Real-world management of hypoparathyroidism: the impact of endocrinology specialist follow-up on biochemical and clinical outcomes - a retrospective cohort study

Abstract

Background

Hypoparathyroidism is a chronic endocrine disorder requiring lifelong management, with real-world data on the impact of follow-up setting on biochemical and clinical outcomes remaining limited. This study aimed to evaluate real-world management of hypoparathyroidism and to investigate whether endocrinology specialist follow-up is associated with improved biochemical control and clinical outcomes.

Methods

This retrospective, single-center study included 186 patients with hypoparathyroidism categorized by follow-up setting (endocrinology vs. non-endocrinology clinics). Demographic, biochemical, and clinical data were collected. The primary outcome was achievement of target serum calcium levels (lower-normal or slightly below-normal range per current guidelines). Multivariate logistic regression was performed to identify independent predictors of target calcium achievement, adjusted for age, sex, eGFR, PTH, treatment doses, and serum 25(OH)D.

Results

The mean age of the cohort was 49.5 ± 12.0 years, 78.5% were female and 82.3% had postsurgical hypoparathyroidism. Overall, 76.3% of patients achieved target serum calcium levels; while target phosphate and 25(OH)D levels were achieved in only 45.2% and 46.9%, respectively.Patients followed by endocrinology specialists demonstrated significantly higher rates of target calcium (96.3% vs. 60.6%, p<0.001), phosphate (53.7% vs. 38.5%, p=0.039), and 25(OH)D achievement (57.3% vs. 29.2%, p=0.002) compared with those followed in non-endocrinology settings. Daily calcium supplementation and calcitriol doses were comparable between groups. Guideline-recommended monitoring, including 24-hour urinary calcium and serum 25(OH)D assessment, as well as complication screening, was performed significantly more frequently in the endocrinology group (all p<0.001). In multivariate analysis, non-endocrinology follow-up was independently associated with lower odds of target calcium achievement (OR: 0.08, 95% CI: 0.02–0.33, p<0.001), while serum 25(OH) D was a positive predictor of target calcium achievement (OR: 1.12, 95% CI: 1.01–1.23, p=0.030). The model demonstrated adequate goodness-of-fit (Hosmer–Lemeshow p=0.127).

Conclusions

Follow-up by endocrinology specialists is independently associated with improved biochemical control in patients with hypoparathyroidism, an effect not explained by differences in medication doses. These findings suggest that specialist follow-up may play an important role in optimizing biochemical target achievement and long-term disease management and support the integration of endocrinology specialist care as a standard component of routine clinical practice in hypoparathyroidism.

Background

Hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by hypocalcemia in the presence of inappropriately low or undetectable parathyroid hormone (PTH) levels, and has gained increasing clinical attention in recent years due to growing recognition of its long-term complications and management challenges [1]. The prevalence of the disorder ranges from 6.4 to 37 per 100,000 individuals, with an estimated incidence of 0.8–2.3 per 100,000 person-years [2]. The etiology of HypoPT is predominantly postsurgical, whereas autoimmune, genetic, and idiopathic forms collectively account for approximately 25% of cases [3]. Despite its low prevalence, HypoPT is a chronic multisystem disorder associated with significant long-term morbidity and involvement of multiple organ systems. Patients with HypoPT are at increased risk of comorbidities, including chronic kidney disease, cardiovascular disease, infections, and depression [4–6]. Impaired quality of life in patients with HypoPT has also been well documented in previous studies [7–9]. Furthermore, patients with HypoPT have been reported to exhibit higher rates of cataracts, antihypertensive and antiepileptic medication use, diabetes mellitus, and dyslipidemia [10, 11]. Conventional therapy for HypoPT still predominantly relies on calcium supplementation and active vitamin D analogues, with the aim of maintaining serum calcium concentrations within the low-normal range while normalizing phosphorus and magnesium levels [12, 13]. Recent international guidelines have emphasized individualized and patient-centered management strategies for chronic HypoPT, focusing not only on biochemical control but also on quality of life, symptom burden, long-term complications, and regular monitoring for comorbidities [14, 15]. However, due to the rarity of the disease and the limited availability of high-quality evidence, current recommendations are still largely based on expert opinion, and substantial heterogeneity and unmet needs persist in real-world clinical practice, particularly regarding the identification and management of patients inadequately controlled with conventional therapy [14–16]. Several factors may explain why non-specialized management could fall short of these recommendations: clinicians less familiar with HypoPT may target mid-normal rather than low-normal or slightly below-normal serum calcium concentrations, may rely on calcium and phosphate alone without regular monitoring of 25-hydroxyvitamin D, magnesium, or 24-hour urinary calcium excretion, and may be less attentive to systematic complication surveillance (e.g., renal imaging, DXA, and ophthalmologic assessment), all of which are emphasized in current consensus guidelines but require sustained, disease-specific familiarity to implement consistently [14, 15].

Given the multisystem burden of HypoPT and guideline recommendations for individualized long-term monitoring, endocrinology specialist follow-up may be particularly important for optimizing biochemical control and complication surveillance. Yet, to the best of our knowledge, whether specialist follow-up influences biochemical and clinical outcomes in patients with HypoPT has not been evaluated in real-world practice. Therefore, this retrospective cohort study aimed to evaluate HypoPT management in a single-center cohort and to investigate whether endocrinology specialist follow-up is associated with improved biochemical target achievement and clinical outcomes.

