APH2016

Human Systems and

Pharmacotherapy 2

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 TOPIC 4

Endocrine System

Part 3
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 Learning Outcomes

At the end of this topic, students should be able to:

1. Explain the anatomy and physiology of the endocrine
system and its functions.
2. Recommend appropriate treatment for common conditions
in the endocrine system.
3. Dispense medications for the endocrine system.
4. Address enquiries using relevant drug information
resources related to the endocrine system.

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 Medical Condition of the
Endocrine System
 Diabetes Mellitus
 Thyroid Disorders
 Menstrual disorders

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 Thyroid Disorders

 “thyroid disorders” -- a variety of disease states affecting thyroid

hormone production AND/OR secretion
 Hypothyroidism – result of decreased thyroid hormone
production
 Hyperthyroidism -- result of increased thyroid hormone
production
 Most common cause of hyperthyroidism is Graves’ disease
 Graves’ disease is named after a doctor called Robert Graves, and
does not mean that your condition is grave or very serious
 Graves’ disease affects women five times more commonly than
men
 Hyperthyroidism is hereditary
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 Singapore Statistics

 No official data on the prevalence of thyroid disorders

 Estimated that 2% to 5% percent of the population has some
form of clinically significant thyroid disorder

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 Physiology

 Thyroid hormones are produced

released by the thyroid gland
 Triiodothyronine (T3)
 Thyroxine (T4)

 T4 and T3 are released into the

bloodstream via proteolysis within the
thyroid cells

 Low levels of thyroid hormone in the

blood stimulate thyrotropin-releasing
hormone (TRH) from hypothalamus to
release thyroid-stimulating hormone
(TSH) from the pituitary [thyroid physiology] Retrieved 09 Nov 2015 from https: //www.myhousecallm
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content/uploads/2010/08/Picture-112.png
 Physiology

 Iodide is a necessary element in the synthesis process

 Inorganic iodide enters thyroid cell and is oxidized by thyroid
peroxidase and bound to thyroglobulin
 2 presentation of iodinated tyrosine residues :
 monoiodotyrosine (MIT) and diiodotyrosine (DIT)
 Couple / combine, resulting in production of T4, T3 or reverse T3
 T4 and T3 released from thyroid into bloodstream

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Physiology

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 Physiology

 Thyroxine (T4)
 Highly protein bound (99.97%)
 Accounts for the long half-life of 7 days
 Only the unbound (free) thyroid hormone is able to diffuse into
the cell, to elicit a biological effect.

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 Physiology

 Triiodothyronine (T3)
 4-5 times more potent/active than T4
 Present at lower concentration in the body
 Most T3 (~80%) derived from deiodination of T4 peripherally
 Reverse T3 – no significant biologic activity
 Less strongly bound to proteins (99.7%)
 Accounts for its shorter half-life of 1.5 days

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 Physiology

 Functions of thyroid hormone : involvement in body

metabolism, growth, and development.

 Vital role in :
 Breathing and heart rate
 Central and peripheral nervous systems
 Body weight
 Muscle strength
 Body temperature

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 Thyroid Disorders

 Hypothyroidism
 Hyperthyroidism

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 Pathophysiology

 Primary hypothyroidism
 A result of thyroid gland failure
 Vast majority of hypothyroidism cases

 Secondary hypothyroidism
 Pituitary failure due to pituitary tumours, surgical therapy and other
autoimmune mechanisms
 Less common

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 Causes

Primary hypothyroidism
 Chronic autoimmune thyroiditis (Hashimoto’s disease)
 Iodine deficiency or radioactive iodine therapy
 X-ray therapy
 Enzyme defects
 Drug induced (e.g. iodides and iodine-containing preparations, lithium,
sulphonyureas, rifampicin, amiodarone)

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 Causes

Secondary hypothyroidism
 Surgery
 Radiation
 Pituitary damage
 Tumours
 Tuberculosis
 Autoimmune disease

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 Risk factors

 Female
 Family history of thyroid disease
 Autoimmune disease, such as type 1 diabetes or celiac
disease
 Received treatment for hyperthyroidism
 Received radiation to the neck or upper chest
 Have had thyroid surgery

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 Symptoms

Symptoms generally result from the cause of low metabolism :

 Cold intolerance
 Dry skin
 Weight gain
 Memory problems
 Constipation
 Fatigue
 Loss of energy
 Growth retardation (dwarfism in children)
 Coarse skin/hair and periorbital puffiness
Patients with secondary hypothyroidism may also have symptoms of
generalised pituitary insufficiency such as abnormal menses
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 Diagnosis

 Based on symptoms
 Blood tests that measure the
 Level of TSH
 Thyroxine

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 Treatment Goals

 Normalise plasma/serum thyroid level

 Minimise symptoms and long term consequences

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 Pharmacology of Drugs

 Thyroid hormone
 Levothyroxine or L-thyroxine

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 Pharmacotherapy

 Treated with thyroid hormone replacement therapy

 Use of thyroxine is brand specific
 Individualised dosage based on the blood test readings of T4
and TSH levels.
 Follow-up blood tests may only need to be done once,
annually, subject to the doctor's discretion as it is usually
stable for life (except during pregnancy).

