Assessing the impact of low baseline parathyroid hormone levels on surgical treatment of primary hyperparathyroidism

Summary Familial hypocalciuric hypercalcaemia (FHH) is a dominantly inherited, lifelong benign disorder characterised by asymptomatic hypercalcaemia, relative hypocalciuria and variable parathyroid hormone levels. It is caused by loss-of-function pathogenic variants in the calcium-sensing receptor (CASR) gene. Primary hyperparathyroidism (PHPT) is characterised by variable hypercalcaemia in the context of non-suppressed parathyroid hormone levels. Unlike patients with FHH, patients with severe hypercalcaemia due to PHPT are usually symptomatic and are at risk of end-organ damage affecting the kidneys, bone, heart, gastrointestinal system and CNS. Surgical resection of the offending parathyroid gland(s) is the treatment of choice for PHPT, while dietary adjustment and reassurance is the mainstay of management for patients with FHH. The occurrence of both FHH and primary hyperparathyroidism (PHPT) in the same patient has been described. We report an interesting case of FHH due to a novel CASR variant confirmed in a mother and her two daughters and the possible coexistence of FHH and PHPT in the mother, highlighting the challenges involved in diagnosis and management. Learning points: Familial hypocalciuric hypercalcaemia (FHH) and primary hyperparathyroidism (PHPT) can coexist in the same patient. Urinary calcium creatinine clearance ratio can play a role in distinguishing between PHPT and FHH. Genetic testing should be considered in managing patients with PHPT and FHH where the benefit may extend to the wider family. Family segregation studies can play an important role in the reclassification of variants of uncertain significance. Parathyroidectomy has no benefit in patients with FHH and therefore, it is important to exclude FHH prior to considering surgery. For patients with coexisting FHH and PHPT, parathyroidectomy will reduce the risk of complications from the severe hypercalcaemia associated with PHPT.

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Abstract 15844: Plasma Parathyroid Hormone is Independently Related to 24-Hour Pulse Wave Velocity in Patients With Primary Hyperparathyroidism - Insights fFom The EPATH Study

Circulation ◽

10.1161/circ.130.suppl_2.15844 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Julia Wetzel ◽

Nicolas Verheyen ◽

Evgeny Belyavskiy ◽

Albrecht Schmidt ◽

Caterina Colantonio ◽

...

Keyword(s):

Parathyroid Hormone ◽

Primary Hyperparathyroidism ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Vascular Function ◽

Pulse Wave ◽

Smoking Status ◽

Strong Predictor ◽

Double Blind ◽

The Impact

Introduction: Accumulating evidence indicated that high parathyroid hormone (PTH) is associated with increased cardiovascular risk. The impact of PTH on vascular structure and function is, however, still unclear. We evaluated the relationship between pulse wave velocity (PWV) as a novel index of arterial stiffness and circulating levels of PTH in patients with PTH-excess (primary hyperparathyroidism (pHPT)). Methods and Results: We analyzed baseline data of the ongoing randomized, double-blind, placebo-controlled “Effect of Eplerenone on Parathyroid Hormone Levels in Patients with Primary Hyperparathyroidism” (EPATH) study. Inclusion criteria were age of at least 18 years and a diagnosis of pHPT according to international guidelines. Standardized blood sampling was performed after an overnight fast and 24h PWV was measured by a validated non-invasive device for ambulatory hemodynamic monitoring (Mobil O Graph, I.E.M., Stolberg, Germany). Our analysis comprised 92 pHPT patients with a mean age of 68.5 +/- 9.7 years (71 % females) and a median PTH of 102 (IQR 81 - 132) pg/ml. Mean 24h PWV was 9.8 +/- 1.8 m/s, mean daytime and mean nighttime PWV were 10.0 +/- 1.7 m/s and 9.6 +/- 1.8 m/s, respectively. In multivariate linear regression analyses adjusted for age, sex, body mass index, smoking status, mean systolic and mean diastolic 24h blood pressure, antihypertensive medication, type 2 diabetes, 25-hydroxyvitamin D, serum calcium, intake of cinacalcet and fasting serum cholesterol PTH emerged as a strong predictor of mean 24h PWV (ß=0.30, p=0.012), daytime PWV and nighttime PWV (ß=0.30, p=0.011 and ß=0.30, p=0.019, respectively). Conclusion: In a selective cohort of patients with pHPT plasma PTH was strongly related to 24h PWV. These data strengthen the notion that PTH may impact on vascular function. Interventional and mechanistic trials are needed to evaluate modulatory effects on vasculature in patients with high PTH.

