The thyroid gland is the body's largest single organ specialized for endocrine hormone production. Its function is to secrete an appropriate amount of the thyroid hormones, primarily (thyroxine, T4) , and a lesser quantity of triiodothyronine (T3) , which arises mainly from the subsequent extrathyroidal deiodination ofT4.

1. ASSISTANT PROFESSOR DR BILAL NATIQ NUAMAN
CONSULTANT ENDOCRINOLOGIST
Al-Iraqia Medical College
2024

2. The thyroid gland is the body's largest single organ
specialized for endocrine hormone production. Its
function is to secrete an appropriate amount of the
thyroid hormones, primarily (thyroxine, T4) , and a
lesser quantity of triiodothyronine (T3) , which
arises mainly from the subsequent extrathyroidal
deiodination ofT4.
In target tissues, T3 interacts with nuclear T3 receptors
that are, in turn, bound to special nucleotide
sequences in the promoter regions of genes that are
positively or negatively regulated by thyroid
hormone.

3. The thyroid hormones promote normal fetal and
childhood growth and central nervous system
development; regulate heart rate and myocardial
contraction and relaxation; affect gastrointestinal
motility and renal water clearance; and modulate the
body's energy expenditure, heat generation, weight, and
lipid metabolism.
In addition, the thyroid contains parafollicular or C cells
that produce calcitonin, a 32-amino-acid polypeptide
that inhibits bone resorption, but has no apparent
physiologic role in humans. However, calcitonin is
clinically important as a tumor marker produced by
medullary thyroid cancers that arise from these cells

5. There are three major thyroid hormone transport
proteins: thyroxine-binding globulin (TBG) ;
transthyretin, and albumin. The plasma protein
binding creates a large circulating thyroid hormone
pool with a stable 7-day plasma half-life and ensures
the homogeneous distribution of thyroid hormones in
target tissues.

6. H i story
Patients with thyroid disease usually complain of one or
more of the following:
( 1 ) thyroid enlargement, which may be diffuse or
nodular;
(2) symptoms of hypothyroidism;
(3) symptoms of hyperthyroidism; or
(4) complications of a specific form of hyperthyroidism-
Graves disease-that may present with striking
prominence of the eyes (exophthalmos) and, rarely,
thickening of the skin over the lower legs (thyroid
dermopathy or pretibial myxedema) .

7. The history should identify risk factors for thyroid disease.
Exposure to ionizing radiation in childhood has been
associated with an increased incidence of thyroid disease,
including cancer. Iodide ingestion in the form of
amiodarone, an iodine-containing antiarrhythmic drug, or
intravenous iodide containing contrast media used in
angiography or CT scanning may induce hypothyroidism or
hyperthyroidism. Residence in an area of low dietary iodide
is associated with iodine deficiency goiter (endemic goiter) .
The family history should be explored with particular
reference to goiter, hyperthyroidism, hypothyroidism, or
thyroid cancer as well as immunologic disorders such as type
1 diabetes, pernicious anemia, alopecia, vitiligo, or
myasthenia gravis,
which may be associated with an increased incidence of
autoimmune thyroid disease. Multiple endocrine neoplasia
types 2A (Sipple syndrome) and 2B with medullary
carcinoma of the thyroid gland are autosomal dominant
conditions.

8. Physical Examination
Normally, the thyroid is just barely palpable, has a smooth surface,
and has a soft to rubbery consistency. The palpable bulbous portion
of each lobe of the normal thyroid gland measures about 2 cm in
vertical dimension and about 1 cm in horizontal dimension above
the isthmus. An enlarged thyroid gland is called a goiter.
Generalized enlargement is termed diffuse goiter; irregular or
lumpy enlargement is called nodular goiter. In Hashimoto
thyroiditis,
the gland is often symmetrically enlarged, firm, and has a
Cobblestone or finely nodular surface. In the atrophic
form of Hashimoto thyroiditis, the gland may not be palpable at
all. In patients with Graves disease, the gland is usually, but not
always, symmetrically enlarged, smooth, and rubbery in
consistency.
Multinodular goiters have one or more distinct nodules, although
both small and large and nodules may not be palpable because of
their location or consistency.

