1. Thyroid Gland
Part 2

2. Physiologic Changes in Thyroid Function
Thyroid Function in the Fetus
At birth, there is a sudden marked rise in TSH, in T4 and in T3
These parameters gradually return to normal over the first month of life
Thyroid Function in Pregnancy
There is an increase in urinary iodide clearance; in areas of low dietary iodine intake, this can cause maternal goiter, or when severe, hypothyroidism
During pregnancy, there is a rise in TBG, Consequently, serum total T4, and to a lesser extent, total T3 concentrations rise
Rising levels of hCG, which has weak TSH receptor agonist activity, contributes to minimal thyroid enlargement
peak at approx. 12 weeks resulting in a transient high-normal or even modestly elevated serum free T4 level and a physiologic suppression of serum TSH
hCG: Human chorionic gonadotropin

3. Physiologic Changes in Thyroid Function
Effects of Acute & Chronic illness on Thyroid Function (Euthyroid Sick Syndrome)
Acute or chronic illness has several striking effects on thyroid function
The most common and earliest effect is inhibition of T4 to T3 conversion
low serum T3 levels are typically accompanied by total and free T4 levels that are normal
cytokines, such as tumor necrosis factor, secreted by inflammatory cells, which inhibits deiodinase enzyme

4. Abnormalities in Thyroid Hormone Synthesis and Release
1-Dietary Iodine Deficiency and Inherited Defects
A very low iodine diet and inherited defects in genes encoding the proteins required for thyroid hormone biosynthesis (dyshormonogenesis) can both result in insufficient hormone production
The major adaptation to low iodide intake is the preferential synthesis of T3 rather than T4
In response, the hypothalamic-pituitary-thyroid axis responds to thyroid hormone deficiency by increasing TSH secretion

5. Abnormalities in Thyroid Hormone Synthesis and Release
1- Dietary Iodine Deficiency and Inherited Defects
Consequently, affected individuals typically present with thyroid gland enlargement (goiter)
which may be sufficient to compensate for inefficient thyroid hormone production
but if not, they develop hypothyroidism
Severely affected neonates and infants can suffer the irreversible effects of thyroid hormone deficiency on development that result in cretinism
Goiter
Cretinism

6. Abnormalities in Thyroid Hormone Synthesis and Release
2- Effects of Iodine Excess on Hormone Biosynthesis
Excess iodide actually inhibits three steps in thyroid hormone production:
iodide trapping
thyroglobulin iodination
and thyroid hormone release from the gland
These inhibitory actions are transient, and the normal thyroid gland “escapes” after 10 to 14 days from these effects of excess iodide
These autoregulatory effects of iodide insulate physiologic thyroid function from short term fluctuations in iodine intake
This effect of iodide has been exploited clinically to produce short-term suppression of thyroid hormone secretion

7. Thyroid Autoimmunity
Autoimmunity is involved in the pathogenesis of many thyroid diseases including:
Graves’ disease (hyperthyroidism)
long-acting thyroid stimulator, an antibody to the TSH receptor, was found in the sera of patients
Hashimoto’s thyroiditis (hypothyroidism)
Postpartum thyroiditis,
role for female sex hormones in the pathogenesis
and certain forms of neonatal thyroid dysfunction
Postpartum thyroiditis some women who have postpartum thyroiditis develop symptoms of only hyperthyroidism or only hypothyroidism, but not both.
first cause mild signs and symptoms similar to those of an overactive thyroid (hyperthyroidism),
Later, as thyroid cells become impaired, mild signs and symptoms of underactive thyroid (hypothyroidism) might develop

8. Thyroid Autoimmunity There are three major thyroidal autoantigens:
Thyroglobulin,
TPO,
and the TSH receptor
Circulating autoantibodies to these antigens are useful markers for thyroid autoimmunity
Thyroid peroxidase ( TPO)

9. Disorders of The Thyroid
Patients with thyroid disease usually complain of one or more of the following:
Hypothyroidism, symptoms of thyroid hormone deficiency
Hyperthyroidism, symptoms of thyroid hormone excess
Thyroid enlargement which may be
diffuse or nodular;

10. Hypothyroidism
Hypothyroidism is a clinical syndrome resulting from a deficiency of thyroid hormones, which in turn results in a generalized slowing down of metabolic processes
Hypothyroidism in infants and children results in:
marked slowing of growth and development,
with serious permanent consequences, including mental retardation, when it occurs in infancy
Hypothyroidism with onset in adulthood causes:
generalized decrease in metabolism,
diminished oxygen consumption,
and deposition of glycosaminoglycans in intracellular spaces, particularly in skin and muscle, producing in extreme cases the clinical picture of myxedema
The symptoms and signs of hypothyroidism in adults are reversible with therapy
Glycosaminoglycans: are long unbranched polysaccharides consisting of a repeating disaccharide unit.

