Neonatal Intensive Care

Dopamine infusion: A possible cause of undiagnosed congenital

hypothyroidism in preterm infants
Luca Filippi, MD; Marco Pezzati, MD; Alessandra Cecchi, MD; Chiara Poggi, MD

Objective: To describe the possibility that dopamine infusion
can prevent early diagnosis of congenital hypothyroidism.
Design: Case report.
Setting: Medical neonatal intensive care unit of a tertiary
academic medical center.
Patients: We report four preterm newborns affected by tran-
sient primary congenital hypothyroidism who showed low serum
thyroxine and normal thyroid-stimulating hormone concentrations
on primary screening performed during treatment with dopamine.
Interventions: Thyroid reevaluation screening after dopamine
discontinuation.
Measurements and Main Results: Thyroid reevaluation showed
elevated thyroid-stimulating hormone levels.
Conclusion: We emphasize that dopamine capacity to suppress
thyroid-stimulating hormone could prevent early diagnosis of
congenital hypothyroidism. We suggest all newborns to be tested
simultaneously for thyroid-stimulating hormone and thyroxine
values at primary screening. A reevaluation of thyroid hormones
after dopamine discontinuation is advisable in patients treated
with dopamine. (Pediatr Crit Care Med 2006; 7:249 –251)
KEY WORDS: congenital hypothyroidism; dopamine; preterm;
newborn; thyroid; screening

N
eonatal screening allows
early identification of con-
genital hypothyroidism (CH)
through the detection of low
serum thyroxine (T4) levels and, in case of
primary hypothyroidism, elevated thy-
roid-stimulating hormone (TSH) levels
(1). Most of European and Japanese neo-
natal screening programs are based on
primary TSH measurements.
In preterm infants dopamine is a first-
choice treatment for inotropic support
(2), but it has been shown to suppress
TSH secretion (3). We describe four pre-
term newborns affected by CH who
showed low T4 and normal TSH concen-
trations on primary screening, performed
during dopamine treatment. Thyroid re-
evaluation screening after dopamine dis-
continuation showed elevated TSH levels.
CASE REPORT
Patient 1. A female infant weighing
750 g was delivered by caesarean sec-
tion at 26!3 wks of gestational age for
From the Neonatal Intensive Care Unit, Department
of Critical Care Medicine, University Careggi Hospital,
Florence, Italy.
The authors did not receive any financial support
for this study.
Copyright © 2006 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000216680.22950.D9
maternal preeclampsia. She was resus-
citated at birth; her Apgar score was
31–75. Surfactant was replaced. Twenty-
four hours later, the infant was extu-
bated, and she received nasal continu-
ous airway pressure for the following 4
days. She presented edema in the lower
limbs. Hypotension [40/20 mm Hg;
mean arterial pressure, 35 mm Hg] re-
quired treatment with plasma and do-
pamine, 4 "g·kg#1·min#1. Early and
persistent jaundice (208.6 "mol/L at 28
hrs) was treated with phototherapy.
Neonatal screening showed a slightly
increased level of TSH and low levels of
T4 (Table 1). An early chronic lung dis-
ease was treated with fluid restriction,
diuretics, and aerosol. Sixteen days af-
ter dopamine discontinuation, very
high levels of TSH and reduced levels of
T4, free thyroxine (FT4), triiodothyro-
nine (T 3), and free triiodothyronine
(FT3) were assessed; thyroglobulin was
within the normal range. Thyroid ultra-
sound was normal and technetium per-
technetate scans revealed regular up-
take of the radioisotope. Treatment
with L-thyroxine, 4 "g·kg#1·day#1, was
started at 28 days of life. In the follow-
ing days, weight growth was regular,
apnoeas disappeared, and electroen-
cephalogram was normal. At the age of
21⁄2 months, the infant was discharged,
and treatment with L -thyroxine was
stopped at the age of 12 months. At
present, the infant is 17 months old;
she presents good clinical conditions
and her thyroid function is normal.
Patient 2. A male infant weighing
1310 g was born at 31 wks of gestational
age by caesarean section for fetal dis-
tress in a twin dizygotic pregnancy. The
male twin had an uneventful hospital-
ization, but periventricular leukomala-
cia affected his outcome. Despite re-
peated epinephrine administration,
cardiac compressions and plasma ex-
pansion were performed, cardiac failure
occurred, and cardiopulmonary resus-
citation was required. Apgar score was
01–35– 610–715. Two doses of surfactant
were administered for respiratory dis-
tress syndrome. Cardiac ultrasonogra-
phy showed restrictive hypertrophic
cardiomyopathy, presumably due to fet-
ofetal transfusion. Treatment consisted
of plasma infusion to increase the pre-
load, propanolol, and low-dose dopa-
mine administration. Renal failure oc-
curred. Seizures were treated with
phenobarbital. Neonatal screening
showed a normal level of TSH and low
levels of T4 (Table 1). Eleven days after
dopamine discontinuation, very high
levels of TSH, with reduced levels of T4,
FT4, and FT3 were detected. Thyroid
ultrasound was normal and scintigra-
phy revealed regular uptake of the ra-
dioisotope. Treatment with L-thyroxine,
4 "g·kg#1·day#1, was started at 28 days

