hypothyroidism introduction and five real cases manipulation. patients with both hypothyroidism and hypertension, elderly dose,diabetes,pregnant ,hemorrhage and osteoporosis and their doses of thyroxin according to american guidelines for 2012.

1. Pharmacotherapeutics
Community Service Program
Field-based study of selected clinical cases
HYPOTHYROIDISM

2. ENDOCRINE DISORDERS
THYROID GLAND /HYPO THYROIDISM

3. Thyroid hormones are essential for:
1- proper fetal growth and development, particularly
development of the central nervous system (CNS).
2- After delivery, the primary role of thyroid hormone is in the
regulation of energy metabolism.
• -Most of the physiologic activity of thyroid hormones is
from the actions of T3.
• - T4 can be thought of primarily as a prohormone.

4. The thyroid gland is the largest endocrine gland in the
body,residing in the neck, anterior to the trachea, between
the cricoid cartilage and the suprasternal notch.
PHYSIOLOGY
The thyroid gland produces two biologically active hormones,
-thyroxine (T4) and
-triiodothyronine (T3).
As well as calcitonin, -The parafollicular C cells of the thyroid
gland produce calcitonin.

5. • Thyroiddisorders:
•
• Changes in hormone secretion can result in hormone
deficiency(hypothyroidism) or excess(hyperthyroidism.)
• HYPOTHYROIDISM
•
•Defination:Hypothyroidism is the most common clinical
disorder of thyroid function. It is the clinical syndrome that
results from inadequate secretion of thyroid hormones

6. • -It is clear that synthetic levothyroxine (LT4) is the
treatment of choice for almost all patients with
hypothyroidism:
• 1-LT4 mimics the normal physiology of the thyroid gland,
which secretes mostly T4 as a prohormone. As needed,
based on metabolic demands,
• 2- peripheral tissues convert thyroxine (T4) to
triiodothyronine (T3).
• - If T3 is used to treat hypothyroidism, the peripheral tissues
lose their ability to control local metabolic rates.
• 3- LT4 also has distinct pharmacokinetic advantages over
T3:.With a 7-day half-life, LT4 provides a very smooth
doseresponse curve

7. Egyptian thyroxine& l-
thyroxine products

8. Case 1:
A hypertensive 60 y man, maintained on valsartan 80
mg daily, 5 years ago started to suffer from fatigue
,cold, skin dryness, constibation,he visited his doctor
and was diagnosed with hypothyroidism ,a
maintained dose of l.thyroxine 50mcg /day was
given to him , 3 years later he had cancer”leukaemia”
and is taking anticancer drug(Interferon alpha)
physician recommended to increase his thyroid
medicine from eltroxin 50 micrograme to
100micrograms daily, he begin to suffer from
headache, nausea and dizziness.

9. • Patient history:
• Weight 90kg, 177cm tall,BP160/110,FBS 100, no family history
of hypothyroidism‫و‬ no other mintained drugs ,or diseases
• Laboratory values:
• TSH:11 milliunits/L (normal 0.5–2.5 milliunits/L)∗
• Free T4: 0.8ng/dL (7.7 pmol/L; normal 0.7–1.9 ng/dL, or 9–24.5
pmol/L)
• ANTI-TPOAB >100
• Serum cholesterol: 180 mg/dL
• Concurrent treatment:
• Valsartan 160mg/daily
• l.thyroxin 100 microgram daily.
• Interferon alpha 3MIU VIAL

10. • Diagnosises:
• It is a Mild hypothyroidism case ( high TSH,NORMAL
T4),with a high property of progression to autoimmune
hypothyroidism.
• cautions:
• Hypothyroidism ,will increase diastolic blood pressure,
• increased levels of total cholesterol and low-density
lipoprotein (LDL) cholesterol and a possible change in
high-density lipoprotein (HDL) cholesterol because of a
change in metabolic clearance, which may lead to more
higher blood pressure.
• Drug- Drug interaction:
• Interferon will decrease l-thyroxin absorption.

