Endocrinology L9

Hypothyroidism
Differentiated Thyroid Neoplasms

Hussein Ali Nwayyir - MD, FICMS, MSc. (Endo.)

Lecturer :University of Basrah, College of Medicine, Department of Medicine
 Hypothyroidism

• Hypothyroidism is a disorder caused by the inadequate secretion of

thyroid hormone.

q Epidemiology
• Affect 1.5%-2% of women and 0.2% of men.
• Predominant age: Incidence of hypothyroidism increases with age;
among persons older than 60 year, 6% of women and 2.5% of men
have laboratory evidence of hypothyroidism.
Etiology
q Primary hypothyroidism (thyroid gland dysfunction)
1. 90% of cases of hypothyroidism.
2. Iodine deficiency the commonest cause is all over the world.
3. Autoimmune (Hashimoto’s thyroiditis) is the most common cause of
hypothyroidism in the west.
4. Thyroid surgery
5. Radioiodine therapy
6. Congenital (prevalence 1/4000 newborn)

q Secondary hypothyroidism
o Pituitary dysfunction, postpartum necrosis, neoplasm, infiltrative
disease causing deficiency of TSH
Clinical Presentation
Ø Fatigue, lethargy, weakness, constipation, weight gain, cold
intolerance, muscle weakness, slow speech, slow cerebration with poor
memory, and menorrhagia.

Ø Skin: dry, coarse, thick, cool, sallow (yellow color caused by

carotenemia); nonpitting edema in the skin of eyelids and hands
(myxedema) secondary to infiltration of subcutaneous tissues by a
hydrophilic mucopolysaccharide substance.

Ø Hair: brittle and coarse; hair loss, loss of outer third of eyebrows.

Ø Facies: dulled expression, thickened tongue, thick and slow-moving

lips.
Clinical Presentation (cont.)
Ø Thyroid gland: may or may not be palpable (depending on the cause
of the hypothyroidism).
Ø Heart sounds distant, possible pericardial effusion (Pleuropericardial
effusion).
Ø Pulse: Bradycardia, rarely atrial fibrillation
Ø Obstructive sleep apnea syndrome

Ø Neurologic: delayed relaxation phase of the deep tendon

reflexes(non-specific seen in hypothermia and those on beta-blockers),
cerebellar ataxia, hearing impairment, poor memory, peripheral
neuropathies with paresthesia.
Ø Musculoskeletal: carpal tunnel syndrome, muscular stiffness,
weakness.
Clinical Presentation (cont.)

q Clinical features of hypothyroidism in children:

Ø Cretinism:
• A congenital condition caused by a deficiency of thyroid hormone
during prenatal development and characterized in childhood by
dwarfism, mental retardation, dry, yellow, cold skin, "pot belly" with an
umbilical hernia. Also called congenital myxedema.

o Juvenile myxedema (Juvenile Hypothyroidism)

o Acquired Hypothyroidism after birth.
Laboratory Tests:
o TSH ≥10 mIU/L
o Low FT4 <0.93 ng/dL
o Thyroid Peroxidase antibodies (TPO-ab) (positive in
autoimmune form).
• The presence of TPO-ab positive in any patient will put him at
increased risk of hypothyroidism later in life.
• Other common laboratory abnormalities: hyperlipidemia,
hyponatremia, and anemia (normochromic normocytic, or microcytic
anemia), macrocytosis is the norm.
Laboratory Tests: (cont.)

ü TSH may be normal if patient has secondary hypothyroidism

ü In general, the degree of TSH elevation correlates with the
clinical severity of the hypothyroidism.

• Increased thyroid peroxidase abs (TPO-Ab) and antithyroglobulin

antibody titers (Anti-Tg) are useful when autoimmune thyroiditis is
suspected as the cause of the hypothyroidism
Treatment

o Levothyroxine (L-thyroxine) 25 to 150 microgram/day, depending

on the patient’s age and severity of the disease.

ü The L-thyroxine dose may be increased every 6 to 8 weeks, depending

on the clinical response and serum TSH level.
ü Dose changed according to TSH level after one month.
ü Food reduces absorption of L-thyroxine (should take on empty
stomach).
o Elderly patients and patients with coronary artery disease should be
started on 12.5 to 25 microgram /day (higher doses may
precipitate angina).
o The average maintenance dose of L-thyroxine is 1.7 microgram
/kg/day (100 to 150 microgram /day in adults).
Treatment (cont.)

q The elderly may require, 1 microgram/kg/day, whereas children

require higher doses (up to 3 to 4 microgram/kg/day).

ü Pregnant patients also have increased requirements.

ü Estrogen therapy may also increase the need for L-thyroxine.
ü Women with hypothyroidism should increase their L-thyroxine dose by
approximately 30% as soon as pregnancy is confirmed.
ü Close monitoring of serum TSH levels and adjustment of L-thyroxine
dose is recommended throughout pregnancy.
Follow-up

ü Periodic monitoring of TSH level is an essential part of treatment.

