Congenital hypothyroidism and nonimmune hydrops fetalis: Associated?

Hydrops fetalis (HF) consists of an abnormal accumulation of fluid in two o r more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema. Almost all observed cases of HF are of the nonim mune type, the causes of which remain undetermined in 15% of patients. We r eport a newborn infant with nonimmune hydrops fetalis (NIHF) and congenital hypothyroidism. The infant's mother was healthy and there were no malforma tions of the placenta or umbilical cord. The infant did not show any struct ural abnormalities of his central nervous, cardiovascular, gastrointestinal , or urinary tract systems, and there was no evidence of anemia, infectious disease, or inborn error of metabolism. An immune-based process was unlike ly, because the blood group of the mother and infant was A-positive and res ults of an indirect Coombs test in the mother and a direct Coombs test in t he infant were negative. The patient's condition gradually improved with me chanical ventilation, repeated thoracocentesis, and total parenteral nutrit ion. By day 5 of age the skin edema, pericardial effusion, and ascites disa ppeared, but accumulation of significant amounts of chylous pleural fluid p ersisted. Because of lethargy, FT, and thyroid-stimulating hormone levels w ere obtained and showed hypothyroidism. Thyroid hormone supplementation was then started, and within 4 days the infant became more vigorous and was we aned from mechanical ventilation. After 7 days, the chylothorax resolved co mpletely as the serum thyroxine level normalized. No reaccumulation of pleu ral effusion was noticed. The infant started to gain weight and was dischar ged from the hospital at 35 days of age. A possible pathophysiologic associ ation between congenital hypothyroidism and NIHF is discussed. NIHF may be caused by lymphatic congestion attributable to an impairment of lymphatic f low and a delayed return of lymph to the vascular compartment. There could be a possibility that because of thyroid hormone deficiency in this patient there was reduced adrenergic stimulation of the lymphatic system. This cou ld result in a sluggish flow of the lymph with engorgement of the lymphatic system, leakage of lymph into the pleura and the interstitial spaces, and the production of chylothorax with NIHF. Animal studies demonstrate a direc t relationship between lymph flow rate or lung liquid clearance and adrener gic receptor activity in the lymphatic system. These observations support o ur hypothesis that deficient adrenergic activity in congenital hypothyroidi sm might lead to chylothorax with NIHF in the fetus. We speculate that thyr oid hormone may play a role in the regulation of adrenergic receptors in th e lymphatic system and lungs, thus modulating both the lymphatic flow rate and lung liquid clearance, and facilitating the resolution of chylothorax. Examination of thyroid functions should be included in the investigation of fetuses and neonates with NIHF of an obscure origin.