How Long After You Start Levothyroxine Should the Labs Be Checked?

Patient Presentation
A 17-year-old female came to clinic in March for an upper respiratory infection. The mother said that she was concerned because her daughter had been having constipation for the past several months and was always cold. The patient stated that she had infrequent bowel movements that were soft, but slightly drier and harder to pass. She had larger amounts of stool that did not clog the toilet and denied large circumference stools, overflow diarrhea, blood, mucous or recent travel. She also said that she always felt cold and that her skin seemed drier since moving to the upper Midwest of the United States from a warm weather region of the world about 6 months ago. She denied weight changes or needing to change clothes sizes. She also denied general fatigue, problems concentrating or menstrual irregularities. The past medical history showed a healthy female with a history of malaria at 6 and 9 years of age. The family history was positive for diabetes, stroke, and hypothyroidism in 2 maternal aunts. The review of systems was otherwise negative, including no galactorrhea, or visual changes.

The pertinent physical exam showed a BMI of 85%. There was a 1 pound weight gain from 3 months previous. Her vital signs were normal. HEENT showed clear rhinrorhea and slightly pink pharynx. She had a diffusely enlarged thyroid without discrete palpable masses within it or external to it. Her hair was slightly coarse consistent with her race and her mother’s appearance. Abdominal examination revealed palpable stool in the right lower quadrant. She was Tanner stage V. Neurological examination showed normal strength, tone and deep tendon reflexes. She had generally dry skin, but no observable edema. The diagnosis of a diffuse goiter along with constipation, cold intolerance and dry skin was made. Although the cold intolerance and dry skin might have been environmentally caused, and the constipation due to nutrition, the goiter and family history raised the concern for acquired hypothyroidism. The relevant work-up confirmed this diagnosis with a thyroid stimulating hormone (TSH) of 49.6 micro-international units/dL (normal up to 4.2) and thyroxine (T4) of .68 nanograms/dL (normal down to .92). The laboratory evaluation demonstrated no thyroid antibodies and an ultrasound showed no specific thyroid nodules. Complete blood count, cholesterol and a random glucose were negative. She was started on levothyroxine with followup in 4 weeks to retest the T4 and TSH. An endocrinology consultation was also ordered. Miralax® was given to help with the constipation while the levothyroxine was taking effect.

Discussion
The thyroid gland synthesizes T4 (the predominate product) and some triiodothyronine (T3). Serum T4 is usually bound to T4-binding globulin (TBG) and transported to the peripheral tissue where it is deiodinated into T3, the more biologically active product. T3 regulates a number of biological processes depending on the end organ. Thyroid releasing hormone (TRH) is made in the hypothalamus, and travels to the pituitary to stimulate TSH release. Serum T4 regulates TRH and TSH by a negative feedback loop. Therefore, classically in hypothyroidism, TSH is high and T4 is low as in this patient.

Acquired hypothyroidism can be found in up to 10% of young females depending on the criteria used, and there is a 2:1 female to male preponderance of the disorder. The presentation in children can be more subtle than in congenital hypothyroidism and may include:

• Slow growth or short stature
• Increased sleep
• Fatigue, lethargy, or inattention
• Weight gain, usually not the cause of obesity though
• Edema – especially facial
• Slow hair or nail growth
• Dry skin and/or sallow complexion
• School performance, poor
• Bradycardia
• Puberty, precocious or late
• Immature upper-to-lower body proportions
• Constipation
• Galactorrhea
• Goiter
• Cold intolerance
• Heat intolerance, tremors, and weight loss can be common if active thyroiditis is occurring

Acquired hypothyroidism can be a solitary problem or associated with other endocrinopathies and it can be associated with anemia and hypercholesterolemia. Although children can have neurological symptoms, acquired hypothyroidism generally is not associated with the long term neurological problems which can be seen in congenital hypothyroidism. An overview of congenital hypothyroidism can be found here. In fact some children may have their hypothyroidism resolve and a trial off medication may be warranted. This is usually tried after growth has finished.

Learning Point
TSH is the most sensitive screening test for hypothyroidism and for most patients it is the measure of efficacy of its treatment. However the T4 usually normalizes before the TSH, and thus T4 is often used in the initial adjustments to treatment.

Levothyroxine a synthetic T4 that has a half-life of 6-7 days. Because of the half-life it takes about 3.5 weeks for serum T4 levels to reach a steady state, therefore repeat laboratory testing is usually done about 4 weeks after initial treatment and/or dosage adjustment. Some patients may require more frequent monitoring though. Laboratories are monitored monthly to every 3 months until a normalization of the T4 and TSH. Once this occurs and is stabilized, laboratories are usually monitored every 6 months. Levothyroxine is considered a relatively safe medication and side effects are usually due to iatrogenic or inadvertent overdosing of the medication.

Questions for Further Discussion
1. What are the causes of acquired hypothyroidism?
2. What should be included in the differential diagnosis of acquired hypothyroidism?
3. What initial laboratory testing is recommended for acquired hypothyroidism?

Related Cases

Disease: Acquired Hypothyroidism | Thyroid Diseases

Symptom/Presentation: Constipation and Encopresis | Neck Mass | Eczematous Dermatitis

Specialty: Endocrinology | Gastroenterology

Age: Teenager

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Thyroid Diseases

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

Setian NS. Hypothyroidism in children: diagnosis and treatment. J Pediatr (Rio J). 2007 Nov;83(5 Suppl):S209-16.

Lomenick JP, El-Sayyid M, Smith WJ. Effect of levo-thyroxine treatment on weight and body mass index in children with acquired hypothyroidism. J Pediatr. 2008 Jan;152(1):96-100.

Custer JW, Rau RE. The Harriet Lane Handbook. 18th. Edit. Elsevier/Mosby Publications: Philadelphia, PA. 2009:881.

Ferry RJ, Bauer AJ, Kemp. Pediatric Hypothyroidism. Medscape. Available from the Internet at http://emedicine.medscape.com/article/922777-overview (rev. 8/12/2010, cited 11/28/2011).

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