II. Definitions
- Hypothyroidism
- Inadequate Thyroid Hormone production from the Thyroid Gland OR
- Insufficient stimulation from the Hypothalamus or the Pituitary Gland
III. Epidemiology: Prevalence (US)
- Congenital: 1 in 4000 newborns
- Adults:
- Age over 65 years: 2-4% (especially older women)
- Overall in U.S.: 0.3-1.0%
- Undiagnosed cases: 13 Million estimated in U.S.
- Gender
- More common in women by 7 fold
- Men: 6 per 10,000
- Women: 40 per 10,000
IV. Physiology
V. Risk Factors
- Autoimmune Disorders
- Diabetes Mellitus
- Celiac Sprue
- Adrenal Insufficiency (Addison Disease)
- Autoimmune Gastric Atrophy
- Congenital Disorders
- Iatrogenic
- Subtotal Thyroidectomy
- Neck Radiation Therapy
- Radioactive Iodine
- See Medications Affecting Thyroid Function
VI. Causes
- Hashimoto's Thyroiditis (Most common cause)
- Congenital Causes
-
Thyroid ablation
- Graves' Disease Management
- Radioactive Iodine (I-131)
- Thyroidectomy
- Neck radiation in cancer treatment
- Graves' Disease Management
- Medications
- See Medications Affecting Thyroid Function
- Severe Iodine deficiency (rare in U.S. due to iodinated salt)
- Secondary Hypothyroidism (Central causes, only 5% of cases)
- Congenital Hypopituitarism
- Pituitary necrosis (Sheehan's Syndrome)
- Pituitary or Hypothalamic lesion
- HIV Infection on highly active Antiretrovirals
- Also associated with low CD4 Counts
- Beltran (2003) Clin Infect Dis 37:579-83 [PubMed]
- Transient Hypothyroidism
- Postpartum Thyroiditis
- Subacute Thyroiditis
- Silent Thyroiditis
- TSH receptor blocking Antibody associated Thyroiditis
VII. Symptoms
-
Generalized
- Fatigue or generalized weakness (99%)
- Lethargy (91%)
- Cold intolerance (89%)
- Weight gain despite diminished food intake
- Edema
- Arthralgias
- Myalgias
- Neuropsychiatric
- Diminished libido
- Headache
- Hoarseness
- Slow thinking
- Forgetfulness (66%)
- Slow speech (91%)
- Depressed Mood
- Difficult Concentration
- Gastrointestinal
- Constipation (61%)
- Dermatologic
- Dry or coarse skin (97%)
- Decreased Sweating (89%)
- Hair Loss (especially outer third of eyebrows)
- Broken nails
- Gynecologic
VIII. Symptoms: Presentations
- Most specific symptoms for Hypothyroidism
- Constipation
- Cold Intolerance
- Dry Skin
- Proximal Muscle Weakness
- Hair thinning or Hair Loss
- Infants and children
- Lethargy
- Failure to Thrive
- Women
- Irregular Menses
- Infertility
- Older patients
- Cognitive decline
IX. Signs
-
General
- Round puffy face or other Facial Edema (79%)
- Periorbital edema or Eyelid Edema (90%)
- Large, thick Tongue or Macroglossia (82%)
- Non-pitting ankle edema
- Hypothermia
- Neuropsychiatric
- Slow speech
- Hoarse voice
- Hypokinesia
- Generalized Muscle Weakness
- Delayed relaxation of Deep Tendon Reflexes
- Patellar Reflex
- Ankle Jerk reflex
- Dermatologic
- Cold, dry, thick Scaling skin
- Affects palms, soles, elbows and knees
- Skin may show yellow-orange discoloration
- Dry coarse brittle hair (76%)
- Dry, longitudinally ridged nails
- Lateral eyebrow thinning
- Cold, dry, thick Scaling skin
- Gastrointestinal
- Cardiopulmonary
- Faint cardiac impulse
- Indistinct heart tones
- Cardiac enlargement
- Bradycardia
- Pericardial Effusion (severe Hypothyroidism)
- Pleural Effusion (severe Hypothyroidism)
- Variable effect on Blood Pressure
- Hypotension may be present
- Diastolic Hypertension
X. Differential Diagnosis
