drugs on thyroid function, drug interactions

1. EFFECT OF DRUGS ON
THYROID FUNCTION
Dr.C.Pallavi
Assistant professor, Pharmacology
SVIMS, SPMC(W), Tirupati

2. Objectives
• Definitions
• Why do we need to know about various drugs that
interfere with thyroid function?
• Hypothalamic–Pituitary–Thyroid Axis
• Metabolism of T4 and T3
• Drugs altering thyroid hormone synthesis & release
• Drugs that interfere with thyroid function testing
• What to do when prescribing medications that interfere
with LT4 therapy
• Conclusion

3. • Primary hypothyroidism- is defined as low levels of blood
thyroid hormone due to destruction of the thyroid gland
• The destruction is usually caused by autoimmunity or an
intervention such as surgery, radioiodine, or radiation
Clinical (overt)
hypothyroidism
Subclinical
hypothyroidism
• characteristic clinical
features
• raised levels of thyroid-
stimulating hormone (TSH)
• reduced levels of T4
• serum TSH is raised
• serum T4 is normal
• there are no symptoms of
thyroid dysfunction

4. • Central hypothyroidism is defined as hypothyroidism due
to insufficient stimulation by thyroid stimulating hormone
(TSH) of an otherwise normal thyroid gland. It can occur at the
level of the hypothalamus or the pituitary gland
• Undertreated primary hypothyroidism is elevation of
serum TSH above target levels, is observed in approximately
20% of primary hypothyroid patients treated with tablet
Levothyroxine.

5. What are the potential deleterious effects
of inadequate levothyroxine?
The 2014 ATA guidelines recommend that :
• The adverse effects of thyroid hormone deficiency include
detrimental effects on the serum lipid profile and progression
of cardiovascular disease.
• Hence the patients with overt hypothyroidism has to be treated
with doses of levothyroxine that are adequate to normalize
serum thyrotropin levels, in order to reduce or eliminate these
undesirable effects.

7. Biosynthesis of thyroid hormones

8. T4 metabolism

9. 1. Drugs that interrupt one or more steps of
thyroid hormone synthesis leading to
hypothyroidism.
a. Iodine uptake: Lithium, Ethionamide.
b. Organification of iodine: Amiodarone, Sulfonamides,
Lithium, Ketoconazole.
2. Drugs that alter thyroid autoimmunity (TAI) causing
changes in overall gland function leading to
hypothyroidism or hyperthyroidism, or mere
appearance of thyroid antibodies in presence of
euthyroid state.
a. Aggravate TAI: Amiodarone, Lithium
b. Induce TAI de novo: Cytokines, Tyrosine Kinase
Inhibitors, Alemtuzumab
3. Drugs that affect follicular cell activity and growth
leading to destructive thyroiditis or goiter:
Lithium, Amiodarone, Cytokines.
Different
mechanisms by
which drugs
influences the
thyroid
hormone
synthesis and
release

10. Someriskfactorsfordrug-inducedhypothyroidisminpeoplenot
takingthyroidsupplements
• Autoimmune thyroiditis (such as Hashimoto disease)
• Previous thyroid disease
• Partial thyroidectomy
• History of radioactive iodine administration
• History of postpartum thyroid disease
• Family history of thyroid disease
• Previous thyroid damage
• Female sex

11. How iodides and iodine containing preparations
affect thyroid function?
• Recommended normal daily intake of iodine is 0.15 mg
• Iodides are hidden in many preparations :
 prescription ones - amiodarone, radiocontrast dyes, povidone
iodine, and iodinated glycerol) and
nonprescription ones - cough and cold preparations, kelp
tablets, herbal preparations, and dietary supplements
• Amiodarone contains 37.5% iodine by weight
• As much as 175 mg of iodide can be released from radiographic
contrast media
• Hypothyroidism is reported in 6% to 10% of patients receiving
amiodarone (Wolff-Chaikoff block)

12. Wolff-Chaikoff block
Iodides
Iodides
Iodides

13. • Iodide-induced hyperthyroidism (Jod-Basedow disease) usually
develops within 3 to 8 weeks after an increase in iodide
supplementation (for example, after the administration of
radiocontrast dye or amiodarone) in persons with
autonomously functioning, nontoxic multinodular goiters (1-
5%).

