Basics
Description
Hypothyroidism that occurs after the neonatal period
Epidemiology
- May develop at any age
- Autoimmune thyroid disorders occur more frequently in children and adolescents with type 1 diabetes and other autoimmune conditions.
- Chronic lymphocytic thyroiditis prevalence correlates with iodine intake; countries with the highest dietary iodine also have the highest prevalence.
Risk Factors
Genetics
- Family history of thyroid disease or other autoimmune endocrinopathies increases risk.
- Genetic predisposition in patients with chronic lymphocytic thyroiditis; 30-40% of patients have a family history of thyroid disease, and up to 50% of their 1st-degree relatives have thyroid antibodies.
- Weak associations of chronic lymphocytic thyroiditis with certain human leukocyte antigen haplotypes; also associated with genotypes of cytotoxic T lymphocyte-associated 4 (CTLA4) and interleukin-18 (IL-18) genes.
- Autoimmune thyroid disease may be part of Schmidt syndrome (type II polyglandular autoimmune disease).
- Genetic syndromes associated with higher incidence of autoimmune thyroiditis:
- Down syndrome
- Turner syndrome (especially those with isochromosome Xq)
Etiology
- Myriad causes (see "Differential Diagnosis")
- Can result from thyroid gland dysfunction (primary hypothyroidism) or from pituitary/hypothalamic dysfunction leading to understimulation of the thyroid gland (secondary and tertiary hypothyroidism)
Commonly Associated Conditions
- Vitiligo
- Alopecia areata
- Pernicious anemia
- Other autoimmune conditions
Diagnosis
History
- Linear growth failure can be the first sign of thyroid dysfunction.
- Declining school performance is a sensitive marker for lethargy and reduced focus.
- Radiation exposure, history of type 1 diabetes, family history of other autoimmune disorders
- Signs and symptoms:
- Early primary hypothyroidism can be asymptomatic.
- Hypothyroid-related symptoms indicate progression from compensated to uncompensated hypothyroidism.
- Hypothyroidism may be preceded in some cases by temporary hyperthyroidism (Hashitoxicosis).
- Goiter may be the presenting sign of acquired hypothyroidism; tenderness suggests an infectious process.
Physical Exam
- Bradycardia: Thyroid hormone has cardiac effects.
- Short stature (or fall-off on growth curve) and increased upper/lower segment ratio: Euthyroidism is required to maintain normal growth.
- Goiter: Note consistency, symmetry, nodularity, signs of inflammation:
- May give a clue regarding cause of hypothyroidism
- May provide a clinical marker to follow during therapy
- Myxedema (water retention) is not limited to subcutaneous tissue; it may also lead to cardiac failure, pleural effusions, and coma.
- Muscle hypertrophy, yet muscle weakness
- Most obvious in arms, legs, and tongue
- Hypothyroidism causes disordered muscle function.
- Delayed relaxation phase of deep tendon reflexes due to slowed muscle contraction
- Pale, cool, dry, carotenemic (yellow-colored) skin due to decreased cell turnover
- Increase in lanugo hair in children; can be reversed with treatment
- Sexual development is an important factor. Hypothyroidism may be associated with either
- Delayed puberty (due to low thyroid hormone level)
- Precocious puberty and galactorrhea (due to elevated TSH)
Diagnostic Tests & Interpretation
Lab
- T4 (low) and TSH (elevated): Elevated TSH with normal T4 indicates compensated (subclinical) primary hypothyroidism.
- Free T4: The most sensitive marker for secondary/tertiary hypothyroidism (TSH elevation lost; total T4 may still be low normal)
- Thyroglobulin antibodies and thyroid peroxidase (microsomal) antibodies are markers for chronic lymphocytic thyroiditis.
