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Title: AMBULATORY CARE CLERKSHIP


1
AMBULATORY CARE CLERKSHIP
  • SUPERVISED BY
  • DR. HALA AL-KALIDI

2
Thyroid disorders
DONE BY AMAL ALZAHRANI, Pharm.D. Candidate
3
Outline
  • Thyroid Hormone regulation
  • Hypothyroidism
  • Hyperthyroidism
  • Case Study

4
Thyroid hormones
  • The thyroid gland removes iodine from the blood
    (which comes mostly from a diet of foods such as
    seafood, bread, and salt) and uses it to produce
    thyroid hormones. The two most important thyroid
    hormones are thyroxine (T4) and triiodothyronine
    (T3) representing 99.9 and 0.1 of thyroid
    hormones respectively.

5
contd
  • The hormone with the most biological activity
    (i.e., the greatest effect on the body) is
    actually T3. Once released from the thyroid gland
    into the blood, a large amount of T4 is converted
    to T3--the more active hormone that affects the
    metabolism of cells.

6
  • Thyroid hormone regulation
  • The thyroid itself is regulated by another gland
    located in the brain, called the pituitary. In
    turn, the pituitary is regulated in part by
    thyroid hormone that is circulating in the blood
    (a "feedback" effect of thyroid hormone on the
    pituitary gland) and in part by another gland
    called the hypothalamus, also a part of the
    brain.

7
contd
  • The hypothalamus releases a hormone called
    thyrotropin releasing hormone (TRH), which sends
    a signal to the pituitary to release thyroid
    stimulating hormone (TSH). In turn, TSH sends a
    signal to the thyroid to release thyroid
    hormones.

8
contd
  • The rate of thyroid hormone production is
    controlled by the pituitary gland. If there is an
    insufficient amount of thyroid hormone
    circulating in the body to allow for normal
    functioning, the release of TSH is increased by
    the pituitary in an attempt to stimulate the
    thyroid to produce more thyroid hormone.

9
contd
  • In contrast, when there is an excessive amount of
    circulating thyroid hormone, the release of TSH
    is reduced as the pituitary attempts to decrease
    the production of thyroid hormone.

10
Hypothyroidism
  • Hypothyroidism is a common endocrine disorder
    resulting from deficiency of thyroid hormone.
  • The patient's presentation may vary from
    asymptomatic to, rarely, coma with multisystem
    organ failure (myxedema coma).
  • The most common cause in the Unites States is
    autoimmune thyroid disease (Hashimoto
    thyroiditis).
  • ??Subclinical hypothyroidism, also referred to as
    mild hypothyroidism, is defined as normal serum
    free T4 levels with slightly high serum TSH
    concentration.

11
contd
  • Myxedema coma is a severe form of hypothyroidism
    that results in an altered mental status,
    hypothermia, bradycardia, hypercarbia, and
    hyponatremia. Cardiomegaly, pericardial effusion,
    cardiogenic shock, and ascites may be present.

12
contd
  • Myxedema coma most commonly occurs in individuals
    with undiagnosed or untreated hypothyroidism that
    are subjected to an external stress such as cold
    exposure, surgery, infection, hypnotics, or other
    medical interventions.

13
Symptoms
  • Most common symptoms
  • Slow heart rate
  • Tiredness
  • Inability to tolerate cold
  • Weight gain
  • Emotional depression
  • Drowsiness, even after sleeping through the night
  • Heavy or irregular menstrual periods
  • Muscle cramps
  • Constipation
  • Later symptoms include
  • Dry, flaky skin
  • Hair loss
  • Impaired memory and difficulty in thinking
  • Voice becomes deeper
  • A numb sensation in the arms and legs
  • Puffiness in the face, especially around the eyes
    (a condition called myxedema, which is an
    indication that the disease has become serious)

14
Physical finding
  • Thin brittle nails
  • Pallor
  • Puffiness of face , eyelids
  • Peripheral edema
  • Thickening of the tongue
  • Bradycardia
  • Hypertension
  • Goiter (1ry )

15
contd
Causes
  •  

Primary hypothyroidism
Peripheral hypothyroidism
Secondary Tertiary hypothyroidism
16
Primary hypothyroidism 
  • Congenital hypothyroidism
  • Antithyroid drugs
  • Hashimotos thyroiditis
  • Postpartum hypothyroidism
  • Spontaneous hypothyroidism in Graves disease
  • Postoperative hypothyroidism
  • Hypothyroidism after radioactive iodine
  • External radiation

