To define hyperthyroidism and hypothyroidism, their ... Disorders- Lecture 1… · 4. Toxic...

• To define hyperthyroidism and hypothyroidism, their

clinical presentation, diagnosis and causes.

• To study the different treatment modalities used for

hyperthyroidism and how to treat hypothyroidism.

• To study how to assess the response of treatment for

hyperthyroidism and hypothyroidism.

• To discuss Thyroid Storm and myxedema coma and how

to manage them.

Introduction.

Hyperthyroid disorders classification.

Pharmacotherapy of hyperthyroidism.

Subclinical hyperthyroidism.

Thyroid storm.

Pharmacotherapy of hypothyroidism.

Subclinical hypothyroidism.

Myxedema coma.

Regulation of Thyroid Hormones Hypothalamic–Pituitary–Thyroid

• Hyperthyroidism is defined as the production

of excessive amounts of thyroid hormones by

the thyroid gland.

• Thyrotoxicosis refers to the clinical syndrome

associated with prolonged exposure to

elevated levels of thyroid hormone.

1. Toxic diffuse goiter (Graves disease):

Most common hyperthyroid disorder (autoimmune) in which

Thyroid stimulating antibodies directed at thyrotropin

receptors mimic TSH and stimulate T3/T4 production.

2. Pituitary adenomas (excessive TSH)

3. Toxic adenoma:

Nodule in thyroid, and autonomous of pituitary and TSH

4. Toxic multinodular goiter (Plummer’s disease):

Several autonomous follicles that, if large enough, cause excessive

thyroid hormone secretion.

5. Painful sub acute thyroiditis:

it is Self-limiting inflammation of the thyroid gland caused by viral

invasion, resulting in release of stored hormone

6. Drug induced :

(e.g., excessive exogenous thyroid hormone doses, amiodarone therapy)

a. ↑↑ free T4 sr conc

b. ↓↓ TSH conc (except in TSH-secreting

adenomas)

c. If examination and history do not provide the

exact etiology, radioactive iodine uptake (RIA)may

be employed:

i. if RAIU elevated →→→→→ (Graves disease, TSH-

secreting adenoma, toxic adenoma, multinodular

goiter)

ii. If RAIU is suppressed →→→→→ (thyroiditis or

hormone ingestion).

iii. assess the presence of thyroid-related antibodies

(thyroid stimulating, thyrotropin receptor, or

thyroperoxidase TPOAb), thyroglobulin, and thyroid

biopsy

Pharmacotherapy of hyperthyroidism

a. To minimize or eliminate symptoms, improve

quality of life.

b. To minimize long-term damage to organs (heart

disease, arrhythmias, sudden cardiac death, bone

demineralization, and fractures).

c. To normalize free T4 and TSH concentrations.

1. Surgery

2. RAI

3. Thioureas

4. Beta Blockers

A. Ablative therapy :

treatment of choice for Graves disease, toxic nodule,

multinodular goiter):

Radioactive iodine (RAI) ablative therapy or surgical

resection for adenomas based on patient preferences

or comorbidities.

Ablative therapy often results in hypothyroidism.

i. Awaiting ablative therapy or surgical resection

(a) Depletes stored hormone.

(b) Minimizes risk of post-treatment hyperthyroidism because

of thyroiditis

ii. Not an ablative or surgical candidate (e.g., serious

cardiovascular disease, candidate not likely to be adherent to

radiation safety).

iii. When ablative therapy or surgical resection fails to normalize

thyroid function.

Anti-thyroid pharmacotherapy usually reserved for:

iv. With high probability of remission with oral therapy with Graves

disease:

(a) Mild disease

(b) Small goiter

(c) Low or negative antibody titers

v. With limited life expectancy

vi. With moderate to severe active Graves ophthalmopathy

Inhibit iodination and synthesis of thyroid hormones; PTU

may block T4/T3 conversion in the periphery as well

Dosing

Propylthiouracil (choice in pregnancy)

Initial: 100 mg by mouth TDS (max 400 TDS)

Once euthyroid, may reduce to 50 mg 2 or 3 times/day

(1) Preferred agent for Graves disease according (AACE)

for most patients unless in firs trimester of pregnancy

(use PTU).

