Overview of the clinical manifestations of hyperthyroidism in adults
Author
Douglas S Ross, MD Section Editor
David S Cooper, MD Deputy Editor
Jean E Mulder, MD
Last literature review version 19.1: January 2011 | This topic last updated: November 18, 2010 (More)
INTRODUCTION — The clinical manifestations of hyperthyroidism are largely independent of its cause.
(See "Disorders that cause hyperthyroidism".) However, the 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 the high serum thyroid hormone concentrations. These include
Graves' ophthalmopathy and infiltrative dermopathy (localized or pretibial myxedema). Most patients
with Graves' hyperthyroidism have a diffuse goiter, but so do patients with other, less common causes
of hyperthyroidism such as painless thyroiditis and thyrotropin (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 the diagnostic approach to
patients with hyperthyroidism are discussed separately. (See "Diagnosis of hyperthyroidism".)
SKIN — The skin is warm (and may rarely be erythematous) in hyperthyroidism due to increased blood
flow; it is also smooth because of a decrease in the keratin layer [1]. Other changes include:
Sweating is increased due to increased calorigenesis; this is often associated with heat
intolerance.Onycholysis (loosening of the nails from the nail bed, Plummer's nails) and softening of the
nails.Hyperpigmentation can occur in severe cases; it appears to be mediated by accelerated cortisol
metabolism, leading to increased corticotropin (ACTH) secretion [2].Pruritus and hives are occasional
findings, primarily in patients with Graves' hyperthyroidism [3].Vitiligo and alopecia areata can occur in
association with autoimmune disorders.Thinning of the hair.
Infiltrative dermopathy occurs only in patients with Graves' hyperthyroidism. The most common site is
the skin overlying the shins, where it presents as raised, hyperpigmented, violaceous, orange-peel
textured papules. (See "Pretibial myxedema in autoimmune thyroid disease".)
EYES — Stare and lid lag occur in all patients with hyperthyroidism. They are due to sympathetic
overactivity, possibly mediated by increased alpha-adrenergic receptors in some tissues [4]. Lid lag is
evaluated by having the patient follow the examiner's finger as it is moved up and down. The patient has
lid lag if sclera can be seen above the iris as the patient looks downward.
As noted above, only patients with Graves' disease have ophthalmopathy. It is characterized by
inflammation of the extraocular muscles and orbital fat and connective tissue, which results in proptosis
(exophthalmos), impairment of eye-muscle function, and periorbital and conjunctival edema.
Ophthalmopathy is more common in patients who smoke cigarettes. (See "Pathogenesis and clinical
features of Graves' ophthalmopathy (orbitopathy)".)
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 a result of proptosis and lid
retraction, and severe proptosis can cause optic neuropathy and even blindness.
CARDIOVASCULAR — Patients with hyperthyroidism have an increase in cardiac output, due both to
increased peripheral oxygen needs and increased cardiac contractility. Heart rate is increased, pulse
pressure is widened, and peripheral vascular resistance is decreased [5]. Systolic hypertension is
common [6]. The left ventricular ejection fraction does not increase appropriately during exercise,
suggesting the presence of a true cardiomyopathy [7]. High- or normal-output congestive heart failure
can occur in patients with severe hyperthyroidism, and congestive heart failure worsens in patients who
already have it. (See "Cardiovascular effects of hyperthyroidism".)
Atrial fibrillation occurs in 10 to 20 percent of patients with hyperthyroidism, and is more common in
elderly patients. In one study, 8 percent of all patients, and 15 percent of patients between ages 70 to
79 developed atrial fibrillation within 30 days of the diagnosis of hyperthyroidism [8]. Even subclinical
hyperthyroidism is associated with an increased rate of atrial ectopy and a three-fold increased risk of
atrial fibrillation (figure 1) [9].
In 60 percent of hyperthyroid patients with atrial fibrillation the rhythm converts spontaneously to sinus
rhythm when the hyperthyroidism is treated; in one study, all who spontaneously converted did so
within four months after becoming euthyroid [10]. Among those who do not convert spontaneously to
sinus rhythm and who undergo successful electrical cardioversion, the two-year risk of recurrent atrial
fibrillation was 59 percent compared with 83 percent of patients whose atrial fibrillation was not
associated with hyperthyroidism [11].