- Anemia
- Autoimmune and Endocrine Disorders
- Mental Health Disorders
- Infection
- Miscellaneous
XI. Labs: Thyroid Function Tests
- See Thyroid Function Testing
- TSH is the primary screening and monitoring test
- Most sensitive marker for Thyroid function
- Indications for Screening
- Pregnancy
- All elderly with depression
- All elderly entering long term care
- Risk Factors (see above)
- Autoimmune disorders (e.g. Diabetes Mellitus, Celiac Disease)
- Congenital disorders (Turner Syndrome, Down Syndrome)
- Iatrogenic (e.g. Subtotal Thyroidectomy, Neck Radiation Therapy, Radioactive Iodine)
- Medications Affecting Thyroid Function
- Protocol
- Monitoring after diagnosis: TSH alone is sufficient
- Screening: TSH with reflex to Free T4
- Interpretation
- Serum TSH increased
- Free T4 low
- Primary Hypothyroidism
- Free T4 normal
- Subclinical Hypothyroidism
- Overt Hypothyroidism unlikely if Serum TSH 6-10
- Consider checking Free T3
- Free T3 is low in congenital absence of T4 to T3 converting enzyme
- Free T3 may also be low due to Amiodarone blocking T4 to T3 conversion
- Free T4 low
- Serum TSH decreased
- Free T4 low: Central Hypothyroidism (secondary Hypothyroidism, rare <5% of cases)
- Urgent endocrinology Consultation
- Obtain head imaging (MRI Brain) with attention toward sella turcica
- Obtain other pituitary-related Hormone levels
- Free T4 high
- Free T4 low: Central Hypothyroidism (secondary Hypothyroidism, rare <5% of cases)
- Serum TSH increased
XII. Labs: Other
-
Lipid profile
- LDL Cholesterol elevated
- Serum Triglyceride elevated
- Serum labs
- Creatine Phosphokinase (CPK) elevated
- Lactate Dehydrogenase (LDH) elevated
- Serum Prolactin increased (see Hyperprolactinemia)
- Serum Sodium decreased (see Hyponatremia)
- Blood count and acute phase reactants
- Complete Blood Count (CBC)
- Refractory Macrocytic Anemia or Normocytic Anemia
- C-Reactive Protein (C-RP) increased
- Complete Blood Count (CBC)
- Urinalysis
XIII. Diagnostics: Electrocardiogram (EKG)
- Bradycardia
- Low amplitude QRS Complexes
- Flattened or inverted T Waves
XIV. Imaging
- Retarded bone growth
XV. Complications
- Hyperlipidemia
- Hypertension
- Infertility
- Neuromuscular dysfunction
- Myxedema Coma (rare, 0.22 per million persons)
- Atrial Fibrillation
XVI. Management: General
- See Thyroid Replacement (Levothyroxine)
- See Subclinical Hypothyroidism for treatment indications
- In general, avoid Liothyronine and desiccated Thyroid (no evidence of benefit, and Cardiovascular Risk)
- Elderly
- See Subclinical Hypothyroidism
- TSH elevations are often transient (often during non-Thyroid related acute conditions)
- Exercise caution when starting Thyroid Replacement in the elderly
- Consider rechecking TSH after acute illness before initiating Thyroid Replacement
- Wong (1981) Arch Intern Med 141(7):873-5 +PMID: 7235805 [PubMed]
- Consider withdrawing Thyroid Replacement
- Indication: Elderly in Community and nursing-home
- May have been diagnosed prior to sensitive TSH
- Trial at decreased dose or off for 6 weeks
- Recheck TSH after trial
- Pregnancy
- See Hypothyroidism in Pregnancy
- Maintaining a euthyroid state throughout pregnancy is critical
XVII. Management: Endocrinology referral indications
- Age <18 years old
- Cardiac disorders
- Concurrent other endocrine disorders
- Hypothyroidism in Pregnancy