Methods

This retrospective, single-center study was conducted using data extracted from the electronic medical record system of a tertiary referral center. Patients were identified using International Classification of Diseases, 10th Revision (ICD-10) codes E20.0, E20.8, E20.9, and E89.2. A total of 186 patients who had at least one documented follow-up visit between January 2025 and March 2026 were included. Eligible patients were those aged ≥ 18 years, with a confirmed diagnosis of hypoparathyroidism for at least 3 years, who had attended at least two outpatient visits during the preceding three years.

Hypoparathyroidism was defined as the presence of hypocalcemia accompanied by low or inappropriately normal parathyroid hormone (PTH) levels on at least two separate occasions. Patients with pseudohypoparathyroidism and pregnant women were excluded.

Demographic data including age at last visit, age at diagnosis, sex, and disease etiology were recorded. Etiology was classified as postsurgical (defined as hypoparathyroidism persisting for more than 12 months following neck surgery) or nonsurgical (including idiopathic, autoimmune, and genetic causes). In patients with postsurgical hypoparathyroidism, the underlying pathology was further categorized as benign or malignant. Follow-up setting was recorded as endocrinology clinic versus non-endocrinology clinics. The non-endocrinology group comprised patients whose hypoparathyroidism-related follow-up was conducted primarily in internal medicine, general surgery, otolaryngology–head and neck surgery, family medicine, or nuclear medicine clinics, as documented in outpatient records. The electronic medical record system did not allow reliable stratification of these patients according to individual specialty across the entire cohort, which should be considered a study limitation.

The most recent biochemical parameters were recorded, including albumin-adjusted total calcium (mg/dL), phosphate (mg/dL), magnesium (mg/dL), PTH (ng/L), estimated glomerular filtration rate (eGFR) (mL/min/1.73 m²), 25-hydroxyvitamin D (25(OH)D) (ng/mL), and 24-hour urinary calcium excretion (mg/24 hour). Treatment-related variables included daily doses of calcium supplementation (mg/day), calcitriol (µg /day), and native vitamin D (IU/day), as well as the use of magnesium supplements, phosphate binders, and thiazide diuretics.

Reference ranges were defined as follows: calcium 8.8–10.6 mg/dL; phosphate 2.5–4.5 mg/dL; magnesium 1.6–2.5 mg/dL; PTH 12–88 pg/mL; and 25(OH)D 20–100 ng/mL. Treatment targets were defined in accordance with current clinical guidelines as: serum calcium in the lower part of or slightly below the reference range; phosphate within the reference range; magnesium within the reference range; and 25(OH)D above 30 ng/mL. Patients were classified according to whether each of these targets was achieved.

All biochemical analyses were performed in the hospital’s central biochemistry laboratory. Serum calcium concentrations were measured using a Beckman Coulter AU5800 chemistry analyzer with the Calcium Arsenazo reagent (Beckman Coulter, Brea, CA, USA). Serum intact parathyroid hormone (PTH) and 25-hydroxyvitamin D [25(OH)D] levels were measured on a Beckman Coulter DxI 800 immunoassay analyzer using the Access Intact PTH assay and the Access 25(OH) Vitamin D Total assay, respectively (Beckman Coulter, Brea, CA, USA).

Hypercalciuria was defined as 24-hour urinary calcium excretion > 300 mg/day in men and > 250 mg/day in women. Chronic kidney disease was defined as eGFR < 60 mL/min/1.73 m². Nephrolithiasis and hepatosteatosis were defined based on ultrasonographic findings. Basal ganglia calcification was identified on cranial computed tomography. Cataract was defined based on a documented history of cataract surgery or a physician-confirmed diagnosis. Osteoporosis was defined as a bone mineral density T-score ≤ − 2.5 on dual-energy X-ray absorptiometry (DXA); for patients aged younger than 50 years or who were premenopausal, a Z-score ≤ − 2.0 was considered below the expected range for age, in accordance with standard interpretation guidelines.

Comorbidities were recorded and categorized as hypertension, diabetes mellitus, dyslipidemia, ischemic heart and cerebrovascular disease, arrhythmia or heart failure, seizure, depression or anxiety. Healthcare utilization was assessed by recording the number of outpatient visits to other specialties (neurology, psychiatry, orthopedics, physical therapy, rheumatology, urology/nephrology, gastroenterology, and ophthalmology) and emergency department visits during the 3-year follow-up period.

Differences between patients followed in endocrinology and non-endocrinology clinics were analyzed with respect to demographic, biochemical, clinical, and treatment-related variables. Statistical analyses were performed using IBM SPSS Statistics software (version 21.0; IBM Corp., Armonk, NY, USA). The distribution of continuous variables was assessed using the Kolmogorov–Smirnov and Shapiro–Wilk tests. Continuous variables are expressed as mean ± standard deviation (SD); categorical variables are presented as frequencies and percentages. Between-group comparisons were performed using the independent samples t-test for normally distributed variables and the Mann–Whitney U test for non-normally distributed variables. Categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. Specifically, Fisher’s exact test was used in place of the chi-square test for all 2 × 2 comparisons in which any expected cell count was < 5, including hypercalciuria, nephrolithiasis, basal ganglia calcification, and osteoporosis; results for these endpoints should be interpreted with caution given the restricted sample sizes. As no formal a priori sample size calculation was feasible given the retrospective design and the rarity of the disease, statistical power for low-prevalence complications was inherently limited, which is acknowledged as a limitation. In addition, the proportion of patients with documented assessment for each diagnostic test (24-hour urinary calcium, renal ultrasonography, cranial computed tomography, dual-energy X-ray absorptiometry, ophthalmologic examination, and serum 25(OH)D and magnesium measurement) was compared between follow-up groups using the chi-square or Fisher’s exact test, as appropriate, to evaluate completeness of guideline-recommended monitoring as a process-of-care indicator.

