Thyrotoxicosis lecture for MD degree endocrinology students

HYPERTHYROIDISM CASE
SCENARIO.
Professor Mohammad Ahmed Bamashmos

case presentation
65-years-old woman was referred urgently from primary care with a history of
progressively increasing shortness of breath and cough for the last 3 weeks. Her
breathlessness initially started on exertion which had now progressed to being
present even at rest. This was associated with a cough which was productive and
contained the scanty amount of whitish sputum without any diurnal variation. She
also complained of three pillow orthopnoea (she normally used one pillow to sleep)
and paroxysmal nocturnal dyspnoea.
On systemic review, she revealed three stone weight loss over a period of 4 months
but there was an intentional element to it. She admitted to more frequent bowel
opening for the last 4–6 weeks.

She was known to have type II diabetes mellitus and occupational asthma. She was
postmenopausal, a social drinker and was an ex-smoker. She was not known to have
any drug allergies and was on metformin, steroid inhalers and valsartan although
admitted to poor medication compliance. She denied any previous hospitalisation and
there was no history of exposure to asbestosis. Her family history was significant for
ischaemic heart disease (father had myocardial infarction).
On examination she was alert, pale but not icteric, and was struggling to finish
sentences due to shortness of breath, her respiratory rate being 24 breaths/minute.
She was apyrexial, tachycardiac at 120 beats per minute, the pulse being irregularly
irregular with a blood pressure of 140/100 mm Hg. Her oxygen saturation was 97% on
room air. She had bibasal crackles in her lungs. The remaining clinical examinations
remained unremarkable.
Initial investigation ;
- CBC ; normal
- liver function and renal function test is normal
- serum electrolytes is normal

Troponins: 20.10 ng/L and 21.60 (0 to 15.6 ng/L).
C reactive protein: 11 mg/L (<5 mg/L).
Blood glucose: 12.6 mmol (below 11.1 mmol/L).
Haemoglobin A1C: 55 mmol/mol (below 42 mmol/mol).
Echocardiogram:
impaired left ventractility ; EF 14%
- severely dilated left atrium
- TR , MR
DD ;
- silent MI resulting in acute ischemic cardiomyopathy
- dilated cardiomyopathy
- hypertensive HF

screening for wider causes of cardiomyopathy was requested including thyroid
function test, serum ACE and ferritin levels.
The thyroid function test revealed:
- Thyroid-simulating hormone (TSH): <0.01 (0.35–3.50 mU/L)
- Thyroxine (free T4): 28.5 (7.5–21.1 pmol/L)
- Triiodothyronine(free T3): 8 (3.8–6.0 pmol/L).
diagnosis ;
Thyrotoxic cardiomyopathy ;
1- what's the Defination of thyrotoxicosis
2- what's the causes ;

Causes With hyperthyroidism
- graves diseases
- MNG
- solitary nodules
-gestational trophoblastic diseases
- hydateiform diseases
- corio carcinoma
- iodine excess
- TSH secreting pituitary adenoma
- Pituitary resistance to thyroid
hormone
without
1 - inflammation and release of
stored thyroid H
- silent thyroiditis
- pot partum thyroiditis
- initial phase of hashimotoes
- viral or post viral infection
- subacute thyroiditis
- toxic drugs effect
- drug induced
- Bacterial or fungel
- - radiation
- 2- extra thyroid source of
hormone
- intake
- - ectopic hyperthyroidism
stroma overii
functional thyroid ca
- Ingestion of contaminated food
3- exposure to excess iodine
jod basedow effect

Rare presentation
• - hiccup
• - periodic paralysis
• - arthralgia
• - symptom in elderly prevalence 0.5- 4%
• in two third same
• in one third ; apathy , tachycardia , weight loss

Diagnosis
1- investigation to diagnose thyrotoxicosis ;
thyroid function test ; ( FT3 , FT4 ,TSH)

The Thyroid Screening Test
1- TSH The thyroid stimulating hormone, or TSH test, is used as a screening test for thyroid disease,
as well as a test for monitoring the correct dose of medication needed for an individual.
Timing ; in early morning
Drugs that should de stopped ;
- biotin also suppress TSH levels, making it look like you are overmedicated, or like you are
hyperthyroid. The American Thyroid Association recommends that patients stop taking biotin for at
least two days before a TSH test.
Refference range ; In recent years, The National Academy of Clinical Biochemists indicated that 95
percent of individuals without thyroid disease have TSH concentrations below 2.5 μIU/mL, and a new
normal reference range was defined by the American College of Clinical Endocrinologists to be
between 0.3 and 3.0 μIU/mL.

