WORKING GROUP
Professor Jean-Louis SCHLIENGER, specialist in internal medicine, chairman, Strasbourg
Dr. Najoua MLIKA-CABANNE, Project Manager, ANAES, Paris
Patrice BLOUIN, pharmacist, Bordeaux
Dr Jean-Victor BUKOWSKI, geriatrician, Roubaix
Dr. Maurice CHUPIN, endocrinologist, Nantes
Dr. Isabelle COLLIGNON, laboratory analyst, Marne-La-Coquette
Dr. Maurice DE BOYSSON, endocrinologist, Bourges
Dr. Richard ISNARD, cardiologist, Paris
Dr. Jean-Luc JAMET, laboratory analyst, Tourcoing
Dr. Edgar KALOUSTIAN, endocrinologist, Compiègne
Dr. Jean-Luc MAS, general practitioner, Bourgoin-Jallieu
Mme Catherine MASSART, laboratory analyst, Rennes
Dr. Réginald MIRA, endocrinologist, Antibes
Professor Vincent ROHMER, endocrinologist, Angers
Professor Hugues ROUSSET, specialist in internal medicine, Pierre-Bénite
Dr. Patrick SOULIÉ, general practitioner, Valderies
Dr. Ewa TESLAR, general practitioner, Paris
READING GROUP
Dr. Michel ALIX, specialist in internal medicine, Caen
Professor Françoise ARCHAMBEAUD, specialist in internal medecine, Limoges
Dr. Louis AUBERT, specialist in internal medicine, Toulon
Dr. Line BALDET, endocrinologist, Montpellier
Dr. Didier BEUTTER, endocrinologist, Vannes
Dr. Philippe CARON, endocrinologist, Toulouse
Dr. Gérard CHABRIER, endocrinologist, Strasbourg
Dr. Françoise CHANTEGREIL, general practitioner, Saint-Mandé
Dr. Joël CHAPUIS, general practitioner, Baouhaye
Professor Alain COHEN-SOLAL, cardiologist, Clichy
Professor Bernard CONTE-DEVOLX, endocrinologist, Marseilles
Dr. Gisèle COUPLET, laboratory analyst, Lille
Dr. François DANY, cardiologist, Limoges
Dr. Alain DAVER, laboratory analyst, Angers
Professor Jean DOUCET, specialist in internal medicine, geriatrician, Rouen
Professor Michel DREYFUS, gynaecologist-obstetrician, Caen
Dr. Hubert DU ROSTU, endocrinologist, Nantes
Dr. Bernard GAY, ANAES Scientific Council, Paris
Dr. Philippe GIRAUD, specialist in internal medicine, endocrinologist, Angers
Dr. Anne GRUSON, ANAES Scientific Council, Paris
Fabrice GERBER, laboratory analyst, Bourg-D’Oisans
Dr. Claudine GUILLAUSSEAU, endocrinologist, Paris
Dr. Chantal HOULBERT, laboratory analyst, Alençon
Dr. Robert KAHN, general practitioner, Marseilles
Dr. Jacques LAGARDE, general practitioner, L’Isle-Jourdain
Dr. Christian LAISNE, cardiologist, Armentières
Dr. Jean-Louis LEGRAND, laboratory analyst, Toulouse
Dr. Michel LÉVÈQUE, general practitioner, Thann
Dr. Christian MARTINET, general practitioner, Saint-Julien-de-L’Escap
Dr. Alain MILLET, general practitioner, Tarcenay
Dr. Patrick NAMBOTIN, general practitioner, Dolomieu
Professor Jacques ORGIAZZI, endocrinologist, diabetologist, Pierre-Bénite
Dr. Patrick POCHET, general practitioner, Clermont-Ferrand
Dr. Alain POTIER, gynaecologist-obstetrician, Marseilles
Dr. Jean-François POUGET-ABADIE, endocrinologist, Niort
Dr. Gilbert ROUANET, general practitioner, Béthune
Dr. Jean-Claude RYMER, laboratory analyst, Créteil
Professor Jean-Louis SADOUL, endocrinologist, Nice
M. Rémy SAPIN, laboratory analyst, Strasbourg
Dr. Jean TARDIEU, geriatrician, Mandelieu
Dr. René THIBON, general practitioner, Nîmes
Dr. Jean-Marie VETEL, geriatrician, specialist in internal medicine, Le Mans
Professor Jean-Louis WEMEAU, endocrinologist, Lille
Dr. Patrice WINISZEWSKI, endocrinologist, Belfort
GUIDELINES
The literature on laboratory diagnosis and monitoring of hyperthyroidism in adults consists
mainly of editorials, case series, recommendations based on expert opinions, or trials conducted
using a very dubious design. The guidelines below are thus essentially based on expert opinion.
The following definitions are used in this study:
1. Hyperthyroidism means thyroid gland overactivity, which increases thyroid hormone
production and leads to thyrotoxicosis.
