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Hyperthyroidism – causes, symptoms, diagnosis, treatment, pathology

Hyperthyroidism – causes, symptoms, diagnosis, treatment, pathology

Learning medicine is hard work! Osmosis makes it easy. It takes your lectures and notes to create
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much more. Try it free today! Hyperthyroidism, which is sometimes referred
to as thyrotoxicosis, is a condition that’s caused by having excess thyroid hormones. Thyroid hormone production is under the control
of the hypothalamus and the pituitary. The hypothalamus secretes thyrotropin releasing
hormone, or TRH, which makes the anterior pituitary secrete thyroid-stimulating
hormone, or TSH. TSH then binds to TSH receptors, which makes
the thyroid secrete thyroxine, or T4, and triiodothyronine, or T3, in the blood. But this is not a one-way street – there’s
also negative feedback happening, meaning when thyroid hormone levels rise, that inhibits
the production of TSH and TRH, halting further production of T3 and T4 – to keep everything
in balance. Normally, some thyroid hormones travel through
the bloodstream bound to thyroxine-binding globulin, and some are in their free form. And the thyroid actually makes more T4 than
T3, and that T4 is converted to the more potent T3 in the periphery. Thyroid hormones then increase the rate of
metabolism in all cells, so they make us think, move, and talk faster, and they also increase
heat generation. They also activate the sympathetic nervous
system, the part of the nervous system responsible for our ‘fight-or-flight’ response, increasing
cardiac output. Thyroid hormones are important – and the occasional
increase is like getting a boost to fight off a zombie or to stay warm during a snowstorm! But with hyperthyroidism, it’s like the
entire body is buzzing at twice the normal rate. So individuals with hyperthyroidism tend to
be hyperactive and talk really fast, and present with tremor in the extremities – as if they’ve
had too much coffee. Also, making so much internal heat makes them
sweat a lot and uncomfortable in warm temperatures. It can also cause anxiety, irritability, and
mood swings, as well as difficulty sleeping – again, think too much coffee. Hyperthyroidism can also cause an increased
appetite, unexplained weight loss, and more frequent bowel movements. On a physical examination, the skin is warm
and moist and their hair is fine and brittle. Classically, individuals have lid retraction,
which makes a person look “wide-eyed” like the stare of a person who’s “frozen
in fear”. Sometimes, pretibial myxedema may be present,
which is a waxy, discolored induration of the skin on the anterior aspect of the lower
legs, with a bumpy feel – like an orange peel. There may be muscle weakness, especially in
the thighs and upper arms, as well as exaggerated deep tendon reflexes. Tachycardia, as well as atrial fibrillation,
or systolic hypertension, may also be present. Females can have menstrual irregularities,
and males can have gynecomastia – or swelling of the breast tissue. However, hyperthyroidism often presents more
subtly, with a single symptom evolving over weeks to months, and even that should prompt
an evaluation for hyperthyroidism. Now, this evaluation comprises of two steps:
first, confirming that the individual has hyperthyroidism, and second, finding out why
they have hyperthyroidism. First one’s easy – get serum levels of free
T3, T4 and TSH. In hyperthyroidism, either free T3 or free
T4, or both are elevated, and they inhibit TSH, so the majority of the time, TSH is low. Elucidating the cause is the fun part. Pathophysiologically, the causes of Hyperthyroidism
can be divided into 4 categories. The first is excessive TSH receptor stimulation,
and an example is Graves’ disease, which is an autoimmune condition where thyroid stimulating
immunoglobulins, or TSIs, bind to the TSH receptor and stimulate excess hormone production. Sometimes, this excessive stimulation makes
the thyroid gland swell up, causing goiter – but the most characteristic finding in Graves’
disease is exophthalmos, which is where the eyes bulge out of their sockets. Exophthalmos is pretty specific for Graves’
disease, and classically causes high thyroid hormone levels, low TSH, and a large thyroid
without any discernible nodules on palpation. Elevated TSI antibodies levels confirms Graves’
disease. Finally, if the diagnosis of Graves is unclear
or if there seems to be another cause of hyperthyroidism, the next step is getting a radioactive iodine
uptake scan, or RAIU, for short. In an RAIU scan – a person is given either
a capsule or a liquid that contains the radioactive isotope of Iodine, typically Iodine-123. Functional thyroid tissue loves Iodine, and
gobbles it up it to make thyroid hormones. So to see how much thyroid tissue is actively
making hormones we perform a scintigraphic scan. The principle is simple – the more active
the thyroid is, the more iodine it takes in, and, as a result, the more radiation it emits. Then a gamma camera is used to pick up the
