Late-Onset Circulatory Dysfunction After Thyroid Hormone

• 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: yagasaki@mwd.biglobe.ne.jpVOLUME 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