ü Patients should be evaluated initially with an office visit and TSH levels
every 6 to 8 weeks until the patient is clinically euthyroid and the TSH
level is normalized.

ü The frequency of subsequent visits and TSH measurement can then be

decreased to every 6 to 12 months.
ü Pregnant patients should be checked every trimester.

ü Measurement of FT4 is used for monitoring therapy in patients with

central hypothyroidism.
 Prepregnancy
and pregnancy
TSH Target<2.5
mu/L

TSH ,TT4
Increase L-T4
each month dose by 30 %
until 28 week
 Subclinical Hypothyroidism

q TSH >5 but less than 10 mIU/L with normal FT4

q Subclinical hypothyroidism occurs in as many as 15% of elderly
patients.

q Subclinical hypothyroidism is associated with an increased risk of

coronary heart disease events and mortality.
q Treatment is individualized.
 Myxedema Coma

ü Decompensated hypothyroidism.

ü Primary symptoms of myxedema coma are altered mental status

and hypothermia.

ü Hypoglycemia, hypotension, hyponatremia, hypothermia, hypercapnia,

hypoxia, bradycardia, and hypoventilation may also occur.
 TSH

N ≥10 mu/L
5-9.9 mu/L
Subclinical Hypothyroidism

IF still suspected, central hypothyroidism ? FT4

TPO
Measure FT4

LOW

Treat with
L-T4

1 month later
TSH

Normal repeat Still high increase L-T4

TSH after 6 months and 1 year until normal TSH each month

TSH each 1 year

 Thyroiditis

q Thyroiditis is a group of inflammatory thyroid disorders.

o Causes destruction of the thyroid gland with the release of stored
thyroid hormones, but no excess synthesis, that why all the symptoms
are transient.
v Classification of Thyroiditis:
1. Chronic lymphocytic thyroiditis (Hashimoto's thyroiditis): most
common inflammatory condition of the thyroid gland and the most
common cause of goiter in the United States.
2. Subacute granulomatous thyroiditis (painful) (de Quervain's
thyroiditis)
3. Subacute lymphocytic thyroiditis (painless)
(1) Postpartum thyroiditis
(2) Sporadic painless thyroiditis
Clinical Course of Subacute Thyroiditis
Ø Clinical features:
ü Typical hyperthyroidism symptoms with or without goiter and or neck
pain.
ü Pain in the neck according to type.
ü Features of hypothyroidism will appear after one month .

Ø Investigations:
o TSH low, FT4 high, thyroid antibodies are positive (TPO-ab).
o ESR can be high in de Quervain's thyroiditis.
o Radioactive iodine uptake (thyroid scan ): reduced uptake.
o On recovery of thyroiditis, hypothyroidism may develop for few weeks
to months.

Ø Treatment:
§ Supportive with beta blockers
§ Spontaneous recovery is a rule in 1-3 months.
 Thyroid Nodule
Ø A thyroid nodule is an abnormality found on physical examination of
the thyroid gland.
Ø Nodules are benign (75%).
q Epidemiology & Demographics:
• Palpable thyroid nodules occur in 5% of the population clinically and
70% by ultrasound.
• Thyroid nodules can be found in 50% of autopsies; however, only one
in 10% is palpable.
• Malignancy is present in 5% of palpable nodules.
• The incidence of thyroid nodules increases with age 45 yr.
• They are found more frequently in women.
• History of prior head and neck irradiation increases the risk of thyroid
cancer.
q Risk Factors for Thyroid Carcinoma in Patients with Thyroid
Nodule:
1) History of head and neck irradiation
2) Age <20 or >45 years
3) Bilateral disease
4) Increased nodule size (>4 cm)
5) New or enlarging neck mass
6) Male gender
7) Family history of thyroid cancer
8) Vocal cord paralysis, hoarse voice
9) Nodule fixed to adjacent structures
10)Extrathyroidal extension
11)Suspected lymph node involvement
12)Iodine deficiency (follicular cancer)
13)High TSH
Physical Findings & Clinical Presentation:

o Palpable, firm, and nontender nodule in the thyroid area should

prompt suspicion of carcinoma.

o Signs of metastasis are regional lymphadenopathy and inspiratory

stridor.

o Signs and symptoms of thyrotoxicosis can be found in functioning

nodules.
Investigation:

q Laboratory tests
o TSH, FT4: should be obtained before thyroidectomy in all patients
with confirmed thyroid carcinoma on FNA biopsy.

o Serum calcitonin: when suspecting medullary carcinoma of the

thyroid and in anyone with a family history of medullary thyroid
carcinoma.

o Serum thyroid autoantibodies: are useful when thyroiditis is

suspected.
Imaging Studies:

Ø Thyroid ultrasound: is useful to evaluate the size of the thyroid and

the number, composition (solid vs. cystic), and dimensions of the
thyroid nodule; solid thyroid nodules have a higher incidence of
malignancy, but cystic nodules can also be malignant.

