Hyperthyroidism (Clinical manifestations)
INTRODUCTION
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The clinical manifestations of hyperthyroidism are largely independent of its cause. However,
disorder that causes hyperthyroidism may have other effects. In particular, Graves' disease,
the most common cause of hyperthyroidism, causes unique problems that are not related to
high serum TH concentrations. These include Graves' ophthalmopathy and infiltrative
dermopathy (localized or pretibial myxedema). Most patients with Graves' hyperthyroidism
have diffuse goiter, but so do patients with other, less common causes of hyperthyroidism
such as painless thyroiditis and TSH-secreting pituitary tumors.
The major clinical manifestations of hyperthyroidism (thyrotoxicosis) will be briefly reviewed
here. More detailed discussions of its effects on specific organ systems as well as diagnostic
approach to patients with hyperthyroidism are discussed separately.
SKIN
1. The skin is warm (and may rarely be erythematous) in hyperthyroidism due to increased
blood flow; it is also smooth because of decrease in keratin layer.
A. Sweating, which increases due to increased calorigenesis; this is often associated with
heat intolerance
B. Onycholysis (loosening of nails from nail bed, Plummer's nails) and softening of nails
C. Hyperpigmentation, which can occur in severe cases; it appears to be mediated by
accelerated cortisol metabolism, leading to increased ACTH secretion
D. Pruritus and hives, which are occasional findings, primarily in patients with Graves'
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hyperthyroidism
E. Vitiligo and alopecia areata, which can occur in association with autoimmune disorders
F. Thinning of hair
Infiltrative dermopathy occurs only in patients with Graves' hyperthyroidism. The most
common site is skin overlying shins, where it presents as raised, hyperpigmented, violaceous,
orange-peel-textured papules.
EYES
1. Stare and lid lag occur in all patients with hyperthyroidism. They are due to sympathetic
overactivity, possibly mediated by increased α-adrenergic receptors in some tissues. Lid lag is
evaluated by having patient follow examiner's finger as it is moved up and down. The patient
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has lid lag if sclera can be seen above iris as patient looks downward.
As noted above, only patients with Graves' disease have ophthalmopathy. It is characterized
by inflammation of extraocular muscles and orbital fat and CNT, which results in proptosis
(exophthalmos), impairment of eye-muscle function, and periorbital and conjunctival edema.
Ophthalmopathy is more common in patients who smoke cigarettes.
Patients with ophthalmopathy may have gritty feeling or pain in their eyes, and may have
diplopia due to extraocular muscle dysfunction. Corneal ulceration can occur as result of
proptosis and lid retraction, and severe proptosis can cause optic neuropathy and even
blindness.
CARDIOVASCULAR
1. Patients with hyperthyroidism have increase in CO, due both to increased peripheral oxygen
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needs and increased cardiac contractility. HR is increased, pulse pressure is widened, and SVR
is decreased. Systolic HTN is common. The LVEF does not increase appropriately during
exercise, suggesting presence of true CMP. High- or normal-output CHF can occur in patients
with severe hyperthyroidism and CHF worsens in patients who already have it.
Af occurs in 10 to 20% of patients with hyperthyroidism, and is more common in elderly
patients. In study, 8% of all patients and 15% of patients between ages 70 to 79 developed Af
within 30 days of diagnosis of hyperthyroidism. Even subclinical hyperthyroidism is associated
with increased rate of atrial ectopy and 3-fold increased risk of Af.
In 60% of hyperthyroid patients with Af, rhythm converts spontaneously to SR when
hyperthyroidism is treated; in one study, all who spontaneously converted did so within 4
months after becoming euthyroid. Among those who do not convert spontaneously to SR and
who undergo successful electrical cardioversion, 2-year risk of recurrent Af was 59%
compared with 83% of patients whose Af was not associated with hyperthyroidism.
The role of anticoagulation is controversial in hyperthyroid patients with Af. In several studies,
10 to 40% of patients with hyperthyroidism and Af had arterial embolus. LAE, which is risk
factor for thrombus formation, is present in about 90% of hyperthyroid patients with Af and
2% of hyperthyroid patients with SR. Based on these results, we usually anticoagulate
hyperthyroid patients with Af. This recommendation is in agreement with guidelines
published in 2006 by ACC/AHA/ESC.
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Other abnormalities, including MVP, MR, and increase in left ventricular mass index have also
been reported.
METABOLIC
1. Serum lipids
A. Patients with hyperthyroidism tend to have low serum total and HDL-c and low
total cholesterol/HDL-c ratio. These values increase after treatment.
2. Hyperglycemia
A. Although thyroxine is not counterregulatory hormone, hyperthyroidism can interfere
with glucose metabolism. It is associated with both increased sensitivity of pancreatic β
cells to glucose, resulting in increased insulin secretion, and antagonism to peripheral
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action of insulin. The latter effect usually predominates, leading to impaired glucose
tolerance in untreated patients.
Adrenal function
A. Interpretation of cortisol response to ACTH stimulation testing may be misleading in
patients with hyperthyroidism because cortisol binding globulin (CBG) levels decrease,
resulting in lower total serum cortisol. In one report of 49 hyperthyroid patients
undergoing ACTH testing, 35% had subnormal total serum cortisol values (<
18 mcg/dL), while only 11% had subnormal free cortisol index (ratio of serum total
cortisol to CBG).
RESPIRATORY
1. Dyspnea and DOE may occur for many reasons in hyperthyroidism.
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Oxygen consumption and CO2 production increase. These changes result in hypoxemia and
hypercapnia, respectively, both of which stimulate ventilation.
3. Respiratory muscle weakness is important cause of dyspnea, and reduced exercise capacity
may be largely due to respiratory muscle weakness and decreased lung volume.
