Hyperparathyroidism

(see also: Renal Osteodystrophy; Remodeling of Bone)

Discussion

• caused by excessive production of parathyroid hormone which leads to hypercalcemia, recurrent nephrolithiasis, pancreatitis, peptic
  ulcers, and mental changes;
• incidence of approx 5 /10,000 pts per year;
• usually affects adults over 50 yrs & occurs more commonly in females;
• causes:
  • in most cases is due to single parathyroid adenoma (80% of patients);
  • malignant tumor: occurs in about 1% of patients with hyperparathyroidism;
    • occurs often in association w/ multiple endocrine neoplasia syndrome, and rarely to parathyroid carcinoma;
    • hyperparathyoidism is sometimes seen in renal cell carcinoma and squamous cell carcinoma;
• diff dx:
  • occult tumor;
  • multiple myeloma (often associated w/ hypercalcemia);
• classification:
  • primary defect of the parathyroid gland w/ hypersecretion of PTH as seen w/ adenoma's of the parathyroid gland;
  • secondaray causes arise from conditions that produces abnormally low ionic plasma Ca levels and thereby stimulates
    production of PTH (see renal disease: effects on bone):
  • tertiary conditions in which PTH secretion has become autonomous after prolonged stimulation of gland owing to secondary parathyroidism;
• references:
  • Primary hyperparathyroidism: incidence, morbidity, and potential economic impact in a community.
  • Pathology of the parathyroids in hyperparathyroidism. Discussion of recent advances in pathology of the parathyroid glands.
  • Recent advances in parathyroid gland pathology.
  • Primary hyperparathyroidism: changing patterns in presentation and treatment decisions in the eighties.

Labratory Diagnosis of Hyperparathyroidism »

Histology of Hyperparthyroidism »

Radiology of HyperParaThyroidism: Chondrocalcinosis

Clinical Presentation

General

• recurrent nephrolithiasis, peptic ulcers, mental changes which has led to the phrase: stones, bones, and groans;"
  • lethargy, somnolence, and polydipsia are also nonspecific findings;

Bone

• PTH mobilizes bone and phosphate;
• releases osteocytic perilacunaar stores (fast)
• increases osteocytic number and activity (slow)
• activates & increases number of osteoclasts, which leads to osteomalacia and more acutely, releases Ca & Phos;
• causes diffuse bone pain and tenderness;
• stimulate bone remodeling, w/ increase in number of BMU;
• brown tumor;
• chondrocalcinosis and calcific periarthritis are common (ossification of soft tissue);
• fractures secondary to diffuse skeletal osteoporosis;
• NEJM: pseudoclubbing: images in medicine
• references:
  • Fractures of the femoral neck in elderly patients with hyperparathyroidism.
  • Joint lesions of hyperparathyroidism.
  • Osteosclerosis in primary hyperparathyroidism.
  • Hyperparathyroidism: tumor of the parathyroid glands associated with osteitis fibrosa.
  • Parathyroid hormone and bone.
  • A case of multiple skeletal lesions of brown tumors, mimicking carcinoma metastases

Kidney

• increases resorption of calcium;
• increases excretion of phosphate;
• stimulates 1,25 (OH)2 vit D3 (calcitriol) production;
• common occurrence of renal calculi (in untreated cases, calculi sometimes caused renal failure);
• increase renal phosphate excretion by decreasing renal tubular reabsorption of phosphate;

Gut

• increases absorption thru vitamin D;
• acting at level of gut (w/ vit D) to incr absorption of calcium;
• gastric ulcers (seen in 25% of patients) & pancreatitis are common;
• pancreatic calcifications;

Neuromuscular

• proximal weakness, easy fatigability, and atrophy of muscles;

Pyschiatric

• individuals w/ serum Ca level of > than 12 mg/dl (2.99 mm/lit) (see hypercalcemia) have mental aberrations, confusion,
  and dementia;
• references
  • Neuropsychologic deficits associated with primary hyperparathyroidism.

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Treatment

• non operative treatment includes adequate calcium intake and avoidance of Vit D;
  • w/ vague constitutional symptoms such as fatigue, weakness, and/or constipation associated w/ mild hypercalcemia then
    surgery is not indicated;
• note that in most patients w/ primary hyperparathyroidism there is little if any disease progression;
• among asymptomatic patients, approximately 25 % will have progressive disease, which can be measured as a signficant
  decrease in bone mass over a decade;
• operative treatment indications:
  • surgical treatment is indicated when clinical symptoms occur along with laboratory or radiographic abnormalities;
  • clinical findings:
    • osteitis fibrosa cystica
    • nephrolithiasis
    • classic neuromuscular symptoms (proximal muscle weakness, atrophy, hyperreflexia, and gait disturbances);
    • hyperparathyroid crisis (a discrete episode of life-threatening hypercalcemia);
  • laboratory and radiographic data;
    • serum calcium concentration of greater than 12 mg per deciliter (3 mmol per liter)
    • marked hypercalciuria (urinary calcium excretion, greater than 400 mg per day [10 mmol per day])
    • markedly reduced cortical bone density (z score for the distal third of the radius, less than -2;
      • z score: standard deviation from mean for sex-matched and age-matched reference population), an unexplained
        reduction in Cr clearance

References

• Fractures of the femoral neck in elderly patients with hyperparathyroidism.
• Joint lesions of hyperparathyroidism.
• Osteosclerosis in primary hyperparathyroidism.
• Hyperparathyroidism: tumor of the parathyroid glands associated with osteitis fibrosa.
• Parathyroid hormone and bone.
• A 10-Year Prospective Study of Primary Hyperparathyroidism with or without Parathyroid Surgery.