Hypothyroidism and myxedema coma

Question 1

What is subclinical hypothyroidism?

Answer 1

increased TSH and normal T4

early form of primary hypothyroidism affecting 10% of population and seen with a serum TSH above the upper limit of normal and a normal free T4. But before making diagnosis need to rule out transient elevation of TSH by repeating labs in 2-3 months.

seen more in women than men and usually due to Hashimoto’s.

, seen commonly in women >60 yrs and does not delay urgent surgical procedures. However, if with severe overt hypothyroidism there may be a risk for afib and need to rule out adrenal insufficiency if going to surgery

Question 2

when do you treat subclinical hypothyroidism with levothyroxine?

Answer 2

if TSH>10 uU/ml treat with levothyroxine

Also if TSH is 7-9.9, the following needs treatment with levothyroxine

pregnant

symptomatic

ovulatory dysfunction,

cardiovascular risk factors (HLD),

presence of goiter,

positive anti-thyroperoxidase antibodies (ATPA)

otherwise need to repeat labs in 2 months to see if this is a transient thing. Free T3 and thyroid peroxidase antibodies could also be measured at that time.

If TSH is 7-9.9 and >70 years old only treat if convincing hypothryoid symptoms

If TSH is 6.9 don’t treat if >70 years old and if <70 years old only treat if there’s convincing symptoms of hypothyroidism or high anti TPO titers

Question 3

When do you treat subclinical hypothyroidism if TSH<10

Answer 3

if TSH <10 but greater than upper limit of normal need to check for positive anti thyroid peroxidase antibody and if positive can give levothyroxine.

Also depends on their age. Generally only treat if >70 years old if there’s convincing symptoms or positive anti thyroid peroxidase antibody.

If negative need to assess patient for goiter, symptoms, pregnancy, ovulatory dysfunction with infertility or hypercolesterolemia

Question 4

subclinical hypothyroidism can progress to

Answer 4

overt hypothyroidism over a period of many months to years

Question 5

what is concerning for overt hypothyroidism?

Answer 5

can have risk of afib.

Question 6

with overt hypothyroidism, what must you also rule out?

Answer 6

If severe hypothyroid, also need to rule out autimmune thyroiditis with a comorbid adrenal insufficiency

Question 7

Algorithm for subclinical hypothyroidism

Answer 7

Question 8

average full replacement dose with levothyroxine in patients with hypothyroidism is

Answer 8

1.6 mcg/kg/day.

No increased risk at starting at full replacement dose in pts with low risk for cardiovascular dx.

with lower doses, patients need to have more labs drawn and doses adjustments prior to getting the optimal dose.

Question 9

why do we not like dessicated thyroid for treatment of hypothyroidism?

Answer 9

dessicated thyroid gland contains more T3 relative to T4 than is normally present in humans. This increases the theoretical risk for osteoporosis and a fib. Not first line therapy for treatment of hypothryoidism.

avoid in pts esp older adult women and women of childbearing age.

Question 10

cardiac manifestations of hypothyroidism

Answer 10

dyspnea, bradycardia, decreased CO due to decreased contractility, hypertension due to increased peripheral vascular resistance, peripheral edema (non pitting, less commonly pitting) and ventricular arrhythmias and increased risk for CAD

Question 11

unexplained pericardial effusion, you should check

Answer 11

TSH for hypothyroidism. May have no signs of cardiac tamponade which suggests that this is a slow accumulation of fluid.

Question 12

Causes of central hypothyroidism

Answer 12

mass lesions (pituitary adenomas)

pituitary surgery, truama irradiation

infiltrative disorders like sarcoidosis and hemachromatosis

pituitary infarction (Sheehan syndrome)

empty sella syndrome

Question 13

features of central hypothyroidism

Answer 13

mild hypothyroid symptoms, other pituitary hormone deficiencies, mass effect symptoms (headache, visual field defects if due to mass

Question 14

diagnosis of central hypothyroidism

Answer 14

low free T4, low or inappropriately normal TSH and MRI of pituitary gland

Question 15

Management of central hypothyroidism

Answer 15

levothyroxine (adjust to keep Free T4 in high normal range) - follow and adjust with following free T4, NOT TSH.

