> Table of Contents > Hypothyroidism, Adult
Hypothyroidism, Adult
Adithi Naidu, MD
Faraz Ahmad, MD
Jason Chao, MD, MS
image BASICS
DESCRIPTION
  • Clinical and metabolic state resulting from decreased levels of free thyroid hormone or from resistance to hormone action
  • Primary (intrinsic thyroid disease) >95% of cases or central (secondary or tertiary resulting from hypothalamic-pituitary disease)
  • Subclinical or overt
  • Subclinical: serum TSH above the upper reference limit with a normal free T4 and normal hypothalamicpituitary-thyroid axis (1)[A]
  • Overt: elevated TSH, usually >10 mIU/L with a subnormal free T4
EPIDEMIOLOGY
Incidence
  • Women: 3.5 per 1,000 persons per year
  • Men: 0.6 per 1,000 persons per year
  • Risk of developing hypothyroidism in women with positive antibodies and elevated TSH was 4% per year and 2-3% per year in those with either alone (1)[A].
Prevalence
  • The National Health and Nutrition Examination Survey III (NHANES III), SHypo (Subclinical hypothyroidism) 9.3%, overt 0.3% in an unselected U.S. population over age 12 years, between 1988 and 1994 with upper limit TSH 4.5
  • Framingham study, 5.9% of women and 2.3% of men over age 60 years had a serum TSH >10 mIU/L.
  • British Whickham survey, 9.3% of women and 1.2% of men had a serum TSH >10 (1)[A].
ETIOLOGY AND PATHOPHYSIOLOGY
  • Primary: abnormality at the thyroid gland (>95% of cases)
  • Most common cause worldwide: environmental iodine deficiency (1) [A]
  • Most common cause in the United States: Hashimoto thyroiditis (autoimmune thyroid disease [AITD])
    • AITD is characterized pathologically by infiltration of the thyroid with sensitized T lymphocytes and serologically by circulating thyroid antibodies.
    • Autoimmunity to the thyroid gland is an inherited defect in immune surveillance, leading to abnormal regulation of immune responsiveness or alteration of presenting antigen in the thyroid (1)[A].
  • Postablative/posttherapeutic: follows radioactive iodine therapy or thyroid surgery for hyperthyroidism, thyroid cancer, benign nodular thyroid disease or neck malignancies
  • Transient hypothyroidism during the course of subacute or painless thyroiditis (silent thyroiditis, most common during postpartum period) and subacute granulomatous thyroiditis
  • Drug use: propylthiouracil, methimazole, lithium, amiodarone, and newer chemotherapeutic agents such as tyrosine kinase inhibitors (sunitinib), interleukin-2, or interferon-&agr;
  • Central: Hypothyroidism due to insufficient stimulation by TSH of an otherwise normal thyroid gland.
  • Can be secondary (level of the pituitary) or tertiary (level of the hypothalamus)
  • Etiology involves genetic defects, tumors, vascular, empty sella syndrome, inflammatory, infiltrative, iatrogenic, posttrauma, or drug related.
RISK FACTORS
  • Women >60 years of age
  • Personal or family history of autoimmune diseases, including type 1 diabetes mellitus, Addison disease, Hashimoto thyroiditis, vitiligo, pernicious anemia
  • Pregnant women or those with previous postpartum thyroiditis
  • Previous head or neck irradiation
  • Past history of thyroid dysfunction or thyroid surgery
  • Abnormal thyroid examination, presence of goiter and/or TPOAb positivity
  • Treatment with amiodarone, lithium, interferon-&agr;, sunitinib, or sorafenib
  • Those with Down syndrome or Turner syndrome
COMMONLY ASSOCIATED CONDITIONS
  • Type 1 diabetes
  • Pernicious anemia
  • Primary adrenal failure (Addison disease)
  • Myasthenia gravis
  • Celiac disease
  • Rheumatoid arthritis
  • Systemic lupus erythematosis
  • Vitiligo
  • Depression
  • Genetic syndromes that have multiple autoimmune endocrinopathies (MAE) such as type 1 MAE and type 2 MAE.
