The document discusses hypothyroidism, including its causes, signs and symptoms, diagnosis, and treatment. Some key points:
- Primary hypothyroidism is caused by failure of the thyroid gland and accounts for 99% of cases. Secondary hypothyroidism is caused by pituitary failure.
- Hashimoto's thyroiditis is the most common cause of hypothyroidism in iodine-sufficient areas. It is an autoimmune disorder more common in women.
- Diagnosis is based on elevated TSH and low free T4 levels. Treatment involves daily levothyroxine replacement therapy with dosages adjusted based on follow up TSH levels.
2. Second most common endocrine disorder after diabetes
Affects at any time during life even during intrauterine period
99% : Primary hypothyroidism(TSH-elevated,FT4-low)
< 1% : secondary hypothyroidism(TSH-low,FT4-low)
Easy to establish the diagnosis and
gratifying to treat
4. Overt hypothyroidism
Adult women : 2%
Adult men : 0.1 to 0.2%
Subclinical hypothyroidism : 9.5%
Congenital hypothyroidism : 1 in 3500 newborns
Prevalence
5.
6. Environmental iodine deficiency -most common cause of hypothyroidism
on a worldwide
In areas of iodine sufficiency, the most common cause of hypothyroidism
is chronic autoimmune thyroiditis (Hashimoto’s thyroiditis).
Autoimmune thyroid diseases (AITDs) have been estimated to be 5-10
times more common in women than in men
This form of AITD increases in frequency with age , and is more common
in people with other autoimmune diseases and family h/o.
7. AITDs are characterized pathologically-infiltration of the thyroid with T
lymphocytes and serologically- thyroid autoantibodies
Anti-thyroid antibodies-anti-thyroglobulin antibodies (Tg Ab), anti-
microsomal/anti-thyroid peroxidase antibodies (TPO Ab), and TSH
receptor antibodies (TSHR Ab)
Approximately 75% pt with chronic autoimmune thyroiditis have elevated
anti-thyroid antibody titers
8. These antibodies were more common in women than men and increased
with age.
Only positive TPO Ab tests were significantly associated with
hypothyroidism.
It predict progression of subclinical HT to overt hypothyroidism—4.3%
per year with TPO Ab vs. 2.6% per year without elevated TPO Ab
9. In central hypothyroidism, serum TSH may be mildly elevated, but
assessment of serum free T4 is usually low(differentiating it from
subclinical primary hypothyroidism).
Consumptive hypothyroidism-rare,in patients with hemangiomas and
other tumors in which type 3 deiodinase is expressed, resulting in
accelerated degradation of T4 and T3
10.
11. Hypothyroidism
Primary secondary
Myxeodermatous Gross Subtle
features
Associated 0 Headache
features Visual field defect
Other pituitary 0 Present
deficiencies
Goitre Present absent
Cardiomegaly Present absent
Cholesterol Increased Normal
TPO Present absent
TSH Increased Low normal
12. Disorders associated with hypothyroidism
other autoimmune disorders- type 1 diabetes, pernicious anemia, primary
adrenal failure (Addison’s disease), myasthenia gravis, celiac disease, RA,
SLE, and rarely thyroid lymphoma
multiple autoimmune endocrinopathies/PGAS
13. The presence of two of the three major characteristics is required to
diagnose the syndrome of MAEs
Type 1 MAE: Addison’s disease, Autoimmune thyroiditis (10%-15%)
Hypoparathyroidism, mucocutaneous candidiasis.
Type 2 MAE(Schmidt’s syndrome): Addison’s disease, autoimmune
thyroiditis, and type 1 diabetes
14. Signs and symptoms of hypothyroidism
signs and symptoms of hypothyroidism tend to be more subtle than those
of hyperthyroidism
Dry skin, cold sensitivity, fatigue, muscle cramps, voice changes, and
constipation are among the most common
Less common, typically associated with severe hypothyroidism are carpal
tunnel syndrome, sleep apnea, hyperprolactinemia and galactorrhea.
euvolemic hyponatremia that can occur in profound hypothyroidism
15. myxedema coma-Severe hypothyroidism may progress to hypothermic
stuporous state with respiratory depression
ppt factors-cold exposures, trauma,infections and adm.of narcotics.
16.
