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Indian Pediatr 2020;57: 75 -76 |
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Consumptive Hypothyroidism Due to Diffuse Hepatic Hemangiomas
Treated With Propranolol Therapy
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Kriti Joshi1, Rishi Bolia2, Ujjal Poddar2 and Preeti
Dabadgao1*
Departments of 1Endocrinology and 2Pediatric Gastroenterology,
Sanjay Gandhi Post Graduate Institute of Medical Sciences,
Lucknow, Uttar Pradesh, India.
Email:
[email protected]
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Infantile hepatic hemangioma
(IHH)-related consumptive hypothyroidism is rare and occurs
as a result of excess thyroid hormone inactivating enzyme,
type-3 iodothyronine deiodinase. We present an infant with
IHH-related hypothyroidism, in whom treatment with
propranolol led to regression of tumor and subsequent
euthyroid status.
Keywords:
Liothyronine, Management, Type 3 deiodinase.
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Consumptive hypothyroidism is a complication of infantile hepatic
hemangioma (IHH) caused by increased expression of type-3 deiodinase
enzyme in the tumor tissue. This enzyme causes increased degradation of
T4 and T3 to reverse T3 (inactive metabolite). When this exceeds the
rate of synthesis of these hormones, a state of hypothyroidism ensues.
Definitive therapy for the hemangioma and reduction in tumor burden
leads to resolution of hypothyroidism. We describe a child who presented
with severe hypothyroidism secondary to consumption by an IHH.
A
3-month-old female baby presented with severe constipation for the past
one month. Parents also complained of dullness, poor cry and abdominal
distention. There was no history of poor feeding, umbilical hernia or
jaundice. The child had been born at term to a primigravida mother with
a birth-weight of 2.2 kg. Her weight at presentation was 4.5 kg –2 SD)
and length 55 cm (–2 to –3 SD). Physical examination revealed pallor,
depressed nasal bridge and macroglossia. Her abdomen was distended and
liver palpable 6 cm below the costal margin. She had an ejection
systolic murmur. The thyroid gland was normally palpable.
An
abdominal ultrasound revealed multiple hypoechoic lesions in the liver.
Contrast-enhanced CT scan showed these lesions to have early enhancement
with persistence in delayed phase consistent with a diagnosis of IHH
(Fig. 1 a). The child was not found to have any cutaneous hemangiomas.
Thyroid function tests showed high TSH >75 mIU/L (0.57–5.54), low-normal
FT4 14.6 pmol/L (60-160) and low T3 <0.62 nmol/L (1.3-2.8) (Web
Table I). Thyroid ultrasound showed a eutopicaly located gland
and thyroid scan showed normal radionuclide uptake. Reverse T3 levels
were raised (607 ng/dL, normal range 10-50) pointing towards peripheral
consumption of thyroid hormone. She was treated with oral levothyroxine
50 µg (11 µg/kg/day). However, even after two weeks, TSH remained high.
Therefore, thyroxine dose was further increased. For the hemangioma,
child was started on prednisolone at the dose of 2mg/kg/d. When even
after 2 weeks of therapy ultrasound did not show any reduction in size
of the lesion, interferon a (6 mu/m2/day alternate day) was added.
During this period the child also developed congestive cardiac failure,
which was treated with digoxin and furosemide.
TSH persisted to
be high even on 112.5 µg (22.5 µg/kg/day) of levothyroxine necessitating
further increase in the dose to 150 µg. As the child was requiring such
high doses of LT4, oral liothyronine (T3) preparation (Bitiron) was
added at a dose of 12.5 µg twice a day (Table I). On
this dose the child remained stable with normalization of thyroid
function. As ultrasound of the abdomen did not reveal any significant
reduction of the tumour mass on interferon alpha therapy, it was
discontinued and propranolol was started (2 mg/kg/d). Over the next 3
months, there was significant reduction in tumor size and in her
thyroxine requirements. Her cardiac status also improved. There was no
bradycardia or hypotension during therapy.