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 Thyroid Hormone

 Levothyroxine (brand name is Euthyrox or Eltroxin)

 Also known as T4
 Synthetic form of thyroxine

MOA
 Mimic endogenous T4 function which readily
converts to T3 (biologically active form)

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 Thyroid Hormone

Usual dosing
 Individualise dosage based on patient's clinical response,
laboratory parameters, age, weight, CV status, concurrent
conditions or medications, and nature of disease being
treated.
 Initially, 50-100 mcg daily, may increase by 25-50 mcg at
approx 3- to 4-week intervals until thyroid deficiency is
corrected and maintenance dose is established.
 Usual maintenance: 100-200 mcg daily.

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 Thyroid Hormone

Contraindication
 Hypersensitivity to the active ingredient or any component
of the formulation

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 Thyroid Hormone

Common side effect

 Minimal side effects as drug is replacing endogenous thyroxine
 If daily dose is exceeded (symptoms disappear when dose is
stopped or reduced)
 Headache
 Nervousness
 Sweating
 Increased appetite
 Diarrhea
 Weight loss
 Insomnia

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 Thyroid Hormone

Drug drug interactions

 Iron
 Calcium Space apart 30mins to 2hrs
 Drugs that affect the absorption of levothyroxine (will adjust
the dose accordingly)

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 Thyroid Hormone

Additional notes
 Chemically stable and inexpensive
 Suitable for pregnancy
 Long T1/2 allow ease of regimen flexibility i.e. once a day
dosing (ease in monitoring)
 Some patients might have differing dose per day, to make
sure patient understands how to take the medication

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 Thyroid Hormone

Special Counselling Points

 Take as a single daily dose on an empty stomach at least 30 minutes
before the first food or beverage of the day
 Swallow with at least ½ a cup of plain water
 Take it at the same time every day
 Take 2 hrs apart from antacids, calcium or iron supplements, aluminium-
containing drugs, high calcium products and milk or dairy products
 Some improvement should be evident after 3 to 4 weeks
 Do not stop the medicine by oneself
 Regular blood test will be ordered by your doctor for monitoring for
blood levels and dose adjustment
 Stick to the same brand of medication as much as possible
 Remember to inform any doctor or dentist that you are on this medication
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 Thyroid Hormone

Monitoring parameters, to see doctor if these symptoms occur

 Allergy symptoms
 Chest pain
 Rapid or irregular heartbeat
 Shortness of breath
 Excessive sweating
 Seizures

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 Pathophysiology

 Hyperthyroidism
 Tumours at pituitary gland release biologically active
TSH that is unresponsive to normal feedback control
 Autoimmune disease (Graves disease).
 Thyroid-stimulating antibodies (TSAb) direct against thyrotropin
receptor.
 Receptor recognised these antibodies like TSH , resulting in continuous
production of T4
 Drug induced (e.g. amiodarone, anti-cancer drugs)

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 Causes

 Graves’ disease
 Toxic multinodular goiter
 Toxic nodule
 Excessive iodine ingestion

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 Risk factors

 Family history of thyroid disease, particularly Graves'

disease
 Chronic illnesses, including pernicious anemia and primary
adrenal insufficiency
 Recent pregnancy, which raises the risk of developing
thyroiditis.

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 Symptoms

Symptoms generally result from the cause of high metabolism :

 Nervousness
 Anxiety
 Palpitations (due to inc in beta-1)
 Easy fatigability
 Heat intolerance
 Loss of weight concurrent with increased appetite
 Irregular menses in women
 Warm moist skin

Graves disease in particular, is commonly presented with exophthalmos

(protruding eyeballs)
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 Diagnosis

 Medical history and physical exam

 Blood tests that measure the
 Level of TSH
 Thyroxine
 Radioiodine uptake test
 Thyroid scan
 Thyroid ultrasound

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 Complications

 Heart problems (e.g. atrial fibrillation, congestive heart

failure)
 Eye problems (e.g. sensitivity to light, and blurring or
double vision)
 Red, swollen skin
 Brittle bones
 Thyrotoxicosis crisis

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 Complications

Thyrotoxicosis crisis
 Rare
 May result in coma, heart failure, or death.
 Symptoms:
 Rapid heartbeat (palpitations)
 Greatly increased body temperature
 Shortness of breath
 Disorientation
 Increased sweating

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 Treatment Goals

 Normalise plasma/serum thyroid level

 Minimise symptoms and long term consequences

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 Pharmacology of Drugs

 Thiourea (thionamide)
 Iodide*
 Beta blocker
 Radioactive iodine*

*for your information

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 Pharmacotherapy

 Treated in three main ways

 Medication
*Radioactive iodine therapy (RAI)
 *Surgery

 All three forms of treatment are able to decrease thyroid

hormone production by the thyroid gland.
 *RAI is the most widely recommended permanent treatment
of hyperthyroidism.