Don’t replace with liothyronine (T3) therapy because it can lead to fluctuations in physiological status and increase risk for thyroxicosis.

We don’t follow T3 because it correlates poorly with overall thyroid physiologic status and less reliable than T4.

corticotropin (ACTH) stimulation test prior to treatment

Question 16

Causes of low TSH and low free T4 (may include hypothyroid and hyperthyroid states)

Answer 16

Question 17

what causes central hypothyroidism

Answer 17

central hypothyroidism is less common than primary hypothyroidism

due to destruction of pituitary thyrotrophs by mass lesions, intracranial radiation therpay. or infiltrative disorders like hemochromatosis and sarcoidosis.

Question 18

to rule out central hypothyroidism need to order this test

Answer 18

get a MRI or CT

Question 19

central hypothyroidism presentation

Answer 19

milder presentation to prmary hypothyroidism and symptoms can vary with coexisting pituitary abnormalities which are present.

can still see fatigue, weight gain, dry skin, hyponatremia, normocytic anemia.

Can’t rely upon TSH (will be low or inappropriately normal) and so need to measure T4 which can confirm this

Question 20

In someone who has central hypothyroidism before you start treatmetn what must you check first

Answer 20

need to check for concurrent adrenal insufficiency because hypothyroid treatment may result in adrenal crisis.

Need to check morning AM cortisol and need a cosyntroponin stimulation test too.

Question 21

primary hypothyroidism

Answer 21

dysfunction with the thyroid hormone resulting in sufficiency

Question 22

Primary vs secondary hypothyroidism

Answer 22

primary is dysfunction at the thyroid level and see high TSH

Secondary hypothyroidism is less common and due to pituitary hypothalamic disease and see LOW TSH.

Question 23

thyroid peroxidase antibody titers are elevated in

Answer 23

autoimmune (Hashimotos) thyroiditis

Present with primary hypothyroidism (low free T4 and elevated TSH) but can also have a transient hyperthryoid phase (elevated free T4 and supressed TSH)

Question 24

if patient has vitiligo, what do you also need to screen pt for?

Answer 24

screen for autoimmune thyroiditis (graves or hashimotos) and DM1

Question 25

if suspecting amiodarone induced thyroid dx, check TSH and then follow algorithm

Answer 25

Question 26

what causes subclinical hypothyroidism commonly?

Answer 26

Hashimoto’s thyroiditis - autoimmune condition where there are antibodies against thyroperoxidase.

Question 27

Amiodarone’s effect on thyroid

Answer 27

Question 28

ATPA or anti thyroperoxidase antibodies are associated with

Answer 28

Hashimoto’s thyroiditis

Question 29

If there’s subclinical hypothyroidism and slightly elevated prolactinoma and amenorrhea with ovulatory dysfunction, does bromocriptine need to started to treat elevated prolactin?

Answer 29

no. Don’t treat the mildly elevated prolactin because the amenorrhea is due to the hypothyroidism. If pt is hypothyroid, there’s elevation in prolactin as it may be secreted along with the attempt to secrete more TSH to stimulate more thyroid hormone.

If you treat subclinical hypothyroidism with levothyroxine the prolactin will go down too. No need for bromocriptine.

Question 30

what is the side effect of overt or subclinical hypothyroidism?

Answer 30

can see ovulatory dysfunction (see mild elevated prolactin), elevated TSH and normal T4, amenorrhea or failure to conceive and normal FSH and LH.

Question 31

When you use clomiphene in a pt who has ovulatory dysfunction and subclinical hypothyroidism?

Answer 31

only use clomiphene if treatment of subclinical hypothyroidism didn’t improve with levothyroxine alone.

clomiphene (selective estrogen receptor modulator which induces ovulation by blocking estrogen receptors in hypothalamus)

Question 32

hospitalized pts will have low T3 due to illness suppressing conversion to T4 to T3. What is this condition called?

In the setting of low TSH need to check what?

Answer 32

Euthyroid sick syndrome - suppression of TSH and T4 production and breakdown and suppression of T4 conversion to T3.