A multivariate logistic regression analysis was conducted to identify independent predictors of achieving target serum calcium levels. Variables included in the model were selected based on clinical relevance and significance in univariate analysis. The model was adjusted for age, sex, eGFR, PTH levels, daily calcium supplementation dose, calcitriol dose, and serum 25(OH)D levels. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs). Model goodness-of-fit was evaluated using the Hosmer–Lemeshow test. A two-sided p-value < 0.05 was considered statistically significant.

The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Prof. Dr. Cemil Taşcıoğlu City Hospital (approval number: 133; date: 30.03.2026). Due to retrospective nature of the study, informed consent was waived.

Results

A total of 186 patients with hypoparathyroidism were included in the analysis. The cohort was predominantly female (78.5%; n = 146), with a mean age of 49.5 ± 12.0 years and a mean age at diagnosis of 36.8 ± 11.2 years. Surgical etiology was the predominant cause of hypoparathyroidism, observed in 82.3% of patients (n = 153), while 17.7% (n = 33) had nonsurgical etiologies including idiopathic, autoimmune, and genetic forms. With respect to follow-up, 44.1% of patients (n = 82) were managed in endocrinology clinics, whereas 55.9% (n = 104) were followed in other clinical settings.

Among patients with postsurgical hypoparathyroidism (n = 153), 57.5% had malignant and 42.5% had benign underlying pathology. The vast majority of malignant cases were papillary thyroid carcinoma, with two cases of medullary and one case of anaplastic thyroid carcinoma also identified. All but two patients with postsurgical hypoparathyroidism had undergone thyroidectomy; the remaining two had undergone parathyroid surgery. Baseline demographic and clinical characteristics of the study population are summarized in Table 1.

Table 1.

Baseline demographic and clinical characteristics of the study population (n = 186)

Variable	Value (n = 186)
Demographic characteristics
Age at last visit (years), mean ± SD	49.5 ± 12.0
Age at diagnosis (years), mean ± SD	36.8 ± 11.2
Female sex, n (%)	146 (78.5)
Male sex, n (%)	40 (21.5)
Etiology
Postsurgical, n (%)	153 (82.3)
Malignant underlying pathology, n (%)	88 (57.5)
Papillary thyroid carcinoma	85 (96.6)
Medullary thyroid carcinoma	2 (2.3)
Anaplastic thyroid carcinoma	1 (1.1)
Benign underlying pathology, n (%)	65 (42.5)
Nonsurgical, n (%)	33 (17.7)
Follow-up setting
Endocrinology clinic, n (%)	82 (44.1)
Other clinics, n (%)	104 (55.9)
Biochemical parameters
Albumin-adjusted calcium (mg/dL), mean ± SD	8.49 ± 0.51
Phosphate (mg/dL), mean ± SD	4.69 ± 0.57
Magnesium (mg/dL), mean ± SD	1.88 ± 0.14 (n = 164)
eGFR (mL/min/1.73 m²), mean ± SD	85.3 ± 9.8
PTH (pg/mL), mean ± SD	9.24 ± 6.61
25(OH)D (ng/mL), mean ± SD	28.9 ± 7.3 (n = 130)
24-hour urinary calcium (mg/day), mean ± SD	158.8 ± 57.7 (n = 86)
Treatment
Calcitriol dose (µg/day), mean ± SD	0.88 ± 0.37
Calcium supplementation (mg/day), mean ± SD	1214.8 ± 462.5 (n = 183)
Vitamin D supplementation (IU/day), mean ± SD	1082.9 ± 425.3
Target achievement
Calcium in target range, n (%)	142 (76.3)
Phosphate in target range, n (%)	84 (45.2)
Magnesium in target range, n (%)*	160 (97.6)
25(OH)D in target range, n (%)**	61 (46.9)
Complications
Hypercalciuria, n (%)***	16 (18.6)
Chronic renal failure, n (%)	7 (3.8)
Nephrolithiasis, n (%)****	4 (3.1)
Basal ganglia calcification, n (%)*****	3 (2.9)
Cataract, n (%)******	27 (23.5)
Seizure, n (%)	10 (5.4)
Osteoporosis (T-score < − 2.5), n (%)*******	2 (2.4)
Comorbidities
Hypertension, n (%)	84 (45.2)
Diabetes mellitus, n (%)	32 (17.2)
Dyslipidemia, n (%)	76 (41.1)
Depression or anxiety, n (%)	34 (18.3)
Ischemic heart and cerebrovascular disease, n (%)	15 (8.1)
Arrhythmia or heart failure, n (%)	7 (3.8)
Hepatosteatosis, n (%)********	92 (70.2)

