Evaluation of the Quality of Life in Moroccan Patients Diagnosed with Hypoparathyroidism

Objective Hypoparathyroidism (HPt) is a rare endocrine disorder often of postsurgical origin, resulting in hypocalcaemia. Several complications have been described including impairment of quality of life (QoL). Our study aims to evaluate the effect of hypoparathyroidism on the QoL of patients diagnosed with HPt. Methods A cross-sectional study was conducted in the Department of Endocrinology, Diabetology, Metabolic Diseases and Nutrition of the Hassan II University Hospital of Fez. We included in our study all patients followed for chronic HPt. Well-being was assessed using the WHO 5 index, and QoL was assessed by the SF-36 questionnaire in its validated Arabic version. Data were entered into Excel and analysed using SPSS 26. Multiple linear regression was utilized to ascertain the variables linked to the QoL in individuals diagnosed with HPt. Results A total of 143 patients with HPt were included in the study, 86.7% of whom were female. The mean age of the patients was 44.6 ± 17.3 years. 89.9% were of postsurgical etiology. The assessment of well-being by the WHO 5 index showed a low score (<50), meaning poor well-being in 44.8%. Regarding the QoL, the assessment showed low scores in the areas of general health (41.7), limitations due to physical condition (40.5), vitality (41.4), and limitations due to psychological condition (42.6). The multiple linear regression model revealed a noteworthy association between low SF-36 score and advanced age (β = −5.91; p < 0.001), surgical etiology (β = 8.71; p < 0.001), low education level (β = −10.1; p < 0.001), and poor compliance with medication (β = −11.3; p < 0.001). However, the relationship between impaired QoL and achievement of normocalcemia was nonsignificant (p=0.69). Conclusions Our work objective is that patients with HPt have a reduced and multifactorial QoL. Despite normocalcemia, it is hypothesized that parathyroid hormone directly influences QoL. These results could serve as a basis for future research.


Introduction
Hypoparathyroidism (HPt) is a rare endocrine disorder responsible for hypocalcemia and hyperphosphatemia due to insufcient levels of parathyroid hormone (PTH) [1].Te most common causes of HPt are postsurgical complications, genetic or autoimmune diseases [2].HPt often arises from thyroid surgery, primarily due to inadvertent damage to the parathyroid glands [3,4].
Te prevalence of HPt in the general population is not adequately documented.A Danish study found a prevalence of 24 cases of HPt per 100,000 population, with 22 postsurgical cases [5].Te reported incidence of chronic postsurgical HPt is highly variable, ranging from 0.3% to 17% [5,6].
In the realm of endocrine disorders, chronic HPt stands out as the sole condition where conventional treatment does not involve hormone replacement.Instead, it necessitates lifelong supplementation with calcium and active vitamin D analogs [7,8], coupled with regular monitoring.Nonetheless, the administration of calcium and vitamin D supplements does not fully reinstate the physiological balance of calcium and phosphorus [9].
Numerous short-and long-term complications have been documented.Büttner et al. [9] underscored a noteworthy supplementary aspect of HPt, specifcally the diminished quality of life (QoL) [9].Assessment of QoL in patients with HPt can help practitioners with optimal management and thus improve communication with patients to increase satisfaction and adherence to care.
As far as our awareness extends, no prior study has examined the infuence of chronic HPt on the QoL among Moroccan patients.
Consequently, our study aims to evaluate the QoL and explore its infuencing factors in Moroccan patients diagnosed with HPt.

Study Design.
A cross-sectional study was conducted at the Department of Endocrinology, Diabetology, Metabolic Diseases and Nutrition of the Hassan II University Hospital of Fez, over the period between January 2021 and January 2022.
Te Hassan II University Hospital of Fez is a regional reference center, and all patients with chronic HPt are treated and followed up in our department.

Inclusion Criteria.
Our study encompassed all patients aged 18 years followed for chronic HPt in our database of patients hospitalized in the department from 2010.HPt was characterized by hypocalcemia and low or inadequate serum PTH.
Confrmation of chronic HPt was established if the condition endured for a duration of ≥6 months and/or if the patient necessitated ongoing treatment with active vitamin D to sustain normocalcemia.
Te patients were contacted, and after elimination of the exclusion criteria, they were called during the period from January 2021 to January 2022 for a face-to-face interview (Figure 1).

