Thyroid Disorders

BY: Zenebe N.
May, 2022
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 Learning Objectives
Upon completion of the chapter, the students will be able to:
Discuss the prevalence of common thyroid disorders
Discuss the relationship between serum TSH levels and primary thyroid
disease, and the advantages for use of TSH levels over other tests such as
serum T4 and T3 levels.
Identify typical signs and symptoms of hypothyroidism/ hyperthyroidism
Describe the management of hypothyroidism/ hyperthyroidism
Discuss the pharmacotherapy of hypothyroidism/ hyperthyroidism,
including advantages and disadvantages of antithyroid drugs versus
radioactive iodine, adverse effects, and patient monitoring.

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 Introduction
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 Thyroid gland (largest endocrine gland) is a

butterfly-shaped gland in the middle of the neck
(16-60 gm).
 Thyroid disorders encompass a variety of dx
states affecting thyroid hormone production or
secretion
 Hyperthyroidism & hypothyroidism are the
clinical & biochemical syndromes of thyroid dx.
Thyroid hormones affect function of every organ system
• Critical for proper fetal growth and development, particularly of
CNS
• Major role is to maintain metabolic stability in adult
Common thyroid disorders
• Globally, more than 2 billion (38%) individuals have inadequate
iodine nutrition, resulting in 74 million people with goiters.

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Thyroid hormone physiology
• Thyroid hormones (T4 and T3) are formed within
thyroglobulin(TG), a large protein produced by follicular cells of
thyroid gland.
• Inorganic iodide enters thyroid follicular cell and is oxidized by
thyroid peroxidase and covalently bound (organified) to tyrosine
residues of thyroglobulin
• Iodinated tyrosine residues monoiodotyrosine (MIT) and
diiodotyrosine (DIT) combine to form iodothyronine(T3) in reactions
catalysed by thyroid peroxidase.

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Cont……
• Thus, two molecules of DIT combine to form T4, and MIT and
DIT join to form T3.
• Proteolysis within thyroid cells releases thyroid hormone
into bloodstream.

• T4 is 99.97% protein bound, and T3 is 99.7% protein bound,

with only unbound or free fractions physiologically active
• And this regulate TSH secretion from pituitary
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Cont.….
• T3 is five times more active than T4.
Two regulations
• Thyroid hormone production is regulated by TSH secreted by
anterior pituitary, which in turn is under negative feedback control by
circulating level of free thyroid hormone and positive influence of
TRH.
• Thyroid hormone production is also regulated by extrathyroidal
deiodination of T4 to T3, which can be affected by nutrition, non-
thyroidal hormones, drugs, and illness
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 Hyperthyroidism
• Hyperthyroidism is excessive thyroid hormone (T4, T3, or both) secretion in
the body.
• Thyrotoxicosis is any syndrome caused by excess thyroid hormone
secretion
• TSH-secreting pituitary tumors release biologically active hormone that is
unresponsive to normal feedback control.
• The tumors may co-secrete prolactin or growth hormone; patients may
present with amenorrhea, galactorrhea, or signs of acromegaly
• Graves’ disease is the most common cause of hyperthyroidism

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Etiology

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Clinical presentation
• Signs and symptoms of hyperthyroidism affect multiple organ
systems.

• Patients may have symptoms for an extended time period

before diagnosis of hyperthyroidism is made.

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 Symptoms of thyrotoxicosis include:

Nervousness, anxiety, palpitations, emotional lability, easy fatigability,

heat intolerance, weight loss concurrent with increased appetite

Increased frequency of bowel movements, proximal muscle weakness

(noted on climbing stairs or arising from a sitting position), and irregular
menses in women.

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 Physical signs include:

Warm, smooth, moist skin and unusually fine hair;

Separation of ends of the fingernails from nail beds (onycholysis);
Retraction of the eyelids and lagging of the upper lid behind the globe
upon downward gaze (lid lag);
Tachycardia at rest, widened pulse pressure, and systolic ejection
murmur;
Occasional gynecomastia in men;
Fine tremor of the protruded tongue and outstretched hands;
Hyperactive deep tendon reflexes.
Thyromegaly is usually present.

