Thyroid – 2: Hyperthyroidism

Last posting (Thyroid – 1) addressed lab tests for Thyroid disease, and Hypothyroidism in specific.  Today, Hyperthyroidism (a.k.a. Thyrotoxicosis).

Symptoms of Hyperthyroidism, be they mild or extreme, may occur with any etiology of the condition.  The first lab abnormality we usually find is an:

• undetectable Thyroid-Stimulating Hormone (TSH <0.01 mU/L)

Hyperthyroidism is then confirmed with a:

• elevated Thyroxine:  Free T4  (FT4)

The main chore is to decide if it’s Graves’ Disease, or one of the usually benign, self-limiting causes of thyrotoxicosis:

• Multinodular Goiter
• Thyroiditis (painful & tender)  [usually viral; very rarely suppurative & serious]
• Painless Thyroiditis
• Post-Partum Thyroiditis
• Drug-Induced (lithium, amiodarone, interferon, tyrosine kinase inhibitors, iodine-containing cough syrups)
• Iatrogenic / Surreptitious (e.g. L-Thyroxine for weight loss)
• Trophoblastic Disease of Pregnancy
• Thyroid Cancer (usually euthyroid)
• “Hashitoxicosis”

The thyroid gland in Graves’ is usually diffusely enlarged (though not always), non-painful & non-tender.  Only Graves’ Disease causes exophthalmos or pretibial Myxedema (infiltrative dermopathy):

Exophthalmos:  Look for a tiny bit of sclera between top of the iris & the upper lid.  If subtle, there may only be “lid lag” (bit of sclera noted when having patient roll eyes from up to down).

Exophthalmos

         

Pretibial Myxedema

         

Most patients with Graves’ won’t have these findings.  Other conditions in the differential are suspected by history (e.g. pain; culprit meds) or physical exam (tenderness; multi-nodular goiter).  But the bottom line is that you need laboratory tests to confirm or rule-out Graves’.

PEARL — Order a Pregnancy Test on all women of childbearing potential with new Thyrotoxicosis.  Since the hCG molecule can stimulate the thyroid, very high titers from Trophoblastic Disease (including choriocarcinoma) stimulate T4 production and likewise suppress the TSH.

For Graves’ Disease, the most specific and sensitive test is the 24-hour Radioiodine Uptake Scan.  It reveals normal or high uptake (low uptake rules Graves’ out).  The only other conditions giving a normal or high uptake are Multinodular Goiter (identifiable on physical exam) and pregnancy-related conditions.  But pregnancy is an absolute contraindication to scan; must rule it out first.

If radioiodine uptake scanning is contraindicated, too expensive, or unavailable, order TSH-Receptor Antibodies (TRAb) and Thyroid Stimulating Immunoglobulins (TSI).  They may be somewhat expensive.

• TRAb — Very sensitive for Graves’, but not so specific.
• TSI — Extremely specific for Graves’, but may be normal in early or mild disease.

What about T3 (triiodothyronine)?  Order it for Hyperthyroidism:

• “T3-Hyperthyroidism” refers to patients with undetectable TSH, classic symptoms, but normal Free T4.  It’s just that most of the T4 has converted peripherally to T3.  Same differential; probably Graves’
• In Graves’, T3 is usually elevated to a greater degree than Free T4 is.  This helps confirm the Dx.  The most common T3 test is “Total T3”, though “total” may not be stated on the lab slip.  In unusual cases, much less commonly than with T4, a Free T3 test may be useful if the regular [Total] T3 isn’t high and you really suspect Graves’.
• DO NOT ORDER “T3 Resin Uptake” (see prior posting)

If you find Graves’, treat it (or send to Endo if you’re not comfy).  If tests for Graves’ are negative, the rest of the differential is self-explanatory:

• Multinodular Goiter  —  Usually visible & certainly palpable on physical exam.  Ultrasound defines the nodules.  Suspicious ones need Fine Needle Aspiration.  Most mutinodular goiters are euthyroid.
• Thyroiditis (painful & tender)  —  Usually viral & self-limiting.  If symptoms are extreme, may be bacterial [very rare], requiring urgent aspiration, culture, Tx.
• Painless Thyroiditis —  Autoimmune, self-limiting.
• Post-Partum Thyroiditis  —  Autoimmune.  Occurs within 12 months of delivery.  Self-limiting.
• Drug-Induced  —  Dx by History (lithium, amiodarone, interferon, tyrosine kinase inhibitors, iodine-containing cough syrups)
• Iatrogenic — L-Thyroxine for Multinodular Goiter.  Decrease the dose, but then be sure to wait 6 weeks or more before rechecking the TSH.
• Surreptitious  —  (L-Thyroxine for weight loss)
• Trophoblastic Disease of Pregnancy  —  This is why we did a pregnancy test before any other hyperthyroid work-up.
• Thyroid Cancer (usually euthyroid)  —  Usually a solitary nodule.  Diagnose by ultrasound and FNA.
• None of Above  —  Probably an occult nodule, malignant or benign.  Get an ultrasound.
• “Hashitoxicosis”  —  A cross between Graves’ & Hypothyroidism.  Results bounce up & down.  Endocrine eventually gets tired & destroys the gland [ablation], after which the patient simply takes L-Thyroxine replacement for life.

Let’s SUMMARIZE all this in another way:

1.  You discover Hyperthyroidism:  undetectable TSH, and elevated FT4.

2.  You do a pregnancy test if pregnancy at all possible [it’s negative].

3.  No history of culprit drug ingestion (L-thyroxine or other)

4.  Physical exam is unrevealing, except perhaps tachycardia:

• No Exophthalmos or Pretibial Myxedema to Dx Graves’
• Thyroid gland may be diffusely enlarged, smooth,  & non-tender, suggesting Graves’, or may be non-palpable
• No multinodular goiter
• No thyroid nodules palpated
• Non-painful, non-tender thyroid (not viral thyroiditis)
• No A. Fib [doesn’t change things, but needs good rate control]

5.  So you order a 24-hour Radioiodine Uptake Scan [normal / high in Graves’].  If unable, order Labs:

• TSH-Receptor Antibodies (TRAb)  —  sensitive for Graves’
• Thyroid Stimulating Immunoglobulins (TSI)  —  specific for Graves’
• T3  [NOT “T3-Resin Uptake”!!!]  —  relative T3 ↑ more than T4 ↑ in Graves’

6.  If the Scan / Labs are compatible with Graves’, you’ve got it.

• TREAT.
• Send to Endocrine if you’re not used to treating, or if you think total thyroid ablation may be best

6a. If the above are negative for Graves’, it’s undoubtedly self-limiting Painless Thyroiditis

• If pregnant within the last 12 months, call it Post-Partum Thyroiditis
• DON’T TREAT.  Follow TSH and FT4.  Both these [presumably] autoimmune conditions are self-limiting
• Hyperthyroidism will resolve, TSH & FT4 seem euthyroid
• Then the TSH ↑ and FT4 ↓  (Hypothyroid Phase)
• Then TSH & FT4 normalize again, condition resolved

6b.  If the above labs don’t behave properly, keep looking for Graves’ by exam

• Ultrasound to R/O Nodules (and characterize them)
• Send to Endocrine for help
• Send to Endocrine if labs are so erratic as to suggest “Hashitoxicosis”

Subclinical Hyperthyroidism

Defined by a low TSH with normal Free T4 and [total] T3.  The causes are the same as for overt Hyperthyroidism.  The debate concerns whether morbidity is significant & treatment indicated [if not, then work-up isn’t either].

FIRST STEP  —  Since Subclinical Hyperthyroidism may resolve on its own, repeat your TSH and FT4 a few times, over several months, before anything else.

• Also order a pregnancy test if pregnancy is possible.

NEXT  —  Decide if you want to work-up and treat.  A normal TSH is 0.5 – 4.5.

• TSH <0.1 warrants work-up and treatment
• TSH >0.1 can be followed
• More caution in the elderly, who are more prone to cardiovascular effects like atrial fibrillation and heart failure.

The work-up?  Same as for overt Hyperthyroidism: test to R/O Graves’.

Central Hyperthyroidism

Due to pituitary adenoma; so rare as not worth discussing.

• Suspect when high TSH & high FT4.
• Most patients have goiters [from excessive thyroid stimulation].

 THYROID NODULES

 When one or more thyroid nodules are discovered on physical exam, the first step is to draw a TSH, to determine how the nodule is functioning.  Hyperfunctioning nodules decrease the TSH by negative feedback.  The higher the TSH, the more likely it’s cancer.

• TSH normal or elevated → Ultrasound to determine need for FNA
• TSH decreased → Thyroid scintography with radioiodine isotope to determine if it’s functioning (hot) or not (cold)
• Cold nodules get ultrasound to determine need for FNA
• High suspicion of cancer by ultrasound may warrant excisional biopsy

And we’re all done with Thyroid Conditions (the most common ones, at least).