Updated treatment of

hypothyroidism
Professor / Mohammed Ahmed Bamashmos
Professor of Internal Medicine and Endocrinology
Faculty of medicine Sanaa university
 prevalence
Of overt hypothyroidism ; 4 %
Of subclinical ; prevalence of subclinical hypothyroidism ranged between 7.5–8.5% in women and 4.4% in men [13,14].
Subclinical hypothyroidism prevalence increases in women with increasing age and is more common in elderly females (7–
18%) than males (2–15%)
Classification
- by time of onset
- congenital
- acquired
-by etiology
- primary
- secondary
- by severity
- overt
- subclinical
- By laboratory
Causes
 Clinical features
1- typical S,S ; fatigue. Weight gain. Trouble tolerating cold. Joint and muscle pain. Dry skin or dry, thinning hair. Heavy or
irregular menstrual periods or fertility problems. slowed heart rate. Depression.

2-Atypical
 Screening
A- important of screening ;
1- The symptoms of hypothyroidism are generally nonspecific, with considerable overlap with other conditions and with the
consequences for the health of advancing age. These symptoms are not useful for diagnosing hypothyroidism and a thyroid function
test is required for a firm clinical diagnosis
2- Lack of knowledge and understanding of hypothyroidism, and a tendency for many people to attribute the symptoms of
hypothyroidism to other causes have led to substantial unawareness and often late diagnosis of hypothyroidism.
3- high prevalence of undiagnosed hypothyroidism ( 4-7% in USA , and Europe )
Note that the diagnoses of hypothyroidism depends on laboratory and not on clinical background
B- Indication ;
A- In pregnant women with history of
- family history , thyroid diseases during pregnancy , complicated pregnancy , recurrent miscarriage , positive ATP
Menstrual irregularities
B- Any patients with history of
- unexplained stunted growth
- CNS ( Dementia , other psychiatric
- CVS ( CVD , Dyslipidemia
- Menstrual irregularity , infertility
C- Any patients with 4 or more of the following symptoms ;
- fatigue ( 88%) , coldness( 84% ) , ( dry skin 77%,) weight gain (72% ) , constipation ( 52%) , sleepiness (
68%)
Types of test used ;
many traditional doctors use only TSH, FT3, FT4 for screening , they omit the measurement of TPO
Important for measurement of TPO as screening tools ;
- symptoms as unexplained fatigue, weakness , weight changes , mood changes , irregular menses
- some patients has symptoms of hypothyroidism with normal TFT and positive TPO
- for product the development of hypothyroidism ( staging )
- in pregnant women with unexplained abortion , miscarriage
- in infertility
- pregnant women with history of autoimmune diseases
Diagnosis ;
A- investigation to diagnose hypothyroidism
1- TFT ;
Types ;
- TSH ;
Important ;
- diagnose all types of hypothyroidism
- monitoring response to therapy in primary , SCH , GH
Other cause of false increase
- physiological increase
- Diurnal variation
- Recovery phase of euthyroid sick syndrome
- recovery phase of subacute , painless or postpartum
- other causes
- Assay variability
- Substance that interfere with TSH assay ( heterophil Abs , RF , Biotin , macro
TSH
- Impaired RF
B- FT3,FT4
- Diagnosis of overt hypothyroidism
- differentiate overt from subclinical
- to determine the response to therapy in secondary
Interpretation of TFT
Primary
- Overt hypothyroidism ( high TSH above 10 , low FT3,FT4 )
- Subclinical ( high TSH 5-10 ug/dl and normal FT4, FT3 )
Secondary and tertiary ( normal or low TSH and low FT3,FT4 )
Gestational hypothyroidism
- TSH is above the trimestric reference rang
B- investigation to know the cause
- Autoantibodies ; ( TPO, TG , Anti TG )
A- TPO antibodies ; Its usually missed as part of investigation as many traditional doctors use only TFT for
diagnosis of hypothyroidism
- important of measurement of TPO
1- For diagnosis of autoimmune thyroiditis ( most common cause of hypothyroidism ( 80-90% )
2- for diagnosis and treatment of SCH
3- To explain persistent of symptoms in hypothyroid patients treated with levothyroxine and target TSH
- important of measurement of TPO antibodies in patients with normal TFT
- in pregnant women with normal TFT ( 11%)
Effect of positive TPO
- premature delivery
- miscarriage - post partum thyroiditis
- abortion
- intrauterine growth retardation
- hypertensive disorders
 - in infertile women ( 30% of infertile has positive TPO ) ; thyroid antibodies appear to be directly
pathogenic to reproductive organs and can impact egg implantation. It’s been shown that thyroid antibodies
can pass through the blood-follicle barrier and create a cytotoxic environment that can damage the maturing
egg, as well as reduce its quality and its fertilization potential.