*for your information

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 Thiourea (Thionamide)

 Propylthiouracil (can also be written as PTU)

 Carbimazole

MOA
 Block thyroid hormone synthesis by inhibiting the
peroxidase enzyme system of thyroid gland  preventing
oxidation of trapped iodide
 Inhibit coupling of MIT and DIT to T4 and T3
 Inhibit peripheral conversion of T4 to T3 (only for PTU)

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 Thiourea (Thionamide)

Usual dosing
 Propylthiouracil
 Initial: 300 to 600 mg daily in 3 equally divided doses (~8-hour
intervals); 400 mg daily in patients with severe hyperthyroidism
and/or very large goiters; an occasional patient will require 600 to
900 mg daily;
 Usual maintenance: 50 to 150 mg daily in 3 equally divided doses
 Adjust dosage as required to achieve and maintain serum T3, T4,
and TSH levels in the normal range.

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 Thiourea (Thionamide)

Usual dosing
 Carbimazole
 Initial: 20 to 60 mg/day given in 1 to 3 divided doses until patient is
euthyroid
 Some experts initiate at a dose of 10 to 20 mg/day if the baseline
free thyroxine (FT4) level is <30 pmol/L, and at 40 mg/day if the
baseline FT4 level is >40 pmol/L (Abraham 2010)
 Usual maintenance dose: 5 to 15 mg once daily; adjust dose as
needed to maintain euthyroid state.
 Duration
 For Graves disease, continue for 12 to 18 months, then assess for
remission
 For toxic multinodular goiter/toxic adenoma, continue indefinitely
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 Thiourea (Thionamide)

Contraindication
 Hypersensitivity to the active ingredient or any component
of the formulation
 Pregnancy (only for carbimazole)

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 Thiourea (Thionamide)

Common side effects

 Stomach discomfort
 Nausea
 Change in taste
 Headache
 Muscle and joint pain

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 Thiourea (Thionamide)

Rare side effects

 Agranulocytosis
 Symptoms include fever, malaise, sore throat, gingivitis and low
granulocyte count
 If it occurs, it is usually during the first 3 months
 Hepatotoxicity
 Hair thinning
 Muscle disorder
 Skin rashes and itchness

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 Thiourea (Thionamide)

Drug drug interactions

 Theophylline
 Prednisolone (only carbimazole)
 Erythromycin (only carbimazole)

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 Thiourea (Thionamide)

Additional notes
 Slow in onset
 Hyperthyroid symptoms will continue for 4-6 weeks after
beginning thioamide therapy
 Initial treatment with beta-blockers or iodides may be
required for symptomatic relief
 Improvement in symptoms and lab parameters should be
seen in 4 to 8 weeks
 Usually not given long term but hyperthyroidism often
comes back after they are stopped
 Propylthiouracil is safe in pregnancy
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 Thiourea (Thionamide)

Special Counselling Points

 Take with food.
 Side effects usually occur in first 8 weeks
 Seek medical attention if experiencing muscle aches or pains, yellowing
of skin or whites of eyes, dark coloured urine, high fever or sore throat
 Full beneficial effects should be seen in 4-8 weeks
 Might be prescribed with beta-blockers or iodides for symptomatic relief
 Regular blood test to check your response to the medication
 Treatment is usually long term
 Do inform the doctor immediately if you are pregnant

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 Thiourea (Thionamide)

Monitoring parameters, to see doctor if these symptoms occur

 Allergy symptoms
 Any infection, especially a sore throat, mouth ulcers or high
fever during treatment
 Muscle aches or pains
 Yellowing of skin or whites of eyes
 Dark coloured urine
 Skin rashes and itch

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 Beta Blockers

 Propranolol
 Atenolol

MOA
 To antagonise beta-receptor mediated effects like
palpitations, anxiety, tremor, and heat intolerance. (they do
not alter synthesis or secretion of thyroid hormone by the
thyroid gland)
 Non-selective beta blockers like propranolol can impair the
conversion of T4 to T3
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 Beta Blockers

Usual dosing
 Propranolol
 For control of cardiovascular effects until euthyroidism established.
 Oral: Initial: 30 to 160 mg/day in 1 to 4 divided doses adjusted for
heart rate and blood pressure

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 Beta Blockers

Usual dosing
 Atenolol
 For control of adrenergic symptoms until euthyroidism is
established
 Oral: Initial: 25 to 50 mg once daily; titrate as needed to control
symptoms (eg, tachycardia, palpitations, tremulousness) up to a
maximum of 200 mg/day in 2 divided doses.
 Doses ≥50 mg/day can be administered in 2 divided doses if
adrenergic symptoms become noticeable toward the end of the
dosing interval with once daily dosing

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 Beta Blockers

 To refer to hypertension on beta blockers on the rest.

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 Beta Blockers

Additional notes
 Used in thyroid storm to blunt the widespread sympathetic
stimulation that occurs in hyperthyroidism
 Prescribed together with thioamides to help with the
symptom relief only (will not affect the thyroxine levels)
 May be prescribed to be used when necessary so be mindful
on how the doctor prescribes

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 Referral to doctor

 When hypothyroidism or hyperthyroidism does not improve

 Adverse effects of thyroid disorder medications

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