The role of anticoagulation is controversial in hyperthyroid patients with atrial fibrillation. In several
studies, 10 to 40 percent of patients with hyperthyroidism and atrial fibrillation had an arterial embolus
[12]. Left atrial enlargement, which is a risk factor for thrombus formation, is present in about 90
percent of hyperthyroid patients with atrial fibrillation and two percent of hyperthyroid patients with
sinus rhythm. Based on these results, we usually anticoagulate hyperthyroid patients with atrial
fibrillation. This recommendation is in agreement with guidelines published in 2006 by the American
College of Cardiology/American Heart Association/European Society of Cardiology [13].
Other abnormalities, including mitral valve prolapse, mitral regurgitation and an increase in left
ventricular mass index have also been reported. (See "Cardiovascular effects of hyperthyroidism".)
METABOLIC / ENDOCRINE
Serum lipids — Patients with hyperthyroidism tend to have low serum total and high-density lipoprotein
(HDL) cholesterol concentrations and a low total cholesterol/HDL cholesterol ratio. These values
increase after treatment [14].
Hyperglycemia — Although thyroxine is not a counterregulatory hormone, hyperthyroidism can
interfere with glucose metabolism. It is associated with both increased sensitivity of pancreatic beta
cells to glucose, resulting in increased insulin secretion, and antagonism to the peripheral action of
insulin [15]. The latter effect usually predominates, leading to impaired glucose tolerance in untreated
patients [16].
Adrenal function — Interpretation of the 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 concentrations. In one report of 49 hyperthyroid patients
undergoing ACTH testing, 35 percent had subnormal total serum cortisol values (<18 mcg/dl), while only
11 percent had a subnormal free cortisol index (ratio of serum total cortisol to CBG) [17].
RESPIRATORY — Dyspnea and dyspnea on exertion may occur for many reasons in hyperthyroidism: (see
"Respiratory function in thyroid disease").
Oxygen consumption and CO2 production increase. These changes result in hypoxemia and hypercapnia,
respectively, both of which stimulate ventilation.Respiratory muscle weakness is an important cause of
dyspnea [18], and reduced exercise capacity may be largely due to respiratory muscle weakness and
decreased lung volume [19].There may be tracheal obstruction from a large goiter.Hyperthyroidism may
exacerbate underlying asthma.Pulmonary arterial systolic pressure is increased [20].
GASTROINTESTINAL — Weight loss is due primarily to increased metabolic rate (hypermetabolism), and
secondarily to increased gut motility and the associated hyperdefecation and malabsorption; rare
patients have steatorrhea. Celiac disease is also more prevalent in patients with Graves' disease [21].
Most patients have hyperphagia, but an occasional patient with mild hyperthyroidism may have
sufficient appetite stimulation that weight is gained (more commonly in younger patients) [22]. Anorexia
may be prominent in elderly hyperthyroid patients [23].
Other changes that may occur include:
Vomiting [24] and abdominal pain, rarely.Dysphagia due to goiter.Abnormalities in liver function tests,
particularly high serum alkaline phosphatase concentrations, and rarely cholestasis.
HEMATOLOGIC — The red blood cell mass is increased in hyperthyroidism, but the plasma volume is
increased more, resulting in a normochromic, normocytic anemia [25]. Serum ferritin concentrations
may be high.
Graves' hyperthyroidism may be associated with autoimmune hematologic disorders such as idiopathic
thrombocytopenic purpura and pernicious anemia, and some patients have antineutrophil antibodies.
Hyperthyroidism may also be prothrombotic [26,27]. As an example, in one small study of thyroid cancer
patients taking levothyroxine in doses causing mild hyperthyroidism, levels of fibrinogen, prothrombin
fragment 1+2, protein S, antithrombin, tPA, PAI-1, and PAI-1/tPA were significantly higher than in
euthyroid controls [28]. Overt hyperthyroid patients have increased von Willebrand factor and
shortened in vitro platelet plug formation times, indicating enhanced platelet function [29].
