Hypothyroidism

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Hypothyroidism Main page
Patient Information
Overview
Classification Primary hypothyroidism Hashimoto's thyroiditis Secondary hypothyroidism Tertiary hypothyroidism
Differentiating different causes of hypothyroidism
Screening
Diagnosis
History and symptoms

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2] Omar Elshafei, MD[3]

Synonyms and keywords:Primary hypothyroidism; Secondary hypothyroidism; Tertiary hypothyroidism; Central hypothyroidism; Overt hypothyroidism; Subclinical hypothyroidism; Myxedema; Decrease thyroid hormone; Hypo-functioning thyroid

Overview

Thyroxine (T4) and triiodothyronine (T3) are produced by the thyroid gland under the control of pituitary thyrotropin. Thyroid hormones regulate almost every organ system, and their deficiency reduces energy metabolism and basal metabolic rate, producing cold intolerance, a lower basal body temperature, and slowing of cardiac, gastrointestinal, and neuromuscular function. Iodine deficiency remains the leading cause of hypothyroidism worldwide, whereas in iodine-replete populations the dominant cause is chronic autoimmune thyroiditis (Hashimoto's thyroiditis), which is several times more common in women than in men and becomes more prevalent with age. Other frequent causes include thyroidectomy, radioiodine therapy, external neck radiation therapy, and drugs such as amiodarone, lithium, interferon, tyrosine kinase inhibitors, and immune checkpoint inhibitors.

Hypothyroidism is classified by the level of the hypothalamic-pituitary-thyroid axis at which the defect lies. Primary hypothyroidism arises within the thyroid gland itself and is characterised biochemically by a raised TSH; central hypothyroidism arises from pituitary or hypothalamic disease and is characterised by a low or inappropriately normal TSH with a low free T4. A further distinction is made between overt disease, in which the free T4 is below the reference interval, and subclinical hypothyroidism, in which the TSH is raised while the free T4 remains normal.

The clinical picture depends far more on the magnitude and the speed of onset of the hormone deficiency than on its cause. Classic features such as fatigue, weight gain, constipation, dry skin, hoarseness, and slowed cognition are common in the general population and perform poorly as diagnostic discriminators, so hypothyroidism is diagnosed biochemically rather than clinically. Central hypothyroidism may be masked by coexisting hypogonadism and adrenal insufficiency, and severe untreated disease can progress to myxedema coma, a rare emergency with hypothermia, bradycardia, hypoventilation, and depressed consciousness. Untreated overt hypothyroidism is also associated with hyperlipidemia, pericardial effusion, heart failure, and infertility. Subclinical hypothyroidism is usually asymptomatic; it may progress to overt disease, but it frequently reverts spontaneously, and randomised evidence has not shown that treating it improves symptoms or quality of life in most adults. Levothyroxine monotherapy remains the treatment of choice, with the dose individualised for body weight, age, cardiac status, and pregnancy.

Classification

Hypothyroidism is classified according to the anatomical level of the defect within the hypothalamic-pituitary-thyroid axis, and within each level by whether the cause is endogenous or exogenous. Transient forms, which recover spontaneously, are separated from permanent forms because they usually require observation rather than lifelong replacement.

Classification		Origin of the defect			Causes
					Endogenous causes	Exogenous causes
		Thyroid	Pituitary	Hypothalamus		Surgery or radiation	Other causes
Primary hypothyroidism		+	-	-	Autoimmune (Hashimoto's) thyroiditis — commonest cause where iodine intake is adequate Congenital hypothyroidism (thyroid dysgenesis, ectopia, agenesis, or dyshormonogenesis) Resistance to TSH (TSH receptor loss-of-function variants) Infiltrative disease: amyloidosis, hemochromatosis, sarcoidosis, Riedel's thyroiditis	After hyperthyroidism or thyroid cancer treatment: Thyroidectomy Radioiodine therapy Radiation for non-thyroid-related head and neck malignancies including lymphoma	Iodine deficiency (and, less often, iodine excess) Drug-induced hypothyroidism or thyroiditis Amiodarone Lithium Thionamides Interferon Immune checkpoint inhibitors Tyrosine kinase inhibitors (sunitinib) Rifampicin Thalidomide Acute infectious (suppurative) thyroiditis Trauma-induced
Transient hypothyroidism		+	-	-	Subacute (de Quervain's) thyroiditis Postpartum thyroiditis Painless (silent) thyroiditis Checkpoint-inhibitor thyroiditis (may recover or become permanent)	Following radioiodine therapy or hemithyroidectomy, before recovery or progression to permanent disease	Withdrawal of exogenous thyroid hormones Iodine load from iodinated contrast media
Central Hypothyroidism	Secondary OR Pituitary originated	-	+	-	Pituitary mass lesions, especially pituitary adenomas Brain cysts and abscesses Meningiomas Dysgerminomas Metastatic tumors Craniopharyngiomas Pituitary apoplexy Sheehan syndrome (postpartum pituitary necrosis) Idiopathic isolated TSH deficiency and congenital combined pituitary hormone deficiency Lymphocytic or granulomatous hypophysitis, including checkpoint-inhibitor hypophysitis	Surgery of pituitary adenomas Radiation therapy to: Pituitary adenomas Other mass lesions near the pituitary gland	Head trauma with injury to the stalk Drugs suppressing thyrotropin secretion (dopamine, high-dose glucocorticoids, bexarotene)
	Tertiary OR Hypothalamus originated	-	-	+	Hemochromatosis Histiocytosis Developmental abnormalities Internal carotid aneurysms Other central nervous system (CNS) tumors Idiopathic isolated TRH deficiency	Radiation in high doses to: Brain Infratemporal Nasopharyngeal Oropharyngeal	Infections Tuberculosis Syphilis Toxoplasmosis Sarcoidosis

