Medical Archive

Introduction

P2 C50 Hypercalcemia and Hypocalcemia

Parathyroid hormone

Chief cells regulate serum free (ionized) calcium via parathyroid hormone (PTH) secretion, which
Increases bone osteoclast activity, releasing calcium and phosphate
Increases small bowel absorption of calcium and phosphate (indirectly by activating vitamin D)
Increases renal calcium reabsorption (distal tubule) and decreases phosphate reabsorption (proximal tubule)
Increased serum ionized calcium levels provide negative feedback to decrease PTH secretion.

Parathyroid hormone-related protein PTHrP

Calcitonin

Hypercalcemia

Primary hyperparathyroidism

Solitary adenoma (80%) Chief cell parathyroid hyperplasia (15%, MEN1, 2A? ??)

Clinical presentation

50%? ???. ??? ?? ??? ?????�.

• Nephrolithiasis
  • Calcium oxalate stones
• Nephrocalcinosis
  • Metastatic calcification of renal tubules (Fig. 15.9), potentially leading to renal insufficiency and polyuria
  • CNS disturbances (e.g., ??, ??, ??, ?? / ??? / ????)
  • Constipation, peptic ulcer disease, and acute pancreatitis
• Osteitis fibrosa cystica
  • Paracrine stimulation of osteoclasts by osteoblasts.
  • Resorption of bone leading to fibrosis and cystic spaces filled with brown fibrous tissue.
• Cardiovascular
  • Hypertension
    • d/t ?renin secretion, sympathetic hyperresponsiveness, and peripheral artery vasoconstriction
    • Treatment of PHPT usually results in normalization of BP
  • LVH, arrhythmias, and vascular and valvular calcification.

Diagnosis

Central: Sono
Distal: 99mTc sestamibi scan (SPECT)
PTH??? ??. ALP ?? (turnover ?), ??? ???? ?? (?? ???, ????)

Operation

P2 C38 Thyroid, Parathyroid, and Adrenal

Genetic defects associated with HPT

Other parathyroid-related causes of hypercalcemia

Genetic disorders causing hyperparathyroid-like syndromes

Familial hypocalciuric hypercalcemia (FHH)

• Pathophysiology
  • Defective G-coupled Ca2+-sensing receptors(CaSRs) in multiple tissues (eg, parathyroids, kidneys).
  • Higher than normal Ca2+ levels required to suppress PTH.
• Clinical manifestations
  • Mild asymptomatic hypercalcemia
  • Reduced urinary excretion of calcium (low UCCR)
  • High normal or mildly elevated PTH.

Malignancy-related hypercalcemia

Vitamin D-related hypercalcemia

Hypercalcemia associated with high bone turnover

Hypercalcemia associated with renal failure

Severe secondary hyperparathyroidism

Renal insufficiency -> ?phosphate excretion.
? serum phosphate binds free calcium.
? free calcium stimulates all four parathyroid glands.

FGF23? ? VitD? ? Osteomalacia

Tertiary hyperparathyroidism

CKD? ???? ????? irreversible clonal outgrowth – refractory (autonomous) hyperparathyroidism

Aluminum intoxication

Milk-alkali syndrome

• Pathophysiology
  • Excessive intake of calcium & absorbable alkali
  • Renal vasoconstriction & decreased GFR
  • Renal loss of sodium & water, reabsorption of bicarbonate
• Symptoms
  • N/V, constipation
  • Polyuria, polydipsia
  • Neuropsychiatric symptoms
• Lab findings
  • Hypercalcemia, metabolic alkalosis
  • AKI, suppressed PTH, hypophosphatemia, hypomagnesemia
• Treatment
  • Discontinuation of causative agent
  • Isotonic saline followed by furosemide

Differential diagnosis: special tests

Treatment of secondary hyperparathyroidism

Treatment	Target PTH level: 150~300pg/mL in CRF stage 5
Phosphate binder (at emergency)	Ca carbonate/acetate: with risk of hypercalcemia Sevelamer hydrochloride: no risk of hypercalcemia
Active vitamin D	Direct action ? for refractory hyperparathyroidism (after revised hypeprphosphatemia)
Calcimimetics	Cinacalcet: increase sensitivity of Ca receptor (Used in refractory hypercalcemia)
VDR activator

Differential diagnosis: special tests

Hypocalcemia

Symptom

Numbness and tingling (particularly circumoral)
Neuromuscular: muscle spasm, convulsion. May be elicited by Chvostek or Trousseau ? latent tetany
CNS: irritability, depression, psychosis

Functional classification

P ?? ??: Hypo-Mg2+, Active Vit.D deficiency

Treatment

Acute symptom
IV Ca gluconate

PTH absent
Vit D or calcitriol + high oral Ca / Mg ?? /
Renal stone ?? ?? thiazide on low sodium diet / PTH

PTH ineffective
Vit D or calcitriol + high oral Ca / Restriction of phosphate in diet

Pseudo-hypoparathyroidism
1A: PTH ? ?? kindey? ??? ??.

Albright�s hereditary osteodystrophy AHO
D/t defective Gs protein ? subunit causing end-organ resistance to PTH.
Autosomal dominant, must be inherited from mother d/t imprinting.
Short stature and short 4th and 5th digits.
Vit.D or calcitriol + high oral Ca

Pseudo-pseudo-hypoparathyroidism
AHO? ??? ????, Lab ??. ??? ?? ?? ??. 
Occurs when defective Gs protein ? subunit is inherited from father.