Exclusion Criteria.
We excluded patients monitored for temporary hypoparathyroidism (those not meeting the criteria for chronic HPt), those with psychiatric conditions, difculties in comprehension or communication, incomplete medical records, and those who declined participation.

Data Collection.
Information was gathered from the medical records of patients diagnosed with chronic HPt under the care of the Department of Endocrinology, Diabetology, Metabolic Diseases, and Nutrition at Hassan II University Hospital in Fez.
Well-being was assessed using the WHO 5 index, and QoL was assessed by the SF-36 questionnaire in its validated Arabic version.Te collected data were recorded on an anonymous datasheet and subsequently incorporated into a computerized database.
Te data used to support the fndings of this study are available from the corresponding author upon request.

Sociodemographic Variables.
Age, sex, education level, and smoking status are the sociodemographic variables.

Clinical and Anthropometric
Variables.Comorbidities such as renal disease, neuropsychiatric conditions, musculoskeletal disorders, and cardiovascular diseases were checked.Additionally, we measured blood pressure, body mass index (BMI), and waist circumference.
Physical symptoms, cognitive, and emotional were assessed using a standard questionnaire based on patientreported complaints.

Paraclinical Variables.
Te results of X-rays (renal ultrasound, X-rays of limbs if necessary) and biological tests (calcium, albumin, PTH, phosphorus, vitamin D, magnesium, and others when necessary) were checked.
Normocalcemia is defned as a blood calcium level in the low normal range of the laboratory where the patient performed the test without causing hypercalciuria.Normocalcemia checked over the last 3 visits.
In general, the biological assessment brought during the consultation is recent, within the last week.

Questionnaires Used. Two questionnaires were used.
(1) Well-Being Was Assessed Using the WHO 5 Index.Five questions inquire about the patient's feelings over the preceding two weeks [10].Six response modalities on a frequency scale are possible: all the time (5), most of the time (4), more than half of the time (3), less than half of the time (2), occasionally (1), and never (0).An overall score is obtained by adding the responses to the fve items, then multiplying this result by 4. Te score ranges from 0 to 100, with a higher score indicating a better state of well-being.A threshold of less than 50 is commonly employed as a screening criterion for identifying individuals at risk of depression. 2 International Journal of Endocrinology (2) QoL Was Assessed by the SF-36 Questionnaire in Its Arabic Version.Te SF-36 questionnaire consists of 36 inquiries that address 8 domains related to both physical and mental health: physical functioning, role limitations due to physical health problems [11], physical pain, general health, vitality, social functioning, role limitations due to emotional health problems, and mental health.Scores on each of the subscales range from 0 to 100, where elevated scores signify enhanced physical functioning and psychological well-being.Terapeutic adherence was defned as acceptance of and compliance with treatment as prescribed.

Statistical Analysis.
Descriptive statistics were employed to depict sociodemographic information, clinical details, and QoL scores.Mean values and standard deviations represented quantitative variables, while percentages characterized qualitative variables.
Univariate analysis was utilized to identify factors linked to QoL, followed by multivariate analysis employing multiple linear regressions to ascertain factors associated with the scores.Te signifcance threshold was set at a p value <0.05.Statistical analyses were conducted using SPSS 26.0 software.

Ethics Statement.
All participants were treated with respect for anonymity and confdentiality.Informed consent was secured.

Population
Characteristics.159 patients were with chronic HPt, 149 were alive, and 143 patients completed the SF-36 questionnaire, resulting in a participation rate of 89.9% (Figure 1).
Te characteristics of the 143 patients are shown in Table 1.Te mean age of the patients was 44.6 ± 17.3 years.Tere was a clear female predominance (86.7%).WHO 5 Index.Te evaluation of well-being using the WHO 5 index revealed that 44.8% had a score below 50 [10], indicating a low level of well-being (Figure 2).

Assessment of Well-Being by the
A score below 50, indicating poor well-being, exhibited a signifcant correlation with advanced age (>60 years, p < 0.001) and the postsurgical etiology of HPt (p � 0.01).

SF-36 (Short Form 36
) QoL Assessment.Te symptoms reported by patients with HPt are summarized in Table 2 [11].