2- measurement of FT3 , FT4 ;
- time ;
- interpretation ;
- optimal range
Recommended test: Free T3 and Free T4
Optimal Free T4 reference range: 15 to 23 pmol/L
Optimal Free T3 reference range: 5 to 7 pmol/L
I recommend testing every four to six weeks when starting a new medication, every two to three months if tracking the impact
of lifestyle changes, and then every six to 12 months once symptoms are stable
Things to consider before testing: I recommend testing your free T3 and free T4 early in the morning, and delaying your
thyroid hormones until after taking the test to ensure accurate results, especially if you are taking T3-containing medications.
Taking your medications before the test can result in a falsely elevated T3 (and sometimes T4), making it look like you are
overmedicated when you are not. Additionally, the supplement biotin, commonly used for hair loss, can also falsely increase
both T4 and T3 levels, making it look like you are overmedicated, or like you are hyperthyroid. The American Thyroid
Association recommends patients stop taking biotin at least two days before a T4 and T3 test.
.

Thyroid Antibodies
There are various types of antibodies against the thyroid gland that can be detected in thyroid
disease. The presence of thyroid antibodies indicates that the thyroid gland has been recognized as
a foreign invader by the immune system and that the thyroid gland is under attack.
1- In Hashimoto’s, triggers contribute to the body developing something called “a lack of self-
tolerance.” This is when the body is no longer able to recognize its own tissue as part of itself, but
instead starts viewing its tissue as a foreign invader. It is no longer “tolerant” of itself, and this is what
leads to an autoimmune condition. When the body begins this breakdown of its immune tolerance,
we’re initially going to see the presence of elevated thyroid antibodies.
In Hashimoto’s, about 80 to 95 percent of patients have thyroid antibodies. (6) Thyroid antibodies are
going to be the first indication of a thyroid problem in many cases. They can be elevated for 5, 10,
sometimes even 15 years, before a change in TSH is even detected. Having elevated thyroid
antibodies, even in the presence of a “normal” TSH, means that it’s only a matter of time before your
thyroid becomes destroyed to the point that it can no longer produce a sufficient amount of
hormones.

Some clinicians will say that once you have thyroid antibodies, you will always have thyroid antibodies, so the
actual number doesn’t matter, as the antibodies can randomly fluctuate. I respectfully disagree.
I believe that antibodies can fluctuate in response to triggers (some as common as stress), and in my
exhaustive experience, they can be an incredibly helpful marker for tracking disease progression.
The most common antibodies in Hashimoto’s are thyroid peroxidase antibodies (TPO antibodies) and
thyroglobulin antibodies (TG antibodies). Most people with Hashimoto’s will have an elevation of one or both of
these antibodies. TPO antibodies are the most common and have been reported in 5 to 38 percent of the
population, depending on the study! (7-18)
Thyroid antibodies are often elevated for decades before a change in TSH is seen in Hashimoto’s.
People with Graves’ disease and thyroid cancer may also have an elevation in thyroid antibodies,
including TPO and TG. However, the most common antibodies found in Graves’ disease are TSH receptor
antibodies, including thyroid-stimulating immunoglobulin (TSI) — this marker is elevated in over 90 percent of
people with Graves’ disease. TSH receptor binding antibody (TRAb), also known as TSH-binding inhibiting
immunoglobulin or TBII, is elevated in over 50 percent of people with Graves’ disease. (19, 20)

