Snapshot 55-year-old woman presents to the clinic for an annual well exam. Routine laboratory tests demontrates elevated levels of hypercalcemia. The patient reports some mild diffuse abdominal pain over the past 2 weeks but otherwise denies any chest pain, palpitations, or fatigue. A follow up PTH level is high. Introduction Clinical definition disorder characterized by the over secretion of parathyroid hormone (PTH) by one or more of the parathyroid glands high levels of PTH leads to increase in serum calcium levels, causing hypercalcemia can be of primary, secondary, or tertiary causes Epidemiology demographics occurs in 0.1% of the population and 90% of cases result from a single adenoma risk factors severe, prolonged calcium or vitamin D deficiency menopause neck radiation lithium use Pathogenesis PTH leads to activation of osteoclasts leading to increased Ca2+ and phosphate reabsorption at the bone stimulates osteoclasts by binding to its receptor on osteoblasts, inducing RANK-L and M-CSF synthesis increased reabsorption of Ca2+ in the distal convoluted tubule at the kidney stimulation of kidney 1α-hydroxylase in the proximal convoluted tubule to increase calcitriol production Classification Primary hyperparathyroidism most commonly results from parathyroid adenoma or hyperplasia associated conditions osteitis fibrosa cystica high osteoclast activity at bone resulting in cystic bone spaces with brown fibrous tissue commonly occurs at the jaw multiple endocrine dysplasia (MEN) 1 and 2A Secondary hyperparathyroidism secondary parathyroid hyperplasia as a result of low Ca2+ absorption and/or high phosphate levels associated conditions chronic renal disease renal disease causes hypovitaminosis D leads to ↓ Ca2+ absorption renal osteodystrophy bone lesions due to secondary hyperparathyroidism Tertiary hyperparathyroidism dysregulation of parathyroid glands following chronic renal disease will secrete PTH regardless of Ca2+ levels associated conditions chronic renal disease renal osteodystrophy Hyperparathyroidism Serum Ca Serum Phos Serum PTH Primary ↑ ↓ ↑ Secondary normal or ↓ ↑ ↑ Tertiary ↑ ↑ ↑ Presentation Symptoms asymptomatic (most common) weakness kidney stones (“stones”) bone pain (“bones”) constipation (“groans”) abdominal/flank pain depression (“psychiatric overtones”) uncommon cause of secondary hypertension Physical exam hypertension Imaging Bone mineral density test dual energy X-ray absorptiometry (DEXA) is the most common test to measure bone mineral density allows for measurement of bone reabsorption Computed tomography (CT) abdominal CT may be indicated to determine if kidney stones or other abnormalities are present Radiograph cystic bone spaces (“salt and pepper”) most common at the skull loss of phalange bone mass with increased concavity subperiosteal thinning (cortical resorption) Sestamibi parathyroid scan allows for visualization of the parathyroid glands indicated if surgery is expected Studies Serum calcium test best initial test primary hyperparathyroidism hypercalcemia secondary/tertiary hyperparathyroidism hypocalcemia/normocalcemia Serum PTH best initial test levels will be elevated in all forms of hyperparathyroidism 24-hour urinary calcium routinely measured in patients to assess risk of renal complications helps to distinguish hyperparathyroidism from familial hypocaloric hypercalcemia (FHH) hypercalciuria/normocalciuria Serum 25-hydroxyvitamin D helps in differentiating from FHH guides management Genetic testing may be indicated in patients suspected of MEN 1 or MEN 2A Differential Paraneoplastic syndrome (e.g., squamous cell cancer of the lung) distinguishing factors serum PTH levels will be low due to negative feedback Familial hypocalciuric hypercalcemia (FHH) distinguishing factors urine calcium will be low Treatment Acute hypercalcemia IV fluids loop diuretics Asymptomatic patients first-line observation with follow-up second-line surgical intervention indicated in select patients with abnormal studies indicating skeletal and renal damage Symptomatic patients (e.g., nephrolithiasis) first-line parathyroid surgery is the only definitive therapy complications include post-op hypocalcemia (e.g., numbness, tingling, and muscle cramps) treat with IV calcium gluconate second-line cinacalcet indicated in patients who are unable to have surgery decreases PTH levels by sensitizing Ca2+ - sensing receptors at the parathyroid gland Complications Peptic ulcer disease ↑ gastrin production stimulated by ↑ Ca2+ Acute pancreatitis ↑ lipase activity stimulated by ↑ Ca2+ CNS dysfunction anxiety, confusion, and coma result of metastatic calcification of the brain