Factors Associated with
QoL. Te outcomes of the univariate analysis demonstrated a noteworthy correlation between diminished QoL (indicated by a lower SF-36 total score) and advanced age (>60 years, p < 0.001), postsurgical etiology (p � 0.004), inadequate therapy adherence (p < 0.031), as well as lower doses of calcium (p � 0.013) and active vitamin D supplementation (p � 0.012).However, the association between QoL and the attainment of normocalcemia was not statistically signifcant (p � 0.69) (Table 3).
Multivariate analysis by multiple linear regression revealed that the items signifcantly associated with lower HPt-related quality of life were advanced age (β � −5.91; p < 0.001) and surgical origin (β � 8.71; p < 0.001), whereas medication adherence and advanced education were signifcantly associated with better QoL (β � −11.3 and −10.1, respectively, p < 0.001), after adjustment for all variables.

Discussion
Our study found impaired QoL in patients with chronic HPt, with reduced well-being.
Research on the QoL of patients with HPt is relatively recent.Various publications, including a recent systematic review [9], have highlighted compromised QoL in patients with HPt undergoing "conventional treatment" with calcium and active vitamin D.  International Journal of Endocrinology 3 In these studies, the QoL outcomes for patients with HPt are assessed by comparing them either to suitable control groups or to the general population.
Te frst study examining the QoL in HPt originates from Germany.In this study, 25 women with postsurgical HPt were compared to 25 women who had undergone thyroidectomy without developing HPt.Te fndings indicated that women with postsurgical hypoparathyroidism reported a lower sense of well-being compared to the control group [12].
In our study, patients with chronic HPt exhibited diminished scores in all domains of the SF-36 questionnaire, indicating a reduced quality of life.Our fndings align with other studies utilizing the same SF-36 questionnaire [13,14], including Cusano et al. [13], who studied 54 patients with postsurgical and autoimmune HPt.Tey observed lower
What is particularly interesting in our study is that among the factors associated with reduced QoL, well-being was the postsurgical etiology.Tis can be explained by concomitant hypothyroidism, as hypothyroidism has already been shown to afect quality of life despite being on Lthyroxine treatment [19].Tus, our study implies that a combination of HPt and hypothyroidism has a greater impact on QoL than HPt itself, in line with comparable studies [12,15].
In our fndings, an association was observed between advanced age and lower quality of life (indicated by a low SF-36 score), a correlation that aligns with previous study results [9,15].Additionally, a higher level of education was identifed as having a positive infuence on the QoL for individuals with HPt.Tis observation is in line with fndings from other studies [13,17].Te reasoning behind this may be that individuals with a higher level of education tend to exhibit better compliance and self-management of the disease.
In our study, the lack of a signifcant association between impaired quality of life and the achievement of normocalcemia (p � 0.69) is consistent with research indicating that, despite calcium and vitamin D supplementation, many patients continue to experience physical, mental, or emotional symptoms [20].Tis suggests that parathyroid hormone (PTH) defciency itself may directly infuence the compromised quality of life.PTH receptors have been identifed in various regions of the central nervous system [21,22], and PTH defciency could impact diferent aspects of QoL.Investigations into PTH replacement therapy [13][14][15][16][17][18][19][20][21][22][23][24] have shown promising outcomes.Further studies are necessary to explore the efects of PTH treatment.
A notable strength of our study is the inclusion of an unselected group, encompassing all patients diagnosed with hypoparathyroidism (HPt).Tis approach renders the sample representative of all causes of HPt, and the study benefts from a relatively robust sample size.Additionally, comprehensive medical and surgical records were accessible for the current research.
Certain limitations should be acknowledged, particularly the face-to-face questionnaires.Tis subjective nature of the data introduces the potential for infuence or bias.

Conclusion
Our study aimed to assess the quality of life in patients with hypoparathyroidism (HPt) undergoing standard treatment, revealing impairment despite stable calcium and vitamin D levels.Several factors, including advanced age and a postsurgical etiology, were associated with reduced quality of life, while a higher education level correlated with better quality of life.
It is hypothesized that parathyroid hormone defciency directly impacts the quality of life, prompting interest in recommending recombinant PTH for HPt management.
Tese fndings could serve as a foundation for further research into the disease burden, encompassing a study of both the direct and indirect costs associated with the condition.

Figure 2 :
Figure 2: Assessment of well-being by the WHO 5 index.

Figure 3 :
Figure 3: QoL in HPt patients according to the SF-36 score (scores on each of the subscales range from 0 to 100, where elevated scores signify enhanced physical functioning and psychological well-being).

Table 1 :
Descriptive data for patients with chronic HPt.

Table 2 :
Symptoms reported by patients with HPt.

Table 3 :
QoL of patients with chronic HPt.