Introduction
Neonatal hyperparathyroidism is a rare clinical entity with various etiologies. Neonatal hyperparathyroidism can be primary or secondary. secondary hyperparathyroidism can be due to maternal hypocalcemia, which may develop during hypoparathyroidism, pseudohypoparathyroidism, chronic renal failure, and renal tubular acidosis.1’6 Neonatal hyperparathyroidism can be fatal or can also result in several sequelae. Intrauterine bone fracture is a rare complication of neonatal hyperparathyroidism.1 In addition, severe respiratory involvement is also encountered in neonatal hyperparathyroidism.
We present a case of neonatal hyperparathyroidism with multiple bone fractures and findings of rickets due to maternal hypoparathyroidism and vitamin D deficiency.
Patient Report
A 3-month-old female infant was referred to this university hospital because of respiratory distress and multiple bone fractures. She was born to a 25-year-old woman by noncomplicated vaginal delivery at 36 gestational weeks. She was the third sibling of the family; she had a healthy brother and sister aged 7 and 4 years, respectively. Her parents were first-degree cousins. Her mother had been suffering recurrent carpopedal spasms for the last 4 years including the pregnancy period but she did not receive any therapy for hypocalcemia.
In her first month of life, the patient failed to gain weight and suffered from recurrent apnea and cyanosis with respiratory distress. When she was 1 month old, she was hospitali/ed at a local community hospital. She was diagnosed with pneumonia and treated with nonspecific parenteral antibiotics. It was also noticed that she had multiple bone fractures with significant deformities on extremities suggesting congenital rickets. At that time serum calcium, phosphorus, alkaline phosphatase (ALP) and 25 hydroxyvitainin D levels were in normal ranges; however, parathyroid hormone (PTH: 98.7 pg/mL, normal: 13-66 pg/mL) was elevated. She was administered 800 U of cholecalciferol per day. After 1 month of hospitalization, there was no improvement in the pulmonary involvement and she was referred to this clinic.
At 3 months of age, her weight was 2,400 g, height 47 cm, head circumference 37 cm. She was tachypneic (respiration rate 60-80 breaths/minute), her heart rate was 166 beats/minute, and axillary body temperature 36.7C. There was significant loss of subcutaneous tissue and decreased muscle tone. On pulmonary examination, subcostal and intercostal retractions were noticed. On chest auscultation, bilateral, widespread, fine crackles with wheezing were present. Enlargement of costochondral junctions and thickening of wrists were detected. There were also deformities on upper and lower extremities.
Results from laboratory examination were as follows: hemoglobin: 10.3 g/dL; hematocrit: 31.8%; leukocytes: 9,000/mm^sup 3^; platelets: 297,000/mm^sup 3^; calcium: 9.3 mg/dL; phosphorus: 4.8 mg/ dL; ALP: 431 U/L (normal:35-462); arterial blood pH: 7.24; bicarbonate: 29.7 mmol/L; partial pressure of oxygen (Po^sub 2^): 45.6 mm Hg; partial pressure of carbon dioxide (PcO^sub 2^): 69.6 mm Hg: O2 saturation: 72.9%; intact PTH: 160 pg/mL (normal 12-65 pg/ mL); 25-hydroxyvitamin D: 35 ng/mL (normal:10-40 ng/mL); sweat chloride test: 7 mEq/L. Chest radiography and thoracic computed tomography (CT) revealed atelectasis on the left lung and compensatory hyperaeration on the right lung. Anterior ends of the ribs were enlarged in the chest radiograph as well. Serum quantitative immunoglobulins G, M, and A were within normal levels. A barium esophagogram showed no gastroeosophageal reflux. An echocardiogram revealed mild mitral insufficiency. Nasopharyngeal aspirate was tested for RSV PCR and found to be positive. Radiographs of the extremity showed multiple fractures at bilateral proximal humerus, distal radius, and distal femur with severe demineralization. There was also clipping, fraying, and widening of metaphysis at the distal ends of radius, humerus, and femur (Figure 1).
Her mother was investigated for overt tetany. The serum concentration of calcium was 4.6 mg/dL; phosphorus: 10.4 mg/dL; ALP: 79 U/L; intact PTH:
Figure 1. The radiologie view of extremities showing multiple fractures at proximal humerus, distal radius, and distal femur bilaterally with severe demineralization and cupping, fraying, and widening of metaphysis at the distal ends of radius, humerus, and femur.
In the follow-up, the patient was treated with intravenous antibiotics, nebulized salbutamol, supplemental oxygen, and chest physiotherapy. Maintenance doses of vitamin D (400 ILJ/day) were administered perorally. Daily 500 mg elemental calcium requirement was provided by enterai feeding. After 5 weeks of intensive care, the clinical picture of severe respiratory distress subsided and atelectasis of the left lung improved. Callus formation on the sites of fracture and recovery in the metaphyses were observed. Intact PTH level decreased to 64 pg/mL and no more fractures were noted.
