Hypothyroidism – Causes, Symptoms, Diagnosis, Treatment

Hypothyroidism also called underactive thyroid or low thyroid is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone It can cause a number of symptoms, such as poor ability to tolerate cold, a feeling of tirednessconstipation, depression, and weight gain. Occasionally there may be swelling of the front part of the neck due to goitre. Untreated hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or cretinism

Thyroid Storm 

Thyroid storm refers to an increasingly rare but still highly dangerous form of thyrotoxicosis that, in addition to the other complaints of hyperthyroidism, is marked by extreme temperature elevation and/or change in mental status, ranging from extreme agitation to coma. Hypothyroid crisis refers to advanced thyroid hormone deficiency manifested by hypothermia and obtundation.

Essentially an exaggeration of thyrotoxicosis featuring marked hyperthermia (104-106°F), tachycardia (HR > 140bpm), and altered mental status (agitation, delirium, coma).


  • Medical: Sepsis, MI, CVA, CHF, PE, visceral ischemia
  • Trauma: Surgery, blunt, penetrating
  • Endocrine: DKA, HHS, hypoglycemia
  • Drugs: Iodine, amiodarone, inhaled anesthetics
  • Pregnancy: post-partum, hyperemesis gravidarum

Scoring (Burch, Wartofsky)

Management Supportive measures

  • Benzodiazepines for agitation Volume resuscitation (with VMI, Thiamine) and cooling Beta-blockade
  • Propranolol 60-80mg PO q4h
  • Propranolol 0.5-1.0mg IV, repeat q15min then 1-2mg q3h
  • Esmolol continuous infusion
  • MTZ/PTU 1-hour prior to iodine
  • Methimazole 20mg (except pregnancy)
  • Propylthiouracil 600mg (hepatotoxic)
  • Steroids: dexamethasone
  • Iodine
  • Endocrinology consultation

Causes of Hypothyroidism

  • Hashimoto: auto-antiboids
  • Thyroidectomy
  • Radiation, radioactive iodine ablation
Group Causes
Primary hypothyroidism Iodine deficiency (developing countries), autoimmune thyroiditis, subacute granulomatous thyroiditis, subacute lymphocytic thyroiditis, postpartum thyroiditis, previous thyroidectomy, previous radioiodinetreatment, previous external beam radiotherapy to the neck
Medication: lithium-based mood stabilizers, amiodarone, interferon alpha, tyrosine kinase inhibitors such as sunitinib
Central hypothyroidism Lesions compressing the pituitary (pituitary adenoma, craniopharyngioma, meningioma, glioma, Rathke’s cleft cyst, metastasis, empty sella, aneurysm of the internal carotid artery), surgery or radiation to the pituitary, drugs, injury, vascular disorders (pituitary apoplexy, Sheehan syndrome, subarachnoid hemorrhage), autoimmune diseases (lymphocytic hypophysitis, polyglandular disorders), infiltrative diseases (iron overload due to hemochromatosis or thalassemia, neurosarcoidosis, Langerhans cell histiocytosis), particular inherited congenital disorders, and infections (tuberculosis, mycoses, syphilis)
Congenital hypothyroidism Thyroid dysgenesis (75%), thyroid dyshormonogenesis (20%), maternal antibody or radioiodine transfer
Syndromes: mutations (in GNAS complex locusPAX8TTF-1/NKX2-1TTF-2/FOXE1), Pendred’s syndrome (associated with sensorineural hearing loss)
Transiently: due to maternal iodine deficiency or excess, anti-TSH receptor antibodies, certain congenital disorders, neonatal illness
Central: pituitary dysfunction (idiopathic, septo-optic dysplasia, deficiency of PIT1, isolated TSH deficiency)

In consumptive hypothyroidism, high levels of type 3 deiodinase inactivate thyroid hormones and thus leads to hypothyroidism. High levels of type 3 deiodinase generally occur as the result of a hemangioma. The condition is very rare.

