Gregory P. Sadler

Negative imaging studies for primary hyperparathyroidism are unavoidable: correlation of sestamibi and high-resolution ultrasound scanning with histological analysis in 150 patients.

Preoperative localization studies with Tc99m-sestamibi have become an integral step in the preoperative assessment of patients with primary hyperparathyroidism (PHPT). This enables scan-directed minimally invasive parathyroidectomy (MIP) to be the preferred treatment for PHPT in many units. This study aimed to identify factors that lead to negative imaging studies in patients with PHPT. Over a 3-year period consecutive unselected patients with PHPT underwent Tc99m-sestamibi scanning and high-resolution ultrasound (US) scanning by the same radiologist. When localization studies were concordant, patients underwent MIP. Those patients with negative imaging studies underwent bilateral neck exploration. Histology slides were independently reviewed and the proportion of chief cells and oxyphil cells within each adenoma was estimated. One hundred and fifty-eight patients underwent localization studies (38 men and120 women, aged 61.8 ± 15.2 years). Sestamibi scans were negative in 52 (32%) and positive in 106 (68%) patients. There was a higher incidence of hyperplasia in the group of patients with negative sestamibi scans (4 out of 52 vs. 4 out of 103, P < 0.05, χ2 test). In patients with negative sestamibi scans the majority of adenomas were formed predominantly from chief cells (26 out of 36) while the majority of patients with adenomas composed predominantly of oxyphil cells had positive scans (21 out of 23) (P < 0.05, χ2 test). The weight of parathyroid adenomas was higher when sestamibi scans were positive (median: 1,180 vs. 517 mg, P < 0.05, Student’s t-test). Successful preoperative localization of parathyroid adenomas using Tc99m-sestamibi scanning is influenced by the cytological predominance of individual tumors. Negative scans might therefore be unavoidable in a subgroup of patients.

Minimally invasive parathyroidectomy without intraoperative parathyroid hormone monitoring in patients with primary hyperparathyroidism

Minimally invasive parathyroidectomy (MIP) is the preferred operation for patients with primary hyperparathyroidism (HPT) and positive preoperative imaging. This non‐randomized case series assessed the long‐term results of MIP performed without the use of intraoperative parathyroid hormone (ioPTH) monitoring.

Parafibromin mutations in hereditary hyperparathyroidism syndromes and parathyroid tumours

Objective  To investigate two patients with the hyperparathyroidism‐jaw tumour (HPT‐JT) syndrome and three patients with familial isolated hyperparathyroidism (FIHP), together with 31 parathyroid tumours (2 HPT‐JT, 2 FIHP and 27 sporadic) for HRPT2 mutations. The HPT‐JT syndrome and FIHP are autosomal dominant disorders that may be caused by abnormalities of the HRPT2 gene, located on chromosome 1q31.2. HRPT2 encodes a 531 amino acid protein, parafibromin, which interacts with human homologues of the yeast Paf1 complex.

One in Four Patients with Follicular Thyroid Cytology (THY3) Has a Thyroid Carcinoma

BACKGROUND Fine-needle aspiration (FNA) biopsy is the cornerstone of assessment of thyroid nodules. Cytological criteria for benign (THY2) and malignant (THY5) aspirates are well established and reliable. When cytology suggests a follicular neoplasm (THY3), only formal histological assessment can differentiate between benign and malignant lesions. The objective of this study was to determine the factors predictive of malignancy in thyroid nodules when cytological assessment is restricted to euthyroid patients living in an area without endemic goiter who undergo routine diagnostic lobectomy once the FNA raises the suspicion of a follicular neoplasm. METHOD Retrospective review of histological and clinical data in a cohort of patients with a palpable thyroid nodule and THY3 cytology. RESULTS Between January 2000 and December 2007, 1981 patients (346 males and 1635 females) underwent 2809 thyroid FNAs. There were 201 THY3 reports (9%). Histology demonstrated thyroid carcinomas in 57 patients (31 follicular carcinomas, 11 Hurthle cell carcinomas, 11 papillary carcinomas, 1 medullary thyroid carcinoma, 1 poorly differentiated thyroid cancer, 1 lymphoma, and 1 metastatic renal carcinoma). Benign tumors were found in 144 patients with follicular adenomas (n = 76), Hurthle cell adenomas (n = 33), multinodular goiter (n = 13), adenomatoid nodules (n = 15), colloid nodules (n = 4), and thyroiditis (n = 3). THY3 cytology was more predictive of malignancy in men (13/34 male symbol vs. 44/167 female symbol, p < 0.001, chi(2) test). The risk for malignancy was 1:4 for the entire group and 1:3 for patients under 30 years and over 60 years. About 17/46 nodules over 40 mm in diameter were carcinomas, compared with only 35/140 in nodules under 40 mm (p < 0.01, chi2 test). CONCLUSION One in four patients with cytological features of a follicular neoplasm has a thyroid carcinoma. A large nodule (>4 cm) with THY3 cytology has a high likelihood of being a cancer, and arguably such patients could be offered total thyroidectomy rather than diagnostic lobectomy.

