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153© Springer International Publishing AG 2018
E. Sydney et al. (eds.), Handbook of Outpatient Medicine,
https://doi.org/10.1007/978-3-319-68379-9_8
Hypothyroidism
Introduction
Hypothyroidism (both overt and subclinical) is one of the
most common endocrine disorders, with a prevalence of 1.9%
in women and 0.1% in men [1, 2]. Prevalence increases with
age in men (0.5%) and women (5.0%) over 60. Treatment of
hypothyroidism is with levothyroxine, which accounted for
over 119 million prescriptions in 2015 [3].
The hallmark of hypothyroidism is the insufficient pro-
duction of thyroid hormones. This can be of a primary
nature (underactivity of the thyroid gland itself) or of a
secondary nature, in which the stimulation of the thyroid
gland by the pituitary or hypothalamic glands is inadequate.
Primary hypothyroidism accounts for the vast majority
(>95%) of cases. In iodine-sufficient parts of the world,
Hashimoto’s autoimmune thyroiditis is the most common
Chapter 8
Thyroid Dysfunction
Nancy A. LaVine
N.A. LaVine, MD (*)
General Internal Medicine, Northwell Health,
2001 Marcus Avenue, Suite S160, New Hyde Park, NY 11042, USA
e-mail: nlavine@northwell.edu
154
cause of hypothyroidism, while iodine deficiency remains an
important cause worldwide [4].
Significant causes of hypothyroidism are listed below:
• Autoimmune thyroiditis
• Severe iodine deficiency
• Non-autoimmune thyroiditis (subacute, silent, and
postpartum)
• Partial or total thyroidectomy or other neck surgery
• Thyroid ablation with radioactive iodine therapy
• External radiation to the head and neck
• Infiltrative diseases of the thyroid (amyloidosis, sarcoid-
osis, hemochromatosis)
• Congenital
• Secondary hypothyroidism (pituitary adenomas, empty
sella, pituitary surgery, extrapituitary tumors, inflamma-
tory or infiltrative diseases)
• Drugs: amiodarone, lithium, interferon, methimazole, pro-
pylthiouracil, iodine, and iodinated contrast agents
Key H&P
The presentation of hypothyroidism can range from com-
pletely asymptomatic to floridly symptomatic. Symptoms
may be influenced by the duration and severity of disease as
well as the age of the patient and his or her sensitivity to
thyroid deficiency. Symptoms can be as minor as mild
fatigue, cold intolerance, constipation, or weight gain or, in
rare cases, as significant as myxedema coma (hypothermia,
coma, pleural and pericardial effusions). The positive predic-
tive values of varied symptoms of hypothyroidism have been
as low as 8–12% in one study [5]. Patients presenting with
newly developed symptoms are more likely to have hypothy-
roidism [6]. Physical exam findings of hypothyroidism can
include goiter, bradycardia, or delayed deep tendon reflexes.
Given the unreliability of history and lack of physical exam
findings, the diagnosis of hypothyroidism in adults is made
N.A. LaVi n e
155
on the basis of biochemical testing. In addition to those
patients presenting with symptoms, there are certain groups
of patients at higher risk for developing hypothyroidism who
may need screening:
• Personal or family history of autoimmune thyroid
disorders
• Autoimmune endocrine disorders (DM type 1, adrenal
insufficiency, ovarian failure)
• Autoimmune disorders (celiac disease, vitiligo, pernicious
anemia)
• Postpartum women
• Treatment of thyroid, pituitary, or hypothalamic glands in
the past
• Radiation to the head and neck
• Turner’s syndrome
• Down syndrome
Decision-Making/Differential Diagnosis
Thyroid-stimulating hormone (TSH) is the first-line test in
the diagnosis of thyroid hormone insufficiency, with a 99%
sensitivity and specificity [7]. An elevated TSH with a
decreased free T4 (FT4) level is the hallmark of primary
hypothyroidism. FT4 alone is less sensitive in detection, and
free T3 levels may not be abnormal unless there is severe
hypothyroidism. The degree of TSH elevation and the level
of free T4 can help further characterize primary hypothyroid-
ism. Patients with overt hypothyroidism will often have a
TSH level greater than 10 mU/L with an FT4 below reference
range. For some patients, TSH may be mildly elevated
(5–10 mU/L) with a low serum FT4. Other patients may have
a milder elevation in TSH (between 5 and 10 mU/L) with an
FT4 in the normal range – this is subclinical (or mild)
hypothyroidism. The distinction between these categories has
important implications for treatment.
8. Thyroid Dysfunction
156
Treatment
Overt Hypothyroidism
There is strong evidence to support treating patients with overt
hypothyroidism (TSH > 10 mU/L) with levothyroxine (LT4)
monotherapy. Treatment is generally lifelong, and as such, a
confirmatory TSH should be checked prior to initiating ther-
apy. Adequate treatment often improves symptoms, as well as
prevents progression of disease and decreases the risk of car-
diovascular events. Untreated overt hypothyroidism can result
in coronary artery disease, atherosclerosis, heart failure,
arrhythmias, and pericardial and pleural effusions, secondary
to effects on lipid profiles, the vascular system, and cardiac
function [8]. The goal of treatment is to restore the euthyroid
state and avoid such complications. Levothyroxine doses
should be titrated to normalize the TSH within the reference
range. Initial dosing can be based on weight, with a dose of
1.6 mcg/kg sufficient to reach a euthyroid state in most patients
[9]. Alternatively, a dose of 25–50 mcg daily can be started and
titrated up. In general, older patients (>60 years old) and those
patients with ischemic heart disease should be started at lower
doses (25–50 mcg) and titrated up over several weeks.
