Payal Patel, MD Pediatric endocrinology fellow January 9, 2014
14 8/12yo F with newly diagnosed Graves disease presents for a 2 nd opinion
2 wks prior: pt seen by PCP for evaluation of a "large neck mass with difficulty swallowing and mild tenderness to touch but no trouble breathing Referred to an endocrinologist who dx ed her with Graves started her on methimazole 30mg PO daily (10mg TID) Labs: T4 35.8 mcu/ml ESR 10 ( <20) ft4 >8 ng/dl (0.76-1.8) T3 > 651 ng/dl (83-215) BMP- within nl limits Thyroid peroxidase Ab 176.4 (0-9)
Constitutional: +diaphoresis, increased appetite, fatigue, weight gain (10lbs in 3 months). Negative for fever. HEENT: +neck swelling, trouble swallowing. Negative for neck stiffness, vision changes. Resp: Negative for cough, choking, chest tightness, SOB CVS: +leg swelling. Negative for chest pain, palpitations. GI: +diarrhea. Negative for nausea, vomiting GU: +frequency. Negative for dysuria, enuresis, menstrual problem. MSK: +myalgias, arthralgias and gait problem (difficulty with balance prior to starting methimazole). Negative for joint swelling. Skin: +dry skin on her hands Neuro: +tremors and headaches. Negative for dizziness, syncope, light-headedness. Psych: +decreased concentration. Negative for confusion, agitation.
Vitals: T 36.8 C, HR 130, bp 132/79, RR 16, wt 50.5 kg (47 th %), ht 151.1 cm (6 th %), BMI 22 (75 th %) General: well-nourished, not diaphoretic, NAD HEENT: oropharynx clear, PERRLA, no scleral icterus, no exophthalmos Neck: nl range of motion. No tracheal deviation or cervical LAD. thyromegaly (lobes 6cm b/l in transverse diameter, smooth, no nodules, no tenderness). CV/Resp/Chest: tachycardia, regular rhythm, no murmur, CTAB, Tanner 4 breasts MSK: No edema, good muscle mass/tone Neuro: alert, brisk symmetric DTRs, tremulous extremities, tremor in hands b/l when outstretched Skin: warm, dry, nl pigmentation, no rash Psychiatric: nl mood, affect and behavior
At dx +2 wks TSH (mcg/dl) <0.01 Total T4 (mcu/ml) 35.8 >24.8 Free T4 (ng/dl) >8 >7.77 Total T3 (ng/dl) >651 >650 TSI (nl <1.3) 4.3 CMP and CBC within nl limits
Methimazole: consider a 1-2 yr course since ~30% of pts will go into remission Typical daily dose = 0.2 0.5 mg/kg/d (range 0.1 1.0) 131 I therapy: not for pts < 5yrs Administer in a single dose to render the pt hypothyroid Thyroidectomy: when definitive therapy is required, the child is too young for 131 I, and surgery can be performed by a skilled thyroid surgeon Bahn, et al. Thyroid 2001.
Increased methimazole to 40mg daily (15/10/15) Atenolol 25mg daily RTC in 4 weeks
4 weeks later: Increased mood labiality Lack of interest in activities or friends 8 weeks later: +6kg weight gain Worsening mood fluctuations Started homebound school At dx +2 wks +4 wks +8 wks TSH (mcg/dl) <0.01 <0.01 <0.01 Total T4 (mcu/ml) 35.8 >24.8 Free T4 (ng/dl) >8 >7.77 2.52 1.23 Total T3 (ng/dl) >651 >650 314 Plan: Continue methimazole and atenolol Plan: Continue methimazole, decreased atenolol
What is the relationship between Graves disease and psych disorders?
Various studies have shown that in children, there is an increased incidence of emotional disturbances (emotional lability, increased irritability) and school problems (declining performance) Overall, the most common psych features associated with hyperthyroidism = anxiety and depression Study by Hu LY, et al. found that there is a higher incidence of subsequent bipolar disorders in patients with hyperthyroidism
21,574 pts with hypethyroidism & 21,574 matched controls Both cohorts = 77.6% F, 22.4% M Hu LY, et al. PLoS ONE 2013.
