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