Lab Interpretation: High thyroid-stimulating hormone (TSH) in adults

ALGORITHM — 

The evaluation of a high thyroid-stimulating hormone (TSH) depends upon whether the TSH was measured to monitor levothyroxine therapy (algorithm 1) or to evaluate thyroid dysfunction (algorithm 2).

MONITOR LEVOTHYROXINE THERAPY — 

For most patients with treated primary hypothyroidism, therapy may be monitored with the TSH alone (algorithm 1). (For patients with central [secondary] hypothyroidism, serum free thyroxine [T4; not TSH] is used to monitor therapy).

Assess for:

●Compliance.

●Medications that may reduce absorption of levothyroxine (eg, calcium carbonate, iron sulfate, omeprazole) (table 1).

●Other factors that may increase thyroid hormone requirements (eg, weight gain, pregnancy, estrogen therapy).

Confirm that levothyroxine is taken daily on an empty stomach with water, ideally an hour before breakfast, and that medications that interfere with its absorption are taken several hours after the dose.

If adherence to the medication regimen is confirmed (and the most recent dose adjustment was at least four to six weeks prior), patients with primary hypothyroidism and high TSH typically require a dose increase. If the TSH is slightly elevated (eg, 5 to 10 mU/L), a small increase of 12 to 25 mcg/day is usually sufficient. If the TSH is ≥10 mU/L to <20 mU/L, a larger dose increase (eg, 25 to 50 mcg/day) is usually necessary. If the TSH is ≥20 mU/L, obtain a free T4 to guide dose increase. The serum TSH should be remeasured six to eight weeks after any change in dose. Further dose adjustments may be needed. (See "Treatment of primary hypothyroidism in adults", section on 'Adjustment of maintenance dose'.)

EVALUATE THYROID DYSFUNCTION — 

In most individuals, measurement of TSH alone is sufficient for the initial evaluation of suspected thyroid dysfunction in the ambulatory setting. (If pituitary or hypothalamic disease is known or suspected, both serum TSH and free T4 should be measured for the initial evaluation).

If the TSH is high, it should be repeated along with a serum free T4. Additional testing may be indicated depending on the clinical setting and the free T4 level (algorithm 2).

Hospitalized or ill patients — In general, TSH should not be assessed in seriously ill patients unless there is a strong suspicion of thyroid dysfunction, since there are many other factors in acutely or chronically ill euthyroid patients that influence TSH secretion. The degree of TSH elevation, the severity of illness, and the suspicion for hypothyroidism determine management. (See "Thyroid function in nonthyroidal illness", section on 'Evaluation'.)

One approach is as follows:

●TSH between upper limit of normal and <10 mU/L – If the patient appears to be recovering from the underlying illness, repeat the TSH in one to two weeks. Few of these patients prove to have hypothyroidism when re-evaluated after recovery from their illness.

●TSH 10 to 20 mU/L – Measure free T4. Treatment with levothyroxine may be appropriate depending on the free T4 level, clinical suspicion of hypothyroidism, and degree of nonthyroidal illness. If uncertain, repeat the TSH and free T4 in one to two weeks. Thyroid function tests may improve in patients recovering from nonthyroidal illness.

●TSH >20 mU/L – Measure free T4:

•Free T4 low – Initiate thyroid hormone.

•Free T4 normal – Repeat TSH and free T4 in one to two weeks.

Myxedema coma is a rare presentation of hypothyroidism. The diagnosis of myxedema coma should be considered in any patient with coma or depressed mental status who also has hypothermia, hyponatremia, and/or hypercapnia, particularly in a patient with a thyroidectomy scar, a history of radioiodine therapy, or hypothyroidism. The serum T4 and triiodothyronine (T3) concentrations are usually very low, and the serum TSH concentration high in patients with myxedema coma due to primary hypothyroidism. (See "Myxedema coma", section on 'Diagnosis'.)

Pregnant women — Hypothyroidism can have adverse effects on pregnancy outcomes, depending upon the severity of the biochemical abnormalities. (See "Hypothyroidism during pregnancy: Clinical manifestations, diagnosis, and treatment", section on 'Pregnancy complications'.)

For pregnant women with an elevated TSH:

●Remeasure TSH along with free or total T4 (total T4 preferred if trimester-specific reference range for free T4 unavailable).

●If subclinical (high TSH with normal free T4) or overt (high TSH with low free T4) hypothyroidism is confirmed, begin thyroid hormone replacement.

●Obtain consultation with a clinician experienced with managing thyroid dysfunction during pregnancy.

