Thyroid

Thyroid
 Largest Endocrine organ in the body
 Involved in production, storage, and release
of thyroid hormone
 Function influenced by
 Central axis (TRH)
 Pituitary function (TSH)
 Comorbid diseases (Cirrhosis, Graves, etc.)
 Environmental factors (iodine intake)
Thyroid (cont)
 Regulates basal metabolic rate
 Improves cardiac contractility
 Increases the gain of catecholamines
 Increases bowel motility
 Increases speed of muscle contraction
 Decreases cholesterol (LDL)
 Required for proper fetal neural growth
Thyroid Physiology
 Uptake of Iodine by thyroid
 Coupling of Iodine to Thyroglobulin
 Storage of MIT / DIT in follicular space
 Re-absorption of MIT / DIT
 Formation of T3, T4 from MIT / DIT
 Release of T3, T4 into serum
 Breakdown of T3, T4 with release of Iodine
Iodine uptake
 Na+/I- symport protein
controls serum I- uptake
 Based on Na+/K+
antiport potential
 Stimulated by TSH
 Inhibited by
Perchlorate
MIT / DIT formation
 Thyroid Peroxidase (TPO)
 Apical membrane protein
 Catalyzes Iodine organification to Tyrosine residues of
Thyroglobulin
 Antagonized by methimazole
 Iodine coupled to Thyroglobulin
 Monoiodotyrosine (Tg + one I-)
 Diiodotyrosine (Tg + two I-)
 Pre-hormones secreted into follicular space
Secretion of Thyroid Hormone
 Stimulated by TSH
 Endocytosis of colloid on apical membrane
 Coupling of MIT & DIT residues
 Catalyzed by TPO
 MIT + DIT = T3
 DIT + DIT = T4
 Hydrolysis of Thyroglobulin
 Release of T3, T4
 Release inhibited by Lithium
Thyroid Hormones
Thyroid Hormone
 Majority of circulating hormone is T4
 98.5% T4
 1.5% T3
 Total Hormone load is influenced by serum
binding proteins (TBP, Albumin, ??)
 Thyroid Binding Globulin 70%
 Albumin 15%
 Transthyretin 10%
 Regulation is based on the free component of
thyroid hormone
Hormone Binding Factors
 Increased TBG
 High estrogen states (pregnancy, OCP, HRT, Tamoxifen)
 Liver disease (early)
 Decreased TBG
 Androgens or anabolic steroids
 Liver disease (late)
 Binding Site Competition
 NSAID’s
 Furosemide IV
 Anticonvulsants (Phenytoin, Carbamazepine)
Hormone Degradation
 T4 is converted to T3 (active) by 5’ deiodinase
 T4 can be converted to rT3 (inactive) by 3 deiodinase
 T3 is converted to rT2 (inactive)by 5 deiodinase
 rT3 is inactive but measured by serum tests
Thyroid Hormone Control
TRH
 Produced by Hypothalamus
 Release is pulsatile, circadian
 Downregulated by T4, T3
 Travels through portal venous system to
adenohypophysis
 Stimulates TSH formation
TSH
 Produced by Adenohypophysis Thyrotrophs
 Upregulated by TRH
 Downregulated by T4, T3
 Travels through portal venous system to cavernous
sinus, body.
 Stimulates several processes
 Iodine uptake
 Colloid endocytosis
 Growth of thyroid gland
TSH Response
Thyroid Lab Evaluation
 TRH
 TSH
 TT3, TT4
 FT3, FT4
 RAIU
 Thyroglobulin, Thyroglobulin Ab
 Perchlorate Test
 Stimulation Tests
RAIU
 Scintillation counter measures radioactivity 6 & 24 hours after
I123 administration.
 Uptake varies greatly by iodine status
 Indigenous diet (normal uptake 10% vs. 90%)
 Amiodarone, Contrast study, Topical betadine
 Symptomatic elevated RAIU
 Graves’
 Toxic goiter
 Symptomatic low RAIU
 Thyroiditis (Subacute, Active Hashimoto’s)
 Hormone ingestion (Thyrotoxicosis factitia, Hamburger
Thyrotoxicosis)
 Excess I- intake in Graves’ (Jod-Basedow effect)
 Ectopic thyroid carcinoma (Struma ovarii)
Iodine states
 Normal Thyroid