emitted radioactive signal, and a Then, a device called a gamma probe is used to obtain
images of the thyroid tissue – the probe is moved back and forth over the thyroid gland,
detecting how much radiation is emitted in different locations. A computer then translates this into pictures
with a white background, where the dark areas representing radiation emitted by the functional
thyroid tissue. A set of these scans is obtained 4 to 6 hours
later, and then another set is obtained 24 hours later. A normal thyroid gland looks like two grey
wings. With Graves’ disease, there’s a diffuse
increase in the uptake of both lobes of the thyroid – so the thyroid appears darker and
larger. If Graves’ disease is confirmed, treatment
should be initiated with antithyroid medication – enter the thionamides, methimazole and propyl-tio-uracil,
or PTU. Thionamides inhibit the enzyme thyroid peroxidase
inside thyroid cells, and that stops thyroid hormone synthesis. For both methimazole and PTU, a high initial
dose is used, and then once euthyroid status is achieved, meaning free T3 and T4 levels
go back to normal, then a lower daily maintenance dose is used. If individuals have really large goiters,
that compress nearby structures, like the trachea, and cause trouble breathing, or the
recurrent laryngeal nerve, causing hoarseness, surgical removal of the thyroid gland – this
is called a thyroidectomy – can be performed. Alright then! Another cause of excessive TSH receptor stimulation
is a TSH-secreting pituitary adenoma, which is when a tumor forms in the pituitary, and
secretes TSH regardless of any negative feedback signals. In this situation, there are high free T3
and T4 levels, with a diffuse increase in the uptake of both lobes, but with high TSH
levels – the only exception to the high thyroid hormones, low TSH rule of hyperthyroidism. In this case, a CT or MRI scan of the head
is done to identify the adenoma, and then the adenoma is surgically removed, through
transsphenoidal adenomectomy. That’s where it’s surgically removed through
the nose – talk about tight working quarters! Another cause of excessive stimulation of
the TSH receptor is high levels of human chorionic gonadotropin, or HCG. HCG is structurally similar to TSH, so it
can bind to the TSH receptor and stimulate it. HCG levels rise normally during the first
trimester of pregnancy, and this sometimes results in a transient state of hyperthyroidism
that resolves on its own. But other causes of excess HCG are HCG-secreting
germ cell tumors of the testicles or ovaries or a hydatidiform mole- which is an abnormal
kind of pregnancy, where the placenta develops with very little fetal tissue, and secretes
too much HCG, but the fetus isn’t viable. Diagnosing germ cell tumors can be done via
computer tomography, magnetic resonance imaging, or an ultrasonography of the pelvis – in females
– or testicles – in males. A hydatidiform mole, on the other hand, may
occur in pregnant females who have HCG levels much higher than normal for the first trimester
of pregnancy. Hyperthyroidism, as well as vaginal bleeding,
and hyperemesis, which is extreme nausea and vomiting are common symptoms. Often, on ultrasound, there are characteristic
aspects of the hydatidiform mole, like an intrauterine mass with cysts that looks like
a “bunch of grapes”. Treatment, of germ cell tumors and hydatidiform
mole, however, is the same, and involves removing either the tumor, or the hydatidiform mole. Ok, now the second category of hyperthyroidism
is unregulated thyroid hormone secretion, and the key word here is nodules. Basically, either one nodule forms in the
thyroid and starts autonomously secreting thyroid hormones – we call this toxic adenoma
-, or more nodules sprout in the thyroid and do the same – which is called toxic multinodular
goiter. These nodules can be felt on palpation, and
on a RAIU scan, the areas with nodules appear darker than the rest of the thyroid. So rather then having a diffuse increase in
the iodine uptake, there’s a heterogenous increase across both lobes. In other words, some spots in the thyroid
gland look darker than other parts. The RAIU scan alone can establish the diagnosis
or either toxic adenoma – a single dark spot – , or toxic multinodular goiter – multiple
dark spots. Easy peasy. And these two conditions are usually treated
with radioiodine therapy. The way it works is a person swallows a capsule
containing a small dose of Iodine-131-which emits radiation – which is different from
the iodine 123 that’s used in the RAIU scan. Functional thyroid tissue takes in this iodine
just the same, though, and the iodine destroys it with radiation – like a Trojan horse. The person may go home after swallowing the
capsule, but shouldn’t have prolonged close contact with pregnant women and young children
for three days, and should drink plenty of fluids – so that the iodine is rapidly flushed
out of their system. Following radioiodine therapy, hyperthyroidism
symptoms usually subside over a few months. And if symptoms persist six months later,
a second dose may be given. Finally, surgery may be used to treat large
