Prevalence of 2% in women and 0.2% in men.

Hyperthyroidism has a prevalence of 0.5-2% in women; however, it is 10 times less common in men. 

Overt hyperthyroidism is defined as sub normal serum thyrotropin concentrations with elevated free T3 or free T4 concentrations.

Overt hyperthyroidism has a prevalence of approximately 0.6% among women (Wang C, Crapo LM).

Incidence of hyperthyroidism is approximately 0.4 cases per 1000 women per year, and the incidence in men is 25% or less of the incidence in women.

The global prevalence of hyperthyroidism in iodine sufficient countries is estimated at 0.2 to 2.5%.

Compared with euthyroidism, overt hyperthyroidism is associated with a 35 to 400% increase in all cause mortality and the 20% increase in cardiovascular mortality.

The increased mortality risk is thought to be related to damage to vascular endothelium and hypercoagulability.

The term thyrotoxicosis refers to all conditions in which thyroid hormone levels are elevated, and may occur due to increase thyroid hormone production, a release of preformed hormones from the thyroid gland due to inflammation, or increases in extrathyroid thyroid hormone availability, due to excess levothyroxine repletion, surreptitious thyroid hormone  ingestion, or struma ovarii.

Thyroid hormone binds to specific thyroid hormone receptors and modify gene transcription in almost all tissues.

Thyroid hormone also has nongenomic activities.

Increases the expression of beta-adrenergic receptors and cyclic AMP isoforms.

Reduces expression of inhibitory G-protein subunits and contributes to thermogenesis (Silva JE, Blanco SDC).

Symptomatic disease, most often manifests as Grave’s disease, most common in women of childbearing age.

Graves’ disease is the most common cause in all age groups.

The most common cause of hyperthyroidism, with an annual incidence of 20-50 cases per hundred thousand persons, and a lifetime risk of 3% in women and 0.5% in men.

Graves’ disease is an autoimmune disorder that has an antibody to the thyrotropin receptor, acts as an agonist to that receptor and unregulates thyroid hormone production.

in Graves’ disease autoantibodies are directed against the thyroid, thyrotropin, receptor, causing increased thyroid, hormone synthesis, and secretion.

In areas of iodine deficiency toxic adenoma and multinodular goiter increases with age, and in these areas these disorders are more common than Graves’ disease in older people (Laurberg P et al).

In toxic adenoma and multinodular goiter autonomous unregulated synthesis of thyroid hormone occurs, and ophthalmopathy and spontaneous remissions do not occur as seen with Graves’ disease.

Thyrotropin is required to stimulate iodine uptake into follicular cells.

Thyrotropin-receptor antibodies activate thyrotropin receptors in Graves’ disease, allowing the radioiodine to concentrate within the entire gland.

In toxic adenoma or toxic nodular goiter thyrotropin level is suppressed by hyperthyroidism and radioiodine is concentrated only in tissue that is autonomous and not subjected to normal regulation by thyrotropin.

Thyroid scintigraphy assesses the activity of the thyroid gland, measuring uptake of iodine or a technectium pertechnetate.

Uptake is diffusely, increased in Graves’ disease, and heterogeneously increased in toxic adenoma or toxic nodules.

Gand vascularity vascularity is generally increased in Graves’ disease with a thyroid ultrasound, demonstrating diffusely increased thyroid vascularity.

Toxic nodular disease has somatic activating variants in genes that regulate hormone synthesis and can autonomously create  excess thyroid hormone.

Toxic nodular disease is the second most common cause of hyperthyroidism.

Toxic nodular disease is more common in iodine deplete regions.

In early pregnancy, hCG stimulates thyroidal thyrotropin receptor, causing increased thyroid hormone synthesis.

Transient gestational thyroid toxicosis occurs in approximately 2 to 11% of pregnancies and is associated with hyperemesis gravidarum.

This hyperthyroidism does not require anti-thyroid treatment, and is not associated with adverse obstetric outcomes.

It generally resolves spontaneously as maternal hCG levels decline.

Other forms of hyperthyroidism require therapy, but antithyroid drugs are associated with newborn abnormalities.

Radioactive iodine is contraindicated in pregnancy.

Auto immunity, infection, some medications, and trauma to the thyroid can cause thyroid inflammation and release of stored hormones into the bloodstream, causing thyrotoxicosis, but not hyperthyroidism, as there is no increase in thyroid hormone synthesis.

In patients with hyperthyroidism secondary to toxic adenoma or toxic nodular goiter treatment with anti-thyroid drugs before radioiodine is administered, and the thyrotropin level is allowed to be normal or high, then the radioactive iodine will concentrate in both all autonomous and normal thyroid tissue.

Patients have beta-adrenergic mediated symptoms with nervousness, irritability, heat intolerance, palpitations and increased bowel motility, and insomnia, diarrhea, excessive sweating, and irregular menses.