* n = 164; ** n = 130; *** n = 86; **** n = 131; ***** n = 102; ****** n = 115; ******* n = 84; ******** n = 131. eGFR, estimated glomerular filtration rate; PTH, parathyroid hormone; SD, standard deviation

The mean albumin-adjusted serum calcium level was 8.49 ± 0.51 mg/dL. Mean serum phosphate was 4.69 ± 0.57 mg/dL, and mean magnesium was 1.88 ± 0.14 mg/dL (n = 164). The mean eGFR was 85.3 ± 9.8 mL/min/1.73 m². Mean PTH level was 9.24 ± 6.61 pg/mL, and mean 25(OH)D level was 28.9 ± 7.3 ng/mL. Among patients with available data (n = 86), mean 24-hour urinary calcium excretion was 158.8 ± 57.7 mg/day. The mean daily calcitriol dose was 0.88 ± 0.37 µg, and the mean daily elemental calcium supplementation was 1214.8 ± 462.5 mg (n = 183). The mean vitamin D supplementation dose was 1082.9 ± 425.3 IU/day. Thirty-five patients (18.8%) were using TZD-class agents, magnesium supplementation was reported in 13 patients (7.0%), whereas phosphate-binding agent use was notably uncommon, observed in only 2 patients (1.1%).

Serum calcium levels were within the target range in 76.3% of patients (n = 142), while 23.7% were outside the target range. Only 45.2% of patients (n = 84) achieved target phosphate levels. Magnesium levels were within the target range in 97.6% of patients with available data (n = 164). Among patients with available 25(OH)D measurements (n = 130), 46.9% (n = 61) achieved the target level of > 30 ng/mL.

Hypercalciuria was present in 18.6% of patients with available 24-hour urine data (n = 86). Chronic kidney disease was identified in 3.8% of the cohort. Nephrolithiasis was detected in 3.1% of patients with available ultrasonographic data (n = 131), and basal ganglia calcification in 2.9% of those assessed by computed tomography (n = 102). Cataract was present in 23.5% of patients with available data (n = 115). Hepatosteatosis was identified by ultrasonography in 70.2% of patients assessed (n = 131). Bone mineral density was assessed by DXA in 84 patients; among these, osteoporosis was documented in 2.4% and no fragility fractures were recorded in the cohort.

With respect to comorbidities, hypertension was present in 45.2%, diabetes mellitus in 17.2%, and dyslipidemia in 41.1% of patients. Depression or anxiety was reported in 18.3%. Ischemic heart and cerebrovascular disease was identified in 8.1%, seizure in 5.4%, and arrhythmia or heart failure in 3.8% of patients.

During the 3-year follow-up period, 39.2% of patients had at least one gastroenterology outpatient visit, 15.6% had nephrology or urology visits, 24.2% had psychiatry visits, 52.7% had ophthalmology visits, 31.3% had physical therapy/orthopedics/traumatology visits, and 32.3% had neurology visits. Emergency department utilization was also common, with 65.1% of patients having at least one emergency admission during follow-up.

Comparison according to follow-up setting: Endocrinology versus Others

Patients followed in endocrinology clinics (n = 82) and those managed in other clinical settings (n = 104) were compared with respect to demographic, biochemical, clinical, and treatment-related variables (Table 2).

Table 2.

Comparison of demographic, biochemical, and clinical characteristics by follow-up setting

Variable	Endocrinology (n = 82)	Other clinics (n = 104)	p-value
Demographics
Age at last visit (years), mean ± SD	49.8 ± 12.1	49.2 ± 12.0	0.340
Age at diagnosis (years), mean ± SD	36.4 ± 12.2	37.1 ± 10.4	0.830
Female sex, n (%)	60 (73.2)	86 (82.7)	0.118
Duration of disease (years), mean ± SD	13.4 ± 8.6	12.1 ± 7.7	0.329
Biochemical parameters
Albumin-adjusted calcium (mg/dL)	8.58 ± 0.25	8.41 ± 0.64	0.054
Phosphate (mg/dL)	4.62 ± 0.59	4.75 ± 0.56	0.139
Magnesium (mg/dL)	1.87 ± 0.13	1.88 ± 0.15	0.313
eGFR (mL/min/1.73 m²)	83.7 ± 11.7	86.5 ± 8.0	0.156
PTH (pg/mL)	8.76 ± 6.95	9.61 ± 6.34	0.161
25(OH)D (ng/mL)	30.5 ± 6.6	26.2 ± 7.7	0.001
24-hour urinary calcium (mg/day)	156.8 ± 55.0	181.5 ± 83.8	0.360
Treatment
Calcium supplementation (mg/day)	1236.3 ± 440.2	1198.1 ± 480.6	0.305
Calcitriol dose (µg/day)	0.89 ± 0.42	0.86 ± 0.31	0.845
Vitamin D supplementation (IU/day), mean ± SD	1112.9 ± 430.8	1059.02 ± 421.3	0.723
Target achievement
Calcium in target range, n (%)	79 (96.3)	63 (60.6)	< 0.001
Phosphate in target range, n (%)	44 (53.7)	40 (38.5)	0.039
Magnesium in target range, n (%)	81 (98.8)	79 (96.3)	0.313
Vitamin D in target range, n (%)	47 (57.3)	14 (29.2)	0.002
Complications
Hypercalciuria, n (%)†	13 (16.5)	3 (42.9)	0.116‡
Chronic renal failure, n (%)	5 (6.1)	2 (1.9)	0.244‡
Nephrolithiasis, n (%)	3 (3.7)	1 (2.0)	1.000‡
Basal ganglia calcification, n (%)	3 (4.0)	0 (0.0)	0.564‡
Cataract, n (%)	11 (13.4)	16 (48.5)	< 0.001
Seizure, n (%)	3 (3.7)	7 (6.7)	0.358
Osteoporosis (T-score < -2.5), n (%)	1 (1.4)	1 (7.7)	0.287‡
Comorbidities
Hypertension, n (%)	29 (35.4)	55 (52.9)	0.017
Diabetes mellitus, n (%)	15 (18.3)	17 (16.3)	0.728
Dyslipidemia, n (%)	33 (40.2)	43 (41.7)	0.837
Depression or anxiety, n (%)	17 (20.7)	17 (16.3)	0.444
Ischemic heart and cerebrovascular disease, n (%)	5 (6.1)	10 (9.6)	0.383
Arrhythmia or heart failure, n (%)	5 (6.1)	2 (1.9)	0.244‡
Hepatosteatosis, n (%)	50 (61.0)	42 (85.7)	0.003

