Novel Method in Performing PTH Washout for Localizing Parathyroid Adenoma: Case Report & an Institute Experience in Qatar

Introduction: Primary hyperparathyroidism (PHPT) is a common cause of hypercalcemia and mostly caused by benign solitary benign adenoma (80 to 85 %). Definite treatment is the surgical removal. The most commonly used diagnostic modalities are Sestamibi scan and neck ultrasound (US) which can be inconclusive in some cases. Parathyroid hormone (PTH) washout obtained with ultrasound guided FNA may be useful to accurately localize the adenoma. In our study we describe a novel method for PTH washout. Methods: First, blood samples are drawn from the patient’s peripheral vein and placed in two yellow top tubes (3 ml of blood in each tube). 1 ml of normal saline (NS) will be add to Tube # 1 (Control tube). The suspected parathyroid lesion aspirate is obtained via US guided FNA. It is washed in 1 ml of NS and added to tube #2 (PTH washout tube). Both tubes are sent to our local laboratory for PTH assay. The ratio of PTH in PTH washout tube to control tube (PTH W/C ratio) is calculated and considered positive if more than 2. Results: Total 16 patients (12 females and 4 males) underwent the PTH washout procedure. All patients had PHPT. Out of 16 patients, 13 had inconclusive Sestamibi scan while 3 patients didn’t have the scan due to pregnancy. PTH W/C ratio was positive in 13 patients (ruled in) and negative (ruled out) in 3 patients. All patients underwent parathyroid surgery. The operative findings and pathology report were consistent with PTH W/C ratio findings. i.e. parathyroid hypercellularity was found in all the 13 patients ruled in by PTH W/C ratio. Post-surgery, biochemical parameters normalized in all. Conclusion: PTH washout is an important tool in localizing parathyroid lesion in PHPT when Sestamibi scan cannot be done or if it is inconclusive. PTH W/C ratio can be performed with our novel method to accurately localize the PTH lesion and improve surgical outcome.

MON-357 Craniofacial Deformities with Hypercalcemia: A Rare Case of Co-Existing Primary Hyperparathyroidism and Paget’s Disease of the Bone Since Young Adulthood

Background: Primary Hyperparathyroidism (PHPT) and Paget’s Disease of the Bone (PDB) are two distinct bone mineral disorders which rarely co-exist. It has been very scarcely reported in the elderly but almost unheard of in young adults. Clinical case A middle-aged Indian lady presents with multiple and recurrent facial and jaw bony swellings, since the age of 12. She had normal developmental as a child, without visual, auditory deficits or limb deformities. No family history of hypercalcemia or endocrine disorders was elicited. At initial diagnosis, biochemical parameters were consistent with PHPT, with mild to moderate hypercalcemia (2.6-3.0 mmol) and concomitant hypophosphatemia (0.6-0.8 mmol/L), elevated intact PTH 10.6pmol/L and ALP persistently more than 350 U/L. She had undergone multiple surgeries to remove the bony swellings, presumed to be brown tumours. She developed medullary nephrocalcinosis approximately 30 years after onset of illness. Over a span of three decades, numerous modalities were employed in attempt to localise the parathyroid lesion, including imaging (ultrasonography, sestamibi with SPECT CT, FDG PET),angiography, venous sampling and exploratory neck surgeries which were unsuccessful. Due to failure in localising the offending parathyroid lesion, it was conceded to maintain her on medical therapy.She was initially started on oral phosphate therapy, intranasal calcitonin and subsequently calcimimetics. Aside from rising ALP levels, her other biochemical parameters remained static. Her diagnosis was re-evaluated when she presented with osteomyelitis of the right mandible requiring surgery. Pre -operative CT imaging showed mixed lytic and sclerotic lesions at the mandible, maxilla, facial bones and skull. It also revealed diffuse thickening of the calvarium with narrowing of the posterior fossa resulting in hydrocephalus, requiring a ventriculoperitoneal shunt insertion. Histopathological examination of the mandible showed a background of osteosclerosis. These findings were inconsistent with PHPT and was most often described in PDB. On the other hand, a repeated skeletal survey showed generalised osteopenia in the small bones of the hand with subperiosteal and terminal phalanges reabsorption which was in keeping with PHPT. Her pelvis, spine and long bones remained normal and bone densitometry was preserved. It was concluded that this patient was suffering from dual pathology, PHPT and PDB and was commenced on bisphosphonates. Conclusion: This lady presented with two diseases which simulate each other despite not being etiologically linked. The aberrancy in the age of onset and the overlapping clinical features of the dual pathology imposed a significant challenge in making the correct diagnosis. Retrospectively, histopathological examination of the bone at an earlier stage of disease may have been the key to solving this perplexing case.

