A 70 year old lady doing occasional household work, without any previous hospitalizations was shifted from another hospital on the ventilator with respiratory failure and resolving pneumonia. She was obese, diabetic, hypertensive and had resolving AKI. Her medications included azithromycin, meropenem , insulin & amlodepin.Her PTH was 265pg /ml (10-65) with corrected Calcium 9 mg/dl (8.4-10.2), phosphorous (P) 3.8mg/dl (2.4-4.5),Vit D less than 8 ng/ml (31-100), Creatinine 1.7mg/dl. Albumin was 3.8 mg/dl. LFT and CBC were normal.

She was successfully extubated with full GCS after 48 hours. 2 days after extubation she became drowsy in the night and got reintubated. She was flexing all four limbs on painful stimuli without localization, no eye opening, down ward gaze and horizontal roving of the eyes with normal pupillary reaction .GCS was E1M4 .MRI brain was normal. EEG showed diffuse slowing and no seizure activity. Na, Mg, RBS , TLC, CRP, LFT ,SaO2 , BP , temperature were normal.Thusall theserelevant causes of acute alteration in sensorium were ruled out.Her Phosphorous(P) was low 1.0 mg/dl for the last two days and creatinine had returned to normal levels 1.1 mg/dl

She was given phosphate supplement 16 mmol IV @ 2 mmol/hr and P corrected to 2.8 mg/dl. After 24 hours she was opening eyes and after 48 hours awake with return of normal sensorium and was extubated. We repeated the PTH and again it was the same 252 pg/ml. An ultrasound of the neck, done for enlarged parathyroids did not reveal any parathyroid enlargement. A Parathyroid radionuclide scan was done to rule out hyperparathyroidism was normal.

Discussion

The patient had hypophosphatemia to the tune of 1.0mg/dl .The incidence of hypophosphatemia is reported to be 5% in hospitalized patients 1 and 40% in ICU patients [1,2 ].Initially her P had been within normal range but the patient had elevated Creatinine with a egfr of 30 ml/min concomitantly due to septic AKI.In AKI patients phosphate excretion gets decreased thus serum phosphate levels increase. In patients with normal baseline phosphate one gets hyperphosphatemia . Our patient’s P was also increased due to AKI but since her baseline P was low the increased level fell in the normal range 3.8 mg/dl. During the next 2 days her Creatinine decreased to 1.2 mg/dl. As AKI resolves it is well known retained electrolytes and solutes are washed out. That is what happened in our patient. With resolution of AKI her true phosphate levels were revealed as the retained phosphate was washed out in the urine.

 Rapid correction of altered sensorium has been seen earlier also with phosphate [3,4].Particular mechanisms for encephalopathy are not known as of now ,but phosphate is important in providing energy to the cells [5]. It is an integral part of ATP which is as an energy source and low phosphorous shifts the oxygen dissociation curve to left thus impairing O2 release to tissues.

What Was The Cause Of Her Hypophosphatemia?

Her vitamin D was also very low and corrected calcium was in the range of 9mg/dl. Her PTH was high and it was thoughtthat it was probably secondary to low vitamin D levels as as there is a compensatory rise of PTH in HypovitaminosisD . In cases of severe hypovitaminosis D there is secondary hyperparathyroidism to correct the hypocalcemia , but the calcium gets only partially corrected and patient continues to be in hypocalcemia or rarely low normal values maybe be seen . In view of the calcium values touching 9 mg/dl it was unlikely that compensatory rise in PTH would be causing this serum calcium value. Thus primary hyperparathyroidism was thought of. It is well known that in such patients of primary hyperparathyroidism and vitamin d deficiency calcium levels maybe normal [6].

 Thu we attributed the hypophosphatemia to primary hyperparathyroidism in the setting of Vit D deficiency. The patient did not have any symptoms suggestive of hyperparathyroidism. Nor was there any other cause for her relative hypercalcemia. We did an Ultrasound and Radionuclide Scan of parathyroid glands which was normal.However US is operator dependent and has a sensitivity of around 70 % and can thus be normal in patients with hyperparathyroidism. Similarly Radionuclide can be normal at times. Critical illness could have also contributed to the fall in Phosphate as multiple factors in the ICU can lead to transcellular shifts which is the commonest cause of hypophosphatemia in the ICU. A review of her records showed that she was having respiratory alkalosis with pH 7.3. Respiratory alkalosis is known to cause shift of phosphate from extracellular to intracellular space. She was also having hyperglycemia requiring insulin infusion. Insulin also causes transcellular shifts leading to decreased serum phosphate levels. Thus these transient factors also probably contributed to the low phosphate. The patient declined exploration of parathyroids and was discharged on Vitamin D calcium and phosphate supplements.

 Thus we made a final diagnosis of

• Hypophosphatemic encephalopathy
• SevereVit D deficiency withhyperparathyroidism
• Hypophosphatemia due to hyperparathyroidism and possible transcellular shifts due to critical illness (respiratory alkalosis, insulin infusion).

1. Bacchetta J, Salusky IB. Evaluation of hypophosphatemia: lessons from patients with genetic disorders. Am J Kidney Dis. 2012; 59: 152-159.
2. Bsar AEME, El-Wakiel SA, El-Harrisi MA, Elshafei ASH. Frequency and risk factors of hypophosphatemia in patients admitted to emergency intensive care unit in Zagazig University Hospitals. Indian J Crit Care Med. 2023; 27: 277-282.
3. Han SA, Park HY, Kim HW, Choi JI, Kang DY, Kim HL, et al. Severe Hypophosphatemia-Induced Acute Toxic-Metabolic Encephalopathy in Continuous Renal Replacement Therapy. Electrolyte Blood Press. 2019; 17: 62-65.
4. Megarbane B,Guerrier G,Baud FJ, Blancher A,Meas T , Guillausseau P. A Possible Hypophosphatemia-induced, life-threatening encephalopathy in diabetic Ketoacidosis: A Case Report. Amer J Med Sci.2007; 333: 384-386
5. Angel MJ, Young GB. Metabolic Encephalopathies. Neurologic Clinics. 2011; 29 : 837-82
6. Silverberg SJ, Bone J.Vitamin D deficiency and primary hyperparathyroidism Miner Res. 2007; 22: 100-104.