Because of the changes in thyroid physiology during normal pregnancy and because there are population differences in the TSH upper reference limit, thyroid function tests should be interpreted using population-based, trimester-specific reference ranges for TSH (and assay method and trimester-specific reference ranges for serum free T4). When population-based, trimester-specific reference ranges are not available, 4 mU/L should be considered the upper limit in pregnant women. (See "Overview of thyroid disease and pregnancy", section on 'Trimester-specific reference ranges' and "Hypothyroidism during pregnancy: Clinical manifestations, diagnosis, and treatment", section on 'Indications for treatment'.)

Ambulatory setting, nonpregnant — For ambulatory patients with a high TSH (confirmed on repeat measurement), evaluation and management depend upon the free T4 level.

Free T4 low — The most common cause of primary hypothyroidism (high TSH with low free T4) in iodine-sufficient areas of the world is chronic autoimmune (Hashimoto's) thyroiditis, indicated by the presence of high serum concentrations of antibodies to thyroid peroxidase (TPO) (table 2). We do not routinely measure TPO antibodies in patients with primary overt hypothyroidism because almost all have chronic autoimmune thyroiditis. (See "Diagnosis of and screening for hypothyroidism in nonpregnant adults", section on 'Diagnosis' and "Disorders that cause hypothyroidism" and "Treatment of primary hypothyroidism in adults", section on 'Initial dose'.)

A patient with a low free T4 and a slightly high serum TSH concentration (eg, 5 to 10 mU/L [normal range 0.5 to 5 mU/L]) could have either primary or, rarely, central hypothyroidism. In central hypothyroidism, serum TSH levels are typically low or inappropriately normal, but TSH may be slightly elevated due, in part, to the secretion of TSH that has reduced biologic activity but normal immunoactivity. Suspect central hypothyroidism in patients with known hypothalamic or pituitary disease and when there are symptoms and signs of other hormonal deficiencies. (See "Central hypothyroidism", section on 'Diagnosis'.)

Free T4 normal — A high TSH (but usually <10 mU/L) with a normal free T4 is consistent with subclinical hypothyroidism. Subclinical hypothyroidism may occur in the presence or absence of mild symptoms of hypothyroidism. Most patients with subclinical hypothyroidism have chronic autoimmune (Hashimoto's) thyroiditis:

●Measure repeat TSH (with reflex to free T4, if offered by the laboratory) in one to three months to confirm diagnosis because the serum TSH can be transiently elevated. If TSH is persistently elevated, measure free T4 if not already measured by the laboratory.

●Some experts measure TPO antibodies in patients with subclinical hypothyroidism, since their titer correlates with the likelihood and rate of progression to permanent overt hypothyroidism and can guide subsequent management (ie, initiation of levothyroxine or ongoing monitoring of TSH).

●In women planning pregnancy or undergoing infertility treatment, the TSH should be repeated and, if elevated, levothyroxine should be initiated before conception.

(See "Subclinical hypothyroidism in nonpregnant adults", section on 'Differential diagnosis' and "Subclinical hypothyroidism in nonpregnant adults", section on 'Identifying the cause' and "Diagnosis of and screening for hypothyroidism in nonpregnant adults", section on 'Thyroid peroxidase antibodies'.)

Free T4 high — The combination of high TSH and high free T4 is relatively uncommon, and depending on the underlying etiology, patients with these thyroid function tests may have clinical signs and symptoms of hyperthyroidism (eg, palpitations, tremor, heat intolerance).

Patients with high TSH and free T4 may have:

●Nonadherence to treatment for hypothyroidism with increased intake of levothyroxine prior to blood sampling (free T4 may be high or normal).

●TSH-secreting pituitary adenoma.

●Resistance to thyroid hormone.

●Assay interference due to the presence of heterophilic antibodies or autoantibodies to TSH.

Amiodarone therapy may also cause an elevated TSH and free T4, particularly early in the course of therapy. In patients with normal underlying thyroid function, serum TSH normalizes after three to six months of therapy, whereas free T4 may remain slightly elevated or in the upper normal range. (See "Amiodarone and thyroid dysfunction", section on 'Transient changes in thyroid function tests'.)

Measure:

●Total T3

Obtain endocrinology consultation for further evaluation and management. (See "TSH-secreting pituitary adenomas", section on 'Diagnosis' and "TSH-secreting pituitary adenomas", section on 'Assay interference' and "Resistance to thyroid hormone and other defects in thyroid hormone action", section on 'Laboratory findings'.)

REFERENCE RANGE — 

The normal reference range for serum TSH in nonpregnant adults is approximately 0.5 to 4 mU/L but can vary depending on the patient population and clinical laboratory. Interpretation of a specific abnormal result should be based upon the reference range reported for that result.

CITATIONS — 

The supporting references for this content are accessible in the linked topics.