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Case Reports Indian Pediatrics 2003; 40:255-257 |
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Spontaneous Improvement of Sever Neonatal Hyperparathyroidism after Failed total Parathyroidectomy |
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AL Shaikh HA Bappal B Nair R AL Khusaiby S* From the Pediatric Endocrinology Unit, and *Department of Neonatology, Department of Child Health, Royal Hospital, Sultanate of Oman, Correspondence to: Dr. Hala Al Shaikh, Royal
Hospital, P.O. Box 1331, Seeb 111, Oman. Manuscript received: August 26, 2002; Initial
review completed: September 13, 2002;
Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant trait characterized by asymptomatic hyper-calcemia and hypocalciuria. The clinical spectrum, however, varies from the asympto-matic child to the neonate with severe life threatening hypercalcemia (severe neonatal hyperparathyroidism) who may require emergency parathyroidectomy for survival. Untreated, this disorder may be lethal or may lead to skeletal deformities and develop-mental delay. Case Report T.Q. was referred to us from a district hospital at 11 days of age with a diagnosis of unresolved pneumonia and hypercalcemia. She was born to a primigravida mother at full term by assisted breech delivery. Parents were Egyptians and non-consanguineous. Birth weight was 2.7 kg, head circumference 34 cm and length 48 cm. Apgar score was normal. She had mild respiratory distress at birth that progressively increased despite treatment with different antibiotics and other supportive measures. Physical examination revealed a weight of 2.4 kg (3rd centile), length of 52 cm (50th centile), and head circumference of 35 cm (>10th centile). She was tachypneic with severe intercostal and subcostal retractions. Chest was clear. Cardio-vascular system and blood pressure were normal. There was hypotonia with normal muscle power. Investigations at our hospital showed, corrected serum calcium (Ca) 3.14 mmol/L (1.8-2.2), phosphate (P) 1.10 mmol/L (1.35-2.3), alkaline phosphatase 894 IU/L, (105-270), magnesium 0.56 mmol/L (0.65-1.25), parathyroid hormone intact molecule (PTH), >32 pmol/L (0.95-6.8), vitamin D-25, 136 ng/L (10-60) and Urinary Ca : Cr ratio of 0.3 (0.08-0.74). Thyroid function test, serum electrolytes, urea, creatinine and liver function tests were normal. Skeletal survey showed generalized osteopenia, with evi-dence of subperiosteal bone resorption. Metaphysis of long bones showed marked destruction with cupping and fraying and a metaphyseal fracture of the left femur. Metacarpal and phalangeal bones, mandible and skull were normal. Deciduous and perma-nent teeth showed absence of calcification of the lamina dura. CT scan of the neck, chest and abdomen were normal. Parents had normal serum calcium and urinary Ca : Cr ratio. Forced saline diuresis and intravenous frusemide therapy were initiated. Serum calcium concentration dropped to 2.5 mmol/L within 48 hours, however, it promptly returned to pretreatment values once treat-ment was discontinued. As respiratory distress progressively increased, total parathyroid-ectomy was attempted at 40 days of age but only three parathyroid glands were identified and removed. In the hope to remove the fourth (right-lower) gland, the right lobe of the thyroid and right half of the thymus were resected. However, histologically no para-thyroid tissue was identified in the resected sections. The excised parathyroid glands measured 5 × 5 mm in size and their frozen section histology was consistent with generalized hyperplasia. The immediate postoperative course was complicated by symptomatic hypocalcemia (1.5 mmol/L). This was treated with calcium supplements. PTH was 4.5 pmol/L. By the end of the 2nd post-operative week, serum calcium concentration gradually rose to pre-treatment levels, 3.4 mmol/L and PTH to 25.3 pmol/L. CT neck, Tc99 thalium subtraction scan and a second exploration of the neck failed to locate the right lower parathyroid gland. Treatment with calcitonin nasal spray was attempted but failed to bring down serum calcium concentration which remained above 3 mmol/L. At the end of 2 years. T.Q. and her family returned back to Egypt for good. The family came back on a short visit to Oman when she was seen in our endocrine clinic after a lapse of 2 years. Her height and weight were <3rd centile. She was asymptomatic and develop-mentally normal. Serum calcium was 2.96 mmol/L, phosphate 0.92 mmol/L, alkaline phosphatase 278 IU/L and PTH 8.2 pmol/L (1.26-7.58). Discussion Neonatal hyperparathyroidism is defined as symptomatic hypercalcemia with skeletal manifestations of hyperparathyroidism in the first six months of life. It often presents in the first few days of life with severe PTH depend-ent hypercalcemia, hypotonia, constipation and respiratory distress(1). The main forms of primary familial hyperparathyroidism presenting in infancy are (a) autosomal recessive familial para-thyroid hyperplasia(2,3), (b) autosomal dominant familial hypocalciuric hyper-calcemia(4), (FHH), resulting from an inactivating mutation of the calcium sensing receptor (CaSR) gene, (c) neonatal severe hyperpara-thyroidism (NSHPT) in children with homozygous(5) or double heterozygous mutations of CaSR gene(6) and (d) sporadic neonatal hyperparathyroidism due to de novo heterozygous CaSR mutation(7). In the above conditions where there is a mutation in the CaSR, the fetal parathyroid glands recognise the serum calcium level as low. It therefore becomes hyperplastic and secretes excess of PTH. The hallmark of such conditions is the low or normal urinary calcium excretion in contrast to hypercalciuria in other forms of primary hyperparathyroidism. TQ presented early in life with hypercalcemia and florid hyperparathyroid bone disease along with low urinary Ca : Cr ratio. The severity of the disease clearly suggests onset of hyperparathyroidism in utero. Parents were nonconsanguineous and family history was negative. This, along with the clinical and biochemical markers, apart from the low serum magnesium, suggest a de novo homozygous inactivating mutation in the CaSR in our patient. Molecular analysis, however, remains the gold-standard investiga-tion to confirm that. The choice of therapy in NSHPT varies from conservative medical management(8) to total parathyroidectomy with or without autotransplantation(9) based on the severity of the disease. Sally et al.(10) reported a case of NSHPT that resolved clinically and radio-logically over a period of 13 months with conservative management. Subtotal parathy-roidectomy usually does not correct neonatal hyperparathyroidism as the remaining para-thyroid gland hypertrophies and continues to maintain the hyperpara-thyroid state. Our patient ended up with subtotal parathyroidectomy as the 4th parathyroid gland could not be identified. The remaining gland probably contributed to her survival in the neonatal period. Immediately after the subtotal parathyroidectomy, PTH concentra-tion dropped to 9.5 pmol/L which is a well-recognized event in the immediate post-operative period following subtotal para-thyroidectomy(9). However, within 2 months, PTH concentration rose to 43.2 pmol/L. Then it gradually decreased from this extremely high value to 8.7 pmol/L at the end of 3 years. Hypercalcemia persisted throughout the course of the disease (serum calcium >3 mmol/L). Similarly, by one year of age, bone mineralization gradually improved; subperiosteal bone resorption resolved, chest deformities and fracture of the long bones healed with progressive improvement in the radiological features of hyperparathyroidism. In other words, the severe hyperparathyroid disease had gradually improved and a benign familial hypocalciuric hypercalcemia picture slowly evolved. This has been described by Pearce et al.(7) and is most probably due to the natural history of this condition. Contributors: HAS, BB, RN helped in data collection and initial drafting. SAK edited the manuscript. HAS will be the guarantor for the manuscript. Funding: None. Competing interests: None stated.
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