Chemical Pathology Flashcards
What are the 3 hormones that are secreted by the thyroid?
T4
T3
Calcitonin- used as a tumor marker in TCA
What is the pathogenesis of congenital hypothyroidism?
Defect in metabolic steps of Thyroid hormones.
What is the mechanism for carbimazole?
interferes with biosynthetic steps of an overactive thyroid
Explain the difference between T3 and rT3.
T3- is the active form of T4, resulting from the deiodination of T4’s outer ring.
rT3- reverse T3 is an inactive form, resulting from the deiodination of the inner ring.
In what conditions are the rT3 formed?
Starvation, severe illness
-limit bodies energy expenditure
How does T3 perform its function?
Enters the cell and binds to receptors in the nucleus
upregulates expression of genes
increase sensitivity to hormones, such as CVS and NS to catecholamines, enhances insulin action
Required for metabolic activity- O2 consumption and ATP hydrolysis increase (mitochondria)
Why does a person remain euthyroid despite the change in a TBG?
When TSH levels increase, more TBG is produced, leading to an increase in total T4 levels. Conversely, when TSH levels decrease, less TBG is produced, leading to a decrease in total T4 levels.
However, it is important to note that only the free, biologically active form of T4 is able to exert its effects on the body. Therefore, even if the total T4 level increases or decreases due to changes in TBG levels, as long as the level of free T4 remains within the normal range, the patient will remain euthyroid (meaning their thyroid function is normal).
Explain how the total level of thyroid hormone can be misleading.
Thyroid hormones (T4 and T3) are transported in the bloodstream by binding to a carrier protein called thyroxine-binding globulin (TBG). However, certain drugs can compete with thyroid hormones for the binding sites on TBG, thereby reducing the effective concentration of TBG. This competition can result in a decrease in the level of total thyroid hormone in the blood, even though the amount of free hormone may remain unchanged.
Measuring total thyroid hormone alone can be misleading because it does not account for changes in TBG concentration or the amount of hormone that is bound to the protein. Measuring free hormone levels directly provides a more accurate reflection of the amount of thyroid hormone available to the body.
What affects TBG levels?
Increase
estrogen
-Oral con pill
-pregnancy
Decrease
Protein-losing states
Malnutrition
Costicosteroids
What are the Thyroid Cancer markers?
Thyroglobulin (anti-thyroglobulin Abs)
-papillary and follicular
Calcitonin
-Medullary
Which conditions can be missed if you test TSH assay?
Secondary Hypothyroidism and sick euthyroid syndrome.
Explain what happens between TSH and fT4 in graves disease.
Graves treated with radio-iodine and antithyroid TSH responds slowly to therapy
overtly low fT4 (hypothyroid)
TSH is still-suppressed
Thyrotoxicosis
What are the symptoms of hyperthyroidism?
Weight loss, sweating, heat intolerance, fatigue
Tachycardia, atrial fibrillation, angina, high output cardiac failure
Agitation, tremor, generalized muscle weakness, proximal myopathy
Diarrhoea, oligomenorrhoea, infertility, goitre Eyelid retraction, proptosis, diplopia (Grave’s disease)
Explain the pathogenesis of graves disease.
Ab to TSH receptor mimics TSH
Activation and constant stimulation of gland and producing of thyroxine
Pituitary TSH suppressed.
What are the laboratory results for graves disease?
High Plasma concentration of T3 + T4
Totally suppressed
What are the clinical features of graves disease and how do they manifest?
Proptosis- bulging eyes, thickening of retroorbital muscles
pre-tibial myxoedema- swelling of soft tissues.
Explain how Gestational Trophoblastic disease causes hyperthyroidism.
Tumour from trophoblastic tissue
Increase HCG
Cross reacts with TSH, Overlapping activity of the alpha globin (same as TSH)
TSH was suppressed and T4 increased
Describe the thyroid storm.
Acute presentation of thyrotoxicosis
hyperpyrexia
dehydration
cardiac failure
What are the causes of hypothyrodism?
Autoimmune hypothyroidism
Atrophic thyroiditis
Hashimoto’s thyroiditis goitre
Iatrogenic
* Post surgery, radioactive iodine, antithyroid drugs
Rare 2 ° hypothyroidism (N/↓TSH) Enzyme defects * Iodine deficiency
What are the thyroid function test results?
TSH high
T3 and T4 Low
Prolactin High due to TRH
Cholesterol High
CK high
What is the complication of congenital hypothyroidism?
Mental retardation
Explain sickle euthyroid syndrome.
Typically, during the acute phase of a serious illness, fT3 and, less often, fT4 concentration drops below normal. TSH is usually normal but may be low in the severely ill. Possible explanations include decreased peripheral conversion of T4 to T3, and inhibition of TSH secretion by cortisol.
Explain the relationship between exercising and insulin
It increases the uptake of glucose in muscles
Describe obesity and overweight.
BMI of
25-30 overweight
30-40 Obese