9.  Tenderness of the gland should be noted. In
patients with Graves disease, the presence of a
bruit by auscultation should be sought, and a
thrill may be palpable over the gland.
 Tracheal deviation by a goiter, cervical
lymphadenopathy possibly related to thyroid
cancer, and jugular venous distention and facial
erythema from thoracic inlet obstruction by a
large goiter should be noted as well.

13. Presenting problems in thyroid disease
 The most common presentations are
hyperthyroidism (thyrotoxicosis),hypothyroidism
and enlargement of the thyroid (goitre or thyroid
nodule).
 Widespread availability of thyroid function tests
has led to the increasingly frequent identification of
patients with abnormal results who either are
asymptomatic or have non-specific complaints such
as tiredness and weight gain.

15. Thyrotoxicosis
 Thyrotoxicosis describes a constellation of clinical
features arising from elevated circulating levels of
thyroid hormone. The most common causes are
Graves’ disease, multinodular goitre, autonomously
functioning thyroid nodules (toxic adenoma) and
thyroiditis

16. Some experts reserve the term "thyrotoxicosis“ for all
conditions in which serum levels of thyroid hormones
are elevated, while the word "hyperthyroidism" is
reserved for those conditions in which the thyroid
gland is synthesizing and secreting excessive
quantities of thyroid hormones. Thus, Graves disease,
toxic multinodular goiter, and TSH-secreting tumor
are examples of "hyperthyroidism," while thyroiditis
and factitious thyrotoxicosis are examples of
thyrotoxicosis, but not true "hyperthyroidism."

18. Clinical assessment

20. Investigations
 The first-line investigations are serum T3, T4 and TSH.
If abnormal values are found, the tests should be
repeated and the abnormality confirmed in view of the
likely need for prolonged medical treatment or
destructive therapy. In most patients, serum T3 and T4
are both elevated, but T4 is
in the upper part of the reference range and T3 is raised
(T3 toxicosis) in about 5%. Serum TSH is undetectable
in primary thyrotoxicosis, but values can be raised in
the very rare syndrome of secondary thyrotoxicosis
caused by a TSH-producing pituitary adenoma.

21. When biochemical thyrotoxicosis has been confirmed,
measurement of TSH receptor antibodies (TRAb,
elevated in Graves’ disease) is recommended. Where
TRAb is not available, radioisotope scanning is an
alternative diagnostic approach.
Other non specific abnormalities are common - An
electrocardiogram (ECG) may demonstrate sinus
tachycardia or atrial fibrillation.
Radio-iodine uptake tests measure the proportion of
isotope that is trapped in the whole gland but have been
largely superseded by 99m technetium scintigraphy
scans, which also indicate trapping, are quicker to
perform with a lower dose of radioactivity, and provide a
higher-resolution image. In low-uptake thyrotoxicosis,
the cause is usually a transient thyroiditis.

25.  Graves disease is the most common form of
thyrotoxicosis. Females are involved about 5 times
more commonly than males.
The disease may occur at any age,
with a peak incidence in the
20- to 40-year age group.
The syndrome consists of
thyrotoxicosis plus one or more
of the following features: (I) goiter,
(2) ophthalmopathy (exophthalmos) , and
(3) dermopathy (pretibial myxedema) .

26. Graves disease is currently viewed as an
autoimmune disease of unknown cause. There is a
strong familial predisposition, in that about 1 5%
of patients with Graves disease have a close
relative with the same disorder.
The thyrotoxicosis results from the production of
IgG antibodies directed against the TSH receptor
on the thyroid follicular cell, which stimulate
thyroid hormone production and proliferation of
follicular cells, leading to goitre in the majority of
patients. These antibodies are termed thyroid-
stimulating immunoglobulins or TSH receptor
antibodies (TRAb) and can be detected in the
serum of >95% of patients with Graves’ disease.

