Paradoxical Inadequate Parathyroid Hormone Secretion Secondary to Severe Hypomagnesemia: A Review of the Literature

Hypocalcemia is a common manifestation frequently encountered secondary to hypomagnesemia. Both calcium and magnesium are essential for maintaining normal cellular physiology, and magnesium plays a pivotal role in modulating neuronal excitation, intracardiac conduction, and myocardial contraction by regulating several ion transporters. Associated disorders may include cardiac arrhythmia, heart failure due to insufficient contractility, and neuromuscular and central nervous system conditions with seizures. One of the most important factors underlying hypocalcemia in hypomagnesemia conditions is the impaired secretion of parathyroid hormone (PTH), referred to as paradoxical hypoparathyroidism. Because there is a positive functional correlation and association between serum magnesium and calcium concentrations, clinical hypocalcemia in cases of magnesium deficiency cannot be sufficiently corrected by supplementation with calcium, vitamin D, or both. In contrast to the clinical relevance of a rapid, consequent and effective detection, differential diagnosis, and subsequent initiation of an appropriate therapy, this phenomenon and underlying pathophysiology are not well understood. In this review we summarize on calcium and magnesium homeostasis through modulation of PTH and vitamin D and elaborate on the mechanism underlying the rare condition of paradoxical inadequate PTH secretion. Based on the relevant literature, our review includes interdisciplinary diagnostic and therapeutic recommendations.