Monitoring of the TSH level is the most sensitive way to
ensure adequate doses of levothyroxine therapy, with moni-
toring every 4–8 weeks between dosage changes. Patients
who have reached a euthyroid state should have TSH moni-
tored every 6–12 months to ensure stability.
Subclinical Hypothyroidism
Patients with subclinical hypothyroidism have an elevated
risk of developing overt hypothyroidism, and several factors
have been shown to increase the risk, including the level of
TSH elevation and the presence of thyroid peroxidase (TPO)
antibodies. Treatment of subclinical hypothyroidism with
levothyroxine remains controversial. Patients with subclinical
hypothyroidism should be monitored yearly for continued
TSH elevation, the development of overt hypothyroidism, or
the development of TPO antibodies (Fig. 8.1).
N.A. LaVi n e
157
Normal Free T4
Elevated TSH
Check Free T4
Decreased Free T4
Overt
Hypothyroidism
Confirm TSH
elevation
Initiate levothyroxine
replacement
TSH >10 mU/L TSH 5-10 mU/L
Initiate levothyroxine
replacement
Symptoms?
Yes No
Consider
levothyroxine
replacement
check TPO
antibodies
if Positive consider
levothyroxine
replacement
if Negative, check
TSH at 6mo. and
then yearly
Subclinical
Hypothyroidism
Fig. 8.1 Treatment algorithm for hypothyroidism
Treatment Challenges
Levothyroxine absorption and metabolism can be affected
by numerous other medications and dietary intake. Both
iron and calcium supplements can interfere with absorp-
tion. Optimal absorption occurs with fasting, so patients
should be advised to take the medication on an empty
stomach. Timing of new medication administration should
be carefully considered. In a patient with inadequate TSH
levels on an optimum weight-based dose, nonadherence
(both with the medication and with fasting) as well as
8. Thyroid Dysfunction
158
absorption problems (such as in celiac disease or previous
GI surgeries) should be considered.
Clinical Pearls
• Clinical symptoms have low positive predictive value in
the diagnosis of hypothyroidism.
• Thyroid-stimulating hormone (TSH) is the first-line test in
the diagnosis of thyroid hormone insufficiency, with a 99%
sensitivity and specificity.
• Monitoring TSH alone in patients on levothyroxine
replacement is adequate to ensure appropriate dosages.
Don’t Miss This!
• Consider nutritional and medication interactions with
levothyroxine in patients with elevated TSH despite seem-
ingly adequate levothyroxine dosing.
Hyperthyroidism
Introduction
Hyperthyroidism is increased thyroid hormone synthesis and
secretion. Thyrotoxicosis is the clinical syndrome of increased
circulating thyroid hormone. Hyperthyroidism is found in
approximately 1.3% of the US population (0.5% clinical and
0.7% subclinical) [10] . Hyperthyroidism can be overt or sub-
clinical, and both will be discussed in this section. The hall-
mark of hyperthyroidism is the detection of a low level of
thyroid-stimulating hormone (TSH) and elevated levels of
either T4 or T3. Subclinical hyperthyroidism is characterized
by low serum TSH and normal levels of T3 and T4.
Key H&P
Symptoms of overt hypothyroidism can vary, with some of
the more prevalent symptoms including fatigue, weight loss,
N.A. LaVi n e
159
tremulousness/palpitations, anxiety, and heat intolerance.
Physical exam findings can include tachycardia, palpable goi-
ter, tremor, and proptosis, and in rare cases, patients can pres-
ent with thyroid storm (tachycardia, agitation, fever, and
altered mental state).
Decision-Making/Differential Diagnosis
The most common etiologies for hyperthyroidism are listed
below. Graves’ disease, caused by autoantibodies stimulating
the TSH receptor, is the most common etiology with 3% of
women and 0.5% of men developing Graves’ disease in their
lifetime [11]. Other important etiologies include thyroiditis
(subacute, silent, or postpartum), which leads to release of
preformed thyroid hormone due to destruction of the thyroid
follicles, and toxic nodular goiter, which is more common in
iodine-deficient areas. The following algorithm outlines a
strategy for diagnosis of the more common etiologies of
hyperthyroidism (Fig. 8.2).
Treatment
Graves’ Disease
The treatment options for Graves’ disease include radioac-
tive iodine (RAI) ablation, antithyroid drugs, and surgical
removal of the thyroid. In the USA, RAI is generally favored
for initial treatment (58.6%) followed by 40.5% of endocri-
nologists opting for antithyroid drugs and only a small minor-
ity (1%) recommending surgical therapy [12]. Beta blockade
is important to minimize clinical symptoms such as palpita-
tions and tremulousness, while other treatments to lower
thyroid hormone levels are undertaken. Propranolol, ateno-
lol, and metoprolol are commonly prescribed. Of note, the
treatment for toxic nodular goiter or toxic adenoma gener-
ally follows that for Graves’ disease.
8. Thyroid Dysfunction
160
Suppressed TSH
Elevated T4
Suppressed TSH
Normal Free T4
Elevated/Normal TSH
Elevated Free T4
Pituitary Adenoma
(TSH Secretion)
Normal TSH
Normal Free T4/T3
Normal
TSH Receptor
Antibodies Present
TSH Receptor
Bodies Absent
Graves Disease
Radionuclide
Uptake Scan
Patchy Uptake Diffuse Uptake
Toxic Multinodular
Goiter or Toxic
Thyroid Nodule
No Uptake
Thyroiditis Graves Disease
Free T3 elevated Free T3 Normal
Subclinical
Hyperthyroidism
Primary
Hypothyroidism
Check Free T3
Check TSH
Receptor Antibodies
Signs/Symptoms
of Hyperthyroidism
Check TSH and
Free T4/T3
Fig. 8.2 Diagnostic algorithm for hyperthyroidism
N.A. LaVi n e