Khandori et al. have expressed concern regarding the absence of data on the levels of vitamin D (25-hydroxy and 1, 25 dihydroxy-vitamin D3) and iPTH. In this study iPTH levels were performed in patients with hypocalcemia with normal renal function and magnesium levels, who did not have clinical and radiological features of rickets. PTH levels were performed in 24 out of 29 patients. Fifteen patients with elevated PTH levels were classified as pseudohypoparathyroidism (PHP) and 9 with low PTH levels were diagnosed as hypoparathyroidism (HP) in accordance to the diagnostic criteria provided in the article(1). Hypocalcemia in the presence of hyperphosphatemia and normal renal function is diagnostic of inefficient PTH action(2). PTH level helps in classifying these patients into HP (low) and PHP (high). Vitamin D metabolite levels as well as phosphaturic and c-AMP response to PTH although important in laboratory evaluation of parathyroid function, are not essential for clinical diagnosis of HP or PHP(2).

Levels of vitamin D metabolites are important in evaluation of patients with hypocalcemic rickets. Normal level of 25-hydroxyvitamin D3 is against the diagnosis of nutritional rickets and points towards the diagnosis of vitamin D refractory rickets (VDDR). Levels of 1,25 dihydroxyvitamin D3 is useful in further classification of VDDR into VDDR 1 (low) and VDDR II (high). In the present series 4 patients had clinical and radiological features of rickets. Levels of 25-hydroxyvitamin D3 were normal in all these patients indicating the diagnosis of VDDR. We did not classify these patients into VDDR 1 and VDDR II as 1,25 dihydroxy-vitamin D3 levels were not performed due to cost constraints. In this regard response to vitamin D metabolites (1-hydroxyvitamin D3 or 1, 25 dihydroxyvitamin D3) is a reasonable alternative to estimation of vitamin D metabolites for classification of VDDR. VDDR 1 responds to physiological doses of 1 hydroxyvitamin D3 while the requirements are much higher in VDDR II.

The present article emphasizes the need for modifying diagnostic protocols for resource poor countries. Diagnostic protocols followed in developed countries may not be suitable for resource poor countries consider-ing their financial and laboratory constraints. We have provided a protocol for screening the etiology of hypocalcemia followed in our clinic in Fig. 1(3). The protocol was designed in order to recommend cost effective and easily available investigations in the initial phase and more demanding investigations only when they are essential.

Rule out tumor lyses/rhabdomyolysis drugs/phosphate load

Phosphate

	Normal/Low	                 Elevated

	Rickets on X-ray wrist	                     		Renal function tests

	Yes	       No	                      Deranged	  Normal

Blood gas	      		Magnesium		CRF		     PTH
Liver function
Malabsorption studies
						        	Low	High

Response to vitamin D3						HP	PHP

No - 1,25 vitamin D3*, Yes - Nutritional rickets     		     Magnesium	  FT4 /TSH
						     CT head	  Ocular 
						     Ocular	  Examination
	High	Low             		     examination       CT head
	VDDR I	VDDR II 			                          Serum  cortisol
						     ECHO Chest 
					             X-ray for thymus

*Response to 1-hydroxyvitamin D3 therapeutic alternative to diagnosis.

Fig 1. Approach to Hypocalcemia

Jyoti Sharma,
Anurag Bajpai,
Madhulika Kabra,
P.S.N. Menon,
Division of Pediatric Endocrinology,
Department of Pediatrics,
All India Institute of Medical Sciences,
New Delhi 110 029.
E-mail: [email protected]