image DIAGNOSIS
PHYSICAL EXAM
  • Dry, coarse, thickened skin
  • Hair loss/brittle hair
  • Coarsening of voice
  • Periorbital puffiness
  • Swelling of hands and feet (nonpitting)
  • Bradycardia
  • Reduced systolic BP; increased diastolic BP
  • Delayed relaxation of deep tendon reflexes
  • Macroglossia
  • Goiter (particularly in patient with Hashimoto thyroiditis)
Geriatric Considerations
  • Characteristic signs and symptoms frequently nonspecific, changed, or absent
  • Normal serum thyrotropin ranges are higher (in those over 65 years of age)
DIFFERENTIAL DIAGNOSIS
  • Chronic fatigue syndrome
  • Depression
  • Euthyroid sick syndrome
  • Congestive heart failure
  • Primary amyloidosis
  • Dementia from other causes
  • Primary adrenal insufficiency
  • Thyrotropin-secreting pituitary adenoma
DIAGNOSTIC TESTS & INTERPRETATION
  • Primary hypothyroidism
    • Elevated TSH (>4.5 mIU/L)
    • Decreased serum free T4
    • Normal TRH stimulation test
  • Central (secondary or tertiary) hypothyroidism
    • Assess only free T4 or free T4 index, not TSH (1)[A].
    • Decreased serum free T4
    • Abnormal TRH stimulation test
    • Antithyroid antibodies absent
    • Imaging of the hypothalamus and pituitary gland
  • Subclinical hypothyroidism
    • Elevated serum TSH (>4.5 mIU/L)
    • Normal serum free T4 (2)[A]
    • Note: Serum free triiodothyronine (T3) or total T3 should not be done to diagnose hypothyroidism (1)[A].
Follow-Up Tests & Special Considerations
  • Antithyroid antibodies may define the cause of primary hypothyroidism but are not necessary in all settings.
  • Drugs that may alter lab results:
    • Drugs that decrease TSH:
      • Thyroid supplement, cortisone, dopamine, octreotide
    • Drugs that increase TSH:
      • Phenytoin, amiodarone, dopamine antagonist (metoclopramide/domperidone, salicylates, oral colecystographic dyes [sodium ipodate]), or estrogen or androgen in excess
  • Disorders that may alter lab results
    • Any severe illness, pregnancy, chronic protein malnutrition, hepatic failure, or nephrotic syndrome
Test Interpretation
SCREENING
  • Patient with risks factors as described above
  • Patient with laboratory or imaging abnormalities
    • Substantial hyperlipidemia or change in lipid pattern
    • Hyponatremia, often resulting from inappropriate production of antidiuretic hormone
    • High serum muscle enzyme concentrations
    • Macrocytic anemia
    • Pericardial or pleural effusion
    • Pituitary or hypothalamic disorder
  • Pregnant women
    • Personal or family history of thyroid disease
    • DM type 1
    • H/o recurrent miscarriage, morbid obesity, or infertility; thyroid peroxidase antibody (TPOAb) should be considered (1)[A].
    • Universal screening not recommended for patients pregnant or planning pregnancy
  • U.S. Preventive Services Task Force does not recommend routine screening for children or adults (1)[A].
  • P.541

  • Recommendations by expert groups:
    • ATA recommend screening in all adults at age 35 years and every 5 years thereafter.
    • AACE recommend screening older patients, especially women.
    • AAFP recommend screening patients 60 years and older.
    • ACOG recommends women with h/o autoimmune disease or strong family h/o thyroid disease should be screened at age 19 years.
image TREATMENT
MEDICATION
First Line
  • Levothyroxine (Synthroid, Levothroid)
    • 1.6 &mgr;g/kg/day; increase by 12.5 to 25 &mgr;g/day every 4 to 8 weeks until TSH in normal range
    • Dosage requirements may vary with age, gender, residual secretory capacity of thyroid gland, other drugs being taken by patient, and intestinal function (1)[A].
    • Elderly patients may require 2/3 of dose used in young adults because clearance is decreased.
    • Levothyroxine should be taken on an empty stomach, ideally an hour before breakfast. Administering at bedtime may result in higher levels than administering in the morning (3)[A]
    • Medications that interfere with its absorption should be taken 4 hours after the T4 dose: ferrous sulfate, proton pump inhibitors, calcium carbonate, bile acid resins.
  • Contraindications
    • Thyrotoxic heart disease
    • Uncorrected adrenocorticoid insufficiency
    • MI, acute
    • TSH suppression, preexisting
  • Precautions
    • Start with lower doses, such as 12.5 to 25 &mgr;g, in elderly and in patients with heart disease.
    • Diabetic patients may need readjustment of hypoglycemic agents with institution of thyroxine (T4).
    • Dosage of oral anticoagulants may need adjustment; monitor prothrombin time while initiating treatment.
    • Elderly patients more susceptible to AFib and osteoporotic fracture with thyroid hormone excess
    • Patients requiring doses that are higher than expected should be evaluated for GI disorders (H. pylori, celiac disease).