multinodular goiters. Ok now. A third category of hyperthyroidism is because
of follicle destruction with release of thyroid hormones, due to thyroiditis – or inflammation
of the thyroid gland. There’s many kinds of thyroiditis, but we’ll
refer to two that can cause hyperthyroidism: Hashimoto’s thyroiditis, and subacute thyroiditis,
also called de Quervain’s thyroiditis. Ok, so Hashimoto’s is an autoimmune form
of thyroiditis, where autoantibodies are directed against the thyroid gland, and, as a consequence,
more and more thyroid tissue is destroyed over time, resulting in chronic hypothyroidism. However, during periods of intense destruction,
the massive release of thyroid hormones can cause transient hyperthyroidism – a state
called “hashitoxicosis”, a mashup of Hashimoto’s, and thyrotoxicosis. On a RAIU scan, both Hashimoto’s and subacute
thyroiditis will present with a near absent radioiodine uptake – meaning less than a healthy
person would have, and translating as a pale thyroid. Subacute thyroiditis may also present with
additional clinical findings, like a painful thyroid, as well as flu-like symptoms like
high fever and muscle aches, which are not usually seen in Hashimoto’s. Additionally, with subacute thyroiditis there
may be a high erythrocyte sedimentation rate or ESR, typically in the range of 60 to 100. In Hashimoto’s there are usually high levels
of anti-thyroperoxidase, or anti-TPO antibodies in the serum. Thyroiditis requires fairly unique treatment. Hashimoto’s thyroiditis, often requires
beta-blockers, like propranolol, to control the transient cardiac symptoms of hyperthyroidism. Hyperthyroidism due to subacute thyroiditis,
often subsides on its own over time, so medication like aspirin, non-steroidal anti inflammatories,
or selective COX-2 inhibitors are used to help with pain and inflammation. For more severe pain, glucocorticoids, like
prednisone, can be used. A final category of hyperthyroidism is having
excess extrathyroid sources of thyroid hormone include iatrogenic causes – like hypothyroid
individuals who are treated with too much thyroid hormone – in which case treatment
is adjusting the doses. It also includes factitious hyperthyroidism
– which is when a person self-administers thyroid hormones without being hypothyroid,
and people might do this when they want to lose weight. In fact, some supplements for weight loss
contain thyroid hormones. Treatment is also fairly intuitive – stopping
the thyroid hormones or supplements. Finally, and here’s one for your Hangman
games – there’s struma ovarii. Struma ovarii is a teratoma made up mostly
of thyroid tissue that grows on the ovaries and secretes thyroid hormones. Yikes. Struma ovarii can be diagnosed with an ultrasound
of the ovaries, a CT, or an MRI scan of the pelvis. An RAIU scan of the pelvic region will demonstrate
higher iodine uptake in the mass than in the thyroid gland. Treatment is surgical removal of the mass,
which should also be examined histologically, to confirm the diagnosis. Finally, it’s important to discuss thyroid
storm, which is also called accelerated hyperthyroidism, like taking a racing car and speeding it up. This can complicate all types of hyperthyroidism,
and it’s where symptoms become so extreme that they can become life-threatening – high
fevers, sweating, an altered mental status, hypotension, and even cardiogenic shock. It’s an emergency. The person needs to be wrapped in cooling
blankets, or given cool IV fluids to bring down their temperature. Then, a beta-blocker, like propranolol, can
be used to help reduce their heart rate and blood pressure. After that, high doses of methimazole or PTU
can be given. Finally, glucocorticosteroids can be given
to help reduce the inflammation. With aggressive therapy, the storm usually
passes in about 1 or 2 days, and full recovery within a week. Okay – so to recap. Hyperthyroidism refers to high circulating
thyroid hormones in the blood, and typically presents with high free T3 and T4, and low
TSH. But, TSH may be high in case of a TSH-secreting
pituitary adenoma. The most common cause is Graves’ disease,
which may present with exophthalmos, elevated serum TSI antibodies, and a diffuse increase
in radioiodine uptake on a RAIU scan. Other common causes are toxic multinodular
goiter and toxic adenoma, which may be felt on palpation, and present with focal increased
uptake in the thyroid. At the other end of the spectrum, there are
the conditions associated with low radioiodine uptake like thyroiditis and extrathyroid sources
of thyroid hormone. Treatment of hyperthyroidism relies on thionamides,
radioiodine therapy and surgery and stopping thyroid hormone medication or adjusting the
doses. Thionamides are recommended in Graves’ disease,
radioiodine therapy is recommended for toxic multinodular goiter, toxic adenoma and struma
ovarii, and surgery is usually reserved for patients with Graves disease or toxic multinodular
goiter that have very large goiters, compressing nearby organs. Finally, thyroid storm is an extreme presentation
of hyperthyroidism, which requires immediate treatment with beta-blockers, thionamides,
and glucocorticoids.

