Vantyghem M C, Ghulam A, Hober C, Schoonberg C, D'Herbomez M, Racadot A, Boersma A, Lefebvre J
Service d'Endocrinologie et Maladies Métaboliques, C.H.R.U., Lille, France.
J Endocrinol Invest. 1998 Apr;21(4):219-25. doi: 10.1007/BF03347306.
Biological assessment of peripheral thyroid hormone action may be important in subclinical hypothyroidism, where decision-making is often difficult. The impairment of urinary cortisol metabolites in overt hypothyroidism reflects an acquired 11 beta hydroxysteroid dehydrogenase (11 beta OHSD) deficiency, and is assessed in terms of a reduction in the tetrahydrocortisone (THE)/tetrahydrocortisol (THF) ratio or THE/THE + alpha THF ratio; the alpha THF/THF ratio reflects 5 beta reductase activity. The aim of this study was to determine if urinary cortisol metabolite ratios are a good index of peripheral thyroid hormone action in subclinical hypothyroidism.
the THE/THF, THE/THF + alpha THF and alpha THF/THF ratios were measured in 24 h urine samples from 3 groups of subjects: 1) 18 euthyroid subjects; 2) 25 patients with elevated serum TSH and low FT4 levels (overt hypothyroidism); and 3) 25 patients with increased serum TSH and normal FT4 levels (subclinical hypothyroidism.
7/25 overtly and 5/25 subclinically hypothyroid patients had a THE/THF + alpha THF ratio below the mean control value -2 SD, while respectively 20/25 and 11/25 patients had a THE/THF ratio below the mean control value -2 SD. The mean THE/THF + alpha THF, THE/THF and alpha THF/THF ratios were significantly different among the 3 groups (ANOVA) and were lower in the overtly hypothyroid group than in the other two groups (Fisher's test); daily urine sodium output was also significantly different between the three groups and lower in the overtly and subclinically hypothyroid groups than in the control group (Fisher's test). FT3 and FT4 both correlated with THE/THF + alpha THF in the overtly hypothyroid patients (r = 0.43; p < 0.05 and r = 0.40; p < 0.05, respectively). In the subclinically hypothyroid patients, TSH correlated with THE/THF + alpha THF (r = 0.44; p < 0.05) and THE/THF (r = 0.43; p < 0.05). FT3, FT4 and TSH levels correlated with THE/THF + alpha THF (p < 0.001), THE/THF (p < 0.001), alpha THF/THF (p < 0.001) and daily natriuresis (p < 0.05) in the whole population (patients + controls). In conclusion, urinary cortisol metabolites, although impaired in overt hypothyroidism, are not an accurate index of peripheral thyroid hormone deficiency in subclinical hypothyroidism. We also identified an increase in the alpha THF/THF ratio in overt hypothyroidism, which may be related to 5 beta reductase disturbances.
在外周甲状腺激素作用的生物学评估在亚临床甲状腺功能减退中可能很重要，因为在这种情况下决策往往很困难。显性甲状腺功能减退中尿皮质醇代谢产物的损害反映了获得性11β羟类固醇脱氢酶（11βOHSD）缺乏，并且根据四氢可的松（THE）/四氢皮质醇（THF）比值或THE/THE +αTHF比值的降低来评估；αTHF/THF比值反映5β还原酶活性。本研究的目的是确定尿皮质醇代谢产物比值是否是亚临床甲状腺功能减退中外周甲状腺激素作用的良好指标。
在3组受试者的24小时尿液样本中测量THE/THF、THE/THE +αTHF和αTHF/THF比值：1）18名甲状腺功能正常的受试者；2）25名血清促甲状腺激素（TSH）升高且游离甲状腺素（FT4）水平低的患者（显性甲状腺功能减退）；3）25名血清TSH升高且FT4水平正常的患者（亚临床甲状腺功能减退）。
25名显性甲状腺功能减退患者中有7名和25名亚临床甲状腺功能减退患者中有5名的THE/THE +αTHF比值低于平均对照值-2标准差，而分别有20/25和11/25的患者THE/THF比值低于平均对照值-2标准差。3组之间的平均THE/THE +αTHF、THE/THF和αTHF/THF比值有显著差异（方差分析），且显性甲状腺功能减退组低于其他两组（Fisher检验）；三组之间的每日尿钠排出量也有显著差异，显性和亚临床甲状腺功能减退组低于对照组（Fisher检验）。在显性甲状腺功能减退患者中，FT3和FT4均与THE/THE +αTHF相关（r = 0.43；p < 0.05和r = 0.40；p < 0.05）。在亚临床甲状腺功能减退患者中TSH与THE/THE +αTHF相关（r = 0.44；p < 0.05）和THE/THF相关（r = 0.43；p < 0.05）。在整个人群（患者+对照）中，FT3、FT4和TSH水平与THE/THE +αTHF（p < 0.001）、THE/THF（p < 0.001）、αTHF/THF（p < 0.001）和每日尿钠排泄量（p < 0.05）相关。总之，尿皮质醇代谢产物虽然在显性甲状腺功能减退中受损，但不是亚临床甲状腺功能减退中外周甲状腺激素缺乏的准确指标。我们还发现显性甲状腺功能减退中αTHF/THF比值增加，这可能与5β还原酶紊乱有关。