(2) Initial: 10–20 mg by mouth OD

(3) Maximal: 40 mg TID

(4) Once euthyroid, may reduce to 5–10 mg/day

(a) Hepatotoxicity issue with PTU (black box warning):

AACE recommends baseline Liver function tests

(b) Rash

(c) Arthralgias, lupus-like symptoms

(d) Fever

(e) Agranulocytosis early in therapy (rare): AACE

recommends baseline CBC.

(a) Slow onset (weeks). Maximal effect may take 4–6 months.

(b) Neither drug appears superior to the other in efficacy.

(c) On a mg-to-mg basis, methimazole is 10 times more

potent than PTU.

(d) Remission rates low: 20%–30%. Remission defined as

normal TSH and T4 for 1 year after discontinuing anti-

thyroid therapy .

(1) Usually 12–18 months

(2) Consider trial off oral therapy if TSH is normal,

antibody titers may help guide decision

(3) Monitor thyroid conc every 1–3 months for up

to 6–12 months after remission (for relapse)

primarily propranolol, sometimes nadolol

Blocks many hyperthyroidism manifestations mediated by β-adrenergic

receptors. Also may block T4 (less active) conversion into T3 (more active)

((e.g., palpitations, tachycardia, tremor, anxiety))

Dosing:

(a) Initial: 20–40 mg by mouth 3 or 4 times/day (Max: 240–480 mg/day)

(e) Primary role is treatment of thyroiditis,

& for acute mgt of symptoms during thyroid storm.

(f) Alternatives to β-b: Clonidine, and non-dihydropyridine CCBs

o Inhibits the release of stored thyroid hormone. Minimal effect on

hormone synthesis.

o Efficacy of Iodines

(a) Primary use is temporary before surgery (7–10 days) to decrease

vascularity and size of the gland (not before RAI).

(c) Used post-ablative therapy (3–7 days) to inhibit thyroiditis-

mediated release of stored hormone

(d) Used acutely in thyroid storm

A 43-year-old woman has received a diagnosis of Graves disease. She is reluctant to try

ablative therapy and wishes to undergo oral pharmacotherapy first. Her thyroid

laboratory values today include TSH 0.22 mIU/L (normal 0.5–4.5 mIU/L) and a free T4

concentration of 3.2 ng/dL (normal 0.8–1.9 ng/dL). She is anxious and always feels

warm when others say it is too cold.

Which would be considered the best drug for initial treatment of her condition?

A. Lugol’s solution.

B. Propylthiouracil.

C. Atenolol.

D. Methimazole.

Case study

Regarding propylthiouracil (PTU) and methimazole in the treatment

of hyperthyroidism, which statement is most appropriate?

A. PTU is clinically superior in efficacy to methimazole.

B. PTU may be associated with increased liver toxicity compared

with methimazole.

C. Both agents are equally efficacious in the treatment of

Hashimoto’s disease.

D. Both medications should be administered three times/day.

A 53-year-old woman with a history of Graves disease underwent ablative therapy 3

years ago. She experienced significant symptom relief and became euthyroid. Her

thyroid laboratory values today include TSH 0.12 mIU/L (normal 0.5–4.5 mIU/L) and

a free T4 concentration of 3.8 g/dL (normal 0.8–1.9 ng/dL). She states that many of

her previous symptoms have now returned but are mild.

Which would be the most appropriate treatment option for her condition?

A. Methimazole.

B. Thyroidectomy.

C. PTU.

D. Metoprolol.

A 53-year-old woman with a history of Graves disease underwent ablative therapy

3 years ago. She experienced significant symptom relief and became euthyroid. Her

thyroid laboratory values today include TSH 0.12 mIU/L (normal 0.5–4.5 mIU/L) and

a free T4 concentration of 3.8 g/dL (normal 0.8–1.9 ng/dL). She states that many of

her previous symptoms have now returned but are mild.

Which would be the most appropriate treatment option for her condition?