Importance
Thyroid antibodies can be used for diagnostic purposes and monitored to track remission. As I mentioned,
thyroid antibodies indicate an active destruction going on against your thyroid. This destruction often comes
with a lot of symptoms that may cause, or be misdiagnosed as depression, panic attacks, anxiety,
miscarriage/infertility, carpal tunnel, hair loss, weight gain, fatigue/laziness, and, of course, the most
disempowering diagnosis of them all… hypochondria.
Hypochondria is a diagnosis I take great offense to because it ignores the patient’s intuition that there is
something wrong. It often leads to shame, disempowerment, helplessness, and the destruction of trust we have
in our own mind and body connection, as well as in the healthcare model and of ever getting well.
The good news is that in many cases, when you have elevated antibodies and a normal TSH, you can not only
reverse all of your symptoms, but you can also prevent damage to your thyroid gland using a root cause
approach.
I found out I had thyroid antibodies in the 2000 IU/mL range, one year before doing a thyroid function retest,
when my thyroid function deteriorated to the point where my doctor thought I would benefit from medications.
Unfortunately, the doctor that initially ran the antibody test told me not to worry about them, and that there was
nothing I could do anyway. I am often saddened that I trusted another person with my health and didn’t do
additional research on my own. I was also highly symptomatic at that time, likely due to the elevated TPO
antibodies. I had new onset panic attacks, social anxiety, hair loss, digestive issues, and fatigue — common
early symptoms of elevated thyroid antibodies.

Thyroid antibodies may be elevated for many years before a change in TSH is seen, and finding
antibodies early can often prevent damage to the thyroid, as well as help with preventing the need for
long-term medications.
As mentioned earlier, thyroid antibodies can also be used as a marker to monitor disease progression
and remission. While any elevation of thyroid antibodies can indicate Hashimoto’s (and some may
have seronegative Hashimoto’s with thyroid antibodies not elevated at all), I like to monitor thyroid
antibodies in clients.

• While not all clinicians will agree to the following ranges, based on research and my clinical
experience, here are the numbers I keep in mind:
• Thyroid antibodies above 500 IU/mL are considered a very aggressive case
of Hashimoto’s
• Antibodies under 100 IU/mL indicate remission, or a less aggressive case
• Antibodies under 35 IU/mL mean you no longer test for Hashimoto’s
according to conventional medicine standards
• Antibodies under 2 IU/mL are optimal (scientists believe that there may be
some antibodies present as part of a normal repair process)

recommend a lot of strategies to make the condition less aggressive and to put it into remission,
in my article on reducing thyroid antibodies, as well as in my books Hashimoto’s:
The Root Cause and Hashimoto’s Protocol. Be sure to check them out to learn how to
lower your antibody levels.
Recommended tests: TPO, TG for Hashimoto’s (and TSI, TBII for Graves’)
Optimal TPO reference range: <2 IU/mL
Optimal TG reference range: <2 IU/mL
Optimal TSI reference range: < 0.55 IU/L
Optimal TBII reference range: 16 to 100 percent inhibition of TSH binding
How often you should test: I recommend monitoring thyroid antibodies every 60-90 days to
see if the changes you’re making in your lifestyle are helping you. A reduction in these antibodies,
especially when accompanied by a reduction in symptoms, is a good indication that your condition
is improving and that you are on the right path with your healing interventions.

2- TO know the cause ;
by ;
- RAIU
- U/ S
- serumTG , autoantibodies

B- thyroid ultrasound ;
in graves
in MNG
single nodules
C- SerumTG
D- Autoantibodies

what is the diagnosis of this case
thyrotoxic cardiomyopathy
is patients has thyrotoxic storm ;
Her Burch and Warthofsky’s Score was 50 (15 points for pulmonary oedema, 10 points
each for AF and rate around 110 and 5 points for temperature and 10 for diarrhea )
suggesting of impending thyroid storm,

- is there is any precipitating factors ;
- 1- abrupt discontinuation of ATDs
- 2- surgery
- 3- trauma
- 4- acute illness as DKA , AMI , HF , CV accident
what's the treatments ;
Drugs that restoreTFT within 10 days ;
- MMS ; dose
- beta blockers ; since patient has bronchospasm use ivabradine ( selective sodium channel blockers
- AF ; use of anticoagulant is controversial
- ACEI
- diuretics

Hyperthyroidism and HF
Thyrotoxicosis cardiomyopathy is a rare complication of thyrotoxicosis with a high risk of fatal outcome.
Cardiomyopathy has been reported as an initial presentation in 6% of patients3 though <1% developed
severe LV dysfunction.5 However, it is very difficult to assess the real incidence of HF entirely related to
hyperthyroidism, as ischaemic, hypertensive or other valvular heart disease have not been
comprehensively excluded.