- The following conditions may test false-positive for acquired hypothyroidism:
- Thyroid-binding globulin deficiency: low total T4 but normal free T4 and TSH
- Peripheral resistance to thyroid hormone: normal/high total T4
- "Euthyroid sick" syndrome: low T4 and T3; normal/low TSH; increased shunting to reverse T3
- The following tests may be affected in acquired hypothyroidism:
- Serum creatinine: elevated due to reduced glomerular filtration rate
- LDL cholesterol level: elevated due to decreased LDL receptor expression
- Creatine kinase: increased; hypothyroidism is a rare cause of rhabdomyolysis.
Imaging
Head MRI for cases of suspected secondary/tertiary hypothyroidism or pituitary or hypothalamic lesion
Differential Diagnosis
- Immunologic
- Chronic lymphocytic thyroiditis (Hashimoto thyroiditis)
- Polyglandular autoimmune syndrome (Schmidt syndrome)
- Infectious
- Postviral subacute thyroiditis
- Associated with congenital infections
- Environmental
- Goitrogen ingestion
- Iodides
- Expectorants
- Thioureas
- Iatrogenic
- Following surgical thyroidectomy for thyroid cancer, hyperthyroidism, or extensive neck tumors
- Following radioiodine ablative therapy for hyperthyroidism or thyroid cancer
- Following head or neck irradiation for cancer treatment
- Medications: lithium, amiodarone, iodine contrast dyes, tiratricol (an OTC fat-loss supplement)
- Metabolic
- Cystinosis
- Histiocytosis X
- Congenital
- Late-onset congenital, large ectopic gland
- Genetic syndromes
- Down syndrome
- Turner syndrome
- Secondary or tertiary hypothyroidism
- Hypothalamic or pituitary disease
- Consumptive hypothyroidism
- Due to increased type 3 iodothyronine deiodinase activity in hemangiomas
Treatment
Medication
l-Thyroxine (synthetic thyroid hormone) replacement
- Indicated for the treatment of overt or compensated hypothyroidism
- 2-5 mcg/kg PO once daily
- Monitor T4 and TSH and titrate dose to maintain normalized thyroid function tests.
- Duration of therapy:
- Lifetime
- In 30% of the cases, children with chronic lymphocytic thyroiditis will undergo spontaneous remission.
- Need for treatment can be reassessed after growth is completed.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Whenever starting medication or adjusting dose, check T4 and TSH at 4-6 week intervals to assess adequacy of the new dose.
- Once dose established, 6-monthly monitoring until linear growth completed
- Monitor response to treatment by measuring T4 and TSH levels to ensure compliance.
Patient Education
Pharmacies in recent years have been recommending that l-thyroxine be administered on an empty stomach. The Drugs and Therapeutics Committee of the Pediatric Endocrine Society recommended that consistency in administration, coupled with regular dose titration based on thyroid function laboratory tests, is more important than improving absorption by restricting intake to only times of empty stomach.
Prognosis
- If patients are adherent, prognosis is excellent.
- Treated patients often resume growth at a rate greater than normal (catch-up growth).
- In children in whom treatment has been delayed, catch-up growth may not fully normalize height to predicted values.
- Other signs and symptoms resolve at a variable rate.
- Goiters in chronic lymphocytic thyroiditis may not completely regress with treatment (enlargement due to persistent inflammation does not correct, although TSH-mediated hypertrophy will).
Complications
- Most significant complication is impaired linear growth.
- Puberty can also be affected.
- Myxedema coma may occur.
- Encephalopathy of varied clinical presentation has been associated with high titers of thyroid antibodies, especially antimicrosomal; this condition responds well to corticosteroid treatment.