Differentiating different causes of hypothyroidism

The causes of hypothyroidism are separated on the basis of the history, the presence of neck pain or goiter, the pattern of thyroid function tests, and thyroid autoantibody status. Routine TRH stimulation testing is no longer recommended for this purpose, since it does not reliably separate pituitary from hypothalamic disease and the reagent is unavailable in many countries; anatomical imaging and assessment of the remaining pituitary axes are used instead.

Cause		History and clinical findings			Laboratory findings				Distinguishing features and confirmatory tests
		Fever	Goiter	Neck pain	TSH	Free T4	T3	TPOAb
Primary hypothyroidism	Autoimmune (Hashimoto's) thyroiditis	-	+/- Diffuse and firm, or atrophic	-	↑	↓	N/↓	↑	Commonest cause where iodine intake is adequate Frequently accompanied by other autoimmune diseases (type 1 diabetes mellitus, celiac disease, vitiligo, pernicious anemia) Heterogeneous hypoechoic pattern if ultrasound is performed; imaging is not required for diagnosis
	Destructive thyroiditis (subacute, painless, postpartum)	+/- Subacute form only	+/-	+ Subacute form only	↓ then ↑	↑ then ↓	↑ then N/↓	N/↑	Biphasic course: an initial thyrotoxic phase from hormone release is followed by a hypothyroid phase and usually by recovery Raised erythrocyte sedimentation rate and C-reactive protein in the subacute form Low radioiodine uptake distinguishes it from Graves' disease
	Post-ablative and drug-induced	-	- Or surgically absent	-	↑	N/↓	N/↓	N/↑	History of thyroidectomy, radioiodine therapy, or neck radiation therapy Drug history: amiodarone, lithium, interferon, tyrosine kinase inhibitors, immune checkpoint inhibitors Amiodarone-induced hypothyroidism does not require withdrawal of the drug
	Iodine deficiency	-	+ Often multinodular	-	↑	N/↓	N/↑	Normal	Endemic geographical distribution; leading cause worldwide Low median population urinary iodine concentration; there is no validated biomarker of individual long-term iodine status
Subclinical hypothyroidism		-	+/-	-	↑	Normal	Normal	N/↑	Usually asymptomatic and detected incidentally A large proportion of mildly raised TSH values normalise on repeat testing, so persistence must be confirmed 2–3 months apart before the label is applied
Central hypothyroidism	Secondary (pituitary)	-	-	-	↓ or inappropriately normal	↓	N/↓	Normal	Signs of other pituitary hormone deficiencies and of a sellar mass (headache, visual field defects) Magnetic resonance imaging of the sella; computed tomography when MRI is contraindicated Adrenal insufficiency must be excluded before levothyroxine is started
	Tertiary (hypothalamic)	-	-	-				Normal	Biochemically indistinguishable from secondary disease; separated by the site of the lesion on magnetic resonance imaging Suggested by prior cranial radiation therapy, head trauma, or infiltrative disease of the hypothalamus
Resistance to TSH		-	- Gland normal or hypoplastic	-	↑	N/↓	N/↓	Normal	Rare; usually detected on newborn screening or as familial unexplained raised TSH with negative antibodies Confirmed by genetic testing of the TSH receptor gene

Screening

• The U.S. Preventive Services Task Force concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening for thyroid dysfunction in nonpregnant, asymptomatic adults (I statement). This is a statement of uncertainty rather than a recommendation against testing, and it does not apply to patients with symptoms, a history of thyroid disease, or a recognised risk factor.
• Targeted case finding with a serum TSH is instead recommended for patients at increased risk, including those with type 1 diabetes mellitus or another autoimmune disease, a first-degree relative with autoimmune thyroid disease, prior neck radiation therapy, thyroidectomy or radioiodine therapy, Down syndrome or Turner syndrome, an abnormal thyroid examination, hyperlipidemia, or treatment with a drug known to affect thyroid function.
• The American Thyroid Association 2026 guidelines do not recommend universal thyroid function screening in women planning pregnancy, in pregnant women, or postpartum, and align with the U.S. Preventive Services Task Force on this point. Instead, TSH testing is offered upon a positive pregnancy test to women with a risk factor for gestational thyroid dysfunction, and all newly pregnant women should undergo clinical evaluation and risk-factor assessment. The American College of Obstetricians and Gynecologists likewise recommends testing only those pregnant individuals with a personal or family history of thyroid disease, type 1 diabetes mellitus, or symptoms suggestive of thyroid disease.
• Risk factors that constitute an indication for thyroid function testing in pregnancy, and the suggested testing frequency, are summarised below.

