to present a case of hypercalcemia associated with thyrotoxicosis in a patient with vitamin d deficiency and review biochemical changes during the course of treatment . we report a case , describe the changes in serum calcium , phosphorus , parathyroid hormone in graves disease and concomitant vitamin d deficiency . our patient had hypercalcemia secondary to thyrotoxicosis alone , which was confirmed by low parathyroid hormone level and resolution of hypercalcemia with treatment of thyrotoxicosis . serum calcium elevation in patients with thyrotoxicosis occurs secondary to hyperthyroidism alone or due to concurrent hyperparathyroidism . vitamin d deficiency can be seen in patients with thyrotoxicosis because of accelerated metabolism , poor intestinal absorption and increased demand during bone restoration phase . coexistence of hypercalcemia and vitamin d deficiency in patients with thyrotoxicosis is rare , but possible , and 25-hydroxyvitamin d levels should be checked . hypercalcemia in thyrotoxicosis should be distinguished from concomitant hyperparathyroidism and confirmed by resolution of hypercalcemia with control of thyrotoxicosis . patients with hypercalcemia and thyrotoxicosis may also have vitamin d deficiency and 25-oh vitamin d levels should be checked . asymptomatic serum calcium elevation has been documented in up to 20% of patients with hyperthyroidism and is related to increased bone resorption.1 we describe a case of hypercalcemia related to thyrotoxicosis and in the presence of vitamin d deficiency . a 34 year old male presented with weight loss of over 35 pounds within 6 months . he also complained of hand tremor , increase in number of bowel movements , and heat intolerance . physical exam revealed tachycardia , presence of lid lag , warm skin , and increased deep tendon reflexes . pertinent laboratory values included a tsh of 0.012 miu / l ( normal , 0.4 to 4.5 ) with a free t4 of 7.85 ng / dl ( normal , 0.8 to 1.8 ) and a free t3 of over 2000 pg / dl ( normal , 230 to 420 ) . thyroid stimulating immunoglobulins ( tsi ) and thyroid peroxidase ( tpo ) antibodies were elevated ( tsi-285 ( normal < 125% baseline ) , and tpo antibodies > 1000 iu / ml ( normal < 35 iu / ml ) ) . thyroid uptake and scan revealed diffusely increased homogeneous uptake throughout the thyroid gland , which was calculated to be 41.5% at 24 hours and is consistent with graves disease . patient s serum calcium was 11.4 mg / dl ( normal , 8.610.2 ) with a normal albumin and serum phosphorus of 5.7 mg / dl ( normal , 2.54.5 ) . the ipth level was 5 pg / ml ( normal , 1065 ) , and the 25-oh vitamin d was 11 ng / dl ( normal , > 30 ) . his 24-hour urine calcium was 571 mg/24 hrs ( normal < 300 mg ) with normal creatinine . patient s blood urea nitrogen was 13 mg / dl ( normal , 725 ) , serum creatinine was 0.75 mg / dl ( normal , 0.791.33 ) , and he had a normal estimated glomerular filtration rate of 95 ml / min per 1.73 m. therapy with methimazole and atenolol successfully controlled sympathetic symptoms . four months later , while off of methimazole , the patient underwent treatment with i131 . when he became euthyroid , the calcium level normalized to 9.9 mg / dl and his phosphorus normalized to 3.5 mg / dl . the most common cause of hypercalcemia in thyrotoxicosis is concurrent primary hyperparathyroidism . in 15%20% of cases however , alterations of calcium metabolism are related to the thyrotoxicosis alone.1 our case illustrates hypercalcemia secondary to thyrotoxicosis alone , as supported by low parathyroid hormone ( pth ) level and resolution of hypercalcemia with treatment of the thyroid disease . a linear correlation exists between serum calcium levels and parameters of thyroid function , which becomes more pronounced in the age group greater than 60 years.2 hypercalcemia in thyrotoxicosis is typically asymptomatic , with calcium levels rarely exceeding 12 mg / dl.3 the intestinal absorption of calcium is usually low in thyrotoxicosis . similarly , renal tubular calcium reabsorption is reduced , leading to hypercalcuria , as seen in this patient.4 the proposed mechanism of hypercalcemia is enhanced bone resorption , unrelated to the pth levels.1,5 high circulating levels of interleukin ( il)-6 seen in hyperthyroidism stimulate bone osteoclastic activity and alter the osteoblastosteoclast coupling.6 triiodothyronine ( t3 ) is known to increase the sensitivity of the bone to il-6.3 the hyperadrenergic state of thyrotoxicosis is also implicated in hypercalcemia . alpha - adrenergic stimulation leads to hypercalciuria and beta - adrenergic stimulation on the bone results in hypercalcemia.7 the pth levels in hypercalcemia of thyrotoxicosis are either suppressed or low normal . the increased metabolic clearance rates in thyrotoxicosis could also lower the pth levels.8 hyperthyroidism causes hyperphosphatemia by augmenting tubular reabsorption of phosphate regardless of pth levels.9,10 a study on 25 untreated hyperthyroid patients by jastrup et al showed low 1,25-(oh)2 vitamin d levels with normal 25-oh vitamin d. this could be explained by reduced 1--hydroxylase activity secondary to hypercalcemia , suppressed pth and hyperphosphatemia.5 our case is unusual because of the presence of hypercalcemia with concomitant vitamin d deficiency . undiagnosed vitamin d deficiency is common and 25-oh vitamin d levels are accurate indicators of the vitamin d status . 