metabolic encephalopathies are among one of the common causes of admission to hospital in the elderly age group .
depending on the severity and rate of development of hypercalcemia , patient can present with mild drowsiness to coma . in more than 90% of cases , hyperparathyroidism is the cause ; however , in an emergency setting , malignancy related hypercalcemia is the commonest cause .
milk alkali syndrome ( mas ) can cause acute , subacute or chronic hypercalcemia , which has been reported as early as in 1923 , though the term mas was coined in 1949 . though it became uncommon after some time , recently it has witnessed resurgence after increased general awareness about osteoporosis and overuse of calcium carbonate and vitamin d. injection teriparatide is known to cause transient hypercalcemia up to 6 hours of its administration ; severe hypercalcemia causing encephalopathy is not known .
here , we report a case of hypercalcemic encephalopathy caused by mas in which a permissive role was played by injection teriparatide and other factors .
an 82-year - old male presented to emergency with history of sudden onset with gradual deterioration of mental sensorium of 8 days duration .
other history elicited from attendants revealed that the patient suffered from low impact fracture of third and fourth lumbar vertebrae 3 months back for which he was evaluated and found to have osteoporosis ( l1l4 vertebrae : t - score 3.1 , z - score 1.1 ; femur neck : t - score 3.0 , z - score 0.7 ) . during evaluation
, he was detected to have prostatic carcinoma for which he was being treated with depot preparation of injection treptorelin acetate [ gonadotropin - releasing hormone ( gnrh ) analogue ] 11.25 mg once in 3 months .
he was prescribed oral calcium carbonate 500 mg thrice daily and cholecalciferol 60,000 u monthly .
however , the patient was consuming 56 tablets of calcium carbonate ( each tablet containing 500 mg elemental calcium ) and his diet consisted of milk ( 1.5 l / day ) and plenty of curd .
he was started on injection teriparatide 20 g daily 10 days back in view of severe osteoporosis . at this time , his serum calcium ( 9.9 mg / dl ) , phosphorus ( 3.8 mg / dl ) and 25(oh ) vitamin d ( 84.4 ng / ml ) levels were normal .
he had limited physical activity in view of his age and disability . on examination , he had normal vital parameters with normal systemic examination except drowsiness and disorientation .
investigations revealed hypercalcemia ( serum calcium 14.3 mg / dl ) , normal phosphate levels ( 3.1 mg / dl ) , normal alkaline phosphatase ( 174 u / l ) , acute kidney injury as evidenced by raised serum creatinine ( 2.3 mg / dl as compared to basal creatinine levels of 0.9 mg / dl )
, metabolic alkalosis ( ph 7.56 , hco 39 meq / l , paco2 47 mm of hg ) and hypokalemia ( serum potassium 2.3 meq / l ) .
his serum parathyroid hormone ( pth ) level was 7 pg / ml ( 10 - 74 pg / ml ) .
he was euthyroid [ t3 1.2 ng/ ml , t4 9.45 g / dl , thyroid stimulating hormone ( tsh ) 4.5 iu / ml ] and eucortisolemic ( cortisol basal 8.3 g / dl , post acth cortisol 24 g / dl ) .
he had low serum testosterone levels ( 0.1 ng / ml ) consistent with gnrh therapy . in view of acute hypercalcemia , hypokalemia , metabolic alkalosis , acute kidney injury and history of consumption of 34 g of calcium carbonate daily ,
he was diagnosed as a case of hypercalcemic encephalopathy due to mas which was probably precipitated by concomitant use of injection teriparatide and immobilization .
his drugs ( calcium carbonate and teriparatide ) were stopped and he was started on intravenous forced diuresis with 3 l of normal saline and 40 mg thrice daily injection of frusemide , with monitoring of cardiovascular status .
he was also given injection zoledronic acid 5 mg in 100 ml normal saline over 30 min .
his clinical and biochemical parameters normalized in 72 hours ( serum calcium 8.6 mg / dl , ph 7.38 , potassium 4.6 meq / l and creatinine 0.7 mg / dl ) .
he was discharged after 6 days of hospital stay on vitamin d sachet ( 60,000 u ) once monthly .
hypercalcemia has various causes , and in an emergency setting , primary hyperparathyroidism , malignancy associated hypercalcemia and mas constitute most of the cases .
our patient was diagnosed with mas on the basis of presence of acute hypercalcemia , hypokalemia , metabolic alkalosis , acute kidney injury and history of consumption of 34 g daily calcium carbonate , with normal phosphate and low pth levels .
milk alkali therapy for treatment of peptic ulcer disease was developed by sippy in 1910 .
it constituted bed rest of 4 weeks duration and multiple doses of milk and cream with alkali .
because of paucity of other treatment options , milk alkali treatment rapidly became standard for treatment of peptic ulcer disease .
burnett for the first time named this syndrome of hypercalcemia , hyperphosphatemia , metabolic alkalosis and renal dysfunction as mas . in pathogenesis of mas , old age , pre - existing renal dysfunction , and ingestion of large dose of calcium carbonate are all known to play a role .
initially , incidence of mas was reported to be 1015% which subsequently reduced on account of availability of effective alternate therapies for peptic ulcer disease .
but the last two decades have seen resurgence of a modern form of mas , where calcium carbonate constitutes the source of calcium and alkali , because many doctors are prescribing calcium supplements due to increase awareness about osteoporosis .
modern mas differs from classical mas in absence of male preponderance and presence of near - normal phosphate levels . in the present case
secondly , at the age of 82 , his estimated glomerular filtration rate will be compromised ( ~53 ml / min by cockcroft and gault equation ) .
however , in our patient with compromised renal function , excessive calcium intake with vitamin d may have predisposed him to the development of hypercalcemia .
finally , on initiation of injection teriparatide , he developed sudden worsening of sensorium and severe symptomatic hypercalcemia , along with deterioration in renal function and the biochemical features suggestive of mas .
it was initially suspected that with the use of teriparatide , a synthetic analogue of pth , the incidence of hypercalcemia would increase . however , mostly transient and mild hypercalcemia is observed but persistent and severe hypercalcemia has been reported .
hence , our patient developed mas secondary to excessive intake of calcium where a permissive role was played by age , immobilization and teriparatide for the development of hypercalcemic encephalopathy .
therefore , it is suggested that when teriparatide therapy is begun , particularly in elderly patients who have limited physical activity , daily total , dietary and supplemental , calcium should be maintained at 1000 mg or less , so as to keep the serum calcium below 10 mg / dl .
 an 82-year - old male , a known case of severe osteoporosis with vertebral fracture and prostatic carcinoma , was treated with gonadotropin releasing hormone analogue , calcium carbonate , cholecalciferol sachet and injection teriparatide . 
 his diet consisted of milk and curd . 
 he developed altered behavior and generalized weakness , and on investigation , hypercalcemia , hypokalemia , and metabolic alkalosis with low parathyroid hormone levels were detected . 
 injection teriparatide was stopped and he was managed with forced saline diuresis and injection zoledronic acid . 
 he was diagnosed as a case of milk alkali syndrome in whom teriparatide and prolonged immobilization played a permissive role in the development of hypercalcemic encephalopathy . 
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