Parathyroid, Thyroid and Recurrent Laryngeal Nerve Anatomy in an Indian Rhinoceros (Rhinoceros unicornis).

INTRODUCTION: The parathyroid gland was first identified in the Indian rhinoceros in 1849 by Sir Richard Owen. We performed a necropsy in an Indian rhinoceros, recapitulating Owen's dissection and display what appear to be the initial identification of the recurrent laryngeal nerve in situ and the anatomy and histology of the largest rhinoceros parathyroid glands yet identified. MATERIALS AND METHODS: Patrick T. Rhino, a 41-year-old Indian rhinoceros was born in 1974. His early years were unremarkable. In 2006, he was donated to White Oak Conservation in Yulee, Florida, where he bred and sustained minor injuries. In his geriatric years, he developed a cataract and degenerative joint disease (DJD). At age 41, he developed progressive ataxia and lameness and was euthanized to minimize suffering when he was unable to stand. ROS, FH, SH and medication history were unremarkable. Physical exam was age and species appropriate. Pre-mortem serum demonstrated: creat 1.8 mg/dL (0.8-2.1), calcium 10.6 mg/dL (9.7-13.1), phos 3.8 mg/dL (2.5-6.7), alk phos 69 U/L (26-158) and intact PTH 44.1 pg/mL (rhinoceros reference range: unknown). Necropsy revealed intervertebral DJD with thoracic spondylosis, which combined with osteoporosis, resulted in thoracic myelopathy and ataxia. The neck block was sent in formalin to the Yale University School of Medicine. RESULTS: Detailed dissection was performed under loupe magnification. Presumed structures were photographed in situ and biopsied. The thyroid was identified deep to the strap muscles, received its blood supply from the inferior and superior thyroid arteries and was blue in color. The right recurrent laryngeal nerve, identified and photographed in situ for the first time in the rhinoceros, was deep to the inferior thyroid artery and was traced throughout its cervical course. Single parathyroid glands identified on the lateral thyroid lobes received their blood supply from the inferior thyroid arteries and were confirmed histologically. They appear to be the largest parathyroids yet identified in the rhinoceros with estimated weights of 6,280 and 11,000 mg, respectively. Although the etiology of the parathyroid gland enlargement is unknown, the specimen has been preserved recapitulating the dissection performed by Sir Richard Owen. CONCLUSION: The parathyroids, thyroid and recurrent laryngeal nerve were identified in an Indian rhinoceros. This appears to be the first display of the rhinoceros recurrent laryngeal nerve in situ, and the parathyroid glands are the largest yet identified in the rhinoceros.

Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus.

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.

Parathyroid surgery in familial hyperparathyroid disorders.

The management of hyperparathyroidism (HPT) in the setting of familial HPT differs between the specific syndromes and is generally complex because of the underlying disease, which predisposes patients to persistent and recurrent HPT. The basic principles of surgery include achieving and maintaining normocalcaemia for the longest time possible, avoiding both iatrogenic hypocalcaemia and operative complications, and facilitating future surgery for recurrent disease. Multiple endocrine neoplasia type 1 (MEN1) is treated with either subtotal parathyroidectomy or total parathyroidectomy with immediate heterotopic autotransplantation of parathyroid tissue. MEN2A, familial isolated HPT and HPT-associated with the hyperparathyroidism-jaw tumour (HPT-JT) syndrome typically can be treated with parathyroidectomy, i.e. subtotal or less. The increased risk of parathyroid cancer in HPT-JT requires special attention. Parathyroid surgery in familial HPT syndromes in the setting of underlying mutations in the calcium receptor (CASR) gene involves radical subtotal parathyroidectomy. Intraoperative parathyroid hormone (PTH) measurements may help guide the extent of parathyroid resection, particularly in the case of multigland HPT. The vast majority of patients with familial HPT who require surgery are best served with bilateral cervical explorations. However, minimally invasive parathyroidectomy (MIP) techniques that have become routine for sporadic HPT at selected institutions may be extrapolated to a subset of cases of familial HPT.

BRAF T1796A transversion mutation in various thyroid neoplasms.

A high prevalence of activating mutation of the B type Raf kinase (BRAF) gene was recently reported in papillary thyroid cancer (PTC). However, the frequency of this mutation in several other types of thyroid neoplasms was not thoroughly investigated. In the present study, in addition to PTC, we evaluated various thyroid tumor types for the most common BRAF T1796A mutation by direct genomic DNA sequencing. We found a high and similar frequency (45%) of the BRAF T1796A mutation in two geographically distinct PTC patient populations: one composed of sporadic cases from North America, and the other from Kiev, Ukraine, that included individuals who were exposed to the Chernobyl nuclear accident. In contrast, we found BRAF mutation in only 20% of anaplastic thyroid cancers and no mutation in medullary thyroid cancers and benign thyroid hyperplasia. We also confirmed previous reports that the BRAF T1796A mutation did not occur in benign thyroid adenomas and follicular thyroid cancers. Specific analysis of the Ukraine patients with confirmed history of radiation exposure failed to show a higher incidence of BRAF mutation. Our results suggest that frequent occurrence of BRAF mutation is inherently associated with PTC, irrespective of geographic origin, and is apparently not a radiation-susceptible mutation. The lack or low prevalence of BRAF mutation in other thyroid neoplasms is consistent with the notion that other previously defined genetic alterations on the same signaling pathway are sufficient to cause tumorigenesis in most thyroid neoplasms.

Minimally invasive parathyroid surgery.

