Clinical burden and healthcare resource utilization among patients with chronic hypoparathyroidism, overall and by adequately vs not adequately controlled disease: a multi-country chart review

Figures & data

Figure 1. Cross-sectional burden of illness design. Demographic characteristics were collected as of the day of initial hypoparathyroidism diagnosis. Hypoparathyroidism-related HRU, symptoms, and comorbidities were collected during the 1-year period prior to the date of chart abstraction. Current treatments and laboratory values were collected on the chart abstraction date and reflect the last recorded treatments and tests. Abbreviation. HRU, health resource utilization.

Table 1. Demographic and disease characteristics, current treatments,^a and current laboratory values^a of all patients with hypoparathyroidism.

Patient characteristics, current treatments, and current laboratory values	All patients (N = 614)
Patient characteristics
Age (years), mean ± SD	43.6 ± 14.8
Sex, n (%)
Female	378 (61.6%)
Male	236 (38.4%)
Race, n (%)
Asian	44 (7.2%)
Black	34 (5.5%)
Caucasian	484 (78.8%)
Hispanic	35 (5.7%)
Other	12 (2.0%)
Pacific Islander	1 (0.2%)
Unknown	4 (0.7%)
Hypoparathyroidism type, n (%)
Autoimmune (acquired)	84 (13.7%)
DiGeorge syndrome (congenital)	14 (2.3%)
Idiopathic	57 (9.3%)
Kearns-Sayre syndrome (congenital)	2 (0.3%)
Post-surgical (acquired)	457 (74.4%)
Hypoparathyroidism duration (months), mean ± SD	46.0 ± 56.8
Current treatment
Oral calcium and vitamin D supplement, n (%)	486 (79.2%)
Oral calcium supplements, n (%)	564 (91.9%)
Oral calcium carbonate, n (%)	508 (82.7%)
Oral calcium carbonate dose (g/d), mean ± SD	1.8 ± 1.0
Oral calcium citrate, n (%)	55 (9%)
Oral calcium citrate dose (g/d), mean ± SD	1.7 ± 1.2
Other calcium supplement, n (%)	7 (1.1%)
Other calcium supplement dose (g/d), mean ± SD	1.3 ± 1.0
Active vitamin D, n (%)	530 (86.3%)
Calcitriol, n (%)	358 (58.3%)
Calcitriol dose (mcg/d), mean ± SD	6.4 ± 17.6
Alfacalcidol, n (%)	120 (19.5%)
Alfacalcidol dose (mcg/d), mean ± SD	3.1 ± 11.0
Thiazide diuretics
Hydrochlorothiazide, n (%)	83 (13.5%)
Hydrochlorothiazide dose (mg/d), mean ± SD	24.8 ± 16.6
Chlorthalidone, n (%)	5 (0.8%)
Chlorthalidone dose (mg/d), mean ± SD	130.0 ± 207.2
Parathyroid hormone
rhPTH (1-84), n (%)	25 (4.1%)
rhPTH (1-84) dose (mcg/day), mean ± SD	49.2 ± 24.4
rhPTH (1-34), n (%)	20 (3.3%)
rhPTH (1-34) dose (mcg/day), mean ± SD	25.8 ± 9.9
Current laboratory values
Serum calcium
n (%)	603 (98.2%)
mmol/L, mean ± SD	2.4 ± 2.2
Urine calcium
n (%)	186 (30.3%)
mmol/24 h, mean ± SD	5.5 ± 3.8
Serum phosphate
n (%)	383 (62.4%)
mmol/L, mean ± SD	1.2 ± 0.7
Serum magnesium
n (%)	187 (30.5%)
mmol/L, mean ± SD	0.6 ± 0.3
Parathyroid hormone intact
n (%)	332 (54.1%)
ng/L, mean ± SD	9.5 ± 14.3
Serum creatinine
n (%)	388 (63.2%)
µmol/L, mean ± SD	85.1 ± 23.1
Glomerular filtration rate^b
n (%)	422 (68.7%)
mL/min/1.73 m^2, mean ± SD	89.1 ± 49.4
Serum bone-specific alkaline phosphatase
n (%)	45 (7.3%)
mcg/L, mean ± SD	81.8 ± 48.6

^a Refers to the latest treatments and laboratory values at the time of chart abstraction.