17
  • Secondary hypothyroidism
  • Pituitary adenoma
  • Selective thyroid-stimulating hormone deficiency
  • Tertiary hypothyroidism
  • Hypothalamic disorders
  • Peripheral hypothyroidism
  • It is due to tissue insensitive to the action of
    thyroid hormone

18
  • Investigation
  • 1) serum T4 T3 both will be low .
  • 2) serum TSH will high except in hypopituitrism .
  • 3) Thyroid antibodies like antithyroglobin are
    raised in Hashimoto's disease

19
Treatment
  • Treatment of hypothyroidism is simple. It
    involves taking daily thyroid hormone replacement
    medication. This supplies the body with thyroid
    hormone to replace what isn't being produced by
    the thyroid gland.

20
Levothyroxine
  • In active form, influences growth and maturation
    of tissues.
  • Produces stable levels of T3 and T4.
  • Administered as a single dose in the morning on
    an empty stomach.
  • May be administered PO/IV/IM.
  • Has long half-life (7-10 d), and parenteral
    dosing is rarely needed (except when PO is
    unavailable, patient is on continuous enteral
    feeds, or in emergency, such as myxedema coma).
  • Initial subtherapeutic doses are recommended to
    avoid the stress of rapid metabolic change in
    elderly patients and in those with coronary
    artery disease or severe COPD.

21
contd
  • Adult Dos
  • 1.6 mcg/kg/d PO initial dose usually 50-100
    mcg/d, higher doses may be required in pregnancy
    in elderly and those with coronary disease, start
    at 25-50 mcg/d PO, increase by 25-50 mcg/d q4-8wk
    until desired response achieved.
  • Maintenance 50-200 mcg PO qam.
  • Subclinical hypothyroidism If treated an initial
    dose of LT4 25-50 mcg/d can be used and titrated
    q6-8wk to achieve a target TSH.
  • Myxedema coma 200-250 mcg IV bolus, followed by
    100 mcg the next day and then 50 mcg/d PO or IV
    along with T3 use smaller doses in patients with
    cardiovascular disease.

22
contd
  • Pediatric Dose
  • Neonate to 6 months 25-50 mcg/d PO
  • 6-12 months 50-75 mcg/d PO
  • 1-5 years 75-100 mcg/d PO
  • 6-12 years 100-150 mcg/d PO
  • gt12years 150 mcg/d PO

23
ADR
  • weight loss
  • tremor
  • headache
  • upset stomach
  • vomiting
  • diarrhea
  • stomach cramps
  • nervousness
  • irritability
  • insomnia
  • excessive sweating
  • increased appetite
  • Fever

24
contd
  • Contraindications Documented hypersensitivity,
    uncorrected adrenal insufficiency acute MI
    uncomplicated by hypothyroidism untreated
    thyrotoxicosis
  • Interactions cholestyramine, sucralfate, iron
    may decrease absorption estrogens may decrease
    response to thyroid hormone therapy in patients
    with nonfunctioning thyroid glands.
  • Pregnancy A - Fetal risk not revealed in
    controlled studies in humans.
  • Precautions Caution in elderly patients and
    patients with renal insufficiency, hypertension,
    ischemia, angina, and other cardiovascular
    diseases periodically monitor thyroid status

25
Liothyronine
  • Synthetic form of the natural thyroid hormone T3
    converted from T4.
  • Used when a rapid effect is desired
    perioperatively or for nuclear medicine studies.
  • Not intended as sole maintenance therapy.
  • Can be used in combination with levothyroxine in
    small doses (5-15 mcg/d).

26
contd
  • Duration of activity is short (half-life is
    12-24 h) and allows for quick dosage adjustments
    in event of overdosage.
  • May be preferred when GI absorption is impaired
    or if peripheral conversion is impaired.

27
contd
  • Adult Dose
  • Initial 25 mcg/d PO in divided bid increase by
    12.5-25 mcg/d PO q1-2wk until desired response
    achievedMaintenance 50-100 mcg/d POMyxedema
    coma 10 mcg IV and repeated q8 -12h until
    patient can take PO maintenance oral dose of T4
    (see aboveElderly patients or patients with
    suspected or known coronary disease Avoid
    because of high risk of cardiovascular
    manifestations
  • Pediatric Dose
  • 5 mcg/d PO increase by 5 mcg q3d until desired
    response achieved

