THYROID PHYSIOLOGY 2

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1.      How is thyroid gland function regulated ?
·         Like any endocrine glands the secretion of thyroid hormones are regulated by pituitary gland and hypothalamus.

2.      How does pituitary gland regulate thyroid hormone synthesis?
·         TSH is a glycoprotein which is secreted by thyrotropes in ant pituitary.
·         TSH release is stimulated by TRH (thyrotrophin releasing hormone).

3.      How does TSH function?
·         It is secreted from ant pituitary in a pulstaile manner.
·         Secretion is high in the evening.
·         It then acts on thyroid hormone by stimulating both adenyl cyclase and phospholipase C enzyme.
·         TSH regulates all the steps of thyroid hormone synthesis.

4.      What are the subunits of TSH?
·         It is composed of Alpha and beta components.
·         Alpha component is common to FSH,LH and HCG.
·         Beta component is specific and is important for its function.

5.      What is negative feedback loop?
Increase in T3 and T4 levels decreases TSH and TRH secretion and vice versa.
T4 is more important in suppression of this TSH and feeback suppression.
6.     

TSH secretion is inhibited by a very small increase in serum T4 and T3 concentrations and it increases in response to very small decrease in serum T4 and T3.



A very tight control of TSH secretion is maintained within a very narrow limit.

An exception is low T3 in case of nonthyroidal illness has little effect on TSH secretion.

7.      What are other hormones that can effect Thyroid synthesis?
·         Dopamine @ > 1 mcg/kg/m – suppresses TSH secretion
·         Dopamine antagonist – increases TSH
·         Cortisol – Suppresses TSH secretion .
·         Somatostatin and analogue octreotide reduce TSH concentration.
All these effects are transient and sustained increase in these hormones do not cause sustained effect.
8.      What are the factors altering peripheral conversion of T4 to T3?


                                

 

 




Peripheral conversion by type 1 deiodinase

BUT TYPE 2 DEIODINASE WHICH IS PREDOMINANT IN BRAIN AND PITUITARY IS ACTIVITY BY HYPOTHYROIDISM AND INHIBITED BY HYPERTHYROIDISM

NO EFFECT OF PTU ON TYPE 2 DEIODINASE.

NOTE: The production of T3 in different tissues is regulated in different ways and that changes in thyroidal or extrathyroidal thyroid hormone production, as manifested by their circulating concentrations, are not the only and, perhaps, not the major determinants of intracellular T3 availability.
Local regulation of T3 production may be particularly important in reducing the impact of thyroid deficiency in tissues such as the brain and pituitary, and this local regulation undoubtedly leads to differences in T3 content in different tissues in patients with nonthyroidal illness.

9.      Can disorders of Thyroid binding globulin present with disease?
NO clinical disease and do not require treatment.
They are found incidentally due to abnormal TFTs.

10.  What is congenital thyroid globulin deficiency and how do they present?
It is X linked Dominant trait
It is characterized by low total T4 but free T4 and TSH are normal.
Confirmed diagnosis by low level or absence of TBG.
No treatment is required
Diagnosis is required to prevent unnecessary treatment for hypothyroidism

11.  What are some acquired causes of TBG deficiency?
Androgens
Anabolic steroids
Glucocorticoids
Liver disease
Severe illness
Nephrotic Syndrome
Protein losing enteropathy.

12.  What is congenital TBG excess?
·         X linked dominant condition
·         Characterised by High total T4 and Variably elevated T3 but normal free T4 and TSH
·         No treatment is required but diagnosis is imp to prevent unnecessary treatment of hyperthyroidism.

13.  What are some of the acquired causes of excess TBG?
Estrogen
Pregnancy
Hepatitis
Porphyria
Heroin
5- flurouracil.

14.  What is familial dysalbuminemic hyperthyroxinemia?
·         It is a autosomal dominant condition
·         It is a condition characterized by abnormal albumin with markedly increased affinity for T4.
·         LABS – high total T4, normal fT3, fT4 and TSH.

15.  What is the relationship of amiadarone with thyroid?
It is a class 3 antiarrhythmic drug which can cause both hyper and hypothyroidism.


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CLICK HERE FOR NEONATAL GRAVES

 THANK YOU
DR NISCHAL 

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