Tertiary prevention of hypothyroidism Avoiding Complications

Potential complications of recognized hypothyroidism and its treatment are preventable with sustained thyroxine therapy and appropriate clinical and laboratory monitoring. Myxedema coma is a life-threatening syndrome of multisystem organ failure resulting from prolonged profound thyroid hormone deficiency, usually with superimposed sepsis, drug intoxication, or an ischemic vascular event (52). Anecdotally, the hypothyroid patient who is elderly or has a history of previous noncompliance, other systemic illness, alcohol abuse, social isolation, and economic deprivation is at greatest risk. A second potential complication in hypothyroid patients who are suboptimally treated is persistence of risk factors for atherosclerosis. In this setting, the serum low-density lipoprotien cholesterol (53) concentration may remain elevated. In one small trial of patients with treated hypothyroidism and ischemic heart disease undergoing follow-up coronary catheterization after angioplasty, the patients with inadequately treated hypothyroidism (i.e., persistently elevated serum TSH concentrations) had a significantly higher rate of progression of their coronary arterial lesions than did patients on an optimal thyroxine replacement dose (54).

For patients with treated hypothyroidism, tertiary prevention includes avoiding complications of thyroid hormone therapy. The first of these is iatrogenic thyrotoxicosis, which in one large population survey was found to occur in more than one-fifth of thyroid hormone-treated patients (2). Appropriate dose selection and adjustment with TSH monitoring can avoid this problem (55). Even the appropriate restoration of euthyroidism with thyroxine can also be associated with two unusual complications that should be anticipated and (when they are probable) prevented. First, ischemic heart disease can be exacerbated by thyroid hormone's positive chronotropic and inotropic actions, which have been reported to cause angina, myocardial infarction, dysrthythmia, and death (56). Consequently, in patients with known coronary artery disease, prominent risk factors for it, or age older than 65 years, treatment should be initiated with a low dose of thyroxine, e.g., 0.025 mg/d. Second, institution of thyroid hormone replacement alone can provoke adrenal insufficiency in patients with associated borderline adrenal cortical function caused by autoimmune adrenalitis in patients with

Table 2

Clinical Practice Guidelines for Thyroid Function Testing and Screening

Guideline

Methods used to analyze evidence

Organization, year

Summary of relevant recommendations

American Thyroid

Association guidelines for the detection of thyroid dysfunction (58)

Consensus statement for good practice and audit measures in the management of hypo-thyroidism and hyperthyroidism (59)

Narrative literature review Expert opiniona

American Thyroid Association, 2000

Narrative literature review Expert opinionc

Royal College of

Physicians of London Society for Endocrinology, 1996

Screening with serum thyrotropin (TSH) every 5 yr for women and men over age 35 yr

Screening for individuals with symptoms and risk factors Addition of serum free thyroxine (FT4) when pituitary or hypothalamic disease suspected

General testing of population unjustified Screening for congenital hypothyroidism Screening patients after thyroid surgery, radioactive iodine treatment, or longstanding lithium treatment; low threshold for screening patients on amiodarone Consideration of screening patients with type I diabetes during first-trimester pregnancy by measuring antithyroid antibody

Biochemical confirmation of hypo-thyroidism with serum TSH and total thyroxine (T4) or FT4

Laboratory medicine Narrative literature review practice guidelines for Expert opinionc the diagnosis and monitoring of thyroid disease testing (60,61)

Newborn screening for Narrative literature review congenital hypo- Expert opinionc thyroidism: recommended guidelines (62)

American Association of

Clinical Chemists American Association of Clinical

Endocrinologists American Thyroid

Association Endocrine Society National Academy of Clinical Biochemistry, 1990 (update in progress)

American Academy of Pediatrics, 1993

Serum TSH for evaluating patients with stable thyroid status; FT4 in patients during first 2-3 mo treatment of thyroid dysfunction Prepregnancy or first-trimester pregnancy screening with serum TSH In patients receiving amiodarone, baseline TSH, thyroid peroxidase antibody, FT4, and FT3; biannual screening of TSH, FT4, and FT3 Assessment of thyroid status (using FT4 or T4 and TSH) in hospitalized patients, when clinical suspicion high Screening within first week of life either with filter paper blood spot primary T4 and backup TSH; or primary TSH with backup T4; or combined primary TSH and T4