Pediatr Crit Care Med 2006 Vol. 7, No. 3 249

Table 1. Demographic data and hormonal profile on investigated patients

Patients 1 2 3 4

Sex Female Male Male Female

Gestational age, wksa 26!3 31 28!6 27!5
Birth weight, g 750 1310 700 730
Caesarean section Yes Yes Yes Yes
Prenatal corticosteroidsb Yes Yes Yes Yes
Apgar score 3–7 0–3–6–7 7–8 4–8
Day of screening 4 5 3 5
Dose of dopamine, "g!kg#1!day#1 3600 2880 4560 8640
TSH, milliunits/L (4.3 & 0.6)c 5.84 3.69 0.86 1.75
T4, nmol/L (68.2 & 4.1)c 32.1 2.3 25.8 37.8
Day of dopamine discontinuation 6 10 4 10
Day of screening re-evaluation 22 21 20 16
TSH, milliunits/L (3.3 & 0.4)d 90.2 100.3 61.6 58.2
FT4, pmol/L (11.0 & 0.4)d 1.28 3.86 7.22 8.33
T4, nmol/L (74.8 & 4.2)d 23.16 52.72 86.92 82.67
FT3, pmol/L (4.3 & 0.1)d 0.15 1.05 2.61 2.95
T3, nmol/L (0.8 & 0.07)d 0.58 1.84 2.13 1.93
Thyroglobulin, nmol/L (177.6–217.5)e 406.2 195.9 179.7 215.6

TSH, thyroid-stimulating hormone; T4, thyroxine; FT4, free thyroxine; FT3, free triiodothyronine; T3, triiodothyronine.
a
Gestational age was determined on the basis of the mother’s menstrual history, obstetrical data, or by Ballard’s score; btwo doses of 12 mg of
betamethasone each were given to mothers 24 hrs apart in cases of imminent premature delivery; cvalues in preterm infants 30 wks of gestation at 7 days
of life (12); dvalues in preterm infants 30 wks of gestation at 14 days of life (12); emedian serum thyroglobulin concentrations, respectively, in appropriate
and small for gestational age premature infants at 21 days of life (values have been converted from ng/mL to nmol/L) (17).