 Inactive Thyroid

 Hyperactive Thyroid
Wolff-Chaikoff
 Increasing doses of I- increase
hormone synthesis initially
 Higher doses cause cessation of
hormone formation.
 This effect is countered by the
Iodide leak from normal
thyroid tissue.
 Patients with autoimmune
thyroiditis may fail to adapt and
become hypothyroid.
Jod-Basedow
 Aberration of the Wolff-Chaikoff effect
 Excessive iodine loads induce
hyperthyroidism
 Observed in several disease processes
 Graves’ disease
 Multinodular goiter
Perchlorate
 ClO4- ion inhibits the Na+ / I-
transport protein.
 Normal individuals show no
leak of I123 after ClO4- due to
organification of I- to MIT /
DIT
 Patients with organification
defects show loss of RAIU.
 Used in diagnosis of Pendred
syndrome
Hypothyroid
 Symptoms – fatigability, cold intolerance, weight gain,
loss of appetite, constipation, low voice, poverty of
movements, loss of memory.
 Signs – Cool, dry and thick skin, swelling of
face/hands/legs, slow reflexes, myxedema, bradycardia,
 Newborn – Retardation, short stature, swelling of
face/hands, possible deafness
 Young female: oligomenorrhoea/amenorrhoea,
menorrhagia, infertility or hyperprolactinaemia.
 Elderly : Symptoms difficult to differentiate from aging
Hypothyroidism
Hypothyroidism
 Types of Hypothyroidism

 Primary – Thyroid gland failure

 Secondary – Pituitary failure

 Tertiary – Hypothalamic failure

 Peripheral resistance
Primary – Thyroid gland failure
 Atrophic (autoimmune) hypothyroidism
 Most common cause of hypothyroidism in UK
 Associated with antithyroid autoantibodies -
lymphoid infiltration - atrophy and fibrosis.
 Six times more common in females, the incidence
increases with age.
 Can be associated with other autoimmune disease
such as pernicious anaemia, vitiligo and other
endocrine deficiencies.
Primary – Thyroid gland failure
 Postpartum thyroiditis
 Transient phenomenon observed following
pregnancy
 May involve hyperthyroidism, hypothyroidism or
the two sequentially.
 It is believed to result from the modifications to
the immune system necessary in pregnancy,
 High chance of this proceeding to permanent
hypothyroidism.
Primary – Thyroid gland failure
 Iodine deficiency
 Found in mountainous areas (the Alps, Himalayas,
South America, Central Africa)
 'endemic goitre‘ , occasionally massive.
 The patients may be euthyroid (compensated
euthyroid) or hypothyroid depending on the severity
of iodine deficiency.
 The mechanism is thought to be borderline
hypothyroidism leading to TSH stimulation and
thyroid enlargement
Hashimoto’s
(Chronic, Lymphocytic)
 Most common cause of hypothyroidism in US
 Result of antibodies to TPO, TBG
 Commonly presents in females 30-50 yrs.
 Usually non-tender and asymptomatic
 Lab values
 High TSH
 Low T4
 Anti-TPO Ab
 Anti-TBG Ab
 Treat with Levothyroxine
Hypothyroid
 Cause is determined by
geography

 Diagnosis

 High TSH, Low FT4

(Primary, check for
antibodies)

 Low FT4, Low TSH

(Secondary or Tertiary,
TRH stimulation test,
MRI)
Hypothyroidism Investigations
 Thyroid and other organ-specific antibodies
 Anaemia, usually normochromic and normocytic,
but may be macrocytic (if associated pernicious
anaemia) or microcytic (in women, due to
menorrhagia)
 Increased serum aspartate transferase levels, from
muscle and/or liver
 Increased serum creatine kinase levels, with
associated myopathy
 Hypercholesterolaemia
Hypothyroidism Treatment
 Levothyroxine (T4) due to longer half life
 Treatment prevents bone loss, cardiomyopathy,
myxedema
 Life long treatment is required, additional dosage
in pregnancy
 In the young and fit, 100 μg daily is suitable,
while 50 μg daily (increased to 100 μg after 2-4
weeks) is more appropriate for the small, old or
frail.
 Clinical improvement in 2wks, full resolution of
symptoms 6 months
Hypothyroidism Treatment
 Special precautions in Patients with ischaemic
heart disease
 Start small dose, 25 μg daily
 Monitor ECG, angina
 Increase dose over 4-6 wks
 Maximum of 100-150 μg/day
 Overeplacement in elderly can lead to atrial
fibrillation
Special hypothyroid conditions
 Borderline hypothyroidism or 'compensated
euthyroidism'
 Low-normal serum T4 levels and slightly raised TSH
levels.
 Treatment with thyroxine is normally recommended
where the TSH is consistently above 10 mU/L, or when
possible symptoms, high-titre thyroid antibodies or lipid
abnormalities are present.
 Where the TSH is only marginally raised, the tests should
be repeated 3-6 months later..
Special hypothyroid conditions
 Myxoedema coma
 Severe hypothyroidism, especially in the elderly
 Confusion or coma, hypothermia, may have severe cardiac
failure, hypoventilation, hypoglycaemia and hyponatraemia.
 Require full intensive care.
 T3 orally or IV in doses of 2.5-5 μg every 8 hours, then
increasing as above. Large IV doses should NOT be used.
 Additional measures, O2, monitoring COP & BP, gradual
rewarming , hydrocortisone 100 mg i.v. 8-hourly, glucose
infusion to prevent hypoglycaemia .
Hyperthyroid
 More common in female (5:1)