Risk factor	Suggested TSH testing frequency
History of subclinical or overt hypothyroidism or hyperthyroidism, including postpartum thyroiditis	At presentation of pregnancy
Known thyroid antibody positivity	Every 4–6 weeks up to mid-pregnancy
Symptoms of thyroid dysfunction or goiter	At presentation of pregnancy
Concurrent use of a medication associated with thyroid dysfunction (amiodarone, lithium, rifampicin, ethionamide, phenobarbital, phenytoin, carbamazepine, recent cancer immunotherapy, iodinated contrast)	At presentation of pregnancy and every trimester
Personal history of autoimmune disease (type 1 diabetes mellitus, pernicious anemia, celiac disease, Addison's disease, vitiligo, premature ovarian failure, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus)	At presentation of pregnancy
Two or more miscarriages, or infertility	At presentation of pregnancy, if not already performed preconception
Down syndrome or Turner syndrome	At presentation of pregnancy
Prior thyroidectomy, or treatment with ionizing radiation to the head and neck or with radioiodine	At presentation of pregnancy and every trimester
Family history of autoimmune thyroid disease	At presentation of pregnancy
Residence in an area of severe iodine insufficiency without iodine-containing supplements or iodized salt	At presentation of pregnancy and every 4–6 weeks up to mid-pregnancy

• Universal newborn screening for congenital hypothyroidism is recommended, because detection and immediate levothyroxine treatment before clinical signs appear prevent the irreversible neurodevelopmental consequences of untreated disease. When resources allow, measurement of total or free T4 should be added to TSH so that central congenital hypothyroidism is not missed.
• In a worldwide view of strategies, screening for cretinism is carried out in many countries including the United States. Screening detects approximately 2000 affected newborns annually in the United States and 12,000 worldwide.
• Neonatal screening may be performed by any of the following laboratory strategies, each with different sensitivity for primary and central disease:
  • Measuring the level of thyroxine hormone (T4)
  • Blood TSH assay
  • Both thyroxine and TSH levels
  • A repeat (second-tier) specimen in preterm, low-birthweight, acutely ill, and same-sex twin neonates, in whom a delayed TSH rise may be missed on the first sample

Diagnosis

Hypothyroidism is a biochemical diagnosis. Serum TSH is the first-line test whenever pituitary and hypothalamic function are intact, because the log-linear relationship between TSH and free T4 makes TSH the more sensitive marker of small changes in thyroid hormone availability. Free T4 is added when the TSH is abnormal, and it must be measured together with TSH from the outset whenever central hypothyroidism is suspected, since an isolated TSH will be falsely reassuring. Clinical scoring systems, ankle reflex relaxation time, serum cholesterol, and muscle enzymes should not be used to diagnose hypothyroidism. Serum T3 has no role in the diagnosis of hypothyroidism.

Several caveats apply to interpretation:

• A single mildly raised TSH should be repeated after 2–3 months before hypothyroidism is diagnosed, because a large proportion of such values normalise spontaneously; in the TRUST screening population more than 60% of screened individuals normalised without treatment.
• The upper reference limit of TSH rises with age, so applying a single fixed cut-off across all age groups over-diagnoses hypothyroidism in older people.
• Intra-individual variation in thyroid function tests is smaller than between-individual variation, so the same assay should be used for serial monitoring in a given patient.
• Assay interference should be considered when results are discordant with the clinical picture: high-dose biotin supplements, heterophile and anti-streptavidin antibodies, and macro-TSH can all produce misleading values.
• Thyroid function tests should not be interpreted during acute non-thyroidal illness, when a low T3, low T4, and low or normal TSH pattern may mimic central hypothyroidism.
• The primacy of TSH over free T4 as the index of tissue thyroid status has been questioned; a systematic review and meta-analysis reported that clinical parameters correlate more closely with thyroid hormone levels than with TSH levels, and the optimal test remains a matter of debate.

Once hypothyroidism is confirmed, thyroid peroxidase antibody is measured to establish an autoimmune cause and to estimate the risk of progression; thyroid ultrasound is not required for the diagnosis and, when performed without an indication, risks detecting incidental nodules.

Symptoms, signs, or a recognised risk factor for hypothyroidism

Measure serum TSH Add free T4 if the TSH is abnormal, and from the outset when pituitary disease is suspected

TSH high Free T4 low

TSH high Free T4 normal

TSH normal

TSH low or inappropriately normal Free T4 low

Overt primary hypothyroidism Check thyroid peroxidase antibody; review drugs, thyroidectomy, radioiodine and neck radiation therapy

Subclinical hypothyroidism Repeat TSH and free T4 after 2–3 months to confirm persistence

Primary hypothyroidism excluded Seek an alternative explanation

Central hypothyroidism MRI of the hypothalamus and pituitary; exclude adrenal insufficiency before levothyroxine

History and symptoms

The common symptoms and signs of clinical hypothyroidism are listed in the table below. Their appearance depends on the degree and duration of hormone deficiency, and individual symptoms are neither sensitive nor specific enough to establish or exclude the diagnosis without biochemical confirmation.