28
contd
  • Contraindications Documented hypersensitivity
    uncorrected adrenal insufficiency acute MI
    uncomplicated by hypothyroidism untreated
    thyrotoxicosis cardiac arrhythmias suspected or
    known coronary disease
  • Interactions as Levothyroxine
  • Pregnancy A - Fetal risk not revealed in
    controlled studies in humans
  • Precautions Caution in elderly patients and
    patients with renal insufficiency, hypertension,
    ischemia, angina, and other cardiovascular
    diseases periodically monitor thyroid status

29
Hyperthyroidism
  • The term hyperthyroidism refers to
    inappropriately elevated thyroid function.
  • Hyperthyroidism presents as a constellation of
    symptoms due to elevated levels of circulating
    thyroid hormones. Because of the many actions of
    thyroid hormone on various organ systems in the
    body, the spectrum of clinical signs produced by
    the condition is broad. The presenting symptoms
    can be subtle and nonspecific, making
    hyperthyroidism difficult to diagnose in its
    early stages without the aid of laboratory data.

30
Symptoms
  • Weight loss
  • Irritability and behavior change
  • Malaise
  • Tremor
  • Palpitation
  • Itching
  • Vomiting
  • Loss of libido
  • Sweating
  • Increased appetite
  • Restlessness
  • Muscle weakness
  • Breathlessness
  • Heat intolerance
  • Thirst
  • Diarrhea
  • Oligomenorrhea
  • Eye complaints

31
Physical finding
  • Thinning of the hair
  • Prominence of the eyes, lid lag, lid retraction
  • Diffusely enlarged goiter
  • Wide pulse pressure
  • Flushed moist skin
  • Palmer erythema

32
Causes
  • Common
  • Graves disease (autoimmune)
  • Toxic nodular goiter
  • Uncommon
  • Acute thyroiditis
  • Post-irradiation
  • Post-partum
  • Gestational thyrotoxicosis
  • Exogenous iodine
  • Drugs (amiodarone, lithium, interferon-alpha)
  • Rare
  • TSH-secreting pituitary tumors
  • Metastatic differentiated thyroid carcinoma
  • Hyperfunctioning ovarian teratoma

33
Investigation
  1. TSH usually low.
  2. FT4 elevated in more than 90 of patient.
  3. Positive thyroid antibodies confirm autoimmune
    origin of hyperthyroidism.

34
Treatment
Antithyroid drugs (thioamide)
Iodine Radioactive iodine
Surgery
Beta blocker
35
Antithyroid medications
  • Mechanism of action
  • Blocks oxidation of iodine in thyroid gland,
    thereby inhibiting thyroid hormone synthesis
  • Propylthiouracil It is more potent than
    carbimazole. It inhibits conversion of T4 to T3,
    while carbimazole does not.
  • Carbimazole
  • Methimazole It is a metabolite of carbimazole.

36
Propylthiouracil
  • DOC in severe thyrotoxicosis
  • Readily absorbed and has a serum half-life of 1-2
    h.
  • Highly protein-bound in the serum.
  • Duration of action is longer than half-life and
    should be dosed q6-8h (but can be administered
    bid).
  • If patient compliance is an issue, methimazole is
    better choice because of qd dosing.
  • Thyroid hormone levels (TSH, free T4, and T3)
    should be reassessed in 4 wk and increased if
    thyroid hormone levels have not significantly
    fallen or decreased if thyroid hormone levels
    have fallen by 50 or more .
  • Usually after thyroid function improves,
    gradually decrease the dose to 50-150 mg/d in
    divided doses (or the patient will become
    hypothyroid).

37
contd
  • Adult Dose
  • Initial dose 100-150 mg PO TID(decrease in dose
    is virtually always required in 4-8 wk when using
    this starting dose)Thyroid storm 150-200 mg PO
    q4-6h
  • Pediatric Dose
  • Neonates 5-10 mg/kg/d PO divided TID Children
    2-7 mg/kg/d PO divided TIDdose must be carefully
    monitored to prevent hypothyroidism

38
contd
  • Contraindications Documented hypersensitivity,
    known liver disease
  • Interactions Antivitamin K activity may
    potentiate activity of oral anticoagulants
  • Pregnancy B - Usually safe but benefits must
    outweigh the risks.
  • Precautions Monitor oral anticoagulant therapy
    closely caution in breastfeeding women (monitor
    infants for hypothyroidism) urticaria, pruritus,
    and arthralgias occur in 5 agranulocytosis
    aplastic anemia occurs in 0.2-0.5 severe
    hepatitis is a rare complication.