Hypercalciuria data available in n = 79 for endocrinology group and n = 7 for non-endocrinology group; Nephrolithiasis data available in n = 82 for endocrinology group and n = 49 for non-endocrinology group; Basal ganglia calcification data available in n = 75 for endocrinology group and n = 27 for non-endocrinology group; Osteoporosis data available in n = 71 for endocrinology group and n = 13 for non-endocrinology group; ‡ p-value calculated using Fisher’s exact test owing to small/sparse cell counts (expected cell count < 5), interpret with caution given small denominators. Bold p-values indicate statistical significance (p < 0.05). NS, not significant; eGFR, estimated glomerular filtration rate; PTH, parathyroid hormone

There were no significant differences between the groups regarding age (49.8 ± 12.1 vs. 49.2 ± 12.0 years; p = 0.340), age at diagnosis (36.4 ± 12.2 vs. 37.1 ± 10.4 years; p = 0.830), and sex distribution. Serum albumin-adjusted calcium, phosphate, magnesium, eGFR, and PTH levels were similar between groups (P > 0.05 for all). Daily doses of calcium supplementation and calcitriol were also comparable, with no statistically significant differences between groups.

Serum 25(OH)D levels were significantly higher in the endocrinology group compared with non-endocrinology clinics (30.5 ± 6.6 vs. 26.2 ± 7.7 ng/mL, p = 0.001). Target biochemical achievement differed substantially between groups. Calcium levels were within the target range in 96.3% of endocrinology-followed patients compared with 60.6% in other settings (p < 0.001). Phosphate target achievement was also significantly higher in the endocrinology group (53.7% vs. 38.5%; p = 0.039), as was 25(OH)D target achievement (57.3% vs. 29.2%; p = 0.002). There were no significant between-group differences in hypercalciuria or chronic kidney disease rates. Cataract was significantly more prevalent among patients followed in non-endocrinology clinics (48.5% vs. 13.4%; p < 0.001), as was hypertension (52.9% vs. 35.4%; p = 0.017). Given the small number of patients with available 24-hour urinary data in the non-endocrinology group (n = 7), and similarly restricted denominators for nephrolithiasis, basal ganglia calcification, osteoporosis, chronic kidney disease, and arrhythmia/heart failure, these comparisons were re-analyzed using Fisher’s exact test and should be interpreted with caution (Table 2).

Disease duration, calculated from the documented date of diagnosis to the date of the most recent follow-up visit, did not differ significantly between endocrinology- and non-endocrinology-followed patients (13.4 ± 8.6 vs. 12.1 ± 7.7 years; Mann–Whitney p = 0.329).

A marked disparity in the completeness of guideline-recommended diagnostic monitoring was also observed between groups (Table 3). Among endocrinology-followed patients, 24-hour urinary calcium collection, renal ultrasonography, ophthalmologic examination, and serum 25(OH)D and magnesium measurement were documented in 86–100% of patients, whereas the corresponding proportions in the non-endocrinology group ranged from only 6.7% (24-hour urinary calcium) to 78.8% (magnesium) (all p < 0.001). Cranial computed tomography and DXA were likewise performed far less frequently in the non-endocrinology group (26.0% and 12.5%, respectively, versus 91.5% and 86.6% among endocrinology-followed patients).

Table 3.