20 thoughts on “Hyperthyroidism – causes, symptoms, diagnosis, treatment, pathology

  1. I am suffering bfrom this problem since 3 years.. After my son birth.. I m too weak.. My still weight is 40 kg.. I am taking drugs like.. Newmercazole and inderal.. But no effects is showing

  2. I'm sweating abnormally and have heat intolerances because of this disease and i literally was born in one of the hottest countries on earth :((

  3. I was diagnosed with multiple sclerosis in 2005, and I was a woman of 40. They put me on Rebif which I took until 2008 and was switched to Copaxone. I had two relapses on Rebif, none on Copaxone. I did notice my balance getting worse, and my memory, as well as muscle spasms.I was placed on Copaxone, it helped me but not very much. My neurologist advised me to try natural treatments and introduced me to Rich Herbal Garden Multiple Sclerosis Disease Herbal formula, I read alot of positive reviews from other patients who used the treatment and i immediately started on the treatment. I had great improvement and relief with this treatment, total decline of symptoms. Great improvement with my Vision problems, co-ordination, balance, muscle, mood etc, I gained back my life with this treatment and can never be thankful enough. Visit Rich Herbal Garden official website w ww .Richherbalgardens .c om I'm 52 now, and have never been healthier.

  4. I got way too skinny bcox of thyroid.. n m depressed about it ,. People are calling me scary girl . Etc etc it's hard to live a normal life now

  5. My antithyroid medication (started taking 2 months ago) has started to cause me severe muscle pains (myopathy?)
    Not sure if this is a cause for concern or just part of it but I'm miserable.

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