A. Methimazole.

B. Thyroidectomy.

C. PTU.

D. Metoprolol.

C.R., a 27-year-old woman, has a 3-month history of intermittent

heat intolerance, sweats, tremor, and severe muscle

weakness, which has limited her ability to climb stairs. Her

weight has increased because of increased appetite. She is

also bothered by the pounding of her heart and some minor

difficulty in swallowing. There is a family history of thyroid

disease, but she denies taking any thyroid medications or any

history of radiation to her neck. C.R. previously received

iodide drops with symptomatic improvement, but her disease

recurred despite its continued administration.

Her other medical problems include type 2 diabetes controlled by diet, and

osteoarthritis treated with aspirin 650 mg orally (PO) every 4 hours. She has a

history of noncompliance with her clinic visits.

Pertinent physical findings include a blood pressure of 180/90 mm Hg, a pulse of

110 beats/minute, hyperreflexia, lid lag, and a diffusely enlarged thyroid gland

that is about four times normal (about 100 g). Laboratory data include the

following:

TT4, 6 mcg/dL (normal, 4.8–10.4)

FT4, 2 ng/dL (normal, 0.7–1.9)

TSH, <0.01 microunits/mL (normal, 0.4–4.0)

TPOAb, 350 international units/mL (normal, <0.8)

Fasting blood glucose, 350 mg/dL

Assess these subjective and objective data.

C.R.’s laboratory findings of a positive TPA and elevated thyroid

hormone levels verify an autoimmune hyperthyroid state.

However, the serum FT4 is elevated only slightly and is

disproportionately low relative to the severity of her symptoms,

the undetectable TSH level, and her other laboratory findings.

The low-normal TT4 could be explained by displacement of T4 from

TBG by aspirin. The possibility of a variant type of hyperthyroidism

known as T3 toxicosis should be considered. The clinical features

include signs and symptoms of thyrotoxicosis, normal or

borderline high FT4, an undetectable TSH level, and elevated T3

levels.

QUESTION

Why were the iodide initially effective in

improving C.R.’s symptoms and later

ineffective? When are iodides indicated?

What is their mechanism of action?

• The inhibitory effect of exogenous iodides on the intrathyroidal

organification of iodides is known as the Wolff-Chaikoff effect.

This is an inherent autoregulatory function of the normal gland

to prevent excessive hormone synthesis in the event of a large

iodide load. The Wolff-Chaikoff effect occurs when

intrathyroidal concentrations of iodides reach a critical level,

and this is not overcome by TSH stimulation. However, as

illustrated by C.R., the gland can escape from this block even

with continued iodide use. The gland escapes by decreasing

iodide transport or by leaking iodide.

• Both mechanisms decrease the critical intrathyroidal iodide level,

thereby decreasing the block to organification. This effect is

illustrated in C.R. Therefore, iodides should not be used as primary

therapy for Graves disease.

• Conversely, some patients are responsive to iodide therapy,

including (a) patients who already have high intrathyroidal iodine

stores (i.e., hot nodules, Graves disease); (b) patients with

underlying defects in organic binding mechanisms (i.e.,

Hashimoto’s); (c) patients who develop drug-induced thyroid

disorders; and (d) patients with Graves disease made euthyroid

with RAI or surgery and who are receiving no thyroid replacement.

The most important pharmacologic effect of iodides is

their ability to promptly inhibit thyroid hormone

release when dosages of 6 mg/day are given. The

mechanism is unknown. Unlike the Wolff-Chaikoff

effect, this effect can be overcome partially by an

increase in TSH secretion.

Thus, the normal gland can escape in 7 to 14 days

because inhibition of thyroid hormone release

stimulates a reflex increase in TSH secretion.

QUESTION

What are the advantages and disadvantages of

the different treatment modalities available for

C.R.?

QUESTION C.R. is started on PTU 200 mg q8h after baseline FT4 and

TSH levels have been obtained. Three weeks later, she

angrily complains that her symptoms are worse and that

the medication is not working; however, she reluctantly

admits to missing doses because of difficulty swallowing,

nausea, vomiting, diarrhea, fatigue, a cough, and a sore

throat. What are the advantages of using either PTU or

methimazole in the treatment of hyperthyroidism?

• In most hyperthyroid adults and children, methimazole

should be considered the thioamide of choice because

of increasing reports of hepatitis, some fatal, from PTU.