^b Reported eGFR value or calculated from serum creatinine using CKD-EPI creatinine equation¹⁸. The reported values were prioritized, and values were calculated for patients who did not have the value reported.

Abbreviations. CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate; n, number; rhPTH, recombinant human parathyroid hormone; SD, standard deviation.

Table 2. Hypoparathyroidism-related symptoms during the 1-year study period among all patients with hypoparathyroidism.

Symptoms,^a n (%)	All patients (N = 614)
Any selected symptoms	365 (59.4%)
Physical
Chest pain	25 (4.1%)
Facial spasm	54 (8.8%)
Fatigue	206 (33.6%)
Headache	91 (14.8%)
Hypoesthesia (facial or oral)	72 (11.7%)
Joint or bone pain	53 (8.6%)
Muscle cramping/pain/fatigue/myalgia	142 (23.1%)
Muscle tightness	60 (9.8%)
Muscle spasms/tetany/muscle twitching	97 (15.8%)
Musculoskeletal pain/stiffness	54 (8.8%)
Paresthesia (including oral)	115 (18.7%)
Tremor	10 (1.6%)
Cognitive
Brain fog/mental lethargy	66 (10.7%)
Inability to focus or concentrate	90 (14.7%)
Inability to multitask	38 (6.2%)
Inability to think through a complicated task	16 (2.6%)
Memory loss or forgetfulness	64 (10.4%)
Sleep disturbances	55 (9.0%)
Emotional
Anxiety/fear/inner unrest	81 (13.2%)
Emotional sensitiveness	60 (9.8%)
Feeling misunderstood/not understood	14 (2.3%)
Feeling sad/down/blue/depressed	39 (6.4%)
Hyperirritability/being hypercritical	27 (4.4%)
Irritability	68 (11.1%)
Nervousness	50 (8.1%)
Social withdrawal/feeling isolated	12 (2.0%)

^a A patient could have more than one symptom.

Abbreviations. n, number; SD, standard deviation.

Table 3. Hypoparathyroidism-related comorbidities during the 1-year study period among all patients with hypoparathyroidism.

Comorbidities,^a n (%)	All patients (N = 614)
Any selected comorbidity	287 (46.7%)
Brain/central nervous system	65 (10.6%)
Basal ganglia calcification	21 (3.4%)
Cerebrovascular disease	8 (1.3%)
Neuropathy	28 (4.6%)
Seizures or convulsions	10 (1.6%)
Other brain/CNS comorbidities	6 (1.0%)
Blood	1 (0.2%)
Leukemia	1 (0.2%)
Other blood comorbidities	0 (0.0%)
Cardiovascular and metabolic disorders	124 (20.2%)
Calcification of cardiac arteries	7 (1.1%)
Cardiac arrhythmia	17 (2.8%)
Cardiac insufficiency	7 (1.1%)
Chronic heart disease	8 (1.3%)
Diabetes without end-organ damage	26 (4.2%)
Hypertension	76 (12.4%)
Ischemic heart disease	9 (1.5%)
QT prolongation	11 (1.8%)
Other cardiovascular and metabolic comorbidities	14 (2.3%)
Connective tissue disease	2 (0.3%)
Edema	10 (1.6%)
Eyes	22 (3.6%)
Cataract formation	21 (3.4%)
Other eye comorbidities	1 (0.2%)
Gastrointestinal system	69 (11.2%)
Constipation	62 (10.1%)
Other stomach/liver/digestive comorbidities	9 (1.5%)
Hemiplegia	0 (0.0%)
Imbalance of calcium/phosphate	130 (21.2%)
Hypercalcemia	21 (3.4%)
Hypercalciuria	26 (4.2%)
Hyperphosphatemia	28 (4.6%)
Hypocalcemia	101 (16.4%)
Other imbalances	0 (0.0%)
Infectious disease	7 (1.1%)
Lung/respiratory	20 (3.3%)
Bronchospasm	7 (1.1%)
Chronic obstructive pulmonary disease	6 (1.0%)
Shortness of breath	7 (1.1%)
Other lung/respiratory comorbidities	9 (1.5%)
Musculoskeletal	42 (6.8%)
Decreased bone mineral density	25 (4.1%)
Tetany	15 (2.4%)
Other musculoskeletal comorbidities	6 (1.0%)
Neuropsychiatric	103 (16.8%)
Anxiety	70 (11.4%)
Cognitive impairment	17 (2.8%)
Dementia	6 (1.0%)
Depression	42 (6.8%)
Other neuropsychiatric comorbidities	1 (0.2%)
Renal	35 (5.7%)
Chronic kidney disease	11 (1.8%)
Nephrocalcinosis	8 (1.3%)
Nephrolithiasis/renal stone	12 (2.0%)
Renal calcification	7 (1.1%)
Other renal comorbidities^b	4 (0.7%)
Solid tumor with metastasis	2 (0.3%)
Solid tumor without metastasis	2 (0.3%)
Other comorbidities^c	4 (0.7%)