Completeness of guideline-recommended diagnostic assessment by follow-up setting

Diagnostic assessment	Endocrinology (n = 82)	Other clinics (n = 104)	p-value
24-hour urinary calcium collected, n/N (%)	79/82 (96.3)	7/104 (6.7)	< 0.001
Renal ultrasonography performed, n/N (%)	82/82 (100.0)	49/104 (47.1)	< 0.001
Cranial CT performed, n/N (%)	75/82 (91.5)	27/104 (26.0)	< 0.001
DXA performed, n/N (%)	71/82 (86.6)	13/104 (12.5)	< 0.001
Ophthalmologic examination documented, n/N (%)	60/82 (73.2)	38/104 (36.5)	< 0.001
Serum 25(OH)D measured, n/N (%)	82/82 (100.0)	48/104 (46.2)	< 0.001
Serum magnesium measured, n/N (%)	82/82 (100.0)	82/104 (78.8)	< 0.001

N denotes the number of patients with documented assessment data available out of the total number of patients in each follow-up group (Endocrinology, n = 82; Other clinics, n = 104). P-values were calculated using the chi-square test or Fisher’s exact test, as appropriate. CT, computed tomography; DXA, dual-energy X-ray absorptiometry; 25(OH)D, 25-hydroxyvitamin D

Predictors of target calcium achievement

A multivariate logistic regression analysis was performed to identify independent predictors of achieving target serum calcium levels (Table 4). Because complete data for all covariates, including serum 25(OH)D, were required for inclusion in the model, the analysis was restricted to 127 of the 186 patients (68.3%) with complete data on all variables; no formal a priori power calculation was performed, and the precision of estimates for covariates with wide confidence intervals (e.g., calcitriol dose) should be interpreted accordingly.

Table 4.

Multivariate logistic regression analysis: predictors of target serum calcium achievement

Variable	B	OR	95% CI	p-value
Follow-up setting (non-endocrinology vs. endocrinology)	−2.526	0.08	0.02–0.33	< 0.001
Age (years)	−0.013	0.99	0.93–1.05	0.662
Sex (male vs. female)	0.224	1.25	0.21–7.48	0.806
eGFR (mL/min/1.73 m²)	−0.012	0.99	0.92–1.07	0.761
PTH (pg/mL)	−0.019	0.98	0.89–1.08	0.692
Calcium supplementation dose (mg/day)	−0.001	0.99	0.998–1.001	0.278
Calcitriol dose (µg/day)	1.177	3.25	0.45–23.53	0.244
25(OH)D (ng/mL)	0.109	1.12	1.01–1.23	0.030

Bold values indicate statistical significance (p < 0.05). OR, odds ratio; CI, confidence interval; eGFR, estimated glomerular filtration rate; PTH, parathyroid hormone; 25(OH)D, 25-hydroxyvitamin D

Follow-up in non-endocrinology clinics was independently associated with significantly lower odds of target calcium achievement compared with endocrinology follow-up (OR: 0.08, 95% CI: 0.02–0.33; p < 0.001). Serum 25(OH)D level was independently and positively associated with target calcium achievement (OR: 1.12, 95% CI: 1.01–1.23; p = 0.030). Age, sex, eGFR, PTH level, daily calcium supplementation dose, and calcitriol dose were not independently associated with target calcium achievement. The model demonstrated adequate goodness-of-fit as assessed by the Hosmer–Lemeshow test (χ² = 12.59, df = 8, p = 0.127).

Discussion

In this real-world, single-center retrospective cohort of 186 patients with chronic HypoPT, endocrinology specialist follow-up was strongly and independently associated with improved biochemical target achievement. Patients managed in endocrinology clinics showed significantly higher rates of target calcium, phosphate, and 25(OH)D achievement compared with those followed in other settings. Non-endocrinology follow-up remained independently associated with markedly lower odds of target calcium achievement after adjustment for demographic, biochemical, and treatment-related variables. To the best of our knowledge, this is among the first real-world studies to directly evaluate the impact of follow-up setting on biochemical and clinical outcomes in chronic HypoPT.

The demographic and clinical characteristics of our cohort were broadly consistent with previously published HypoPT populations. The predominance of female patients (78.5%) and postsurgical etiology (82.3%) aligns with the Turkish HIPOPARATURK-NET study, the PARADIGHM registry, the Argentine Hipopara-Red cohort, and the Spanish multicenter cohort by Díez et al. [17–20]. The high proportion of malignant surgical pathology (57.5%), predominantly papillary thyroid carcinoma, reflects the referral pattern of our tertiary center. The rising incidence of thyroid cancer in Türkiye, partly attributed to overdiagnosis, may be contributing to an increasing burden of postsurgical HypoPT, and this should be considered when interpreting the generalizability of our findings [21].

Overall, 76.3% of patients achieved target serum calcium levels; however, phosphate and 25(OH)D targets were met in only 45.2% and 46.9%, respectively. Although magnesium levels appeared within the reference range in 97.6% of patients with available measurements, the mean magnesium level of 1.88 ± 0.14 mg/dL was close to the lower bound of the normal range (1.6–2.5 mg/dL), suggesting that many patients may be functioning near a suboptimal threshold without overt hypomagnesemia being detected. These results highlight a well-recognized limitation of conventional management: treatment targets in HypoPT extend beyond calcium alone, yet phosphate, magnesium, and vitamin D adequacy are frequently overlooked. Comparable gaps have been reported in other real-world cohorts; calcium was maintained in the normal range in only 46.1% in the HIPOPARATURK-NET study, hyperphosphatemia was present in 42% of patients in the Hipopara-Red cohort, and only 19.6% of patients met all four biochemical targets in a study by Önder et al. [17, 19, 22]. The persistent heterogeneity in monitoring practices across clinical settings, as also described in consensus reports, is reflected in our findings: systematic measurement of magnesium, 25(OH)D, and 24-hour urinary calcium was incomplete in the non-endocrinology group, highlighting the gap between guideline recommendations and clinical practice [14–16, 23].

