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