^a A patient could have more than one comorbidity.

^b Other renal comorbidities include acute renal failure and calcinosis.

^c Other comorbidities include alcoholic cirrhosis, Cowden syndrome, multiple endocrine neoplasia, thyroid cancer.

Abbreviations. CNS, central nervous system; n, number; QT, time interval between the start of the Q wave and the end of the T wave in the heart’s electrical cycle.

Table 4. Hypoparathyroidism-related health resource utilization during the 1-year study period among all patients with hypoparathyroidism.

Hypoparathyroidism-related health resource utilization	All patients (N = 614)
Patients with at least one hospitalization, ER, or OP visit, n (%)	557 (90.7%)
Patients with at least one hospitalization, n (%)	120 (19.5%)
Number of hospitalizations, mean ± SD	1.5 ± 1.4
Number of hospitalizations for management of hypoparathyroidism, mean ± SD	1.4 ± 0.8
Number of hospitalizations for management of hypoparathyroidism-related comorbidities,^a mean ± SD	1.5 ± 1.6
Number of other hospitalizations, mean ± SD	1.2 ± 0.6
Patients with at least one ER visit, n (%)	252 (41.0%)
Number of ER visits, mean ± SD	2.4 ± 1.8
Number of ER visits for management of hypoparathyroidism, mean ± SD	2.0 ± 1.2
Number of ER visits for management of hypoparathyroidism-related comorbidities,^a mean ± SD	1.5 ± 1.1
Number of ER visits for management of treatment adverse events, mean ± SD	1.4 ± 0.7
Number of other ER visits	2.4 ± 2.0
Patients with at least one OP visit, n (%)	539 (87.8%)
Number of OP visits, mean ± SD	3.3 ± 2.2
Number of OP visits for management of hypoparathyroidism, mean ± SD	2.8 ± 1.6
Number of OP visits for management of hypoparathyroidism-related comorbidities,^a mean ± SD	1.9 ± 1.3
Number of OP visits for management of treatment adverse events, mean ± SD	1.5 ± 1.2
Number of other OP visits, mean ± SD	2.4 ± 1.5

^a Renal stone, neuropathy, etc.

The study period was the 1-year period prior to chart abstraction. The definitions of NAC and AC are described in the ‘Patient cohorts’ section of the Methods.

Abbreviations. AC, adequately controlled; ER, emergency room; n, number; NAC, not adequately controlled; OP, outpatient; SD, standard deviation.

Figure 2. Proportions of patients with AC and NAC hypoparathyroidism. The definitions of guideline-based NAC are described in the ‘Patient cohorts’ section of the Methods. Abbreviations. AC, adequately controlled; N, number; NAC, not adequately controlled.

Table 5. Comparisons of demographic and disease characteristics and current treatments^a between patients with NAC and AC disease.

