thyroid ca - cold nodules with iodine uptake

[fleshwound]

cold = malignant
but papillary carcinoma has positive iodine uptake. Doesn't that make it hot? And follicular carcinoma also absorbs iodine avidly. where did my brain go wrong?

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[addy]

I've basically given up trying to get the details with this iodine uptake nonsense. It should be straight forward but it's not...I'm just going with cold = cancer; hot = not

 

[thehundredthone]

You might be approaching the concept of the scan (and hot and cold nodules) backwards. It is only a nodule that seems clinically hyperfunctional (i.e. low TSH) that mandates a radiouptake scan to differentiate cold from hot nodules. In an overwhelming majority of cases such a hyperfunctioning nodule is likely to be the dominant nodule of a toxic multinodular goiter. So let me preface by saying that the discussion of hot and cold malignant nodules already has you in the albino zebras with a horn on their forehead section of medicine.

Follicular adenomas certainly can have high iodine uptake, if functional. Only about 1% of follicular adenomas can lead to manifest hyperthyroidism. Follicular carcinomas and papillary carcinomas can also have positive iodine uptake if they are functional, but this is even more uncommon.

Quoting from some PubMed articles:

On radioiodine thyroid scintigraphy, functioning follicular adenomas avidly concentrate radioiodine and may suppress iodine uptake in the rest of the thyroid gland. In contrast, most follicular adenomas are hypofunctioning on thyroid scintigraphy... Most follicular cancers are nonfunctional, but there are rare cases of functioning follicular cancers... A low serum TSH level suggests the possibility of a “toxic adenoma.” In these patients, a free thyroxine and a free triiodothyronine level should be measured and an iodine-123 thyroid scan should be obtained to distinguish a hyperfunctioning nodule from a hypofunctioning nodule.

The few larger retrospective series mention an incidence of thyroid cancer among hyperthyroid patients between 1 and 5.8%. According to the latest guidelines from the American Thyroid Association, hyperthyroid nodules with positive radioactive marker uptake on scintigraphy do not require fine-needle aspiration (FNA) or ultrasound evaluation because of the overall low incidence of malignancy in these lesions... The larger series show a higher prevalence of follicular thyroid carcinomas, which represent more than half (56%)of all cases we found. Since hot thyroid papillary carcinomas are found less frequently, they seem to be more often published as individual clinical cases: 11 out of 18 published case reports were papillary carcinomas. A significant fraction of these papillary carcinomas (minimum 25%, probably more since the subtype of all papillary carcinomas could not be found), including those found in the larger series, are of the follicular variant. A possible explanation may be that the follicular variant produces more colloid
than the conventional papillary carcinoma, in which colloid depletion is relatively common.

Underlying biology:

The metabolism of radioiodine in papillary and follicular carcinoma is profoundly altered. When compared with normal thyroid tissue, several defects are present in cancer tissue: (a) iodine uptake, via the sodium-iodide symporter (NIS), is always decreased and is undetectable in about a third of patients; (b) iodine organification is markedly reduced; (c) the effective half-life of iodine in tumor tissue is always shorter; and (d) response to TSH stimulation is usually present, even in the absence of clinically evident 131I uptake.

A little clinical, but reading my post this thread may also help.

In summary, cold = suspect malignancy and do an FNAC, although very few nodules (cold or hot) are malignant. It is unlikely the USMLE will ask you whether a thyroid malignancy will show up as a cold or hot nodule, more likely they will ask whether it is a cold or a hot nodule that raises the suspicion of malignancy.

 

[Lavan]

Also, to keep in mind, the determination of hot/cold is relative to the rest of the thyroid gland. So while a cancer may take up iodine, it is typically not hyperfunctional relative to the gland. For exams

cold = concerning
hot = not

is all you need.