**5.2 Secondary HPT**

Secondary HPT, unlike primary HPT, is a systemic and non-intrinsic pathology of the parathyroid gland, the consequence of which affects the functioning and metabolism of the parathyroid glands. It is the result of a parathyroid response to a tendency of hypocalcemia in order to maintain calcium homeostasis. It occurs due to low calcium absorption and vitamin D deficiency. Hypovitaminosis D is the main cause of secondary HPT in developed countries, in which confinement and low sun exposure occur frequently. As a result, there is a decrease in intestinal calcium absorption and a tendency towards serum hypocalcemia. The feedback mechanism stimulates the parathyroid glands and increases PTH synthesis, mobilizing calcium from the bones to maintain intravascular calcium homeostasis. Another important cause of secondary HPT is CKD, in which the kidney injury generates low calcium reabsorption in the distal renal tubules with consequent hypocalcemia. It is also in the kidney that the conversion of vitamin D (cholecalciferol) to its active form (calcitriol) occurs through the enzyme alpha1-hydroxylase. In CKD, this conversion is impaired and shows a consequent decrease in serum calcitriol rates and intestinal calcium absorption. As a result, there is an increase in PTH production and osteoclastic activity to try to normalize serum calcium levels. In advanced cases, there is intense damage to bone health, with osteoporosis, severe bone pain, fibrous osteitis, and even pathological fractures [16, 28, 29]. At the same time, renal injury causes phosphate retention, with an increase in serum inorganic phosphate.

**75**

impairments [35].

are above the normal.

*Parathyroid Glands and Hyperparathyroidism: A General Overview*

The chronic renal patient with secondary HPT frequently presents with major bone disease, bone pain, itching, cardiovascular disorders, and, in advanced cases,

Tertiary HPT manifests itself through an evolution of secondary HPT. In these cases, the continuous stimulus to the overproduction of PTH leads the autonomy of the parathyroid glands to produce PTH in high amounts. In the case of CKD, many patients undergo kidney transplants, expecting normalization of calcium reabsorption, conversion of vitamin D to its active form (calcitriol), and a consequent drop in PTH levels and normalization of the calcium rates. However, autonomous parathyroid glands maintain PTH overproduction even with renal calcium reabsorption normalized. The main consequence is the increase of the calcium serum levels. Most patients are asymptomatic, although some maintained bone pain and risk of fractures. In these cases, persistent hypercalcemia, chronic renal graft dysfunction, bone disease progression, cardiovascular events, and the risk of developing nephrolithiasis in the transplanted renal graft justify the early treatment of the disease [7, 30].

In HPT, anamnesis and physical examination are of fundamental importance for

Hypercalcemia is the main consequence of the primary HPT. In most cases, the disease is asymptomatic, occupying more than 80% of cases [21, 26, 31]. This condition was introduced after the 1970s, when routine laboratory tests began to be performed in asymptomatic patients [32]. However, they can develop symptoms that usually begin when calcium levels exceed 12 mg/dL and include manifestations in several systems. Neurological disorders manifest with changes in the level of consciousness, confusion, or lack of concentration. Gastrointestinal manifestations, such as nausea, epigastric pain due to peptic disease, or even pancreatitis, can be found. Nephrolithiasis can occur, mainly of repetition, polydipsia or polyuria. Bone pain and pathological fractures are also reported, in addition to brown tumors in the bone skeleton. Cardiovascular manifestations and heart rhythm disorders are also associated with hypercalcemia [33]. We can measure ionized serum calcium or total calcium. The total calcium measurement needs to be adjusted, because much of it is bonded with serum albumin. The formula can be shown in the following: corrected calcium = measured total serum calcium in mg/dL + 0.8 × (4.0 − patient's serum albumin concentration in g/dL) [21]. Vitamin D participates actively in the diagnosis of primary HPT. The Institute of Medicine (IOM) affirms an evidence that the disease is more active when the vitamin D levels are below normal [21, 34]. A variant of primary HPT is the normocalcemic HPT, when presents with levels of PTH above normal and normal levels of serum calcium. The evolution of these cases can be stable, without clinical complications or laboratory alterations, increase the serum calcium concentration, or cause bone, kidney, or cardiovascular

Secondary HPT caused by CKD normally courses with normal or low levels of serum calcium. Thus, the history of CKD, especially dialysis, is fundamental for the diagnostic interpretation. The symptoms are due to bone disease with bone pain that can be of different intensities and pathological fractures with difficulty in movement. The pruritus also is most frequent, especially when the phosphate levels

*DOI: http://dx.doi.org/10.5772/intechopen.92785*

pathological bone fractures [28, 29].

**5.3 Tertiary HPT**

**6. Diagnosis**

accurate diagnosis.

The chronic renal patient with secondary HPT frequently presents with major bone disease, bone pain, itching, cardiovascular disorders, and, in advanced cases, pathological bone fractures [28, 29].
