Transcript Kim C. MD, University of Southern California Medical Center

Congenital Hypothyroidism Presenting
with Myxedema Coma
Christine Kim, MD1, Robyn Kuroki, MD2
1Department of Internal Medicine-Pediatrics
2Department of Pediatrics
Los 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 LAD
CHEST: coarse breath sounds b/l, no wheeze/retractions, no stridor, SMR (B) 1
CARDIAC: S1 +S2, regular rhythm, heart rate 50-60’s no murmurs/gallops/rubs
ABD: protuberant abdomen, small umbilical hernia, soft, nontender no HSM
GU: SMR 1 female
EXT: short fingers and toes, short arms and legs, broad edematous hands b/l
NEURO: deep tendon reflexes hypereflexic with markedly delayed return
phase
SKIN: pale, dry boggy skin, with myxedematous changes, multiple nevi with
raised nevi at external ear canal on left
In the hospital
Labs
145
109
14
250
3.5
22
0.7
Ca 10.6
Phos 2.4
Mg 1.9
99.7
7.1
8.2
268
21.2
14.8
N77 L19 M4 B0.1
58
6.5
35
0.2
3.3
24
0.1
CK 87
LDH 215
PT 16.4s
INR 1.31
PTT 20.3s
Lactate 4.3
Ammonia 32
CRP 5.3
VBG: pH 7.3 pCO2 50 pO2 45 HCO3 25 BD 1.1 O2 75%
Endocrine Labs
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TSH 208
FT4 <0.4
FT3 <1.1
Thyroglobulin 4.2
Thyroglobulin Ab <1
• PTH 66
• Prolactin 113.4
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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
Skeletal
Survey
• 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
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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%)
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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…
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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 @
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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 therapy
 Developmental or
maturational changes
 Increased social interactions
 Prevent myxedema coma
 Prevent hospitalizations
 Compatible with
life/sustains life
Cons to therapy
 Menses
 Increased caretaking
responsibilities
 Increased medical
monitoring
 Behavioral changes
(aggressiveness, mood
liability)
Case report cont.
Prior to Therapy
7 months after therapy
References
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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 Insufficiency
B. Diabetes mellitus
C. Learning disorder
D. Normal adult height
E. 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).