12. American therapy guidelines:
-When to treat hypothyroidism TSH levels above 10 mIU/L should be treated which
patients
-Levo-Thyroxine is the drug of choice,
- The daily dosage of L-thyroxine is dependent on age, sex, and body weight.
-L-thyroxine absorption within 30 minutes of breakfast is not as effective as when it is taken
4 hours after the last meal . Another study showed that taking it 60 minutes before
breakfast on an empty stomach was better
• --At the start of therapy and with each change in dose, recheck the TSH in 6- to 8-week intervals.
• If the TSH is not in the target range (0.5–2.5 milliunits/L), change the dose by 10% to 20% and
then
• recheck the TSH 6 to 8 weeks later. As the dose is titrated, assess the patient’s symptoms.Many
patients will improve quickly, and
• many patients will feel the best if the TSH is titrated to lownormal to middle-normal levels (0.5–1.5
milliunits/L)
-LT4 prescriptions should be written as microgram doses to avoid potential errors when
written as milligram doses (e.g., 250 mIU/L dispensed when 0.025 mg is ordered).
-Decreases in L-thyroxine requirements occur as patients age, following significant weight
loss due to decreased lean body mass

13. -Coronary artery disease may be exacerbated by treatment of hypothyroidism.
The dose of thyroxine should be increased slowly in patients with coronary
artery disease, with careful attention to worsening angina, heart failure, or
arrhythmias.
-Patients with mild or subclinical hypothyroidism do not need to be started on
the full replacement dose because they still have some endogenous
hormone production. Start these patients on 25 to 50 mcg/day, and titrate
every 6 to 8 weeks based on TSH levels. Over time, it is likely that the LT4
dose will need to be increased slowly as the patient’s thyroid gland loses
residual function.
4-Regardless of the degree of hypothyroidism, patients older than 50-60 years,
in cardiac disease without evidence of coronary heart disease (CHD) may
be started on doses of25- 50 μg daily, adjusted in steps of12.5- 25mcg
every 4 weeks according to response (guided by serum TSH),usual
maintenance dose 50 -200mcg
-Overtreatment, indicated by a subnormal TSH, should be avoided
since it increases the risk osteoporosis and atrial fibrillation.

14. • Evaluation:
• This patient treatment is NON convenient with the American guidelines therapy,
DUE TO physician ignorance for dose initiation , stepping and stabilization, as he
had to initiate a dose of 25 then stepping it in12.5- 25mcg dose every 4 weeks till
reach a maintenance dose .
• AS WHEN the TSH is not in the target range (0.5–2.5 milliunits/L), he change the
dose by more than10% to 20% as new l- thyroxine dose ihas to be (55-
60mcg/day).
• Patient counseling:
1-Educate patients about the benefits of proper therapy, the importance of adherence,
and the importance of receiving a consistent LT4 product.
2- Some patients will take excessive amounts of LT4 in an effort to “feel better” or as a
weightloss treatment. Explain to patients that excessive amounts ofLT4 will not
improve symptoms more than therapeutic
doses and that this drug is not an effective treatment for obesity.
3-Counsel patients that they should take the LT4 dose at least 2 hours before or 6 hours
after the calcium or iron dose.
4-to avoid taking any supplements (calcium, iron)that will effect thyroxin absorption.
5-avoid diet that will alter thyroxine absorption as fibers, gripe fruit.
6- careful monitoring for exacerbation of cardiac symptoms
7-Frequent monitoring for BP, and blood glucose, triglyceride ,LDL level to avoid any
complications.
8-frequent monitoring for TSH annually.
9- take l-thyroxine 4 hrs after last meale or 60 min before breakfaste on empty stomach.