of life. The infant was then transferred
to another hospital, nearer to the par-
ents’ residence. Porencephaly and tet-
raplegia dramatically characterized his
clinical course.
Patient 3. A male infant weighing
700 g was born at 28!6 wks of gestational
age by caesarean section because of intra-
uterine growth retardation and reverse
umbilical blood flow. His mother suffered
from autoimmune thyroiditis, which was
treated with L-thyroxine. Apgar score was
71– 85. A mild respiratory distress syn-
drome required nasal continuous airway
pressure. Fresh frozen plasma and dopa-
mine, 8 "g·kg#1·min#1, were adminis-
tered because of hypotension (40/20 mm
Hg; mean arterial pressure, 34 mm Hg)
and absent diastolic flow in the anterior
cerebral arteries. Early jaundice (218.9
"mol/L at 32 hrs) was treated with pho-
totherapy. Recurrent apnoeas required
nasal continuous airway pressure for
about 13 days. Neonatal screening
showed low levels of TSH and T4 (Table
1). The infant presented irregular feeding
tolerance and weak weight growth.
Sixteen days after dopamine discon-
tinuation, he had a high TSH level, with
low FT3 and FT4 values. Thyroid peroxi-
dase antibodies and thyroglobulin anti-
bodies were positive, even if their levels
were lower than maternal ones. Thyroid
ultrasound study was normal, and tech-
netium pertechnetate scans revealed ir-
regular uptake of the radioisotope with
localized functioning areas. Treatment
with L-thyroxine, 4 "g·kg#1·day#1, was
started at 21 days. The following days, the
weight growth was regular and apnoeas
disappeared. At the age of 67 days, the
infant was discharged. Remission of hy-
pothyroidism occurred within 3 months
and scintigraphy showed a normal thy-
roid gland.
Patient 4. A female infant weighing
730 g was delivered at 27!5 wks of gesta-
tional age by caesarean section for mater-
nal preeclampsia, intrauterine growth re-
tardation, and abruptio placentae. She was
resuscitated at birth; Apgar score was 41–
85. After 12 hrs of mechanical ventilation,
nasal continuous airway pressure was ad-
ministered for the following 3 days. Hypo-
tension (42/20 mm Hg; mean arterial pres-
sure, 34 mm Hg) required treatment with
plasma and dopamine, 6 "g·kg#1·min#1.
Jaundice (222.3 "mol/L at 36 hrs) was
treated with phototherapy. Neonatal
screening showed a normal level of TSH
and low levels of T4 (Table 1). Cerebral
ultrasonography showed a grade II intra-
ventricular hemorrhage. Ten days after do-
pamine discontinuation, her TSH level was
high, with low FT3 and FT4 values; thyro-
globulin was within the normal range. A
thyroid ultrasound study was normal, and
technetium pertechnetate scans revealed
regular uptake of the radioisotope. Treat-
ment with L-thyroxine, 4 "g·kg#1·day#1,
was started at 20 days of life. Her further
course was uneventful, and she was dis-
charged at 73 days of life, with no severe
complications. At present, the infant is 9
months old, she presents good clinical con-
ditions, and she is still under treatment
with L-thyroxine.
METHODS
T4 and TSH concentrations were measured
in the specimen for primary screening by
means of a commercial assay kit (AutoDelfia
Neonatal TSH and T4, Wallac O.Y., Turku,
Finland) using the enzyme-linked immunoas-
say method with the AutoDelfia spectropho-
tometer WALLAC 1235. Newborns who
showed T4 values of $51.5 nmol/L or TSH
values of %10 milliunits/L on primary screen-
ing were called back for reevaluation. In these
infants, iodothyronines, TSH, and thyroglob-
ulin were measured by double-antibody im-
munoradiometric assay systems (IRMA for
TSH, T4, T3, FT4, and FT3; ICN Pharmaceuti-
cals, Orangeburg, NY; and ELSA-hTG, Scher-
ing, Segrate, Milan, Italy).
Our institutional review board approved
the publication of this case report.
DISCUSSION
Neonatal screening programs are suc-
cessfully used to diagnose neonatal hypo-
thyroidism, which affects 1 of every
3000 – 4000 newborns (4). The purpose of
most neonatal screening programs is the
detection of a primary CH by measuring
TSH in filter blood spots (5). However,
the Tuscany screening program consists