Symptoms of Hypothyroidism 

Constitutional Weight gain, cold intolerance, fatigue
Cardiopulmonary Dyspnea, decreased exercise capacity
Neuropsychiatric Impaired concentration and attention
Musculoskeletal Extremity swelling
Gastrointestinal Constipation
Reproductive Irregular menses, erectile dysfunction, decreased libido
Integumentary Coarse hair, dry skin, alopecia, thin nails
Vital signs Bradycardia, hypothermia
Cardiovascular Prolonged QT, increased ventricular arrhythmia, accelerated CAD, diastolic heart failure, peripheral edema
Neurologic Lethargy, slowed speech, agitation, seizures, ataxia/dysmetria, mononeuropathy, delayed relaxation of reflexes
Musculoskeletal Proximal myopathy, pseudohypertrophy, polyarthralgia
Gastrointestinal Ileus

Additional Symptoms of Hypothyroidism

Generalized decreased basal metabolic rate can present as apathy, slowed cognition, skin dryness, alopecia, increased low-density lipoproteins, and increased triglycerides. Hypothyroidism can decrease sympathetic activity leading to decreased sweating, bradycardia, and constipation. Patients can present with myopathy and decreased cardiac output because of decreased transcription of sarcolemmal genes.

Hyperprolactinemia can be caused by hypothyroidism. Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates prolactin and TSH release. Prolactin release can suppress testosterone, LH, FSH, and GnRH release. Prolactin can also cause breast tissue growth.

Symptoms related to decreased metabolic rate

  • Bradycardia
  • Fatigue
  • Cold intolerance
  • Weight gain
  • Poor appetite
  • Hair loss
  • Cold and dry skin
  • Constipation
  • Myopathy, stiffness, cramps, entrapment syndromes
  • Delayed deep tendon reflex relaxation

Symptoms from generalized myxedema

  • Myxedematous heart disease
  • Puffy appearance with doughy skin texture
  • Hoarse voice with difficulty articulate words
  • Pretibial and periorbital edema

Symptoms of hyperprolactinemia

  • Amenorrhea or menorrhagia
  • Galactorrhea
  • Erectile dysfunction, infertility in men
  • Decreased libido

Other symptoms

  • Depression
  • Impaired concentration and memory
  • Goiter
  • Hypertension

Congenital hypothyroidism

  • Umbilical hernia
  • Hypotonia
  • Prolonged neonatal jaundice
  • Poor feeding, absence of thirst (adipsia)
  • Decreased activity
  • Pot-belly, puffy-face, protuberant tongue
  • Poor brain development

Diagnosis of Hypothyroidism 

Free thyroxine

Free thyroxine (fT4) is generally elevated in hyperthyroidism and decreased in hypothyroidism. Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are:

Patient type Lower limit Upper limit Unit
Normal adult 0.7, 0.8 1.4, 1.5,1.8 ng/dL
9, 10, 12  18, 23 pmol/L
Infant 0–3 d 2.0 5.0 ng/dL
26 65 pmol/L
Infant 3–30 d 0.9 2.2 ng/dL
12 30 pmol/L
31 d – 18 y
0.8 2.0 ng/dL
10 26 pmol/L
Pregnant 0.5 1.0 ng/dL
6.5 13 pmol/L

Total triiodothyronine

Total triiodothyronine (Total T3) is rarely measured, having been largely superseded by free T3 tests. Total T3 is generally elevated in hyperthyroidism and decreased in hypothyroidism.

Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are:

Test Lower limit Upper limit Unit
Total triiodothyronine 60,75 175, 181 ng/dL
0.9, 1.1 2.5,2.7 nmol/L

Free triiodothyronine

Free triiodothyronine (fT3) is generally elevated in hyperthyroidism and decreased in hypothyroidism.

Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are:

Patient type Lower limit Upper limit Unit
Normal adult 3.0 7.0 pg/mL
3.1 7.7 pmol/L
Children 2–16 y 3.0 7.0 pg/mL
1.5 15.2 pmol/L

Thyroxine-binding globulin [Carrier proteins]

An increased thyroxine-binding globulin results in increased total thyroxine and total triiodothyronine without an actual increase in hormonal activity of thyroid hormones.