• PTU should be reserved for use in thyroid storm, during

the first trimester of pregnancy because of rare

teratogenicity from methimazole, and in those allergic

to methimazole (except agranulocytosis and hepatitis)

who are not candidates for RAI or surgery

• Compared with PTU, methimazole is also less

hepatotoxic and less expensive, requires daily

ingestion of fewer numbers of tablets, and is not

associated with a bitter tablet taste.

• However, PTU is preferred in thyroid storm

because, unlike methimazole, it also blocks the

peripheral conversion of T4 toT3.

• Why was the thioamide therapy

ineffective in C.R.?

• Was the dose of PTU appropriate?

• The inadequate response in C.R. suggests poor adherence to the

thioamide dosing regimen or a delayed response caused by prior

iodide loading of the gland.

• The best option for C.R. is to change to 30 to 40 mg of

methimazole, given once daily to improve adherence, or divided

into two doses to decrease GI distress.

• After methimazole is given for 4 to 6 weeks to achieve

euthyroidism, the daily dosage can be reduced gradually by 25% to

30% monthly to a dosage that maintains euthyroidism, usually 5 to

10 mg/day of methimazole.

What additional objective baseline

data should be obtained to monitor both the

efficacy and toxicity of thioamides?

• Before thioamides are administered, a baseline FT4 and TSH should

be obtained. A baseline white blood cell (WBC) count with

differential can also help differentiate the leukopenia associated

with hyperthyroidism from drug-induced leukopenia or

agranulocytosis .

• Baseline liver function tests can assist in the evaluation of

thioamide-induced hepatotoxicity .

• A repeat FT4 and TSH should be obtained after 4 to 6 weeks on

therapy and 4 to 6 weeks after any change in the dosing regimen.

• Once the patient is euthyroid on maintenance dosages, thyroid

function tests can be obtained every 3 to 6 months.

How long should C.R. be continued

on thioamide treatment?

Most data support a 12- to 18-month course of

treatment to achieve remission rates of

approximately 60%.

Treatment periods of 1 to 2 years are justifiable in

adherent patients.

Therapy can be reinstituted if hyperthyroidism

reappears shortly after therapy is discontinued.

Question 8

What adjunctive therapy might help

alleviate some of C.R.’s symptoms while

awaiting the onset of thioamide’s

effects?

Because of C.R.’s history of diabetes, the effects of Beta Blockers

in patients with diabetes must be considered . If β-blockers are

instituted, a cardioselective β-blocker would be a better choice

for patients on therapy that can cause hypoglycemia.

The appropriate dosage should be based on clinical and

objective improvement of hyperthyroid symptoms, such as a

reduction in heart rate.

Metoprolol 25 to 50 mg BID can be started initially and the

dosage titrated to maintain the heart rate at less than 90

beats/minute. Otherwise, diltiazem, verapamil, or a retrial of

iodides is warranted.

Question 9

A pruritic area over the pretibial aspects of both

legs as well as several maculopapular erythematous

patches and abdominal tenderness were noticed

during C.R.’s physical examination.

Do these reactions require the discontinuation of

her PTU?

• In C.R., PTU should be stopped while awaiting results of thyroid

function tests, transaminases, and bilirubin.

• Routine monitoring of liver function tests is not recommended

during thioamide therapy because patients can be

asymptomatic. However, routine monitoring might be

reasonable in patients with a history of liver disease and risk

factors for hepatitis (e.g., alcohol use).

• All patients receiving thioamides should be questioned closely

during the first 2 months of therapy for symptoms of hepatitis,

and hepatic function tests should be obtained if appropriate.

C.R.’s PTU is discontinued because she experienced

agranulocytosis and hepatitis, and surgery is

scheduled for her when granulocyte level returns to

normal.

What thyroid preparation is needed for C.R. before

thyroidectomy? What postoperative complications

are associated with thyroidectomy?

• C.R. should be in a euthyroid state at the time of surgery to

avoid precipitation of thyroid storm and morbidity.

• Generally, iodides, thioamides, or propranolol can be used.

• The combination of iodides and propranolol is more effective

than either used alone.

