adults with subclinical hypothyroidism. New England Journal of Medicine. 2017;376(26):2534–2544. doi:10.1056/NEJMoa1603825 PMID 28402245 Randomised controlled trial

Related topics

Reviewed by the Physiotherapist India Team. · Human Physiology contents