Subtotal Parathyroidectomy for Secondary Hyperparathyroidism in CKD-mineral and bone disorder

Educational disclaimer. This article is a historical surgical case report accompanied by an updated discussion. It is for clinician education and is not medical advice. Management of CKD–mineral and bone disorder (CKD-MBD) and parathyroidectomy in dialysis patients should follow current clinical practice guidelines and individualized assessment by the treating nephrology and endocrine-surgery teams.

Subtotal Parathyroidectomy for Secondary Hyperparathyroidism in CKD-MBD

Introduction

In 1960 Stanbury and colleagues reported the first patient with chronic renal failure and advanced bone disease to have marked skeletal improvement after parathyroidectomy (Stanbury et al., Lancet 1960). This case of severe secondary hyperparathyroidism (SHPT) with renal osteodystrophy is presented as a historical exemplar, followed by a contemporary discussion of the diagnosis and management of CKD–mineral and bone disorder (CKD-MBD), the umbrella term that has replaced “uremic osteodystrophy” since the KDIGO 2017 Clinical Practice Guideline Update (Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group, 2017). The term renal osteodystrophy is now reserved for the bone-histology subtype of CKD-MBD. Surgical options remain subtotal parathyroidectomy, total parathyroidectomy with heterotopic autotransplantation, or total parathyroidectomy without autotransplantation, and are now guided by intra-operative PTH (IOPTH) monitoring.

Historical case report

A 33-year-old woman, VB, became hypertensive during her first pregnancy. Hypertension remained inadequately controlled after delivery, and ten years later she was in renal failure and began hemodialysis. She subsequently developed pains in her hands, back, and feet, with progressive bony deformities including kyphoscoliosis, and fractured both clavicles and several ribs. Lower-limb pain produced a limp, with paraesthesias. On admission she was nearly bedridden, pale, with deformities of the clavicles, chest, thoracic spine, and pelvis; hip movement was severely restricted; the soles, palms, and nails were dyschromic; fingers were clubbed.

Laboratory and imaging:

Test	Result	Unit
Hb	7	g/dL
PCV	0.21
WBC	3.6×10^9	/L
Plts	145×10^9	/L
PT	13.4 s	(12.5)
PTT	39.7 s	(31.0)

Predialysis: Na+ 134, K+ 5.4, HCO3- 20 mmol/L; Urea 31 mmol/L; Creatinine 1350 µmol/L.
Postdialysis: Na+ 140, K+ 4.1, HCO3- 20; Urea 16.4; Creatinine 750 µmol/L.
Glucose 4.0, Ca 2.75, Phos 1.1, Alk Phos 117, Bili 16, Prot 70/Alb 37/Glob 33, GGT 13, SGOT 9, Amylase 340.
C-terminal iPTH >25,000 pg/mL (61–315 pg/mL); N-terminal iPTH high (10–65 pg/mL). FEV1 Modern equivalent: In current practice C-terminal and N-terminal radioimmunoassays are obsolete; the standard is the 2nd-generation intact PTH (iPTH) assay (with optional 3rd-generation whole/bioactive PTH excluding the 7-84 fragment) interpreted against the KDIGO 2017 dialysis target of approximately 2–9× the upper limit of normal (Souberbielle et al., 2022).

Radiographs showed the classic features of severe hyperparathyroid CKD-MBD: the “pepper-pot” skull, resorption of the medial ends of the clavicles and rib fractures, acro-osteolysis of distal phalanges with radial subperiosteal resorption of middle phalanges, the “rugger-jersey” spine, and deformation of the pelvic rami and right femoral neck (Figs. 1–3).

She was diagnosed with secondary hyperparathyroidism and severe CKD-MBD. Medications included calcitriol, aluminium hydroxide, methyldopa, and propranolol on a renal-failure diet. Skeletal fractures and deformities were the indication for parathyroidectomy.

Modern equivalent: Aluminum-based phosphate binders are no longer recommended; current practice substitutes non-calcium binders (sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide, ferric citrate) with selective use of calcium-based binders, alongside active vitamin D analogs (calcitriol, paricalcitol, doxercalciferol, alfacalcidol) and calcimimetics (cinacalcet, etelcalcetide; or evocalcet in Japan) before consideration of parathyroidectomy (KDIGO 2017; Chertow et al., EVOLVE, NEJM 2012; Cernaro et al., 2024).

On the day prior to surgery the patient was hemodialysed. At operation four enlarged parathyroid glands were identified and confirmed on frozen section. Subtotal parathyroidectomy was performed, leaving the parathyroid remnant tagged with a silk ligature. Postoperatively she received intravenous and oral calcium. On postoperative day 2 paraesthesia, cramps, and a serum calcium of 1.3 mmol/L developed; supplementation was escalated and normocalcemia was restored. She was discharged on day 8 on oral calcium. A wound hematoma during outpatient hemodialysis was aspirated. At two months she was walking comfortably without support but required continued supplemental calcium. The excised glands weighed 3.5 g and showed chief-cell proliferation with focal oxyphil and water-clear areas and severely reduced intraparenchymal fat; one gland was nodular and another was attached to the thymus.