The most striking finding was the magnitude of the difference in biochemical target achievement between groups: calcium target was achieved in 96.3% of endocrinology-followed patients versus 60.6% in other settings. Phosphate and vitamin D target achievement rates were also significantly higher among endocrinology-followed patients. Crucially, daily doses of calcium supplementation and calcitriol were comparable between groups, indicating that the benefit of specialist care is unlikely to be explained by more intensive pharmacological treatment or aggressive dosing alone. Rather, it may reflect differences in the quality and structure of disease management.

This interpretation is supported by the marked disparity in the completeness of monitoring and complication screening between groups. Patients followed outside endocrinology clinics were substantially less likely to undergo recommended assessments, including 24-hour urinary calcium measurement, serum 25(OH)D evaluation, renal ultrasonography, cranial computed tomography, and DXA assessment. Although some of these investigations are recommended selectively rather than universally, the overall pattern suggests less systematic surveillance of disease-related complications and treatment adequacy in non-specialized settings.

Current international guidelines emphasize that successful management of chronic HypoPT requires considerably more than prescribing calcium and active vitamin D analogues. Optimal care involves regular biochemical reassessment, individualized dose titration, attention to dietary calcium and phosphate intake, appropriate timing and distribution of calcium supplementation throughout the day, optimization of vitamin D status, and periodic evaluation for long-term complications [14, 15]. Accordingly, the superior biochemical outcomes observed in endocrinology-followed patients may reflect greater adherence to these comprehensive management principles rather than differences in medication dose itself.

Taken together, our findings suggest that under-monitoring and less structured disease management, rather than undertreatment, may represent the principal mechanism underlying the lower rates of biochemical target achievement observed in non-endocrinology settings.

In the multivariate model, 25(OH)D was an independent and positive predictor of target calcium achievement. Notably, serum 25(OH)D assessment was performed almost universally among endocrinology-followed patients, whereas monitoring was substantially less frequent in non-endocrinology settings. Together with the higher achieved 25(OH)D levels observed in the endocrinology group, these findings suggest that systematic vitamin D surveillance and optimization may be one mechanism through which specialist care improves biochemical control [24].

Beyond biochemical outcomes, two clinical findings merit attention. First, cataract was significantly more prevalent in patients followed outside endocrinology clinics (48.5% vs. 13.4%). The overall cataract prevalence in our cohort (23.5%) is consistent with the Turkish cohort [17]. In the literature, Ku et al. reported significantly higher risk of cataract, while Underbjerg et al. did not find an increased risk, and a meta-analysis reported cataract with 17% [4, 10, 25]. The striking between group difference may reflect cumulative exposure to suboptimal calcium phosphate balance in patients without dedicated specialist oversight, as lens calcification in HypoPT is related to chronic dysregulation of calcium-phosphate homeostasis. However, given the retrospective, cross-sectional nature of data, causality cannot be established and selection bias cannot be excluded. A longer duration of poorly controlled, fluctuating calcium-phosphate levels prior to the study window in non-endocrinology-followed patients could, in principle, also contribute to the higher cataract prevalence, since lens opacification accumulates over years. However, approximate overall disease duration did not differ significantly between groups (13.4 vs. 12.1 years, p = 0.329), arguing against differential disease chronicity alone as the explanation, although cumulative biochemical control quality over time, which could not be reconstructed retrospectively from single time-point measurements, remains a plausible unmeasured confounder. Furthermore, ophthalmologic assessment was itself substantially less complete in the non-endocrinology group (31.7% vs. 100% of patients; Table 3); because cataract was defined from documented diagnoses, the true between-group difference in cataract prevalence could be even larger than observed if undiagnosed cases in the less-screened group were identified, or, conversely, the comparison could be biased if ophthalmologic referral in non-endocrinology settings was preferentially triggered by symptomatic, more advanced disease. This ascertainment asymmetry further limits causal interpretation of the cataract finding.

Second, hypertension was more prevalent in the non-endocrinology group (52.9% vs. 35.4%). The overall hypertension burden (45.2%) and cardiovascular comorbidity profile observed in our cohort are consistent with growing literature documenting cardiovascular risk in HypoPT [6, 26]. A high prevalence of antihypertensive use has been documented in comparison with population-based controls in the German survey [11]. These findings should be interpreted cautiously given the observational design.

Hepatosteatosis, identified ultrasonographically in 70.2% of assessed patients, represents a novel and noteworthy finding. While hypertension, diabetes, and dyslipidemia have been documented as comorbidities in HypoPT, and metabolic dysfunction associated steatotic liver disease is increasingly prevalent globally, we are not aware of prior data specifically linking HypoPT with hepatic steatosis [10, 27, 28]. The observation warrants investigation in prospective studies with standardized hepatic assessment.

The skeletal phenotype of HypoPT is complex: increased BMD is well recognized, yet may not translate into reduced fracture risk, as bone microarchitecture and quality are altered beyond what standard DXA can capture [20, 29, 30]. Current guidelines recommend regular DXA monitoring in chronic HypoPT [14, 15]. In our cohort, DXA was performed in 84 patients; among those assessed, two cases of osteoporosis were identified, and no fragility fractures were recorded. The limited assessment rate introduces ascertainment bias, and systematic prospective evaluation with standardized protocols is warranted.

