Hypothyroidism

Dr.HASSAN EL MEEDANI
UNDERSUPERVISION OF DR.AMAL AL ALI
CONSULTANT FM,ASSOCIATE DIRECTOR OF FM PROGRAM

Objectives

Case discussion
Epidemiology
Classification
Causes
Clinical approach
Screening
Diagnosis
Hypothyroidism with pregnancy
Treatment and dose adjustment
Referral and consultation

Case 1
A 27 years old, female, presents to the office with a chief
complaint of chronic fatigue for about 4 months. She reports
17 pounds weight gain over the last 3 months, despite a
decreased appetite . She became more sleepy lately.

What is your approach for the case above ?

How can the diagnosis best be confirmed?
What is the MOST likely cause of this patients
disease ?

LABORATORY RESULTS for the patient are

WBC: 4,500 cells/mm3
Hb: 11 g/dL
Hct: 32%
MCV 91
TSH: 22.3 IU/mL (0.4 to 4.8)
Free T4: 0.56 ng/dL (0.93 to 1.70)
List the expected laboratory finding for this
patient
How should this patient be managed ?

Your patient is started on 25 mcg levothyroxine (Synthroid) and

is scheduled to return in 2 months.
At follow-up, she reports a general improvement in symptoms
but is not back to normal. She reports continues constipation,
lack of energy, and feeling depressed. She has not lost any further
weight . Laboratory results are as follows:
TSH: 11.8 IU/mL
Free T4: 0.75 ng/dL (0.93 to 1.70)
What adjustments, if any, should be made to her
regimen ?
How you follow up your patient ?

Case 2
A 25-year-old woman complains of fatigue and cold intolerance
increasing over the past 3 months.
On examination, she manifests dry skin, which she says is a change from
her usual. She admits to be puzzled and saddened over the situation.
heart rate is 65 b/m with regular rhythm. Bp123\80 ..TSH level is 0.3
IU/mL (0.4 to 4.8).
She gives a further history of difficult labor with sever bleeding required
ICU admission.
What is the most likely cause of her condition ?
What is the most important consideration in the management of
this patient ?

Case 3
A 38-year-old woman is seen in your office for a complete
baseline health assessment. She feels well and tells you that
she is wonderfully healthy except for lack of energy she have
lately .
You perform thyroid function test that show her TSH to be
elevated 10mu/l and her free T4 to be normal.
What is your diagnosis ?
What is your management approach for this patient ?

Types:
Subclinical hypothyroidism is characterized by a serum TSH

above the upper reference limit in combination with a normal

free thyroxine (T4). This designation is only applicable when
thyroid function has been stable for weeks or more, the
hypothalamic-pituitary-thyroid axis is normal, and there is no
recent or ongoing severe illness.
Overt Hypothyroidism elevated TSH, usually above 10 mIU/L,
in combination with a subnormal free T4.

Epidemiology
Data blow derived from the National Health and Nutrition
Examination Survey (NHANES III) in USA.
The prevalence of subclinical disease was 4.3% and overt
disease 0.3%.
The prevalence increases with age, and is higher in females
than in males. Ratio 2:1
It is estimated that nearly 13 million Americans have
undiagnosed hypothyroidism.

Causes
Hypothyroidism may occur as a result of gland failure
(Primary), or insufficient thyroid gland stimulation by the
hypothalamus or pituitary gland (Secondary).
Primary Hypothyroidism result from congenital
abnormalities, autoimmune destruction (Hashimoto disease),
iodine deficiency, and infiltrative diseases.
Autoimmune thyroid disease is the most common etiology of
hypothyroidism in the United States.
The Most common cause worldwide is iodine deficiency.

Contd
Iatrogenic.
Disorders generally associated with transient hypothyroidism
include postpartum thyroiditis, subacute thyroiditis, silent
thyroiditis, and thyroiditis associated with thyroid-stimulating
hormone (TSH) receptor-blocking antibodies.
Drugs classically associated with thyroid dysfunction include
lithium, amiodarone, interferon alfa, interleukin-2, and
tyrosine kinase inhibitors .

Contd
Central hypothyroidism occurs when there is insufficient
production of bioactive TSH due to :
a) Pituitary or hypothalamic tumors (including
craniopharyngiomas), inflammatory (lymphocytic or
granulomatous hypophysitis) or infiltrative diseases.
b)Hemorrhagic necrosis
c)Surgical and radiation treatment for pituitary or hypothalamic
disease.

Contd
Consumptive hypothyroidism is a rare condition that may
occur in patients with hemangiomata and other tumors in
which type 3 iodothyronine deiodinase is expressed, resulting
in accelerated degradation of T4 and triiodothyronine (T3).