- patients with goiter
- for prevention strategy of hypothyroidism (
- for staging of hashimotos
1- Stage 1 ;
- no symptoms
- TFT is normal
- only genetic
2- Stage 2 ;
- positive antibodies
-start to exhibit a whole bunch of different non-specific symptoms like fatigue, anxiety, stress,
miscarriages, weight gain, and just feeling unwell. Without verifying the presence of thyroid antibodies,
these types of symptoms may not be associated with developing thyroid disease, and they may end up being
misdiagnosed as other things such as anxiety, fatigue (perhaps even laziness!), depression, menopause, or
even hypochondria. I have personally seen a number of clients who were diagnosed with depression
3- Stage 3 ;
- positive antibodies
- TSH at the range of SCH
4- Stage 4 ;
- overt hypothyroidism
5- Stage 5 ;
- overt hypothyroidism with other autoimmune diseases
- For scoring ; ( THEA score )
Aim ; to expect the development of hypothyroidism within 5 years ;
It depends on the following
- TSH level
- TPO
- Family history
interpretation ;
to product the development of hypothyroidism within 5 years
classification
- low ( 0-7)
- medium ( 8-10)
- high ( 11-15)
-very high (16-21).
B - Serum TG , anti TG ;
Other investigation
- Urine iodine
- neck U/S
- Pituitary MRI
 Treatment
treatment indication ;
- In overt hypothyroidism
Adverse effect of overt hypothyroidism if not treated
Complications of untreated hypothyroidism can include the following.
1-Mental health changes
Hypothyroidism affects your mind as well as your body. It can slow your thoughts, make you forgetful,
and affect your ability to concentrate. In fact, hypothyroidism is one of the reversible causes of
dementia. , depression
2- Goiter
3- CVD ( HF, CAD )
4- Nerve damage ( pain , numbness , muscle weakness of upper limb )
5-myxedema coma
6- infertility
7- effect on pregnancy
 treatment types ;
- Levothyroxine ;
1- benefit ;
- improvement of S,S
- Restoration of TSH level

2- formula
3- precaution ;
- time ;
- instruction ;
 Dose ;
- starting dose ; this depends on ;
A- Age of the patients ;
in the neonate
- neonate to 6 months ; 10-15
- 6 months to 1 years ; 8-10 mcg/kg/ day
- 1-2 years ; 6-8 mcg/kg/day
-Older than 2 years ; 5-6mcg/kg/day
- Young and middle age ≤ 65 years who have no comorbidities or CV risk factors ; 1.6 mcg/kg/day
- In elderly ;
B- any associated comorbid
Risk factors ; patients at high risk start low and go slow ; 12.5-25
treatment monitoring ;
After initiating the first dose recheck TSH after 4-6 weeks ;
A - if the treatment target is reached ;
Continuous the same dose and recheck TSH level every 4-6 months then annually
B- if the treatment target is not reached adjust the dose every 4-6 weeks
Do dose readjustment
protocol
Factors that effect levothyroxine dose ;
1- pharmaceutical
- formulation ( tab, gel , liquid , storage condition )
-Administration route ( oral ,IV , IM )
- Dosing regimen ( dose frequency , time of the day )
- concomitant administration of other thyroid hormone
2- Pathophysiological
- Thyroid disorders ( types , degree and progression ) and etiology
- Comorbidities ( types , degree , progression )
-Age , sex , BMI , pregnancy )
-Genetic variation
-Malabsorption
-Changes in the underlying thyroid function
3- Behavioral ;
- concomitant intake of medication , food stuffs and food supplements
- poor compliance
Treatment monitoring ;
- clinical ; by observing for any symptoms of overt or under treatment
- laboratory ; TSH level ; every 4-6 months
the prevalence of over and under treatment ;
48%
The adverse effect of over or under treatment
A - of under treatment ;
- Intrauterine and neonate ( poor growth and brain development
-Children and adolescence ( poor growth , poor growth of teeth and bone , cognitive disturbance
- Young adults ( Poor mental function , CVD as low cardiac output , HTN , high total and LDL , hair loss , dry skin ,
reduced lung function , decreased GFR
-Fertile female ( menstrual disturbance , infertility , pregnancy loss , post partum thyroiditis
-Elderly ( heart failure , increased CV mortality , poor cognition
B - of over treatments ;
- MI ( 15 % )
-Arrhythmia ( 96% )
- osteoporosis
Treatment remission ;
criteria ;
- clinical
- Laboratory
failure to achieve remission
1- clinical ;
Defination ; its defined as persistent symptoms of hypothyroidism These symptoms can include fatigue, low energy levels,
weight management difficulties, low mood, impaired memory, and brain fog