29. As agranulocytosis occurs very suddenly and is
potentially fatal.
Patients typically present with fever and evidence of
infection, usually in the oropharynx, and each patient
should therefore receive written instructions to
discontinue the medication and contact their doctor
for a blood count, should this situation arise.

30. ‘factitious thyrotoxicosis’ by consuming excessive
amounts of a thyroid hormone preparation, most
often levothyroxine. The exogenous levothyroxine
suppresses pituitary TSH secretion and hence
iodine uptake, serum thyroglobulin and release of
endogenous thyroid hormones. The T4:T3 ratio
(typically 30: 1 in conventional thyrotoxicosis) is
increased to above 70: 1 because circulating T3 in
factitious thyrotoxicosis is derived exclusively from
the peripheral monodeiodination of T4 and not
from thyroid secretion. The combination of
negligible iodine uptake, high T4:T3 ratio and a low
or undetectable thyroglobulin is diagnostic.

31.  Atrial fibrillation occurs in about 10% of patients with
thyrotoxicosis. The incidence is higher in men and
increases with age, so that almost half of all males with
thyrotoxicosis over the age of 60 are affected. Moreover,
subclinical thyrotoxicosis is a risk factor for atrial
fibrillation. Characteristically, the ventricular rate is
little influenced by digoxin but responds to the
addition of a β-blocker. Thromboembolic vascular
complications are particularly common in thyrotoxic
atrial fibrillation so that anticoagulation is required,
unless contraindicated. Once thyroid hormone and
TSH concentrations have been returned to normal,
atrial fibrillation will spontaneously revert to sinus
rhythm in about 50% of patients but cardioversion may
be required in the remainder.
Atrial fibrillation in thyrotoxicosis

32. Thyrotoxic crisis (‘thyroid storm’) This is
a rare but life-threatening complication of
thyrotoxicosis. The most prominent signs are fever,
agitation, delirium, tachycardia or atrial fibrillation
and, in the older patient, cardiac failure. Thyrotoxic
crisis is a medical emergency and has a mortality of 10%
despite early recognition and treatment. It is most
commonly precipitated by infection in a patient with
previously unrecognized or inadequately treated
thyrotoxicosis. It may also develop in known
thyrotoxicosis shortly after thyroidectomy in an ill-
prepared patient or within a few days of 131I therapy,
when acute radiation damage may lead to a transient
rise in serum thyroid hormone levels. Urgent specialist
endocrine input should be sought in cases of suspected
‘thyroid storm’, both to confirm the diagnosis and
provide advice on appropriate treatment.

33. Patients should be rehydrated and given propranolol,
either orally (80 mg 4 times daily) or intravenously (1–
5 mg 4 times daily). Both glucocorticoids
(hydrocortisone 100 mg IV every 8 hours) and iodine
are important in reducing the conversion of T4 to
active T3. Sodium ipodate, a radiographic contrast
medium (500 mg per day orally), will restore serum T3
levels to normal in 48–72 hours.
Where sodium ipodate is not available, potassium
iodide or Lugol’s solution are reasonable alternatives.
Oral propylthiouracil (PTU) (200 mg every 4 hours)
should be given to inhibit the synthesis of new
thyroid hormone. PTU is preferred to carbimazole as
it also inhibits the conversion of T4 to T3. If the
patient is unconscious or uncooperative, PTU and
propranolol can be administered by nasogastric tube.
After 10–14 days the patient can usually be maintained
on carbimazole alone.

34. Hypothyroidism
Hypothyroidism is a common condition with various
causes , but autoimmune disease (Hashimoto’s
thyroiditis) and thyroid failure following 131I or
surgical treatment of thyrotoxicosis account for
over 90% of cases, except in areas where iodine
deficiency is endemic. Women are affected
approximately six times more frequently than men.