Clinical Presentation
Symptoms of hypothyroidism may
vary with age and sex.
Infants and children may present
more often with lethargy and
failure to thrive.
Women who have hypothyroidism
may present with menstrual
irregularities and infertility.
In older patients, cognitive decline
may be the sole manifestation.

Common Symptoms
Arthralgia
Cold intolerance
Constipation
Depression
Difficulty concentrating
Dry skin
Fatigue
Hair thinning/hair loss
Memory impairment
Menorrhagia
Myalgia
Weakness
Weight gain

Clinical Signs
Bradycardia
Coarse facies
Cognitive impairment
Delayed relaxation phase of
deep tendon reflexes
Diastolic hypertension
Edema
Goiter
Lateral eyebrow thinning
Low-voltage electrocardiography
Macroglossia
Periorbital edema
Pleural and pericardial effusion

Laboratory results
Elevated C-reactive protein
Hyperprolactinemia
Hyponatremia
Increased creatine kinase
Increased low-density lipoprotein cholesterol
Increased triglycerides
Normocytic, Macrocytic anemia
Proteinuria

screening
American Thyroid Association
Women and men >35 years of age should be screened every 5
years.
American Association of Clinical Endocrinologists
Older patients, especially women, should be screened.
American Academy of Family Physicians
Patients 60 years of age should be screened.

American College of Physicians

Women 50 years of age with an incidental finding suggestive
of symptomatic thyroid disease should be evaluated.
U.S. Preventive Services Task Force
Insufficient evidence for or against screening.
Royal College of Physicians of London
Screening of the healthy adult population unjustified.

Screening
While there is no consensus about population screening for
hypothyroidism, there is compelling evidence to support case
finding for hypothyroidism in those with:
Autoimmune disease, such as type 1 diabetes
Pernicious anemia
First-degree relative with autoimmune thyroid disease
history of neck radiation to the thyroid gland including radioactive
iodine therapy for hyperthyroidism and external beam radiotherapy
for head and neck malignancies
Prior history of thyroid surgery or dysfunction
Abnormal thyroid examination
Psychiatric disorders
Taking amiodarone or lithium

Diagnosis
The best laboratory assessment of thyroid function, and
the preferred test for diagnosing primary hypothyroidism,
is a serum TSH test.
If the serum TSH level is elevated, testing should be
repeated with a serum free thyroxine (T4) measurement.

HIGH
NORMAL

22

LOW

FREE THYROXINE or FT4

BASIC THYROID EVALUATION

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

HIGH
NORMAL

EUTHYROID

23

LOW

FREE THYROXINE or FT4

BASIC THYROID EVALUATION

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

HIGH
NORMAL

PRIMARY
HYPOTHYROID
24

LOW

FREE THYROXINE or FT4

BASIC THYROID EVALUATION

LOW

NORMAL

High

THYROID STIMULATING HORMONE - TSH

HIGH
NORMAL

PRIMARY
HYPERTHYROID

25

LOW

FREE THYROXINE or FT4

BASIC THYROID EVALUATION

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

HIGH
NORMAL

SECONDARY
HYPOTHYROID
26

LOW

FREE THYROXINE or FT4

BASIC THYROID EVALUATION

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

HIGH
NORMAL

SECONDARY
HYPERTHYROID

27

LOW

FREE THYROXINE or FT4

BASIC THYROID EVALUATION

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

HIGH
NORMAL

SUB-CLINICAL
HYPERTHYROID

28

LOW

FREE THYROXINE or FT4

BASIC THYROID EVALUATION

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

HIGH
NORMAL

SUB-CLINICAL
HYPOTHYROID

29

LOW

FREE THYROXINE or FT4

BASIC THYROID EVALUATION

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

HIGH
NORMAL
LOW

NON THYROID
ILLNESS or NTI
30

FREE THYROXINE or FT4

BASIC THYROID EVALUATION

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

HIGH
NORMAL

NTI or Pt.
on ELTROXIN

31

LOW

FREE THYROXINE or FT4

BASIC THYROID EVALUATION

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

NTI or Pt.
on ELTROXIN

SECONDARY
HYPERTHYROID

NORMAL

SUB-CLINICAL
HYPERTHYROID

EUTHYROID

SUB-CLINICAL
HYPOTHYROID

SECONDARY
HYPOTHYROID

NON THYROID
ILLNESS - NTI

PRIMARY
HYPOTHYROID
32

HIGH

PRIMARY
HYPERTHYROID

LOW

FREE THYROXINE or FT4

BASIC THYROID EVALUATION

LOW

NORMAL

HIGH

THYROID STIMULATING HORMONE - TSH

 Overt primary hypothyroidism is indicated with an elevated

serum TSH level and a low serum free T4 level.
An elevated serum TSH level with a normal range serum
free T4 level is consistent with subclinical hypothyroidism.
A low serum free T4 level with a low, or inappropriately
normal, serum TSH level is consistent with secondary
hypothyroidism and will usually be associated with further
evidence of hypothalamic-pituitary insufficiency.

