AMBULATORY CARE CLERKSHIP

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AMBULATORY CARE CLERKSHIP

• SUPERVISED BY
• DR. HALA AL-KALIDI

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Thyroid disorders
DONE BY AMAL ALZAHRANI, Pharm.D. Candidate
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Outline

• Thyroid Hormone regulation
• Hypothyroidism
• Hyperthyroidism
• Case Study

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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.

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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.

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• 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.

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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.

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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.

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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.

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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.

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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.

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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.

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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)

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Physical finding

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

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contd
Causes

•  

Primary hypothyroidism
Peripheral hypothyroidism
Secondary Tertiary hypothyroidism
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Primary hypothyroidism 

• Congenital hypothyroidism
• Antithyroid drugs
• Hashimotos thyroiditis
• Postpartum hypothyroidism
• Spontaneous hypothyroidism in Graves disease
• Postoperative hypothyroidism
• Hypothyroidism after radioactive iodine
• External radiation

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• 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

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• 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

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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.

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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.

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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.

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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

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ADR

• weight loss
• tremor
• headache
• upset stomach
• vomiting
• diarrhea
• stomach cramps

• nervousness
• irritability
• insomnia
• excessive sweating
• increased appetite
• Fever

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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

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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).

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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.

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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

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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

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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.

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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

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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

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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

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Investigation

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

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Treatment
Antithyroid drugs (thioamide)
Iodine Radioactive iodine
Surgery
Beta blocker
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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.

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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).

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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

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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.

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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.

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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

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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

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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.

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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

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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

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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.

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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

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• Case study

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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.

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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

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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

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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
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contd

• Problem list
• Hypothyroidism
• Hyperlipidemia
• Microcytic Hypochromic Anemia

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Plan

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

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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.

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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.

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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

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...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

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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.

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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.

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