• Propranolol used alone has been associated with thyroid crisis

postoperatively and may be less effective than iodides in

decreasing gland friability and vascularity.

• Because C.R. received only 1 week of thioamide therapy, it is

likely that her gland still contains large stores of hormone;

therefore, pretreatment is necessary.

• In addition to the risks of anesthesia and surgery,

postoperative complications include

hypoparathyroidism, adhesions, laryngeal nerve

damage, bleeding, infection, and poor wound

healing.

• However, complications can be minimized if the

surgery is performed by experienced surgeons

Subclinical Hyperthyroidism

defined as a situation of Low or undetectable TSH with normal T4

Treatment :

a. Oral antithyroid drug alternative to ablative therapy in young pts

with Graves disease

b. β-Blockers may be of benefit to control cardiovascular morbidity,

especially with atrial fibrillation.

4. If untreated, screen regularly for the development of overt

hyperthyroidism (increased free T4 concentrations).

life-threatening decompensated thyrotoxicosis. (Mortality

rate 20%).

Precipitating causes:

Trauma, infection, antithyroid agent withdrawal, severe

thyroiditis, Post-ablative therapy (especially if not adequate

pretreatment)

Presentation: Fever, tachycardia, vomiting, dehydration,

coma, tachypnea, delirium.

PTU

i. 500- to 1000-mg loading dose, then 250 mg every 4 hours

ii. Can use methimazole 60–80 mg daily

b. Iodide therapy 1 hour after PTU initiation (dosed as above) to block hormone

release

c. β-Blocker therapy: control symptoms and block conversion

d. Acetaminophen as antipyretic therapy, if needed (avoid NSAIDs because of

displacement of protein-bound thyroid hormones)

Corticosteroid therapy: Prednisone 300 mg intravenous loading dose then

100 mg every 8 hours (or equivalent dosages of, e.g., dexamethasone,

hydrocortisone). Prophylaxis against relative adrenal insufficiency and may

block conversion of T4 to T3.

1. Hashimoto’s disease:

Most common hypothyroid disorder (Autoimmune)

2. Iatrogenic:

Thyroid resection or radioiodine ablative therapy for ttt of hyperthyroidism

3. Iodine deficiency (most common)

4. Secondary causes

i. Pituitary insufficiency

ii. Drug induced (e.g., amiodarone and lithium)

Hypothyroid disorders : :

a.↓↓ free T4 sr conc

b. ↑↑ TSH conc, usually above 10 mIU/L

(normal or low if central hypothyroidism)

c. Thyroid antibodies such as antithyroid

peroxidase and antithyroglobulin

autoantibodies

Clinical presentation

a. Levothyroxine or T4 (drug of choice)

i. Dosing

(c) Dose titration based on response (control of symptoms, normalization of

TSH and free T4)

(a) Initial:

(1) healthy adults →→→→→→, 1.6 mcg/kg (use IBW) per day

(2) 50–60 years age →→→→→→ 50 mcg/day.

(3) patient with CVD →→→→→→ 12.5–25 mcg/day.

(b) Taken in the morning on an empty stomach 30–60 minutes before breakfast or

at bedtime 4 hours after last meal; separate from other medications.

• (a) (4 – 8) weeks to assess response in TSH

after initiating or changing therapy (about a

7-day half-life for T4). May take longer for TSH

to achieve steady-state concentrations

• (b) Use free T4 rather than TSH if secondary

hypothyroidism.

(a) Hyperthyroidism

(b) Cardiac abnormalities but less than T3

because of slow absorption and then onset.

(c) Linked to risk of fractures (usually at

higher doses or over-supplementation)

A 63-year-old woman has Hashimoto’s disease. Her thyroid laboratory values

today include the following: TSH 10.6 mIU/L (normal 0.5–4.5mIU/L) and a free

T4 concentration of 0.5 ng/dL (normal 0.8–1.9 ng/dL). She feels consistently

rundown and has dry skin that does not respond to the use of hand creams.

Which would be considered the best drug for initial treatment of her condition?

