MEDICAL MANAGEMENT

Submitted by:
Cura, Jonathan
Luis, Mary Ann Krisna

In general, hypothyroidism is treated with levothyroxine (LT4) (Bharaktiya, S, et.al.. 2009). In oral form, thyroid hormone is best absorbed on an empty stomach. The major toxic reactions to levothyroxine over dosage are symptoms of hyperthyroidism. (Harvard Women’s Health Watch 2009).

A meta-analysis of randomized controlled trial of thyroxine-triiodothyronine combination therapy (T4 + T3) versus thyroxine monotherapy (T4) for treatment of clinical hypothyroidism found no difference in the effectiveness of the combination therapy vs monotherapy in fatigue, body weight, total cholesterol, LDL-C, HDL-C and triglyceride levels. (Grozinsky-Glasberg S, Fraser A, Nahshoni E, et. al., 2006). Hence, T4 monotherapy remains the treatment of choice.

On the other hand, hypothyroid patients who are prone in developing osteoporosis are encouraged to take calcium supplement. It has been said that calcium supplement might alter L-T4 requirements for both replacement and interventional therapy. A cohort study of 20 patients who were receiving long-term levothyroxine therapy and calcium carbonate showed reduced total levothyroxine absorption over 6 hours. Ca supplement reduces the efficacy and may form insoluble chelates with levothyroxine, resulting in decreased absorption. (Mazokopakis, E.E., Giannakopoulos, T.G., and Starakis, I.K., 2008). Consultation with the physician and a change in drug administration schedule might minimize or eliminate the interaction between calcium carbonate and levothyroxine.

In pregnant patients with hypothyroidism, T4 therapy is recommended. The U.S. Food and Drug Administration (FDA) categorized levothyroxine as Pregnancy Category A, meaning, it doesn’t appear to cause any harm to the fetus. (Glendenning, P., 2008). Increased dose requirements by 30% should be anticipated during pregnancy. A prospective study of 20 pregnancies were observed in women with hypothyroidism. The serum thyrotropin level increased during the first 10 weeks of gestation, prompting an increase in the levothyroxine dose to maintain the thyrotropin concentration. (Alexander, E.K., et.al., 2004). Therefore, women with hypothyroidism should contact their health care provider and be instructed to increase their levothyroxine intake on confirmation of pregnancy.

Newborns with elevated TSH should be treated with thyroid hormone replacement until they are aged 2 years to eliminate any possibility of permanent cognitive deficits caused by hypothyroidism. (Ferry, R.J. and Bauer, A.J., 2008). Hypothyroidism in premature-born infants is at high risk in developmental disability compared with term infants. Transient hypothyroxinaemia of prematurity as characterized by low blood thyroxine (T4) is common in infants under 30 weeks' gestation at birth, occurring in up to 69%. A randomized control trial of T4 supplementation showed an improved Mental Development Index (MDI) and Psychomotor Development Index (PDI) at 2 years among infants born premature who had received T4 supplement. (Williams, F.L., Visser, T.J., Hume, R., 2004).

The U.S. Food and Drug Administration has not approved of liquid suspensions of levothyroxine in children as it can lead to unreliable dosage. Parents should be provided with oral form and be taught proper administration. The pills can be crushed in a spoon; dissolved with a small amount of breast milk, or water before administration, and administered to the child with a syringe or dropper. The pills should not be mixed in a full bottle. Toddlers readily chew the tablets without problems or complaints. (Postellon, D.C., 2008).

Myxedema coma is a life-threatening condition; therefore, patients with this disorder must be stabilized in an intensive care unit to preserve vital function. The first 24-48 hours are critical. (Citkowitz, E. 2008).

Thyroid hormone replacement is the mainstay therapy for patients with myxedema coma. They usually require large doses of IV replacement to quickly correct low thyroid hormone blood level. Oral thyroid hormone is usually not used for myxedema coma because it may take days or weeks to obtain the blood level. General guidelines suggest administration of IV levothyroxine at a loading dose of 500-800 mcg and followed by a daily IV dose of 50-100 mcg. The daily dose is administered until the patient is able to take medication by mouth. (Schraga, E.D., 2009).

