Ans. b. Hyperparathyroidism (Ref: Schwartz 9/e p1377-1380; Sabiston 19/e p928-932; Bailey 26/e 771-774 25/e p800- 804: Harrison 19/e 2470-2474, 18/e p3100-3105)The most likely diagnosis in a 40-year-old female presenting with multiple lytic bone lesions, fracture clavicle and periosteal resorption of 2nd and 3rd metatarsals is hyperparathyroidism.'The distinctive bone manifestation of hyperparathyroidism is osteitis fibrosa cystica. X-ray changes include resorption of the phalangeal tufts and replacement of the usually sharp cortical outline of the bone in the digits by an irregular outline (subperiosteal resorption). In recent years, osteitis fibrosa cystica is very rare in primary hyperparathyroidism, probably due to the earlier detection of the disease. '- Harrison 18/e p3102Primary HyperparathyroidismPHPT arises from increased PTH productionQ from abnormal parathyroid glands and results from a disturbance of normal feedback control exerted by serum calcium.More common in womenQSolitary adenomaQ is the MC cause (in 80%)Parathyroid adenomas are most commonly located in inferior parathyroid glandsQ.Increased PTH production leads to hypercalcemia via:Increased GI absorption of calciumIncreased production of vitamin D3Reduced renal calcium clearanceEtiology:Exposure to Low-dose therapeutic ionizing radiation and familial predispositionRenal leak of calciumDeclining renal function with ageAlteration in the sensitivity of parathyroid glands to suppression by calciumLithium therapyGenetics:Most cases of PHPT are sporadicAlso associated with MEN-1, MEN-2A. isolated familial HPT, and familial HPT with jaw-tumor syndromeClinical Features:Patients with PHPT formerly presented with the 'classic' pentad of symptoms:* Kidney stonesQ* Painful bonesQ* Abdominal groansQ* Psychic moansQ* Fatigue overtonesQAlteration in the 'typical' patient with PHPT due to widespread use of automated blood analyzers.Patients are more likely to be minimally symptomatic or asymptomatic.Currently, most patients present with weakness, fatigue, polydipsia, polyuria, nocturia, bone and joint pain. constipationQ, decreased appetite, nausea, heartburn, pruritus, depression, and memory loss.Renal calculi are typically composed of calcium phosphate or oxalateQOsteitis fibrosa cystica in advanced PHPTPathognomonic radiologic findings on X-rays of hands, characterized by:Subperiosteal resorptionQ (most apparent on the radial aspectQ of middle phalanxQ of 2nd and 3rd fingers)Bone cystsQTufting of distal phalangesQDiagnosis:Elevated serum calcium and intact PTH or two-site PTH levels, without hypocalciuria establishes the diagnosis of PHPT with virtual certaintyQDecreased serum phosphate (50%) and elevated 24-hour urinary calcium (60%) in PHPTQLocalization:99mTc-labeled sestamibi: Most widely used and accurate modalityQ (sensitivity >80% for detection of parathyroid adenomas)Treatment:Parathyroidectomy for patients having 'classic' symptoms of PHPT or <50 yearsQSERM and bisphosphonates are used to lower serum calcium and increase BMD in PHPT.Indications for Parathyroidectomy in Asymptomatic Primary HPT* Serum calcium >1 mg/dL above the upper limits of normal* Life-threatening hypercatcemic episode* Creatinine clearance reduced by 30%* Kidney stones on abdominal x-rays* Markedly elevated 24-h urinary calcium excretion (> 400 mg/d)* Substantially decreased bone mineral density at the lumbar spine, hip, or distal radius* Age <50 years* Long-term medical surveillance not desired or possible