Apakah hiperparatiroidisme primer?
Hiperparatiroidisme primer (PHPT) adalah sejenis penyakit di mana kelenjar paratiroid (empat kelenjar terletak berhampiran atau pada tiroid di leher) membesar dan menghasilkan terlalu banyak hormon paratiroid. Penyakit ini menjejaskan 1% orang dewasa. Pengeluaran berlebihan hormon paratiroid akan mengganggu tahap kalsium di dalam badan, yang boleh menyebabkan pelbagai masalah kesihatan lain, seperti osteoporosis (penyakit yang melemahkan tulang) dan patah tulang, penyakit buah pinggang kronik, penyakit kardiovaskular, dan disfungsi kognitif (penurunan keupayaan mental), serta pengurangan kualiti hidup berkaitan kesihatan.
Bagaimanakah hiperparatiroidisme dirawat?
Paratiroidektomi (pembedahan pembuangan kelenjar atau kelenjar paratiroid yang tidak normal) ialah pilihan utama rawatan untuk penghidap PHPT. Paratiroidektomi dijangka dapat menyembuhkan PHPT dan memperbaiki komplikasi tidak diingini berkaitan penyakit ini.
Apa yang kami ingin ketahui?
Kami ingin mengetahui sama ada paratiroidektomi adalah lebih baik daripada terapi perubatan atau pemerhatian mudah untuk menyembuhkan PHPT ringan tanpa gejala dan memperbaiki komplikasi yang berkaitan penyakit seperti osteoporosis, ketumpatan tulang yang rendah, batu karang, penyakit buah pinggang, penyakit kardiovaskular (penyakit yang menjejaskan jantung dan saluran darah) dan disfungsi kognitif. Kami juga ingin menentukan sama ada paratiroidektomi mempunyai sebarang kesan yang tidak diingin dan sama ada ia akan meningkatkan kualiti hidup berkaitan kesihatan penghidap PHPT.
Apa yang telah kami lakukan?
Kami mencari kajian rawak terkawal (RCT) yang membandingkan paratiroidektomi dengan pilihan rawatan yang bukan pembedahan pada orang dewasa yang menghidap PHPT. Kami membandingkan dan merumuskan keputusan kajian dan menilai tahap keyakinan kami terhadap bukti berdasarkan faktor-faktor seperti kaedah dan saiz kajian.
Apa yang telah kami temui?
Kami mengenal pasti hanya lapan RCT, yang mendaftarkan 433 orang dewasa. Secara keseluruhan, 164 orang dewasa menjalani paratiroidektomi, dan 163 (99%) telah sembuh enam hingga 24 bulan selepas pembedahan. Berbanding dengan terapi perubatan atau pemerhatian mudah, paratiroidektomi mungkin boleh menghasilkan peningkatan besar dalam kadar kesembuhan. Kami tidak mempunyai maklumat tentang kesan paratiroidektomi pada osteoporosis atau penyakit kardiovaskular. Walau bagaimanapun, kajian yang disertakan melaporkan langkah-langkah yang berkait rapat dengan keadaan ini. Paratiroidektomi mungkin mempunyai sedikit atau tiada kesan pada ketumpatan mineral tulang belakang dan pinggul selepas satu hingga ke dua tahun, tetapi kami sangat tidak pasti dengan keputusan ini. Bukti mengenai kesan paratiroidektomi pada pecahan ejeksi ventrikel kiri (peratusan darah yang meninggalkan ruang jantung kiri pada setiap degupan jantung) juga sangat tidak pasti. Paratiroidektomi, berbanding dengan pemerhatian, mungkin mempunyai sedikit atau tiada kesan pada kejadian teruk yang tidak diingini atau pada kemasukan ke hospital untuk pembetulan tahap kalsium yang luar biasa tinggi dalam darah. Bukti yang didapati juga sangat tidak pasti mengenai kesan paratiroidektomi terhadap kematian akibat sebarang sebab. Akhirnya, tiga RCT melaporkan keputusan mengenai kualiti hidup berkaitan kesihatan. Penemuan adalah sangat berbeza antara satu sama lain, dan kami tidak pasti tentang kesan paratiroidektomi terhadap kualiti hidup berkaitan dengan kesihatan berbanding dengan pemerhatian.
Apakah batasan bukti?
Kami hanya sederhana yakin terhadap bukti mengenai kadar penyembuhan kerana laporan RCT tidak mengandungi maklumat yang mencukupi untuk membuktikan kaedah mereka boleh dipercayai. Walau bagaimanapun, kami mempunyai sedikit atau sangat sedikit keyakinan pada keputusan yang lain kerana kaedah kajian yang digunakan mungkin tidak boleh dipercayai, kajian tidak mengukur kesan PHPT secara langsung, dan kajian mendaftarkan sedikit peserta.
Sejauh manakah bukti ini terkini?
Bukti adalah terkini sehingga 26 November 2021.
In accordance with the literature, our review findings suggest that parathyroidectomy, compared to simple observation or medical (etidronate) therapy, probably results in a large increase in cure rates of PHPT (with normalisation of serum calcium and parathyroid hormone levels to laboratory reference values). Parathyroidectomy, compared with observation, may have little or no effect on serious adverse events or hospitalisation for hypercalcaemia, and the evidence is very uncertain about the effect of parathyroidectomy on other short-term outcomes, such as BMD, all-cause mortality and quality of life. The high uncertainty of evidence limits the applicability of our findings to clinical practice; indeed, this systematic review provides no new insights with regard to treatment decisions for people with (asymptomatic) PHPT. In addition, the methodological limitations of the included studies, and the characteristics of the study populations (mainly comprising white women with asymptomatic PHPT), warrant caution when extrapolating the results to other populations with PHPT.