Symptoms	Constitutional	HEENT	Neuromuscular and psychiatric	Other findings
More common	Fatigue Cold intolerance Decreased sweating Hypothermia Coarse skin Weight gain	Hoarseness Goiter Fullness in the throat and neck	Depression Emotional lability Attention deficit Impaired memory	Macroglossia Obstructive sleep apnea Paresthesia Nerve entrapment syndromes (carpal tunnel syndrome) Constipation Bradycardia and delayed relaxation phase of the deep tendon reflexes Blurred vision (central hypothyroidism)
Less common	Puffiness Hair loss Fever If accompanied by thyroiditis	Sore throat Periorbital edema	Slowed speech and movements Ataxia Myopathy with raised creatine kinase	Pituitary hyperplasia followed by hyperprolactinemia Myxedema coma (with non-pitting edema) Cardiomegaly Pericardial effusion and low-voltage complexes on the electrocardiogram Ascites Hyperlipidemia Galactorrhea Infertility Hyponatremia

Subclinical hypothyroidism has been associated in large pooled cohort analyses with a modestly increased risk of coronary heart disease events, including myocardial infarction, and of heart failure events, particularly when the TSH is 10 mIU/L or above; these associations are graded and have not been shown by randomised trials to be reversible with levothyroxine.

Differentiating hypothyroidism from other diseases

Central hypothyroidism shares its presentation with the other causes of hypopituitarism, and primary hypothyroidism is distinguished from all of them by an elevated TSH with otherwise normal anterior pituitary hormones.

Disease	Onset	Manifestations					Diagnosis
		History and symptoms				Physical examination	Laboratory findings	Confirmatory test	Imaging	Other investigations
		Traumatic delivery	Lactation failure	Menstrual irregularity	Other features
Sheehan's syndrome	Acute	++	++	Oligo/amenorrhea	Symptoms of: Adrenal insufficiency Hypothyroidism	Breast tissue atrophy Decreased axillary and pubic hair growth	Pancytopenia Eosinophilia Hyponatremia Low fasting plasma glucose Decreased levels of anterior pituitary hormones in blood	Clinical diagnosis supported by combined anterior pituitary hormone assessment Low baseline prolactin with a blunted stimulated response is among the more sensitive findings	CT/MRI: Sequential pituitary enlargement followed by Shrinkage and necrosis leading to decreased sellar volume or empty sella	Dynamic pituitary testing where an equivocal basal profile requires clarification
Lymphocytic hypophysitis	Acute	+/-	+	Oligo/amenorrhea	Associated with autoimmune conditions, and with immune checkpoint inhibitor therapy Generalized headache Retro-orbital or bitemporal pain Mass lesion effects such as visual field defects	DI Autoimmune thyroiditis	Decreased pituitary hormones (Gonadotropins most commonly, and ACTH with checkpoint inhibitors) Hyperprolactinemia (40%) GH excess	Pituitary biopsy: lymphocytic infiltration	CT and MRI: features of a pituitary mass Diffuse and homogeneous contrast enhancement	Assays for: Anti-TPO Anti-Tg Ab
Pituitary apoplexy	Acute	+/-	++	Oligo/amenorrhea	Severe headache Nausea and vomiting Paralysis of eye muscles (diplopia) Changes in vision	Visual acuity defects CN palsies (nerves III, IV, V and VI)	Decreased levels of anterior pituitary hormones in blood	MRI	CT without contrast: haemorrhage appears as a hyperdense lesion MRI if CT is inconclusive	Blood tests may be done to check: PT/INR and aPTT Pituitary hormonal assay
Empty sella syndrome	Chronic	-	+	Oligo/amenorrhea	Erectile dysfunction Headache Low libido	Signs of raised intracranial pressure may be present Nipple discharge	Decreased levels of pituitary hormones in blood	MRI	Empty sella containing CSF	Dynamic pituitary hormone stimulation testing
Simmonds' disease/Pituitary cachexia	Chronic	+/-	+	Oligo/amenorrhea	Cachexia Premature aging	Progressive emaciation Loss of body hair	Decreased levels of anterior pituitary hormones in blood	MRI	Performed to identify the underlying pituitary lesion	Dynamic pituitary hormone stimulation testing
Primary hypothyroidism	Chronic	+/-	-	Oligomenorrhea/menorrhagia	Cold intolerance Constipation	Dry skin Bradycardia Hair loss Myxedema Delayed relaxation phase of the deep tendon reflexes	Elevated TSH with low free T4 (overt) or normal free T4 (subclinical) The remaining anterior pituitary hormones are normal, which is the key discriminator from hypopituitarism	Serum TSH with free T4	Not required for diagnosis; performed only to exclude a pituitary cause when the TSH is low or inappropriately normal	Anti-TPO and anti-Tg antibody assays
Central hypothyroidism	Chronic	+/-	+/-	Oligo/amenorrhea	Milder and less specific than primary disease Features of the underlying sellar lesion	Signs of coexisting hypogonadism and adrenal insufficiency	Low free T4 with a low or inappropriately normal TSH Other pituitary axes commonly deficient	Free T4 interpreted together with TSH and the other pituitary axes	MRI of the hypothalamus and pituitary	Adrenal insufficiency must be excluded before levothyroxine is started
Hypogonadotropic hypogonadism	Chronic	-	-	Oligo/amenorrhea	Hot flushes Energy and mood changes Decreased libido	Breast tissue atrophy Decreased maturation of vaginal mucosa	Low estrogen or testosterone Low or inappropriately normal FSH and LH, in contrast to the raised gonadotropins of primary gonadal failure	Paired FSH, LH and sex steroid measurement	MRI to exclude a hypothalamic or pituitary cause	Genetic testing (karyotype) Measurement of total and free testosterone and 17-hydroxyprogesterone concentrations
Hypoprolactinemia	Chronic	-	+	-	Infertility Subfertility	Puerperal agalactogenesis	Low serum prolactin	Prolactin assay, ideally in the 3rd trimester or early postpartum	MRI to exclude a pituitary cause	LH, FSH Thyrotropin and free thyroxine
Panhypopituitarism	Chronic	-	+	Oligo/amenorrhea	Polyuria Polydipsia Features of hypothyroidism and hypoadrenalism	Growth failure Bitemporal hemianopsia Papilledema	All pituitary hormones decreased	MRI	MRI of the sella to identify the causative lesion	Left hand and wrist radiograph for bone age
Primary adrenal insufficiency/Addison's disease	Chronic	-	-	-	Hypoglycemia Hypotension	Dehydration Hyperpigmentation Loss of pubic and axillary hair	Hyponatremia with or without hyperkalemia Raised plasma renin activity with low aldosterone Raised ACTH with low morning cortisol	Cosyntropin (ACTH) stimulation test	Abdominal CT to define the adrenal cause	Anti-adrenal antibody testing
Menopause	Chronic	-	+/-	Oligo/amenorrhea	Hot flashes Insomnia Weight gain and bloating Mood changes	Vaginal atrophy Loss of pelvic muscle tone	↑ FSH ↓ Estradiol and inhibin	FSH greater than LH	Normal	Endometrial biopsy where bleeding is abnormal