Need to check T3 in the setting of low TSH to make sure that this is not hyperthyroidism. Euthyroid sick syndrome will have low T3.

Thyroid function recovers in a few weeks after acute illness.

Question 33

What is euthyroid sick syndrome?

Answer 33

the thyroid shuts down from acute illness.

See suppression of TSH, decreased T4 production and clearance, altered T4 protein binding, and decreased conversion of T4 to T3 (enzyme 5 monodeiodinase has reduced activity during illness).

TSH is suppressed because of illness and medications (steroids, dopamine, octreotide)

On labs: T3 drops first (due to decreased conversion from T4), then see drop in TSH and T4 (suppressed)

Question 34

is thyroxine therapy beneficial in euthyroid sick syndrome?

Answer 34

no. thyroid will start working after recovery from illness.

Question 35

Why is reverse T3 levels high in euthyroid sick syndrome?

Answer 35

Because enzyme 5 monodeidinase (that converts T4 to T3) is responsible for breaking rT3 down. However this enzyme level is suppressed so less T4 to T3 and less rT3 levels are broken down.

rT3 also elevated in renal failure

Question 36

Causes of central hypothyroidism are:

Answer 36

pituitary adenoma (most common)

pituitary surgery or radiation

infiltrative dx with hemachromatosis

infarction (Sheehan’s syndrome)

hypothalamic lesions.

Question 37

Sheehan’s syndrome is

Answer 37

loss of pituitary gland due to infarction from hemorrhagic blood loss.

See failure to lactate, lethargy, weight loss, loss of sexual hair. Can present months to years after delivery with milder symptoms. Can see multihormone deficiency. Need to evaluate pituitary and adrenal gland and so need to get a cortsyntropin stimulation test to see if there’s adrenal insufficiency

Question 38

ACTH deficiency presents as

Answer 38

hypotension, dizziness, fatigue and hair loss. ACTH stimulates release of adrenal and ovarian androgens which regulates pubic and axillary hair development in females.

Question 39

vital signs of myxedema coma

Answer 39

hypothermia,

bradycardia,

diastolic hypertension (narrow pulse pressure

hypoventilation

Question 40

Examination findings of myxedema coma

Answer 40

decreased mental status or coma

non pitting edema of face and hands and tongue

psychosis, seizure, or coma

Question 41

lab findings of myxedema coma are:

Answer 41

low free T4 and hyponatremia and hypoglycemia

the mild hypoglycemia may be due to underlying adrenal suppression and this corrects naturally with thyroid hormone therapy and steroids.

Question 42

what other medical conditions are seen with myxedema coma?

Answer 42

pericardial efflusions

concurrent adrenal insufficiency

hypothalamic pituitary dysfunction

Question 43

how to manage the patient with myxedema coma?

Answer 43

give parenteral levothyroxine T4 and liothyronine T3

give glucocorticoids and (hydrocortisone)

Question 44

what is myxedema coma?

How is it managed? What medications to start?

Answer 44

this is a lifethreatening condition (30-40%) mortality and treatment should be initiate without waiting for resutls of serum TSH and free T4

Give both levothyroxine and liothyronine T4 IV until pt stabilizes.

Because adrenal insufficiency may exist also give hydrocortisone

May also need abx if concerned for infection.

Question 45

Myxedema chart

Answer 45

Question 46

pt presents with macroglossia, hypothermia, and gradual worsening of mental status and facial edema

Answer 46

myxedema coma.

Question 47

Treatment of hypothyroidism

what is the replacement dose for levothyroxine?

Answer 47

weight based replacement of levothyroxine of 1.6 ug/kg lean body weight.

older pts >65 yrs or older initial dose of 25-50 ug/day due to effects of thyroid hormone on myocardial oxygen demand.

then follow up TSH in 6-8 weeks

must treat anyone who has subclinical hypothyroidism with TSH >10 to prevent development of cardiovascular dx and hypercholesterolemia

Question 48

what happens to thyroid hormone requirements in pregnancy?

Answer 48

thyroid hormone requirements increase during pregnancy due to increased metabolic demands.

