bubble_chart Overview

Secondary hyperparathyroidism occurs when there are factors in the body that stimulate the parathyroid glands, particularly low blood calcium and magnesium levels or high blood phosphorus levels. The glands become hyperplastic and hypertrophic in response to stimulation, secreting excessive parathyroid hormone to compensate and maintain normal blood calcium and phosphorus levels. This condition is commonly seen in vitamin D deficiency, severe renal insufficiency, osteomalacia, pregnancy, or lactating women.

bubble_chart Etiology

(1) Osteomalacia due to various causes

1. Vitamin D deficiency: Reduced intestinal calcium absorption leads to hypocalcemia, stimulating parathyroid hyperplasia and excessive hormone secretion.

2. Gastrointestinal, hepatobiliary, and pancreatic diseases cause malabsorption of fat-soluble vitamin D, resulting in effects similar to insufficient vitamin D intake and leading to hypocalcemia.

3. Chronic kidney disease, renal insufficiency, and loss of nephrons reduce the glomerular filtration rate, increasing blood phosphorus and decreasing blood calcium ions, thereby stimulating parathyroid hormone secretion. This reduces phosphorus reabsorption in the renal tubules to lower blood phosphorus levels. However, in the early stages of renal insufficiency, serum immunoreactive parathyroid hormone is already elevated. When the filtration rate drops to 40 ml/min, the increase in serum hormone concentration becomes more pronounced. If renal insufficiency worsens, blood phosphorus levels remain significantly elevated, and parathyroid hormone levels rise correspondingly. Additionally, renal insufficiency impairs the activation metabolism of vitamin D, reducing the formation of 1,25-(OH)₂

D₃, which affects intestinal calcium absorption and exacerbates hypocalcemia.

4. Long-term phosphate deficiency and hypophosphatemia: These are often due to renal tubular acidosis, such as Fanconi syndrome, hereditary hypophosphatemia, or prolonged use of aluminum hydroxide. Both impaired vitamin D activation metabolism and hypophosphatemia can cause osteomalacia and hypocalcemia, stimulating the parathyroid glands.

(2) Pseudohypoparathyroidism: Due to the lack of response in target organ cells to parathyroid hormone, hypocalcemia and hyperphosphatemia stimulate the parathyroid glands.

(3) Excessive calcitonin: For example, in medullary thyroid carcinoma, excessive calcitonin can also stimulate the parathyroid glands.

(4) Others: Such as pregnancy, lactation, hypercortisolism, etc.

Hypocalcemia and hyperphosphatemia stimulate parathyroid hyperplasia and hypertrophy. Excessive parathyroid hormone acts on bones, causing bone resorption, and on the kidneys, promoting phosphorus excretion. Therefore, fibrous osteitis may develop on the basis of primary conditions like osteomalacia. Blood phosphorus levels vary depending on the disease cause: they are low in general vitamin D deficiency and renal tubular disorders but high in glomerular disorders, while alkaline phosphatase levels are elevated in all cases. Pathologically, it is difficult to distinguish between secondary and primary hyperplasia and hypertrophy. Long-term overactivity or stimulation can lead to adenoma formation. If an adenoma develops on the basis of secondary hyperplasia, it is termed tertiary hyperparathyroidism.

bubble_chart Treatment Measures

Due to different disease causes, the treatments also vary, primarily involving the removal of stimulating factors such as hypocalcemia, hypomagnesemia, hyperphosphatemia or hypophosphatemia, and hypercalcitoninemia.

1. In cases of simple vitamin D deficiency and pseudohypoparathyroidism, generally only an appropriate amount of vitamin D supplementation is needed to correct abnormal blood calcium and phosphorus levels.

2. For hypophosphatemia caused by renal tubular disorders and vitamin D metabolism phosphorus disorders, neutral phosphate supplementation is recommended, 2–4 g daily, combined with vitamin D at varying doses of 50,000–400,000 units per day, or 1a(OH)D at 0.5–2.0 μg daily.

3. In cases of chronic renal insufficiency or failure: ① Oral administration of aluminum hydroxide or aluminum carbonate can bind large amounts of inorganic phosphorus, effectively reducing phosphorus absorption. If bone disease is mild, this may sometimes be effective; ② Oral calcium salts or increasing the calcium content in dialysis fluid can supplement calcium deficiency and inhibit parathyroid secretion. Renal osteodystrophy is only observed in patients where the dialysis fluid calcium content is below 5.6 mg%; ③ Vitamin D should then be used cautiously, starting with an oral dose of 50,000–60,000 units daily. After 3–4 weeks, the dose can be gradually increased if necessary, up to around 400,000 units daily, or its activated preparations may be used; ④ For patients planning to undergo kidney transplantation, subtotal parathyroidectomy should be performed, as hyperparathyroidism can persist for months or even years after transplantation, and hypercalcemia is detrimental to the transplanted kidney and the body.