Thyroid Hormonal Disease (Magnotti, 4/17/2024)

 A recording of this presentation is available HERE.

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Thanks to Dr. Mike Magnotti, SMGR Endocrinologist, for an excellent presentation on Hypo and Hyperthyroid. This was a jam-packed presentation. Check out the link above or my notes below.

Hypothyroidism

Hypothyroidism is characterized by non-specific and relatively common constellation of symptoms, including fatigue, weight gain, mental cloudiness, cold intolerance, etc. Plenty of people with these symptoms believe they have thyroid disease (and will even feel better on thyroid replacement), but this doesn't mean they actually have thyroid disease. 

Of note, weight gain is a known symptom of hypothyroidism, but obesity is not generally caused by hypothyroidism. Treating a patient's hypothyroidism can help mood, mental acuity, and focus but likely little (if any) weight loss.

Also of note, alopecia 2/2 hypothyroid takes a very LONG time to get better -- 6 months to 1 year, even with normalization thyroid hormone. Patients need to either be patient or use another med (e.g. Rogaine) in the meantime.

The only test you need to diagnose hypothyroidism is TSH. A normal TSH range is 0.5 to about 5 and excludes thyroid disease (except in very rare cases). Always want to check twice (there are lots of transient highs that can self-resolve), on repeat TSH, also check FT4, consider thyroid antibodies (not recommended in guidelines). Ft4 distinguishes between subclinical and clinical hypothyroidism. Antibody results do NOT change treatment, but can be helpful to patients to know WHY they have hypothyroid. No need to monitor antibodies -- levels change due to immune system activity and do not indicate illness state. 

High TSH, low FT4--> overt hypothyroidism, treat with levothyroxine

High TSH, normal FT4--> subclinical hypothyroidism, consider treatment**

If thyroid antibodies are elevated, dx is most likely Hashimoto's thyroiditis

TSH increases with age. A TSH of 6-8 may be normal in patients >70 years old; TSH can also be low in younger people (0.3-0.5 can be normal in young).

**Treat patients with subclinical hypothyroidism if they have symptoms, if TSH>10 (even no symptoms because of reduced risk CAD), TSH 7-10 if under 65. Only treat elderly patient <7 if you really believe they are symptomatic. 

Note: Biotin supplements alter the ability of the assay to detect thyroid hormones (it doesn't change actual thyroid hormone). Must be high dose biotin-- e.g. those in hair and nail formulations. Should avoid products with biotin 3 days before the assay. Biotin generally makes people look hyperthyroid (Low TSH, high FT4)

Treatment of hypothyroidism

Treatment of hypothyroidism is Levothyroxine (T4)

1.6 mcg/kg/day is the FULL replacement dose of thyroid hormone (patients with NO thyroid will need this full dose)

• If older patient, start slow to avoid cardiac issues, arrhythmia
• Younger person with a very HIGH TSH probably needs most of the high replacement dose right up front. If they have a lower TSH, can start with 1/2 the dose
• take 30 minutes before food, 4 hours before calcium/iron/vitamin (absorption). 
• brand does NOT matter unless someone has intolerance to fillers/dyes in a certain brand
• Tirosint brand is a gel cap formulation with no filler, also liquid version, theoretically has least likelihood of having adverse reaction, but very expensive
• For rare patients who are super sensitive to batch variations, use the same brand to maintain consistent
• Only use TSH to monitor (goal is anywhere in the normal range), titrate to patient's feeling about how they feel
• no need to monitor T3 levels, which vary more with stress and illness (helpful in hyperthyroidism)
• Never use T3 alone! Our system has no way to regulate T3 levels in our body. T3 is the more active form. There is internal regulation of conversion T4>T3 (e.g. hospitalized patients have inhibition of conversion, normal stress response), but T3 is unregulated.
  

T3/T4 combination not generally recommended as first line treatment because most people feel fine on T4 alone. T3 is converted to T4 via deiiodinase. There are some (rare) patients with reduced ability to convert T4 to T3 (no ability is not compatible with life). Most people feel better on T3 because it gives them more energy. T3 makes people feel better like caffeine makes people feel better. 

• Most trials adding T3 to T4 show no benefit, though a few studies show some benefit. Hard to quantify symptoms energy, focus, sleep. Some people feel a rush when they take T3. 
• Consider adding T3 if patients are not better on T4 (but not an excessive amount)
• T3 has a very short half-life (needs to be taken am/pm, e.g. 7am, 3pm)
• Armour thyroid formulation (pig and cow thyroid) contains more T3 than normal human (4:1 ratio T4:T3 in Armour, humans generally have T4: T3, 13-16:1)
• if you check T3 levels, you will see relatively high T3, low T4 and normal TSH
• more variability from batch to batch (higher risk over-replacement)
• Dr. Magnotti generally does not recommend Armour, unless a patient is stable on it and you are just continuing it
• If you want to give T3, should dose separately
• T4 is 4x potent as T3
• Goal is maintain ratio T4/T3 13-16:1, e.g. 5mcg T3, 75mcg T4
• T3 only comes as 5mcg and 25 mcg. Generally don't use 25mcg pills
• Do NOT use T3 in pregnancy (doesn't cross placenta, so mom can be euthyroid and baby can be hypothyroid)
• Only monitor via TSH, symptoms

Secondary hypothyroidism is VERY rare. Unlikely to be de novo or surprising diagnosis. Patients with known pituitary tumor, history of pituitary or sella radiation, other pituitary hormone deficits (prolactin, LH, FSH). In these rare patients, TSH is useless. You treat using FT4 to monitor, goal mid normal.