Treatment
Most patients will require lifelong thyroid hormone therapy.
The normal thyroid gland makes two hormones: T4 and T3. Although
T4 is produced in greater amounts, T3 is the biologically active form.
Approximately 80%of T3 is derived from the peripheral conversion of
T4. Because T3 preparations have short biologic half-lives,
hypothyroidism is treated almost exclusively with once-daily
synthetic thyroxine preparations. Once absorbed, synthetic thyroxine,
like endogenous thyroxine, undergoes deiodination to the more
biologically active T3.

 The starting dosage of levothyroxine in young, healthy adults

for complete replacement is 1.6 mcg per kg per day.
Levothyroxine dosing for infants and children is weight-based
and varies by age.
Thyroid hormone is generally taken in the morning, 30 minutes
before eating.

 Patients who have difficulty with morning levothyroxine dosing

may find bedtime dosing an effective alternative.
In a well-designed study conducted in the Netherlands,
bedtime dosing of levothyroxine resulted in lower TSH and
higher free T4 levels, but no difference in quality of life.
Alternatively, patients with marked difficulty in adhering to a
once-daily levothyroxine regimen can safely take their entire
week's dosage of levothyroxine once weekly.

Special Populations
Six populations deserve special consideration:
(1) older patients
(2) patients with known or suspected ischemic heart disease
(3) pregnant women
(4) patients with persistent symptoms of hypothyroidism despite
taking adequate doses of levothyroxine
(5) patients with subclinical hypothyroidism
(6) patients suspected of having myxedema coma

OLDER PATIENTS AND PATIENTS WITH

ISCHEMIC HEART DISEASE
Initial dosage is generally 25 mcg or 50 mcg daily, with the
dosage increased by 25 mcg every three to four weeks until the
estimated full replacement dose is reached.
Thyroid hormone increases heart rate and contractility, therefore
increases myocardial oxygen demand. Starting at higher doses
may precipitate acute coronary syndrome or an arrhythmia.
However, there are no high-quality studies that show that lower
starting doses and slow titration result in fewer adverse effects
than full-dose levothyroxine replacement in these patients.

PREGNANCY
Thyroid hormone requirements increase during pregnancy.
In one prospective study, 85% of pregnant patients required a
median increase of 47% in their thyroid hormone requirements.
These increases in levothyroxine dosing were required as early
as the fifth week of pregnancy in some patients, which is before
the first scheduled prenatal care visit.

 It is recommended that women on fixed doses of levothyroxine

take nine doses each week (one extra dose on two days of the
week), instead of the usual seven, as soon as pregnancy is
confirmed.
Serum TSH should be measured at four to six weeks'
gestation, then every four to six weeks until 20 weeks'
gestation, then again at 24 to 28 weeks' and 32 to 34 weeks'
gestation (Grade C).

 The increase in thyroid hormone requirement lasts throughout

pregnancy.
Hypothyroidism during pregnancy should be treated with
levothyroxine, with a serum TSH goal of less than 2.5 mIU per
L (Grade A).
Screening for hypothyroidism in pregnancy apply only for high
risk pregnant ladies for hypothyroidism(Grade C).

Effects of Hypothyroidism on Pregnancy

Outcomes
Maternal

Fetal

Anemia

Miscarriage

Hypertension

Preterm delivery

Preeclampsia

Low birth weight

Abruptio
placenta

Stillbirth

Postpartum
hemorrhage

Psychoneurologic
impairment

PATIENTS WITH PERSISTENT SYMPTOMS

A small number of patients with hypothyroidism, mostly women,
treated with an adequate dose of levothyroxine will report
persistent symptoms such as fatigue, depressed mood, and
weight gain despite having a TSH level in the normal range.
Some patients may have an alternative cause for their
symptoms; so a limited laboratory and clinical investigation is
reasonable.
Combination T3/T4 therapy, in the form of desiccated thyroid
hormone preparations (thyroid USP, Armour thyroid) or
levothyroxine plus liothyronine (Cytomel), is sometimes
prescribed for those patients.