15. A 45 y man used to suffer from hyperthyroidism ,
was taking carbimazole tab for 10 y then had a
radioactive Iodine therapy.
After 3 y his states dramatically changed to
hypothyroidism, and now is using eltroxin 100 mcg
tab.
He is also a diabetic(type 2) and asmthatic patient
Case 2:

16. • Patient history:
• Weight 90k9, 177cm tall, FBS 140,BP 150/90, no family
history of hypothyroidism, no other mintained drugs ,or
diseases
• Laboratory values:
• TSH 30 mcg/ml,
• FT4 .9, ng/dL (7.7 pmol/L; normal 0.7–1.9 ng/dL, or 9–
24.5 pmol/L)
• Concurrent treatment:
• Eltroxin 100 mg tab.
• Glimepride 3m tab ,
• Salbutamol Evohaler .1mg/dose
• Formeterolfumarate 12mcg/cap”inhalation”
• Budesonide 400 mcg/dose caps

17. • Diagnosises:
• It is a iatrogenic Primary Hypothyroidism case,due to a
large dose of radioactive iodine.
• Drug- Disease interaction:
• Inhaler Glucocorticoid may has little decrease effect on
TSH level “LOCAL”
• Drug- Drug interaction:
• Levothyroxine may interfere with blood glucose control
and reduce the effectiveness of glimepiride and other
diabetic medications.
• Cautions:
• Diabetes mellitus with long standing hypothyroid, has to
increase dose of anti-diabetic drugs including insulin.

18. 2-Patients being treated for hypothyroidism should have serum
TSH measurements done at 4-8 weeks after initiating treatment
or after a change in dose. Once an adequate replacement dose
has been determined, periodic TSH measurements should be
done after 6 months and then at 12-month intervals, or more
frequently if the clinical situation dictates otherwise.
3- The average replacement dose is 1.6 mcg/kg POdaily,and
most patients require doses between75-150mcg/daily
4-In primary hypothyroidism, the goal of therapy is to
maintain plasma TSH within the normal range.
5-after initiation of therapy. The dose of thyroxine then should be
adjusted in 12- to 25-mcg increments at intervals of 6-8 weeks
until plasma TSH is normal.
American therepy guidelines:

19. • --At the start of therapy and with each change in dose,
recheck the TSH in 6- to 8-week intervals.
• If the TSH is not in the target range (0.5–2.5 milliunits/L),
change the dose by 10% to 20% and then
• recheck the TSH 6 to 8 weeks later. As the dose is titrated,
assess the patient’s symptoms.Many patients will improve
quickly, and
• many patients will feel the best if the TSH is titrated to low
normal to middle-normal levels (0.5–1.5 milliunits/L)
• Provide a brand-name LT4 product, and do not allow the
patient to be switched to different products. If the product
is switched, check a TSH in 6 weeks and retitrate the dose.

20. •Therapeutic endpoints in the treatment of
hypothyroidism
• The most reliable therapeutic endpoint for the treatment of
subclinical hypothyroidism is the serum TSH value,and
FT4
• Confirmatory total T4, free T4, and T3 levels do not have
sufficient specificity to serve as therapeutic endpoints by
themselves, nor do clinical criteria. Moreover, when serum
TSH is within the normal range, free T4 will also be in the
normal range.5-2.5 mIU/L

21. • Evaluation:
• This patient thereby is not convenient with the American
guidelines therapy,
• As periodic TSH measurements should be done after 6
months and then at 12-month intervals, or more frequently
in patients over the age of 60.
• Initiation dose must be within 75-100 mcg/day
• Then stepping in intervals of 25mcg every6-8 weeks till
reach an adqate dose =144(1.6*90kg)/day
• Patient counseling:
• Monitor your blood sugar levels closely. You may need a
dose adjustment of your diabetic medications during and
after treatment with levothyroxine.

