**3. Physiology**

*Mineral Deficiencies - Electrolyte Disturbances, Genes, Diet and Disease Interface*

rhino, being reported as "a small, compact yellow glandular body attached to the thyroid at the point where the veins emerge" [3, 4]. However, the definitive discovery of the parathyroid glands in humans was made in 1877 by Swede Ivar Sandström, a medical student at Uppsala University, Sweden, publishing his work in which he wrote: "Almost three years ago I found on the thyroid gland of a dog a small organ, hardly as big as a hemp seed, which was enclosed in the same connective tissue as the thyroid, but could be distinguished therefrom by the light color. Microscopically the examination revealed glandular tissue completely different from that of the thyroid" [4]. After identification in dogs, he finally dissected such structures in human cadavers, calling them *glandulae parathyroidae* (**Figure 1**). Later, in 1891, Eugene Gley reported symptoms of tetany when these glands were removed during thyroidectomies [5]. At the beginning of the twentieth century, the theory described by Jacob Erdheim emerged, which related hypertrophy of parathyroid tissue as a response to bone disease (osteomalacia and/or cystic fibrous osteitis). This theory was rejected by Felix Mandl in 1925, who performed the first parathyroid surgery in Vienna. Initially, it was believed that bone lesions were a consequence of a parathyroid deficiency, and to prove it, transplantation of cadaveric parathyroid tissues was performed in patients with cystic bone lesions and hypercalciuria. With the procedure unsuccessful, Mandl proceeded with cervical exploration and identified a 21 × 12 × 12 mm parathyroid "tumor," which was resected, observing the patient's improvement [6]. Still in 1925, Collip brought a breakthrough in studying the function of PTH, by treating patients with tetany due

to parathyroidectomy with relative PTH extract with relative success [4].

*Original drawing by Ivar Sandström of human parathyroid glandular anatomy [4].*

The term tertiary HPT came up with Dr. Walter St. Goar, when describing a case report in the New England Journal of Medicine, number 268, in 1963, of a patient with CKD and functional parathyroid autonomy [7]. McPhaul, in 1964, published

**70**

**Figure 1.**

PTH plays a central and fundamental role in homeostasis of the control of calcium and phosphorus in the body. It is produced by the parathyroid glands, composed mainly of main cells, and, to a lesser extent, by oxyphil cells [1, 4]. Studies show that, over time, the main cells are replaced by oxyphil cells, which are more sensitive to PTH production, especially in cases of CKD [9, 10]. Its action on renal, bone, and, indirectly, intestinal cells implies a rapid increase in the extracellular flow of calcium (**Figure 2**). This hormone is a peptide with 84 amino acids and a molecular weight of 9500 Da. It has a short half-life (2–3 min) and is broken down into the amino-terminal and carboxy-terminal portions. Only the amino-terminal portion has biological effects on the body, while the carboxy-terminal portion remains inactive. PTH binds to specific membrane receptors in renal and bone cells, fibroblasts, chondrocytes, vascular smooth muscle, adipocytes, and placental trophoblasts [11].