Hypothyroidism must also be differentiated from other endocrine causes of hyponatremia, because normal thyroid and adrenal function is a prerequisite for diagnosing the syndrome of inappropriate antidiuretic hormone secretion.

Disease	Mechanism and causes	Clinical features	Diagnosis and management
SIADH	Excessive release of antidiuretic hormone from the posterior pituitary or an ectopic source, producing water retention, hyponatremia, and a clinically euvolaemic state	Nausea and vomiting Cramps Irritability and confusion Seizures, stupor or coma when severe or rapid in onset	Hyponatremia below 135 mmol/l Effective serum osmolality below 275 mosm/kg Urine sodium concentration above 40 mmol/l Low plasma uric acid with a raised fractional excretion of urate Absence of edematous states such as cardiac failure, liver cirrhosis and nephrotic syndrome Normal adrenal and thyroid function — hypothyroidism and adrenal insufficiency must be excluded before the diagnosis is made
Cerebral salt wasting syndrome	Renal sodium loss during intracranial disease, producing hyponatremia with contraction of the extracellular fluid volume. Causes include trauma, tumor and hematoma	Hypovolaemia Hyponatraemia	Distinguished from SIADH by clinical and biochemical evidence of volume depletion Treated with hydration and sodium replacement
Adrenal insufficiency	Primary disease affects both glucocorticoid and mineralocorticoid secretion; secondary and tertiary disease spare mineralocorticoid function because aldosterone is regulated separately. Common causes include autoimmune adrenalitis, adrenal hemorrhage, infection, cancer, and withdrawal of exogenous steroid therapy	Fatigue and muscle weakness Loss of appetite and weight loss Abdominal pain, diarrhea, vomiting Sparse axillary hair, hyperpigmentation and orthostatic hypotension in chronic primary disease Fever and hypotension in acute adrenal crisis	White blood cell count with moderate neutropenia, lymphocytosis and eosinophilia Hyperkalemia, hypoglycemia and hyponatremia Low morning plasma cortisol Definitive test is the cosyntropin or ACTH stimulation test Management is glucocorticoid with, in primary disease, mineralocorticoid and sodium chloride replacement; in adrenal crisis, fluids and hydrocortisone are given immediately after the cortisol sample is drawn
Hypopituitarism	Deficiency of one or more anterior pituitary hormones, from pituitary or sellar tumors, head trauma, infection, empty sella, infiltration, congenital defects, or idiopathic causes	Fatigue and weight loss Decreased libido and appetite Facial puffiness and anemia Infertility and cold intolerance Amenorrhoea and inability to lactate in postpartum women Decreased facial or body hair in men and short stature in children	History and physical examination including visual field testing, with basal hormone profiling and MRI Replacement of the deficient peripheral hormones: hydrocortisone, thyroxine, testosterone or oestradiol, and growth hormone where indicated Hydrocortisone must be started before thyroxine Lifelong monitoring of hormone levels and of symptoms of deficiency or excess is required
Hypothyroidism	Deficient thyroid hormone production or action, with the causes set out in the classification section above, including congenital, autoimmune, drug-induced, post-surgical, post-radiation and infiltrative aetiologies such as amyloidosis	Fatigue and constipation Dry skin, puffy face and hoarseness Weight gain and cold intolerance Muscle weakness and myopathy Raised blood cholesterol and bradycardia Depression and impaired memory	Diagnosis rests on serum TSH with free T4; signs and symptoms are neither sensitive nor specific TSH is the single most useful test for screening, diagnosis and treatment follow-up whenever the pituitary is normal Serum T3 has no diagnostic role The drug of choice for treatment is levothyroxine
Psychogenic polydipsia	Primary polydipsia with excessive water intake, from an adverse effect of a medication, traumatic brain injury, a psychiatric disorder such as schizophrenia, or a hypothalamic defect	Polyuria and polydipsia Confusion and lethargy Psychosis Seizures in severe dilutional hyponatremia	Evaluation requires exclusion of other causes of polyuria, hyponatremia and SIADH, including thyroid and adrenal disease The water deprivation test is the gold standard Management combines fluid restriction with behavioral and pharmacologic measures