Untreated hyperthyroidism can result in cardiac arrhythmias, congestive heart failure, osteoporosis, adverse obstetric outcomes, and metabolic derangements, such as increased risk resting energy expenditure, and gluconeogenesis.

For hyperthyroidism, the most common symptoms are tachycardia, palpitations, nervousness, tremor, increased blood pressure and heat intolerance.

About 2% of older people with hyperthyroidism present with apathetic hyperthyroidism with minimal symptoms.

Clinical manifestations of hyperthyroidism are often related to hypermetabolism, excessive thyroid hormone, an increase in oxygen consumption, metabolic changes in protein metabolism, immunologic stimulation of diffuse goitre, and ocular changes of exophthalmos.

Patients with Graves’ disease or toxic nodules may report increase neck size or symptoms of compression, such as this dysphasia, orthopnea, or voice changes.

Thyroid pain and tenderness of present in subacute thyroiditis.

Subclinical hyperthyroidism is usually asymptomatic or causes symptoms similar to but milder than those of overt hyperthyroidism.

Associated with catabolic effects of circulating thyroid hormone with weight loss, fatigue, increased appetite, muscle weakness, and bone loss.

Atrial fibrillation occurs in 5-15% of patients, compared to 1.5-2.% of the general population.

Atrial fibrillation is the most common cardiac complication.

Associated with an increase in cardiovascular mortality.

Use of anticoagulation in thyrotoxic associated atrial fibrillation is controversial, as hyperthyroidism is not an independent risk factor for stroke/systemic embolism (Bruere H et al).

Cardiac findings include atrial fibrillation, heart failure, tachycardia, and exacerbation of coronary artery disease.

Untreated disease may lead to atrial fibrillation, congestive heart failure and cardiomyopathy.

Severe disease may be associated with fever and delirium, referred to as thyroid storm.

Thyroid storm may be associated with a mortlity rate of 20-50% (Burch HB, Wartofsky L).

Increased all cause and circulatory mortality in patients with overt hyperthyroidism reflecting effect of excess thyroid hormone, radioiodine treatment or the development of hypothyroidism.

Dyspnea may be present due to increased oxygen consumption, respiratory muscle weakness, and anemia.

Increased gut motility may cause increased bowel movements.

Myopathy may result in muscle weakness.

Hypokalemic thyrotoxic periodic paralysis an uncommon complication of hyperthyroidism often associated with Graves’ disease.

Hypokalemic thyrotoxic periodic paralysis occurs primarily in Asian patients (90%), and has a 20:1 male to female ratio.

Causes include Graves disease, toxic multinodular goiter, thyroid adenoma, iodine induced due to iodine contrast media or amiodarone, thyroiditis, sub acute thyroiditis or factitious.

Treatment with radioactive iodine often followed by a period of subclinical hyperthyroidism and than eventually hypothyroidism in about 50% of patients.

Subclinical hyperthyroidism refers to subnormal serum thyrotropin with normal levels of free T3 and free T4.

Subclinical hyperthyroidism associated with a TSH value of less than 0.45 mlU/L.

Subclinical hyperthyroidism has a prevalence of 0.7% in the US.

Subclinical hyperthyroidism evaluation includes history and physical exam, thyroid US, radioactive iodine upake and scan, BMD, ECHO study, CBC, chemistry profile, FT4, free T3/total T3, TSH, possibly thyroid antibody levels to assess the process.

Physical examination includes possibly tachycardia, systolic hypertension, a stare, lid lag, tremor, and proximal weakness.

Thyroid nodules, diffusely enlarged thyroid, and sometimes a bruit may be palpable.

Orbitopathy is the most common extra thyroidal Graves disease manifestation, occurring in up to 25% of patients.

Orbitopathy may present with conjunctive erythema, orbital, edema, lid retraction, and proptosis.

Other extrathyroidal Graves’ disease manifestations include pre-tibial myxedema, which occurs in about 1.5% and acropachy, the swelling of digits and nail clubbing, which occurs in 0.3%.

Subclinical hyperthyroidism treatment should begin after repeating thyroid function studies at 3 and 6 months to establish persistence of the problem.

Subclinical hyperthyroidism may not persist with TSH levels returning to normal.

Subclinical hyperthyroidism may progress to hyperthyroidism in about 1% of cases.

Subclinical hyperthyroidism associated with a persistent TSH equal or <0.1mU/L should be treated in all individuals 65 years or older, in postmenopausal women not on estrogens or bisphosphonates, patients with cardiac risks, heart disease or osteoporosis and in those with hyperthyroid symptoms.

Overt hyperthyroidism is a risk factor for low bone mineral density and osteoporotic fractures in old women.

Subclinical hyperthyroidism occurs in about 1% of men and 1.5% of women older than 60 years of age (Helfand M).