Patient characteristics and current treatments	NAC (n = 172)	AC (n = 442)	NAC vs AC p-value
Demographic and disease characteristics
Age (years), mean ± SD	43.7 ± 14.3	43.5 ± 15.0	0.88
Sex, n (%)
Female	108 (62.8%)	270 (61.1%)	0.77
Male	64 (37.2%)	172 (38.9%)
Race, n (%)
Asian	9 (5.2%)	35 (7.9%)	0.52
Black	7 (4.1%)	27 (6.1%)
Caucasian	140 (81.4%)	344 (77.8%)
Hispanic	13 (7.6%)	22 (5.0%)
Other	3 (1.7%)	9 (2.0%)
Pacific Islander	0 (0.0%)	1 (0.2%)
Unknown	0 (0.0%)	4 (0.9%)
Hypoparathyroidism type, n (%)
Autoimmune (acquired)	25 (14.5%)	59 (13.3%)	0.70
DiGeorge syndrome (congenital)	2 (1.2%)	12 (2.7%)
Idiopathic	16 (9.3%)	41 (9.3%)
Kearns-Sayre syndrome (congenital)	1 (0.6%)	1 (0.2%)
Post-surgical (acquired)	128 (74.4%)	329 (74.4%)
Hypoparathyroidism duration (months), mean ± SD	42.2 ± 47.8	47.5 ± 59.9	0.30
Current treatment
Oral calcium and vitamin D supplement, n (%)	145 (84.3%)	341 (77.1%)	0.06
Oral calcium supplements, n (%)	162 (94.2%)	402 (91.0%)	0.25
Oral calcium carbonate, n (%)	147 (85.5%)	361 (81.7%)	0.32
Oral calcium carbonate dose (g/day), mean ± SD	1.9 ± 1.2	1.7 ± 9.3	0.07
Oral calcium citrate, n (%)	16 (9.3%)	39 (8.8%)	0.98
Oral calcium citrate dose (g/d), mean ± SD	1.7 ± 1.0	1.7 ± 1.3	0.93
Other calcium supplement, n (%)	1 (0.6%)	6 (1.4%)	0.68
Other calcium supplement dose (g/day), mean ± SD	0.6 ± 0.0	1.4 ± 1.1	0.53
Active vitamin D, n (%)	153 (89.0%)	377 (85.3%)	0.29
Calcitriol, n (%)	106 (61.6%)	252 (57.0%)	0.57
Calcitriol dose (mcg/day), mean ± SD	9.3 ± 20.9	5.2 ± 15.9	<0.05^b
Alfacalcidol, n (%)	31 (18.0%)	89 (20.1%)	0.23
Alfacalcidol dose (mcg/day), mean ± SD	3.8 ± 8.7	2.9 ± 11.7	0.69
Thiazide diuretics
Hydrochlorothiazide, n (%)	33 (19.2%)	50 (11.3%)	<0.05^b
Hydrochlorothiazide dose (mg/day), mean ± SD	28.3 ± 22.0	22.4 ± 11.3	0.12
Chlorthalidone, n (%)	3 (1.7%)	2 (0.5%)	0.14
Chlorthalidone dose (mg/day), mean ± SD	41.7 ± 14.4	262.5 ± 335.9	0.30
Parathyroid hormone
rhPTH (1-84), n (%)	13 (7.6%)	12 (2.7%)	<0.05^b
rhPTH (1-84) dose (mcg/day), mean ± SD	43.4 ± 21.5	55.4 ± 26.8	0.23
rhPTH (1-34), n (%)	10 (5.8%)	10 (2.3%)	<0.05^b
rhPTH (1-34) dose (mcg/day), mean ± SD	20.0 ± 0.0	31.5 ± 11.6	<0.01^b

^a Refers to the latest treatments at the time of chart abstraction.

^b Statistically significant difference at p < 0.05.

The definitions of NAC and AC are described in the ‘Patient cohorts’ section of the Methods.

Abbreviations. AC, adequately controlled; NAC, not adequately controlled; n, number; rhPTH, recombinant human parathyroid hormone; SD, standard deviation.