High estrogen levels increase thryoxine binding gloublin TBG and this casues increased thryoid hormone proudction to saturate the increased number of thyroid hormone binding sites on TBG but patients with primary hypothyroidism are unable to increase thyroid binding production

Thus, pts with primary hypothyroidism on levothyroxine therapy need a 25%-50% increase over pre pregnancy dose

Question 49

what do we do with pregnant pts who have primary hypothyroidism?

Answer 49

need to empirically increase levothyroxine by 30% (2 additional levothyroxine doses each week) at time of pregnancy is first detected. TSH should be measured every 4 weeks

Dose should be adjusted to maintain TSH within trimester specific norms (lower than non pregnant reference ranges

Question 50

Complications of not adequately treating pregnant women with hypothyroidism

Answer 50

Undertreated hypothyroidism increases risk for maternal preeclampsia and placental abruption and fetal complications (preterm birth and fetal death)

Question 51

Drug drug interactions with levothyroxine

Answer 51

Some drugs will increase thyroxine binding globulin and so it can affect how much of the free hormone binds and so this will need adjustment based on those drug amounts.

For example: OCP/pregnancy/progesterone/esterogen increases thyroxine binding globulin and so may need to slightly increase levothyroxine dose

Question 52

if pt who is on levothyroxine gets started on testosterone what changes do you need to make to their levothyroxine?

Answer 52

androgens and anabolic steroids leads to a reduction in thyroxine binding gloublin and so this increases the amount of metabolically active free thyroxine and causes almost hyperthyroid scenario

so levothyroxine dose needs to lowered a little to prevent thyrotoxicosis

Question 53

IF pt is on levothyroxine and starts taking tamoxifene or raloxifene for breast cancer, what should be done with their levothyroxine dose?

Answer 53

estrogen or SERMs (tamoxifen or raloxifene) incrase serum thyroxine binding globulin and so this decreases the total circulating free thyroxine hormone and so need to increase levothyroxine a little bit.

Same thing is true with pregnancy because of the increased estrogen.

Question 54

what medications decreases absorption of levothyroxine?

Answer 54

calcium carbonate and iron supplements. These meds bind to levothyroxine and reduce absorption by 25%. PPI also decreases absorption due to increasing gastric PH

Levothyroxine needs to be separated from iron or multivitamins by 4 hrs.

Drinking it with coffee will also decrease its absorption too.

levothyroxine is absorbed in the jejunum and ileum.

Question 55

most common cause of pituitary masses

Answer 55

most common cause of central hypothyroidism due to direct compression by the tumor and late effects of surgery or radiation therapy

if cause not known, need MRI of pituitary to rule out mass lesion .

if has central hypothryoidism need to rule out other abnormaliteis (ACTH, GH, gonadotroponins)

Question 56

what is a struma ovarii?

Answer 56

thyroid tissue in an ovarian tumor (usually teratomas) which can hyperfunctio nand cause hyperthyroidism.

Question 57

what is hasitoxicosis?

Answer 57

this is seen with autoimmune thyroid dx and these have transient thyroxicosis similar to Graves dx followed by permanent hypothyroidism.

Question 58

If patient is on levothyroxine for hypothyroidism, which is the most reliable to lab to titrate the levothyroxine?

Answer 58

TSH.

TSH is most reliable marker of levothyroxine therapy as it reflects the biological activity of the thyroid hormone in tissues.

Don’t look at T4 or T3 unless the patient has secondary (central) hypothyroidism and isn’t making TSH. Then rely on T4 levels to titrate levothyroxine.

Question 59

When are checking thyroid peroxidase (TPO) antibodies helpful?

Answer 59

only helpful for cases of subclinical hypothyroidism, recurrent miscarriages and euthyroid diffuse goiters.

if diagnosis of Hashimotos’ is already established no benefit.

Question 60

Treatment of subclinical hypothyroidism in pts who are older than 70 years old:

Answer 60

should be conservative.

So if pt has subclinical hypothyroidism and has TSH>10 treat

If pt has subclinical hypothyroidism and TSH>7-9.9 and some symptoms like fatigue or constipation - it depends on their age if you treat.

generally if greater than 70 years old don’t treat unless there’s convincing symptoms of hypothyroidism or elevated anti TPO titers.