Hyperthyroidism

last authored: Oct 2009, David LaPierre
last reviewed:

 

Introduction

Hyperthyroidism describes an overactive thyroid. Thyrotoxicosis results from overactive thyroid.

 

 

 

The Case of Bob R

a simple case introducing clincial presentation and calling for a differential diagnosis. To get students thinking.

return to top

 

 

 

Causes and Risk Factors

Iodine excess does not, on its own, cause hyperthyroidism. However, in people with an underlying condition such as Grave's disease or toxic nodule, high T3 and T4 levels will result. Amiodarone is full of iodine. Interestingly, iodine excess can lead to hypothyroidism via the Wolff-Chaikoff effect.

 

Graves disease, or diffuse toxic hyperplasia, accounts for up to 85% of hyperthyroidism. It is an autoimmune condition, with many different antibodies produced. Graves disease has a peak incidence in adolescence, with a F:M of 5:1.One of the most important is the anti-TSH receptor, which mimics the action of TSH and increases T4 production. Thyroid-stimulating innumoglobulins (TSIs) may also be present. Lastly, blocking antibodies may also be present.

 

toxic nodules: Nodules are very common, affecting up to 50% of population. Their prevalence increases seen with age. If one or several become autonomous, they can overproduce T4 independent of TSH. Toxic nodules are seen in the 4th decade primarily.

 

postpartum thyroiditis: usually see within first 6 months

 

subacute thyroiditis: Usually due to post-infectious inflammation and hormone release. It is usually temporary, lasting until hormone is used up. As the gland heals hormone production decreases, and transient hypothyroidism is usual. Euthyroidism normally follows.

 

toxic mulitnodular goitre: Virtually all longstanding goitres become multinodular. Most patients are euthyroid, but a large minority become hyperthyroid. Often a TSH receptor mutation can be identified. Incidence is most common in patients over 50. Opthalmopathy is rare.

 

drug-induced thyroiditis: Offending drugs can include amiodarone (high levels of iodine), interferon alpha, interleukin 2, and lithium

 

exogenous thyroid hormone: can be iatrogenic, patient error, or a deliberate attempt to fool the physician.

 

secondary hyperthyroidism: Central dysfunction and TSH oversecretion is a rare cause of hyperthyroidism.

 

congenital hyperthyroidism results from transfer of maternal activating antibodies across the placenta.

 

return to top

 

 

 

Pathophysiology

The various causes of hyperthyroidism, as described above, each have specific ways of increasing thyroxine production. These all act to saturate and overactivate thyroid hormone receptors.

 

Elevated hormone levels leads to increased basal metabolic rate. Energy production exceeds the body's needs, resulting in increased heat production, diaphoresis, and potential fever.

Cardiovascular

  • atrial fibrillation
  • congestive heart failure

Gastrointestinal

  • sympathetic hyperstimulation leads to hypermotility, and malabsorption.

Other

  • loss of

loss of bone mineral density

Smoking increases incidence of Graves' disease, and can worsen attending opthalmopathy. Lithium may be a risk factor for hyperthyroidism, along with hypothyroidism.

 

accumulation of polysaccharides in the anterior shin.

Grave's ophtalmopathy results from antibody activation of soft tissues of the eyes.

 

Thyroid storm results in an acute decrease in TBG, resulting in high levels of free hormone. T3 also increases the density of beta-adrenergic receptors.

return to top

 

 

 

Signs and Symptoms

There are many signs and symptoms of hyperthyroidism, many of which are caused by a hypermetabolic state or sympathetic overactivity.

  • history
  • physical exam

History

Common symptoms include:

constitutional:

  • weight loss
  • poor sleep and fatigue (classically, crash in the afternoon)
  • weakness
  • sweating
  • heat intolerance: "if you're in a room and everyone else is comfortable, where do you fit?"

gastrointestinal

  • increased appetite
  • increased stool looseness and frequency

neurological

  • anxiety, irritability, and poor concentration
  • emotional lability
  • tremor
  • psychosis
  • coma

cardiovascular

  • tachycardia
  • chest discomfort mimicking angina
  • palpitatons

other

  • diaphoresis
  • lighter menses, oligomenorrhea, amenorrhea

Other components to inquire into:

  • recent pregnancy (postpartum thyroiditis)
  • recent viral illness, with tender neck (subacute thyroiditis)
  • family history, younger age of onset (Graves' disease)

Congenital hyperthyroidism can cause:

  • tachycardia, heart murmur, and heart failure
  • irritability
  • craniosynostosis
  • poor feeding
  • failure to thrive

 

Ophalmopathy

  • exopthalmos
  • sympathetic overactivation
    • diplopia
    • lid retraction
    • loss of gaze

Dermopathy

  • myxedema

Physical Exam

Thyroid exam is clearly of some importance:

  • thyroiditis can cause painful neck and occasional jaw and ears
  • nodules can feel lumpy or bumpy

 

Skin tends to be soft, warm, and flushed because of increased blood flow and peripheral vasodilation.

