- 1. Freund Publishing House Ltd., London Journal of Pediatric
Endocrinology & Metabolism, 23, 153-158 (2010) Late-Onset
Circulatory Dysfunction After Thyroid Hormone Treatment in an
Extremely Low Birth Weight Infant Hideaki Yagasaki1, Kisho
Kobayashi2, Atsushi Nemoto1, Atsushi Naito1, Kanji Sugita2, and
Kenji Ohyama2 1Division of Neonatology, Perinatal Center, Yamanashi
Prefectural Central Hospital and 2 Department of Pediatrics,
Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
ABSTRACT KEY WORDS Late-onset circulatory dysfunction (LCD)
islate-onset circulatory dysfunction, hypothyroid- a phenomenon
specific to premature infantsism, extremely low birth weight
infant, adrenal and is characterized by sudden onset of hypo-
insufficiency natremia, hypotension, oliguria and non-
physiological weight gain, without an obviousINTRODUCTION cause, in
premature infants after stabilization of circulation and
respiration. The cause of Premature infants often have poor
pituitary LCD is not clear, but adrenal insufficiency in function
and hormone synthesis, and often deve- premature infants is a
severe syndrome lop relative hormone insufficiency. In Japan, a
because steroid replacement therapy is often number of premature
infants with late-onset essential to treat the symptoms. We report
a circulatory dysfunction (LCD; or late-onset rare case of a
premature infant who developed circulatory collapse) have been
reported1. This an LCD crisis the day after thyroxine replace-
syndrome is classified as adrenal insufficiency of ment therapy.
The female infant was born at prematurity (AOP) when steroids need
to be 25 weeks of gestational age, weighing 672 g, administered to
overcome impaired adrenal and appeared to have hypothyroidism, with
function. LCD is usually characterized by sudden free T4 of 0.19
ng/dl and elevated TSH levels onset of hyponatremia, hypotension,
oliguria, of 26.3 IU/ml at Day 14. She developed an and
non-physiological weight gain, without an LCD crisis the day after
starting thyroxine obvious cause, in infants after stabilization of
treatment. She received steroid replacement circulation and
respiration. Some LCD cases are therapy for 4 weeks and her adrenal
function considered to show relative adrenal insufficiency
progressively recovered. She also needed thy- because volume
expanders (physiological saline roxine supplementation for 13
weeks, which or plasma albumin agents) and inotropic agents
maintained her thyroid function as euthyroid. are often
ineffective, whereas steroid replacement Because she exhibited
cortisol insufficiency therapy is usually effective2. On the other
hand, and thyroid hormone insufficiency, the ante- hypothyroxinemia
is often reported in premature cedent thyroid hormone replacement
may be infants3, and many trials of thyroxine replacement
responsible for the onset of LCD. We must therapy (predominantly
levothyroxine) have been consider monitoring adrenal function when
reported4. However, it is unclear whether thy- starting thyroxine
therapy in premature roxine replacement is effective in terms of
neuro- infants with hypothyroxinemia. developmental outcome in
premature infants. Some cases of premature infants who developed
Reprint address:LCD after receiving thyroxine treatment for Hideaki
Yagasaki M.D. hypothyroxinemiahaverecentlybeen Department of
Pediatrics Yamanashi Prefectural Central Hospital experienced in
Japanese neonatal intensive care 1-1-1 Fujimi, Kofuunits (NICU).
These cases have not been reported Yamanashi 400-8506, Japan yet,
and the relationship between thyroxine e-mail:
[email protected] 23, NO. 1-2, 2010153
2. 154 H. YAGASAKI ET AL.therapy and LCD is unclear. Therefore,
we reportwas very low (2.0 g/dl), relative adrenal here an
extremely low birth weight infant who insufficiency was suspected.
developed LCD after thyroxine treatment.Based on these findings, we
diagnosed LCD and started steroid therapy (hydrocortisone, 1
mg/dose, twice per day), and continued thyroxine PATIENT REPORT
therapy. Her blood pressure and urine volume improved within 24
hours, she was able to A female infant was born at the gestational
continue milk feeding, and showed weight gain. age of 25 weeks and
1 day, with a birth weight of The clinical course after steroid
therapy is shown 672 g and height of 31.5 cm. She was the first in
Figure 2. Her steroid therapy was continued for child of healthy
parents of Brazilian nationality. 40 days after the first
administration. Thyroxine Her mother was admitted to our hospital
due to therapy was set to 5.0 g/day between Days 15 premature
rupture of the membranes, and her and 116. On Day 116, her body
weight had laboratory data were WBC 13,000/l and CRP increased to
1,700 g and thyroxine was dis- 0.56 mg/dl. Therefore, continuation
of pregnancy continued. Her thyroid hormone status was was
difficult and an emergency Cesarean section maintained as euthyroid
and, 1 month later, her was performed. Antenatal steroids were not
TSH, free T3 and free T4 levels were 2.58 administered because of
the emergency delivery. IU/ml, 3.68 pg/ml and 1.28 ng/dl,
respectively. The infant had a 1-min Apgar score of 5 and a 5- On
day 160, we performed a CRH loading test to min score of 7.
Therefore, she was intubated assess her adrenal function, and the
results are while in the delivery room for positive pressure shown
in Figure 3. The CRH loading test ventilation and she was then
admitted to our revealed normal adrenal function, although a NICU.
TRH administration test was not performed at The clinical course of
the emergency period is that time. The patient was discharged on
Day 165 shown in Figure 1. She was treated with intra- weighing
3,586 g and continued treatment at an tracheal surfactant due to
respiratory distress outpatient department. At this time, she had
syndrome; antibiotics, gamma-globulin and granu- chronic lung
disease (CLD) and mild deafness, locyte-colony stimulating factor
due to infection; without periventricular leukomalacia (a major and
inotropic agent (dopamine) and indomethacin complication associated
with LCD). because of the presence of patent ductus arteriosus.
After stabilizing her respiratory and circulatory status,
breast-milk feeding was started DISCUSSION at day 5 and her body
weight increased slightly. Fourteen days after birth, her
laboratory Here, we have reported a rare case of an examination
revealed hypothyroidism; her serumextremely low birth weight infant
who had free T3 concentration was 1.65 pg/ml, free T4 cortisol
insufficiency and thyroid hormone was 0.19 ng/dl and TSH was 26.3
IU/ml. insufficiency. We considered that it would be Therefore,
thyroxine therapy (5.0 g/day) was dangerous to treat hypothyroidism
in a premature commenced. The next day (Day 15), she
suddenlyinfant, and it was difficult to assess the associ-
developed hyponatremia (serum Na: 129 mEq/l), ation between LCD and
thyroxine therapy. hypotension (blood pressure: 45/24 mm Hg; The
underlying pathogenesis of LCD is
