The thyrotropin reference range should remain unchanged.
BACKGROUND
Recent recommendations to decrease the upper limit of the TSH reference range from 4.5 to 2.5 mIU/liter, based on the high proportion of normal people whose serum TSH is less than 2.5 mIU/liter and the observation that those with TSH between 2.5 and 4.5 mIU/liter [upper reference range (URR)] have increased risk of progression to overt hypothyroidism (Whickham, 20-yr data), have not been subjected to critical analysis.


METHODS
The study subjects were from the Reference Group of NHANES III, 14,333 people more than 12 yr old, without known thyroid disease or antithyroid antibodies; 85% had TSH levels below 2.5 mIU/liter, and 2.3% had subclinical hypothyroidism (SCH). An additional 9.7% had URR TSH, representing 20.6 million Americans, who would also be identified as SCH if the upper TSH limit were decreased. Many with URR TSH do not have thyroid disease.


METHODS
The time of phlebotomy is important, because the TSH level varies throughout the day, with early morning values greater than later ones, and is accentuated by sleep deprivation, strenuous exercise, or working during the night or evening shifts. Repeated measurements in the same individual vary considerably over months.


RESULTS
About half of those with URR TSH probably have thyroid disease, but most with thyroid disease, antithyroid peroxidase antibodies, have TSH below 2.5 mIU/liter. Those with URR TSH with thyroid disease probably have minimal thyroid deficiency, without any reported adverse health consequences or benefit of treatments with levothyroxine.


CONCLUSIONS
Because routine levothyroxine treatment is not recommended for SCH, it is certainly not warranted in individuals with URR TSH. For all patients with URR TSH, it is reasonable to determine serum TSH every 1-2 yr.
Surks
Martin I
MI
Division of Endocrinology and Metabolism, Department of Medicine, Montefiore Medical Center, 111 East 210th Street, Bronx, New York 10467, USA. msurks@westnet.com
Goswami
Gayotri
G
Daniels
Gilbert H
GH
D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy; D012016:Reference Values; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000627:therapeutic use
D013972:Thyrotropin; D013974:Thyroxine