Secondary hyperparathyroidism is a common complication of chronic kidney disease (CKD), driven by phosphate retention, reduced calcitriol synthesis, hypocalcemia, and progressive parathyroid hyperplasia. With prolonged stimulation, parathyroid glands may undergo nodular and monoclonal expansion, resulting in reduced expression of calcium-sensing receptors and vitamin D receptors. This can lead to autonomous PTH secretion despite hypercalcemia, a state termed tertiary hyperparathyroidism (THPT).

THPT is particularly important in patients with ESRD receiving long-term dialysis because persistent hyperparathyroidism contributes to severe bone disease, hypercalcemia, hyperphosphatemia, vascular and soft-tissue calcification, calciphylaxis, and impaired quality of life. Medical treatment with phosphate binders, vitamin D analogues, and calcimimetics may be effective in selected patients; however, parathyroidectomy remains an important option in severe or refractory disease.

Data on THPT among Indian dialysis patients remain sparse. This study was undertaken to determine the prevalence of THPT among ESRD patients on hemodialysis and to describe their demographic profile, clinical manifestations, biochemical abnormalities, imaging findings, and management.

Study design and setting This was a descriptive observational study conducted across intensive care units in MKCG medical college, Berhampur.Thestudy period was from year 2020 to 2022. Participants All patients with ESRD receiving maintenance hemodialysis who attended the nephrology clinic during the study period were screened. Written informed consent was obtained from all participants. In patients unable to provide consent, consent was obtained from the responsible attendant. Biochemical assessment Serum calcium, phosphorus, albumin, and ALP were measured once every two months. Patients with elevated serum calcium and serum phosphorus underwent serum PTH estimation. Patients with serum PTH >600 pg/mL were evaluated further for possible THPT. Hypercalcemia was defined as serum calcium >10.5 mg/dL. Hyperphosphatemia was defined as serum phosphorus >4.5 mg/dL. Serum calcium was measured using the Arsenazo III method, serum phosphorus by the ultraviolet ammonium molybdate method, serum albumin by bromocresol green method, ALP by kinetic method, and PTH by chemiluminescence assay. The laboratory reference range for ALP was 20–140 IU/L and for serum albumin was 3.4–5.4 g/dL. Imaging assessment Patients fulfilling biochemical criteria underwent neck ultrasonography to identify parathyroid nodules. Technetium-99m sestamibi scintigraphy was subsequently performed for localization of suspected parathyroid adenomas or hyperplastic glands. Management Patients with severe hypercalcemia, symptomatic hyperparathyroidism, or clinically significant complications were considered for parathyroidectomy. Cinacalcet was used in patients managed medically, along with non-calcium phosphate binders. Statistical analysis Data were recorded in a predesigned proforma and entered into Microsoft Excel 2007. Entries were double-checked for errors. Categorical variables were summarized as frequencies and percentages. Continuous variables were expressed as mean ± standard deviation.

A total of 311 ESRD patients on hemodialysis were screened. Eleven patients fulfilled the study criteria for THPT, resulting in a prevalence of 3.5%. The mean age of patients with THPT was 55.7 ± 6.9 years. There were eight males and three females. Mean dialysis vintage was 5.3 ± 0.3 years.

Biochemical profile

The biochemical characteristics of patients with THPT are shown in Table 1.

Table 1. Demographic and biochemical characteristics of patients with THPT

All patients had hypercalcemia, hyperphosphatemia, and markedly elevated PTH and ALP levels.

Clinical features

Bone pain was reported by all 11 patients (Table 2). Fatigue was present in nine patients (81.8%), restriction of mobility in six patients (54.5%), peptic ulcer disease in two patients (18.0%), and mental status changes and history of renal calculi in one patient each (9.0%).

Table 2. Clinical manifestations in patients with THPT

Imaging findings

Neck ultrasonography identified parathyroid adenomas in only three of the 11 patients (Table 3). Two patients had bilateral inferior parathyroid adenomas, while one patient had a single parathyroid nodule.

