Indian Pediatrics 2002; 39:276-282  

Hypocalcemia – Clinical, Biochemical, Radiological Profile and Follow-up in a Tertiary Hospital in India

From the Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110 029, India.

Correspondence to: Dr. P.S.N. Menon, Additonal Professor, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110 029, India.

E-mail: [email protected]

Manuscript received: March 26, 2001;
Initial review completed: May 3, 2001;
Revision accepted: August 1, 2001.

Hypocalcemia is a common biochemical abnormality presenting as medical emergency as well as chronic diagnostic dilemma. Its manifestations are varied emphasizing the need of estimation of serum calcium in varied clinical settings. Data concerning clinical, laboratory features and management of hypocalcemia in Indian children is scarce. This study was undertaken to document these features.

Records of patients with hypocalcemia enrolled in the Pediatric Endocrinology Clinic of this hospital from January 1989 to October 2000 were reviewed. For the purpose of the study, hypocalcemia was defined as total serum concentration levels less than 8.0 mg/dl with normal concentrations of serum albumin. Data regarding presenting features, family history, biochemical findings, radiological investigations and hormonal assays were obtained. The diagnostic criteria used and the protocols for investigation and management that were followed are summarized in Tables I and II. Details of treatment and complications were recorded and analyzed.

Twenty-nine children aged 3 days to 10 years were enrolled in the study. The cohort included 25 boys and 4 girls. The etiological diagnoses included hypoparathyroidism (HP, 9 cases), pseudohypoparathyroidism (PHP, 15 cases), vitamin D dependent rickets (VDDR, 4 cases) and hypomagenesemia (1 case). Details of age at presentation, sex distribution and clinical features are provided in Table III.

Clinical Features: Seizures, present in 23 children at the onset, constituted the common-est presenting features. Two other patients developed seizures later in the course. All cases that presented before 5 years of age had seizures while only one out of the four older children had seizures. Generalized tonic clonic seizures were the only seizure-type noted in the study. Other manifestations included short stature and obesity, carpopedal spasm, congestive cardiac failure and bony deformities (Table III). Two cases with PHP were diagnosed after CT scan as part of evaluation of seizures which revealed bilateral basal ganglia calcification. Cataracts were found in 5 cases (1 HP, 4 PHP). Features of Albright’s hereditary osteodystrophy (AHO) were present in 4 cases of PHP. Hearing was normal in all patients. Delayed dentition and enamel hypoplasia were present in two cases. Two children had developmental delay.

Investigaions: Laboratory investigations are summarized in Table IV. Serum calcium levels at presentation ranged from 2.0 - 7.4 mg/dl with higher values in VDDR as compared to HP and PHP. Hyperphos-phatemia (based on age adjusted values of serum phosphate) was present in 8 cases of HP (88%) and 13 cases of PHP (86.7%) while hypophosphatemia was found in 3 cases of VDDR (75%). EEG was abnormal in 4 patients (1 HP, 2 PHP and 1 VDDR). Non-contrast CT scan revealed basal ganglia calcification in 2 cases with HP (22%) and 4 cases with PHP (26.6%). Echocardiography and cortisol levels were normal in all patients with HP while thyroid profile was normal in subjects with PHP.

Management and Follow-up: Follow-up period ranged from 3 months to 10 years (mean 5.2 years). Calcium levels normalized in patients with HP and PHP following standard treatment. Three patients developed hypercalciuria (2 PHP and 1 HP) and were started on thiazide diuretics. No episode of hypercalcemia or nephrocalcinosis was observed. Three patients with VDDR res-ponded to conventional doses (30-60 ng/kg/day) of 1 hydroxy vitamin D3 with normaliza-tion of calcium levels and healing of rickets. One child required higher doses of 1 hydroxy vitamin D3 (200 ng/kg/day) and was diag-nosed as VDDR II. The child with hypo-magnesemia responded to magnesium sulfate. Seventeen patients were on anti-epileptic drugs that were tapered after normalization of calcium levels.

Discussion

Important causes of hypocalcemia include HP, PHP, chronic renal failure and VDDR as in this series(1). There is a male preponder-ance in this study. the reason for which is not clear. Interestingly, most cases presented in early infancy. The onset of hypocalcemia in patients with PHP and VDDR was much earlier as compared to western reports (2-4). We could not find Indian data regarding the age of onset of PHP and VDDR. Low 25-hydroxy vitamin D3 levels have been reported in pregnant women in India and other developing countries(5,6). Vitamin D deficiency and osteomalacia in mothers has been associated with congenital rickets emphasizing the role of vitamin D in in utero calcium transport(7). Vitamin D plays a crucial role in transplacental transport of calcium; lowered maternal levels may result in impaired acquisition of calcium by the neonate and the consequent low calcium stores(8). This may be responsible for the early presentation of disorders of calcium homeostasis in our series.