Table 6. Comparisons of hypoparathyroidism-related comorbidities during the 1-year study period between patients with NAC and AC disease.

Comorbidities, n (%)	NAC (n = 172)	AC (n = 442)	NAC vs AC p-value
Any selected comorbidity	99 (57.6%)	188 (42.5%)	<0.01^c
Brain/central nervous system	29 (16.9%)	36 (8.1%)	<0.01^c
Basal ganglia calcification	11 (6.4%)	10 (2.3%)	<0.05^c
Cerebrovascular disease	4 (2.3%)	4 (0.9%)	0.23
Neuropathy	12 (7.0%)	16 (3.6%)	0.12
Seizures or convulsions	3 (1.7%)	7 (1.6%)	1.00
Other brain/CNS comorbidities	2 (1.2%)	4 (0.9%)	0.67
Blood	0 (0.0%)	1 (0.2%)	1.00
Leukemia	0 (0.0%)	1 (0.2%)	1.00
Other blood comorbidities	0 (0.0%)	0 (0.0%)
Cardiovascular and metabolic disorders	45 (26.2%)	79 (17.9%)	<0.05^c
Calcification of cardiac arteries	5 (2.9%)	2 (0.5%)	<0.05^c
Cardiac arrhythmia	7 (4.1%)	10 (2.3%)	0.27
Cardiac insufficiency	2 (1.2%)	5 (1.1%)	1.00
Chronic heart disease	4 (2.3%)	4 (0.9%)	0.23
Diabetes without end-organ damage	9 (5.2%)	17 (3.8%)	0.59
Hypertension	25 (14.5%)	51 (11.5%)	0.38
Ischemic heart disease	2 (1.2%)	7 (1.6%)	1.00
QT prolongation	7 (4.1%)	4 (0.9%)	<0.05^c
Other cardiovascular and metabolic comorbidities	7 (4.1%)	7 (1.6%)	0.07
Connective tissue disease	1 (0.6%)	1 (0.2%)	0.48
Edema	1 (0.6%)	9 (2.0%)	0.30
Eyes	8 (4.7%)	14 (3.2%)	0.52
Cataract formation	7 (4.1%)	14 (3.2%)	0.76
Other eye comorbidities	1 (0.6%)	0 (0.0%)	0.28
Gastrointestinal system	22 (12.8%)	47 (10.6%)	0.54
Constipation	22 (12.8%)	40 (9.0%)	0.22
Other stomach/liver/digestive comorbidities	1 (0.6%)	8 (1.8%)	0.22
Hemiplegia	0 (0.0%)	0 (0.0%)
Imbalance of calcium/phosphate	51 (29.7%)	79 (17.9%)	<0.01^c
Hypercalcemia	6 (3.5%)	15 (3.4%)	1.00
Hypercalciuria	12 (7.0%)	14 (3.2%)	0.06
Hyperphosphatemia	14 (8.1%)	14 (3.2%)	<0.05^c
Hypocalcemia	38 (22.1%)	63 (14.3%)	<0.05^c
Other imbalances	0 (0.0%)	0 (0.0%)
Infectious disease	4 (2.3%)	3 (0.7%)	0.10
Lung/respiratory	9 (5.2%)	11 (2.5%)	0.14
Bronchospasm	4 (2.3%)	3 (0.7%)	0.10
Chronic obstructive pulmonary disease	3 (1.7%)	3 (0.7%)	0.36
Shortness of breath	4 (2.3%)	3 (0.7%)	0.10
Other lung/respiratory comorbidities	4 (2.3%)	5 (1.1%)	0.28
Musculoskeletal	16 (9.3%)	26 (5.9%)	0.18
Decreased bone mineral density	8 (4.7%)	17 (3.8%)	0.82
Tetany	6 (3.5%)	9 (2.0%)	0.38
Other musculoskeletal comorbidities	4 (2.3%)	2 (0.5%)	0.05
Neuropsychiatric	37 (21.5%)	66 (14.9%)	0.07
Anxiety	22 (12.8%)	48 (10.9%)	0.59
Cognitive impairment	7 (4.1%)	10 (2.3%)	0.27
Dementia	2 (1.2%)	4 (0.9%)	0.67
Depression	20 (11.6%)	22 (5.0%)	<0.01^c
Other neuropsychiatric comorbidities	0 (0.0%)	1 (0.2%)	1.00
Renal	18 (10.5%)	17 (3.8%)	<0.01^c
Chronic kidney disease	6 (3.5%)	5 (1.1%)	0.08
Nephrocalcinosis	5 (2.9%)	3 (0.7%)	<0.05^c
Nephrolithiasis/renal stone	4 (2.3%)	8 (1.8%)	0.75
Renal calcification	4 (2.3%)	3 (0.7%)	0.10
Other renal comorbidities^a	3 (1.7%)	1 (0.2%)	0.07
Solid tumor with metastasis	2 (1.2%)	0 (0.0%)	0.08
Solid tumor without metastasis	1 (0.6%)	1 (0.2%)	0.48
Other comorbidities^b	1 (0.6%)	3 (0.7%)	0.84

