Primary hyperparathyroidism (PHPT) is a common endocrine disease characterized by hypercalcemia due to inappropriately high parathyroid hormone secretion. While in the typical, symptomatic form of the disease diagnosis is set easily and standard management is surgical removal of the hyperfunctioning parathyroid (HP), this may not be the case in more subtle forms of PHPT, such as the asymptomatic and the normocalcemic PHPT. Localization of the HP could also be challenging, especially in small-sized adenomas, ectopic lesions or multiglandular disease. An experienced surgical team is essential to achieve curative parathyroidectomy. In this article, we used illustrative clinical vignettes to dissect the approach to the patient with PHPT, from the diagnosis establishment to the suggested investigation to identify classical and non-classical PHPT features and the methodology to locate the abnormal tissue. Accordingly, we elaborated on appropriate management, both surgical and conservative.

OBJECTIVE: Multiple groups have created clinical practice guidelines (CPGs) for the management of primary hyperparathyroidism (PHPT). This report provides a rigorous quality assessment using the Appraisal of Guidelines for Research & Evaluation Instrument (AGREE II) to identify high-performing guidelines and areas for improvement.
METHODS: A systematic review was conducted to isolate CPGs addressing the management of PHPT. Guideline data was extracted and quality ratings were assigned by four independent reviewers. Intraclass correlation coefficients (ICC) were calculated to ensure interrater reliability.
RESULTS: Twelve guidelines were assessed. The American Association of Endocrine Surgeons (AAES) guideline had the highest mean scaled score across all domains (73.6 ± 31.4%). No other published guideline achieved a \"high\" quality designation. The highest scoring domain was \"clarity of presentation\" (mean 60.5 ± 26.5%). The lowest scoring domain was \"applicability\" (mean 19.8 ± 18.2%). Scoring reliability was excellent, with ICC ≥ 0.89 for all AGREE II 6 domains.
CONCLUSIONS: Although several working groups have developed guidelines to address PHPT management, only those published by the AAES meet all methodologic quality criteria necessary to ensure incorporation of recommendations into clinical practice. Future guidelines would benefit from the development of tools, resources, monitoring criteria that enhance applicability.

The clinical manifestation of multiple endocrine neoplasia type 2 (MEN2) in terms of developing medullary thyroid cancer (MTC), pheochromocytoma (PCC), and/or primary hyperparathyroidism (PHPT) is related to the respective pathogenic variant of the RET proto-oncogene. The aim of this study is to retrospectively analyze the individual, genotype-dependent clinical manifestations of a large cohort of MEN2 patients. By comparing their clinical profile with currently existing evidence-based knowledge, an optimal therapy and prevention strategy in terms of prophylactic thyroidectomy and clinical follow-up could be ensured. This is a retrospective single-center study of 158 MEN2 patients who were diagnosed and/or surgically treated at a tertiary referral care center between 1990 and 2022. All participants were categorized according to their pathogenic variant of the RET proto-oncogene. Subsequently, the clinical manifestation of the disease and its time of occurrence was documented. Our analysis showed results in line with existing studies, except for a considerably lower-than-predicted occurrence of PCC in patients with V804M/L mutations. This study supports the current recommendation regarding the pathogenic variant-dependent management of this rare cancer-associated syndrome.

OBJECTIVE: The purpose of this review is to provide updated recommendations for the surgical management of primary (pHPT) and renal (rHPT) hyperparathyroidism, formulating a new guideline of the German Association of Endocrine Surgeons (CAEK).
METHODS: Evidence-based recommendations for the diagnosis and therapy of pHPT and rHPT were assessed by a multidisciplinary panel using PubMed for a comprehensive literature search together with a structured consensus dialogue (S2k guideline of the Association of the German Scientific Medical Societies, AWMF).
RESULTS: During the last 20 years, a variety of new preoperative localization procedures, such as sestamibi-SPECT, 4D-CT, and various PET/CT procedures, were established for pHPT. High-resolution imaging, together with intraoperative parathyroid hormone (IOPTH) measurement, enabled focused or minimally invasive surgery to become the most favored surgical technique. Patients with pHPT and nonlocalizing imaging have a higher risk of multiglandular disease. Surgical therapy provides very high cure rates, with a clear relation to the surgeon\'s experience in parathyroid procedures. Reoperative parathyroidectomy, children with pHPT or familial forms, and parathyroid carcinoma are addressed and require special surgical expertise. A multidisciplinary team of experienced nephrologists, transplant, and endocrine surgeons should assess the diagnosis and treatment of renal HPT.
CONCLUSIONS: Surgery is the only curative treatment for pHPT and should be considered for all patients with pHPT. For rHPT, a more selective approach is required, and parathyroidectomy is indicated only when conservative treatment options fail. In parathyroid carcinoma, the adequacy of local resection influences local disease control.

