Congenital Hypothyroidism Presenting with Myxedema Coma

Christine Kim, MD1, Robyn Kuroki, MD2

1Department of Internal Medicine-Pediatrics2Department of PediatricsLos Angeles County + University of Southern California Medical Center

ID: 36 y/o female from Guadalajara with untreated congenital hypothyroidism

CC: Respiratory distress

History of Present Illness:• 1 week PTA: Congestion and nasal discharge causing

decreased sleep x 3 days

• Outside clinic: IM injection of antibiotic x3 days, given 5 days of Azithromycin along with Albuterol syrup, phenergan, prednisolone and Tylenol

• DOA: Worsening congestion and difficulty swallowing, Episodes of perioral cyanosis lasting 3 min

• ROS: no fevers, +constipation (daily suppositories), +night-time snoring, + dry skin, decreased activity level from baseline

Development @ Baseline•Social (~12 mo): work for toy, play pat-a-cake, indicate wants, waves bye-bye, rolls ball with examiner•Language (expressive ~6mo; receptive ~10mo): nods/shakes her head, hand gestures•Fine Motor (~6 mo): raking grasp, pass cube, take 2 cubes•Gross Motor (~10 mo): crawls, sits up by herself, walks with both hands being held and supported, turns pages of books, not toilet trained

Physical Exam

Vital signs BP: 123/72, HR: 63, RR: 12, , T 97.8, Pain: 0/10 Weight: 16.5 kg Height: 81 cm BMI: 25.1 kg/m2 HC: 51cm GENERAL: very small for stated age , coarse facial features, appearing about 2-3

years old, non-verbal HEENT: large anterior fontanelle open and flat, deep set nose, large dry lips,

large thick partially visible tongue, poor dentition, coarse/sparse hair, (frenulum attached)

NECK: thick neck, no palpable goiter or thyroid nodules, + shotty cervical LADCHEST: coarse breath sounds b/l, no wheeze/retractions, no stridor, SMR (B) 1CARDIAC: S1 +S2, regular rhythm, heart rate 50-60’s no murmurs/gallops/rubsABD: protuberant abdomen, small umbilical hernia, soft, nontender no HSMGU: SMR 1 femaleEXT: short fingers and toes, short arms and legs, broad edematous hands b/lNEURO: deep tendon reflexes hypereflexic with markedly delayed return phaseSKIN: pale, dry boggy skin, with myxedematous changes, multiple nevi with

raised nevi at external ear canal on left

In the hospital

Labs

145

3.5

109

22250

14

0.7

Ca 10.6Phos 2.4Mg 1.9

586.5

3.3

0.2

0.1

35

24

CK 87LDH 215PT 16.4sINR 1.31PTT 20.3s

8.27.1

21.2

99.7

268

14.8

N77 L19 M4 B0.1

Lactate 4.3Ammonia 32CRP 5.3

VBG: pH 7.3 pCO2 50 pO2 45 HCO3 25 BD 1.1 O2 75%

Endocrine Labs

• TSH 208• FT4 <0.4• FT3 <1.1• Thyroglobulin 4.2• Thyroglobulin Ab <1

• PTH 66• Prolactin 113.4

• AM Cortisol 17.6• LH <1.0• FSH 2.1• Estradiol 21• DHEAS 23• GH 0.8• IGF-1 <25

• Vit D 25-OH 11

CXR/KUB

• Cardiomegaly• Increased interstitial markings

• Distended stomach• Immature skeleton

Skeletal Survey

• Widened sutures• Wormian bones

SkeletalSurvey

• Flattening of bodies

• Thoraco-lumbar kyphosis

• Cretinoid epiphyseal dysgenesis

• Shortening of long bones

Bone Age

• Carpal bone age ~3 yrs

• Distal bones ~1yr 3mo

MRI Brain

• Mildly prominent pituitary gland

• No sellar mass

Studies

Echo: decreased ejection fraction, mild aortic insufficiency, heart walls that appear to have myxedematous changes

Thyroid U/S: no evidence of thyroid tissue within neck

Learning Objectives

• Review Congenital Hypothyroidism• Know about the uncertainties in managing

adults with congenital hypothyroidism who have never been treated before

Congenital Hypothyroidism• Thyroid hormone deficiency at birth

– Most common treatable causes of mental retardation

• Screening: newborn screening since mid-1970’s

• Incidence– 1: 4,000-3,000 newborns– Hispanic, American Indian/Alaska Native people

(1:2,000-700 newborns)– Black 1:3,200-17,000

Etiology• Common form of thyroid dysgenesis

– Aplasia– Hypoplasia– Ectopic gland (66%)

• Cause of thyroid dysgenesis is unknown (85% sporadic, 15% hereditary)

– Mutations– Inborn errors of T4 synthesis, secretion, or utilization (2/3 heritable

cases)• Transient Hypothyroidism

– Maternal Autoimmune thyroiditis– Maternal medication for Graves’ disease

• Endemic cretinism from iodine deficiency

Screening• Started in Mid-1970’s• Measure T4 & TSH > 48 hrs of life

– T4 – false-positive rate 0.30%– TSH – false-positive 0.05%– Preterm infants have higher false-positive– Not affected by diet or transfusion; but total exchange transfusion