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 Graves’ disease
Manifested by hyperthyroidism, diffuse thyroid enlargement, and
extrathyroidal findings of exophthalmos, pretibial myxedema, and
thyroid acropachy.
 Subacute thyroiditis,
Patients have severe pain in the thyroid region, which often extends to
the ear.
Systemic symptoms include fever, malaise, myalgia, and signs and
symptoms of thyrotoxicosis.
The thyroid gland is firm and exquisitely tender on physical
examination.
 Painless thyroiditis:
Most patients present with mild thyrotoxic symptoms; lid retraction and
lid lag are present, but exophthalmos is absent.
The thyroid gland may be diffusely enlarged without tenderness.
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Exophthalmos

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Goiter

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Thyroid storm
• Thyroid storm is a life-threatening medical emergency characterized
by severe thyrotoxicosis, high fever(>39.4°C), tachycardia, tachypnea,
dehydration, coma, nausea, vomiting, and diarrhea.

• Precipitating factors include infection, trauma, surgery, radioactive iodine

(RAI) treatment & withdrawal from anti-thyroid drugs.

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Diagnosis
• Low TSH serum concentration
• because pituitary gland try to compensate for excess T3 and T4
hormones in the blood

• Low TSH level (<0.5 M.U/L) will signify thyrotoxicosis.

• Elevated free and total T3 and T4 serum concentrations, particularly in

more severe disease.
• Thyroid stimulating antibodies (TSAb)
• Thyroglobulin
• Thyrotropin receptor antibodies
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 Treatment
Desired outcome

Normalize production of thyroid hormone;

Minimize symptoms and long term consequences; and

To provide individualized therapy based on the type and severity of

disease, patient age and gender, existence of nonthyroidal conditions, and
response to previous therapy.

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 Treatment
Non-Pharmacologic Therapy
Surgical removal of thyroid gland should be considered in
patients with:
Large gland (>80 g)

Severe ophthalmopathy (also known as thyroid eye disease

(TED)

A lack of remission on anti-thyroid drug treatment

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 Cont.…
• In addition to surgery, the solitary nodule, whether hot or cold, can be
treated with percutaneous ethanol injection therapy.
• For hot nodules, radioiodine is the therapy of choice.
• If thyroidectomy is planned, propylthiouracil (PTU) or methimazole is
usually given until patient is biochemically euthyroid (usually 6–8
weeks), followed by addition of iodides (500 mg/day) for 1–14 days
before surgery to decrease vascularity of gland.
• Propranolol has been used for several weeks preoperatively and 7–10 days
after surgery to maintain pulse rate <90 beats/min.
• Combined pretreatment with propranolol and 10–14 days of KI also has
been advocated.

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Pharmacologic Therapy
THIOUREAS (THIONAMIDES)
PTU, Carbimazole and methimazole block thyroid hormone synthesis
by inhibiting peroxidase enzyme

Preventing oxidation of trapped iodide and subsequent incorporation

into iodotyrosines and ultimately iodothyronine (“organification”); and

by inhibiting coupling of MIT and DIT to form T4 and T3.

 PTU (but not methimazole) also inhibits peripheral conversion of T4 to T3.

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Usual initial doses include:
• PTU 300 to 600 mg daily (usually in three or four divided doses)
• Methimazole 30 to 60 mg daily given in three divided doses.
Improvement in symptoms and laboratory abnormalities should occur
within 4 to 8 weeks, at which time a tapering regimen to maintenance
doses can be started
• Typical daily maintenance doses are methimazole 5–30 mg and PTU
50–300 mg.

• The patient should remain on continuous anti-thyroid drug therapy for

12 to 24 months.
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 Propylthiouracil (PTU)
• Initial dose: 300-400mg/day in 3 divided doses
• Maximum dose: 900mg/day
• Maintenance dose: 100-200mg/day
 Carbimazole
• Initial dose: 30-40mg/day divided in 2-3 doses
• Maximum dose: 60mg/day
• Maintenance dose: 5-15mg/day
Titrated down the dose based on thyroid function tests
Monitor patients every 6–12 months after remission.