OBJECTIVE: The aim of this study was to determine the adherence to consensus guidelines on preoperative imaging of patients with primary hyperparathyroidism (pHPT) in real local practice.
METHODS: This was a retrospective multicenter cohort study of 411 patients undergoing parathyroidectomy for pHPT from 2007 to 2017 in three referral centers.
RESULTS: In 286/411 patients (69%) the preoperative imaging workup adhered to guidelines (utilizing ultrasound and parathyroid scintigraphy). In patients in whom guidelines were followed 63% were discharged within one day versus 37% in whom guidelines were not followed (P < .0005). The use of a bimodality imaging workup, starting with ultrasound and parathyroid scintigraphy followed by imaging upscaling aiming for anatomical and functional concordance, was a predictor for the performance of a minimally invasive parathyroidectomy (OR 4.098, 95% CI 2.296-7.315, P < .0005).
CONCLUSIONS: The level of compliance to preoperative imaging guidelines is suboptimal in this population. Patients in whom adherence was achieved showed a shorter length of stay. More education of physicians is required regarding the appropriate preoperative imaging workup in pHPT.
METHODS: 2b (individual cohort study).

BACKGROUND: The risks of primary hyperparathyroidism (pHPT) to pregnant women and their fetuses appear to increase commensurate with serum calcium levels. The management strategy for pHPT must be adapted in pregnancy and should reflect the severity of hypercalcemia. However, no guidelines exist to assist clinicians.
METHODS: The experience of a high-volume multidisciplinary endocrine surgical service in treating a consecutive series of pregnant women with pHPT referred for parathyroidectomy is presented and data are compared with a nonpregnant cohort with pHPT. A review of pHPT and pregnancy outcomes in the literature is provided.
RESULTS: Seventeen pregnant women and 247 age range-matched nonpregnant women with pHPT were referred for surgery over 11 years. Mean serum calcium level was higher in the pregnant cohort (2.89 vs 2.78 mmol/L; P = 0.03). Preoperative localization with ultrasound succeeded in eight pregnant women (47%) and sestamibi scanning did in two of six (33% imaged preconception), compared with 84 (34%) and 102 (42%) control subjects, respectively (not significant). Parathyroidectomy was performed under general anesthesia between 12 and 28 weeks\' gestation with no adverse pregnancy outcomes resulting. Cure rate was 100% vs 96% in controls.
CONCLUSIONS: pHPT in pregnancy is a threat to mother and child. Medical management may be appropriate in mild disease, but in moderate to severe disease, parathyroidectomy under general anesthesia in the second trimester is safe. Localization using ionizing radiation/MRI is unnecessary, because surgical intervention in a high-volume multidisciplinary setting has excellent outcomes. Guidelines on the topic would assist clinicians.

The purpose of this review is to assess the most recent evidence in the management of primary hyperparathyroidism (PHPT) and provide updated recommendations for its evaluation, diagnosis and treatment. A Medline search of \"Hyperparathyroidism. Primary\" was conducted and the literature with the highest levels of evidence were reviewed and used to formulate recommendations. PHPT is a common endocrine disorder usually discovered by routine biochemical screening. PHPT is defined as hypercalcemia with increased or inappropriately normal plasma parathyroid hormone (PTH). It is most commonly seen after the age of 50 years, with women predominating by three to fourfold. In countries with routine multichannel screening, PHPT is identified earlier and may be asymptomatic. Where biochemical testing is not routine, PHPT is more likely to present with skeletal complications, or nephrolithiasis. Parathyroidectomy (PTx) is indicated for those with symptomatic disease. For asymptomatic patients, recent guidelines have recommended criteria for surgery, however PTx can also be considered in those who do not meet criteria, and prefer surgery. Non-surgical therapies are available when surgery is not appropriate. This review presents the current state of the art in the diagnosis and management of PHPT and updates the Canadian Position paper on PHPT. An overview of the impact of PHPT on the skeleton and other target organs is presented with international consensus. Differences in the international presentation of this condition are also summarized.

OBJECTIVE: Knowledge about compliance with recommendations derived from the positional statement of the European Society of Endocrine Surgeons on modern techniques in primary hyperparathyroidism surgery and the Third International Workshop on management of asymptomatic primary hyperparathyroidism is scarce. Our purpose was to check it on a bi-national basis and determine whether management differences may have impact on surgical outcomes.
METHODS: An online survey including questions about indications, preoperative workup, surgical approach, intraoperative adjuncts, and outcomes was sent to institutions affiliated to the endocrine surgery divisions of the National Surgical Societies from Spain and Portugal. A descriptive evaluation of the responses was performed. Finally, we assessed the correlation between the different types of management with the achievement of optimal results, defined as a cure rate equal or greater than the median of all interviewed institutions.
RESULTS: Fifty-seven hospitals (41 Spanish, 16 Portuguese) answered the survey. First-ordered imaging tests were neck ultrasound and sestamibi scan. Facing negative or non-concordant results, 44 % of surgeons ordered additional tests before first-time surgery, and 84 % before reoperations. When indicated, selective parathyroidectomy was an acceptable option for 95 % of institutions as first-time surgery and for 51 % in reoperations. Intraoperative parathormone measurements were used by 92 % of departments. The surgical outcomes were good in most institutions (median cure rate 97 %) and were influenced mostly by the presence of an endocrine surgery unit in the surgical department (p = 0.038).
CONCLUSIONS: Practice of Iberian endocrine surgeons is consistent with current recommendations on surgery for primary hyperparathyroidism, with variability in some areas.