GENITOURINARY — Urinary frequency and nocturia are common in hyperthyroidism, although the
mechanism is uncertain. Possible causes include primary polydipsia [30] and hypercalciuria. Enuresis is
common in children.
In women, serum sex hormone-binding globulin (SHBG) concentrations are high, which results in high
serum estradiol concentrations and low-normal serum free (unbound) estradiol concentrations, high
serum luteinizing hormone (LH) concentrations, a reduced mid-cycle surge in LH secretion,
oligomenorrhea, and anovulatory infertility [31,32]. Amenorrhea can occur in women with severe
hyperthyroidism.
In men, the increase in serum SHBG concentrations results in high serum total testosterone
concentrations, but serum free (unbound) testosterone concentrations are normal or low [33,34].
Serum LH concentrations may be slightly high. Extragonadal conversion of testosterone to estradiol is
increased, so that serum estradiol concentrations are high. These changes can cause gynecomastia,
reduced libido, and erectile dysfunction [31,35]. Spermatogenesis is often decreased or abnormal, eg,
more spermatozoa are abnormal or non-motile [34].
BONE — Thyroid hormone stimulates bone resorption, resulting in increased porosity of cortical bone
and reduced volume of trabecular bone [36]. The loss in cortical bone density is greater than that of
trabecular bone. Serum alkaline phosphatase and osteocalcin concentrations are high, indicative of
increased bone turnover. The increase in bone resorption may lead to an increase in serum calcium
concentrations, thereby inhibiting parathyroid hormone secretion and the conversion of calcidiol (25hydroxyvitamin D) to calcitriol (1,25-dihydroxyvitamin D). In addition, the metabolic clearance rate of
calcitriol is increased. These changes can result in impaired calcium absorption and an increase in
urinary calcium excretion. The net effect is osteoporosis and an increased fracture risk in patients with
chronic hyperthyroidism. (See "Bone disease with hyperthyroidism and thyroid hormone therapy".)
Graves' disease may also be associated with thyroid acropathy, with clubbing and periosteal new bone
formation in the metacarpal bones or phalanges. Patients with thyroid acropachy commonly present
with asymptomatic clubbing, severe ophthalmopathy, and dermopathy; a high percentage are cigarette
smokers [37].
NEUROPSYCHIATRIC — 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 [38]. Insomnia is
also common. Symptoms often worsen in patients with preexisting psychiatric disorders.
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. (See "Neurologic manifestations
of hyperthyroidism and Graves' disease".)
GERIATRIC HYPERTHYROIDISM — Hyperthyroidism in elderly patients may be apathetic, rather than
having hyperactivity, tremor, and other symptoms of sympathetic overactivity [39]. However, two-thirds
of such patients have symptoms similar to those in younger patients [40]. In cross-sectional studies of
patients with hyperthyroidism, older patients had a reduced risk for the presence of several classical
symptoms (ie, heat intolerance, tremor, nervousness) but a higher prevalence of weight loss and
shortness of breath compared with younger patients [40,41]. Older patients also had a higher rate of
atrial fibrillation and moderate to severe ophthalmopathy [41].
Elderly patients with Graves' hyperthyroidism are less likely to have a goiter. Toxic multinodular 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 percent of elderly hyperthyroid patients, due primarily to coexistent
conduction system disease.
INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. (See
"Patient information: Hyperthyroidism (overactive thyroid)" and "Patient information: Antithyroid
drugs".) We encourage you to print or e-mail these topic reviews, or to refer patients to our public web
site, www.uptodate.com/patients, which includes these and other topics.
SUMMARY
The classic symptoms of hyperthyroidism include weight loss, heat intolerance, tremor, palpitations,
anxiety, increased frequency of bowel movements, and shortness of breath. Goiter is commonly found
on physical examination. (See individual sections above).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. (See 'Geriatric hyperthyroidism' above.)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). (See "Pathogenesis and
clinical features of Graves' ophthalmopathy (orbitopathy)" and "Pretibial myxedema in autoimmune
thyroid disease".)
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