Supportive Therapy
Mechanical ventilation is often needed if respiratory acidosis, hypercapnia or hypoxia is significant. Patients with hypothermia should be covered with regular blankets; the use of external heat (e.g.: warming blankets, heating pads, etc.) should be avoided because the resulting peripheral dilation may lead to hypotension and cardiovascular collapse. (Beynon, J., Akhtar, S., and Kearney, T. 2008). Hypertonic saline and glucose may be required to alleviate severe dilutional hyponatremia and the occasional hypoglycemia. (Larsen, Kronenber, et.al., 2003).


-Patient adherence and compliance to therapeutic regimen therefore should be a top priority to prevent worsening of hypothyroid condition, which can lead to myxedema coma. Overall, levothyroxine is still the preferred form of thyroid hormone replacement in all patients with hypothyroidism.


References:
Alexander, E.K., et. al. (2004). Timing and Magnitude of Increases in Levothyroxine Requirements During Pregnancy in Women with Hypothyroidism. New England Journal of Medicine 2004; 351:241-9.

Lazarus, J.H, and Premawardhana, L.D.K.E. (2006). Management of Thyroid Disorders. Postgrad Med J 2006; 82:552–558. doi: 10.1136/pgmj.2006.047290

Schraga, E.D. (2009). Hypothyroidism and Myxedema Coma: Treatment & Medication. Last updated 10-December-2009. Retrieved February 16, 2010 from Emedicine Database: http://emedicine.medscape.com/article/768053-treatment

Bharaktiya, S. (2009). Hypothyroidism: Treatment & Medication. Last updated 23-July-2009. Retrieved February 16, 2010 from Emedicine Database: http://emedicine.medscape.com/article/122393-treatment

Grozinsky-Glasberg S, Fraser A, Nahshoni E, et al (2006). Thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. Jul 2006; 91(7):2592-9

Beynon, J., Akhtar, S., and Kearney, T. (2008). Predictors of Outcome of Myxedema Coma. Critical Care. 2008; 12(1): 111. doi: 10.1186/cc6218.

Citkowitz, E.(2008). Myxedema Coma or Crisis: Treatment & Medication. Last updated 05-August-2008. Retrieved February 17, 2010 from Emedicine Database: http://emedicine.medscape.com/article/123577-treatment

Postellon, D.C. (2008). Congenital Hypothyroidism. Last updated 28-May-2008. Retrieved February 17, 2010 from Emedicine Database: http://emedicine.medscape.com/article/919758-treatment

Williams, F.L., Visser, T.J., Hume, R., et.al. (2004). Developmental Trends in Cord and Postpartum Serum Thyroid Hormones in Preterm Infants. The Journal of Clinical Endocrinology & Metabolism 89(11):5314. doi: 10.1210/jc.2004-0869

Harvard Women’s Health Watch (2009). Treating Hypothyroidism. Retrieved February 16, 2010 from Harvard Health Publications, Harvard Medical School Website: http://www.health.harvard.edu/newsletters/Harvard_Womens_Health_Watch/2009/December

Glendenning, P. (2008). Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline. Clin Biochem Rev Vol 29 | May 2008 | pg. 83-85

Mazokopakis, E.E., Giannakopoulos, T.G., and Starakis, I.K. (2008). Interaction Between
Levothyroxine and Calcium Carbonate. Can Fam Physician. 2008 January; 54(1): 39

Ferry, J.R. and Bauer, A.J. (2008). Hypothyroidism (Pediatrics: General Medicine). Last updated 10-July-2008. Retrieved February 17, 2010 from Emedicine Database: http://emedicine.medscape.com/article/922777-treatment

Larsen, P.R., Kronenber, H.M., et.al. (2003). Williams Textbook of Endocrinology. 10 edition. PA: Elsevier Science (Saunders). pg 562