Secondary hyperparathyroidism

Excess PTH production secondary to chronic hypocalcemia (or hyperphosphatemia). Typically caused by chronic kidney disease (CKD) with decreased phosphate excretion and vitamin D activation. Also seen with vitamin D deficiency or malabsorption. The parathyroid glands are normal but respond to low Ca by enlarging and overproducing PTH (unlike primary HPT which is an intrinsic gland problem).

• Secondary HPT is a major component of CKD–mineral bone disorder. Persistent high PTH leads to renal osteodystrophy (bone pain, fractures, skeletal deformities) and extra-skeletal calcifications (vascular or soft tissue calcification) in kidney failure patients. Controlling secondary HPT in CKD reduces skeletal complications and improves patient outcomes. It's important to differentiate secondary vs primary HPT by lab values: secondary has high PTH with low/normal Ca (in contrast to primary HPT's high Ca).

• Chronic kidney disease patients, especially with GFR <30 (Stage 4–5) or on dialysis: present with diffuse bone and joint pain, muscle weakness, and calcific deposits in skin causing itching (pruritus). Skeletal exam may show bone fragility or skeletal deformities (e.g., "rugger-jersey" spine on X-ray).
• Lab findings: hypocalcemia (or low-normal Ca), hyperphosphatemia (in CKD), and markedly ↑PTH. If due to vitamin D deficiency (without CKD), phosphate may be low or normal, but Ca is low and PTH high.
• In vitamin D deficiency or malabsorption (e.g., celiac disease): secondary HPT can manifest as osteomalacia (bone pain, pseudofractures) in adults or rickets in children. These patients have high PTH due to chronic hypocalcemia from low vitamin D.

1. Determine the cause of high PTH with low Ca: check renal function (BUN/Cr, GFR) and 25-OH vitamin D level in any patient with elevated PTH and no hypercalcemia.
2. CKD management: control hyperphosphatemia (dietary phosphate restriction and phosphate binders) and ensure adequate vitamin D levels (supplement vitamin D3 if deficient; use calcitriol or analogs if CKD stage 4–5) to reduce PTH drive.
3. Monitor trends: in CKD, PTH levels rise as GFR falls – monitor PTH periodically. Escalate therapy if PTH exceeds target range (e.g., add calcitriol or calcimimetics) to prevent severe bone disease.
4. Differentiate from tertiary HPT: tertiary is suspected when a CKD patient develops high Ca along with high PTH (parathyroids become autonomous). In secondary HPT, Ca remains low or normal. So a rise in Ca in a dialysis patient signals tertiary hyperparathyroidism.
5. No need for localization imaging in secondary HPT: all parathyroid glands are diffusely hyperplastic (imaging is reserved for primary/tertiary when planning surgery).

1. Treat the underlying cause: for CKD, manage phosphate and vitamin D. Use phosphate binders (e.g., sevelamer, calcium acetate) with meals to reduce phosphate absorption, and supplement active vitamin D (calcitriol or analogs) to increase Ca absorption and directly suppress PTH.
2. Add calcimimetics like cinacalcet (especially in dialysis patients) to trick parathyroid glands into reducing PTH secretion – this lowers PTH and calcium levels. Aim to keep PTH in an acceptable range rather than completely normal (to avoid adynamic bone).
3. In vitamin D deficiency, replenish vitamin D (ergocalciferol or cholecalciferol) and calcium as needed – this will decrease PTH. Monitor PTH after correction to ensure it normalizes.
4. Refractory cases: if PTH remains extremely high (>800–1000) despite medical therapy, or if there's calciphylaxis, a surgical subtotal parathyroidectomy may be indicated even before transplant.

• Remember: in secondary HPT, PTH is high, Ca is low – opposite of primary/tertiary where both PTH and Ca are high.
• Radiologic clues: secondary HPT causes subperiosteal bone resorption (erosions on radial aspect of middle phalanges) and "salt-and-pepper" skull and rugger-jersey spine on X-ray due to chronic high PTH.
• Severe secondary HPT (untreated) can cause calcific deposition in arteries and skin (calciphylaxis) – highlighting the need for aggressive management in ESRD.

• Calciphylaxis: uncontrolled secondary HPT with high Ca×P product can lead to calcific uremic arteriolopathy – painful skin ulcers and gangrene with high mortality; requires urgent intervention (aggressive medical therapy, consider parathyroidectomy).
• Emergence of hypercalcemia in a patient with secondary HPT (especially post-transplant) → indicates tertiary HPT (autonomous PTH) and need for surgical management.

1. CKD Stage 3+ or other risk factor → screen for rising PTH, Ca, phosphate.
2. If PTH elevated + Ca low/normal → secondary HPT. Address vitamin D status: replace 25-OH D if low; limit dietary phosphate.
3. If PTH remains high and GFR <30 or phosphate high → start phosphate binders and low-phosphate diet; add active vitamin D (calcitriol) to suppress PTH.
4. In dialysis patients, if PTH is above target (e.g., >300–600) despite binders and calcitriol → add cinacalcet (calcimimetic) to further reduce PTH.
5. If PTH is persistently very high and patient has hypercalcemia or severe bone pain/calcifications → consult surgery for possible parathyroidectomy (prevent progression to tertiary HPT).

• Dialysis patient with high phosphate, low calcium, very high PTH, and bone pain → secondary hyperparathyroidism due to CKD (renal osteodystrophy).
• Elderly patient with malnutrition (or GI malabsorption) who has bone pain and muscle weakness; labs show low vitamin D, hypocalcemia, elevated PTH → secondary HPT from vitamin D deficiency (causing osteomalacia).