Prevalence ; 15%, continue to have persistent symptoms
Causes ; ( pathophysiology of resistance symptoms to levothyroxine )
A- low tissue levothyroxine hypothesis
failure to achieve normal tissue level of T3 ( due to decrease level of type 2 deiodinase in the tissue specially the
brain )
B- the somatic symptoms and related disorders hypothesis due to ;
- impairment of psychological stress
- functional impartment
- health care stress
C- Autoimmune and neuro inflammatory hypothesis
D- other physical and psychological comorbidities hypothesis
- physical comorbidities ;
- other autoimmune diseases ( adrenal insufficiency )
- vitamin and iron deficiency
- Chronic diseases ( CLD , CRD )
- sleep apnea
- chronic infection ( Lyme diseases , HIV , infectious mononucleosis
- psychiatric disorders ( depression 13% )
- over weight , pregnancy , lack of exercise
2- laboratory ;
- Defination ; Refractory hypothyroidism is defined as the presence of biochemical signs(serum TSH>4.5 mU/L, 6 weeks
after the dose increase) or clinical hypothyroid symptoms of a LT4 dose>1.9 µg/kg/day (2). Poor compliance and persistence
is the most common cause of failed LT4 therapy
- prevalence ; Up to 15-20% of patients under LT4 medication experience treatment-refractory hypothyroidism according to
the literature
Causes ;
diagnosis ;
Treatment of refractory hypothyroidism
According to the cause ;
1- non compliance ;
oral - once weekly levothyroxine dose ; its safe , effective and well tolerated
- dose ; its 7 times the daily dose
- FT3 ,FT4 well increase after 82hour of treatment and return to normal after 8 days
- its safe and well tolerated and no side effect
- not use in elderly and IHD
2- malabsorption
- Rectal administration of LT4 has been tried mostly in the form of suppositories.
It has lower bioavailability and efficiency due to slow release of LT4 in the rectum
dose ; twice that of oral dose
- IV
- Subcutaneous
To the best of our knowledge, two reports of subcutaneous LT4 administration have been published (4,5). The first case
failed because of painful local reaction due to injection of the entire dose of 10 mL at one single site. In a second report of
2013, a split dosage using two injection sites was successful.
The major advantage of subcutaneous application is simple handling, which can be done by the patients themselves.
Furthermore, it can be performed in patients under anticoagulation and with coagulopathies. Similar to the preceding report,
we demonstrated that off-label use of subcutaneous LT4 is safe and effective in patients with refractory hypothyroidism.
Subcutaneous injection of drugs, as in other diseases like diabetes, seems to be the most suitable route of administration in
persons with malabsorption of LT4. This may be particularly important for persons with inflammatory bowel disease, short
bowel syndrome and total parenteral nutrition (4)
 Gestational hypothyroidism
1- Defination ;
2- classification ;
3- causes ;
- Hashimotos diseases ( it occurs in 2 to 3 out of 100 pregnant )
- iodine deficiency
- overtreatment of hyperthyroidism
4- diagnosis ;
- of overt hypothyroidism ;
TFT ;
- TSH ;
If the trimestric range is available ( TSH is above )
- first ; 0.1- 2.5
- second ; 0.2-3
- third ; 0.3-3
 if the trimestric reference rang is not available by serum TSH concentrations greater than 2·5 mIU/L in the first trimester and
greater than 3 mIU/L in the second and third trimesters.
In SCH ;
- TSH ; is above the trimestric reference range
- normal FT4 , FT3
2- TPO antibodies ;
- in overt ; 70-90%
- in subclinical 30-60%
- in isolated hypothyroxinemia 10%
- in pregnant with normal TFT ( 11% )
Adverse effect of hypothyroidism in pregnancy ;
Effect on mothers
- risk of premature birth
- low birth weight
- miscarriage
- gestational hypertension
- preeclampsia
- post partum hemorrhage
- myopathy
Effect on the fetus
- cognitive impairment
- neurological abnormalities
- congenital hypothyroidism
treatment ;
- indication ;
- patient who are diagnosed as having hypothyroidism before pregnancy
- patient who are diagnosed as having hypothyroidism during pregnancy
- overt or subclinical
- pregnant women with positive TPO and normal TFT
Dose ;
overt hypothyroidism ;
- diagnosed before pregnancy increase dose by 25-50
- diagnosed during pregnancy ;
I – overt ;
Pregnant patients with newly diagnosed hypothyroidism should receive initial treatment at 1.8 mcg/kg/day. Adjust the dose every four
weeks as needed.