Treatment

Initial Management

• Confirm that the biochemical abnormality is persistent before committing a patient to lifelong therapy. Overt hypothyroidism with a clearly low free T4 is treated without delay; an isolated, mildly raised TSH is repeated after 2–3 months.
• In suspected central hypothyroidism, exclude and treat coexisting adrenal insufficiency before starting levothyroxine, since thyroid hormone accelerates cortisol clearance and may precipitate an adrenal crisis.
• A levothyroxine dose of 1.6 µg/kg/d is considered the full thyroid hormone treatment dose for nonpregnant adults with primary hypothyroidism. However, to avoid overtreatment, lower doses (eg, 25-50 µg/d) are typically prescribed for older adults and patients with cardiovascular disease (eg, atrial fibrillation, coronary artery disease). Where there is established coronary artery disease or a prior myocardial infarction, the dose is escalated slowly and any deterioration in angina prompts a pause in titration.
• Administer levothyroxine on an empty stomach, 30–60 minutes before breakfast or at bedtime at least 3 hours after the last meal, and separate it from calcium and iron salts, proton pump inhibitors, bile acid sequestrants, sucralfate and soy products by at least 4 hours.
• Myxedema coma is an endocrine emergency managed in an intensive care setting. In a systematic survey of 698 published and unpublished cases reported between 2004 and 2024, the estimated incidence was 0.12 (95% CI, 0.10%–0.14%) per million per year, precipitating factors were identified in 77.6% (95% CI: 73.7%–81.5%) of patients, and the overall mortality rate was 38.8% (271/698, 95% CI: 34.9%–42.7%), with shock and multiple organ failure the commonest causes of death. Altered mental status was present in 88.9% (95% CI: 86.9%–90.9%) of confirmed cases, hypothermia in approximately 71.9% (95% CI: 68.0%–75.8%), and a heart rate below 60 bpm in 66.2% (95% CI: 62.3%–70.1%). Management is based on expert consensus rather than randomised evidence and comprises:
  • Airway protection and mechanical ventilation where hypoventilation, hypercapnia or depressed consciousness require it
  • Intravenous levothyroxine as a loading dose followed by daily maintenance, with the addition of intravenous liothyronine in the most severely affected patients, using lower doses in older patients and those with coronary artery disease or arrhythmia
  • Empirical stress-dose intravenous hydrocortisone until coexisting adrenal insufficiency has been excluded
  • Passive external rewarming, cautious correction of hyponatremia and hypoglycemia, and haemodynamic support
  • Identification and treatment of precipitants, most often infection, cold exposure, sedatives, and interruption of thyroid hormone replacement
  • Continuous cardiac monitoring, since bradycardia, low-voltage complexes, a prolonged QT interval and pericardial effusion may be evident on the electrocardiogram