o The introduction of high-resolution ultrasonography has made it

possible to detect many nonpalpable nodules (incidentalomas) in the
thyroid (found at autopsy in 30% to 60% of cadavers).
o Most of these lesions are benign. For most patients with nonpalpable
nodules that are incidentally detected by thyroid imaging, simple
follow-up neck palpation is sufficient.
Thyroid Scan
q A thyroid scan can be performed with technetium-99m pertechnetate,
iodine-123, or iodine-131.
q Iodine isotopes are preferred because up to 35% of nodules that
appear functioning on pertechnetate scanning may appear
nonfunctioning on radioiodine scanning.
1. Classifies nodules as hyperfunctioning (hot), normally functioning
(warm), or nonfunctioning (cold); cold nodules have a higher incidence
of malignancy.
2. Scan has difficulty in evaluating nodules near the thyroid isthmus or
at the periphery of the gland.

• Both thyroid scan and ultrasound provide information about the risk of
malignant neoplasia based on the characteristics of the thyroid nodule,
but their value in the initial evaluation of a thyroid nodule is limited
because neither provides a definite tissue diagnosis.
Fine-Needle Aspiration (FNA) Biopsy

q A fine-needle aspiration (FNA) biopsy is the best diagnostic study; the

accuracy can be >90%, but it is directly related to the level of
experience of the physician and the cytopathologist interpreting the
aspirate.

q FNA give 5% cancer, 20% indeterminate, and 75% benign.

q FNA biopsy is less reliable with cystic thyroid lesions; surgical excision
should be considered for most thyroid cysts not abolished by
aspiration.
 Thyroid Carcinoma
o There are four major types of thyroid carcinoma: papillary, follicular,
anaplastic, and medullary.
q Epidemiology & demographics
• Thyroid cancer is the most common endocrine cancer,
• Female/male ratio is 3:1.
• Median age at diagnosis: 45 to 50 years
q Clinical presentation
• Presence of thyroid nodule
• Hoarseness and cervical lymphadenopathy
• Painless swelling in the region of the thyroid
q Etiology
• Risk factors: prior neck irradiation
• Multiple endocrines neoplasia II (medullary carcinoma)
Subtypes:
q Papillary Carcinoma:
ü 80% of all thyroid cancers
ü Most frequently occur in women during second or third decade
ü Histologically, psammoma bodies (calcific bodies present in papillary
projections) are pathognomonic; found in 35% to 45% of papillary
thyroid carcinomas
ü Spread is by lymphatics and by local invasion

q Follicular Carcinoma:
ü 10% of all thyroid cancer
ü More aggressive than papillary carcinoma
ü Incidence increases with age
ü Tends to metastasize by hematogenous spread to bones, producing
pathologic fractures
Subtypes:

q Anaplastic Carcinoma:
ü 1% of all thyroid cancer
ü Very aggressive neoplasm
ü Fatal within short duration

q Medullary Carcinoma:
ü 5% of all thyroid cancer
ü Unifocal lesion: found sporadically in elderly patients
ü Bilateral lesions: associated with pheochromocytoma and
hyperparathyroidism; this combination is known as MEN-II and is
inherited as an autosomal-dominant disorder.
Laboratory Tests:

§ Thyroid function studies are normal.

§ TSH, FT4, and serum thyroglobulin levels should be obtained before

thyroidectomy in patients with confirmed thyroid carcinoma.

§ Increased plasma calcitonin assay in patients with medullary

carcinoma (tumors produce calcitonin).

§ Fine-needle aspiration biopsy is the best method to assess a thyroid

nodule
Imaging Studies:

§ Thyroid ultrasound can detect solitary solid nodules that have a high
risk of malignancy.

§ However, a negative ultrasound does not exclude the diagnosis of

thyroid carcinoma.

§ Thyroid scanning with iodine-123 or technetium-99m can identify

hyperfunctioning (cold) nodules, which are more likely to be
malignant. However, warm nodules can also be malignant.
Treatment:
q Papillary Carcinoma:
• Total thyroidectomy followed by L-thyroxine to suppress serum TSH
concentrations to <0.1 mIU/L.
• Radiotherapy with iodine-131 (after total thyroidectomy) for persistent
local disease.
q Follicular Carcinoma:
1. Total thyroidectomy.
2. Radiotherapy with iodine-131

ü Postoperative hypothyroidism is treated by L-thyroxin to prevent any

increase in TSH, which could stimulate the growth of tumor of Papillary
or Follicular type.
Treatment:

q Anaplastic Carcinoma:
ü At diagnosis, this neoplasm is rarely operable; palliative surgery is
indicated for extremely large tumor compressing the trachea.
ü Management is usually restricted to radiation therapy or chemotherapy

q Medullary Carcinoma:
ü Thyroidectomy should be performed.
ü Patients and their families should be screened for pheochromocytoma
and hyperparathyroidism.
Prognosis:

Ø Prognosis varies with the type of thyroid carcinoma: 5-yr survival

approaches 80% for follicular carcinoma and is approximately 5% with
anaplastic carcinoma.