Treatment target ;
- TSH target ;
- first trimester ; 2.5
- second and third ; 3
Subclinical hypothyroidism ; 1.2ug/kg/day
Treatment follow up
- check TSH level evert 4-6 weeks during the first trimester and once during the
second and third trimester
treatment target ;
- TSH level less than 2.5 or within trimestric reference range
 Subclinical hypothyroidism
Defination ;
prevalence
- in general
- in pregnant ( 15-28% )
Causes ;
- Autoimmune ( Hash motoes thy
- suboptimal treatment of overt hyperthyroidism
- partial thyroidectomy
- radioactive iodine ablation
-radiation
-drugs ( iodine contrast , amiodarone , lithelium , tyrosine kinase
- iodine deficiency or excess
Diagnosis ;
- TFT
- Autoantibodies ( 50% )
Clinical features ;
- no symptoms
- fatigue , unexplained weight gain , constipation , depression , dry cold skin , menstrual irregularity
Treatment ;
-Adverse effect of untreated
1- progression to overt hypothyroidism ( 33-55% over 10-20 years )
2- metabolic syndrome , obesity and DM
3- Dyslipidemia
4- CV and endothelial dysfunction ( increased risk of MI , Atherosclerosis )
5- stroke
6- psychiatric and cognitive dysfunction
7- neuromuscular dysfunction
8- bone health
9- infertility and recurrent miscarriage
10- pregnancy complication
- if serum TSH level is more than 10 treat
- if serum TSH level is 5-10 ; not to treat if ;
- very old
- negative TPO
- No compiling indication
indication for treatments ;
- young
- progressive increase
- positive TPO
- Compiling indication ;
- S,S
- Pregnancy , infertility , menstrual
-CVD
- CNS
Dose ;
- in young ; 50-75UG
- in elderly ;
Indication of levothyroxine therapy in euthyroid patients ;
any patients with normal TFT and positive TPO antibodies as ;
- pregnant women with positive TPO and TSH above 2.5
- stage 2 Hashmotoies
- infertile women with TSH level more than 2.5
- goiter
Other strategies to decrease TPO
mechanisms of corrective actions to reduce thyroid antibodies are:
- Trigger reduction
-Oxidative stress reduction (with antioxidants)
-Oral tolerance
-Immune modulation ( vitamin D )
-Immune suppression ( Prednisolone ,
-Target removal
1- trigger reduction ;
- toxin ; as iodine excess , copper ,mercury arsenic
- infection ( candida , HP , HCV , CMV, EBV )
- Emotional and physical stress
- Nutrient deficiency ( selenium , vit D , B vitamin , iodine , iron , zinc )
- food sensitivity ( Gluten, Dairy , soy , Grains , eggs , Nuts , Seeds )
- Hormonal shift ( puberty , pregnancy ,
2- oxidative stress ;
- iodine restriction Iodine restriction has been shown to reduce oxidative stress, and according to various
studies, some people have been able to lower thyroid antibodies by restricting their iodine intake.
- use of selenium
A dosage of 200 mcg per day has been found to reduce thyroid antibodies in clinical trials. [41] In some studies,
selenium cut the antibodies significantly within six months.
In my survey, people taking a selenium supplement helped 63 percent of respondents feel better. Thirty-four
percent saw no difference,
- Thyroid Medications to Prevent Oxidative Stress
indication of levothyroxine in ;
- stage 2 hashmotoies
- in stage 3 ( SCH)
- In pregnancy with positive Abs and TSH above 2.5
- in infertility ( aim is to suppress TSH level
3- immune suppression ;
Prednisone and prednisolone are common corticosteroid drugs used for immunosuppression. Limited studies have
been done relating to the use of steroids in extreme cases of Hashimoto’s encephalopathy, as well as one study relating
to pregnant women going through In Vitro Fertilization (IVF). [71]
In the IVF study, the presence of thyroid antibodies was associated with decreased rates of pregnancy and live birth, and
the use of low dose prednisolone helped those women with thyroid antibodies have greater success when going through
IVF.
Generally, immune-suppressing steroids can reduce thyroid antibodies, but in my view, only for short-term. When you
withdraw the steroid, the thyroid antibodies can flare back up again.
4- immune modulation
- vitamin d
- omega