Hyperparathyroidism in pregnancy

Hyperparathyroidism is a rare disease during pregnancy, which has increased risks, including miscarriage and fetal growth restriction. However, the diagnosis of hyperparathyroidism is frequently not recognised or delayed as symptoms are non-specific and calcium is not routinely measured. With a thorough medical history and clinical suspicion, early diagnosis and treatment can reduce the risk of some pregnancy complications. A 35-year-old woman presented at 13/40 with hyperemesis gravidarum. She had elevated serum calcium and a parathyroid lesion on ultrasound. She underwent a parathyroidectomy with rapid normalisation of her calcium. Histopathology confirmed a parafibromin-deficient parathyroid tumour, suggestive of hyperparathyroidism jaw tumour syndrome. At 30/40, she presented with pre-eclampsia (hypertension, hyper-reflexia, proteinuria and intrauterine growth restriction) and had a caesarean section at 30+1/40, delivering a male infant, 897 g (fifth percentile). She had a prior 12-month history of chronic constipation and nephrolithiasis but was not investigated further despite elevated calcium (2.82 mmol/L).

Ultrasound elastography score and strain index in different parathyroid lesions

Background Despite significant improvement in imaging quality and advanced scientific knowledge, it may still sometimes be difficult to distinguish different parathyroid lesions. The aims of this prospective study were to evaluate parathyroid lesions with ultrasound elastography and to determine whether strain index can help to differentiate parathyroid lesions. Methods Patients with biochemically confirmed hyperparathyroidism and localised parathyroid lesions in ultrasonography were included. All patients underwent B-mode US and USE examination. Ultrasound elastography scores and strain index of lesions were determined. Strain index was defined as the ratio of strain of the thyroid parenchyma to the strain of the parathyroid lesion. Results Data of 245 lesions of 230 patients were analysed. Histopathologically, there were 202 (82.45%) parathyroid adenomas, 26 (10.61%) atypical parathyroid adenomas, and 17 (6.94%) cases of parathyroid hyperplasia. Median serum Ca was significantly higher in atypical parathyroid adenoma patients than parathyroid hyperplasia patients (P = 0.019) and median PTH was significantly higher in APA compared to PA patients (P < 0.001). In 221 (90.2%) of the parathyroid lesions, USE score was 1 or 2. The median SI of atypical parathyroid adenomas was significantly higher than parathyroid adenomas and hyperplasia lesions (1.5 (0.56–4.86), 1.01 (0.21–8.43) and 0.91 (0.26–2.02), respectively, P = 0.003). Conclusion Our study revealed that SI of parathyroid lesions as well as serum calcium, parathyroid hormone levels, and B-mode US features may help to predict the atypical parathyroid adenoma. Ultrasound elastography can be used to differentiate among parathyroid lesions and guide a surgical approach.

Primary hyperparathyroidism with surgical indication and negative or equivocal scintigraphy: safety and reliability of PTH washout. A systematic review and meta-analysis

Objective Despite the improvements in ultrasound (US) and scintigraphy, 10–20% of patients with primary hyperparathyroidism (PHPT) still have discordant findings. We performed a systematic review and meta-analysis to assess the safety and the diagnostic performance of US-guided PTH washout (FNA-PTH) in patients with PHPT, a suspected parathyroid lesion on US but negative or equivocal scintigraphy. Methods The review was registered on PROSPERO (CRD42019124249). PubMed, Scopus, CENTRAL and Web of Science were searched until February 2019. Original articles reporting complications and diagnostic performance of FNA-PTH in biochemically and histopathologically diagnosed PHPT were selected. The risk of bias of included studies was assessed through QUADAS-2. Summary operating points were estimated using a random-effects model. Results Out of 2573 retrieved papers, nine cohort studies were included in the review. No major procedure-related complications were found. Pooled sensitivity was 95% (95% CI: 91–98; I 2: = 14%) and positive predictive value was 97% (95% CI: 93–100; I 2: = 39%). There were not enough data for specificity and negative predictive value to perform a meta-analysis. However, pooling results of all lesions, they were estimated to be 83 and 73%, respectively. Conclusions In patients with biochemically proven PHPT and discordant imaging, FNA-PTH was a safe and accurate procedure. In this specific setting of patients, FNA-PTH could be used as a rule-in test for minimally invasive parathyroidectomy.