If a relapse occurs, alternate therapy with RAI is preferred over a second
course of antithyroid drugs, because subsequent courses are less likely to
induce remission.
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Minor adverse reactions include
 Pruritic maculopapular rashes, arthralgias, fever, and benign
transient leukopenia (WBC count <4000/mm3 or 4 × 109/L).

Major adverse effects include

• Agranulocytosis (with fever, malaise, gingivitis, Aplastic
anemia
• lupus-like syndrome and polymyositis (inflammatory myopathy)
• GI intolerance
• Hepatotoxicity (occurring in 0.1% to 0.2% of patients)
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IODIDES
 Iodide acutely blocks thyroid hormone release, inhibits thyroid
hormone biosynthesis by interfering with intra-thyroidal iodide use,
and decreases size and vascularity of the gland.
KI a stable form of iodine that blocks uptake of iodine into
the thyroid gland

 Symptom improvement occurs within 2 to 7 days of initiating

therapy, and serum T4 and T3 concentrations may be reduced for a
few weeks.
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Potassium iodide is available as
A saturated solution (SSKI, 38 mg iodide per drop) or

As Lugol’s solution, containing 6.3 mg of iodide per drop

It works by shrinking the size of the thyroid gland and by decreasing the
amount of thyroid hormones the body makes.

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Adverse effects include
 Hypersensitivity reactions (skin rashes, drug fever, rhinitis, conjunctivitis);

 Salivary gland swelling;

 “Iodism” (metallic taste, burning mouth and throat, sore teeth and
sometimes stomach upset and diarrhea)

 Gynecomastia

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Adrenergic Blockers
Ameliorate thyrotoxic symptoms such as palpitations, anxiety,
tremor, and heat intolerance

They have no effect on peripheral thyrotoxicosis

Propranolol and nadolol partially block the conversion of T4 to T3,

but this contribution to the overall therapeutic effect is small

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Beta blockers: for symptom control until thyroid state is
achieved.
• Propranolol, 20-40mg, PO every 8-12 hours
OR
• Atenolol 25-100mg, PO, daily
OR
• Metoprolol 25-100mg, PO, daily or in two divided doses

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Beta-Adrenergic Receptor Blockade in the Treatment of Thyrotoxicosis

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 Radioactive Iodine
Sodium iodide–131 is an oral liquid that concentrates in the thyroid and initially
disrupts hormone synthesis by incorporating into thyroid hormones and thyroglobulin.
Choice for Graves’ disease, toxic autonomous nodules, toxic multinodular goiters.
β-Blockers are the primary adjunctive therapy
If iodides are administered, they should be given 3–7 days after RAI to prevent
interference with uptake of RAI in the thyroid gland.
Use of lithium as adjunctive therapy to RAI has benefits of increased cure rate,
shortened time to cure, and prevention of posttherapy increases in thyroid hormone
levels.
A single dose of 4000–8000 rad results in a euthyroid state in 60% of patients at 6
months or sooner.
A second dose of RAI should be given 6 months after the first RAI treatment if the
patient remains hyperthyroid.
Hypothyroidism commonly occurs months to years after RAI.
The acute, shortterm side effects include mild thyroidal tenderness and dysphagia.
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Treatment of Thyroid Storm
Initiate the following therapeutic measures promptly:
1. suppression of thyroid hormone formation and secretion,
2. antiadrenergic therapy,
3. administration of corticosteroids, and
4. treatment of associated complications or coexisting factors that may
have precipitated the storm.
• PTU in large doses may be the preferred thionamide because it blocks
peripheral conversion of T4 to T3 in addition to interfering with thyroid
hormone production.
• However, β-blockers and corticosteroids serve the same purpose.
• Methimazole has a longer duration of action, which offers a theoretical
advantage.
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Iodides, which rapidly block the release of preformed thyroid hormone,
should be administered after a thionamide is initiated to inhibit iodide
utilization by the overactive gland.
General supportive measures,
Acetaminophen as an antipyretic (avoid aspirin or other nonsteroidal anti-
inflammatory drugs, which may displace bound thyroid hormone),
Fluid and electrolyte replacement, sedatives, digoxin, antiarrhythmics,
insulin, and antibiotics should be given as indicated.