A. Levothyroxine.

B. Liothyronine.

C. Desiccated thyroid.

D. Methimazole.

Case study A 76-year-old woman recently given a diagnosis of Hashimoto’s disease

presents with mild symptoms of lethargy, weight gain, and intolerance to

cold. Her thyroid-stimulating hormone (TSH) is 12.2 mIU/L, and her free

thyroxine (T4) is below normal limits. Her current weight is 47 kg. She has a

history of hypertension and coronary artery bypass surgery 2 years ago.

Which would be the most appropriate initial treatment for this patient?

A. Levothyroxine 25 mcg once daily.

B. Levothyroxine 75 mcg once daily.

C. Liothyronine 25 mcg once daily.

D. Liothyronine 75 mcg once daily.

Case study

Subclinical Hypothyroidism

• Elevated TSH with normal T4. Often the result of early Hashimoto’s disease.

• Whom to treat :

TSH between 4.5 and 10 mIU/L and:

i. Symptoms of hypothyroidism

ii. Antithyroid peroxidase antibodies present

iii. History of cardiovascular disease, heart failure, or risk factors for such

b. Initial daily dosages of 25–75 mcg recommended

• If untreated, screen regularly for the development of overt hypothyroidism

(decreased free T4 concentrations).

Case study A 66-year-old white woman has a TSH concentration of 10.8 (normal

0.5–4.5 mIU/L) and a free T4 concentration of 1.0 (normal 0.8–1.9

ng/dL). She has dry skin and feels lethargic. Which one of the

following is the most correct assessment?

A. She has subclinical hypothyroidism, which should be treated.

B. She has subclinical hyperthyroidism, which should be treated.

C. She has subclinical hypothyroidism, which should not be

treated.

D. She has subclinical hyperthyroidism, which should not be

treated.

Case study

life-threatening decompensated hypothyroidism. (Mortality rate

30%–60%)

Precipitating causes:

Trauma, infections, heart failure, medications (e.g., sedatives,

narcotics, anesthesia, lithium, amiodarone)

Presentation:

Coma is not required and is uncommon despite terminology,

altered mental state (very common), diastolic hypertension,

hypothermia, and hypoventilation.

Pharmacotherapy :

a. IV thyroid hormone replacement

i. T4: 100- to 500-mcg loading dose, followed by 75–100

mcg/day,. (Lower in pts ē CVD)

b. Antibiotic therapy:

Given common infectious causes, some advocate empiric

therapy with broad-spectrum antibiotics.

c. Corticosteroid therapy

i. Hydrocortisone 100 mg TID (or equivalent steroid)

ii. Can be discontinued if random cortisol concentration

not found to be depressed

M.W., a 70-kg, 23-year-old voice student, thinks that her neck has

become “fatter” during the past 3 to 4 months. She has gained 10 kg,

feels mentally sluggish, tires easily, and finds that she can no longer

hit high notes. Physical examination reveals puffy facies, yellowish

skin, delayed DTRs, and a firm, enlarged thyroid gland.

Laboratory data include the following results:

FT4, 0.6 ng/dL (normal, 0.7–1.9)

TSH, 60 microunits/mL (normal, 0.4–4.0)

TPA antibodies, 136 international units/L (normal, <0.8)

Assess M.W.’s thyroid status based on her clinical and

laboratory findings.

M.W. presents with many of the clinical features of

hypothyroidism. These include weight gain, mental

sluggishness, easy fatigability, lowering of the voice

pitch, puffy facies, yellowish tint of the skin, delayed

DTRs, and enlarged thyroid.

The diagnosis of hypothyroidism is confirmed by her

laboratory findings of a low FT4, an elevated TSH value,

and positive TPA antibodies.

What would you recommend as appropriate

starting and maintenance dosages of T4 for

M.W.?

o Because M.W. has no identifiable risk factors for cardiotoxicity that

require careful dosage titration (e.g., old age, cardiac disease, long

duration of hypothyroidism), she can be started on an estimated full

replacement dose of 125 mcg daily of l-thyroxine (70 kg × 1.7

mcg/kg/day = 120 mcg).

o An alternative conservative approach would be to start with 100 or 112

mcg/day, check the FT4 or FT4I and TSH tests after 6 to 8 weeks of

therapy, and if the TSH is still elevated without any symptoms of toxicity,

increase the dosage to 125 mcg/day.

o The appropriate replacement dose will produce a TSH of 1 to 2

microunits/mL, normalize FT4 or FT4 I levels, and reverse clinical

symptoms of hypothyroidism.

o Generally, dosing adjustments should not exceed monthly increments of

12.5 to 25 mcg/day.