4. There may be tracheal obstruction from large goiter.
5. Hyperthyroidism may exacerbate underlying asthma.
6. Pulmonary arterial systolic pressure is increased.
GASTROINTESTINAL
1. Weight loss is due primarily to increased metabolic rate (hypermetabolism), and secondarily
to increased gut motility and associated hyperdefecation and malabsorption; rare patients
have steatorrhea. Celiac disease is also more prevalent in patients with Graves' disease. Most
patients have hyperphagia, but occasional patient with mild hyperthyroidism may have
sufficient appetite stimulation that weight is gained (more commonly in younger patients).
Anorexia may be prominent in elderly hyperthyroid patients.
2. Other changes that may occur.
A. Vomiting and abdominal pain, rarely
B. Dysphagia due to goiter
C. Abnormalities in LFT, particularly high serum ALP and, rarely, cholestasis
HEMATOLOGIC
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RBC mass is increased in hyperthyroidism, but plasma volume is increased more, resulting in
normochromic, normocytic anemia. Serum ferritin concentrations may be high.
2. Graves' hyperthyroidism may be associated with autoimmune hematologic disorders such as
ITP and pernicious anemia, and some patients have anti-neutrophil antibodies.
3. Hyperthyroidism may also be prothrombotic. As example, in meta-analysis of 51 studies
evaluating effect of thyroid hormone excess (exogenous or endogenous) on coagulation
system, excess thyroid hormone was associated with rise in prothrombotic factors, including
factors VIII, IX, fibrinogen, vWF, and PAI-1. Similar findings were noted in patients with either
overt or subclinical hyperthyroidism.
GENITOURINARY
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Urinary frequency and nocturia are common in hyperthyroidism, although mechanism is
uncertain. Possible causes include primary polydipsia and hypercalciuria. Enuresis is common
in children.
In women, serum SHBG are high, which results in high serum estradiol and low-normal serum
free estradiol, high serum LH, reduced mid-cycle surge in LH secretion, oligomenorrhea, and
anovulatory infertility. Amenorrhea can occur in women with severe hyperthyroidism.
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In men, increase in serum SHBG results in high serum total testosterone, but serum free
testosterone are normal or low. Serum LH may be slightly high. Extra-gonadal conversion of
testosterone to estradiol is increased, so that serum estradiol is high. These changes can
cause gynecomastia, reduced libido, and erectile dysfunction. Spermatogenesis is often
decreased or abnormal, eg, more spermatozoa are abnormal or non-motile.
BONE
1. Thyroid hormone stimulates bone resorption, resulting in increased porosity of cortical bone
and reduced volume of trabecular bone. The loss in cortical bone density is greater than that
of trabecular bone. Serum ALP and osteocalcin are high, indicative of increase bone turnover.
The increase in bone resorption may lead to increase in serum calcium, thereby inhibiting PTH
secretion and conversion of calcidiol to calcitriol. In addition, metabolic clearance rate of
calcitriol is increased. These changes result in impaired calcium absorption and increase in
urinary calcium excretion. The net effect is osteoporosis and increased fracture risk in
patients with chronic hyperthyroidism.
2. Graves' disease may also be associated with thyroid acropathy, with clubbing and periosteal
new bone formation in metacarpal bones or phalanges. Patients with thyroid acropathy
commonly present with asymptomatic clubbing, severe ophthalmopathy, and dermopathy; a
high percentage is cigarette smokers.
NEUROPSYCHIATRIC
1. Patients with thyrotoxicosis may experience behavioral and personality changes, such as
psychosis, agitation, and depression. Less overt manifestations that are more common in
less severe thyrotoxicosis include anxiety, restlessness, irritability, and emotional lability.
Insomnia is also common. Symptoms often worsen in patients with preexisting psychiatric
disorders.
2. These behavioral manifestations are accompanied by cognitive impairments, particularly
impaired concentration, confusion, poor orientation and immediate recall, amnesia, and
constructional difficulties. Other neurologic manifestations are discussed separately.
GERIATRIC HYPERTHYROIDISM
1. Hyperthyroidism in elderly patients may be apathetic, rather than having hyperactivity,
tremor, and other symptoms of sympathetic overactivity. However, two-thirds of such
patients have symptoms similar to those in younger patients. In cross-sectional studies of
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patients with hyperthyroidism, older patients had a reduced risk for the presence of several
classical symptoms (heat intolerance, tremor, nervousness) but a higher prevalence of weight
loss and shortness of breath compared with younger patients. Older patients also had a
higher rate of atrial fibrillation and moderate to severe ophthalmopathy.
Elderly patients with Graves' hyperthyroidism are less likely to have a goiter. Toxic
multi-nodular goiter is more common in the elderly, although the majority of hyperthyroid
patients at any age have Graves' hyperthyroidism. In addition, elderly patients often have
persistent constipation. Tachycardia of 100 beats per minute is absent in 40% of elderly
hyperthyroid patients, due primarily to coexistent conduction system disease.
SUMMARY
1. The classic symptoms of hyperthyroidism include weight loss, heat intolerance, tremor,
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palpitations, anxiety, increased frequency of bowel movements, and shortness of breath.
Goiter is commonly found on physical examination.
Elderly patients may have fewer classical manifestations of hyperthyroidism. However,
weight loss, shortness of breath, and atrial fibrillation occur more commonly in older than
younger patients.
The clinical manifestations of hyperthyroidism are largely independent of its cause. However,
the disorder that causes hyperthyroidism may have other effects. In particular, Graves'
disease causes unique problems that are not related to the high serum thyroid hormone
concentrations. These include Graves' ophthalmopathy and infiltrative dermopathy (localized
or pretibial myxedema).