1. N Engl J Med. 2017 Jun 29;376(26):2534-2544. doi: 10.1056/NEJMoa1603825. Epub
2017 Apr 3.

Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.

Stott DJ(1), Rodondi N(1), Kearney PM(1), Ford I(1), Westendorp RGJ(1), Mooijaart
SP(1), Sattar N(1), Aubert CE(1), Aujesky D(1), Bauer DC(1), Baumgartner C(1),
Blum MR(1), Browne JP(1), Byrne S(1), Collet TH(1), Dekkers OM(1), den Elzen
WPJ(1), Du Puy RS(1), Ellis G(1), Feller M(1), Floriani C(1), Hendry K(1), Hurley
C(1), Jukema JW(1), Kean S(1), Kelly M(1), Krebs D(1), Langhorne P(1), McCarthy
G(1), McCarthy V(1), McConnachie A(1), McDade M(1), Messow M(1), O'Flynn A(1),
O'Riordan D(1), Poortvliet RKE(1), Quinn TJ(1), Russell A(1), Sinnott C(1), Smit 
JWA(1), Van Dorland HA(1), Walsh KA(1), Walsh EK(1), Watt T(1), Wilson R(1),
Gussekloo J(1); TRUST Study Group.

Collaborators: Lakwijk YA, Ford G, Robinson TG, Dayan C, Bennett K, Dinnett E,
Syme C, de Craen AJM, McSkimming P, Stevenson A, Gillespie L, Douglas E.

Author information: 
(1)From the Academic Section of Geriatric Medicine, Institute of Cardiovascular
and Medical Sciences (D.J.S., K.H., P.L., M. McDade, T.J.Q.), the Robertson
Centre for Biostatistics, Institute of Health and Wellbeing (I.F., S.K., A.M., M.
Messow, R.W.), and the Institute of Cardiovascular and Medical Sciences (N.S.),
University of Glasgow, Glasgow, and Care of the Elderly-Rehabilitation, Monklands
Hospital, NHS Lanarkshire, Airdrie (G.E.) - all in the United Kingdom; the
Department of General Internal Medicine, Inselspital, Bern University Hospital
(N.R., C.E.A., D.A., C.B., M.R.B., M.F., C.F., D.K., H.A.V.D.), and the Institute
of Primary Health Care (N.R., M.F.), University of Bern, Bern, and the Service of
Endocrinology, Diabetes, and Metabolism, University Hospital of Lausanne,
Lausanne (T.-H.C.) - all in Switzerland; the Department of Epidemiology and
Public Health (P.M.K., J.P.B., C.H., G.M., A.O., D.O., C.S., K.A.W., E.K.W.), the
Pharmaceutical Care Research Group, School of Pharmacy (S.B., M.K., K.A.W.), the 
School of Nursing and Midwifery (V.M.), and the Department of General Practice
(A.R., E.K.W.), University College Cork, and the Health Research Board Clinical
Research Facility, Mercy University Hospital (M.K.) - all in Cork, Ireland; the
Department of Public Health and Center for Healthy Aging, University of
Copenhagen (R.G.J.W.), and the Department of Medical Endocrinology, Copenhagen
University Hospital Rigshospitalet (T.W.), Copenhagen, and the Department of
Internal Medicine, Copenhagen University Hospital Herlev, Herlev (T.W.) - all in 
Denmark; the Departments of Gerontology and Geriatrics (S.P.M.), Internal
Medicine (O.M.D.), Clinical Epidemiology (O.M.D.), Clinical Chemistry and
Laboratory Medicine (W.P.J.E.), Public Health and Primary Care (R.S.D.P.,
R.K.E.P., J.G.), and Cardiology (J.W.J.), Leiden University Medical Center, and
the Institute for Evidence-based Medicine in Old Age (S.P.M.), Leiden, and
Radboud University Medical Center, Nijmegen (J.W.A.S.) - all in the Netherlands; 
and the Departments of Medicine, Epidemiology, and Biostatistics, University of
California, San Francisco, San Francisco (D.C.B.).

Comment in
    N Engl J Med. ;377(14 ):e20.
    N Engl J Med. ;377(14):e20.
    N Engl J Med. ;377(14 ):e20.
    N Engl J Med. ;377(14 ):e20.
    Ann Intern Med. 2017 Aug 15;167(4):JC14.

BACKGROUND: The use of levothyroxine to treat subclinical hypothyroidism is
controversial. We aimed to determine whether levothyroxine provided clinical
benefits in older persons with this condition.
METHODS: We conducted a double-blind, randomized, placebo-controlled,
parallel-group trial involving 737 adults who were at least 65 years of age and
who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99
mIU per liter; free thyroxine level within the reference range). A total of 368
patients were assigned to receive levothyroxine (at a starting dose of 50 μg
daily, or 25 μg if the body weight was <50 kg or the patient had coronary heart
disease), with dose adjustment according to the thyrotropin level; 369 patients
were assigned to receive placebo with mock dose adjustment. The two primary
outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on
a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is
0 to 100, with higher scores indicating more symptoms or tiredness, respectively;
minimum clinically important difference, 9 points).
RESULTS: The mean age of the patients was 74.4 years, and 396 patients (53.7%)
were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at
baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the
placebo group, as compared with 3.63 mIU per liter in the levothyroxine group
(P<0.001), at a median dose of 50 μg. We found no differences in the mean change 
at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and
0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95%
confidence interval [CI], -2.0 to 2.1) or the Tiredness score (3.2±17.7 and
3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No
beneficial effects of levothyroxine were seen on secondary-outcome measures.
There was no significant excess of serious adverse events prespecified as being
of special interest.
CONCLUSIONS: Levothyroxine provided no apparent benefits in older persons with
subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST
ClinicalTrials.gov number, NCT01660126 .).

DOI: 10.1056/NEJMoa1603825 
PMID: 28402245  [Indexed for MEDLINE]