Unmasking of primary hyperparathyroidism by Vitamin D therapy.

A 38-year-old female on Vitamin D therapy presented with hypercalcemia induced acute kidney injury. Evaluation revealed primary hyperparathyroidism (PHPT) and iatrogenic hypervitaminosis D. After medical stabilization, she underwent surgical removal of the parathyroid adenoma, and made a full recovery. This case highlights unmasking of subclinical hyperparathyroidism by vitamin D therapy leading to severe hypercalcemia.

Introduction

Hypercalcemia is a common and overlooked biochemical abnormality, with an annual incidence of 0.1–0.2%. The prevalence is 1.07–3.9% in the general population, and 0.17–2.92% in hospitalized patients.[12]

Primary hyperparathyroidism (PHPT) occurs as a result of increased and uncontrolled secretion of parathyroid hormone (PTH) because of hyperfunction of one or more parathyroid glands. The cause of hyperfunction of parathyroid glands is, in the majority of cases, adenoma, followed by hyperplasia, and carcinoma. The main manifestations are hypercalcemia, calciuria with an increased tendency to urolithiasis and polyuria that leads to dehydration and loss of weight. Reabsorption of phosphate in the kidneys is decreased and that leads to hypophosphatemia.[3]

For many people, the word “vitamin” expresses a beneficial and essential component for healthy life and some like to take supplements including Vitamin D without a physician order. While Vitamin D toxicity is rare, most of the reported cases are due to over supplementation.[4]

Case Report

A 38-year-old female presented for evaluation of raised creatinine (1.5 mg/dl). Patient complained of 10 kg weight loss in 2 months and constipation. She had been on Vitamin D 60,000 IU weekly for 2 months presumably for low Vitamin D level.

On enquiry, there was no history of fever, anorexia, nausea, vomiting or diarrhea. History pertaining to other systems was unremarkable. Initial investigations showed normal urinalysis; hemoglobin 10 g/dl, total lymphocyte count 8800/mm3, platelet 280,000/mm3, serum bilirubin 0.8 mg/dl, aspartate aminotransferase/alanine aminotransferase 23/13 U/L, total protein 6.8 g/dl, serum albumin 3.2 g/dl, serum creatinine 1.5 mg/dl, serum Na + 137 mmol/l, serum K + 3.4 mmol/l, serum calcium 15.9 mg/dl, serum phosphorous 2.2 mg/dl. In view of severe hypercalcemia, the patient was admitted.

Physical examination was unremarkable. Investigations showed high 25(OH) Vitamin D (25(OH) D) at 100 ng/ml and elevated iPTH at 1464.90 pg/ml. Serum protein electrophoresis was normal. Electrocardiography showed short QT interval of 260 ms. USG kidneys showed normal sized kidneys. Computed tomography of the neck showed parathyroid adenoma of the left lower pole [Figures 1 and 2]. Sestamibi scan confirmed the parathyroid adenoma [Figure 3].

Figure 1

Computed tomography neck (cross-section) showing the left parathyroid adenoma

Figure 2

Computed tomography neck (left lateral view) showing the left parathyroid adenoma

Figure 3

Sestamibi scan showing left parathyroid adenoma

She was treated with intravenous (IV) saline, furosemide, calcitonin, steroids, and zolendronate. After stabilization, excision of the parathyroid adenoma was done. The adenoma was 2 cm × 1.5 cm, and it weighed 0.9 g. Serum calcium progressively improved over the next few days. The PTH level dropped to 516 pg/ml the day after surgery.

When seen in the outpatient clinic after 1-week, serum calcium was 8.6 mg/dl, and serum creatinine was 0.8 mg/dl.

Discussion

Vitamin D is an important pro-hormone that plays an important role in calcium homeostasis and bone mineral metabolism. The adult recommended daily allowance is 15 mcg (600 IU).[5] Excess of Vitamin D or its metabolites can cause hypercalcemia and hypercalciuria. The mechanism of hypercalcemia is a combination of increased intestinal calcium absorption and bone resorption induced by Vitamin D and decreased renal clearance resulting from dehydration. Toxic effects occur when 25(OH) D is in excess of 80 ng/ml.

Hyperparathyroidism is the most common cause of hypercalcemia in the general population. A single enlarged parathyroid gland (adenoma) is the cause of PHPT in 80–85% of cases. These adenomas are benign, clonal neoplasms of parathyroid chief cells that lose their normal sensitivity to calcium. PHPT presents in one of the three ways in 60–80% asymptomatic with mild hypercalcemia and discovered during routine laboratory testing. Other 20–25% of patients have a chronic course manifested by mild or intermittent hypercalcemia, recurrent renal stones and complications of nephrolithiasis; in these patients the parathyroid tumor is small (<1 g). 5–10% have severe and symptomatic hypercalcemia and overt osteitis fibrosa cystica; in these patients the parathyroid tumor is usually large (>5.0 g). Patients with parathyroid carcinoma typically have severe hypercalcemia with “classical” renal and bone involvement. Our patient probably had asymptomatic mild hypercalcemia as is seen in 60–80% of cases with primary hyperparathyroidism. Vitamin D therapy and hypervitaminosis D unmasked this hyperparathyroidism by causing severe hypercalcemia.

The diagnosis of PHPT is established by laboratory testing showing hypercalcemia with inappropriately normal or elevated blood levels of PTH as was seen in our patient. Hypercalciuria, hypophosphatemia, phosphaturia are other laboratory findings. Hyperchloremic acidosis may be present, and the ratio of serum chloride to serum phosphorus is elevated. All of these were seen in our patient.

Nonspecific treatment of hypercalcemia includes IV normal saline and furosemide to increase urinary calcium excretion,[67] calcitonin which increases renal calcium excretion and decreases bone resorption by interfering with osteoclast maturation,[8910] bisphosphonate, which binds to bone hydroxyapatite and inhibits calcium release by interfering with osteoclast-mediated bone resorption[1112] and steroids, which increase the metabolism of the Vitamin D and decrease the absorption of the calcium in the gut.

Our patient was treated with nonspecific measures until the diagnosis of HPT was made. Thereafter surgical excision of parathyroid adenoma was done, and patient made a complete recovery.

Conclusion

Hypercalcemia is common but often overlooked. In majority of the cases, it is due to PHPT with mildly elevated calcium and often asymptomatic. Iatrogenic hypervitaminosis D in this case unmasked PHPT. With surgical removal of parathyroid adenoma, there was complete recovery.