250 Pediatr Crit Care Med 2006 Vol. 7, No. 3

of simultaneous T4 and TSH testing to
detect infants with hypopituitary hypo-
thyroidism (6). Early diagnosis is very
important because a reduction in thyroid
function could increase the risk of an
unfavorable neurodevelopmental progno-
sis in preterm infants (7).
Dopamine is a first-choice drug for
hemodynamic stabilization in infants (2).
Acting on specific D2 receptors, dopamine
affects hypophyseal function and inhibits
the release of TSH, prolactin, growth hor-
mone, and other hypophyseal hormones
(8). In newborn infants, dopamine can
induce suppression of TSH secretion,
even if an immediate increase in the TSH
level is observed after its discontinuation
(4). Recently, a relationship between do-
pamine infusion and transient hypothy-
roidism of prematurity was demonstrated
(9).
Dopamine capacity to suppress TSH
secretion could prevent early diagnosis of
primary CH if the primary screening is
based on significant levels of TSH of %20-
milliunits/L values (10). The four patients
reported showed TSH values normal or
slightly increased compared with values
of very-low-birth-weight newborns at 7
days of life (11, 12). They were reevalu-
ated because T4 values were much lower
than expected (13) and because reevalua-
tion was performed after the discontinu-
ation of dopamine infusion. The finding
of high TSH levels allowed us to exclude
the diagnosis of transient hypothyroxine-
mia of prematurity and of nonthyroidal
illness, both rather common conditions
in premature infants (14). The diagnosis
of euthyroid sick syndrome was consid-
ered unlikely because this syndrome is
usually present with decreased levels of
total T4 and TSH (15).
Levels of TSH observed on reevalua-
tion screening were too high to hypoth-
esize a rebound after dopamine discon-
tinuation; moreover, such rebound
should be characterized also by an in-
crease of T4 levels (3).
Based on a normal thyroid ultrasound
study with normal thyroglobulinemia
and the lack of family history of hypothy-
roidism, transient CH was suspected in
the patients, even if a precise diagnosis is
difficult in a stormy neonatal phase. In
fact, to determine whether CH is perma-
nent or transient, each infant must be
tested for thyroid function after T4 treat-
Pediatr Crit Care Med 2006 Vol. 7, No. 3
ment cessation at 3 yrs of age or beyond.
Eutopic hypothyroidism, such as thyroid
dyshormonogenesis, was ruled out in our
patients because of normal thyroglobu-
linemia.
No newborn was treated with iodine-
containing contrast fluids or was exposed
to cutaneous, mucosal, or oral iodides.
Regrettably, no urinary iodine measure-
ments were obtained to detect the pres-
ence or absence of iodine excess or defi-
ciency.
These cases would have been misdiag-
nosed at screening if only TSH values had
been measured. Based on this clinical ob-
servation, it could be wise to modify the
screening strategy for newborns treated
with dopamine. To delay the initial
screening until dopamine infusion is sus-
pended would reduce the occurrence of
false-negative results; however, it would
increase the risk of false-positive results
because the suspension of dopamine
treatment is followed by a rebound in-
crease of TSH plasma levels (3). A lower
TSH cut-off level for CH in very-low-
birth-weight newborns under dopamine
treatment could be considered as an al-
ternative possibility, but TSH values
could be very low in these neonates, as
evident in patient 3.
In conclusion, we suggest to test si-
multaneously TSH and T4 values in the
primary screening of all newborns. The
evidence of low T4 values, even in the
presence of low–normal TSH values, may
mask an occult CH. Extremely preterm
infants should be re-screened again at 32
wks of corrected age (1), although a sin-
gle study recently suggested that a rou-
tine second screening may not be needed
for detection of CH in very-low-birth-
weight infants (16). A reevaluation of thy-
roid hormones after dopamine discontin-
uation is advisable in all patients treated
with dopamine.
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