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Drug Dosages Used in the Management of Thyroid Storm

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Hypothyroidism

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 Pathophysiology
• The vast majority of hypothyroid pts have thyroid gland failure
(primary hypothyroidism).
• The causes include chronic autoimmune thyroiditis (Hashimoto’s dx),
iatrogenic hypothyroidism, enzyme defects, thyroid hypoplasia and ingestion of
goitrogens
 Iodine deficiency is the most common cause of primary hypothyroidism in
developing countries

• Pituitary failure (20 hypothyroidism) is an uncommon cause resulting from

 Pituitary tumors,
 Surgical therapy,
 External pituitary radiation,
 Postpartum pituitary necrosis (sheehan syndrome),
 Trauma, and
 Infiltrative processes of the pituitary (eg, metastatic tumors, tuberculosis) 41
 Clinical Presentation
 Adult manifestations of hypothyroidism include dry skin, cold intolerance,
weight gain, constipation, weakness, fatigue, muscle cramps, myalgia,
stiffness, and loss of ambition or energy, muscle cramps, myalgia, and
stiffness.
 Menorrhagia and infertility are common in women.
 In children, thyroid hormone deficiency may manifest as
 growth retardation.
 Physical signs include coarse skin and hair, cold or dry skin, periorbital
puffiness, bradycardia, and slowed or hoarse speech.

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Myxedema coma

• Is a rare consequence of hypothyroidism manifested by hypothermia,

advanced stages of hypothyroid symptoms & altered sensorium ranging
from delirium to coma.

• Mortality rates of 60%–70% necessitate immediate and aggressive

therapy.

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 Diagnosis
• A rise in TSH level is first evidence of primary hypothyroidism

• Many patients have a free T4 level within normal range

• Mild(subclinical hypothyroidism) is present when a patient has an

elevated TSH (usually below 10 mIU/L)

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 Diagnosis
TSH is the best screening test
o TSH >20 micro unit/ml: highly suggestive primary hypothyroidism
o Mildly elevated TSH (<20microunits/ml): needs freeT4
determination
o Mildly elevated TSH with normal free T4: subclinical
hypothyroidism

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 Treatment of Hypothyroidism
Goals of Treatment:
 Restore thyroid hormone concentrations in tissue,
 Provide symptomatic relief,
 Prevent neurologic deficits in newborns and children, and
 Reverse the biochemical abnormalities of hypothyroidism

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Treatment of Hypothyroidism
• Levothyroxine (L-thyroxine, T4) is the drug of choice for thyroid
hormone replacement and suppressive therapy b/c it is chemically
stable, relatively inexpensive, free of antigenicity, and has uniform
potency;

• however, any of the commercially available thyroid preparations can

be used.

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 Levothyroxine
Starting dose
• Young patients with no cardiovascular disease 100mcg/day
• Elderly patients with no obvious cardiac disease 50mcg/day
• Patients with established cardiac disease 25-50mcg/day

• Dose adjustment
• Dose adjustment should be made after 2-3 months
• Dose increments by 25-50mcg/day in 2-3months
• After normalization of TSH, annual follow up of TSH
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• Levothyroxine is the drug of choice for pregnant women,
and the objective of the treatment is to decrease TSH to 1 mIU/L &
to maintain free T4 in the normal range.
• Liothyronine (synthetic T3) has uniform potency but has a higher
incidence of cardiac adverse effects, higher cost, and difficulty in
monitoring with conventional laboratory tests.

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• Excessive doses of thyroid hormone may lead to heart failure,
angina pectoris & myocardial infarction.