 More common in 20-40 yrs age

 Nearly all cases (> 99%) are caused by

intrinsic thyroid disease; a pituitary cause is
extremely rare
Hyperthyroid
 Common Causes
 *Graves
 Adenoma
 Multinodular Goiter
 *Subacute Thyroiditis
 *Hashimoto’s Thyroiditis
 Rare Causes
 Thyrotoxicosis factitia, struma ovarii, thyroid
metastasis, TSH-secreting tumor, hamburger
Hyperthyroid
 Symptoms – Wt loss, increase in appetite,
Palpitations, nervousness, fatigue, diarrhea,
sweating, heat intolerance
 Signs – Increase BP, HR, Thyroid enlargement
(?), tremor,

 Graves' disease: Eye signs, pretibial myxoedema

(infiltration on the shin) and thyroid acropachy
(clubbing, swollen fingers and periosteal new
bone formation
Hyperthyroid – Symptoms & signs
 Elderly,a frequent presentation is with atrial
fibrillation, other tachycardias and/or heart failure

 Children, excessive height or excessive growth rate,

or with behavioural problems such as hyperactivity.
They may also show weight gain rather than loss.

 So-called 'apathetic thyrotoxicosis' in some elderly

patients presents with a clinical picture more like
hypothyroidism.
Hyperthyroid – Symptoms & signs
Hyperthyroidism Investigations
 Lab workup
 TSH
 FT4
 RAIU

 Other Labs
 Anti-TSH-R Ab, Anti-TPO Ab, Anti-TBG Ab
 FT3
 FNA
 MRI, US
Hyperthyroidism Treatment
 Three ways: antithyroid drugs, radioiodine and
surgery.
 Choice of therapy
 Symptomatic relief: (NOT to be used alone)
 As many of the manifestations of hyperthyroidism are
mediated via the sympathetic system, beta-blockers are used.
 They also decrease peripheral conversion of T4 to T3.
 Propanolol is drug of choice
Hyperthyroidism Treatment
 Antithyroid drugs
 Carbimazole, propylthiouracil, thiamazole
(methimazole)
 Drugs inhibit the formation of thyroid hormones and
also have immunosuppressive (carbimazole) action.
 As T4 has long half-life (7 days), clinical benefit is
not apparent for 10-20 days
 Agranulocytosis is major side effect (watch for
unexplained fever, sore throat)
Antithyroid drug regimen
 Gradual dose titration
1. Review after 4-6 weeks and reduce dose of carbimazole
depending on clinical state and T4/T3 levels.
2. When clinically and biochemically euthyroid, stop beta-
blockers.
3. Review after 2-3 months and, if controlled, reduce carbimazole.
4. Gradually reduce dose to 5 mg daily over 6-24 months if
hyperthyroidism remains controlled.

5. When the patient is euthyroid on 5 mg daily carbimazole,

discontinue.
Antithyroid drug regimen
 'Block and replace' regimen
 full doses of carbimazole 40 mg/day, (suppress
the thyroid completely) + thyroxine 100 μg/day
 Advantages – No risk of under or over treatment
 Full utilization of immunosupression property of
carbimazole
 NOT to be used in pregnancy as T4 crosses
placenta less easily than carbimazole
Hyperthyroidism Treatment
 Radioactive iodine
 Commonly used in US
 I131 is used
 Accumulates in thyroid gland and destroys gland by
local radiation
 Patients must be rendered euthyroid before treatment,
stop antithyroid drugs 4 days before radioiodine, and
not recommence until 3 days after radioiodine
 Contraindicated in pregnancy, breast feeding
Hyperthyroidism Treatment
 Subtotal thyroidectomy
 Stop antithyroid drugs before surgery
 10-14 days before surgery give potassium iodide
(60 mg three times daily), which reduces the
vascularity of the gland.
 Complications –
 Early postoperative bleeding and tracheal compression
 Recurrent laryngeal nerve damage
 Transient hypocalcemia
 Graves
 Most common cause of hyperthyroidism
 Result of anti-TSH receptor antibodies
 Yersinia enterocolitica, Escherichia coli and other Gram-
negative organisms contain TSH binding sites.
 Have genetic susceptibility
 Thyroid eye disease accompanies, Graves' dermopathy,
lymphadenopathy and splenomegaly may occur.
 Autoimmune disorders such as pernicious anaemia,
vitiligo and myasthenia gravis may be associated.
Graves
 Diagnosis
 Symptoms of hyperthyroidism
 Clinical exopthalmos and goiter
 Low TSH, normal/high FT4, anti-TSH Ab (Optional)

 If no clinical findings I123 may demonstrate increased uptake.