39
Methimazole
  • Inhibits thyroid hormone by blocking oxidation of
    iodine in thyroid gland. However, not known to
    inhibit peripheral conversion of thyroid hormone.
  • Readily absorbed and has serum half-life of 6-8
    h.
  • Less protein-bound than PTU and generally is not
    used in pregnancy because of increased placental
    transfer.
  • Has higher transfer rate into the milk of
    lactating women.
  • Duration of action is longer than half-life and
    should be dosed q12-24h.Usually after thyroid
    function improves, dose must be decreased or
    patient will become hypothyroid.

40
contd
  • Adult Dose
  • Initial dose 20-40 mg/d PO or PR (suppository
    or retention enema) qd or divided bidUsual
    maintenance dose 2.5-15 mg/d PO or PR
    (suppository or retention enema)
  • Pediatric Dose
  • 0.2 mg/kg/d PO

41
contd
  • Contraindications
  • Documented hypersensitivity breastfeeding
    women known liver disease
  • Interactions
  • Inhibits vitamin K activity and may potentiate
    activity of oral anticoagulants toxicity
    increased with coadministration of lithium and
    potassium iodide
  • Pregnancy
  • D - Unsafe in pregnancy
  • Precautions
  • Monitor oral anticoagulant therapy closely
    caution in breastfeeding women (monitor infants
    for hypothyroidism) urticaria, pruritus, and
    arthralgias occur in 5 agranulocytosis occurs
    in 0.2-0.5

42
Iodine
  • In severe thyrotoxicosis from Graves disease or
    subacute thyroiditis, iodine or iodinated
    contrast agents have been administered to block
    T4 conversion to T3 and the release of thyroid
    hormone from the gland. This therapy is reserved
    for severe thyrotoxicosis because its use
    prevents definitive therapy of Graves
    thyrotoxicosis with radioactive iodine for many
    weeks. Either a saturated solution of potassium
    iodide (SSKI) at 10 gtt twice daily or iopanoic
    acid/ipodate (1 g/d) can be administered with
    rapid reduction in T3 levels.
  • Preoperative preparation iodine treatment (to
    decrease gland vascularity), An additional
    benefit from stable iodide therapy, besides the
    reduction in thyroid hormone excretion, is a
    demonstrated decrease in thyroid blood flow and
    possible reduction in blood loss during surgery.

43
Radioactive iodine therapy Sodium iodide I-131
(Iodotope)
  • the most common treatment of hyperthyroidism in
    adults in the US.
  • it is effective, safe, and does not require
    hospitalization. It is administered orally as a
    single dose, in capsule or liquid form.
  • The patient is given a capsule or a drink of
    water containing radioactive iodine. After being
    swallowed, the "radioiodine" is rapidly absorbed
    by the overactive thyroid cells No other tissue
    or organ in the body is capable of retaining
    radioactive iodine therefore, few adverse
    effects develop. and over a period of several
    weeks, the radioactive iodine damages the cells.
  • The result is the thyroid shrinks in size,
    thyroid production falls and blood levels return
    to normal. The radioactivity disappears from the
    body within a few days. Hyperthyroidism can
    reoccur from several months to many years after
    this therapy

44
contd
  • Adult Dose 75-200 µCi/g of thyroid multiplied by
    estimated thyroid gland size/24-h radioiodine
    uptake
  • Pediatric Dose Not established
  • Contraindications Documented hypersensitivity
    pregnant or breastfeeding women
  • Interactions Coadministration with lithium may
    result in hypothyroid effects
  • Pregnancy X - Contraindicated in pregnancy
  • Precautions Discontinue antithyroid therapy for
    3-4 d before administration not usually
    administered to patients with severe
    ophthalmopathy because good clinical evidence
    indicates that usually mild, but occasionally
    severe, worsening of thyroid eye disease occurs
    after radioactive iodine therapy

45
Beta-adrenergic receptor blockers
  • Reduce many of the symptoms of thyrotoxicosis,
    including tachycardia, tremor, and anxiety.
  • Usually propranolol 20-80 mg PO TID is
    recommended because of CNS penetration.
  • Calcium channel blockers for tachycardia
    sometimes are used when beta-blockers are
    contraindicated or not tolerated.