1,25-(oh)2 vitamin d levels are variable and do not consistently represent vitamin d status . in vitamin d deficiency only about 10% of dietary calcium and 60% of phosphorus is absorbed.11 with levels less than 30 ng / dl , the intestinal calcium absorption is significantly impaired , which leads to increase in pth , activation of the conversion of 25-oh vitamin d to 1,25-(oh)2 vitamin d , and the subsequent increase in the intestinal calcium absorption to 30% and phosphorus to 80%.11,12 in our patient , hypercalcemia from thyrotoxicosis caused suppression of pth levels , despite coexisting vitamin d deficiency . patients with secondary hyperparathyroidism from vitamin d deficiency usually have increased renal tubular calcium reabsorption and phosphaturia , leading to low or low - normal serum phosphorus.1315 our patient , on the contrary , presented with hyperphosphatemia , hypercalcemia and hypercalciuria , despite being vitamin d deficient . it is important to check magnesium levels in this situation , because the compensatory increase in pth does not occur in hypomagnesemia , even when the 25-oh vitamin d levels fall below 20 ng / dl.16 thyrotoxicosis is less commonly recognized as an acquired cause of vitamin d deficiency , which can persist for several months following the treatment of hyperthyroidism . low 25-(oh ) vitamin d levels , less than 30 ng / dl , can be seen in hyperthyroid patients.14 vitamin d metabolism is accelerated up to eight times in thyrotoxic patients , when compared to euthyroid controls.17 intestinal vitamin d absorption is decreased in a few hyperthyroid patients secondary to rapid transition time of food , malabsorption and diarrhea.18 in addition , vitamin d deficiency may be induced in some patients with graves disease after treatment with anti - thyroid drugs , which is due to the increased demand for vitamin d and calcium during bone restoration.19 the definitive treatment for hypercalcemia in thyrotoxicosis is correction of underlying thyroid disease . beta - blockers may also reduce serum calcium with or without affecting renal calcium metabolism.7,20 it is important to also monitor the vitamin d levels while treating hyperthyroidism . treatment of vitamin d deficiency with calcidiol , despite the presence of hypercalcemia , has been shown to be beneficial.21 it is thus seen from our case that the complex concurrence of thyrotoxicosis , hypercalcemia and vitamin d deficiency is uncommon , but possible . hypercalcemia in thyrotoxicosis should be distinguished from concomitant hyperparathyroidism and confirmed by resolution of hypercalcemia with control of thyrotoxicosis . patients with hypercalcemia may also have vitamin d deficiency and 25-oh vitamin d levels should be checked .
objective : to present a case of hypercalcemia associated with thyrotoxicosis in a patient with vitamin d deficiency and review biochemical changes during the course of treatment.methods:we report a case , describe the changes in serum calcium , phosphorus , parathyroid hormone in graves disease and concomitant vitamin d deficiency . 
 we compare our findings to those reported in literature.results:our patient had hypercalcemia secondary to thyrotoxicosis alone , which was confirmed by low parathyroid hormone level and resolution of hypercalcemia with treatment of thyrotoxicosis . 
 the case was complicated by a concomitant vitamin d deficiency . 
 serum calcium elevation in patients with thyrotoxicosis occurs secondary to hyperthyroidism alone or due to concurrent hyperparathyroidism . 
 hypercalcemia from thyrotoxicosis is usually asymptomatic and is related to bone resorption . 
 vitamin d deficiency can be seen in patients with thyrotoxicosis because of accelerated metabolism , poor intestinal absorption and increased demand during bone restoration phase . 
 coexistence of hypercalcemia and vitamin d deficiency in patients with thyrotoxicosis is rare , but possible , and 25-hydroxyvitamin d levels should be checked . 
 the definite treatment for hypercalcemia in thyrotoxicosis is correction of thyroid function.conclusion:hypercalcemia in thyrotoxicosis should be distinguished from concomitant hyperparathyroidism and confirmed by resolution of hypercalcemia with control of thyrotoxicosis . 
 patients with hypercalcemia and thyrotoxicosis may also have vitamin d deficiency and 25-oh vitamin d levels should be checked .