Ten days after starting L-thyroxine therapy, M.W.

continues to complain of tiredness, fatigue, and

difficulty singing despite excellent adherence.

Thyroid function tests show a TT4 of 4 mcg/dL, an FT4 of

0.5 ng/dL, and a TSH of 40 microunits/mL.

What therapeutic options are available? How

should M.W.’s thyroid function tests be

interpreted?

o FT4 or FT4I and TSH should be checked about 6 to 8

weeks after the initiation of therapy because T4 has a

half-life of 7 days, and three to four half-lives are

needed to reach steady-state levels.

o Levels obtained before this time (as in M.W.) may

be misleading and should be interpreted cautiously.

o No change in her l-thyroxine dosage should be

attempted at this time.

o Eight weeks later, on a routine follow-up visit, M.W. still feels

tired and not back to her normal self. She denies any symptoms

of hyperthyroidism. Her thyroid function tests show:

TT4 of 14 mcg/Dl

TT3 of 100 ng/dL

FT4 of 1.9 ng/dL

TSH of 3.5 microunits/mL.

How should M.W.’s thyroid function tests be interpreted?

What changes, if any, should be recommended in her

therapeutic regimen?

if an elevated TT4 and FT4 are noted without any symptoms of

thyrotoxicosis (as in M.W.), the dosage should not be

decreased; rather, a trough FT4 and TSH level should be

obtained to eliminate excessive dosing or any laboratory

artifacts.

Alternatively, obtaining a level at least 9 hours after

levothyroxine administration also seems appropriate.

In M.W., the lack of hyperthyroid symptoms suggests

euthyroidism, and no changes in her therapeutic regimen

should be attempted until trough levels are available.

Evaluation for other causes of fatigue should be explored.

• R.B., a 65-year-old, agitated woman arrived at the emergency

department complaining of chest pain unrelieved by nitroglycerin

(NTG). Her medical problems include alcoholic cardiomyopathy, angina,

and hypothyroidism.

• Although she has been advised repeatedly to take her T4 regularly, she

continues to take it sporadically. An FT4 drawn 4 months ago was 0.5

ng/dL. Haloperidol 2 mg IM and morphine sulfate 10 mg IM were given

for the agitation.

• After the injection, the nurse noticed mental depression, lethargy, and

shallow breathing. R.B.’s oral temperature was 34.5◦C, and she exhibited

chills and shakes.

What is your assessment of R.B.’s

subjective and objective data?

R.B. has several symptoms consistent with myxedema coma. The

classic features are hypothermia and an altered sensorium that

ranges from stupor to coma.

Other predominant features include hypoxia, carbon dioxide

retention, severe hypoglycemia, hyponatremia, and paranoid

psychosis. Typical physical findings include a puffy face and eyelids, a

yellowish discoloration of the skin, and loss of the lateral eyebrows.

Pleural and pericardial effusions and cardiomegaly may be present.

Because myxedema coma frequently occurs in older women, it is

often difficult to distinguish the signs and symptoms from dementia

or other disease states, as illustrated by R.B.

What would be a reasonable therapeutic

plan for the management of R.B.’s

myxedema coma?

Thyroxine 400 to 500 mcg should be given IV initially in

patients younger than 55 years of age without cardiac

disease to saturate empty TBG sites and raise the

serum T4 level to 6 to 7 mcg/dL.

This initial dose can be adjusted based on the patient’s

weight and other restrictive factors (e.g., age, cardiac

disease).

The initial T4 dosage for R.B. should be reduced to 300

mcg/day to avoid worsening her angina.

Maintenance doses should be titrated to the patient’s

clinical response.

Appropriate measures should be taken to relieve

R.B.’s chest pain while ruling out the possibility of an

MI.

The use of a narcotic antagonist such as naloxone may

be beneficial in this instance because it can reverse the

effects of the morphine. Naloxone can also comatose

patients intoxicated with alcohol.