Incident comorbidities and complications are documented in the literature [11, 19, 20, 23]. The substantial burden of healthcare utilization observed in our cohort including ophthalmology (52.7%), neurology (32.3%), and emergency department visits (65.1% with at least one admission during follow-up) underscores the multisystem burden of HypoPT and the management challenges associated with conventional supplementation therapy, which does not replace the physiological functions of PTH [31].

Importantly, even among endocrinology-followed patients, phosphate and vitamin D targets were achieved in only 53.7% and 57.3%, respectively. These persistent biochemical gaps reflect a fundamental limitation of conventional therapy: calcium supplementation and active vitamin D analogues cannot fully replicate normal calcium-phosphate homeostasis [31, 32]. Recent guidelines and comprehensive reviews emphasize the growing evidence for PTH replacement as a more physiologically rational approach [14, 15, 29, 31, 32]. Our real-world data, demonstrating persistent biochemical shortfalls even under specialist care, lend further support to broader consideration of PTH replacement therapy in patients with inadequately controlled HypoPT, particularly those with frequent emergency presentations, ongoing hypercalciuria, or failure to achieve biochemical targets despite specialist management.

Several limitations of this study warrant consideration. First, and most importantly, patients followed in endocrinology clinics may differ systematically from those followed elsewhere with respect to disease severity, treatment adherence, health literacy, or ease of healthcare access. We cannot exclude the possibility that more engaged patients were preferentially retained in, or referred to, specialist follow-up, or conversely that less compliant patients defaulted to non-specialized care. Such selection effects may have contributed substantially to the observed associations, independent of any causal effect of follow-up setting itself.

The retrospective, single-center design limits the generalizability. As a tertiary referral center with a high thyroid and parathyroid surgery volume, our cohort likely includes a disproportionate number of patients with a postsurgical HypoPT following surgery for thyroid malignancy. Our findings may not be directly generalizable to primary care-based or community hospital-based HypoPT populations with a different etiological mix. The observational design precludes causal inference, particularly for the cross-sectionally assessed clinical complications (cataract, hypertension, and other comorbidities), for which temporality between exposure (follow-up setting) and outcome could not be established, and unmeasured confounders including patient adherence, health literacy, socioeconomic factors, and disease severity at the time of follow-up assignment may have contributed to the observed differences. No formal sensitivity analysis (e.g., multiple imputation) was performed to address missing biochemical and imaging data; given that missingness itself differed substantially by follow-up setting and was unlikely to be random, complete-case analyses for variables with extensive missingness (24-hour urinary calcium, vitamin D, and imaging-based complications) should be interpreted as conservative, exploratory estimates rather than definitive effect sizes. Biochemical data reflected only the most recent available measurements rather than longitudinal trajectories, limiting assessment of temporal trends. Monitoring completeness differed between groups, introducing information bias. This differential completeness, quantified directly in Table 3, means that between-group comparisons of complications with substantial missingness (hypercalciuria, nephrolithiasis, basal ganglia calcification, and osteoporosis) were likely underpowered, and the corresponding non-significant findings should not be interpreted as evidence of equivalence between groups. Quality of life data were not available. These limitations highlight the need for prospective multicenter studies with standardized monitoring protocols and longitudinal outcome assessment to better define the impact of specialist follow-up on long-term outcomes in HypoPT.

Conclusions

In this real-world single-center cohort, follow-up by endocrinology specialists was strongly associated with superior biochemical target achievement in patients with chronic HypoPT, independent of treatment doses. These findings suggest that the benefits of specialist care may extend beyond pharmacological treatment alone and may reflect more structured monitoring, optimization of conventional therapy, patient education, and systematic assessment of disease related complications. The substantial burden of emergency department utilization, cataract, hypertension, and the persistent gaps in phosphate and 25(OH)D target achievement underscore the ongoing challenges of long-term HypoPT management in routine clinical practice. Collectively, our findings support the integration of endocrinology specialist follow-up as a standard component of long-term HypoPT care and highlight the need for prospective multicenter studies to determine whether improved monitoring strategies and emerging treatment approaches can translate into better long-term clinical outcomes.

Abbreviations

HypoPT

Hypoparathyroidism

PTH

Parathyroid hormone

eGFR

Estimated glomerular filtration rate

DXA

Dual-energy X-ray absorptiometry

25(OH)D

25-hydroxyvitamin D

ICD-10

International Classification of Diseases, 10th Revision

SD

Standard deviation

OR

Odds ratio

CI

Confidence interval

CKD

Chronic kidney disease

IU

International unit

Author contributions

SDC: conceptualization, study design, data collection, data analysis, drafting and revision of the manuscript. MA: data collection, critical revision of the manuscript. Both authors read and approved the final manuscript.

Funding

This study received no specific funding from any public, commercial, or not-for-profit funding agency.

Data availability

The datasets generated and/or analyzed during the current study are not publicly available due to institutional and ethical restrictions regarding patient confidentiality but are available from the corresponding author on reasonable request, subject to approval by the relevant institutional ethics committee.

Declarations

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Prof. Dr. Cemil Taşcıoğlu City Hospital (approval number: 133; date: 30.03.2026). Due to the retrospective nature of the study, informed consent was waived by the ethics committee.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.