Pathophysiology of Hyper and Hypothyroidism

1
Pathophysiology of Hyper and Hypothyroidism
2
Hyperthyroid Background

• Serum TSH in patients with primary
  hyperthyroidism (which accounts for 99.9 of the
  cases of hyperthyroidism) is low. A very low
  value (lt0.01) is diagnostic of hyperthyroidism
• Exceptions include conditions that primarily
  affect the hypothalamus/pituitary.

3
Etiology of Hypethyroidism

• Graves Disease (60-70)
• Autoimmune disorder
• Antibody (Ab) directed against various thyroid
  proteins
• Commonly Ab against TSH receptor
• Acts as TSH receptor agonist mimics effect of
  TSH
• Ab against other thyroid proteins (e.g.,
  peroxidase thyroglobulin) can also be present

4
Graves Disease Patient
5
Etiology of Hypethyroidism

• Toxic Multinodular Goiter (20-30)
• Occurs when large thyroid follicles gain partial
  autonomy and begin secreting T4
• Subacute Thyroiditis
• Due to destruction of thyroid gland by illness or
  autoimmune destruction
• Destruction of follicles, not secretion, leads to
  release of hormone

6
Etiology of Hypethyroidism

• Toxic Adenoma (3-5)
• Caused by a single hyperfunctioning follicular
  thyroid adenoma
• Metastatic Thyroid Carcinoma (rare)
• Molar Hydatiform Pregnancy and Choriocarcinoma
• hCG shares alpha chain with TSH
• Excessive level causes crossover stimulation

7
Hyperthyroidism in Animals
Cats are prone to hyperthyroidism
8
Therapy of Hyperthyroidism

• Thionamides
• Propylthiouracil PTU and methimazole
• Inhibit thyroid hormone synthesis through
  inhibition of Thyroidal peroxidase (TPO)
• Subsequent steps also prevented
• Prevention of oxidation of trapped iodine
• Inhibition of coupling of iodotyrosines

9
Therapy of Hyperthyroidism

• Radioactive Iodine (I-131) Ablation
• Almost always used along with surgery in cases of
  metastatic thyroid carcinoma
• Surgery
• Subtotal or near total thyroidectomy

10
Question

• Why did Mohammad Ali train for his title boxing
  match comeback by taking thyroxine?

11
Hypothyroidism

• Serum TSH is invariably increased in patients
  with primary hypothyroidism (which accounts for
  99 of cases of hypothyroidism) and is one of the
  most specific tests in medicine virtually
  nothing else raises the serum TSH.

12
Examples of thyroid function tests in various
thyroid conditions
13
Primary Hypothyroidism

• Primary hypothyroidism is due to defect within
  the thyroid gland.
• This is by far the most common cause accounting
  for 98 of cases of hypothyroidism

14
Primary Hypothyroidism

• Iodide Deficiency
• A problem in many less well-developed countries.
• Goiter is common in these areas
• Some children develop cretinism

15
Primary Hypothyroidism

• Hashimoto's (Chronic) Thyroiditis
• The most common cause of hypothyroidism
• Cause of Hashimoto's thyroiditis is autoimmune
  destruction of the thyroid gland
• More common in women
• Strong familial component
• Thyroid antibodies (anti-thyroglobulin and/or
  anti-TPO antibodies) are present in the majority
  of patients

16
Secondary Hypothyroidism

• In adults, it is almost always due to pituitary
  disease
• Example TSH secreted by the pituitary may not be
  as biologically active

17
Tertiary Hypothyroidism

• Tertiary hypothyroidism is due to hypothalamic
  disease (e.g. tumors, radiation)

18
Resistance to Thyroid Hormone

• Peripheral Resistance to thyroid hormone is
  caused by genetic defects in the thyroid hormone
  nuclear receptor resulting in abnormal binding
  and defective gene transcription
• Peripheral resistance is uncommon

19
Therapy of Hypothyroidism

• The treatment of hypothyroidism is oral thyroxine
  (T4).
• Levothyroxine, also known as L-thyroxine,
  synthetic T4 sold under various brand names
• TSH level is used as a marker for euthyroidism
  TSH within the normal range is the goal of
  treatment