Large-scale multi-national, multi-ethnic and long-term RCTs are needed to explore the potential short- and long-term benefits of parathyroidectomy compared to non-surgical treatment options with regard to osteoporosis or osteopenia, urolithiasis, hospitalisation for acute kidney injury, cardiovascular disease and quality of life.
Primary hyperparathyroidism (PHPT), a disorder in which the parathyroid glands produce excessive amounts of parathyroid hormone, is most common in older adults and postmenopausal women. While most people with PHPT are asymptomatic at diagnosis, symptomatic disease can lead to hypercalcaemia, osteoporosis, renal stones, cardiovascular abnormalities and reduced quality of life. Surgical removal of abnormal parathyroid tissue (parathyroidectomy) is the only established treatment for adults with symptomatic PHPT to prevent exacerbation of symptoms and to be cured of PHPT. However, the benefits and risks of parathyroidectomy compared to simple observation or medical therapy for asymptomatic and mild PHPT are not well established.
To evaluate the benefits and harms of parathyroidectomy in adults with PHPT compared to simple observation or medical therapy.
We searched CENTRAL, MEDLINE, LILACS, ClinicalTrials.gov and WHO ICTRP from their date of inception until 26 November 2021. We applied no language restrictions.
We included randomised controlled trials (RCTs) comparing parathyroidectomy with simple observation or medical therapy for the treatment of adults with PHPT.
We used standard Cochrane methods. Our primary outcomes were 1. cure of PHPT, 2. morbidity related to PHPT and 3. serious adverse events. Our secondary outcomes were 1. all-cause mortality, 2. health-related quality of life and 3. hospitalisation for hypercalcaemia, acute renal impairment or pancreatitis. We used GRADE to assess the certainty of the evidence for each outcome.
We identified eight eligible RCTs that included 447 adults with (mostly asymptomatic) PHPT; 223 participants were randomised to parathyroidectomy. Follow-up duration varied from six months to 24 months.
Of the 223 participants (37 men) randomised to surgery, 164 were included in the analyses, of whom 163 were cured at six to 24 months (overall cure rate 99%). Parathyroidectomy compared to observation probably results in a large increase in cure rate at six to 24 months follow-up: 163/164 participants (99.4%) in the parathyroidectomy group and 0/169 participants in the observation or medical therapy group were cured of their PHPT (8 studies, 333 participants; moderate certainty).
No studies explicitly reported intervention effects on morbidities related to PHPT, such as osteoporosis, osteopenia, kidney dysfunction, urolithiasis, cognitive dysfunction or cardiovascular disease, although some studies reported surrogate outcomes for osteoporosis and cardiovascular disease. A post-hoc analysis revealed that parathyroidectomy, compared to observation or medical therapy, may have little or no effect after one to two years on bone mineral density (BMD) at the lumbar spine (mean difference (MD) 0.03 g/cm 2 , 95% CI −0.05 to 0.12; 5 studies, 287 participants; very low certainty). Similarly, compared to observation, parathyroidectomy may have little or no effect on femoral neck BMD after one to two years (MD −0.01 g/cm 2 , 95% CI −0.13 to 0.11; 3 studies, 216 participants; very low certainty). However, the evidence is very uncertain for both BMD outcomes. Furthermore, the evidence is very uncertain about the effect of parathyroidectomy on improving left ventricular ejection fraction (MD −2.38%, 95% CI −4.77 to 0.01; 3 studies, 121 participants; very low certainty).
Four studies reported serious adverse events. Three of these reported zero events in both the intervention and control groups; consequently, we were unable to include data from these three studies in the pooled analysis. The evidence suggests that parathyroidectomy compared to observation may have little or no effect on serious adverse events (RR 3.35, 95% CI 0.14 to 78.60; 4 studies, 168 participants; low certainty).
Only two studies reported all-cause mortality. One study could not be included in the pooled analysis as zero events were observed in both the intervention and control groups. Parathyroidectomy compared to observation may have little or no effect on all-cause mortality, but the evidence is very uncertain (RR 2.11, 95% CI 0.20 to 22.60; 2 studies, 133 participants; very low certainty).
Three studies measured health-related quality of life using the 36-Item Short Form Health Survey (SF-36) and reported inconsistent differences in scores for different domains of the questionnaire between parathyroidectomy and observation.
Six studies reported hospitalisations for the correction of hypercalcaemia. Two studies reported zero events in both the intervention and control groups and could not be included in the pooled analysis. Parathyroidectomy, compared to observation, may have little or no effect on hospitalisation for hypercalcaemia (RR 0.91, 95% CI 0.20 to 4.25; 6 studies, 287 participants; low certainty). There were no reported hospitalisations for renal impairment or pancreatitis.
Diterjemah oleh Alya Nur Asmalina binti Ahmad Nazri (RCSI UCD Malaysia Campus). Disunting oleh Shazlin Shaharudin (Universiti Sains Malaysia). Untuk sebarang pertanyaan berkaitan terjemahan ini, sila hubungi cochrane@rcsiucd.edu.my