With reference to thyroid function:
a) Briefly outline the thyroid function/hormone profile expected in the sick euthyroid syndrome or non-thyroidal illness syndrome (NTIS).
b) For each of the following drugs, list its effect(s) on thyroid function.
c) Briefly outline your pharmacological approach to the treatment of thyrotoxic crises. Include in your answer the rationale for each drug used.
a)
b)
i. Amiodarone
Inhibition of peripheral conversion T4 to T3
ii. Propranolol
Inhibition of peripheral conversion T4 to T3
iii. Glucocorticoids
Inhibition of peripheral conversion T4 to T3
Suppression of TSH secretion
iv. Opiates
Suppression of TSH secretion
c)
A sequential, multidrug approach is vital and the order of therapy is important. Three pathways need consideration-halting synthesis, preventing release of stored hormone and blockade of peripheral effects including blocking conversion of T4 toT3 as well as control of adrenergic symptoms.
Halting synthesis:
First line therapy with Thionamides- thiouracils (Propylthiouracil or PTU) and or imidazoles (methimazole and carbimazole) may be used. Both block thyroperoxidase coupling of idotyrosine residues in formation of T4 and T3.PTU (not imidazoles) will also block peripheral conversion of T4 to T3.
Both given gastrically/PO/retention enema.
Halting release:
Thionamides block synthesis only but not secretion of preformed glandular stores of hormone. Separate treatment is needed to inhibit proteolysis of colloid and continuing release of T3 and 4. Inorganic iodine therapy either with orally administered Lugol solution or potassium iodide should be used. Iodine should only be used 30 -60 minutes
AFTER administration of Thionamides since hormone synthesis may be stimulated.
Alternatives include Li Carbonate and some of the older radiographic contrast agents.
Blocking peripheral action:
B blockade is essential to control peripheral actions of thyroid hormone.
Propranolol is commonly used either gastrically or IV. A drop in T3 levels may be seen with its use (decreases T3-T4 conversion). Glucocorticoids have a role in that they also block conversion of T4 to T3 and may treat any relative adrenal or vasomotor insufficiency that occurs.
The sick euthyroid syndrome is discussed in greater detail elsewhere.
In brief, the TFT abnormalities are:
The drugs which affect thyroid metabolism are also discussed in another chapter("The influence of drugs on thyroid function")
In short:
In not so short:
TSH | Inhibition of release | |
Stimulation of release |
Antipsychotics, especially amisulpiride |
|
T3 and T4 synthesis | Inhibition of thyroid synthetic function |
Thiouracils (eg. propylthiouracil) Imidazoles (eg. carbimazole) |
Stimulation of thyroid synthetic function |
Inorganic iodine (eg. potassium iodide) - if you have a normal thyroid gland Iodinated contrast agents (high iodine content) |
|
T3 and T4 release from the thyroid gland | Inhibition of release |
Inorganic Iodine (eg. potassium iodide) Iodinated contrast agents (high iodine content) |
Stimulation of release |
Amiodarone (by thyroiditis) |
|
Conversion of T4 into T3 | Inhibition of conversion | |
Stimulation of conversion |
Selenium (a cofactor in T4-T3 conversion; selenium supplementation will not result in a supranormal T3 level - merely a return to normal) |
|
Transport of thyroid hormones by binding to thyroid-binding globulin (TBG) |
Increased TBG levels (thus decreased free T3) |
|
Decreased TBG levels (thus increased free T3) |
Niacin (nicotinic acid) |
|
Increased binding of T4 to TBG | ||
Decreased binding of T4 to TBG (by displacement) |
Aspirin and salicylates in general Frusemide (and ethacrynic acid) |
|
Clearance of T4 | Increased clearance | |
Decreased clearance |
Glycosylflavones in millet-rich diets of the poor in the developing world, or in the weird hippies who think it is healthy to emulate them. |
The management of thyrotoxic crisis is well summarised by the college answer, but could be whittled down to point-form to improve the cerebral dwell-time among time-poor exam candidates:
For those uncomfortable with the austere minimalism of point-form, an extensive rambling digression is also available.
UpToDate has an excellent entry on this topic, for the paying customer.
Alternatively, one can attempt to piece things together from free-full-text articles, and from this Life In The Fast Lane summary.
Zargar, A. H., et al. "Prevalence and pattern of sick euthyroid syndrome in acute and chronic non-thyroidal illness-its relationship with severity and outcome of the disorder." JOURNAL-ASSOCIATION OF PHYSICIANS OF INDIA 52 (2004): 27-32.
Peeters, Robin P., et al. "Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients." Journal of Clinical Endocrinology & Metabolism 88.7 (2003): 3202-3211.
Baruah, M. P., and R. J. Singh. "Effects of drugs on thyroid function." Thyroid Research and Practice 9.1 (2012): 3.