17. TSH level
TSH is the primary screening test for thyroid dysfunction.
diurnal variation
TSH secretion is exquisitely sensitive to both minor increases and
decreases in serum free T4
abnormal TSH levels occur during developing hypothyroidism and
hyperthyroidism before free T4 abnormalities are detectable
18. Pitfalls encountered when interpreting
serum TSH levels
normal reference range(0.5-5) may widen with increasing age . Thus, not
all patients who have mild TSH elevations are hypothyroid and therefore
would not require thyroid hormone therapy.
TSH supressed in acute illness & levels may increase to levels above
normal(<20 mIU/L)during the recovery phase from non thyroidal illness
Thus, in hospitalized patients TFT performed only if there is a high index
of suspicion for thyroid dysfunction
19. Serum TSH typically falls during the first trimester of pregnancy due to
the thyroid stimulatory effects of hCG and returns to normal in the
second trimester
TSH secretion may be inhibited by drugs such as octreotide,and
bexarotene.
20. anorexia nervosa pt may have low TSH levels in combination with low
levels of free T4.
In central hypothyroidism, may have mildly elevated serum TSH levels,
generally not above 6 or 7 mIU/L, due to secretion of bioinactive isoforms
of TSH by nonfunctioning pituitary adenoma
TSH levels may also be elevated in thyroid hormone resistance syndrome
in association with elevated serum thyroid hormone levels.
21. Heterophilic ab,rheumatoid factor, and autoimmune anti-TSH antibodies
may cause falsely elevated serum TSH values
Adrenal insufficiency may be associated with TSH elevations that are
reversed with glucocorticoid replacement
Coexistence of hypothyroidism
Thyroid gland resistance to TSH in hypocortisol state
Compensatory mechanism
22. Measurement of T4 and T3
T4/T3 are bound to specific binding proteins-thyroid binding globulin
(TBG) and,transthyretin,prealbumin and albumin.
approximately 99.97% of T4 is protein-bound, levels of serum total T4 will
be affected by factors that alter binding proteins.
assessment of s.free T4 has now largely replaced s.total T4 as a measure of
thyroid status
FT4 is measured by serum free T4 index and direct immunoassay
23.
24. s.free T4 is the primary test for detecting hypothyroidism in pt with
hyperthyroidism Rx with antithyroid drugs or surgical or radioiodine-
s.TSH may remain low for many weeks to months
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 administration
25. In pregnancy, measurement of serum total T4 is recommended over the
free T4
Because of TBG are increased in pregnancy, so free T4 may yield lower
values
total T4 increases during the pregnancy so reference range is ~1.5-fold that
of the nonpregnant range.
26. ~99.7% of T3 proein bound.
free T3 conc.measured by direct immunoassay
However, serum T3 measurement, whether total or free, has limited utility
in hypothyroidism because levels are often normal due to
hyperstimulation of the remaining functioning thyroid tissue by elevated
TSH and up-regulation of type 2 deiodinase.
levels of T3 are low in the absence of hypothyroidism-ex.pts with severe
illness because of reduced peripheral conversion of T4 to T3 and increased
inactivation of thyroid hormone
27. When to measure antiTPO ab
with subclinical hypothyroidism.
In pts with a diffuse, firm goiter
In the presence of other autoimmune disease such as type 1 diabetes or
Addison’s disease, chromosomal disorders such as Down’s or Turner’s syndrome,
and therapy with drugs such as lithium, interferon alpha, and amiodarone TPO
Ab measurement may provide prognostic information on the risk of developing
hypothyroidism.
Recurrent miscarriage/abortions
29. Whom to screen
-autoimmune disease, such as pernicious anemia
-first-degree relative with autoimmune thyroid disease
-history of neck irradiation
-prior history of thyroid surgery
-abnormal thyroid examination
-psychiatric disorders
-taking amiodarone or lithium
30.
31. When to treat hypothyroidism
overt hypothyroidism
TSH levels above 10 m IU/L
TSH levels of 5-10 mIU/l
-TPO positivity
- Goitre
- Dyslipidemia
- Anemia
- h/O AID or F/H of AITD
-Infertility
-Pregnancy
-Psychiatric disorders
32. treatment of hypothyroidism
daily L-thyroxine
1.6 μg/kg/day(Ideal body weight)
Patients who are athyreotic (after total thyroidectomy and/or radioiodine
therapy) and those with central hypothyroidism may require higher doses
while patients with subclinical hypothyroidism or after treatment for
Graves’ disease may require less.