Hyperthyroidism and HF and CAD

Hyperthyroidism and Arrythemia
The incidence of arrhythmias in thyrotoxicosis is varied. Sinus tachycardia is the most
common occurring in 42%–73% of cases8 followed by AF. There are a wide range of
figures quoted from different studies about the prevalence of AF in hyperthyroidism.
The figures range between 2% and 20% in comparison with 2.3% in the general
population (ie, with normal thyroid function). The chances of developing AF due to
hyperthyroidism increase with age and with comorbidities such as ischaemic heart
disease and valvular disease.9 When viewed from another angle, it has recently been
estimated that 1%–1.5% of patients with AF have evidence of hyperthyroidism.

1- Thionamide
indication ;
1-As a short-term treatment in people with Graves' hyperthyroidism, to prepare for thyroid
surgery or radioiodine.
2- As initial treatment in Graves' disease for one to two years to see if the disease resolves.
Approximately 30 percent of people with Graves' disease will have a remission after one to two
years. Antithyroid drugs can be used to control hyperthyroidism while waiting to see if remission
occurs.
3- To treat hyperthyroidism associated with toxic multinodular goiter or a toxic adenoma
("hot nodule"), usually to prepare for thyroid surgery or radioiodine.
4- To treat hyperthyroidism during pregnancy
5- long-term treatment of hyperthyroidism due to Graves' disease, toxic multinodular
goiter, or toxic adenoma when the person prefers to avoid definitive therapy with radioiodine or
surgery. Approximately 80 percent of people with Graves' disease will have a remission after 10
years.

Mechanism of action ;
- inhibition of thyroid hormone synthesis
Its main effect seems to be the inhibition of the ‘organification’ of inorganic iodine. Also, it has been
suggested that ATDs inhibit the coupling reaction
PTU inhibit the prepheral conversion ofT4
- auto immune effect
The effects of ATDs, whether direct or indirect, on thyroid autoimmunity have been interesting (9). Some
in vitro clues show that thionamide ATDs might have direct effects on intrathyroidal T cells (10, 11) and
HLA Class II expression by thyrocytes (12), as well as in vivo effects for increasing suppressor T cells and
decreasing intrathyroidal activated T cells
- antioxidant effect

types
Two antithyroid drugs are currently available in the United States: propylthiouracil and methimazole (brand name:
Tapazole). Carbimazole (which is converted into methimazole in the body) is available in Europe and parts of Asia
but not in the United States.

Dose ;
it depends on ;
- severity of hyperthyroidism
- level of F.T4
- on body weight
Carbimazole and methemazole ;
starting dose ; 15-40 mg per day in single or divided or 5-40mg
maximum dose ; 60 – 80 mg mg
maintenance dose ; 5- 10 mg
propylthiouracil ;
starting dose ; 50- 200mg three times daily
maximum dose ; 800 – 1000mg
maintenance dose ; 100 mg to 200mg
I n children and adolescents with GD, MMI is the preferred ATD with a daily dose in the range of 0.1-1 mg/kg.The
ATA recommended approach for MMI prescription in patients aged ≤ 18 years is as follows: birth-1 year, 1.25 mg
daily; 1-5 years, 2.5-5 mg daily; 5-10 years, 5-10 mg daily; and 10-18 years, 10-20 mg daily (1). ATDs do not require
any dose adjustment in renal or liver diseases

when euthyroid state is obtained ( 4-6 weeks of therapy )
Defination of eu thyroid state ( normal FT3 , FT4 butTSH is still low )
start maintenance dose ATD dose adjustment should be performed according to results of
periodic clinical and biochemical monitoring. During early months of therapy, serum freeT4 and
totalT3 are appropriate biochemical markers which should be assessed within 2-6 weeks after the
ATD initiation.
If euthyroidism is obtained, the ATD dose can be reduced by 30-50% and after reaching the
minimum dose required for maintenance of the euthyroid condition, intervals of monitoring can
be increased to every 2-3 months and even every 6 months in the setting of long-term therapy
duration of therapy ; 12-18 months or whole life
Indication of stopping therapy ;
- FT4 , FT3 ,TSH level is normal
- negative antiTSH receptor antibodies

risk factors of poor response to therapy
-severe degree of hyperthyroidism
- large goiture
- a high triiodothyronine-to-thyroxine ratio in the serum (when unitless, more than 20)
- patients with higher baseline levels of antithyrotropin-receptor antibodies probably have a
lower likelihood of remission.
- age and sex
- smoking
- presence of opthalmopathy
- duration of symptoms before starting therapy
Remission from GD is generally defined as normal thyroid function for at least 1 year after the
ATD discontinuation
-

