Definition and Clinical FeaturesTop
Secondary hypoparathyroidism is a condition characterized by decreased parathyroid hormone (PTH) secretion, which results from the inhibitory effect of PTH-independent hypercalcemia (Table 1). Symptoms of the underlying condition—the actual cause of hypercalcemia—may be observed along with the symptoms of hypercalcemia.
Laboratory tests reveal hypercalcemia and low serum PTH levels.
Differential diagnosis should include other causes of PTH-independent hypercalcemia.
Treatment should address both the underlying condition and hypercalcemia.
Hypercalcemia with high PTH levels (PTH-dependent):
1) Primary hyperparathyroidism:
b) Hereditary (MEN 1, MEN 2A)
c) Lithium salt-induced
2) Mutations of the gene encoding the calcium-sensing receptor (familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism)
3) Antibodies binding to the calcium-sensing receptor
4) Paraneoplastic endocrinopathy (secretion of PTH by neoplasms)
5) Congenital or acquired deficiency of FGF-23 and the Klotho protein
Hypercalcemia with low PTH levels (PTH-independent):
1) Cancer (increased secretion of PTHrP as well as osteolytic cytokines, chemokines, prostaglandins, and Dkk-1 protein)
2) Intoxication with vitamin D or its metabolites
3) 1,25(OH)2D3 secreted by granulomas (sarcoidosis) or lymphomas
4) Vitamin A intoxication (increased osteolysis)
5) Thyrotoxicosis (increased osteolysis)
6) Thiazide diuretics, theophylline (decreased urinary calcium excretion)
7) Milk-alkali syndrome (Burnett syndrome: excessive use of calcium-containing drugs that neutralize gastric acid or excessive consumption of dairy products)
8) Long-term immobilization (calcium mobilization from bone)
9) Polyuria in patients with AKI caused by rhabdomyolysis
10) Adynamic bone disease in patients with CKD receiving RRT (impaired calcium deposition in bone)
11) Williams syndrome (deletion or translocation of the gene encoding elastin)
AKI, acute kidney injury; CKD, chronic kidney disease; FGF-23, fibroblast growth factor 23; MEN, multiple endocrine neoplasia; PTH, parathyroid hormone; PTHrP, parathyroid hormone-related peptide; RRT, renal replacement therapy.