33. Dose: 50 µg and built up weekly
Dose 25 µg and built up weekly
Advanced systemic disease, Elderly, CAD
Start with 100 µg : Pregnancy
secondary hypothyroidism first initiate with glucocorticoids and
later add LT4
Monitor TSH at 6 weeks and later 6 monthly
34. Starting with full replacement versus low dosages leads to more rapid
normalization of serum TSH but similar time to symptom resolution
However, patients with subclinical hypothyroidism do not require full
replacement doses. Doses of 25-75 μg daily are usually sufficient for
achieving euthyroid levels.
35. L-thyroxine take with water 60 minutes before breakfast or at bedtime 4
hours after the last meal on an empty stomach, is superior
L-thyroxine should be stored per product insert at 20°C-25°C, (range, 15°C-
30°C) and protected from light and moisture.
It should not be taken with substances or medications that interfere with
its absorption or metabolism.
36. Because approximately 70% of an orally administered dose of L-thyroxine
is absorbed, individuals unable to ingest L-thyroxine should initially
receive 70% or less of their usual dose intravenously
Crushed L-thyroxine suspended in water should be given to patients
receiving enteral feeding through nasogastric and other tubes.
For optimal absorption feeding should be interrupted with doses given as
long as possible after feeding and at least 1 hour before resuming feeding
37. Myxedema coma
L-thyroxine 500 ug iv stat f/b 100 ug/day
Hydrocort 50 mg q6hrly
Ventilatory support
Space blankets
Treat the ppt factors
38. Dose adjustments are guided by serum TSH, measured after 6 weeks
following initiation of therapy, dosage adjustments, or change in the L-
thyroxine preparation
In the case of central hypothyroidism-assessment of free T4, not TSH
should guide therapy
clinical manifestations of hypothyroidism, such as chronic skin changes,
may take up to 3-6 months to resolve after serum TSH has returned to
normal
39.
40.
41.
42.
43.
44. Dosage adjustments
In pregnancy thyroid hormone requirements are increased, then revert
back to baseline after delivery
generally when medications influencing absorption, plasma binding, or
metabolism are added or discontinued
Decreases in L-thyroxine requirements occur in old age and following
significant weight loss.
45. Clinical monitoring
For onset of anginal symptoms
exacerbation of adrenal insufficiency
Patients on high doses of L-thyroxine (>200 μg/d) with persistently
elevated TSH levels may be noncompliant or malbsorption
46. avoid overtreatment this has been reported in 20%pts
The principal adverse consequences of subtle or frank overtreatment are
cardiovascular , skeletal, and possibly affective disturbances . The elderly
male are particularly susceptible to atrial fibrillation, while
postmenopausal women are prone to accelerated bone loss
47. Therapeutic endpoints in
the treatment of hypothyroidism
The most reliable therapeutic endpoint for the treatment of primary
hypothyroidism is the s.TSH is within the normal range, free T4 will also
be in the normal range
48. When to consult an endocrinologist
Children and infants
Patients in whom it is difficult to render and maintain a euthyroid state
Pregnancy
Women planning conception
Cardiac disease
Presence of goiter, nodule, or other structural changes in the thyroid gland
Presence of other endocrine disease such as adrenal and pituitary disorders
Unusual constellation of thyroid function test results
Unusual causes of hypothyroidism such as those induced by drugs
49. Hypothyroidism during pregnancy
Overt untreated hypothyroidism during pregnancy may adversely affect
maternal and fetal outcomes
spontaneous miscarriage, preterm delivery, preeclampsia, maternal
hypertension, postpartum hemorrhage, low birth weight and stillbirth,
and impaired intellectual and psychomotor development of the fetus.
50. 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 <ULN for trimester and that serum total T4 is in the normal
reference range for pregnancy
51. Serum TSH and total T4 measurements should be monitored every 4
weeks during the first half of pregnancy and at least once between 26 and
32 weeks gestation to ensure that the requirement for L-thyroxine has not
change
Serum TSH levels decline in the first trimester when serum human
chorionic gonadotropin levels are high and rise after 10-12 weeks gestation
T4-increased in pregnancy(1.5 times of non pregnant values)
53. overt hypothyroidism does not appear to be more common in the obese
population than in the general population
myxedema may present with weight loss
obesity may have an impact on the HPT as evidenced by relatively
elevated TSH levels in morbidly obese adults and children with normal
anti-thyroid antibody titers ,T4 and T3 levels.
Caution-while diagnosing subclinical hypothyroidism in the setting of
marked obesity
54. The diagnosis of subclinical or overt hypothyroidism must be considered
in every patient with depression.
All patients receiving lithium/amiodarone therapy require periodic
thyroid evaluation- induce goiter and hypothyroidism
