Hypothyroidism is a condition in which the thyroid gland is underactive, resulting in a deficiency of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). In very rare cases, hormone production may be sufficient, but thyroid hormones may have insufficient peripheral effects. Hypothyroidism may be congenital or acquired. Congenital hypothyroidism is usually caused by thyroid dysplasia or aplasia. The etiology of acquired hypothyroidism is typically autoimmune (Hashimoto thyroiditis) or iatrogenic. The pathophysiology of hypothyroidism is characterized mainly by a reduction of the basal metabolic rate and generalized myxedema. Typical clinical features include fatigue, cold intolerance, dry skin, and constipation. More severe manifestations include myxedematous heart disease and myxedema coma, which may be fatal if left untreated. In adults, the diagnosis is established based on serum thyroid-stimulating hormone (TSH) and free T4 levels (FT4). Children with congenital hypothyroidism often have umbilical hernias and, without early treatment, can develop severe developmental delay. Accordingly, for hypothyroidism 24–48 hours after birth is required by law in most states. Therapy for both acquired and congenital hypothyroidism consists of lifelong treatment with levothyroxine and regular checkups to monitor disease activity.
Prevalence: more common in women
- Women: up to 12:1,000
- Men: up to 4:1,000 
Epidemiological data refers to the US, unless otherwise specified.
Primary hypothyroidism: insufficient thyroid hormone production
- Hashimoto thyroiditis
- Postpartum thyroiditis (subacute lymphocytic thyroiditis) 
- subacute granulomatous thyroiditis) (: often subsequent to a flu-like illness 
- Iatrogenic: e.g., post thyroidectomy, radioiodine therapy, antithyroid medication (e.g., amiodarone, lithium)
- Nutritional (insufficient intake of iodine): the most common cause of hypothyroidism worldwide, particularly in iodine-deficient regions
- Riedel thyroiditis: occurs in IgG4-related systemic disease
- Wolff-Chaikoff effect
- Thyroid dysplasia: a disorder of embryologic development characterized by abnormal development and/or location of thyroid tissue (e.g., lingual thyroid)
- Secondary hypothyroidism: pituitary disorders (e.g., pituitary adenoma) → TSH deficiency
- Tertiary hypothyroidism: hypothalamic disorders → TRH deficiency
|Overview of common causes of primary hypothyroidism|
|Hashimoto thyroiditis ||Postpartum thyroiditis ||Subacute granulomatous thyroiditis (De Quervain) ||Congenital hypothyroidism ||Riedel thyroiditis |
|Clinical course|| || || || |
|Goiter||Structure|| || || || || |
|Pain|| || || || || |
|Iodine uptake on scintigraphy|| || || || || |
|Pathology findings|| || || |
- Primary hypothyroidism: peripheral (thyroid) disorders → T3/T4 are not produced (↓ levels) → compensatory ↑ TSH
- Secondary hypothyroidism: pituitary disorders → ↓ TSH levels → ↓ T3/T4 levels
- Tertiary hypothyroidism: hypothalamic disorders → ↓ TRH levels → ↓ TSH levels → ↓ T3/T4 levels
Effects of hypothyroidism 
- Generalized decrease in the basal metabolic rate → decreased oxygen and substrate consumption, leading to:
- Decreased sympathetic activity leads to:
- Decreased transcription of sarcolemmal genes (e.g., calcium ATPases) → decreased cardiac output, myopathy
- Hyperprolactinemia: ↑ production is stimulated by TRH → suppression of LH, FSH, GnRH, and testosterone and stimulation of breast tissue growth
- Myxedema: due to accumulation of glycosaminoglycans and hyaluronic acid within the reticular layer of the dermis
Symptoms related to decreased metabolic rate
- Fatigue, decreased physical activity
- Cold intolerance
- Decreased sweating
- Hair loss (Queen Anne sign), brittle nails, and cold, dry skin
- Weight gain (despite poor appetite)
- Hypothyroid myopathy , myalgia, stiffness, cramps
- Woltman sign: a delayed relaxation of the deep tendon reflexes, which is commonly seen in patients with hypothyroidism, but may also be associated with advanced age, pregnancy, and diabetes mellitus.