- Thyroid Gland structural abnormality (e.g. Goiter or thryoid Nodule)
- Poor response to Thyroid Replacement
XVIII. Management: Persistent Symptoms despite normal range TSH
- See Fatigue
- Consider Drug Interaction with Levothyroxine
- See Levothyroxine
- Consider other causes
- Alternative replacement strategies are not typically recommended
- Dessicated Thyroid Hormone or Armour Thyroid
- Not recommended by American Association of Endocrinology
- T3 concentrations are high in Armour Thyroid and increase the risk of cardiovascular toxicity
- Combination T3 (Liothyronine, Cytomel) and T4 (Levothyroxine) Therapy
- See Liothyronine (Cytomel)
- T3 dosing is 1/14 of T4 dosing
- T3 should not be used alone without concurrent T4
- Adding T3 to T4 was initially found to improve neuropsychiatric symptoms
- Most studies suggest no benefit and are often associated with iatrogenic Hyperthyroidism
- Dessicated Thyroid Hormone or Armour Thyroid
XIX. Management: Abnormal TSH despite previously stable dose
- Non-compliance with Thyroid Replacement (missed doses)
- Consider especially if doses >200 mcg/day
- Change in formulation (e.g. manufacturer change, or generic to brand name)
- Avoid changes in formulation and recheck TSH 4-6 weeks after such changes occur
- Hormonal changes
- Pregnancy (maintaining euthyroid state in pregnancy is critical)
- Oral Contraceptives or Estrogen Replacement started or stopped
- Decreased Levothyroxine absorption or Drug Interaction
- See Levothyroxine for Drug Interactions and Food Interactions
- Levothyroxine taken with meals
XX. References
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Related Studies
Definition (NCI_CTCAE) | A disorder characterized by a decrease in production of thyroid hormone by the thyroid gland. |
Definition (NCI) | Abnormally low levels of thyroid hormone.(NICHD) |
Definition (NCI_NCI-GLOSS) | Too little thyroid hormone. Symptoms include weight gain, constipation, dry skin, and sensitivity to the cold. |
Definition (CSP) | deficiency of thyroid gland activity; characterized by decreased basal metabolic rate, fatigue and lethargy, sensitivity to cold, and menstrual disturbances; untreated it progresses to myxedema; in infants severe hypothyroidism leads to cretinism. |
Definition (MSH) | A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. |
Concepts | Disease or Syndrome (T047) |
MSH | D007037 |
ICD9 | 244.9 |
ICD10 | E03.9 |
SnomedCT | 190290003, 267465007, 237572004, 267377003, 190274003, 154660000, 40930008 |
LNC | MTHU020783, LA14303-4 |
English | Hypothyroidism, Hypothyroidisms, Unspecified hypothyroidism, HYPOTHYROIDISM, THYROID ACTIVITY DECREASED, Hypothyroidism, unspecified, hypothyroidism, hypothyroidism (diagnosis), Thyroid activity decreased, Hypothyroidism NOS, Hypothyroidism [Disease/Finding], hypothyroidisms, hypothyroid, Unspecified acquired hypothyroidism, Underactive Thyroid, Thyroid insufficiency, Thyroid deficiency, Hypothyroidism NOS (disorder), underactive thyroid, Hypothyroid, Hypothyroidism (disorder), deficiency; thyroid, insufficiency; thyroid, subthyroidism, thyroid; deficiency, thyroid; insufficiency, Hypothyroidism, NOS, Hypothyroidism [Ambiguous] |
French | HYPOTHYROIDIE, Hypothyroïdisme non précisé, Activité thyroïdienne diminuée, DIMINUTION ACTIVITE THYROIDIENNE, Hypothyréose, Hypothyroïdie, Hypothyroïdisme |
