Surgical management of primary hyperparathyroidism: state of the art

Importance Identifying parathyroid glands correctly before a surgical procedure is essential to perform minimally invasive surgery. First-line tests with discordant or negative results underscore the need for more accurate imaging tests, thus decreasing the requirement for bilateral neck exploration or reintervention. Objective To review the available evidence to determine positive predictive value, negative predictive value, sensitivity, and specificity in clinical cases in which18F-fluorocholine positron emission tomography–computed tomography (PET/CT) could be useful as a method to locate the lesions, and the benefits and controversial aspects of the method. Evidence Review A search was conducted using the PubMed Central and Cochrane Library databases for studies published in English from July 26, 2014, to November 30, 2018, using the search terms18 choline,18F choline,18F-choline,18 fluorocholine PET CT,hyperparathyroidism,primary hyperparathyroidism,secondary hyperparathyroidism,tertiary hyperparathyroidism,persistent hyperparathyroidism,recurrent hyperparathyroidism,ectopic hyperparathyroidism, andparathyroid adenoma. Other inclusion criteria were reporting at least 1 of the following measurements: negative or positive predictive value, sensitivity, and specificity of18F-fluorocholine PET/CT in the diagnosis of hyperparathyroidism (HPT). Exclusion criteria were language other than English, use of a tracer other than18F-fluorocholine, reports of a single case, and studies not related to HPT. The Oxford Centre classifications for levels of evidence were used. Findings Sixteen studies fulfilled the inclusion criteria, comprising a total of 619 patients. Selected studies included 10 prospective cohort studies, 5 retrospective cohort studies, and 1 case series. Of the subtypes of HPT diagnosed using18F-fluorocholine PET/CT, 579 were primary HPT, 22 were secondary HPT, 1 was tertiary HPT, and 7 were associated with multiple endocrine neoplasia type I. Pathologically, the neoplasms comprised 459 adenomas, 59 hyperplasia, and 19 double adenomas. Conclusions and Relevance 18F-fluorcholine PET/CT may be indicated when results of first-line tests are negative or discordant and in challenging clinical situations where locating the source of HPT is difficult.

Usefulness of 18F-Fluorocholine Positron Emission Tomography–Computed Tomography in Locating Lesions in Hyperparathyroidism: A Systematic Review

Summary Long-term follow-up is initially considered appropriate for the majority of patients with primary hyperparathyroidism (PHPT) having small increases in calcium levels ( < 2·8 mmol/l) and lacking the ‘classical’ symptoms of PHPT. The supportive reasoning is that many such patients never progress to more severe biochemical or clinical disease. There are, however, arguments in favour of early surgical treatment of such patients but adequately powered studies have not been carried out in this subgroup of patients to asses the impact of PHPT on their quality of life, cardiovascular risk and bone density. Progressive loss in bone mineral density and an increased risk of bone fracture become increasingly significant in an ageing population. Left ventricular hypertrophy, an increased risk of arrhythmia and/ or myocardial infarction in addition to changes in atherogenic lipid profile and impaired glucose tolerance may translate into an increased risk of premature death in this group of patients. Changes in the quality of life identified using standardized questionnaires are sometimes recognized by patients only in retrospect (i.e. after resolution of symptoms following successful para-thyroidectomy). In addition, many series fail to assess and record accurately such symptoms. Multicentre cohort studies of patients with asymptomatic PHPT randomized to immediate or delayed surgical treatment could address some of the debated issues highlighted in this review. Until such studies are set up, most surgeons would consider that parathyroid surgery should represent the first choice of treatment for all patients, but many physicians would favour a long-term follow-up. Nevertheless, the threshold for referral for surgical treatment has been lowered since the introduction of scan-directed minimally invasive parathyroidectomy, which enables the experienced parathyroid surgeon to successfully treat patients with PHPT with a minimum of complications as a day-case operation. In the context of improved surgical treatment, we need more data on the benefits or otherwise in so-called asymptomatic patients with a thorough assessment of their bone quality, cardiovascular risk and quality of life.

Asymptomatic hyperparathyroidism - need for multicentre studies

Lithium is frequently used in the treatment of bipolar disease. Although lithium-associated hyperparathyroidism (LAH) is well documented, reports concerning its pathologic findings are sparse. Because of a high-reported incidence of multiglandular disease, focused exploration for LAH is controversial. From 1995 to 2007, data from 1207 consecutive patients who underwent concise parathyroid exploration for sporadic primary hyperparathyroidism (PHP) directed by quick intraoperative parathyroid hormone monitoring (QPTH) were reviewed to identify patients with LAH. Anatomic findings were determined. All patients had >5 months of follow-up. The incidence of LAH was 16/1207 (1.3%). The rate of multiglandular disease was not higher in LAH: present in 25% (4/16) patients with LAH and 12.3% (146/1191) patients without LAH (p = 0.13 Fisher two-tailed test). Among 16 patients with LAH, 12 (75%) had a single adenoma. The use of QPTH allowed unilateral exploration in 8 of 12 patients with single adenoma. Parathyroid exploration resulted in durable biochemical cure for all 16 patients with LAH. Multiglandular disease seems to be no more frequent in patients with LAH than in patients with primary hyperparathyroidism (PHP) without LAH. Patients with LAH can be safely and effectively managed with selective unilateral exploration directed by intraoperative PTH monitoring.

Appropriate surgical treatment of lithium-associated hyperparathyroidism.

Purpose
Patients with primary hyperparathyroidism, pHPT, present with milder symptoms than previously. Some, but not all studies, suggest that this change in clinical pattern also implies lower preoperative parathyroid hormone (PTH) and/or calcium levels and smaller adenomas. This is important since reports indicate that smaller adenomas are more difficult to detect on preoperative imaging, possibly increasing the risk of surgical failure.

Changing biochemical presentation of primary hyperparathyroidism.

Indications for operative intervention in patients with asymptomatic primary hyperparathyroidism: practice patterns of endocrine surgery.

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Indications for operative intervention in patients with asymptomatic primary hyperparathyroidism: practice patterns of endocrine surgery.