Medical Therapy

• Levothyroxine monotherapy remains the standard of care for hypothyroidism; no consistently strong evidence supports the superiority of alternative preparations.
• Thyrotropin levels are typically checked 6 to 8 weeks after initiating therapy or after switching the dose or preparation, and annually after the thyrotropin level has normalized.
• Combination levothyroxine/liothyronine therapy has been examined in fourteen clinical trials, which have not shown a consistent benefit over levothyroxine alone. A joint American, British and European Thyroid Association consensus concluded that combination therapy may be considered, as an experimental approach and after shared decision making, only in patients who remain symptomatic despite a normal TSH on adequate levothyroxine and in whom other causes of the symptoms have been excluded.
• Desiccated thyroid extract and compounded thyroid hormone preparations are not recommended, and they should be switched to levothyroxine monotherapy before conception.
• Subclinical hypothyroidism. The TRUST randomised trial enrolled 737 adults aged at least 65 years with a persisting thyrotropin level of 4.60 to 19.99 mIU per liter and a normal free thyroxine; at a median dose of 50 μg, levothyroxine produced no difference in the mean 1-year change in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% CI, −2.0 to 2.1). A secondary analysis showed no benefit even in the subgroup with a high baseline symptom burden. A systematic review and meta-analysis of 21 randomised trials found no clinically relevant benefit of thyroid hormone therapy on quality of life or thyroid-related symptoms, and a BMJ Rapid Recommendation panel issued a strong recommendation against thyroid hormones for adults with subclinical hypothyroidism, explicitly excluding women trying to conceive, patients with a TSH above 20 mIU/L, those with severe symptoms, and young adults such as those aged 30 years or under. Treatment continues to be offered conventionally when the TSH is 10 mIU/L or above, and considered case by case in younger, symptomatic, antibody-positive or goitrous patients.
• Central hypothyroidism. Levothyroxine is first-line therapy, but TSH cannot be used to titrate it. The dose is adjusted against free T4, with a target in the upper part of the reference interval, and the sample should be taken before the daily dose.
• Persistently elevated TSH despite an apparently adequate dose should prompt assessment of adherence and of malabsorption from celiac disease, atrophic gastritis, Helicobacter pylori infection or bariatric surgery, and review of interacting drugs, before the dose is escalated further.

Raised TSH with a normal free T4, confirmed persistent on repeat testing 2–3 months apart

Pregnant, planning pregnancy or undergoing fertility treatment? If yes, follow the pregnancy pathway below. If no, stratify by TSH and age

TSH ≥10 mIU/L

TSH raised but <10 mIU/L Younger adult, symptomatic, TPOAb positive or goiter

TSH raised but <10 mIU/L Age about 65 years or older

Levothyroxine conventionally offered

Shared decision making; a time-limited trial with a predefined stopping rule is reasonable

Levothyroxine generally not offered; monitor and treat if overt disease develops

Procedural / Surgical Therapy

• There is no procedural or surgical treatment for hypothyroidism itself. Thyroidectomy, radioiodine therapy and neck radiation therapy are causes of hypothyroidism rather than treatments for it, and after any of them thyroid function must be monitored so that replacement is started when required.
• Surgery is directed at the structural or infective consequences of thyroid disease rather than at the hormone deficiency:
  • Thyroidectomy for a large goiter causing compressive symptoms, dysphagia or retrosternal extension, or where malignancy is suspected. Hypothyroidism persists or worsens after surgery and lifelong replacement is required.
  • Drainage and antibiotic therapy for acute suppurative thyroiditis, with computed tomography or ultrasound to define an abscess and to identify an underlying pyriform sinus fistula.
  • Decompressive surgery for Riedel's thyroiditis with airway or oesophageal compromise.
  • Pericardiocentesis for a haemodynamically significant pericardial effusion, which is otherwise managed by thyroid hormone replacement alone.
• Emergency thyroidectomy has a role in amiodarone-induced thyrotoxicosis with rapidly deteriorating cardiac status, but amiodarone-induced hypothyroidism does not require withdrawal of amiodarone and is treated with levothyroxine when overt, while subclinical forms may simply be followed.
• Malabsorptive procedures, including bariatric surgery, alter levothyroxine absorption; liquid or soft-gel formulations, or parenteral administration in the perioperative period, may be required, with dose reassessment after the operation.

Long-Term Management

• Once the thyrotropin level has normalized, it is checked annually. Serum thyrotropin level should also be checked after a weight change of 4.5 kg or greater, if the patient is experiencing new symptoms of hypothyroidism, or if a medication such as amiodarone is initiated that may affect thyroid function.
• Avoid overtreatment. A suppressed TSH on replacement is associated with atrial fibrillation, reduced bone mineral density and fracture, particularly in older adults, and confers no symptomatic advantage.
• Persistent symptoms despite a TSH within the reference interval should prompt a search for alternative explanations — anemia, celiac disease, obstructive sleep apnea, depression, vitamin D deficiency, other autoimmune disease — rather than automatic escalation of the dose or a switch to a non-levothyroxine preparation.
• Reinforce adherence and consistent timing of administration at each review, and re-check thyroid function 6–8 weeks after any change in brand, formulation or interacting medication.
• A consultation with an endocrinologist should be considered for patients with hypothyroidism if they:
  1. are pregnant or planning conception
  2. have a cardiovascular disease (eg, atrial fibrillation, coronary artery disease) or other endocrine disorders (eg, adrenal and pituitary disease, primary or secondary adrenal insufficiency)
  3. have medication-induced hypothyroidism
  4. have a history of thyroid cancer
  5. are being treated with levothyroxine but have difficulty maintaining a euthyroid state

Special Populations

Preconception and pregnancy

The American Thyroid Association 2026 guidelines supersede the 2017 recommendations and change the approach in several respects: thyroid peroxidase antibody status no longer guides the decision to treat subclinical hypothyroidism, the timing of diagnosis relative to the first trimester does, and repeat testing is emphasised before treatment is started because a substantial proportion of mild abnormalities resolve spontaneously.