Additional Reading
- Ai J, Leonhardt JM, Heymann WR. Autoimmune thyroid diseases: etiology, pathogenesis, and dermatologic manifestations. J Am Acad Dermatol. 2003;48(5):641-659. [View Abstract]
- Ban Y, Tomer Y. Genetic susceptibility in thyroid autoimmunity. Pediatr Endocrinol Rev. 2005;3(1):20-32. [View Abstract]
- Haugen BR. Drugs that suppress TSH or cause central hypothyroidism. Best Pract Res Clin Endocrinol Metab. 2009;23(6):793-800. [View Abstract]
- Monzani A, Prodam F, Rapa A, et al. Endocrine disorders in childhood and adolescence. Natural history of subclinical hypothyroidism in children and adolescents and potential effects of replacement therapy: a review. Eur J Endocrinol. 2012;168(1):R1-R11. [View Abstract]
- Nabhan ZM, Kreher NC, Eugster EA. Hashitoxicosis in children: Clinical features and natural history. J Pediatr. 2005;146(4):533-536. [View Abstract]
- Nebesio TD, Wise MD, Perkins SM, et al. Does clinical management impact height potential in children with severe acquired hypothyroidism? J Pediatr Endocrinol Metab. 2011;24(11-12):893-896. [View Abstract]
- Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med. 2003;348(26):2646-2655. [View Abstract]
- Radetti G, Maselli M, Buzi F, et al. The natural history of the normal/mild elevated TSH serum levels in children and adolescents with Hashimoto's thyroiditis and isolated hyperthyrotropinaemia: a 3-year follow-up. Clin Endocrinol (Oxf). 2012;76(3):394-398. [View Abstract]
- Stathatos N, Wartofsky L. Perioperative management of patients with hypothyroidism. Endocrinol Metab Clin North Am. 2003;32(2):503-518. [View Abstract]
- Wasniewska M, Corrias A, Salerno M, et al. Thyroid function patterns at Hashimoto's thyroiditis presentation in childhood and adolescence are mainly conditioned by patients' age. Horm Res Paediatr. 2012;78(4):232-236. [View Abstract]
- Weber G, Vigone MC, Stroppa L, et al. Thyroid function and puberty. J Pediatr Endocrinol Metab. 2003;16(Suppl 2):S253-S257. [View Abstract]
- Zeitler P, Solberg P; Pharmacy and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society. Food and levothyroxine administration in infants and children. J Pediatr. 2010;157(1):13.e1-14.e1. [View Abstract]
Codes
ICD09
- 244.9 Unspecified acquired hypothyroidism
- 244.8 Other specified acquired hypothyroidism
- 245.2 Chronic lymphocytic thyroiditis
- 246.8 Other specified disorders of thyroid
ICD10
- E03.9 Hypothyroidism, unspecified
- E03.8 Other specified hypothyroidism
- E06.3 Autoimmune thyroiditis
- E03.4 Atrophy of thyroid (acquired)
SNOMED
- 111566002 acquired hypothyroidism (disorder)
- 237519003 Autoimmune hypothyroidism (disorder)
- 237520009 Hypothyroidism due to Hashimotos thyroiditis (disorder)
- 190309006 thyroid atrophy (disorder)
FAQ
- Q: What happens if my child forgets a dose?
- A: Give the dose as soon as you remember. If it is the next day, give 2 doses.
- Q: How long will my child have to take these pills?
- A: Probably for life.
- Q: Are there any side effects from the medication?
- A: No. The medication contains only the hormone that your child's thyroid gland is not making. The hormone is made synthetically, so there is also no infectious risk.
- Q: If my child takes twice the dose, will his or her growth catch up faster?
- A: Your child may grow a little faster but will also have adverse effects from having too much thyroid hormone.
- Q: Does the medication have to be taken at any particular time of day?
- A: No, but consistently choosing the same time of day helps to remember to take it. Do not take simultaneously with soy products, iron-containing medication, calcium supplements, or raloxifene (an antiestrogen medication) because they can cause malabsorption of levothyroxine.
- Q: What if my child needs surgery?
- A: Treatment of hypothyroidism such that the patient is euthyroid (normal thyroid status) prior to surgery is preferable whenever possible (only exception is ischemic heart disease requiring surgery). Euthyroid sick syndrome, which is common in very ill patients, should not be treated.