  • Brittle hand and nails; onycholysis
  • facial flushing
  • Pre-tibial myxedema in Grave's disease only
  • diffuse goitre can by caused by follicular proliferation

 

Cardiac manifestations are among the earliest and most consistent, and include:

  • hypertension with wide pulse pressures
  • tachycardia
  • palpitations and arrhythmias, particularly atrial fibrillation
  • bruit

Increased cardiac output and cardiomegaly can occur. Congestive heart failure can develop in elderly patients with pre-existing heart disease.

 

 

Neurological symptoms, due to sympathetic overactivity, include:

  • tremor (put a piece of paper on their hand)
  • restlessness, hyperactivity
  • proximal muscle weakness, along with decreased muscle mass
  • hyperreflexia

 

Ocular changes include a wide-eyed, staring gaze and lid lag due to sympathetic activity. Exopthalmos is seen in Graves disease due to autoantibody induced retroorbital tissue and muscle swelling.

Graves': periorbital edema. Eyes can become red, itchy, and watery because of difficulty closing eyelids.

There can be problems with convergence and upward gaze.

 

 

Musculoskeletal effects include skeletal muscle atrophy, with fatty infiltration. Thyroid hormone also stimulates bone resorption, resulting in osteoporosis.

 

return to top

 

 

Investigations

  • lab investigations
  • diagnostic imaging

Lab Investigations

 

Endocrine changes decrease GnRH = changes in ovulation and menses

 

TSH

T3/T4

antibodies

radio findings

other

Grave's Disease

down

up
  • TSH-receptor
  • thyroid peroxidase
  • thyroglobulin
  • TSH-R on ocular fibroblasts

increased due to receptor stimulation

  

multinodular goitre

variable

up

no

uneven, with some hot nodules

  

postpartum thyroiditis

down

up

destructive

  • sometimes a-thyroglobulin
    

hyperfunctional thyroid adenoma/adenocarcinoma

down

up

no

cold

  

thyroid storm

down

up

same as Graves

  

bad news

facitious hyperthyroidism

down

up

no

    

TSH-secreting pituitary adenoma

up

up

no

    

subacute thyroiditis

down

up

no

cold (ghost-like)

self-limited

 

 

Fine needle aspiration is usually not helpful for overactive, 'hot' nodules.

Diagnostic Imaging

 

Radioactive uptake and scan can show levels and areas of uptake.

normal is 5-20% uptake.

Grave's disease: diffuse scan, with high uptake. (check this)

thyroiditis: decreased uptake

nodules: high uptake, with cold areas over the rest

 

return to top

 

 

Differential Diagnosis

Thyroid carcinoma should be excluded with solitary nodules, especially in children.

return to top

 

 

Treatments

Beta blockers and calcium channel blockers can be used to control tachycardia and palpitations.

 

NSAIDs or steroids can be used for thyroiditis pain.

 

Antithyroid drug therapy for Grave's or nodules includes propylthiouracil (PTU) and methimazole (Tapazole). These medications interfere with the organification of iodine, and also reduce hormone production, inhibit peroxidase catalyzed reactions, block coupling of iodothyrosines, and inhibit T4 conversion to T3.

These drugs are the treatment of choice in pregnancy and in children. Drugs are typically given for 1-2 years, with potential relapses within the first 6 months or even many years later.

PTU is usually started at 75-100 mg tid, and should be decreased by 1/3 after 4-6 weeks if TSH or T4/T3 have returned to normal.

 

Radioactive iodine is the definitive treatment for Graves disease. It is used when antithyroid drugs fail to achieve remission after 6-24 months and in patients at risk of relapse, such as those with severe symptoms or large goiter. It cannot be used at start due to risk of inflammation and thyroid storm. Hypothyroidism is common post-treatment.

 

Surgery is rare due to risks and complications.

 

Thyroid storm is a medical emergency. Block hormone synthesis with PTU or methimazole. Iodide

T4 to T3 conversion can be blocked with glucocorticoids.

Treat fever aggressively, with acetaminophen, prochlorperazine, and a cooling blanket.

Remove circulating thyroid hormones.

 

return to top

 

 

 

Consequences and Course

return to top

 

 

 

 

Additional Resources

return to top

 

 

Topic Development

authors:

reviewers:

 

return to top