22. Case 3:
A 77 y female with hyper thyroidism developed osteoporosis
and .12 years ago she had a first lobe thyrodoctomy , 2 years
ago she noticed an enlargement at the base of the neck, after
physical examination. ..physician decided to remove the
second lobe.
After surgery he prescribed a lifetime therapy of:
Eltroxin 100 mcg to be taken daily after breakfast
Calcitron 50 mg daily to be taken after breakfast
This year she suffered from abdominal pain and fatigue.
Tests showed increased cholesterol level

23. • Patient history:
• Weight 120kg, 170cm,75 years, no family history of hypothyroidism,
no other mintained drugs ,or diseases
• Laboratory values:
• TSH:25 milliunits/L (normal 0.5–2.5 milliunits/L∗
• Free T4: 0.6ng/dL (7.7 pmol/L; normal 0.7–1.9 ng/dL, or 9–24.5
pmol/L)
• Total cholesterol: 277 mg/dL
• LDL: 187 mg/dL
• HDL: 29 mg/dL
• Triglycerides: 350 mg/dL
• Concurrent treatment:
• L-thyroxine 100mg tab
• Calcium D3F tab
• atorstatine 20mg tab
• Omeprazole 20mg caps
• Alendronate 10mg tab
• Orlistate 120mg cap.

24. • Diagnosises:
• Primary Hypothyroidism ,Iatrogenic (surgery)
• cautions:
• Hypothyroidism can cause increased levels of total cholesterol
and low-density lipoprotein (LDL) cholesterol and a possible
change in high-density lipoprotein (HDL) cholesterol because of
a change in metabolic clearance.
• Drug-Disease:
• In adequate thereby of l-thyroxine may increase the
osteoporosis development
• Drug- Drug interaction:
• Using calcium carbonate together with levothyroxine may alter
the absorption of levothyroxine.
• Omeprazole alter levo thyroxine absorption
• Orlistate also alter the levo thyroxine absorption.

25. American thereby guidelines:
• Postmenopausal women should receive aggressive
osteoporosis therapy to prevent LT4-induced bone loss
• . One recent study demonstrated that L-thyroxin
absorption within 30 minutes of breakfast is not as
effective as when it is taken 4 hours after the last meal .
Another study showed that taking it 60 minutes before
breakfast on an empty stomach was better
• elderly patients absorb L-thyroxine less efficiently they
often require 20-25% less per kilogram daily than younger
patients, due to decreased lean body mass
• Dosage adjustments are also necessary, generally when
medications influencing absorption

26. • The full replacement dose in patients over age 75 is lower,
about 1 mcg/kg per day. In the elderly, the starting dose is
25 to 50 mcg/day, and the dose is titrated to the normal
range .5-2.5mcg/ml
• If the TSH is not in the target range (0.5–2.5 milliunits/L),
change the dose by 10% to 20% and then
• recheck the TSH 6 to 8 weeks later. As the dose is titrated,
assess the patient’s symptoms.Many patients will improve
quickly, and
• many patients will feel the best if the TSH is titrated to low
normal to middle-normal levels (0.5–1.5 milliunits/L)

27. • Evaluation:
• This patient treatment is not convenient with the American
guidelines therapy, :
• she must take eltroxin on an empty stomach
• Initiation dose has to be 25-50mcg/ml/day
• Stepping tilll maintance dose of
,(1mcg/ml*120=120mcg/ml/day).
• Patient counseling:
• You should separate the administration of levothyroxine
and calcium ,orlistast and omeprazole by at least 4 hours.
• You should limit your consumption of grapefruit juice to no
more than 1 quart per day during treatment with
atorvastatin, and l-thyroxine.
• Adequate monitoring, for triglyceride , LDL, osteoporosis to
avoid complications

28. Case 4
A 39 y female WITH puitatry gland dysfunction, 3 weeks ago
started a condition of paleness, weigh gain -despite of low
appetite - and continues fatigue progressively increased
her CBC showed iron deficiency anemia , longer menstrual
period, she started an anemia
treatment for 2 monthes ago but no improvement

29. Concurrent treatment:
vit b12 ,folic acid 500mcg tablet,IRON supplements.
Bromocriptine ,And l-thyroxine initial dose 75 mcg/ml/day
History:
no other mintained drugs ,or diseasesage 39 yrs ,
Mother with hypothyroidism
LAB TESTS:
Low FT4, and high TSH,high prolactine ,normal TBG
.:

30. Diagnosises:
hypothyroidism ,It is a secondary
not a primary inherited because FREE T4 is low .
Drug -drug interaction:
Iron supplements may interfere with l-thyroxine absorption

31. American thereby guidelines:
Thyroxin is the drug of choice. The average replacement dose
is 1.6 mcg/kg PO daily, and most patients require
doses between 75 and 150 mcg/daily.
-after initiation of therapy. The dose of thyroxine then should be
adjusted in 12- to 25-mcg increments at intervals of 6-8weeks
- In secondary hypothyroidism, plasma TSH cannot be used to
adjust therapy. The goal of therapy is to maintain the plasma
free T4 near the middle of the reference range.
-The dose of thyroxine should be adjusted at 6- to 8-week intervals
until this goal is achieved.
-Thereafter, annual measurement of plasma free T4 is adequate to
monitor therapy.

32. Evalution:
This patient thereby is convenient with American guidelines
thereby.

33. Case 5
A 28 y female suffers from hypothyroidism and is maintained
on levothyrixin 50mcg daily .last month she became
pregnant , her physician recommended to increase the
dose to 100mcg daily also confirmed on following up TSH
and T4 levels continuously

34. Thereby guide lines:
Pregnancy, in which thyroxine requirements often
increase in the first trimester
Thyroxin is the drug of choice. The average replacement dose is 1.6
mcg/kg PO daily, and most patients require
doses between 75 and 150 mcg/daily.
-after initiation of therapy. The dose of thyroxine then should be adjusted in
12- to 25-mcg increments at intervals of 6-8weeks
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35. References
• Pharmacotherapy principles and practice
• https%3A%2F%2Fwww.aace.com%2Ffiles%2Ffinal-file-
hypo-guidelines.pdf&h=LAQHI5ZEu
• Washington_manual_of_medical_therapeutics
• A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-
edition
• BNF fifth edition

36. In monitoring patients with hypothyroidism on L-thyroxine replacement, blood for assessment of serum
free T4 should be collected before dosing because the level will be transiently increased by up to 20%
after L-thyroxine administrationValues tend to be lowest in the late afternoon and highest around the
hour of sleep. In light of this, variations of serum TSH values within the normal range of up to 40%-
50% do not necessarily reflect a change in thyroid status.
The lower range of normal for serum TSH in pregnancy is generally 0.1-0.2 mIU/L lower than the normal
range for those who are not pregnant
The normal range for TSH values, with an upper limit of 4.12 mIU/L is largely based on NHANES III (11)
data, but it has not been universally accepted. Some have proposed that the upper normal should be
either 2.5 or 3.0 mIU/L (86) for a number of reasons:
• The distribution of TSH values used to establish the normal reference range is skewed to the right by
values between 3.1 and 4.12 mIU/L.
• The mean and median values of approximately 1.5 mIU/L are much closer to the lower limit of the
reported normal reference range than the upper limit.
When a woman with hypothyroidism becomes pregnant, the dosage of L-thyroxine should be increased as
soon as possible to ensure that serum TSH is <2.5 mIU/L and that serum total T4 is in the normal
reference range for pregnancy. Moreover, when a patient with a positive TPOAb test becomes
pregnant, serum TSH should be measured as soon as possible and if >2.5 mIU/L, T4 treatment should
be initiated. Serum TSH and total T4 measurements should be monitored every 4 weeks during the
first half of pregnancy (233) and at least once between 26 and 32 weeks gestation to ensure that the
requirement for L-thyroxine has not changed. • When risk factors for thyroid disease are excluded,
the upper reference limit is somewhat lower.

37. Thank you
Presented by:
Noha Ahmed Khater 110036
Heba Mohamed Mahmoud 110038
Hba Ablsalam Ibraheem 110039
Tasneem Fathy Ghareeb 110045
Fawda Mohamed Lkomy 110046
Mohamed Lsaid Hussin 110047
Marwa Mohamed Awad 110049
Mayar Adel Shaat 110050
Hanouf Hassan Ibraheem 110051