Table I Trend of Thyroid Profile and Thyroid Hormone Requirements in the Index Case
|
Age |
Weight |
TSH |
T4 |
T3 |
Levothyroxine |
T3 dose |
Treatment | |
(mo) |
(Kg.) |
(mIU/L) |
(nmol/L) |
(nmol/l) |
dose (mcg) |
(mcg) |
For IHH | |
3 | |
>75 |
FT4 -14.8 | |
<0.62 (pmol/L) |
- |
- | |
4 |
4.1 |
- |
110 |
0.72 |
75 |
- |
Prednisolone | |
5 | |
26.1 |
230 |
- |
112.5 | |
Prednisolone + Interferon | |
6 |
5 |
0.44 |
116 |
<0.62 |
150 |
25 |
Propranolol | |
7 | |
0.15 |
149 |
<0.62 |
100 |
25 | | |
8 | |
<0.01 |
136 |
2.51 |
75 |
12.5 | | |
9 | |
0.02 |
149 |
2.66 |
50 |
12.5 | | |
11 | |
0.068 |
101 |
2.8 |
37.5 |
12.5 | | |
15 | |
0.05 |
133 |
2.65 |
25 |
Stopped | | |
16 | |
0.52 |
88 |
3.1 |
18.75 |
- |
Stopped | |
18 |
10 |
1.7 |
126 |
3.1 |
12.5 |
- | | |
21 | |
0.97 |
100 |
1.5 |
Stopped |
- | | |
23 | |
1.5 |
89 |
2.8 |
- |
- | | |
Normal ranges: TSH:0.57-5.54 mIU/L, T4: 60-160 nmol/L, T3:1.3-2.8 nmol/L, FT4: 14-31 pmol/L; TSH: Thyroid stimulating hormone. |
Liothyronine could be
tapered and stopped after 5 months. After 10 months of propranolol
treatment, repeat CT imaging showed complete resolution of tumor and
propranolol was stopped (Fig. 1b). Thyroxine doses were
tapered and finally stopped at the age of 21 months. (Table I).
On follow-up until the age of two years the child remained euthyroid,
with age appropriate developmental milestones, and normal liver
appearance on ultrasound scans.
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| Fig. 1 (a)
Contrast-enhanced computed tomograph of abdomen in
venous phase showing diffuse involvement of liver by
hemagiomas, (b) Post-propanolol therapy showing complete
resolution of hemagiomas. |
In IHH with consumptive
hypothyroidism, supra-physiological doses of thyroxine are required to
counteract the deactivation of T4 by the D3 deiodinase. As untreated or
inadequately treated hypothyroidism in the first year of life can have
severe consequences, like impaired neurodevelopmental outcome,
aggressive treat-ment of babies with consumptive hypothyroidism is
mandated. Most children respond to high doses of thyro-xine, though
addition of liothyronine to the treatment regimen has been reported to
help in normalization of T3 levels and earlier restoration of
euthyroidism [1]. Combined therapy may be useful in challenging cases
where there is high rate of consumption of thyroid hormones.
Definitive therapy for hypothyroidism is treatment of IHH. Traditionally
high dose corticosteroids have been the first line therapy [2]. However,
steroids can have adverse effects and also increase the thyroid hormone
requirement by inducing type-3 deiodinase activity and impair T4 to T3
conversion leading to further worsening of thyroid function. Second line
therapy consisted of vincristine, interferon and cyclophosphamide [2].
Intractable cases need hepatic artery embolization, segmental resection
or liver transplantation.
Propranolol was first suggested as
therapy for cutaneous hemangiomas in 2008 and since then has been used
for IHH as well with recent data showing a complete response in >90%
patients [3-5]. Some of the proposed mechanisms of action include
vasoconstriction, decreased renin production, inhibition of
angiogenesis, and stimulation of apoptosis [5]. Adverse effects of the
drug may be bronchospasm, bradycardia, hypotension, and hypoglycemia
[3]. However, our patient did not demonstrate any of the above
complications and rather showed resolution of cardiac failure.
Propranolol should possibly be offered as first line therapy to infants
with diffuse IHH, especially those with hypothyroidism, as rapid
normalization of thyroid function is highly desirable to ensure normal
neurodevelopment.
Contributors: All authors were involved in
case-management and manuscript preparation, and approved the final
version of manuscript. All authors agree to be accountable for all
aspects related to the study.
Funding: None; Competing interest:
None stated.
REFERENCES
1. Osada A,
Araki E, Yamashita Y, Ishii T. Combination therapy of propranolol,
levothyroxine, and liothyronine was effective in a case of severe
consumptive hypothyroidism associated with infantile hepatic hemangioma.
Clin Pediatr Endocrinol. 2019;28:9-14.
2. Dickie B, Dasgupta R,
Nair R, Alonso MH, Ryckman FC, Tiao GM, et al. Spectrum of hepatic
hemangiomas: management and outcome. J Pediatr Surg. 2009;44:125-33.
3. Leaute-Labreze C, Hoeger P, Mazereeuw-Hautier J, Guibaud L,
Baselga E, Posiunas G, et al. A randomized, controlled trial of oral
propranolol in infantile hemangioma. N Engl J Med. 2015;372:735-46.
4. Emir S, Ekici F, Ikiz MA, Vidinlisan S. The association of
consumptive hypothyroidism secondary to hepatic hemangioma and severe
heart failure in infancy. Turk Pediatri Ars. 2016;51:52-6.
5.
Yang K, Peng S, Chen L, Chen S, Ji Y. Efficacy of propranolol treatment
in infantile hepatic haemangioma. J Paediatr Child Health. 2019.
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