Two cases of spontaneous remission of primary hyperparathyroidism due to auto-infarction: different management and their outcomes

Summary Spontaneous remission of primary hyperparathyroidism (PHPT) due to necrosis and haemorrhage of parathyroid adenoma, the so-called ‘parathyroid auto-infarction’ is a very rare, but previously described phenomenon. Patients usually undergo parathyroidectomy or remain under close clinical and biochemical surveillance. We report two cases of parathyroid auto-infarction diagnosed in the same tertiary centre; one managed surgically and the other conservatively up to the present time. Case #1 was a 51-year old man with PHPT (adjusted (adj.) calcium: 3.11 mmol/L (reference range (RR): 2.20–2.60 mmol/L), parathyroid hormone (PTH) 26.9 pmol/L (RR: 1.6–6.9 pmol/L) and urine calcium excretion consistent with PHPT) referred for parathyroidectomy. Repeat biochemistry 4 weeks later at the surgical clinic showed normal adj. calcium (2.43 mmol/L) and reduced PTH. Serial ultrasound imaging demonstrated reduction in size of the parathyroid lesion from 33 to 17 mm. Twenty months later, following recurrence of hypercalcaemia, he underwent neck exploration and resection of an enlarged right inferior parathyroid gland. Histology revealed increased fibrosis and haemosiderin deposits in the parathyroid lesion in keeping with auto-infarction. Case #2 was a 54-year-old lady admitted with severe hypercalcaemia (adj. calcium: 4.58 mmol/L, PTH 51.6 pmol/L (RR: 1.6–6.9 pmol/L)) and severe vitamin D deficiency. She was treated with intravenous fluids and pamidronate and 8 days later developed symptomatic hypocalcaemia (1.88 mmol/L) with dramatic decrease of PTH (17.6 pmol/L). MRI of the neck showed a 44 mm large cystic parathyroid lesion. To date, (18 months later), she has remained normocalcaemic. Learning points: Primary hyperparathyroidism (PHPT) is characterised by excess parathyroid hormone (PTH) secretion arising mostly from one or more autonomously functioning parathyroid adenomas (up to 85%), diffuse parathyroid hyperplasia (<15%) and in 1–2% of cases from parathyroid carcinoma. PHPT and hypercalcaemia of malignancy, account for the majority of clinical presentations of hypercalcaemia. Spontaneous remission of PHPT due to necrosis, haemorrhage and infarction of parathyroid adenoma, the so-called ‘parathyroid auto-infarction’, ‘auto-parathyroidectomy’ or ‘parathyroid apoplexy’ is a very rare in clinical practice but has been previously reported in the literature. In most cases, patients with parathyroid auto-infarction undergo parathyroidectomy. Those who are managed conservatively need to remain under close clinical and biochemical surveillance long-term as in most cases PHPT recurs, sometimes several years after auto-infarction.

Giant parathyroid adenoma: differential aspects compared to parathyroid carcinoma

Summary The 85% of cases of primary hyperparathyroidism (PHPT) are due to parathyroid adenomas (PA) and less than 1% to parathyroid carcinomas (PC). The PA usually measure <2 cm, weigh <1 g and generate a mild PHPT, whereas the PC usually exceeds these dimensions and are associated with a severe PHPT. However, giant PA (GPA), which is defined as those larger than 3 g, has been documented. Those may be associated with very high levels of PTH and calcium. In these cases, their differentiation before and after surgery with PC is very difficult. We present a case of severe PHPT associated with a large parathyroid lesion, and we discuss the differential aspects between the GPA and PC. Learning points: In parathyroid lesions larger than 2 cm, the differential diagnosis between GPA and PC should be considered. Pre and postsurgical differentiation between GPA and PC is difficult; however, there are clinical, analytical and radiographic characteristics that may be useful. The depth/width ratio larger or smaller than 1 seems to be the most discriminatory ultrasound parameter for the differential diagnosis. Loss of staining for parafibromin has a specificity of 99% for the diagnosis of PC. The simultaneous presence of several histological characteristics, according to the classification of Schantz and Castleman, is frequent in PC and rare in GPA.