Discussion
The patient in our case suffered from neonatal hyperparathyroidism due to maternal hypoparathyroidism associated with vitamin D deficiency. She had severe multiple intrauterine bone fractures leading to deformities and respiratory failure. Neonatal hyperparathyroidism may result from several diseases related to maternal hypocalcemia. Maternal hypocalcemia causes reduced maternal- fetal calcium transfer and subsequently fetal hypocalcemia and hyperparathyroidism. One of the main causes of maternal hypocalcemia is hypoparathyroidism. In fact hypoparathyroidism in pregnancy leads to fewer symptoms of hypocalcemia. Serum calcium concentrations of these women were found to be higher than in the preconceptual period. Increases in 1,25-dihydroxyvitamin D and intestinal calcium absorption are suggested to be the reasons for a lower calcium and calcitriol requirement and fewer symptoms of hypocalcemia in maternal hypoparathyroidism during pregnancy.7 Nevertheless, the mother of our patient had vitamin D deficiency in addition to hypoparathyroidism. Vitamin D deficiency may impede a rise in 1,25 hydroxyvitamin D level leading to severe hypocalcemia. Although the vitamin D level was low in the mother it was found to be in normal range in our patient. The fetus is thought to be entirely dependent on the mother for its supply of 25-hydroxyvitamin D, which is believed to cross the placenta.8 The normal vitamin D level in our patient can be explained by sufficient vitamin D supplementation since birth.
Striking pulmonary abnormalities have been described in rickets. Lobar and segmentai atelectasis, compression atelectasis under the internal projections of the rachitic rosaries at the costocondral junctions, and interstitial pneumonitis are some of these changes. Besides, as most children with rickets have malnutrition, they tend to have recurrent pulmonary infections.9 Our patient’s atelectasis, persistent pneumonia, and hypoxia can be described by her rickets- like chest deformities.
The duration and severity of neonatal hyperparathyroidism secondary to maternal hypoparathyroidism are variable. Some patients with neonatal hyperparathyroidism can be asymptomatic without any biochemically or radiologie findings. However, maternal hypoparathyroidism can result with spontaneous abortions, stillbirth, and neonatal deaths.1,10,11 The range of calcium levels in these patients also varies. Serum PTH levels in neonatal hyperparathyroidism generally normalize in a short period of time. Long-head et al1 reported 2 infants with congenital hyperparathyroidism, in 1 of whom serum PTH concentrations were normalized just after birth, and in the other, 12 days after delivery. Contrarily, another patient with neonatal hyperparathyroidism and vitamin D deficiency had high PTH levels for 3 months postnatally.2 Vitamin D deficiency in this patient probably contributes to persistent hyperparathyroidism. Our patient also had high PTH levels for approximately 4 months. The reason for prolonged hyperparathyroidism and the Findings of active rickets on plain radiographs were attributed to insufficient calcium supplementation and undernutrition in this patient.
Neonatal hyperparathyroidism due to maternal causes can result in severe life-threatening complicadons. Follow-up during pregnancy is the most important preventive approach while early diagnosis and appropriate management of the affected infant is essential for avoiding morbidity and mortality.
REFERENCES
1. Loughead JL, Mughal Z, Mimouni F, et al. Spectrum and natural history of congenital hyperparathyroidism secondary to maternal hypocalcemia. AmJPmnatol. 1990:7:350-355.
2. Sann L, Thomas DA, Frederich A, et al. Congenital hyperparathyroidism and vitamin D deficiency due to maternal hypoparathyroidism. Ada Pediatr Scand. 1976;65:381-385.
3. Vidailhet M, Monin P, Andre M, et al. Neonatal hyperparathyroidism secondary to maternal hypoparathyroidism. Arch Fr Pediatr. 1980; 37:305-312.
\4. Glass EJ, Barr DCi. Transient neonatal hyperparathyroidism secondary to maternal pseudohypoparathyroidism. Arch Dis Child. 1981;56:565-568.
5. Savani RC, Mimouni F, Tsang RC. Maternal and neonatal hyperparathyroidism as a consequence of maternal renal tubular acidosis. Pediatrics. 1993;91:661-663.
6. Levin TL, States L, Greig A, Goldman HS. Maternal renal insufficiency: a cause of congenital rickets and secondary hyperparathyroidism. Pediatr Radial. 1992:22:315-316.
7. Kovacs CS, Kronenberg HM. Maternalfetal calcium and bone metabolism during pregnancy, puerperium and lactation. Endocr Rm. 1997; 18:832-872.
8. Salle BL, Delvin EE, Lapillonne A, et al. Perinatal metabolism of vitamin D. Am/amNute2000;71:1317S-1324S.
9. Khajaui A, Amirhakimi GH. The rachitic lung. Pulmonary finding in 30 infants and children with malnutritional rikets. Clin Pediatr. 1977;16:36-38.
10. Eastell R, Edmonds CJ, de Chayal RC, McFadyen IR. Prolonged hypoparathyroidism presenting eventually as second trimester abortion. Br MedJ. (Clin Res Ed) 1985:291:955-956.
11. Anderson GW, Musselman L. The treatment of tetany in pregnancy. Am J Obstet Gynecol. 1942:43:547-567.
AyferAlikasifoglu, MD1
E. Nazli Gone, MD1
Ebru Yalcin, MD?
Deniz Dogru, MD2
Nursen Yordam, MD1
Clin Pediatr. 2005;44:267-269
Hacettepe University, Divisions of1 Pediatrie Endocrinology and 2Pulmonary Medicine, Ankara, Turkey.
Reprint requests and correspondence to: Ayfer Alikasifoglu, MD, Associate Professor of Pediatrics, Hacettepe University, Division of Pediatrie Endocrinology, Ankara, Turkey 06100.
2005 Westminster Publications, Inc., 708 Glen Cove Avenue, Glen Head, NY 11545, U.S.A.
Copyright Westminster Publications, Inc. Apr 2005
Comments