14. Medications that alter thyroid function tests
in euthyroid people
Decreased TSH
(below
normal but
detectable
Increased TSH
(usually <10
U/L)
Increased Free
T4
Decreased Free
T4
Dopamine,
Levodopa,
Bromocriptine,
Glucocorticoids
(>0.5 Mg/Day
Dexamethasone,
100 Mg/Day
Hydrocortisone),
Octreotide,
Amphetamines
Metoclopramide
>1 Mg/Kg
Amiodarone,
Iodinated
contrast media
IV furosemide
>80 mg/day,
Nonsteroidal
agents
(Salicylates >2
g/day,
Diclofenac,
naproxen),
IV heparin,
amiodarone,
Iodinated contrast
media
Phenytoin,
Carbamazepine

15. Medications that affect T4 binding with
plasma proteins
Medications
• Estrogen and Estrogen-
containing contraceptive pills
• Androgens, Anabolic Steroids
• Tamoxifen citrate
• Heroin, Methadone
hydrochloride
• Fluouracil
• Mitotane
• Nicotinic acid and
• Glucocorticoids
Medical conditions with altered
TBG
• Nephrotic syndrome

16. Drugs inhibiting conversion of T4 to T3
• Amiodarone
• Iodinated contrast media (for example, ipodate, iopanoic
acid, and tyropanoate)
• Betablockers
• Corticosteroids

17. Medications that affect T4 requirements
• Cytochrome P-450 hepatic enzyme inducers (for example, Rifampin,
Rifabutin, Phenytoin, Carbamazepine, And Phenobarbitone) can
increase the metabolic elimination of T4 and T3 by 20%
• Patients who are already on T4 replacement may need higher doses
to maintain euthyroidism
• Ritonavir, a potent P-450 mixed hepatic enzyme inhibitor and
inducer, can increase thyroxine glucuronidation, necessitating a
twofold increase in thyroxine dosage to maintain euthyroidism
• SSRIs like Sertraline
• Lithium
• Amiodarone
• Aminoglutethimide, Mitotane, 5-FU
• Clofibrate, estrogens

18. Drugs that impair the absorption of
Exogenous Thyroxine
• Iron preparations
• Aluminum-containing products (such as sucralfate, antacids,
and didanosine)
• Sodium polystyrene sulfonate
• Resin binders
• Calcium carbonate
• Coffee
• Proton pump inhibitors, H2R blockers
• Patients should take levothyroxine at least 4hours before or
after taking any medication that might interfere with
absorption to minimize this interaction

21. • In this study, out of 76 patients who are on interfering
medications,TSH averaged 5.88 ± 5.68 mU/L among 29 patients
who had complications when compared to patients without
complications.

22. • No. of complications(mean ± SD) per patient is 2.72 ± 1.2 Vs
1.23 ± 0.5

23. Conclusion
• The accurate interpretation of abnormal thyroid function test
results may be complicated by the concomitant presenceof
medications and nonthyroidal illnesses.
• It is important that clinicians recognize the effects of drugs on
laboratory interpretation, drug-induced thyroid illnesses,
and exogenous thyroid requirements to prevent medical
treatments that may be dangerous or that inappropriately
increase the cost of caring for patients.

24. References
1. Salvatore Benvenga et al. A minimum of two years of
undertreated primary hypothyroidism, as a result of drug-
induced malabsorption of l-thyroxine, may have metabolic
and cardiovascular consequences. Journal of Clinical &
Translational Endocrinology;16 (2019) 100189
2. Dong BJ. How medications affect thyroid function. West J
Med. 2000 Feb;172(2):102-6.
3. Baruah MP, Singh RJ. Effects of drugs on thyroid function.
Thyroid Res Pract 2012;9:3-6.