Hypothyroid in pregnancy

• As soon as woman is pregnant, increase the dose up front 20-30% (right away) because risk of hypothyroidism on the fetus is WAY higher than hyperthyroidism 
• Check TSH q4 weeks (up through the second trimester)
• No T3 alone in pregnancy 
• Current goal in pregnancy is TSH<2.5
• Immediately after delivery, back to usual delivery
• Recheck TSH 8-12 weeks post partum (not too soon) because lots of women have post partum thyroiditis, which can confuse things and make you worried they have levothyroxine too high
• Let patient symptom guide 

If patient diagnosed with hypothyroidism during pregnancy. Guidelines vary about screening. 

BUT . . .

If TSH>4, treat

If TSH <2.5, no treatment

If between 2.5-4, check TPO, especially if recurrent miscarriage.

Starting dose based on level of TSH. If above 15-20, be more aggressive

Recheck 4 weeks even though not fully equilibrated.

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Hyperthyroidism can definitely be more complex than hypothyroidism; there are more causes to consider, and the treatment is more nuanced.

Best first test for hyperthyroidism is TSH.

• If TSH is LOW, check BOTH FT4 and FT3 (elevations in either can cause overt disease),
• Also check TSI and/or TRAB (same test, different assay). 
• If Ab positive, your patient almost certainly has Grave's disease.
• If TSH is LOW, but BOTH FT4 and FT3 are normal>> this is by definition, subclinical hyperthyroid. 
• Treat subclinical hyperthyroidism if TSH<0.1 (or <0.3 if older, atrial fibrillation).
• CV risks of hyperthyroidism are definitely increased when TSH<0.1.
• If TSH is NORMAL with elevations in FT4 or FT3, this either secondary hyperthyroidism (VERY very very rare) OR T4 resistance (genetic)
• Refer to endocrine.

Additional lab findings: isolated elevation in alk phos is common with significant hyperthyroidism, will go down when treated. Transaminitis can be caused by methimazole but sometimes is also seen in hyperthyroidism.

Causes of hyperthyroidism

Grave's disease is by far the main cause of hyperthyroidism (75-80%, especially in younger patients), toxic multinodular goiter relatively more common in older population, also single functional nodule. Knowing the cause of hyperthyroidism doesn't impact who needs to be treated but can influence treatment decisions. 

• +TSI and no palpable nodules on exam (usually sizeable on exam, 2-4 cm) >> patient almost certainly has Grave's disease (no scan needed)
• -TSI and/or no nodules on exam >> need uptake scan (to r/o functional nodule)
• If palpable nodule>> need both ultrasound and uptake scan
• Toxic multinodular goiter usually is HUGE, nodular on exam

NOTE: If TSH is NOT close zero, the radioactive uptake scan is not reliable (even at 0.2 or 0.3, scan will generally be normal). If you cannot get uptake scan, ultrasound can be helpful (even without nodules). they evaluate blood flow. If blood flow is low, likely thyroiditis. High blood flow, likely Grave's. 

If no uptake>> likely dx thyroiditis (unless people taking iodine supplements, kelp, seaweed, or recent contrast in last 3 months. Amiodarone can also cause no uptake, even 3 months after taking it.

If normal or increased uptake>> dx Grave's

If uptake in single nodule>> dx toxic solitary nodule

Patchy uptake all around >> toxic multinodular goiter

Treatment of hyperthyroidism

3 options: methimazole, iodine (I-131), thyroidectomy. Beta blocker for symptom management

Methimazole is first line for most causes. 

Methimazole 10 mg/day, 20 mg/day, 40 mg/day for mild (<2x ULN), mod (2x ULN), severe (>2x ULN) disease, respectively. Taper down to 5-15mg (usual maintenance dose). Leave people on methimazole for 1-2 years before stopping. Want to be sure to have negative TSI (antibody) if they have positive to begin with. Don't stop methimazole in anyone who still has antibody at the receptor (+TSI is causing the hyperthyroidism).

There are some exceptions.

• Iodine should be considered for young women who desire pregnancy and people without eye disease
• Younger women who desire pregnancy may benefit from treatment with iodine treatment because methimazole can take years to get into remission. 
• Can get pregnant 6-9 months, need normal TSH (with levothyroxine). 
• Even after 3-4 years, with methimazole may not be in remission. Delays childbearing.
• Iodine is also great for single toxic nodule because people will come out euthyroid. Likely curative. Normal gland not affected. 
• Very severe hyperthyroidism in a younger person, especially with a large gland, they are very unlikely to have long-term remission at all with methimazole. Consider iodine vs. surgery.
• Surgery may be best option if need to get thyroid hormone levels down quickly. It will still take weeks (body has to metabolize FT4 already floating around)
• Consider surgery in case of: 1) very large goiter,  2) need for rapid correction, 3) concern for malignancy, 4) combo hyperthyroid+ hyperparathyroidism

Hyperthyroid eye disease: Send to neuro-ophtho if thyroid eye disease. Iodine can worsen thyroid eye disease. (if mild, can do Iodine with 3-4 months of prednisone to protect against progression). 

Hyperthyroid in pregnancy: 

Do NOT treat subclinical disease. 

Use PTU in first trimester, change to methimazole in 2nd and 3rd trimesters.

Target Total T4 and Total T3 in the high normal range, which is 1.5x ULN for pregnancy range due to higher estrogen, binding globulin.