Primary hyperparathyroidism
Pathogenesis (disease development)
Primary hyperparathyroidism is the term used when there is a primary disease of the parathyroid glands (lat. : glandulae parathyroideae) with increased production of parathyroid hormone and resulting hypercalcemia (calcium excess). When the extracellular calcium level is increased, the parathyroid gland reacts by reducing the production and secretion (secretion) of parathyroid hormone. In primary hyperparathyroidism, this control loop is disturbed. The parathyroid glands produce parathormone in excess of demand, causing a pathological increase in serum calcium levels (hypercalcemia (excess calcium)). The cause lies in the parathyroid glands themselves. The following pathogenetic mechanisms are described in the literature:
- The “set point” is shifted: Reduction of parathyroid hormone production and secretion occurs only at a higher extracellular calcium concentration.
- The parathyroid gland is enlarged and the production and secretion of parathyroid hormone increased. Furthermore, the physiological regulation is impaired.
Etiology (causes)
Biographical causes
- Genetic burden – familial clusters are known (familial primary hyperparathyroidism).
Disease-related causes
- Adenoma (benign growth) of the parathyroid gland (solitary epithelial adenoma/single enlarged parathyroid gland); in 80-85% of cases.
- Hyperplasia of the parathyroid glands – all four epithelial corpuscles are enlarged; in 15-20% of cases.
- Carcinoma of the epithelial corpuscles; very rare (<1% of cases).
Secondary hyperparathyroidism
Pathogenesis (disease development)
Secondary hyperparathyroidism is when a nonparathyroid disorder results in a decrease in serum calcium (hypocalcemia (calcium deficiency)) and the parathyroid glands subsequently secrete more parathyroid hormone. The underlying, primary disorder may be in calcium, phosphate or vitamin D metabolism. Consequently, it may be hypocalcemia (calcium deficiency), hyperphosphatemia (phosphate excess), or decreased 1,25(OH)2 vitamin D levels. These disorders can be caused by a wide variety of diseases. Most commonly, secondary hyperparathyroidism occurs in vitamin D deficiency or in end-stage renal failure (“severely advanced renal impairment”). The latter is referred to as “renal secondary hyperparathyroidism.” In the context of renal insufficiency, phosphate excretion is reduced (→ hyperphosphatemia (phosphate excess)). Increased complex formation of phosphate and free calcium occurs. The result is hypocalcemia (calcium deficiency). In addition, impaired renal function limits the activity of 1α-hydroxylase, resulting in insufficient synthesis of 1,25-dihydroxycholecalciferol. This process also promotes the development of hypocalcemia (calcium deficiency) and ultimately leads to hyperparathyroidism.
Etiology (causes)
Behavioral causes
- Diet
- Inadequate dietary intake of vitamin D and calcium (malabsorption).
Disease-related causes
- Anorexia nervosa (anorexia nervosa)
- Chronic renal insufficiency (kidney weakness) with decreased vitamin D 3 activation and phosphate retention.
- Hepatic causes of secondary hyperparathyroidism with normal renal function:
- Alcoholic cirrhosis (liver shrinkage).
- Primary biliary cirrhosis of the liver
- Cholestasis (bile stasis)
- Maldigestion (“poor digestion”)/malabsorption (disorder in the absorption of food in the intestine) – due to gastrectomy (stomach removal), celiac disease, inflammatory bowel disease such as Crohn’s disease or ulcerative colitis, lactose intolerance (lactose intolerance).
- Renal osteopathy (bone changes (osteomalacia / bone softening) caused by chronic renal insufficiency (kidney weakness)) → Renal secondary hyperparathyroidism.
- Total parenteral nutrition (artificial nutrition by special infusion solutions).
- Vitamin D-dependent rickets
Medication
- Antiepileptic drugs
Other causes
- Dialysis treatment
- Lack of exposure to sunlight (UV deficiency).
Tertiary hyperparathyroidism
Pathogenesis (disease development)
Tertiary hyperparathyroidism describes hypercalcemia (calcium excess) that develops during the course of secondary hyperparathyroidism that has existed for a long time (years/decades). The regulation of secretion (release) of parathyroid hormone by the level of serum calcium is absent. The parathyroid glands autonomously (independently) produce parathyroid hormone.
Etiology (causes)
Disease-related causes
- Long-standing secondary hyperparathyroidism associated with renal insufficiency.
Other causes
- Dialysis treatment