Technetium-99m sestamibi scintigraphy demonstrated involvement of one gland in two patients, two glands in six patients, three glands in two patients, and all four glands in one patient. Inferior parathyroid glands were more commonly involved.

Table 3. Number of parathyroid glands involved on imaging

Management and outcomes

Four patients consented to surgery. Indications for surgery included severe hypercalcemia (serum calcium >11.5 mg/dL) and symptomatic hyperparathyroidism, particularly bone pain, fatigue, and mental status changes. Histopathology confirmed adenomatous transformation in operated patients.

Following surgery, mean serum PTH decreased to 364.3 ± 25.8 pg/mL, mean serum calcium decreased to 9.5 ± 0.3 mg/dL, and mean ALP decreased to 505.3 ± 26.2 IU/L(Table 4).

Six patients were treated medically with cinacalcet in doses ranging from 15 to 90 mg/day along with non-calcium phosphate binders.

Table 4. Postoperative biochemical parameters in operated patients

In this single-centre study, THPT was identified in 3.5% of ESRD patients on maintenance hemodialysis. This finding highlights that autonomous hyperparathyroidism remains a clinically relevant complication in patients with prolonged CKD-related secondary hyperparathyroidism.

The mean dialysis vintage in our cohort was more than five years, supporting the established association between prolonged dialysis exposure and progressive parathyroid hyperplasia. The patients had marked hypercalcemia, hyperphosphatemia, high ALP, and substantially elevated PTH concentrations, indicating severe high-turnover bone disease. Bone pain and fatigue were the most common clinical manifestations, and more than half of the patients had restricted mobility, emphasizing the functional burden of THPT.

Ultrasonography identified parathyroid lesions in only a minority of patients, whereas sestamibi scintigraphy provided better localization and demonstrated multigland involvement in most cases. Inferior parathyroid glands were more frequently affected. These findings support the utility of functional imaging in the preoperative evaluation of patients with suspected THPT, particularly when ultrasonography is non-diagnostic.

Only four patients underwent surgery, largely because of consent-related limitations. In operated patients, there was a substantial reduction in PTH, calcium, and ALP levels after surgery, supporting parathyroidectomy as an effective treatment in severe symptomatic disease. Cinacalcet was used in six patients as medical therapy along with non-calcium phosphate binders. Calcimimetics act by increasing the sensitivity of the calcium-sensing receptor to extracellular calcium and can reduce PTH secretion and serum calcium levels in THPT.

The reported prevalence of refractory hyperparathyroidism varies across studies because of differences in diagnostic definitions, dialysis duration, access to calcimimetics, and thresholds for surgery. In the present study, the use of a biochemical screening strategy followed by imaging allowed identification of clinically significant THPT in a resource-limited setting.

Limitations

This study has several limitations. First, the sample size was small and the study was conducted at a single tertiary care centre, limiting generalizability. Second, patients with early autonomous disease may have been missed if serum calcium, ALP, or PTH values did not cross the screening thresholds. Third, only ESRD patients on hemodialysis were included; findings may not apply to patients on peritoneal dialysis or those with earlier stages of CKD. Fourth, the response to cinacalcet was not assessed systematically using serial biochemical measures and repeat sestamibi imaging. Finally, long-term clinical outcomes after surgery or medical treatment were not available.

THPT was present in 3.5% of ESRD patients receiving hemodialysis in this tertiary care cohort. Affected patients had severe hypercalcemia, hyperphosphatemia, markedly elevated PTH and ALP, and a high burden of skeletal symptoms. Sestamibi scintigraphy was valuable for localization of involved glands. Parathyroidectomy resulted in marked postoperative biochemical improvement in patients who underwent surgery, while cinacalcet was used as medical therapy in others. Larger multicentre prospective studies are needed to establish the epidemiology, diagnostic pathways, and long-term outcomes of THPT in Indian dialysis populations.

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