11. Myxedema

12. Other symptoms of Hypothyroidism
Cardiovascular signs
Bradycardia
Pulmonary function
shallow, slow respirations
Renal function
impaired with decreased glomerular filtration rate
Neuromuscular system
Muscle weakness
Central nervous system
fatigue, lethargy and inability to concentrate
Lethargy: خمول

13. Hypothyroidism Etiology of hypothyroidism
Hypothyroidism may be classified as
Primary
thyroid failure (most common)
Etiology
Hashimoto’s thyroiditis:
Radioactive iodine therapy for Graves’ disease
Subtotal thyroidectomy for Graves’ disease
Excessive iodide intake
Iodide deficiency
Inborn errors of thyroid hormone synthesis
Drugs (Lithium)
Removal of majority of both lobes leaving behind 4-5 grams (equivalent to the size of a normal thyroid gland) of thyroid tissue on one or both sides
The mechanism by which lithium inhibits thyroid hormone release is not well understood. In vitro, lithium decreases colloid droplet formation within thyroid follicular cells, a reflection of decreased pinocytosis of colloid from the follicular lumen

14. Peripheral resistance to the action of thyroid hormones
Secondary
due to pituitary TSH deficiency
Tertiary
due to hypothalamic deficiency of TRH
Peripheral resistance to the action of thyroid hormones

15. Diagnosis of Hypothyroidism
If antithyroid antibodies are absent and the indication for therapy uncertain, the medication could be withdrawn for 6 weeks and determinations made for FT4 and TSH. The 6-week period of withdrawal is necessary because of the long half-life of T4 (7 days) and to allow the pituitary gland to recover after a long period of suppression.
The 6-week period of withdrawal is necessary because of the long half-life of T4 (7 days) and to allow the pituitary gland to recover after a long period of suppression.

16. Treatment
Hypothyroidism is treated with Levothyroxine (synthetic T4) which is available in pure form and is stable and inexpensive
Because T4 is converted to T3 in peripheral tissues, both hormones become available, even though only one is administered
The course of untreated hypothyroidism is one of slow deterioration, potentially leading eventually to myxedema coma and death

17. Hyperthyroidism & Thyrotoxicosis
Hyperthyroidism  is a condition in which the thyroid gland produces and secretes excessive amounts of thyroid hormones
Thyrotoxicosis is the clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormones
It results in a generalized acceleration of metabolic processes
In most instances, thyrotoxicosis is due to hyperactivity of the thyroid gland, or hyperthyroidism

18. Symptoms of Hyperthyroidism
Cardiovascular signs
Tachycardia
Neuromuscular system
Tremor
Neurological
Anxiety

19. Graves’ Disease
Graves’ disease is the most common form of thyrotoxicosis
Females are involved about five times more commonly than males
Autoimmune disease of unknown cause
The syndrome consists of one or more of the following features:
thyrotoxicosis
goiter
ophthalmopathy
dermopathy
inflammation of the eyes and bulging eyes.

20. Treatment of Graves’ Disease
Although autoimmune mechanisms are responsible for the syndrome of Graves’ disease, management has been largely directed toward controlling the hyperthyroidism
Three good methods are available:
Antithyroid Drug therapy
inhibiting TPO-mediated iodination of thyroglobulin
Surgery
Partial or total thyroidectomy
and radioactive iodine therapy (131I)
destroys thyroid cells
A dangerous and short lived fission product. Iodine 131 is a radioisotope with a very short half-life of 8.02 days, making it highly radioactive

21. Other Forms of Thyrotoxicosis
Toxic Adenoma
A functioning adenoma hypersecreting T3 and T4 causes hyperthyroidism
These lesions start out as a small autonomously functioning nodule that slowly increases in size to produce excessive quantities of thyroid hormones
This gradually suppresses endogenous TSH secretion, which results in reduced function of the contralateral lobe of the gland
nodules are solid, raised areas in or under the skin that are larger than 0.5 centimeters.

22. Scanning of Thyroid Gland
Normal
Graves’ disease
Scan using 123I
Scan using  Technetium (Tc)
Solitary toxic nodule
Toxic multinodular goiter
Technetium: radioactive metal. I 123:  The isotope's half-life is hours
Note suppression of contralateral lobe (left) by toxic nodule (right)

23. Thyroid Hormone Resistance Syndromes
Two forms of resistance to thyroid hormones are recognized:
Generalized resistance to thyroid hormones (GRTH)-
75% of reported cases are familial
mutations in the thyroid hormone receptor
transport across cell membrane, thyroid hormone response elements, co-activators, co-repressors
Selective pituitary resistance to thyroid hormones (PRTH)- (resistance in the pituitary gland but not in peripheral tissues)
(resistance in the pituitary gland and in most or all of the peripheral tissues)

24. Nontoxic Goiter Nontoxic goiter is not associated with hyperthyroidism
Can be diffuse or nodular
May result from TSH stimulation due to inadequate thyroid hormone synthesis
Worldwide, iodine deficiency remains the most common cause of nontoxic goiter

25. Thyroiditis Subacute Thyroiditis Chronic Thyroiditis
is an acute inflammatory disorder of the thyroid gland most likely due to viral infection
self-limited thyroid condition 
associated with a triphasic clinical course of hyperthyroidism, hypothyroidism, and return to normal thyroid function
no specific treatment is required
Chronic Thyroiditis
Hashimoto’s thyroiditis
autoimmune disorder in which antibodies directed against the thyroid gland lead to chronic inflammation
Over time, however, this results in impaired ability of the thyroid gland to produce thyroid hormones

26. Thyroid Nodules & Thyroid Cancer
Thyroid nodules are common
Benign Thyroid Nodules
But thyroid cancer is a relatively rare condition
Follicular carcinoma
Medullary carcinoma
disease of the C cells (parafollicular cells)

27. Laboratory Tests Useful in the Differential Diagnosis of Hyperthyroidism
RAIU: Radioactive iodine uptake
GRTH: generalized resistance to thyroid hormone
PRTH: Pituitary resistance to thyroid hormone