Low serum thyrotropin levels associated with risk of atrial fibrillation and with cardiovascular mortality.

A low serum thyrotropin level is the best test to detect thyroid dysfunction, and the highest sensitivity and specificity for the diagnosis of thyroid dysfunction.

Thyroid hormone may circulate is T3, or is T4, a prohormone, which is converted to T3 in peripheral tissues.

T3 is the physiologically active form of thyroid hormone.

Free T4 levels can be used to assess the degree of hyperthyroidism.

T3 levels can also help establish the cause and severity of thyrotoxicosis.

The total T3: T4 ratio is generally more than 20: 1 and Graves’ disease or toxic nodules, but less than 20:1 in thyroiditis.

Suppresses TSH to <0.1 mcU/mL, and levels above this exclude the diagnosis.

Heparin therapy may increase plasma free T4.


Treatment is patient centered, individualized, and takes into account the individuals age, comorbidities, severity of disease, likelihood of remission, plans for pregnancy, and available surgical experts.

Treatment options relate to the underlying etiology.

Beta blockers may decrease heart rate and improve hyper adrenergic symptoms, but are relatively contraindicated in bronchospastic disease.

Beta blockers are  primary therapy for thyrotoxicosis due to thyroiditis, because it is a self limited disorder.

Most patients with overt hypothyroidism from autonomous thyroid nodules of Graves’ disease will require treatment with anti-thyroid drugs, radioactive iodine ablation, or surgery.

Untreated, overt thyrotoxicosis is associated with osteoporosis, atrial fibrillation and rarely high output heart failure due to the excess of thyroid hormone affecting thyroid hormone receptors present in the bone and heart.

Atrial fibrillation is present in 10 f  to 25% of patients with thyrotoxicosis and higher rates in men and those older than 65 years.

Treatment must be initiated emergently if patients have acute coronary syndrome, congestive failure or thyroid storm is present.

Treatment includes inhibition of thyroid hormone synthesis by propylthiouracil, inhibition of thyroid hormone secretion by iodine and inhibition of the cardiovascular effects of hyperthyroidism by beta antagonists.

Corticosteroids may be recommended because it inhibits T4 conversion to T3.

Plasma free T4 is measured every 3-7 days and when the level approaches normal range propylthiouracil and iodine are gradually decreased.

Antithyroid drugs, can decrease thyroid hormone synthesis, and secretion, and can restore euthyroidism  with hyperthyroidism.

For  patients with Graves’ disease, anti-thyroid drug treatment can be discontinued after 12 to 18 months if seer and thyroid tropin levels have normalized in the patient no longer test positive for thyrotropin receptor antibodies.

Thyrotropin receptor antibody titers typically decline over the course of treatment and resolve in 70 to 80% of patients by 18 months of therapy.

Remission rates a year following treatment, after  an initial 12 to 18 months of anti-thyroid drug therapy are 30 to 50%.

Radioactive iodine can be provided 2-3 weeks after the initial treatment is initiated.

In patients who do not receive remission after 12 to 18 months of anti-thyroid medications definitive therapy with radioactive or thyroidectomy is considered.

Thyroid storm consists of severe, uncontrolled,  hyperthyroidism and is associated with multiorgan system failure with  a mortality rate of 3.5 to 17%.

Treatment of thyroid storm includes rapid reduction of circulating T3 levels using antithyroid drugs, glucocorticoids, beta blockade, inorganic iodide and cholestyramine.


Subclinical hyperthyroidism is associated with increased risk for hip fractures in older men (Lee JS et al).

Subclinical hyperthyroidism is associated with increased risk of hip and other fractures, particularly among those with TSH level of less than 0.10 and in those with endogenous subclinical hyperthyroidism.

Subclinical hyperthyroidism refers the presence of a low serum thyrotropin level and a normal serum T4 level found in approximately 2% of a screened population.

Subclinical hyperthyroidism has only a small increase with advancing age.

Subclinical hyperthyroidism associated with atrial fibrillation.

Subclinical hyperthyroidism with TSH levels of 0.1 mU/L or less associated in the Framingham Heart Study with a relative adjusted risk of 3.8 for developing atrial fibrillation.

Most common forms of endogenous subclinical hyperthyroidism include Graves disease in younger individuals, mutinodular goiter in older patients and solitary autinomous nodules.

Subclinical hyperthyroidism associated with osteopenia.

Subclinical hyperthyroidism associated with coronary aryery disease, AF, cardiac dysfunction, increased heart rate, increased LV mass, plasma fibrinigen levels and carotid-intima-media thickness.

Subclinical hyperthyroidism associated with increased total risk of coronary artery disease mortality, AF, with highest risks when thyrotropin is lower than 0.1 mIU/L (ICollet T-H et al).

A false positive diagnosis of hyperthyroidism may occur due to immunoassay interference with biotin, a soluble vitamin commonly used to supplement for hair and nails.

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