36. In adults, the common features of moderate to
severe hypothyroidism include easy fatigability; cold
sensitivity; weight gain (generally < 5 kg);
constipation; menstrual abnormalities, especially
menorrhagia; and muscle cramps.
Physical findings may include a cool, rough, dry skin;
puffy face and hands; a hoarse, husky voice; and
slow reflexes. Reduced conversion of carotene to
vitamin A and increased blood levels of carotene
may give the skin a yellowish color. However, many
or all of the symptoms and signs are diminished or
absent in patients with milder degrees of thyroid
failure.

37. Hashimoto’s thyroiditis
 Hashimoto’s thyroiditis (or ‘chronic autoimmune
thyroiditis’) is characterised by destructive lymphocytic
infiltration of the thyroid, ultimately leading to a varying
degree of fibrosis and thyroid enlargement. It has atrophic
and goitrous variants.
 Hashimoto’s thyroiditis increases in incidence with age
and affects approximately 3.5 per 1000 women and 0.8 per
1000 men each year. Many present with a small or
moderately sized diffuse goitre, which is characteristically
firm or rubbery in consistency. Around 25% of patients are
hypothyroid at presentation.

38. In the remainder, serum T4 is normal and TSH normal
or raised, but these patients are at risk of developing
overt hypothyroidism in future years. Antithyroid
peroxidase antibodies are present in the serum in
more than 90% of patients with Hashimoto’s
thyroiditis. There is an increased risk of thyroid
lymphoma, although this is exceedingly rare.
Levothyroxine therapy is indicated as treatment for
hypothyroidism and also to shrink an associated
goitre. In this context, the dose of levothyroxine
should be sufficient to suppress serum TSH to low
but detectable levels.

39. Hypothyroidism may be classified as
( 1 ) primary which is by far the most common,
(2) secondary due to pituitary TSH deficiency,
(3) tertiary due to hypothalamic TRH deficiency, or
( 4) peripheral thyroid hormone resistance.

40. Clinical assessment

41. Hypothyroidism with onset in
adulthood causes diminished
calorigenesis and oxygen
consumption; impaired cardiac,
pulmonary, renal, gastro -
intestinal, and neurological
functions and deposition of
Glycos aminoglycans in
intracellular spaces,
particularly in skin and muscle,
producing in extreme cases the
clinical picture of myxedema.

44.  If the serum FT4 is normal, and the serum TSH is
elevated slightly, a situation termed subclinical
hypothyroidism.
 Subclinical hypothyroidism is usually due to
underlying Hashimoto thyroiditis, which can be
confirmed by assessing anti-TPO Ab titers. In
patients with secondary or central hypothyroidism,
the serum FT4 will be low and serum TSH will be low
or normal, rather than elevated.
 Since serum TSH rises with advancing age, some
healthy elderly persons may have mildly elevated
serum TSH (eg, 5-7 mU/L) , that can mimic
subclinical hypothyroidism.

45. Treatment of hypothyroidism
 Replacement doses of levothyroxine in adults range
from 0 . 0 5 to 0.2 mg/d, with a mean of about 0 . 1 25
mg/d. The dose of T4 varies according to the patient's
age and body weight
 In adults, the mean replacement dose of T4 is about 1 .7
Ug/kg/d,. In older adults, the replacement dose is
usually lower, about 1 .6 Ug/kg/d,
 After 4 to 6 weeks, the final dose is adjusted based on
the serum TSH level. The goal is to normalize the
serum TSH , and increase the dose at 4- to 6-week
intervals based on serum TSH measurements.