46
Surgery
  • Because of excellent effectiveness in regulating
    thyroid function with antithyroid medications and
    radioactive iodine, thyroidectomy is reserved for
    special circumstances, including the following
  • Severe hyperthyroidism in children
  • Pregnant women who are noncompliant or intolerant
    of antithyroid medication
  • Patients with very large goiters or severe
    ophthalmopathy
  • Patients who refuse radioactive iodine therapy
  • Refractory amiodarone-induced hyperthyroidism
  • Patients who require normalization of thyroid
    functions quickly, such as pregnant women, women
    who desire pregnancy in the next 6 months, or
    patients with unstable cardiac conditions

47
  • Case study

48
Case study
  • AM is a 40 years old female came to endocrine
    clinic on 18/03/2008 for follow up, she is a
    known case of hypothyroidism, she was
    thyrotoxicosis took radioactve iodine then, she
    became hypothyroidism.
  • She was complained of malaise, palpitation,
    general weakness slight wt loss.
  • She diagnosed with Microcytic Hypochromic Anemia
    in this visit.

49
contd
  • Past medical history (PMH)
  • Hypothyroidism for 4 years
  • Hyperlipidemia for 2 years
  • Family history (FH)
  • Unremarkable
  • Social history (SH)
  • Married , non-smoker
  • Current medication
  • Thyroxine 150 mcg QD
  • Simvastatin 20 mg QD

50
Objective
  • Vital signs
  • Temp. 37C
  • RR.15\min,
  • BP.129\65 mmHg
  • HR.75 bpm
  • Calculation
  • IBW 47.8 kg
  • ABW 66 kg
  • Pt. 37.5 over wt

51
contd
  • Lab report

Reference range Result Test name
0.27 - 4.2 ulU/L 0.012 L TSH
2.8 - 22 pmol/L 2.96 FT3
12 - 22 pmol/L 28.90 H FT4
3.9 6.7 mmol/L 6.5 Glucose, random
0 5.20 mmol/L 4.53 Cholesterol
0.30 2.30 mmol/L 0.58 TGL
0.9 1.55 mmol/L 1.05 HDL
0 3.57 mmol/l 3.13 LDL
12 15 g/dl 10.5 L Hb
80 94 fL 75 MCV
52
contd
  • Problem list
  • Hypothyroidism
  • Hyperlipidemia
  • Microcytic Hypochromic Anemia

53
Plan
  • Decrease Thyroxine dose to 125 mcg QD
  • Simvastatin 20 mg QD

54
Assessment
  • FOR HYPOTHYRODISM
  • continue on same drug L-thyroxin 125 mcg QD,
    regular monitor of TSH,T3 T4 every 2-3 months
    to check the efficacy of the drug.
  • Be aware about some drugs that may increase or
    decrease thyroid function test like (iodine,
    amiodarone, lithium, glucocorticoid, estrogen
    androgen)
  • PATIENT EDUCATION
  • This drug must be taken in the morning on empty
    stomach, avoid food for at least 1hr after taking
    this drug.
  • Other drugs that patient use must be taken after
    4-6 hrs of thyroxine, because many drugs can
    affect thyroxine absorption like calcium
    carbonate, ferrous sulfate, cholestyramine,
    sucralfate and aluminum hydroxide. Other drugs
    increase thyroxine clearance like estrogen,
    rifampin, carbamazepine phenytion.

55
contd
  • For hyperlipidemia
  • Because of normal level of lipid profile patient
    can continue on the same medication.
  • Monitor for liver enzyme CPK.
  • PATIENT EDUCATION
  • This drug recommended to be taken at night before
    sleeping
  • We should tell the patient this drug may cause
    muscle pain if it occurred she must tell her
    physician also may cause GIT upset.

56
contd
  • For Anemia
  • First should identify the cause, then
  • Instruct the patient about diet saturated with
    iron like liver, honey other
  • If patient still anemic should be giving iron
    supplement take with food

57
...contd
  • Risk of DM
  • Random blood sugar for this pt. was at boarder
    line so, Should educate patient about Life style
    modification, which is include
  • Reduced total calorie intake and avoid or
    decrease the food saturated with fat and sugar.
  • Increase physical activity, wt reduction and
    maintain regular exercise.
  • Regular check for blood sugar

58
Recommendation
  • We need more investigation to know the cause of
    cause of anemia iron store in the body.
  • Usual starting dose of Zocor for hyperlipiedmia
    is 40 mg QD.

59
Take home point
  • Hypothyroidism hyperthyroidisms are common
    endocrine problem that affect 15 of women 5
    of men.
  • Thyroid function tests are essential to detect,
    evaluate monitor thyroid disease.
  • Practitioner should be alert to drugs that cause
    thyroid illness.

60
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61
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