Definition, Etiology, PathogenesisTop
Secondary hyperparathyroidism refers to reversible parathyroid hormone (PTH) hypersecretion by hypertrophic parathyroid glands, mainly due to the reduced influx of calcium ions to parathyroid cells.
Causes: Chronic kidney disease (CKD) (the most frequent cause; hyperparathyroidism develops at a glomerular filtration rate [GFR] ≤45 mL/min/1.73 m2), acute kidney injury (AKI), diseases associated with chronic hypocalcemia, vitamin D deficiency (hereditary or acquired), gastrointestinal malabsorption syndromes, malnutrition, and hypermagnesemia.
Persistent parathyroid stimulation and PTH hypersecretion lead to hypertrophy and hyperplasia of the parathyroid glands. Over time, the function of the hypertrophic parathyroid glands may become autonomous (see Tertiary Hyperparathyroidism).
Clinical Features and Natural HistoryTop
Signs and symptoms depend on the underlying condition that causes chronic hypocalcemia, its duration, and prior treatment. Secondary hyperparathyroidism in patients with CKD leads to the development of renal osteodystrophy associated with high bone turnover (see Chronic Kidney Disease).
1. Biochemical tests: High serum PTH levels, frequently hypocalcemia or serum calcium levels in the lower range of the normal limits, abnormalities related to the underlying condition (most frequently elevated serum creatinine and phosphate levels in patients with CKD), usually low 25(OH)D levels, diminished 1-25(OH)2D3 levels.
2. Imaging studies may reveal enlarged parathyroid glands (best seen on computed tomography [CT] scans) and various bone lesions similar to those found in primary hyperparathyroidism.
Elevated serum PTH levels and hypocalcemia (or normal serum calcium levels) in a patient with an underlying disease known to cause secondary hyperparathyroidism (eg, CKD or low 25(OH)D levels).
Treatment of the underlying condition. If this is not feasible, use symptomatic treatment, which involves:
1) Correction of hyperphosphatemia.
2) Correction of hypocalcemia.
3) Active vitamin D metabolites (calcitriol), precursors that require no renal hydroxylation (alfacalcidol), or analogues (eg, intravenous paricalcitol administered via a central venous catheter during hemodialysis at doses calculated on the basis of serum PTH levels).
4) If the above treatment is ineffective in lowering PTH, use a calcimimetic: cinacalcet 30 to 90 mg/d (unless the patient has hypocalcemia).
5) Surgical treatment of secondary hyperparathyroidism may be required when failure of the above measures results in persistent elevation of PTH and ongoing and/or worsening symptoms. Despite advances in medical treatment, 10% of patients with end-stage renal disease will require parathyroid surgery that is tailored to the renal disease and the likelihood of renal transplant: subtotal parathyroidectomy is preferred in patients in whom renal transplant is anticipated, and total parathyroidectomy with parathyroid transplant in those with no immediate plan for renal transplant.
Management of secondary hyperparathyroidism in patients with CKD: see Chronic Kidney Disease.