What is the relationship between Graves disease and psych disorders? What is the role of 131 I in the treatment of pediatric GD? What is the risk for cancer with 131 I in the treatment? What are the controversies associated with 131 I in the treatment?
Goal = induce hypothyroidism Lower doses may residual/partially irradiated thyroid tissue increased risk for thyroid cancer Dose should be >150 uci/g of thyroid tissue Larger glands (50-80g): 200 300 uci/g >80 g: consider thyroidectomy Rivkees S, et al. Pediatrics 2003.
Risk of invasive cancer (%) Birth-39 yrs: 1.77 40-59 yrs: 8.69 60-69 yrs: 12.89 >70 yrs: 32.16 Lifetime: 40.84 Jemal A et al. CA Cancer J Clin 2010. Royal H. Seminars in Nuclear Medicine 2008.
Per Lee JA, et al. thyroid cancers after radiation exposure usually present after several decades, with 1/3 presenting after >20 yrs Results from historical studies are mostly based on lowdose tx Full malignant potential for the whole body with high-dose RAI is unknown Potentially increased risk for hyperparathyroidism and cardiovascular disease with RAI tx vs. thyroidectomy Safa AM, et al. N Engl J Med, 1975.
Nausea and mild thyroid tenderness: 1-3 d after tx self-limited and respond to NSAIDs Thyroid storm: reported rarely, 1 14 d after tx Pts with thyrotoxicosis and very large goiters at highest risk Worsening ophthalmopathy: reported in small % of adults If +profound ophthalmopathy, adjunctive prednisone therapy x3 months has been shown to prevent the worsening of eye disease after tx Very rare in children; worsening of eye disease has not been observed Possible hyperparathyroidism Not supported by case-controlled studies
Higher incidence of subsequent bipolar disorder in pts with hyperthyroidism (F>M) Since the majority of pediatric pts with GD will require definitive tx, studies suggest that RAI should be considered as 1 st -line tx in specific pts (>5yrs, with goiters <80g) Otherwise, RAI may be an appropriate 2 nd -line tx for pts with severe complications, poor compliance, or lack of response to ATD tx Lack of long-term data on pts who have received HD RAI Therefore, potential risks of HD RAI should weighed against ATD tx and surgery
Bahn RS, Burch HB, Cooper DS, Garber JR, et al. The American Thyroid Association and American Association of Clinical Endocrinologists Taskforce on Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists 2011. Thyroid 2001;21:612-619. Saxena KM, Crawford JD, Talbot MB. Childhood thyrotoxicosis: a longer term perspective. Br Med J 1964; 2:1153-1158. Hu LY, Shen CC, Hu YW, Chen MH, et al. Hyperthyroidism and Risk for Bipolar Disorders: A Nationwide Population-Based Study. PLoS ONE 2010;8(8): e73057. Jemal A, Siegel R, Xu J, Ward E. Cancer Statistics, 2010. CA Cancer J Clin 2010;60:277-300. National Research Council. Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2. The National Academies Press 2006. Rivkees SA, Cornelius EA. Influence of Iodine-131 Dose on the Outcome of Hyperthyroidism in Children. Pediatrics 2003;111(4):745-749. Rivkees SA and Dinauer C. An Optimal Treatment for Pediatric Graves Disease Is Radioiodine. JCEM 2007;92: 797-800. Safa AM, Schumacher OP, Rodriguez-Antunez AR. Long-term Follow-up Results in Children and Adolescents Treated with Radioactive Iodine ( 131 I) for Hyperthyroidism. N Engl J Med 1975;292(4):167-71. Lee JA, Grumbach MM, and Clark OH. The Optimal Treatment for Pediatric Graves Disease Is Surgery. JCEM 2007;92(3):801 803.