• Allergic or idiosyncratic reactions can occur with the thyroid &

thyroglobulin,

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Treatment of Myxedema Coma
• Immediate and aggressive therapy with IV bolus levothyroxine, 300 to
500 mcg, has traditionally been used.

• Initial treatment with IV liothyronine or a combination of both

hormones
• Glucocorticoid therapy with IV hydrocortisone 100 mg q8 hrs
• Maintenance levothyroxine doses are typically 75 to100 mcg IV until the
pt stabilizes & use oral therapy.

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Summary

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 Case 1
• CC: I’m so jumpy and sweaty and hungry, and I’m losing weight
• TS is a 29-year-old woman who comes to the clinic stating, “I’m so
jumpy and sweaty and hungry, and I’m losing weight. I think I’m
losing my mind. What is wrong with me? Is it because I’m pregnant?”
She first noticed these symptoms 4 months ago, and they have
worsened steadily since she became pregnant 2 months ago. She
feels anxious for no reason and has trouble sleeping. She has noticed
that her appetite has increased, although she has lost about 1 kg (2.2
lb) over the past 2 months despite being pregnant. Sometimes she
can feel her heart beating in her chest, but she denies chest pain or
syncope.
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Cont.…..
Her only medications are a prenatal vitamin, occasional ibuprofen for
headaches, and an herbal product for boosting energy. She thinks that her
mother had some kind of thyroid problem when she was pregnant
PE:
VS: Pulse 122 beats/min, BP 106/71, RR 12, temperature
37.4°C (99.3°F)
HEENT: Diffusely enlarged thyroid; mild exophthalmos
CV: Tachycardic
exts: Fine tremor
Skin: Warm, moist, and soft
ECG: Sinus tachycardia
Uterine ultrasound: 6-week-size fetus 54
Labs
Electrolytes, CBC normal. TSH less than 0.1 mIU/L (reference
range 0.5 to 2.5 mIU/L); free T4 (FT4) 3.6 ng/dL (reference
range) 0.7 to 1.9 ng/dL, or 9.0 to 24.5 pmol/L); +ve TSHR-SAbs

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• What is the most likely diagnosis of TS
• What therapeutic options exist for TS’s Graves’ disease while
she is pregnant?
• Could the herbal product be causing any of her signs and
symptoms?
• What pharmacotherapy would you recommend? Would you
change it after she has her baby?
• How would you initiate and titrate therapy?
• What would you tell TS regarding the cause of her signs and
symptoms, significance of her abnormal thyroid function
tests, and therapeutic options?
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Case 2
• WM, a 49-year-old woman, comes to the clinic
complaining of fatigue, lethargy, heavy periods, dry
skin, and feeling cold all the time for the past 6 months.
She thought it was because she was going through
“the change,” but the symptoms have not improved
despite her primary care provider telling her she was
not perimenopausal. She has noticed a 4.8-kg (10.5-lb)
weight gain over the past 6 months. Her provider gave
her a prescription for sertraline, but she did not get it filled
because she did not think she was depressed. She takes no
medications other than occasional acetaminophen for headache
and milk of magnesia for constipation. Her vital signs and
physical examination, including pelvic examination findings, are
normal.
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TSH: 8.6 mIU/L (0.5 to 4.5 mIU/L)a
Free T4: 0.9 ng/dL (0.7 to 1.9 ng/dL
Wt: 74 kg (163 lb); ht: 5 ft, 5 in (165 cm); BMI: 27.2 kg/m2
1. What is the likely diagnoses of MW
2. What are the sign and symptoms of MW
3. What would you recommend regarding her LT4 dose and
monitoring?
4. What would you tell WM regarding the significance of her
symptoms, elevated TSH level, and risk versus benefits of LT 4
therapy?

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 Evaluation of therapeutic
outcomes
 Serum TSH concentration is the most sensitive and specific
monitoring parameter for adjustment of levothyroxine dose.
 Concentrations begin to fall within hours and are usually
normalized within 2 to 6 weeks
 Check both TSH and T concentrations every 6 weeks until a
euthyroid state is achieved.
 An elevated TSH level indicates insufficient replacement

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 THANKS!

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