 Desiccated thyroid hormone preparations are not recommended

by the AACE for the treatment of hypothyroidism, and a metaanalysis of 11 randomized controlled trials of combination T 3/T4
therapy versus T4 monotherapy showed no improvements in
bodily pain, depression, or quality of life.
A subsequent study showed that a small subset of patients who
have a specific type 2 deiodinase polymorphism may benefit
from combination therapy.
However, there is insufficient evidence to recommend the use of
combination T3/T4 in treatment of primary hypothyroidism.
Furthermore, genetic testing for a type 2 deiodinase
polymorphism is not practical.

Adrenal insufficiency (rare)

Alternative
Causes of Persistent Symptoms in
Anemia
Patients
with Normal-Range TSH Levels
B deficiency
12

Iron deficiency
Chronic kidney disease
Depression, anxiety disorder, and/or somatoform disorders
Liver disease
Obstructive sleep apnea
Viral infection (e.g., mononucleosis, Lyme disease, human
immunodeficiency virus/AIDS)
Vitamin D deficiency

Common Reasons for Abnormal TSH Levels on a

Previously Stable Dosage of Thyroid Hormone
Decreased absorption of thyroid hormone:
a) Patient is now taking thyroid hormone with food.
b)Patient takes thyroid hormone within four hours of calcium,
iron, soy products, or aluminum-containing antacids.
c) Patient is prescribed medication that decreases absorption
of thyroid hormone, such as cholestyramine (Questran),
colestipol (Colestid), orlistat (Xenical), or sucralfate (Carafate).
Patient nonadherent to thyroid hormone regimen (missing
doses).

 Patient is now pregnant or recently started or stopped estrogencontaining oral contraceptive or hormone therapy.
Generic substitution for brand name or vice versa, or substitution
of one generic formulation for another.
Patient started on sertraline (Zoloft), another selective serotonin
reuptake inhibitor, or a tricyclic antidepressant.
Patient started on carbamazepine (Tegretol) or phenytoin
(Dilantin).

SUBCLINICAL HYPOTHYROIDISM
Subclinical hypothyroidism is a biochemical diagnosis defined by
a normal-range free T4 level and an elevated TSH level.
Patients may or may not have symptoms attributable to
hypothyroidism. On repeat testing, TSH levels may
spontaneously normalize in many patients.
However, in a prospective study of 107 patients older than 55
years, an initial TSH level greater than 10 to 15 mIU per L was
the variable most strongly associated with progression to overt
hypothyroidism.

 Elevated thyroid peroxidase antibody titers also increase the risk

of progressing to frank thyroid gland failure, even when the TSH
level is less than 10 mIU per L.
Treatment with levothyroxine should be considered for patients
with:
1 Initial TSH levels greater than 10 mIU per L.
2 Elevated thyroid peroxidase antibody titers.
3 Symptoms suggestive of hypothyroidism and TSH levels
between 5 and 10 mIU per L.
4 Pregnancy or are attempting to conceive.

Myxedema coma
Myxedema coma is a rare but extremely severe manifestation
of hypothyroidism that most commonly occurs in older women
who have a history of primary hypothyroidism.
Mental status changes including lethargy, cognitive
dysfunction, and even psychosis, and hypothermia are the
hallmark features of myxedema coma.
Hyponatremia, hypoventilation, and bradycardia can also occur.

 Because myxedema coma is a medical emergency with a high

mortality rate, even with appropriate treatment, patients should
be managed in the ICU where proper ventilatory, electrolyte,
and hemodynamic support can be given. Corticosteroids may
also be needed.
A search for precipitating causes such as infection, cardiac
disease, metabolic disturbances, or drug use is critical.

Treatment Summary

Levothyroxine Dosing Guidelines for Hypothyroidism in

Adults
Nonpatientspregnant
1.6 mcg per kg per day initial dosage.
Older patients; patients with known or suspected cardiac disease
25 or 50 mcg daily starting dosage; increase by 25 mcg every three to
four weeks until full replacement dosage reached.
Pregnant patients
Increase to nine doses weekly (one extra dose on two days of the week)
at earliest knowledge of pregnancy; refer to endocrinologist.
Patient with subclinical hypothyroidism
- TSH < 10 mIU per L: 50 mcg daily, increase by 25 mcg daily every six
weeks until TSH = 0.35 to 5.5 mIU per L.
- TSH 10 mIU per L: 1.6 mcg per kg per day.

When to refer patients with

hypothyroidism:

Age??.
Cardiac disease.
Coexisting endocrine diseases.
Myxedema coma suspected.
Pregnancy.
Presence of goiter, nodule, or other structural thyroid
gland abnormality.
Unresponsive to therapy.

References :
American academy of endocrinologists
American thyroid assosciation
American academy of family physicians
Uptodate .com

thank you