Infant girl with deafness and abnormal TFTs. August 8, 2013 Matt Wise, MD/Katie Stanley All ages
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1 Infant girl with deafness and abnormal TFTs August 8, 2013 Matt Wise, MD/Katie Stanley All ages
2 HPI 4 month old AA girl when initially evaluated in endocrine clinic Birth: full term, uncomplicated preg/delivery BW 5lb 5oz (SGA), length 18 (SGA) No neonatal complications (normal formula feeding, no jaundice) Failed multiple hearing screens, noisy breathing referred to ENT
3 ENT Evaluation 3 months old Narrow ear canals Inspiratory stridor Otoacoustic emissions: failed bilaterally Brainstem evoked responses: no response at 90dB b/l Laryngoscopy: laryngomalacia Dx: sensorineural deafness (bilateral) laryngomalacia Plan: hearing aid trial; referral to Endocrinology
4 Thyroid Function Tests Age TSH Free T4 3 weeks weeks weeks
5 Endo Evaluation - No lethargy, slow movements, or hoarse cry -Normal feeding - Normal urine/stool output + noisy inspiratory breathing + dry, light patches of skin on face Development: babbling, head lift, eye tracking
6 PMH Sensorineural deafness Laryngomalacia Abnl TFTs Eczema SH Parents live separatey but both involved Meds: HC 1% cream FH Father 6 0, healthy Mother 5 3, healthy Pat GM: dx hyperthyroid age 40, surgery No congenital hypothyroidism or hearing loss
7 Physical Exam Length 56.5 cm (<2%); Weight 4.9 kg (<2%); HC: 39cm (13%) Weight for length: 46%ile HR 131 BP 64/32 General: She is active. No distress. No midline defects HENT: Fontanelles open, normal size; Mucous membranes are moist. Normal tongue Eyes: EOM are normal. Pupils are equal, round, and reactive to light. Neck: No thyromegaly Cardiovascular: Normal rate and regular rhythm. No murmur heard. Pulmonary/Chest: Effort normal, +inspiratory stridor Abdominal: Soft. Nondistended. No hernia Genitourinary: normal external female genitalia Musculoskeletal: Normal range of motion. Neurological: She is alert. She displays normal reflexes. Normal tone Skin: +erythematous macule on forehead; patches of hypopigmented, scaly skin on left cheek and chin
8 H E A D Growth Charts LENGTH
9 Differential Dx: Subclinical hypothyroidism in infants -Dysgenesis Hemiagenesis, unilobular hypopasia -Dyshormonogenesis Pendred syndrome -TSH resistance 11.8% in 1 series had heterozygous TSH receptor mutations -Transient: Maternal antibody mediated Iodine deficiency or exposure
10 Further Evaluation & Mgmt TSH Free T4 TSH-R Ab negative SLC26A4 genetic testing Age TSH Free T4 3 weeks weeks weeks weeks Discussed risks/benefits of starting replacement therapy Started 37.5 mcg (7.65 mcg/kg) po daily f/u TFTs in 4 wks
11 Clinical Questions What is cause and clinical findings of Pendred syndrome? What is the perchlorate discharge test and what is its use in distinguishing causes of dyshormonogenesis?
12 Pendred Syndrome -AR SLC26A4 -Typical mild, subclinical Hypothyroidism - Goiter in late childhood -10% of all hereditary deafness - chloride/bicarb exchanger in inner ear
13 Perchlorate Discharge Test Tg RAI
14 Perchlorate Discharge Test Tg
15 Perchlorate Discharge Test Tg Radioactivity decreases by <10% perchlorate
16 Perchlorate Discharge Test Tg
17 Perchlorate Discharge Test Tg
18 Perchlorate Discharge Test Tg perchlorate
19 Perchlorate Discharge Test Tg perchlorate Radioactivity decreases by >10-15% by diffusing out of thyroid considered abnl Usually >20-30% in Pendred
20 Perchlorate Discharge Test There seems to be little additional diagnostic value in performing a perchlorate discharge test, which has a relatively high false-negative rate (~5%) in demonstrating partial iodine organification defect in patients with SLC26A4 mutations.
21 Back to our patient
22 Take Home Points Pendred syndrome is caused by a defect in an iodine transporter on the apical membrane of thyroid cells, and results in mild, generally subclinical hypothyroidism The perchlorate discharge test can distinguish causes of dyshormonogenesis, including Pendred syndrome, but is less useful due to false + s and increasing availability of genetic testing
23 References Monzani et al. Natural history of subclinical hypothyroidism in children and adolescents and potential effects of replacement therapy: a review. Eur J Endocrinology 2013; 168:R1-11. Calebiro et al. Frequent TSH receptor genetic alterations with variable signaling impairment in a large series of children with nonautoimmune isolated hyperthyrotropinemia. JCEM 2012; 97:E O Grady et al. Subclinical hypothyroidism in childhood. Arch Dis Child 2011; 96: Weiss R, Refetoff S Genetic Diagnosis of Endocrine Disorders.
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