Hyperthyroidism
last authored: Oct 2009, David LaPierre
Introduction
The Case of...
a simple case introducing clincial presentation and calling for a differential diagnosis. To get students thinking.
Causes and Risk Factors
Iodine 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.
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. One of the most important is the anti-TSH receptor, which mimics the action of TSH and increases T4 production. Easiest to measure is anti-TPO.
Graves disease has a peak incidence in adolescence, with a F:M of 5:1.
Smoking increases incidence of Graves' disease, particularly the attending opthalmopathy. Lithium may be a risk factor for hyperthyroidism, along with hypothyroidism.
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.
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.
mulitnodular goitre: Virtually all longstanding goitres become multinodular. Most patients are euthyroid, but a large minority become hyperthyroid.
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.
Pathophysiology
The various causes of hyperthyroidism, as described above, each have specific ways of increasing thyroxine production.
Elevated hormone levels leads to increased basal metabolic rate
In the gut, sympathetic hyperstimulation leads to hypermotility, and malabsorption.
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:
- tremor
- palpitatons
- anxiety, irritability, and poor concentration
- increased stool looseness and frequency
- weight loss
- heat intolerance: "if you're in a room and everyone else is comfortable, where do you fit?"
- diaphoresis
- lighter menses
- poor sleep and fatigue (classically, crash in the afternoon)
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
- Pre-tibial myxedema in Grave's disease only
Cardiac manifestations are among the earliest and most consistent, and include:
- hypertension with wide pulse pressures
- tachycardia
- palpitations and arrhythmias, particularly atrial fibrillation
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)
- 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.
Goiter caused by follicular proliferation.
Skeletal muscle can become atrophied, with fatty infiltration. Thyroid hormone also stimulates bone resorption, resulting in osteoporosis.
Investigations
- lab investigations
- diagnostic imaging
Lab Investigations
Endocrine changes decrease GnRH = changes in ovulation and menses
TSH |
T3/T4 |
antibodies |
radio findings |
course |
|
Grave's Disease |
down |
up |
|
increased due to receptor stimulation |
|
multinodular goitre |
variable |
up |
no |
uneven, with some hot nodules |
|
postpartum thyroiditis |
down |
up |
destructive
|
||
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 |
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
Differential Diagnosis
Thyroid carcinoma should be excluded with solitary nodules, especially in children.
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 and methimazole, drugs that inhibit TPO and reduce hormone production, inhibit peroxidase catalyzed reactions, inhibiting organifiaction of iodine, blocking coupling of iodothyrosines, and inhibiting T4 conversion to T3.
These drugs are the treatment of choice in pregnancy and in children. They are typically given for 1-2 years, with potential relapses within the first 6 months or even many years later.
- Side effect of these drugs is rapidly developing agranulocytosis (0.5%); patients should be warned to report fever or sore throat immediately. Baseline CBC can be useful.
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.
Hypotyroidism is common post-treatment.
Surgery is rare due to risks and complications.
Consequences and Course
Additional Resources
Topic Development
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