Modern equivalent: Contemporary intra-operative practice adds intra-operative PTH (IOPTH) monitoring with the Miami criterion (>50% drop from the highest pre-excision baseline at 10 minutes after excision predicts cure) to confirm adequate resection and guide remnant size (Wilhelm et al., AAES JAMA Surgery 2016). Postoperative hypocalcemia of this severity is recognized as hungry bone syndrome (HBS), treated with IV calcium gluconate, oral calcitriol, and magnesium repletion, with frequent labs (often every 4–6 h initially) (StatPearls Hungry Bone Syndrome; Anwar et al., 2022).

Discussion

1. Pathology — CKD-MBD framework

Patients with advanced CKD develop a systemic disorder of mineral and bone metabolism (CKD-MBD) manifesting as (i) laboratory abnormalities (calcium, phosphate, PTH, 25-OH vitamin D, alkaline phosphatase, FGF23), (ii) renal osteodystrophy on bone histology, and (iii) extraskeletal calcification (vascular and soft-tissue), per KDIGO 2017. Bone-histology subtypes follow the TMV (Turnover–Mineralization–Volume) classification: high-turnover osteitis fibrosa (hyperparathyroid bone disease), low-turnover adynamic bone disease, mixed uremic osteodystrophy, and osteomalacia. Pathogenesis involves decreased renal 1,25-dihydroxyvitamin D synthesis, phosphate retention, hypocalcemia, an altered parathyroid set point, and bony resistance to PTH, with FGF23/Klotho axis dysregulation now recognized as an early driver (KDIGO 2017; Hu et al., 2025 SHPT in dialysis review).

2. Preventive and medical management

KDIGO 2017 endorses a stepwise medical ladder for SHPT in dialysis patients before parathyroidectomy is considered (KDIGO 2017):

1. Dietary phosphate restriction, adequate dialysis dose, and management of metabolic acidosis.
2. Phosphate binders — prefer non-calcium binders (sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide, ferric citrate); use calcium-based binders (calcium acetate, calcium carbonate) selectively. Aluminum-based binders are no longer recommended because of aluminum toxicity (encephalopathy, osteomalacia, microcytic anemia).
3. Active vitamin D / analogs — calcitriol, paricalcitol, doxercalciferol, alfacalcidol — to suppress PTH while monitoring calcium and phosphate.
4. Calcimimetics — oral cinacalcet (Sensipar; FDA-approved 2004), IV etelcalcetide (Parsabiv; FDA-approved 2017), or oral evocalcet (KHK7580; Japan). The pivotal EVOLVE trial (cinacalcet in dialysis SHPT) did not significantly reduce the primary composite of death and major CV events on intention-to-treat analysis but reduced calciphylaxis in a pre-specified secondary analysis (Chertow et al., NEJM 2012; Floege et al., 2015 calciphylaxis sub-analysis).
5. Parathyroidectomy for refractory or complicated disease (see indications below).

KDIGO 2017 recommends targeting iPTH at approximately 2–9× the upper limit of normal of the assay in dialysis patients (CKD G5D), with avoidance of extremes (KDIGO 2017).

3. Investigations

Biochemistry includes serum calcium (with albumin correction), phosphate, alkaline phosphatase (and bone-specific ALP where available), 25-OH vitamin D, magnesium, and 2nd-generation intact PTH (with 3rd-generation whole PTH used selectively). Radiographic features such as the “pepper-pot” skull, subperiosteal phalangeal resorption, and “rugger-jersey” spine remain useful teaching findings but are usually present only in advanced disease. Bone biopsy with double tetracycline labeling is the gold standard when bone-histology subtype is needed to guide therapy (KDIGO 2017; Souberbielle et al., 2022).

Preoperative localization

Contemporary practice uses cervical ultrasound, 99m-Tc sestamibi SPECT/CT (sensitivity ≈92%), and, for reoperative or persistent disease, four-dimensional CT (4D-CT) (sensitivity ≈91%) to identify ectopic, supernumerary, or persistent enlarged glands (Mariano et al., 2025 4D-CT vs sestamibi SPECT/CT). The earlier dictum that “preoperative localization is unnecessary in SHPT” no longer reflects practice in most centres, particularly for reoperation.

4. Indications for parathyroidectomy

KDIGO 2017–aligned indications include:

• SHPT refractory to optimized medical therapy (active vitamin D analog plus calcimimetic plus binder).
• Persistent hypercalcemia, severe hyperphosphatemia, or rising calcium–phosphate product despite therapy.
• Calciphylaxis (calcific uremic arteriolopathy).
• Severe symptomatic bone disease — fractures, bone pain, proximal myopathy.
• Progressive vascular or soft-tissue calcification in a transplant-eligible candidate.
• Severe pruritus refractory to medical therapy.