Reference ranges:

Lower limit Upper limit Unit
12 30 mg/L


Reference ranges:

Lower limit Upper limit Unit
1.5 30 pmol/L
1 20  μg/L

Treatments of Hypothyroidism

Myxedema Coma


  • Critical illness: sepsis (especially PNA), CVA, MI, CHF, trauma, burns
  • Endocrine: DKA, hypoglycemia
  • Drugs: amiodarone, lithium, phenytoin, rifampin, medication non-adherence
  • Environmental: cold exposure


  • History: hypothyroidism, thyroidectomy scar, and acute precipitating illness
  • Hypothermia: temp <95.9°F (or normal in presence of infection)
  • AMS: lethargy, confusion, coma, agitation, psychosis, seizures
  • Hypotension: refractory to volume resuscitation and pressors
  • Bradypnea: with hypercapnia and hypoxia
  • Skin: non-pitting edema of face and hands
  • Hyponatremia


  • Airway protection
  • Fluid resuscitation
  • Thyroid hormone replacement
  • Young, otherwise healthy patients: T3 10ug IV q4h
  • Elderly, cardiac compromise: 300ug IV x1
  • Steroids: dexamethasone 1h prior to thyroid hormone
  • Treat precipitating illness

Hormone Replacement

Most people with hypothyroidism symptoms and confirmed thyroxine deficiency are treated with a synthetic long-acting form of thyroxine, known as levothyroxine (L-thyroxine). In young and otherwise healthy people with overt hypothyroidism, a full replacement dose (adjusted by weight) can be started immediately; in the elderly and people with heart disease, a lower starting dose is recommended to prevent over supplementation and risk of complications. Lower doses may be sufficient in those with subclinical hypothyroidism, while people with central hypothyroidism may require a higher than average dose


Adding liothyronine (synthetic T3) to levothyroxine has been suggested as a measure to provide better symptom control, but this has not been confirmed by studies. In 2007, the British Thyroid Association stated that combined T4 and T3 therapy carried a higher rate of side effects and no benefit over T4 alone. Similarly, American guidelines discourage combination therapy due to a lack of evidence, although they acknowledge that some people feel better when receiving combination treatment.[rx] Treatment with liothyronine alone has not received enough study to make a recommendation as to its use; due to its shorter half-life it needs to be taken more often

Subclinical hypothyroidism

There is little evidence whether there is a benefit from treating subclinical hypothyroidism, and whether this offsets the risks of overtreatment. Untreated subclinical hypothyroidism may be associated with a modest increase in the risk of coronary artery disease. A 2007 review found no benefit of thyroid hormone replacement except for “some parameters of lipid profiles and left ventricular function”. There is no association between subclinical hypothyroidism and an increased risk of bone fractures, nor is there a link with cognitive decline.

Since 2008, consensus American and British opinion have been that in general people with TSH under 10 mIU/l do not require treatment. American guidelines recommend that treatment should be considered in people with symptoms of hypothyroidism, detectable antibodies against thyroid peroxidase, a history of heart disease or are at an increased risk for heart disease if the TSH is elevated but below 10 mIU/l.

Desiccated animal thyroid

Desiccated thyroid extract is an animal-based thyroid gland extract, most commonly from pigs. It is combination therapy, containing forms of T4 and T3. It also contains calcitonin (a hormone produced in the thyroid gland involved in the regulation of calcium levels), T1 and T2; these are not present in synthetic hormone medication. This extract was once a mainstream hypothyroidism treatment, but its use today is unsupported by evidence; British Thyroid Association and American professional guidelines discourage its use

Interpretation of Thyroid Function Tests

None Normal Normal
Hyperthyroidism Low High
Hypothyroidism High Low
Subclinical hyperthyroidism Low Normal
Subclinical hypothyroidism High Normal
Sick euthyroid Low Low


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