A distinction is made between different types of hyperthyroidism:
• Overt hyperthyroidism (also called clinical hyperthyroidism) where there is a
combination of clear clinical signs and abnormal laboratory values (TSH low, T4
and/or T3 high);
• Subclinical hyperthyroidism (also called masked or asymptomatic hyperthyroidism)
which is used to describe cases where symptoms are unclear and laboratory values are
abnormal (TSH concentration low, T4 and/or T3 concentrations normal or at the upper
limit of normal).
2. TSH, free T4 (FT4) and free T3 (FT3) are considered to be abnormal when values are
outside the laboratory’s range of normal.
LABORATORY TESTS USEFUL FOR THE DIAGNOSIS OR MONITORING OF
HYPERTHYROIDISM
The following recommendations are made concerning sampling and analysis:
 The laboratory should state which analytical method was used and specify the reference
range of values to be used when interpreting the findings. The method used for
determination of TSH should preferably be a third-generation method;
 Once TSH has been determined, the serum should be kept in the laboratory (for a
maximum of 7 days at +4°C). Thus further tests can be performed, without requiring a
further sample to be taken from the patient;
 When T4 or T3 has to be measured, it is recommended that only the free fraction of the
hormones be determined.
Tests which are useful for positive diagnosis of hyperthyroidism, regardless of cause, are TSH,
free T4, and very occasionally, free T3 (for T3 hyperthyroidism). For monitoring, add TSH
receptor antibodies in Graves’ disease (see table):
The proposed guidelines are classified as grade A, B or C depending on the level of
evidence of the studies on which they are based:
• A grade A guideline is based on scientific evidence established by trials of a high
level of evidence, for example randomised controlled trials of high power and free
of major bias, and/or meta-analyses of randomised controlled trials, decision
analysis based on properly conducted studies;
• A grade B guideline is based on presumption of a scientific foundation derived
from studies of an intermediate level of evidence, for example randomised
controlled trials of low power, well-conducted non-randomised controlled trials,
cohort studies;
• A grade C guideline is based on studies of a lower level of proof, for example case-
control studies, case series, etc.
If there is no evidence, the proposed guidelines are based on agreement among
professionals.
STRATEGY FOR USING LABORATORY TESTS TO DIAGNOSE
HYPERTHYROIDISM
As a first-line test, it is both necessary and sufficient to determine TSH. Any other tests which
may be useful in reaching the diagnosis are second-line tests and depend on the result of the
TSH test and the clinical picture. In practice, there are three possible situations:
 TSH value normal:
The specificity of this test means that a diagnosis of hyperthyroidism is eliminated (Grade C),
unless the clinical picture is very strongly suggestive of thyrotoxicosis. In this case,
measurement of TSH should be completed by measurement of free T4. An increased free T4
value suggests hyperthyroidism of hypothalamo-pituitary origin, or thyroid hormone resistance
syndrome;
 TSH value low:
Free T4 should be measured to confirm the diagnosis (Grade C) and to determine the severity of
hyperthyroidism before treatment is started;
• TSH low or undetectable and free T4 high: clear hyperthyroidism;
• Low or even undetectable TSH, with normal or abnormal free T4: work-up must be
continued with measurement of free T3;
– free T3 high in a symptomatic patient: T3 hyperthyroidism,
– free T3 normal in a patient who has few symptoms or is monosymptomatic:
subclinical hyperthyroidism;
• Special case: when TSH is low, but close to the reference range, and the clinical picture
remains highly suggestive, TSH should be measured again, using a third-generation
method known to have good specificity, together with determination of free T4.
At the same time, the cause of the hyperthyroidism should be investigated.
Table. Usefulness of tests used for positive diagnosis of hyperthyroidism,
aetiologic diagnosis, and monitoring
First-line
tests
Second-line
tests
Tests which
are not
useful
TSH
Free T4, and free T3 if
free T4 is normal and
TSH is low
TRH test, except in very
unusual circumstances
TPO antibodies
Thyroglobulin antibodies
TSH receptor antibodies
Thyroglobulin
Thyroxine-binding
globulin
Blood iodine / urinary
iodine
ESR, C-reactive protein
(CRP)
Lipids
TPO antibodies (autoimmune
hyperthyroidism)
TSH receptor antibodies (Graves’
disease)
Thyroglobulin (thyrotoxicosis
factitia)
Blood iodine /Urinary iodine
(iatrogenic hyperthyroidism)
ESR, C-reactive protein (CRP)
(subacute granulomatous
thyroiditis)
TRH test (TSH-secreting adenoma,
resistance to thyroid hormones)
Thyroxine-binding globulin
Lipids
TSH, free hormone
(whichever was abnormal)
T4 or T3
TSH receptor antibodies,
in Graves’ disease
Thyroglobulin
Thyroxine-binding
globulin
Blood iodine / urinary
iodine
ESR, C-reactive protein
(CRP)
Lipids
Positive diagnosis
of hyperthyroidism Aetiologic diagnosis Monitoring