The multiple genetic causes of central hypothyroidism

[helvella]

OK - so it takes a bit of thought. But if you rely exclusively on TSH, as we see so often, it is simply impossible to diagnose central hypothyroidism. Yet it becomes fairly simple when FT4 and FT3 are also tested. At least, it should be enough to raise the question as to why the results are discordant.

Identifying the genes, and variants, is an important step, especially in that it potentially provides proof for diagnosis, but basic identification is far more important. It shouldn't matter why - genes, trauma, other disease processes - to begin with.

Best Pract Res Clin Endocrinol Metab. 2017 Mar;31(2):255-263. doi: 10.1016/j.beem.2017.04.003. Epub 2017 Apr 17.

The multiple genetic causes of central hypothyroidism.

Persani L1, Bonomi M2.

Author information

1 Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Division of Endocrine and Metabolic Diseases, San Luca Hospital, Istituto Auxologico Italiano, Milan, Italy. Electronic address: [e-mail].

2 Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Division of Endocrine and Metabolic Diseases, San Luca Hospital, Istituto Auxologico Italiano, Milan, Italy.

Abstract

An insufficient stimulation by thyrotropin (TSH) of an otherwise normal thyroid gland represents the cause of Central Hypothyrodism (CeH). CeH is about 1000-folds rarer than Primary Hypothyroidism and often represents a real challenge for the clinicians, mainly because they cannot rely on adequately sensitive parameters for diagnosis or management, as it occurs with circulating TSH in PH. Therefore, CeH diagnosis can be frequently missed or delayed in patients with a previously unknown pituitary involvement. A series of genetic defects have been described to account for isolated CeH or combined pituitary hormone defects (CPHDs) with variable clinical characteristics and degrees of severity. The recently identified candidate gene IGSF1 appears frequently involved. This review provides an updated illustration of the different genetic defects accounting for CeH.

Copyright © 2017 Elsevier Ltd. All rights reserved.

KEYWORDS:

central hypothyroidism; combined pituitary hormone deficiency; hypothyroidism; pituitary; thyrotropin; thyrotropin-releasing hormone

PMID: 28648512

DOI: 10.1016/j.beem.2017.04.003

ncbi.nlm.nih.gov/pubmed/286...

[BadHare]

Thanks Helvella!

Wish I'd had that yesterday, but might print it for my GP/

[Saggyuk]

Yes, I think that tsh, t4 and t3 should be done every time as standard anyway for these reasons and because tsh gives you so little to go by lol!

No, it really doesn't matter the cause but I suppose identification of genes could also be helpful in knowing who to monitor every few years for associated disorder so can be identified at a much earlier stage before years of feeling unwell. However, I think I'd rather not know anyway otherwise just expecting something that may never happen as is never definite gene or no gene. Also, we would all have to be happy with our genes being identified and documented lol

I suppose it's useful for cases that are not meeting all requirements for diagnosis and tests are inconclusive.

Regardless, from the posts I've read on here, I'm losing hope that many GPs can actually identify anything at all lol! I don't even expect them to know everything, same as I don't expect lawyers to know every case in every area, I just expect them to have enough knowledge to suspect when somethings not quite right and therefore a little googling is required

[Andyb1205]

A good additional read!

"A recent study led by researchers at McGill and published earlier this year in the journal Endocrinology has begun to unlock this mystery for what appears to be the most common genetic cause of central hypothyroidism by providing, for the first time, an understanding of the underlying mechanism of the disorder [...] “One thing that continues to surprise us is the heterogeneity of the disorder,” notes Dr. Bernard. “Family members with the same mutation have differing extents of hypothyroidism – some mild, some extreme."

publications.mcgill.ca/repo...

[helvella Administrator Thyroid UK in reply to Andyb1205]

Well worth reading - thank you.