• If + confirm thyroid US or thyroid uptake scan• If maternal autoimmune thyroid disease measure TSH-binding

inhibitor Ig• If iodine exposure/deficiency measure urinary iodine

Clinical Manifestations

Infants protected for 1st few wks of life– Fraction of maternal thyroid

hormone crosses placenta• >40 wk GA• HC Slightly higher % due to brain

myxedema• Large fontanels & wide sutures• Macroglossia• Distended abdomen with

umbilical hernia• Skin mottling• Goiters (5-10%)• Sensorineural deafness (10%)• Other congenital anomalies (10%)

• Slow to feed• Constipation• Lethargic• Sleep more, needs to be

awakened to feed• Hoarse cry• Cool to touch• Hypotonic with slow reflexes• Prolonged jaundice

If undiagnosed at a later age…

• Slow linear growth• Loss of IQ• Ataxia• Gross/fine motor

incoordination• Hypotonia & spasticity• Speech disorders• Attention deficit• Strabismus• Sensoriuneural deafness (10%)

Disease Management

• Levothyroxine (~10-15 m/kg/day)– Goal: T4 1.2-2.3 ng/dL TSH <6 mU/L– Monitor T4 & TSH @

• 2 & 4 wks after treatment• q1-2 months in 1st year• q3-4months between 1-3 yrs• 2-4wks after any change in dosage

Myxedema Coma

• Myxedema coma is a medical emergency, typically caused by a precipitating event in a patient with chronically untreated hypothyroidism

To treat, or not to treat….For in this unique case

Pros to therapyDevelopmental or

maturational changesIncreased social interactionsPrevent myxedema comaPrevent hospitalizationsCompatible with

life/sustains life

Cons to therapyMensesIncreased caretaking

responsibilitiesIncreased medical

monitoringBehavioral changes

(aggressiveness, mood liability)

Case report cont.

Prior to Therapy 7 months after therapy

References• Boersma, B., et al. Catch-up Growth after Prolonged Hypothyroidism. Eur J Pediatr. 1996.

155:362-367.• Congenital Hypothyroidism, Nongoitrous,2. Centre for Arab Genomic Studies• Dubuis, J., et al. Outcome of Severe Congenital Hypothyroidism: Closing the Developmental

Gap with Early High Dose Levothyroxine Treatment. J of Clinical Endo and Met. 1996. 81(1):222-227.

• Eberle, Andrea. Congenital Hypothyroidism Presenting as Apparent Spondyloepiphyseal Dysplasia. Am Journ of Med Genetics. 1993. 47:464-467.

• Hirayama, T., et al. The Longitudinal Course of Two Cases with Cretinism Diagnosed After Adolescence. J. Nippon Med Sch 2003. 70(2):175-178.

• Ishikawa, N. et al. A Case of Turner Syndrome with Congenital Hypothyroidism Untreated until Age 38 Years. Horm Res. 2003. 59:50-54.

• Kaye, C. & Committee on Genetics. Newborn Screening Fact Sheets. Pediatrics 2006. 118:e934-e963.

• Meyers D, Haering S. Screening for Congenital Hypothyroidism in Newborns:A Literature Update for the U.S. Preventive Services Task Force. AHRQ Publication No. 08-05109-EF-1. Rockville, MD: Agency for Healthcare Research and Quality, 2008.

• Oerbeck, B., et al. Congenital Hypothyroidism: Influence of Disease Severity and L-Thyroxine Treatment on Intellectual, Motor, and School-Associated Outcomes in Young Adults. Pediatrics Oct 2003. 112 (4):923-930.

• Rose, S., Brown, R. Update of Newborn Screening and Therapy for Congenital Hypothyroidism. Pediatrics. June 2006. 117(6):2291-2303.

Question

• A 13 year-old diagnosed with congenital hypothyroidism was brought in by mother after missing appointments for >1 yr. Physical examination reveals length at the 5th percentile, weight at the 10th percentile, dry skin, and non pitting edema in bilateral lower extremities. Mother also concerned with constipation. You order TSH and FT4 and increase the thyroid hormone replacement therapy from 50mcg to 100mcg.

Question

Of the following, the MOST likely long-term outcome in this child:

A. Adrenal InsufficiencyB. Diabetes mellitusC. Learning disorderD. Normal adult heightE. Precocious puberty

Answer - C• Children who have severe hypothyroidism at birth tend to have poorer

intellectual outcomes than their siblings, even if therapy is started in the first few days after birth

• With continued and appropriate thyroid hormone therapy, this child should grow normally in height, and adult height should be appropriate for the family. However, this child has been chronically undertreated for many months.

• Congenital hypothyroidism is not associated with adrenal insufficiency, although acquired hypothyroidism because of chronic lymphocytic thyroiditis may be associated with the development of autoimmune adrenal insufficiency (Addison disease).

• Precocious puberty is not an outcome of congenital hypothyroidism unless a child is overtreated with thyroid hormone and develops premature maturation, which is very unusual. Some children who have severe acquired hypothyroidism have manifested signs of sexual precocity that disappear after treatment of the hypothyroidism (Van Wyk-Grumbach syndrome).