Molecular pathogenesis of follicular cell derived thyroid cancers

Thyroid cancers are the most common endocrine malignancy. Radiation exposure, family history of thyroid cancer and some inherited conditions are the most important predisposing factors for the development of thyroid cancer. Three mitogenic signalling pathways have been described in the thyroid cell, which are influenced by various stimulatory and inhibitory hormones, growth factors and neurotransmitters. Various proto-oncogenes and oncogenes like ras, braf, trk, met and RET also play a role in the signal transduction systems. Two theories have been described in thyroid cancer pathogenesis, the foetal cell carcinogenesis theory and the more common, multistep carcinogenesis theory. The multistep carcinogenesis theory is now the accepted model in many human cancers, including thyroid cancer. The early events of tumour formation are the consequence of activation of either various growth factors or the proto-oncogenes like ras, met or ret. This results in the formation of differentiated thyroid cancers like the papillary, follicular or Hurthle cell cancers. The later stages of tumour formation involve further activation of proto-oncogenes and loss or inactivation of tumour suppressor genes like p53. Based on this theory, follicular carcinomas are generated from follicular adenomas and papillary carcinomas from precursor cells generated from thyrocytes. Anaplastic carcinoma may develop from papillary or follicular carcinoma by dedifferentiation. In this review article, we highlight the molecular pathogenesis of thyroid tumours.

Asymptomatic hyperparathyroidism - need for multicentre studies

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.

Morbidity after thyroid surgery: patient perspective.

To evaluate patient perception of morbidity after thyroid surgery.

Mechanical bridge to recovery in pheochromocytoma myocarditis

Background. A 27-year-old male presented with exercise-related symptoms of chest tightness, palpitations, breathlessness and severe headache, with occasional nausea, dizziness, and blurred vision. Apart from a family history of coronary artery disease there was no other medical history of note.Investigations. Clinical examination, treadmill exercise test (Bruce protocol), electrocardiography, MRI of the abdomen, blood tests, chest radiography, coronary angiography, two-dimensional echocardiography, transesophageal echocardiography, microscopy of the tumor, 131iodine metaiodobenzylguanidine scan.Diagnosis. Pheochromocytoma myocarditis.Management. Intra-aortic balloon pump, levosimendan and dobutamine infusion, α-blockade with phentolamine, surgical removal of the pheochromocytoma, Levitronix® (Levitronix LLC, Waltham, MA) left ventricular assist device implantation.

Parathyroidectomy is safe and improves symptoms in elderly patients with primary hyperparathyroidism (PHPT)

Objective  Parathyroidectomy for primary hyperparathyroidism (PHPT) is curative in over 95% of cases. Although PHPT affects up to 2% of the elderly population, whose life expectancy may be a decade or more, such patients may be denied surgery because of perceived risk. This study investigates the outcomes of surgery for PHPT in the elderly.

Utilization of Fine-needle Aspiration in Patients Undergoing Thyroidectomy at Two Academic Centers across the Atlantic

Although fine-needle aspiration (FNA) has been accepted as a first-line test in patients with thyroid masses, the utilization of FNA varies even among experienced surgeons. To determine its utility we compared FNA results, pathology, and clinical results in patients who underwent thyroidectomy in two major endocrine centers on both sides of the Atlantic: one in the United States (US) and another in the United Kingdom (UK). Between January 1997 and March 1998 a total of 84 patients underwent thyroid surgery at the UK center, and 143 underwent thyroidectomy at the US center. The most common indication for thyroidectomy at the UK center was compressive goiter (CG), whereas follicular neoplasm (FN) was the most common indication at the US center. Bilateral thyroid resections, frozen section utilization, and thyroid cancer surgery were more common at the US center. Thyroidectomy for symptomatic multinodular goiter and Graves’ disease was more prevalent at the UK center. Thyroid gland weights were also significantly greater in the UK, indicating a higher incidence of endemic goiter. FNA was more commonly employed in the US center (84% vs. 52%; p < 0.001). Despite the differing utilization of FNA at these major endocrine centers, only one thyroid cancer at each institution was not detected preoperatively (both patients had a benign FNA result). Therefore there were no clinically significant thyroid cancers found in patients who did not undergo preoperative FNA. In conclusion, FNA appears to be differentially utilized depending on the incidence of endemic goiter, Graves’ disease, and thyroid cancer. In this series no clinically significant thyroid cancers were found in patients who did not undergo preoperative FNA. Therefore in the hands of experienced thyroid surgeons, FNA can be utilized selectively based on the clinical presentation.