 Treatments
 Medical – Propothyouracil, Methimazole, Propranolol
 Surgical – Subtotal Thyroidectomy
 Radiation – RAI ablation [I131(Ci/g) x weight / %RAIU]
THYROID EYE DISEASE
 Also known as dysthyroid eye disease or ophthalmic
Graves' disease.
 TSI is thought to be antibody
 But can occur can occur in patients who may be
hyperthyroid, euthyroid or hypothyroid.
 More common in smokers, exacerbation common after
radioiodine treatment (15% vs 3% on antithyroid drugs).
 Inflammation of retrorbital tissue and extraocular
muscles.
 Swelling and oedema
THYROID EYE DISEASE
 Proptosis :Soreness, painful watering or
prominence of the eyes and the 'stare' of lid
retraction
 Can develop corneal ulcerations
 Limitation of movements in severe cases
 Increased pressure on the optic nerve may
cause optic atrophy.
THYROID EYE DISEASE Treatment
 Eye manifestations DO NOT parallel the
degree of biochemical thyrotoxicosis, nor the
antithyroid therapy suppresses symptoms.
 Exophthalmos should be measured to allow
progress to be monitored

 MRI of the orbits will exclude other causes

and show enlarged muscles and oedema.
THYROID EYE DISEASE Treatment
 Methylcellulose or hypromellose eyedrops- lubrication
 Sleeping upright, eyelids can be taped in night.
 Systemic steroids (prednisolone 30-120 mg daily)
usually reduce inflammation
 Irradiation of the orbits is used in severe instances
 Lid surgery
 Surgical decompression of the orbit(s)
 Corrective eye muscle surgery, Plastic surgery
The fetus and maternal Graves' disease
 Mother with h/o graves will have TSI
 Mother euthyroid and fetus hyperthyroid
 Fetal heart rate > 160/min
 Maternal treatment with carbimazole and/or
propranolol may be used.
 To prevent mother going in hypothyroidism treat
mother also with T4 (T4 does not cross placenta that
easily compared to carbimazole)
Subacute Thyroiditis
(DeQuervain’s, Granulomatous)
 Acute viral infection of thyroid gland
 Presents with viral prodrome, thyroid tenderness,
and hyperthyroid symptoms
 Lab values
 Variable TSH, T4
 High ESR
 No antibodies
 Treatment
 NSAID
 Prednisone (?)
 Levothyroxine (?)
Subacute Thyroiditis
(DeQuervain’s, Granulomatous)
Euthyroid Sick
 Results from inactivation of 5’-Deiodinase, resulting
in conversion of FT4 to rT3.
 Generally occurs in critically ill patients, but may
occur with DM, malnutrition, iodine loads, or
medications (Amiodarone, glucocorticoids)
 Treatment
 Avoid above medications
 Treat primary illness
 T3, T4 not helpful
Thyroid Storm or Crisis
 Rapid deterioration of hyperthyroidism with
hyperpyrexia, severe tachycardia and extreme
restlessness.
 Precipitated by stress, infection, surgery in an
unprepared patient, or radioiodine therapy.
 Diagnosis
 Clinical – tachycardia, hyperpyrexia, thyrotoxicosis
symptoms
 Labs (Low TSH, High T4, FT4)
Thyroid Storm Treatment
 Propranolol IV vs. Verapamil IV
 Propylthiouracil, Methimazole
 Sodium Iodide
 Acetamenophen, cooling blankets
 Plasmapheresis (rare)
 Surgical (rare)
Goiter
 Enlargement of thyroid gland
 Can be physiological or pathological
 Person can be euthytoid, hypothyroid or
hyperthyroid
 Physiological – puberty, pregnancy
 Pain in goiter - thyroiditis, bleeding into a
cyst or (rarely) a thyroid tumour.
Goiter
 Endemic goiter
 Caused by dietary deficiency of Iodide
 Increased TSH stimulates gland growth
 Also results in cretinism
 Goiter in developed countries
 Hashimoto’s thryoiditis
 Subacute thyroiditis
 Other causes
 Excess Iodide (Amiodarone, Kelp, Lithium)
 Adenoma, Malignancy
 Genetic / Familial hormone synthesis defects
 Excessive doses of carbimazole or propylthiouracil
Goiter
 Palpate goiter for its consistency, nodules,
size shape, movement with swallowing.
 Try to locate the lower margin to know
retrosternal extension
 Surgery if
 Possibilities of malignancy
 Tracheal compression
 Cosmetic reason
Goiter - Investigations
 Thyroid function tests - TSH plus free T4 or
T3
 Ultrasound - delineating nodules (cystic or
solid).
 Chest and thoracic inlet X-rays - tracheal
compression, retrosternal extensions
 Fine-needle aspiration (FNA).