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Aging and disease    2019, Vol. 10 Issue (3) : 520-529     DOI: 10.14336/AD.2018.0817
Orginal Article |
Subclinical Hypothyroidism: is it Really Subclinical with Aging?
Robin Gourmelon1, Sandrine Donadio-Andréi2, Karim Chikh1,3,4,5, Muriel Rabilloud6, Elisabetta Kuczewski3, Anne-Sophie Gauchez5,7,8,10, Anne Charrié1,3,4,5, Pierre-Yves Brard10, Raphaëlle Andréani10, Jean-Cyril Bourre10, Christine Waterlot8, Domitille Guédel8, Anne Mayer8, Emmanuel Disse1, Charles Thivolet1, Hélène Du Boullay8, Claire Falandry1, Thomas Gilbert1, Anne François-Joubert8, Antoine Vignoles1, Catherine Ronin2, Marc Bonnefoy1,*
1Service de Gériatrie, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France.
2Siamed’Xpress, Hôtel Technologique Morandat, 13120 Gardanne, France.
3Hospices Civils de Lyon, 69002 Lyon, France.
4Laboratoire de Biochimie et Biologie Moléculaire, Centre de Biologie Sud, Centre Hospitalier Lyon Sud 69 495 Pierre Bénite Cedex, France.
5Société Française de Médecine Nucléaire, Groupe de Biologie Spécialisée, 75237 Paris Cedex 05, France.
6Service de Biostatistiques, Hospices Civils de Lyon, Lyon, France.
7UMR-S INSERM 1039, 38000 Grenoble, France.
8Service de Médecine Nucléaire, Centre Hospitalier Métropole Savoie, 73000 Chambéry, France.
9Pôle de Biologie, Centre Hospitalier et Universitaire de Grenoble, CS 10217 38043 Grenoble Cedex 9, France.
10Service d’Endocrinologie, Centre Hospitalier Métropole Savoie, 73000 Chambéry, France
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No recent study has focused on clinical features of subclinical hypothyroidism (SCH), especially in older patients. TSH measurement has remarkably evolved these last 20 years and thus reconsideration is needed. In our prospective multicenter study (2012-2014) including 807 subjects aged <60 years (<60y) and 531 subjects ≥60 years (≥60y), we have monitored 11 hypothyroidism-related clinical signs (hCS) together with TSH, FT4, FT3 and anti-thyroperoxidase antibodies values. hCS expression has been compared in patients with SCH vs euthyroidism in each age group. The number of hCS above 60y of age were found to be more elevated in the euthyroid population (1.9 vs 1.6, p<0.01) than in the SCH population (2.3 vs 2.6, p=0.41) while increase in hCS is limited to SCH subjects in the <60y group (p<0.01). The percentage of subjects with at least 3 signs increased with SCH in the <60y group (42.6% vs 25.0%, p<0.01) but not ≥60y (34.4% vs 33.9%, p=0.96). In older individuals, only three hCS could be related to both SCH and a decreased T3/T4-ratio (0.26 vs 0.27, p<0.01), suggesting either a reduced activity of TSH, or an adaptive response with aging. While hCS are clearly associated with SCH in patients <60y, they are not so informative in older subjects. TSH measurements carried out on the basis of hCS need to be interpreted with caution in aged patients. A reassessment of the TSH reference range in older patients is clearly needed and should be associated to more appropriate monitoring of thyroid dysfunction

Keywords thyroid deficiency      aging      symptoms      TSH     
Corresponding Authors: Bonnefoy Marc   
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These authors contributed equally to this work

Just Accepted Date: 07 September 2018   Online First Date: 06 September 2018    Issue Date: 07 September 2018
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Articles by authors
Robin Gourmelon
Sandrine Donadio-Andréi
Karim Chikh
Muriel Rabilloud
Elisabetta Kuczewski
Anne-Sophie Gauchez
Anne Charrié
Pierre-Yves Brard
Raphaëlle Andréani
Jean-Cyril Bourre
Christine Waterlot
Domitille Guédel
Anne Mayer
Emmanuel Disse
Charles Thivolet
Hélène Du Boullay
Claire Falandry
Thomas Gilbert
Anne François-Joubert
Antoine Vignoles
Catherine Ronin
Marc Bonnefoy
Cite this article:   
Robin Gourmelon,Sandrine Donadio-Andréi,Karim Chikh, et al. Subclinical Hypothyroidism: is it Really Subclinical with Aging?[J]. Aging and disease, 2019, 10(3): 520-529.
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Figure 1.  Flowchart of the recruitment, selection and exclusion process of the cohort.
Groups & Classes<60 years≥60 years
Euthyroid**1.6±1.6(n=739) ††1.9±1.7(n=469)

4.1-10.0mIU/L range:
TPOAbs (-)2.4±1.9(n=37)1.8±2.0(n=42)
TPOAbs (+)3.0±2.3(n=28)2.7±2.3(n=16)
Table 1  Mean number of overall clinical signs.
Figure 2.  Mean TSH (A), FT3 (B), FT4 (C) levels and FT3/FT4 ratios (D) as a function of TSH levels

Asterisks indicate significant differences between age groups (**, p<0.01) and crosses indicate significant differences between normal (0.17-4.05 mIU/L) and elevated (>4.05 mIU/L) TSH groups or difference between the absence/presence of TPOAbs when TSH is in the 4.1-10.0mIU/L range (†, p<0.05; ††, p<0.01).

Figure 3.  Percentage of subjects with 0, 1, 2, or 3 or more clinical signs by TSH groups

Data from all subjects (A), subjects <60y (B) and ≥60y (C) are presented.

Figure 4.  Prevalence of individual hypothyroidism-related clinical signs according to age

Age groups are <60y (white bars) and ≥60y (black bars). A) euthyroid subjects (TSH, 0.17-4.05mIU/L); B) subclinical hypothyroid subjects (TSH, >4.05mIU/L). Bars with an asterisk are significantly different between <60y and ≥60y groups (*p<0.05; **p<0.01).

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