• Where laboratory- and trimester-specific reference intervals are unavailable, a TSH reference interval of 0.1–4.0 mU/L can be used during the first and second trimesters; in centres where the non-pregnancy upper limit is well above 4.5 mU/L, 0.5 mU/L may be deducted from that upper limit instead.
• Recent data indicate that mild overt and subclinical hypothyroidism in pregnancy persist on retesting in fewer than half of untreated women, so confirmatory testing may be offered when the TSH is below 6 mU/L. New-onset overt hypothyroidism with a TSH equal to or above 6 mU/L, or that persists after retesting, should be treated with levothyroxine.
• Profound subclinical hypothyroidism with a TSH above 10 mU/L should be treated. For mild subclinical hypothyroidism diagnosed in the first trimester, levothyroxine may be considered after shared decision making; for mild subclinical hypothyroidism diagnosed after the first trimester, levothyroxine should not be offered and follow-up TSH testing can be performed after 4–6 weeks. This reflects randomised trials in which treatment started at a median of 12 weeks and 3 days, or on average at 17 weeks, did not improve obstetric outcomes or offspring IQ.
• For euthyroid women who are thyroid peroxidase or thyroglobulin antibody positive with infertility, levothyroxine treatment should not be offered, regardless of the TSH concentration or miscarriage history; TSH and free T4 may instead be rechecked every 3–6 months.
• For women taking levothyroxine, a TSH within the normal range but below 2.5 mU/L may be targeted preconception and during pregnancy. Newly diagnosed overt hypothyroidism in pregnancy may be dosed using full replacement of 1.5–1.7 mcg/kg/day plus an additional 20–30% for gestation.
• Most women on established levothyroxine require a dose increase of approximately 25% by week 12 and approximately 50% by week 20; the dose can therefore be raised by about 25% upon a positive pregnancy test, either by increasing the daily dose or by taking two extra daily doses per week. Overtreatment is more likely in women with a prepregnancy TSH below 1.5 mU/L, a prepregnancy dose above 100 mcg/day, or who use the two-extra-tablets-per-week approach.
• Serum thyrotropin level should be measured approximately every 4 weeks until midgestation and at least once near 30 weeks' gestation. At delivery the dose is returned to the prepregnancy dose and thyroid function is tested after 6 weeks.
• Liothyronine and desiccated thyroid extract should not be used in pregnancy, because the resulting relative excess of T3 and deficit of T4 may reduce thyroid hormone availability to the fetal brain. When switching, every 5 mcg of liothyronine may be considered equivalent to 20 mcg of levothyroxine, and every 60 mg grain of desiccated thyroid equivalent to 88 mcg of levothyroxine.
• Pregnant and lactating women should achieve a daily iodine intake of 250 mcg; 150 mcg/day of supplemental iodine is advised, ideally starting at least 3 months before conception, and sustained intake exceeding 500 mcg daily should be avoided.

Raised TSH identified in pregnancy Measure free T4 and thyroid peroxidase antibody

Interpret free T4 against a laboratory- and trimester-specific interval where available

Free T4 low Overt hypothyroidism

Free T4 normal Subclinical hypothyroidism

TSH <6 mU/L: confirmatory testing within 3 weeks may be offered TSH ≥6 mU/L or persisting on retesting: start levothyroxine

TSH >10 mU/L: start levothyroxine Mild, first trimester: may be considered after shared decision making Mild, after the first trimester: should not be offered; recheck TSH in 4–6 weeks

Older adults

• The upper reference limit of TSH rises with age, and randomised evidence in adults aged 65 years and over shows no symptomatic benefit from treating subclinical hypothyroidism. A higher treatment target for TSH is appropriate in the eighth decade, and lower starting doses of 25–50 µg/day are used to avoid precipitating angina or atrial fibrillation.

Cardiovascular disease

• Start at 25–50 µg/day and titrate slowly in patients with coronary artery disease, prior myocardial infarction, atrial fibrillation or heart failure. Some degree of residual biochemical hypothyroidism may be preferable to precipitating myocardial ischaemia; revascularisation may occasionally need to precede full replacement.

Neonates and children

• In congenital hypothyroidism, correctly dosed levothyroxine should be started immediately once the diagnosis is made, with frequent laboratory follow-up to keep thyroid hormone levels within target, timely reassessment of whether treatment must continue, attention to neurodevelopment and neurosensory function, and family education. A planned transition of care from paediatric to adult services is required for all affected individuals.

Central hypothyroidism

• Titrate against free T4 rather than TSH, targeting the upper part of the reference interval, and always after adrenal insufficiency has been excluded or treated.

Drug-induced disease

• Amiodarone-induced hypothyroidism does not require withdrawal of amiodarone; overt disease is treated with levothyroxine while subclinical forms may be followed without treatment.
• Lithium, interferon, tyrosine kinase inhibitors and immune checkpoint inhibitors all warrant baseline and periodic thyroid function monitoring; checkpoint-inhibitor thyroiditis is frequently biphasic and the resulting hypothyroidism is often permanent.

Hospitalised and critically ill patients

• Thyroid function testing should be avoided during acute non-thyroidal illness unless thyroid disease is strongly suspected, and treatment should not be initiated on the basis of the low T3 pattern alone.