- Entrapment syndromes (e.g., carpal tunnel syndrome)
- Symptoms related to generalized myxedema
- Symptoms of hyperprolactinemia
- Further symptoms
- Initial evaluation: thyroid function tests (TFTs)
- Further investigations: May be indicated to evaluate underlying etiology based on clinical suspicion (See also “.”)
Thyroid function tests 
- Free or total T3: may be measured alongside FT4, but they are not used for the diagnosis of hypothyroidism
|Overview of TFT findings in the evaluation of suspected hypothyroidism |
|Subclinical hypothyroidism||Mildly ↑||Normal||Normal|
|Overt hypothyroidism||Primary hypothyroidism|| |
Normal or ↓
|Secondary and tertiary hypothyroidism|| |
|Low T3 syndrome||Normal||Normal||↓ Free T3 and ↑ reverse T3|
|Low T3 low T4 syndrome||↓||↓|
Avoid routine TSH screening in acutely ill patients unless a thyroid disturbance is the suspected cause (e.g., myxedema coma), since other non-thyroid illnesses can interfere with serum TSH and results may be unreliable. 
Serum thyroid antibody testing can confirm suspected autoimmune thyroid disease. Additionally, thyroid peroxidase antibody measurements may also be considered in patients with subclinical hypothyroidism or recurring miscarriages.
- Thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb): detectable in the majority of patients with autoimmune hypothyroidism
- TSH receptor antibodies (TRAbs): detectable in up to 20% of cases of autoimmune hypothyroidism 
Associated laboratory findings 
Other routine blood tests are not required for the diagnosis but may show characteristic changes.
- CBC: mild anemia
- BMP: hyponatremia (in acute hypothyroidism) , hypoglycemia (rare) 
- Lipid profile: hypercholesterolemia (increased LDL), hyperlipidemia
- Creatine kinase: increased in hypothyroid myopathy 
Imaging has no role in the primary evaluation of hypothyroidism but may be indicated if structural abnormalities are present or suspected.
Nonthyroidal illness syndrome (NTIS) 
Pathophysiology: multifactorial and not fully understood 
- Thyroid gland function typically remains normal.
- Cytokines (e.g., interleukin 6) are thought to cause various changes in levels of circulating TSH and thyroid hormones.
- Altered deiodinase enzyme activity leads to:
- Various factors, e.g., protein loss due to nephrotic syndrome, may also lead to decreased levels of thyroid-binding globulin.
- Signs and symptoms of the underlying illness
- Typically no classic symptoms of hyper- or hypothyroidism
- NTIS is typically diagnosed incidentally following TFT screening done in critically ill patients to rule out thyrotoxicosis or hypothyroidism as the underlying cause, e.g., patients with unexplained tachyarrhythmias or heart failure, suspected myxedema coma, or a strong family history of thyroid disease.
- TSH is typically normal in both low T3 syndrome and low T3 low T4 syndrome.
- Rarely, TSH may also be slightly low, but not enough to explain the low FT3 and/or FT4.
- Consult endocrinology as the interpretation of TFTs in critically ill patients is complex and can be misleading.
- Continued treatment of underlying illness
- Thyroid hormone replacement is usually not recommended. 
Other differential diagnoses 
The following conditions can mimic one or more manifestations of hypothyroidism:
- central hypothyroidism) (can also be a cause of
- and other causes of
- Other causes of
- and other systemic infections
The differential diagnoses listed here are not exhaustive.
General principles 
Hypothyroidism is treated with lifelong hormone substitution.
Levothyroxine: synthetic form of T4
- First-line choice for the treatment of hypothyroidism
- Peripherally converted to T3 (biologically active metabolite) and rT3 (biologically inactive metabolite)
- Liothyronine; : synthetic form of T3
- Levothyroxine: synthetic form of T4
- Starting dose and monitoring requirements vary depending on factors such as age and comorbidities.
- Reassess treatment response regularly to avoid under- and overtreatment.