  • Significant possible interactions
    • Oral anticoagulants, insulin, oral hypoglycemic, estrogen, OCP, PPI, cholestyramine
    • Ferrous sulfate, calcium carbonate, antacids, laxatives, colestipol, sucralfate, ciprofloxacin, and cholestyramine may decrease absorption.
  • Controversy exists whether subclinical hypothyroidism should be treated. Cochrane Review found no improvement in survival, cardiovascular morbidity, or health-related quality of life. Some evidence indicates improvement in lipid profiles and left ventricular function. Subclinical hypothyroidism should be treated in patients with iron deficiency anemia and in patients with TSH >10 (2, 4, 5)[B].
  • If surgery is elective, render patient euthyroid prior to procedure.
  • If surgery is urgent, proceed with individualized replacement therapy preoperatively and post-operatively.
Pregnancy Considerations
  • Replacement therapy may need adjustment; average dose increase from 25-50% (6)[A].
  • TSH levels should be monitored monthly during 1st trimester; goal TSH of 2 to 2.5 mIU/L for 1st trimester, <3.0 mIU/L for 2nd trimester, and <3.5 mIU/L for 3rd trimester (6)[A].
  • Postpartum: Check TSH levels at 6 weeks (6)[A].
  • Painless subacute thyroiditis may occur in postpartum period, leading to transient hypothyroidism lasting 3 months. Treatment with replacement therapy may be warranted. Up to 30% of these individuals develop permanent hypothyroidism.
Second Line
  • No benefit to adding triiodothyronine (T3) to T4 (6)[A]
  • Desiccated thyroid hormone is not recommended for the treatment of hypothyroidism (1).
ISSUES FOR REFERRAL
  • Children and infants
  • Pregnancy or women planning conception
  • Patient in whom it is difficult to maintain a euthyroid state
  • Cardiac disease
  • Presence of goiter, nodule, or other structural changes in the thyroid gland
  • Presence of adrenal or pituitary disorders (1)[C]
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
  • Myxedema coma (decompensated severe untreated hypothyroidism)
  • True clinical emergency (requires ICU care)
  • Profound hypothermia and unconsciousness
  • Increased risk of shock and potentially fatal arrhythmias
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Monitor TSH and free T4 every 4 to 8 weeks after initiating treatment or after change in dose. Once stabilized, periodic TSH level should be done after 6 months and then at 12-month intervals or more frequently if the clinical situation dictates otherwise (1)[B].
  • Follow cardiac status closely in older patients.
  • Check TSH more frequently in pregnancy, initiation of estrogen supplementation, or after large changes in body weight.
  • In central hypothyroidism, TSH unreliable; must monitor free T4 and T3
  • Thyroid hormones should not be used to treat obesity in euthyroid patients (1)[A].
PATIENT EDUCATION
  • Stress importance of compliance with thyroid replacement therapy.
  • Explain need for lifelong treatment.
  • Further education required for patients taking multiple medications that may interact
  • Instruct to report to physician any signs of infection or heart problems.
  • Describe signs of thyrotoxicity.
  • High-bulk diet may help avoid constipation.
PROGNOSIS
  • Return to normal state is the rule.
  • Relapses will occur if treatment is interrupted.
  • If untreated, may progress to myxedema coma
REFERENCES
1. Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologist and the American Thyroid Association. Thyroid. 2012;22(12):1200-1235.
2. Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012;379(9821):1142-1154.
3. Khandelwal D, Tandon N. Overt and subclinical hypothyroidism: who to treat and how. Drugs. 2012;72(1):17-33.
4. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on thyroid hormone replacement. Thyroid. 2014;24(12):1670-1751.
5. Villar HC, Saconato H, Valente O, et al. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst Rev. 2007;(3):CD003419.
6. Alexander EK, Marqusee E, Lawrence J, et al. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. N Engl J Med. 2004;351(3):241-249.
Codes
&NA;
ICD10
  • E03.9 Hypothyroidism, unspecified
  • E06.3 Autoimmune thyroiditis
  • E89.0 Postprocedural hypothyroidism
Clinical Pearls
&NA;
  • Monitor TSH and free T4 every 4 to 8 weeks after initiating treatment or after change in dose. Once stabilized, periodic TSH level should be done after 6 months and then at 12-month intervals, or more frequently if the clinical situation dictates otherwise (1)[B].
  • Screening test: TSH levels (1)[A]
  • Serum free T3 or total T3 should not be done to diagnose hypothyroidism (1)[A].
  • Dosage requirements may vary with age, gender, residual secretory capacity of thyroid gland, other drugs being taken by patient, and intestinal function (1)[A].