Cord serum measurements in offspring of mothers with thyroid abnormalities Confirmatory serum measurements, serial serum T4 and TSH, as well as consideration of thyroid scan in infants with abnormalities Confirmation after age 3 yr with discontinuation of levothyroxine for 30 d, followed by serum TSH, T4

( continued)

Table 2 (continued)

Guideline

Methods used to analyze evidence

Organization, year

Summary of relevant recommendations

Periodic Health

Examinations: Summary of AAFP Policy Recommendations and Age Charts (63) Screening for congenital hypothyroidism (64)

Screening for congenital hypothyroidism (65)

Screening for thyroid disease (66)

Screening for thyroid disease (67)

Systematic literature review performed by U.S. Preventive Services Task Force Expert opinionc Systematic literature reviewb

Systematic literature review observational trials

Systematic literature reviewb b

American Academy of Family Physicians, 1996,2001

Canadian Task Force on Preventive Health Care, 1994,1998

U.S. Preventive Services Task Force, 1996

Systematic literature review Meta-analysis of

American College of Physicians- American Society of Internal Medicine, 1997

U.S. Preventive Services Task Force, 1996

Screening patients over age 60 yr recommended

Good evidence to support screening on all newborns during first week of life using routine TSH followed by T4 if necessary

Good evidence to support screening on all newborns, including those born at home, optimally between d 2 and 6 Choice of screening test determined by state requirements Screening women older than 50 yr with a sensitive TSH; FT4 when TSH is undetectable or > 10 mU/L Poor evidence to support screening women younger than age 50 and men Careful follow-up of patients with mild hypothyroidism Fair evidence to support exclusion of routine screening of thyroid disease in asymptomatic adults in periodic health examination

Screening for thyroid disorders and thyroid cancer in asymptomatic adults (68)

Subclinical hypo-thyroidism during pregnancy (69)

Systematic literature review adapted from U.S. Preventive Services b

Canadian Task Force on Preventive Health Care, 1994,1999

Task Force

Narrative literature review Expert opinionc

Despite insufficient evidence, recommend low threshold for screening with serum TSH in high-risk patients, including elderly, postpartum women, and persons with Down's syndrome Poor evidence to support screening of asymptomatic adults High level of clinical suspicion should be maintained in perimenopausal and postmenopausal women American Association of Routine screening with serum TSH Clinical Endocrinologists, reasonable early in pregnancy 1999 Screening with TSH recommended in women considering pregnancy Screening with serum TSH recommended in pregnant women with: goiter, antithyroid antibodies, family history of thyroid disease, autoimmune endocrine disease, symptoms suggestive of hypothyroidism, history of levothyroxine treatment b

Self-funded. Governmental funding. cNot specified.

autoimmune thyroiditis (see next paragraph) and in patients with hypopituitarism. Therefore, in patients with clinical features suggesting primary adrenal insufficiency (e.g., weight loss, hyperpigmentation, nausea, or vomiting) or pituitary disease (e.g., visual field deficits, diplopia, or hypogonadism), the possibility of hypoadrenalism should be excluded by adrenocorticotropic hormone stimulation testing.

Although autoimmune thyroiditis is not a complication of hypothyroidism per se, patients affected with it are also at risk of developing a relatively small set of associated autoimmune disorders. The polyglandular autoimmune syndrome type II includes hypothyroidism, primary adrenal insufficiency, and type I diabetes (57). Less commonly, hypothyroidism may occur in the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (or polyglan-dular autoimmune syndrome type I). Autoimmune thyroid disorders are associated with increased risk of developing pernicious anemia and gastric achlorhydria caused by intrinsic factor and parietal cell autoimmunity. Patients with autoimmune thyroiditis should be monitored for vitamin B12 deficiency with periodic complete blood counts and, whenever the disorder is seriously suspected, serum vitamin B12 measurement. Vitiligo, leukotrichia (prematurely gray hair), and alopecia areata have also been associated with autoimmune thyroiditis; although these disorders are often distressing, their prevention is not currently possible.

In conclusion, hypothyroidism occurs commonly, generates morbidity and mortality, and may be prevented at all stages of disease progression. Once hypothyroidism has been identified and treated with thyroxine, special attention to optimal dose management, complications of therapy, and the potential development of associated diseases can improve the clinical course and quality of life for affected individuals.

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