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Primary hyperparathyroidism with normal serum intact parathyroid hormone levels

QJM ◽

10.1093/qjmed/93.6.365 ◽

2000 ◽

Vol 93 (6) ◽

pp. 365-367 ◽

Cited By ~ 27

Author(s):

C. MISCHIS-TROUSSARD

Keyword(s):

Parathyroid Hormone ◽

Primary Hyperparathyroidism ◽

Normal Serum ◽

Intact Parathyroid Hormone ◽

Hormone Levels

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Surgical Management of Normocalcemic Primary Hyperparathyroidism and the Impact of Intraoperative Parathyroid Hormone Testing on Outcome

Otolaryngology ◽

10.1177/0194599818793879 ◽

2018 ◽

Vol 159 (4) ◽

pp. 630-637 ◽

Cited By ~ 11

Author(s):

Gina Trinh ◽

Eleni Rettig ◽

Salem I. Noureldine ◽

Jonathon O. Russell ◽

Nishant Agrawal ◽

...

Keyword(s):

Parathyroid Hormone ◽

Primary Hyperparathyroidism ◽

Surgical Management ◽

Intraoperative Parathyroid Hormone ◽

The Impact

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Serum phosphate levels modify the impact of parathyroid hormone levels on renal outcomes in kidney transplant recipients

Scientific Reports ◽

10.1038/s41598-020-70709-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Yohei Doi ◽

Takayuki Hamano ◽

Naotsugu Ichimaru ◽

Kodo Tomida ◽

Yoshitsugu Obi ◽

...

Keyword(s):

Parathyroid Hormone ◽

Kidney Transplant ◽

Serum Phosphate ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Hormone Levels ◽

Renal Outcomes ◽

The Impact

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Contemporary surgical treatment of primary hyperparathyroidism without intraoperative parathyroid hormone measurement

Annals of The Royal College of Surgeons of England ◽

10.1308/rcsann.2015.0048 ◽

2015 ◽

Vol 97 (8) ◽

pp. 603-607 ◽

Cited By ~ 6

Author(s):

OA Mownah ◽

G Pafitanis ◽

WM Drake ◽

JN Crinnion

Keyword(s):

Parathyroid Hormone ◽

Surgical Treatment ◽

Primary Hyperparathyroidism ◽

Frozen Section ◽

Lateral Approach ◽

Preoperative Imaging ◽

Surgical Cure ◽

Focused Parathyroidectomy ◽

Intraoperative Parathyroid Hormone ◽

Iopth Measurement

Introduction Primary hyperparathyroidism (pHPT) is usually the result of a single adenoma that can often be accurately located preoperatively and excised by a focused operation. Intraoperative parathyroid hormone (IOPTH) measurement is used occasionally to detect additional abnormal glands. However, it remains controversial as to whether IOPTH monitoring is necessary. This study presents the results of a large series of focused parathyroidectomy without IOPTH measurement. Methods Data from 2003 to 2014 were collected on 180 consecutive patients who underwent surgical treatment for pHPT by a single surgeon. Preoperative ultrasonography and sestamibi imaging was performed routinely, with computed tomography (CT) and/or selective venous sampling in selected cases. The preferred procedure for single gland disease was a focused lateral approach guided by on-table surgeon performed ultrasonography. Frozen section was used selectively and surgical cure was defined as normocalcaemia at the six-month follow-up appointment. Results Focused surgery was undertaken in 146 patients (81%) and 97% of these cases had concordant results with two imaging modalities. In all cases, an abnormal gland was discovered at the predetermined site. Of the 146 patients, 132 underwent a focused lateral approach (11 of which were converted to a collar incision), 10 required a collar incision and 4 underwent a mini-sternotomy. At 6 months following surgery, 142 patients were normocalcaemic (97% primary cure rate). Three of the four treatment failures had subsequent surgery and are now biochemically cured. There were no complications or cases of persistent hypocalcaemia. Conclusions This study provides further evidence that in the presence of concordant preoperative imaging, IOPTH measurement can be safely omitted when performing focused parathyroidectomy for most cases of pHPT.

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