Indications for treatment 
- Overt hypothyroidism: Initiate treatment.
- Subclinical hypothyroidism: Treat select cases. 
Ensure follow-up is in place for patients with subclinical hypothyroidism if treatment is not initiated.
Levothyroxine replacement 
- In primary hypothyroidism, levothyroxine is gradually titrated according to serial TSH measurements targeting a normal level, for example:
- In secondary hypothyroidism, dosage is titrated according to FT4 levels.
|Dosage and administration of levothyroxine|
|Monitoring and dose adjustments|| |
Dosing in consultation with endocrinology is recommended for: 
In patients with hypothyroidism who are pregnant, the levothyroxine dose must be increased in line with increased demand. Hypothyroidism adversely affects the development of the fetal nervous system. 
Long-term therapy considerations 
- Side effects: Overtreatment can lead to symptoms of thyrotoxicosis.
- Drugs that reduce levothyroxine absorption include PPIs, calcium salts, ferrous sulfate, and bile acid sequestrants.
- Treatment with estrogens may necessitate a dose increase.
- Treatment with androgens may necessitate a dose reduction.
- Glucocorticoids interfere with thyroid hormone metabolism and the dose of levothyroxine may need to be reduced.
- Reasons for treatment failure
Some individuals may misuse synthetic thyroid hormones for weight loss. 
Myxedema coma 
- Definition: : extremely rare, potentially life-threatening decompensation of preexisting thyroid hormone deficiency
- Clinical presentation
- Laboratory studies
- ECG: low-voltage QRS complexes, nonspecific T-wave changes 
- CSF analysis: slightly ↑ CSF protein 
- Treatment 
- Disposition: Admission to critical care is typically warranted for ventilatory support, invasive monitoring, and management of electrolytes and fluids. 
- Prognosis: Even with treatment, mortality rates of up to 60% have been described. 
Suspect myxedema coma in patients with typical symptoms and a history of hypothyroidism, and initiate treatment immediately without waiting for laboratory results! 
- Primary thyroid lymphoma
- Increased cardiovascular risk
- Carpal tunnel syndrome 
We list the most important complications. The selection is not exhaustive.
- Perform ABCDE survey.
- Secure airway and begin ventilatory support if there is respiratory failure.
- Establish IV access and send blood samples for thyroid function tests, cortisol, BMP, CK, LDH, and coagulation panel.
- Start fluid resuscitation and vasopressors as needed.
- Begin continuous cardiac and respiratory monitoring and consider invasive BP monitoring.
- Check core temperature and consider passive rewarming.
- Identify and treat hypoglycemia.
- Urgently consult endocrinology and critical care for admission.
- Administer IV hydrocortisone together with or prior to thyroid hormone replacement and continue until concomitant adrenal insufficiency is ruled out. 
- Start IV levothyroxine and IV liothyronine.
- Identify and treat precipitating factors.
- Admit to ICU.
- Sporadic (∼ 85% of cases) 
- Hereditary (∼ 15% of cases)
- Fetal iodine deficiency syndrome: Congenital hypothyroidism caused by iodine deficiency in utero (rare in iodine-sufficient areas). 
Possible neonatal features
- Abdominal distention
- Delayed passage of meconium
- Umbilical hernia
- Prolonged neonatal jaundice
- Decreased activity, poor feeding, and adipsia
- Hoarse cry, macroglossia
- Failure to thrive (length affected more than weight)
- Cretinism: a complication of severe, untreated congenital hypothyroidism that leads to impaired development of the brain and skeleton, resulting in skeletal abnormalities (e.g., short stature and delayed fontanelle closure) and permanent intellectual disabilities 
Most children with congenital hypothyroidism do not have symptoms at the time of birth because the placenta supplies the fetus with maternal thyroid hormone. For this reason, neonatal screening is vital even if children are asymptomatic. Irreversible intellectual disabilities can be avoided through early initiation of adequate therapy!
- Neonatal screening to measure TSH levels 24–48 hours after birth is required by law.
- Increased TSH levels indicate congenital hypothyroidism.