Seizures were the commonest presenting feature of hypocalcemia as in previous studies. All the seizures in this series were generalized tonic clonic type, hypocalcemia is known to give rise to other seizure types as well(9). Several of these patients were initially managed with anti-epileptic drugs without success. This study demonstrate the importance of arriving at an etiological diagnosis in patients with seizures so that unnecessary treatment with anti-epileptic drugs could be stopped. All the patients with convulsions and basal ganglia calcification in particular should be evaluated for disorders of calcium homeostasis.

Older children with hypocalcemia present with tetany, paraesthesias, carpopedal spasm and laryngospasm, and seizures are less common(1). Patients with HP and PHP may have extrapyramidal signs including choreo-athetosis, dystonic posturing and parkinson-ism due to basal ganglia calcification(1). Cataracts are common complications of hypo-calcaemia as in our series. This emphasizes the need for screening for cataract in all cases of hypocalcemia. Calcium is closely linked to cardiac contractility and pronounced hypo-calcemia can be associated with cardiac dys-function and congestive cardiac failure (11,12). One of our patients with VDDR presented with dilated cardiomyopathy, which responded to correction of calcium levels.

Albright herediatary osteodystrophy (AHO) characterized by round facies, short stature and brachydactyly is suggestive of PHP Ia, the commonest variant of PHP. All patients with hypocalcemia and their relatives should be evaluated for AHO(13). Only four patients with PHP in this series had AHO. As features of AHO develop over time, more patients may develop it later. Hearing, although normal in our patients, should be evaluated in patients with HP as atrophy of tympanic membrane has been reported(14). Hypocalcemia with hyperphosphatemia due to lack of phosphaturic action of PTH is the hallmark of deficient PTH states(15). Hypocalcemia and hyperphosphatemia with normal renal functions is pathognomonic of deficient PTH action. Majority of our cases with HP and PHP had hyperphosphatemia while VDDR was associated with hypophos-phatemia. In HP, bone remodeling is reduced and levels of serum alkaline phosphatase (SAP) are normal. On the other hand the resistance to PTH in PHP is variable; the homeostatic system is inactive, while the remodeling system remains functional(1). Thus in PHP, SAP can be elevated and bony deformities resembling rickets may occur(16,17). Three patients with PHP had radiological features of hyperparathyroidism. Hypomagnesemia causes hypocalcemia by decreasing PTH secretion as well as diminishing peripheral responsiveness to PTH(18). Hypoclacemia is refractory to calcium supplements and is corrected only by magnesium repletion as in our case.

Patients with HP and PHP require vitamin D metabolites in addition to calcium supple-ments; 1,25 dihydroxy vitamin D3 (10-100 ng/kg/day) or 1 hydroxy vitamin D3 (25-50 ng/kg/day) is required for maintenance of normocalcemia. We used 1-hydroxy vitamin D3 as liver functions were normal in all the patients and due to lower cost. Serum calcium, phosphate and 24 hour urinary calcium or urinary calcium: creatinine ratio must be monitored during therapy(1). Patients with HP are prone to develop hypercalciuria and nephrocalcinosis due to defective distal tubular resorption of calcium. Thus calcium levels should be maintained at the lower limit of normal (8.5-9.0 mg/dl). Resistance to PTH in PHP is limited to the proximal tubule while the calcium preserving action on distal tubule is preserved(1). Thus patients with PHP have lower calcium requirements and are less prone to hypercalciuria as compared to patients with HP. However, all the patients with PHP in this series required continual calcium supplements and two of them developed hypercalciuria. In PHP the suppression of hyperparathyroidism is essential to inhibit the effect of PTH on the skeletal system. As these patients are believed to be less prone to hypercalciuria, the serum calcium levels should be maintained at 9.0-10.0 mg/dl. Occurance of hypercalciuria in two patients with PHP may indicate that calcium levels lower than these may be required in Indian children with PHP to prevent nephrocalcinosis. VDDR I responds to physiological doses of 1 hydroxy vitamin D3 while the requirements are much higher in VDDR II. Titration of dose of vitamin D to maintain requsite calcium levels is a reasonable therapeutic alternative to the estimation of vitamin D metabolites that is expensive and not readily available.

Contributors: All the authors were involved in patient management. JS and AB planned the study, collected data, performed literature review and drafted the manuscript. MK was involved in drafting the manuscript and reviewed it. PSNM was involved in the design of the study and critically reviewed the manuscript. He will act as the guarantor of the study.

Funding: None.

Competing interests: None stated.

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