^a Other renal comorbidities include acute renal failure and calcinosis.

^b Other comorbidities include alcoholic cirrhosis, Cowden syndrome, multiple endocrine neoplasia, and thyroid cancer.

^c Statistically significant difference at p < 0.05.

The study period was the 1-year period prior to chart abstraction. The definitions of NAC and AC are described in the ‘Patient cohorts’ section of the Methods.

Abbreviations. AC, adequately controlled; CNS, central nervous system; NAC, not adequately controlled; n, number; QT, time interval between the start of the Q wave and the end of the T wave in the heart’s electrical cycle.

Table 7. Comparisons of hypoparathyroidism-related health resource utilization between patients with NAC and AC disease during the 1-year study period.

Hypoparathyroidism-related health resource utilization	NAC (n = 172)	AC (n = 442)	NAC vs AC p-value
Patients with at least one hospitalization, ER, or OP visit, n (%)	159 (92.4%)	398 (90.0%)	0.44
Patients with at least one hospitalization, n (%)	48 (27.9%)	72 (16.3%)	<0.01^b
Number of hospitalizations, mean ± SD	0.5 ± 1.3	0.2 ± 0.5	<0.001^b
Patients with at least one ER visit, n (%)	82 (47.7%)	170 (38.5%)	<0.05^b
Number of ER visits, mean ± SD	1.2 ± 2.1	0.9 ± 1.4	<0.05^b
ER visits for management of hypoparathyroidism, mean ± SD	0.9 ± 1.3	0.7 ± 1.1	0.07
ER visits for management of hypoparathyroidism-related comorbidities,^a mean ± SD	0.2 ± 0.8	0.1 ± 0.4	<0.01^b
ER visits for management of treatment adverse events, mean ± SD	0.1 ± 0.4	0.1 ± 0.3	0.26
Other ER visits	0.0 ± 0.1	0.0 ± 0.4	0.30
Patients with at least one OP visit, n (%)	154 (89.5%)	385 (87.1%)	0.49
Number of OP visits, mean ± SD	3.6 ± 3.0	2.6 ± 2.0	<0.001^b
OP visits for management of hypoparathyroidism, mean ± SD	2.9 ± 2.0	2.3 ± 1.6	<0.001^b
OP visits for management of hypoparathyroidism-related comorbidities,^a mean ± SD	0.5 ± 1.2	0.2 ± 0.7	<0.01^b
OP visits for management of treatment adverse events, mean ± SD	0.2 ± 0.8	0.1 ± 0.4	0.17
Other OP visits, mean ± SD	0.0 ± 0.2	0.0 ± 0.3	0.62

^aRenal stone, neuropathy, etc.

^bStatistically significant difference at p < 0.05.

The study period was the 1-year period prior to chart abstraction. The definitions of NAC and AC are described in the ‘Patient cohorts’ section of the Methods.

Abbreviations. AC, adequately controlled; ER, emergency room; n, number; NAC, not adequately controlled; OP, outpatient; SD, standard deviation.

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