Spanish | HIPOTIROIDISMO, Hipotiroidismo no especificado, Actividad del tiroides disminuida, TIROIDES, ACTIVIDAD DISMINUIDA, hipotiroidismo, SAI (trastorno), hipotiroidismo, SAI, hipotiroidismo (trastorno), hipotiroidismo, Hipotiroidismo |
German | HYPOTHYREOSE, Schilddruesenaktivitaet erniedrigt, unspezifische Hypothyreose, Hypothyreose, nicht naeher bezeichnet, SCHILDDRUESENAKTIVITAET VERMINDER, Hypothyreose, Hypothyreoidismus |
Dutch | verlaagde schildklieractiviteit, niet-gespecificeerde hypothyroïdie, deficiëntie; schildklier, insufficiëntie; schildklier, schildklier; deficiëntie, schildklier; insufficiëntie, Hypothyroïdie, niet gespecificeerd, hypothyroïdie, Hypothyreose, Hypothyreoïdie, Thyreoïdie, hypo- |
Italian | Attività tiroidea diminuita, Ipotiroidismo non specificato, Ipotiroidismo |
Portuguese | Hipotiroidismo NE, Actividade tiroideia diminuída, DIMINUICAO DA ACTIVIDADE TIROIDEI, HIPOTIROIDISMO, Hipotiroidismo, Hipotireoidismo |
Japanese | 詳細不明の甲状腺機能低下症, 甲状腺機能低下症, 甲状腺機能低下, コウジョウセンキノウテイカ, コウジョウセンキノウテイカショウ, ショウサイフメイノコウジョウセンキノウテイカショウ |
Swedish | Hypotyreos |
Finnish | Kilpirauhasen vajaatoiminta |
Russian | GIPOTIREOIDIZM, GALLA BOLEZN', GIPOTIREOZ, ГАЛЛА БОЛЕЗНЬ, ГИПОТИРЕОЗ, ГИПОТИРЕОИДИЗМ |
Czech | Blíže neurčená hypotyreóza, Hypotyreóza, Snížená činnost štítné žlázy, hypotyreoidismus, hypotyreóza, hypothyreóza |
Korean | 상세불명의 갑상샘 기능저하증 |
Croatian | HIPOTIREOZA |
Polish | Niedoczynność tarczycy |
Hungarian | Hypothyreosis, Pajzsmirigy aktivitás csökkenése, Nem meghatározott hypothyreosis |
Norwegian | Hypotyreoidisme, Lavt stoffskifte, Hypotyreose |
Ontology: Myxedema (C0027145)
Definition (NCI) | A condition characterized by severe hypothyroidism that is caused by autoimmune thyroid gland disorders, surgical reduction of thyroid tissue, radiation exposure, and viral infections. Signs and symptoms include generalized fatigue, lethargy, increased body weight, pale, edematous and thickened skin, low blood pressure, constipation and cold intolerance. |
Definition (CSP) | condition characterized by a dry, waxy type of swelling with abnormal deposits of mucin in the skin and other tissues; it is produced by a functional insufficiency of the thyroid gland, resulting in deficiency of thyroid hormone. |
Definition (MSH) | A condition characterized by a dry, waxy type of swelling (EDEMA) with abnormal deposits of MUCOPOLYSACCHARIDES in the SKIN and other tissues. It is caused by a deficiency of THYROID HORMONES. The skin becomes puffy around the eyes and on the cheeks. The face is dull and expressionless with thickened nose and lips. |
Concepts | Disease or Syndrome (T047) |
MSH | D009230 |
ICD10 | E03.9 |
SnomedCT | 190274003, 154660000, 267465007, 43153006 |
English | Myxedema, Myxedemas, MYXOEDEMA, MYXEDEMA, myxedema, myxedema (diagnosis), Myxedema NOS, Myxedema [Disease/Finding], Mucin in skin, Myxoedema, Myxedema (disorder), Hypothyroidism/myxoedema, Myxedema, NOS, Myxoedema, NOS, myxoedema |
French | MYXOEDEME, Myxoedème |
Portuguese | MIXEDEMA, Mixedema |
Spanish | MIXEDEMA, Mixoedema, mixedema (trastorno), mixedema, Mixedema |
German | MYXOEDEM, Myxoedem, Myxödem |
Swedish | Myxödem |
Czech | myxedém, Myxedém |
Finnish | Myksedeema |
Russian | MIKSEDEMA, МИКСЕДЕМА |
Dutch | myxoedeem, Hypothyreoàdie/myxoedeem, Myxoedeem |
Japanese | ネンエキスイシュ, 粘液水腫 |
Croatian | MIKSEDEM |
Polish | Obrzęk śluzowaty |
Hungarian | Myxoedema |
Norwegian | Myksødem |
Italian | Mixedema |