relapse ;
time of occurrence ;
Relapse usually occurs within the first three to six months after medication is stopped.47Thereafter, the rate of recurrence decreases
and plateaus after one to two years, for an overall recurrence rate of approximately 50 to 60 percent About 75 percent of women in
remission who become pregnant will have a postpartum relapse of Graves' disease or the development of postpartum thyroiditis.72
Lifelong follow-up is required for patients in remission, since spontaneous hypothyroidism may develop decades later in some of them
prevalence ; 50-60% in graves
risk factors ;
depression, hypochondriasis, paranoia, mental fatigue, and “problems of daily life”
- positive antiTSH receptor antibodies
- duration of treatment
Treatment ;
The likelihood of relapse is increased in patients with normal serum levels of free thyroxine and triiodothyronine but suppressed serum
thyrotropin levels.69
Treatment of relapse ; If radioiodine therapy is selected after a relapse, the outcome may be influenced by the prior use of antithyroid drugs.
When used to normalize thyroid function before radioiodine therapy, propylthiouracil, but not methimazole, increases the failure rate of the
radioactive iodine.36,74-76This “radioprotective” effect of propylthiouracil may be related to its ability to neutralize iodinated free radicals
produced by radiation exposure, a property evidently not shared by methimazole.75The radioprotective effect can be overcome by increasing
the radioiodine dose.
•

Resistance to ATDs
Defination ; failure to achieve clinical and laboratory evidence of euthyroid state
after 3 months of maximum dose 40-60mg of carbimazole or methimazole or
PTU of 800mg
Prevalence ; 1%
mechanism ;
1- multidrug resistance gene
2- low base lineTG auto antibodies
Treatments ;
surgery or radio
preoperative
- iodine solution and beta blockers for 10 days
- steroid

other drugs
1- iodine therapy
- types
- mechanism of action
- indication
- duration
- 2- beta blockers ;
- 3- lithium
- 4-

treatment of the cause
1- graves diseases

• Diagnosis ;
• -TSH, FT3, FT4
• - Autoantibodies
• - RAIU
• -Thyroid U/S
•

2-TOXIC ADENOMA ORTOXIC MULTINODULAR GOITERA
Diagnosis ;
-TFT
- Negative autoantibodies
- RAIU
Thyroid U/S
Treatment
Antithyroid medications can control hyperthyroidism, but do not induce remission of
hyperthyroidism associated with toxic adenoma or toxic multinodular goiter.Therefore,
radioactive iodine ablation and thyroidectomy are the main treatment options for these
conditions.Thyroidectomy is favored if a nodule or goiter causes compressive symptoms.
Antithyroid medications may be used for long-term treatment in select patients who
refuse ablation or who have a contraindication to thyroidectomy.35,36

3-THYROIDITIS
Diagnosis ;
- In autoimmune thyroiditis ;
1-TFT
2- RAIU ; LOW
3- Autoantibodies
4- U/S
- POST infection ;
1-TFT
2- RAIU ; low
3- negative autoantibodies

- destruction
treatment
Painless thyroiditis and subacute thyroiditis are self-limiting conditions that usually
resolve spontaneously within six months.There is no role for antithyroid medications or
radioactive iodine ablation in the treatment of thyroiditis. Beta blockers may be used if
needed to control adrenergic symptoms. Pain associated with subacute thyroiditis may
be relieved with a nonsteroidal anti-inflammatory drug.

4- amiodarone induced
1- pathogenesis ;

• 4- B-HCGT INDUCED ;
indication for testingTFT ;
if the level of beta HCGT is more than 50000 iu / l regardless of the cause
Beta HCGT of 25000 is roughly equivalent to Mu /l ofTSH
TSH is suppressed if BHCGT is more than 400000
treatment

GRAVES OPTHALMOPATHY ;
PREVALENCE
RISK FACTORS
GRADING

thyrotoxicosis and preganancy
• Causes ;

• diagnosis ;
• Indication

• diagnosis ;
-TSH level is below the normal trimestric range
- FT3, FT4 Is above the normal

Thyrotoxicosis lecture for MD degree endocrinology students

Thyrotoxicosis lecture for MD degree endocrinology students

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