An isolated PTH value (e.g., >1000 pg/mL) is no longer an absolute trigger; decisions integrate symptom burden, bone disease, calcimimetic response, and transplant candidacy (KDIGO 2017; Hu et al., 2025).

5. Parathyroidectomy — strategy and technique

Three strategies are accepted, each with trade-offs supported by 2025 comparative data (Hu et al., 2025 systematic review; Wilhelm et al., AAES 2016):

Strategy	Description	Trade-offs
Subtotal PTx	Resect 3.5 glands; leave a well-vascularized remnant (e.g., 50–80 mg) tagged with non-absorbable suture or clip	Lower postop calcium/calcitriol burden; higher recurrence; remnant in known location for reoperation
Total PTx + heterotopic autotransplant	Resect all four glands; place 1–2 mm fragments in forearm (avoid AVF arm) or sternocleidomastoid; cryopreserve when possible	Lower 12-month PTH and recurrence; greater early postop resource use; risk of graft failure (cryopreservation mitigates)
Total PTx without autotransplant	Resect all four glands without autotransplant; selected cases (e.g., not transplant-eligible, calciphylaxis)	Accepts hypoparathyroidism and adynamic-bone risk; may reduce vascular calcification progression in select patients

Operative principles (Wilhelm et al., AAES 2016):

• Bilateral neck exploration in SHPT (because all four glands are typically hyperplastic).
• Wide excision of perithyroidal fatty tissue and routine transcervical thymectomy to detect supernumerary glands (occur in 2.5–13%, often in the cervical thymus).
• Intra-operative PTH (IOPTH) with Miami criterion (>50% drop from highest pre-excision baseline at 10 minutes) to confirm adequate resection.
• Cryopreservation of parathyroid tissue when available, to allow delayed autotransplant for graft failure.
• For autotransplant in dialysis patients, avoid the AVF/access arm to spare present and potential vascular-access sites.

Modern series report persistence/recurrence in the low single digits to ~10%, generally lower after total PTx + autotransplant than after subtotal PTx (Hu et al., 2025 systematic review).

6. Outcome and postoperative care

Hungry bone syndrome (HBS) is the predictable postoperative state in severe SHPT, with rapid skeletal uptake of calcium, phosphate, and magnesium following PTH withdrawal. Management includes a pre-operative-to-postoperative IV calcium gluconate infusion, oral calcitriol, magnesium repletion, and frequent monitoring (every 4–6 hours initially), titrated to maintain normocalcemia for 5–7 days or until biochemistry stabilizes (StatPearls Hungry Bone Syndrome; Anwar et al., 2022).

Bone pain, pruritus, proximal myopathy, and mood symptoms commonly improve after parathyroidectomy; structural deformities and established vascular calcification typically persist and continue to contribute to cardiovascular morbidity and mortality. Cinacalcet reduced calciphylaxis in the EVOLVE secondary analysis (Floege et al., 2015).

Calciphylaxis (calcific uremic arteriolopathy)

Calciphylaxis is a serious, often fatal vascular calcification syndrome in advanced CKD. Current management combines wound care, optimization of calcium–phosphate balance and PTH (including parathyroidectomy in selected refractory cases), discontinuation of warfarin where possible, intravenous sodium thiosulfate (limited evidence), and emerging therapies including SNF472 (hexasodium fytate / vasifytate), INZ-701 (recombinant ENPP1-Fc), and the adaptive BEAT-Calci platform trial (Bover et al., 2025 calciphylaxis review).

7. Tertiary hyperparathyroidism after kidney transplantation

Tertiary HPT — persistent hypercalcemia with inappropriately elevated PTH after successful kidney transplantation — affects a sizeable minority of transplant recipients with pre-existing severe SHPT. Untreated tertiary HPT contributes to allograft dysfunction, nephrocalcinosis, fracture risk, and persistent bone loss. Treatment options include cinacalcet and parathyroidectomy (subtotal or total + autotransplant) for refractory, symptomatic, or biochemically severe cases (Lou et al., tertiary HPT review).

Conclusion

This historical case remains a vivid reminder of the devastating skeletal and systemic consequences of long-standing untreated SHPT. In modern practice the burden of disease is substantially reduced by early CKD-MBD prevention with non-aluminum phosphate binders, active vitamin D analogs, and calcimimetics, with KDIGO-aligned PTH targets in dialysis. Parathyroidectomy — subtotal, total with heterotopic autotransplantation, or total alone — is reserved for refractory or complicated disease, performed with preoperative localization, IOPTH monitoring, and routine transcervical thymectomy, and supported by structured management of hungry bone syndrome and an awareness of calciphylaxis and tertiary hyperparathyroidism after kidney transplantation.

References

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