A 40-year-old woman is evaluated for mildly elevated blood pressure. She complains of occasional low back pain, but she is otherwise in good health. Her other medical problems include type 2 diabetes mellitus, hyperlipidemia, and gastroesophageal reflux disease. She lives a sedentary lifestyle and spends the majority of her time indoors. Her mother suffered from a hip fracture at the age of 55. She has no family history of cancer. Her blood pressure is 144/90 mm Hg and pulse is 78/min. Her BMI is 32 kg/m². Physical examination is unremarkable. Laboratory results are as follows: Dual energy x-ray absorptiometry (DEXA) T scores: She is treated with 50,000 IU of vitamin D2 (ergocalciferol) weekly for 4 weeks. Repeat laboratory data shows a serum calcium of 11.4 mg/dL and parathyroid hormone (PTH) levels of 75 pg/mL (normal 10-65 pg/mL). Which of the following is the most likely diagnosis?

Question

Quizplus · Accepted Answer

This patient presents with a borderline high calcium and low vitamin D that is most consistent with primary hyperparathyroidism (PHPT) with concurrent vitamin D deficiency. Both of these are very commonly encountered clinical problems and often coexist. Vitamin D deficiency can sometimes mask hypercalcemia in PHPT, which is unmasked with vitamin D repletion (as seen in this patient). Serum calcium is low-normal to low in vitamin D deficiency, but high-normal in PHPT with vitamin D deficiency. 11ec193a_97a1_4983_853d_ef9e3bc50dd6_MD0002_00 Parathyroid hormone levels in PHPT with vitamin D deficiency are relatively higher than PHPT alone because there is a component of secondary hyperparathyroidism. The PTH levels drop after vitamin D repletion but do not completely normalize. Interestingly, treatment of vitamin D deficiency in PHPT with overt hypercalcemia does not lead to hypercalcemic crisis. (Choice A) Granulomatous disease causes hypercalcemia from the unregulated conversion of 25-hydroxy vitamin D to 1,25 dihydroxy vitamin D, resulting in increased intestinal calcium absorption. Hypercalcemia in these patients is PTH-independent because high calcium and 1,25 dihydroxy vitamin D suppress PTH. (Choice B) Similar to granulomatous disease, malignancy-induced hypercalcemia is PTH-independent and PTH levels are usually < 20 pg/mL. (Choice D) Vitamin D deficiency with serum 25-hydroxyvitamin D levels < 20 ng/mL can lead to decreased intestinal absorption of calcium and resultant PTH secretion. However, serum calcium levels in secondary hyperparathyroidism due to vitamin D deficiency are borderline low to normal. (Choice E) Vitamin D intoxication sometimes causes PTH-independent hypercalcemia due to intestinal calcium absorption. However, this patient's treatment of vitamin D deficiency with 4 weeks of ergocalciferol should not result in vitamin D intoxication. Educational objective: Vitamin D deficiency can mask hypercalcemia in primary hyperparathyroidism (PHPT) and present as a normal to high-normal calcium that increases once vitamin D is repleted. The diagnosis is confirmed with a disproportionately elevated PTH level that is usually higher than the PTH level seen in PHPT without vitamin D deficiency. __________ References: Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. (http://www.ncbi.nlm.nih.gov/pubmed/19193909) Clinical significance of vitamin D deficiency in primary hyperparathyroidism, and safety of vitamin D therapy. (http://www.ncbi.nlm.nih.gov/pubmed/21079532)

A 40-Year-Old Woman Is Evaluated for Mildly Elevated Blood Pressure