46.  T4 should be given before breakfast, when the
stomach is empty. Malabsorptive states or concurrent
administration of soy products, aluminum hydroxide
antacids, bile acid-binding resins such as
cholestyramine and colestipol, calcium supplements,
sucralfate, or iron compounds decrease T4
absorption., Other drugs, such as the antiseizure
medication carbamazepine, may increase thyroid
hormone requirements by increasing T 4 metabolism.
Proton pump inhibitors such as omeprazole may also
impair T 4 absorption, possibly because gastric acid is
needed for dissolution of the tablets. Estrogen
replacement may increase T4 requirements by
increased binding of free T4 to TBG. T4 has a
sufficiently long half-life (7 days) , so that if the
patient is unable

47. Myxedema coma
 an extremely rare condition, is the end stage of untreated
hypothyroidism
 It is characterized by progressive weakness, stupor,
hypothermia, hypoventilation, hypoglycemia, and
hyponatremia, and it may ultimately result in shock and
death.
 It occurs most frequently in the winter in older female
patients with underlying pulmonary and vascular disease,
and the mortality rate may be greater than 50%.

48. Examination reveals bradycardia and marked hypothermia,
with
body temperature as low as 24° C .The patient is usually an
obese elderly woman with yellowish skin, a hoarse voice, a large
tongue, thin hair, puffy eyes, ileus, and slow reflexes. There may
be signs of other illnesses such as pneumonia, myocardial
infarction, cerebral thrombosis, or gastrointestinal bleeding.
Seizures,
bleeding episodes, hypocalcemia, or hypercalcemia may occur.
Laboratory clues to the diagnosis of myxedema coma include
high serum carotene, hyponatremia, elevated BUN and
creatinine, elevated serum cholesterol, and increased
.Pleural, pericardia!, or abdominal effusions with high
protein content may be present. Serum tests reveal a low FT 4
and a markedly elevated TSH. Thyroid autoantibodies are
usually strongly positive, indicating underlying Hashimoto
thyroiditis. The ECG shows sinus bradycardia and low voltage.

50. Asymptomatic abnormal thyroid
function tests
 One of the most common problems in medical
practice is how to manage patients with abnormal
thyroid function tests who have no obvious signs
or symptoms of thyroid disease. These can be
divided into three categories.

51. Subclinical thyrotoxicosis
 Serum TSH is undetectable and serum T3 and T4 are at
the upper end of the reference range. This combination
is most often found in older patients with multinodular
goitre. These patients are at increased risk of atrial
fibrillation and osteoporosis, and hence the consensus
view is that they have mild thyrotoxicosis and require
therapy, either with radio active iodine or low dose
thionamide. Otherwise, annual review is essential, as
the conversion rate to overt thyrotoxicosis with elevated
T4 and/or T3 concentrations is 5% each year.

52. Subclinical hypothyroidism
 Serum TSH is raised and serum T3 and T4
concentrations are at the lower end of the reference
range. This may persist for many years, although there
is a risk of progression to overt thyroid failure,
particularly if antibodies to thyroid peroxidase are
present or if the TSH rises above 10 mIU/L.
 In patients with non- Specifc symptoms, a trial of
levothyroxine therapy may be appropriate. In those
with positive autoantibodies or a TSH greater than 10
mIU/L, it is better to treat the thyroid failure early
rather than risk loss to follow-up and subsequent
presentation with profound hypothyroidism.
Levothyroxine should be given in a dose sufficient to
restore the serum TSH concentration to normal.

53. Non-thyroidal illness (‘sick euthyroidism’)
 This typically presents with a low serum TSH, raised T4 and
normal or low T3 in a patient with systemic illness who does
not have clinical evidence of thyroid disease. These
abnormalities are caused by decreased peripheral
conversion of T4 to T3 (with conversion instead to reverse
T3), altered levels of binding proteins and their affinity for
thyroid hormones, and often reduced secretion of TSH.
During convalescence, serum TSH concentrations may
increase to levels found in primary hypothyroidism. As
thyroid function tests are difficult to interpret in patients
with non-thyroidal illness, it is wise to avoid performing
thyroid function tests unless there is clinical evidence of
concomitant thyroid disease. If an abnormal result is found,
treatment should only be given with specialist advice and
the diagnosis should be re-evaluated after recovery.

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