Reference intervals in the diagnosis of thyroid... - Thyroid UK

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Reference intervals in the diagnosis of thyroid dysfunction: treating patients not numbers

PR4NOW profile image

A new article by Prof Jonklaas. Some hope perhaps. The full article is behind a paywall. Perhaps someone could get a full copy. PR


Although assigning a diagnosis of thyroid dysfunction appears quite simple, this is often not the case. Issues that make it unclear whether thyroid function is normal include transient changes in thyroid parameters, inter-individual and intra-individual differences in thyroid parameters, age-related differences, and ethnic variations. In addition, a statistically calculated distribution of thyroid analytes does not necessarily coincide with intervals or cutoffs that have predictive value for beneficial or adverse health outcomes. Based on current clincial trial data, it is unclear which individuals with mild thyroid-stimulating hormone elevations will benefit from levothyroxine treatment. For example, only a small number of patients with thyroid-stimulating hormone values of more than 10 mIU/L have been studied in a randomised manner. Even if therapy is initiated for abnormal thyroid function, not all treated individuals are maintained at the desired treatment target, and therefore might still be at risk. The consequence of this is that each patient's thyroid function needs to be assessed on an individual basis with the entire clinical picture in mind. Monitoring also needs to be vigilant, and the targets for treatment reassessed continually.

9 Replies

Thanks for posting. I will try and get a copy from the British Library sometime although I can't make it available.

This Summary doesn't make me hopeful! It's still the same old focus on primary hypothyroidism and the belief that blood tests are definitive. Blood tests are very useful, they identify primary hypothyroidism at an early stage for most patients and perhaps give an indication of deiodinase activity and thyrotrope performance. Blood tests fail to identify the large group of patients who fall within reference intervals but nontheless are profoundly hypothyroid (I'm using a loose definition of hypothyroidism, referring to signs and symptoms not thyroidal secretion).

It's nice to see an endocrinologist using the correct term 'reference interval', this is inded progress, the implicit acknowledgement that a reference interval is not a 'range' and definitively not a diagnostic range.

PR4NOW profile image
PR4NOW in reply to jimh111

jimh111 it is nice to see reference interval used. It is evident to me that there is a crack opening in the thinking of endocrinologists. The question is how long it will take. PR

I'll try

PR4NOW profile image
PR4NOW in reply to diogenes

Diogenes, she referenced more recent studies from the group. Nothing from Dr. Ito, maybe you should send her a copy. She did mention Prof. Thienpont's work.

There is also an interesting looking article on "Distinguishing reference intervals and clinical decision limits—a review by the IFCC Committee on Reference Intervals and Decision Limits." PR

20. Hoermann R Larisch R Dietrich JW Midgley JE

Derivation of a multivariate reference range for pituitary thyrotropin and thyroid hormones: diagnostic efficiency compared with conventional single-reference method.

Eur J Endocrinol. 2016; 174: 735-743

22. Hoermann R Midgley JE Giacobino A et al.

Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment.

Clin Endocrinol (Oxf). 2014; 81: 907-915

Also one by Dr. Dietrich et al.

23. Goede SL Leow MK Smit JW Dietrich JW

A novel minimal mathematical model of the hypothalamus-pituitary-thyroid axis validated for individualized clinical applications.

Math Biosci. 2014; 249: 1-7

shaws profile image

Thanks for posting PR4NOW - will there ever be a solution or revolution regarding the diagnosing/prescribing for patients?

Also those in Organisation seem to never read Research and do NOT read anything that will improve their patients' wellbeing and health. Imagine withdrawing T3 without notice and leaving people high and dry and in a panic. What's worse is making False Statements about NDT in order to get it withdrawn and not responding to John Lowe's Rebuttal upon NDT. So, in the UK it is levothyroxine or nil by mouth.

PR4NOW profile image
PR4NOW in reply to shaws

shaws, it is frustrating how long it takes but at least there is beginning to be some movement. I have a relative in the UK that can only use NDT, I understand the seriousness of the situation all too well. PR

m7-cola profile image
m7-cola in reply to shaws

I agree. It makes me so angry to think of the harm done to so many of us in withdrawing T3. And I cannot understand the apparent lack of interest in learning from their patients shown by doctors and endocrinologists.

Johannes Dietrich is getting this for me so I'll send it on via PM if you mail me. However, in the references it's very interesting that our paper (hitherto neglected) on the effects of univariate and bivariate development of reference ranges and inclusion/exclusion of patients within or without the range has been quoted here. This is because the correct bivariate analysis for FT4 and TSH, rather than being rectangular in univariate analysis, is elliptical and includes in the normal range some subclinicals which the univariate does not. They must thus realise at last that the way ranges are worked out is important for diagnostic decision making.

I found a link for this paper :

Being a sci-hub link it may become unavailable quite quickly, so if you want a copy download it now.

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