Download Pathophysiology of Thyroid Disorders

Pathophysiology of Thyroid
Disorders
Ebenezer Nyenwe, MD
Assistant Professor of Medicine
Division of Endocrinology, Diabetes and Metabolism
College of Medicine
University of Tennessee Health Science Center
Memphis, TN

Congenital Hypothyroidism and/or Goiter result from defects in
iodine binding mechanism.
Mutations in NIS.
Abnormalities in synthesis of TG or TPO.

Cyanates and Perchlorate compete with iodine for NIS thus
predisposing to iodine deficiency and goiter (goitrogens).

Pendred’s syndrome is an autosomal recessive disorder due to
mutation in pendrin gene- deafness, goiter and impaired thyroid
hormone synthesis

The release of thyroid hormone is inhibited by high iodine load
(Wolff-Chaikoff effect) and Lithium
 Thyroid
hormone binding to TBG is inhibited by
Phenytoin, Salicylate, salsalate, furosemide,
fenclofenac and mitotane.
 Low
TBG levels occur nephrotic syndrome
 High
TBG levels
Familial-X-linked genetic disorder
Acquired- pregnancy, estrogen, hepatitis
.
 TSH
secretion is decreased byDopamine,
Dobutamine,
Somatostatin,
Acute high dose glucocorticoids,
Baroxetene.
Mutations in the TSH receptor can result in
activation or inhibition of the receptor.
A clone of such cells with constitutive activation
could give rise to autonomous nodules.
Pathophysiology of Thyroid Disorders

Iodine deficiency (IDD)- about a billion people live in
iodine deficient regions.
Goiter
Hypothyroidism
Impaired mental function (cretinism in severe
cases)
Impaired physical development
Increased perinatal mortality

Autoimmune thyroid disease
TSH receptor
Thyroid peroxidase
Thyroglobulin

Goiter
Goiter is the enlargement of the thyroid glandDiffuse
Solitary nodule or
Multinodular
EtiologyAutoimmune
Familial
Genetic abnormalities involving TG, NIS, TPO, pendrin and
TSHR are associated with goiter and
hypothyroidism.

Growth factors- EGF, IGF-1, FGF, TGF and VEGF

Environmental factors- iodine deficiency, cigarette smoking,
drugs eg lithium, goitrogens.

Neoplasia




Laboratory Investigations
Thyroid function test- TSH, Total T4, Free T4, Total T3,
Free T3
Thyroid antibodies- TSI, TPO,
Thyroglobulin and anti TG
Thyroxine binding globulin
Imaging
 Thyroid ultrasound
 Radioactive iodine uptake and thyroid scan
 CT, MRI, PET scan

Fine needle aspiration biopsy/cytology
 Histopathology
Ultrasound Features Suggestive of Malignancy

Solid hypoechoeic nodule

Absence of cystic elements

Microcalcification

Irregular shape

Thick wall

Absence of halo

hypervascularity
.
Features Suggestive of Thyroid Malignancy

Age - < 20 or > 70 years

Male

History of Radiation

Family history of Thyroid cancer or MEN 2

Rapid growth

Recent dysphagia, dypsnoea or dysphonia
.
.
Papillary
CA
Abnormal Thyroid function Tests in Euthyroid subjects.
 Non
thyroidal illness
 Pregnancy
 Psychiatric
 Liver
illness
disease
 Familial
variant binding proteins
 Thyroid
hormone resistance
Case # 1.
A 24-year-old female college student who started using oral contraceptive pill six
months ago was found to have abnormal thyroid function test (TFT) while being
investigated for excessive weight gain. She had no history of heat or cold
intolerance and no change in appetite or bowel habit. Her sleeping pattern had
remained unchanged. She denied palpitation, tremors or sweating. Her
menstrual cycle was normal. Physical examination revealed a young woman
who was overweight (BMI= 28), pulse rate= 82/min, BP= 122/75 mmHg. No
proptosis. Thyroid gland was not palpable. The rest of the physical exam was
unremarkable.
Labs.
CMP= within normal limits
CBC= Within normal limits
TSH= 2.4 µU/ml ( 0.5-5.0)
Free T4 = 1.8ng/dl (0.7-2.0)
Total T3 = 210ng/dl ( 70- 190)
Total T4= 15µg/dl (5-12)
1.
2.
3.
4.
5.
What abnormalities do you identify in her TFT?
What is the etiology of this woman’s abnormal TFT?
What is your diagnosis?
What intervention would you recommend at this point?
What are the other causes of this abnormality?
Case #2 and # 3
A 22-year-old African-American woman presents with a two-month history of weight loss
despite increased appetite, insomnia, heat intolerance and sweating. She has also
noticed increasing episodes of palpitations and exertional dyspnea as well as difficulty
with climbing stairs and combing her hair. On further questioning she admitted to
tremors, fidgeting, lose bowel motions and scanty menstrual periods but no
ammenorrhoea. Physical exam showed BMI= 20, pulse = 112/min, regular, large
volume, BP= 144/62 mmHg, RR= 18/min. She had bilateral proptosis with lid lag and lid
retraction on the left side but no ophthalmoplegia. She had soft, non-tender, diffuse
thyromegaly, which was about two times enlarged with audible bruit, but no cervical
lymphadenopathy. Auscultation of the heart revealed tachycardia with a third heart
sound but no murmur. She had tremor of the out stretched hands which were warm and
moist. Deep tendon reflexes were brisk but she had some difficulty standing up from her
chair.
Labs
CMP= within normal limits
CBC= Within normal limits
TSH= 0.001 µU/ml ( 0.5-5.0)
Free T4 = 3.8ng/dl (0.7-2.0)
Total T3 = 228ng/dl ( 70- 190)
1.What is your clinical Diagnosis?
2. What is the pathophysiology of her disease?
3. How would you confirm your clinical diagnosis?
4. What other tests might be helpful in her management?
5. What treatment would you recommend for this patient?
Patient presents 6 months after treatment with complaints of weight gain,
constipation, somnolence and sluggishness with dry skin, hair loss and
menorrhagia. Pulse= 54/min, BP= 130/98 mmHg. Thyroid gland which had
diminished in size was very firm and non-tender. Deep tendon reflexes showed slow
relaxation after initial normal upstroke.
Labs
TSH= 30.4 µU/ml ( 0.5-5.0)
Free T4 = 0.31 ng/dl (0.7-2.0)
Total T3 = 52 ng/dl ( 70- 190)
1. What is your diagnosis?
2. What is the pathophysiology of her disease?
3. What treatment would you recommend at this time?
4. How long will you treat her?
Case #4
A 65-year-old man with history of diabetes, hypertension, hyperlipidemia admitted to
the coronary care unit for acute myocardial infarction was found to have the
following TFT on the third day of admission.
TSH= 4.0 µU/ml ( 0.5-5.0)
Free T4 = 1.1 ng/dl (0.7-2.0)
Total T3 = 50 ng/dl ( 70- 190)
1. What is you Diagnosis?
2. What is the reason for the low T3 in this patient?
3. How would you treat this patient?