Hyperparathyroidism ( PTH)

also see Other bone disorder (Labs)

PTH Overview

PTH function:

bone resorption of Ca2+ and PO4.
kidney reabsorption of Ca2+ in distal convoluted tubule.
reabsorption of PO4 in proximal convoluted tubule.
1,25-(OH)2 D3 (calcitriol) production by stimulating kidney 1α-hydroxylase.
PTH  serum Ca2+,  serum (PO4),  urine (PO4).
production of macrophage colony-stimulating factor and RANK-L (receptor activator of NF-κB ligand). RANK-L binds RANK on osteoblasts Ž osteoclast stimulation and Ca2+.

Regulation:

 serum Ca2+ = Ž  PTH secretion.
serum Mg2+ = Ž  PTH secretion.
↓↓ serum Mg2+ = Ž PTH secretion.
Common causes of  Mg2+ include diarrhea, aminoglycosides, diuretics, and alcohol abuse.

 
Primary Secondary Tertiary
PTH (intact PTH)
Ca
 PO4
 ALP
Vit D (may be normal)
 cAMP in urine
PTH (intact PTH)
Ca
 PO4
ALP
Vit D
Mg
↑↑ PTH
Ca
May present with:
- Weakness and constipation (“groans”)
- Abdominal/flank pain (kidney stones, acute pancreatitis)
- Depression (“psychiatric overtones”)

 
- Most often in chronic renal disease (causes hypovitaminosis D, ↓  Ca2+ absorption. hyperphosphatemia)
- ↓ GI Ca2+ absorption
- Hyperparathyroidism is present in >50% of patients who have a GFR <60 mL/min.
- Independently associated with increased mortality and an increased prevalence of cardiovascular disease.
- In patients with stage 4 chronic kidney disease, monitoring:
  - Serum Ca and phos levels q 3–6 Mo
  - Bone-specific Alk-phos q 6–12 Mo
 
- Goal = normalizing these values.
 
Ref: ITE 2014, Q31
- Squamous Cell Carcinoma (lung) = PTH-Like (PTHrP) = Hypercalcemia = Renal Calculi
- Renal cell carcinoma,
- Breast cancer
Imaging
1. DXA Scan
2. Sestamibi scannig and Ultrasonography
3. +/- MRI, CT Neck

 
Management:
1. IV Fluids (Oral Hydration 2-3 L daily)
2. Rarely Lasix AFTER Hydration.
2. Bisphosphonates IV for everyone (Pamidronate) - Only useful temporarily, may take 2-3 days to reach maximum effect.
3. Calcintonin - for secondary Hyperparathyroidism in hemodialysis pt and in moderate-to-severe primary hyperparathyroidism unamenable to surgery.

 
Parathyroidectomy Criteria:
All Symptomatic/Pregnant patients Asymptomatic patient with:
Surgery

OR

Bisphosphonate
Calcintonin

  • age < 50 yr
  • PTH > 1000
  • Serum Ca > 11.2 ( > 1.0mg/dl above the upper limit of normal)
  • Urine Ca > 400
  • BMD < T -2.5 or previous fragility fracture
  • Worsening Renal Function

 


ITE 2013 - Question # 13
A 47-year-old postmenopausal female falls while carrying groceries into her house and sustains a right distal radial fracture. A chemistry panel reveals a calcium level of 11.2 mg/dL (N 8.6–10.6) and further evaluation leads to a diagnosis of primary hyperparathyroidism.

Which one of the following is the best course of treatment for this patient?

A) Estrogen replacement therapy
B) Long-term bisphosphonate therapy
C) Daily furosemide treatment with increased oral fluids
D) Elimination of calcium and vitamin D from the diet
E) Referral to a surgeon for consideration of parathyroidectomy

ANSWER: E

Ref: Marcocci C, Cetani F: Clinical practice. Primary hyperparathyroidism. N Engl J Med 2011;365(25):2389-2397. 2) Pallan S, Rahman MO, Khan AA: Diagnosis and management of primary hyperparathyroidism. BMJ 2012;344:e1013

 

44. A 56-year-old male with diabetes mellitus, hypertension, and chronic renal insufficiency presents for follow-up of his chronic medical conditions. Results of his most recent metabolic panel included an estimated glomerular filtration rate of 30 mL/min/1.73 m2 (N >60) and a calcium level of 10.4 mg/dL (N 8.5–10.2). Medication reconciliation reveals he is not taking the sevelamer (Renagel, Renvela) prescribed by the consulting nephrologist.

You explain to the patient that he should be taking sevelamer to lower his serum calcium. The drug accomplishes this by

A) blocking the effect of parathyroid hormone
B) blocking excessive vitamin D levels, thus decreasing intestinal calcium absorption and increasing renal calcium excretion
C) blocking intestinal absorption of phosphate, which lowers parathyroid hormone secretion
D) directly blocking excessive calcium absorption in the intestines
E) directly increasing the renal excretion of both calcium and phosphate

ANSWER: C


Ref: Longo DL, Fauci AS, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, ed 18. McGraw-Hill, 2012, pp
3096-3120.