The standard bilateral neck exploration in primary hyperparathyroidism (HPTH) has been challenged in the recent years by the general trend toward less invasive surgery. The development of more reliable preoperative imaging techniques such as Sestamibi scanning and high definition ultrasonography coupled with improvements in intraoperative rapid assays of intact parathyroid hormone have allowed unilateral explorations in most patients with primary HPTH. This article reviews the currently available preoperative parathyroid localization studies as well as the currently used minimally invasive parathyroidectomy (MIP) techniques, such as open approaches, radioguided surgery and endoscopic procedures. While some techniques are more popular than others, careful selection of patients with primary HPTH has resulted in comparable cure rates to the standard bilateral parathyroid exploration.

In vitro accumulation of technetium-99m-sestamibi in human parathyroid mitochondria.

BACKGROUND: Technetium-99m-sestamibi (sestamibi) is the imaging agent of choice for preoperative parathyroid localization. The subcellular localization of sestamibi uptake in enlarged parathyroid glands in patients with hyperparathyroidism has not been determined. This study investigated the mechanism of retention of sestamibi by human parathyroid tissue. METHODS: Twenty-three freshly harvested and 15 cryopreserved parathyroid glands excised from patients with primary or secondary hyperparathyroidism were analyzed for subcellular localization of Tc-99m-sestamibi. Tissues were incubated with 100 microCi of sestamibi and isolated for mitochondria by differential centrifugation, and the integrity of subcellular fractions was quantified with the mitochondrial enzyme marker, succinate dehydrogenase. RESULTS: Ninety-two percent of sestamibi activity was associated with mitochondria. Furthermore, after adding the mitochondrial uncoupler, carbonylcyanide m-chlorophenylhydrazone (CCCP), to fresh parathyroid tissues, 84.96% and 73.86% of sestamibi was released from the mitochondrial and tissue fragment components, respectively. In addition, sestamibi activity in the mitochondrial component of cryopreserved human parathyroid tissue decreased to the same amount as the CCCP-treated group. CONCLUSIONS: These data confirm that mitochondrial activity is the major component of sestamibi uptake by human parathyroid tissue in patients with hyperparathyroidism.

Primary hyperparathyroidism: what every orthopedic surgeon should know.

The diagnosis of hyperparathyroidism should rarely by missed by the orthopedic surgeon. When a patient presents with a pathologic fracture, routine serum calcium should be obtained. If there is evidence of elevated serum calcium or any of the pathognomonic findings of primary hyperparathyroidism on plain radiographs, total and ionized calcium and an intact parathyroid hormone levels should be obtained to make the diagnosis (Figure 5). When patients require surgical treatment for an orthopedic condition and also need surgery for hyperparathyroidism, the procedures can be safely performed simultaneously. Simultaneous parathyroidectomy corrects the underlying endocrinopathy, thereby improving the outcome of the orthopedic procedure. In addition, these procedures can easily be performed simultaneously under one anesthetic and thereby minimize cost and length of hospitalization.

A "pheo" lurks: novel approaches for locating occult pheochromocytoma.

Most, but not all, pheochromocytomas can be localized by computed tomography or magnetic resonance imaging. Here we introduce two novel approaches for localization of pheochromocytoma in a patient in whom conventional imaging modalities failed to show the tumor. First, we establish that measurements of plasma free metanephrines coupled with vena caval sampling are useful for localizing occult pheochromocytoma, particularly when elevations in plasma catecholamines are slight or intermittent. Second, we show that positron emission tomographic scanning using the imaging agent 6-[18F]fluorodopamine as a substrate for the norepinephrine transporter offers a highly effective method for tumor localization. These novel approaches may be of value in difficult cases, where biochemical and clinical evidence of pheochromocytoma is compelling, yet conventional imaging modalities fail to locate the tumor.

Human telomerase reverse transcriptase expression in Diff-Quik-stained FNA samples from thyroid nodules.

Fine-needle aspiration (FNA) is a highly sensitive method in the differential diagnosis of thyroid nodules. However, 10% of thyroid FNAs are indeterminate for cancer, and thus additional markers may be useful diagnostically. The authors have demonstrated previously that human telomerase reverse transcriptase (hTERT) gene expression is useful in the distinction of benign lesions from malignant lesions. They therefore wondered whether the detection of hTERT gene expression was feasible using archival slides. To establish an experimental system, ribonucleic acid was extracted from human anaplastic thyroid carcinoma cell line (ARO) in cytologic specimens, and reverse transcription-polymerase chain reaction (RT-PCR) for hTERT expression was performed. RT-PCR analysis for hTERT gene detection was then performed using 58 Diff-Quik-stained archival FNA samples collected retrospectively. RT-PCR for human thyroglobulin (hTg) or beta-actin gene expression served as a positive control. Successful PCR results were obtained from 48 of the 58 cases. All 10 slides in which no RT-PCR products were noted were older than 3 years. hTERT gene expression was demonstrated in FNAs from two of seven cases (29%) of hyperplastic nodule, one of one case (100%) of Hashimoto's thyroiditis, three of eight cases (38%) of follicular adenoma, three of eight cases (38%) of Hürthle cell adenoma, three of four cases (75%) of follicular carcinoma, two of two cases (100%) of Hürthle cell carcinoma, and 11 of 18 cases (61%) of papillary carcinoma. All but one of the available 33 corresponding frozen samples exhibited the same RT-PCR results. This study demonstrates that Diff-Quik-stained thyroid FNA specimens less than 3 years old can be used for the detection of hTERT gene expression by RT-PCR. This test, along with careful cytopathologic examination, may improve our ability to differentiate benign lesions from malignant lesions in indeterminate FNA samples from thyroid nodules.

Randomized prospective evaluation of frozen-section analysis for follicular neoplasms of the thyroid.

OBJECTIVE: To evaluate the clinical utility of frozen section in patients with follicular neoplasms of the thyroid in a randomized prospective trial. SUMMARY BACKGROUND DATA: The finding of a follicular neoplasm on fine-needle aspiration prompts many surgeons to perform intraoperative frozen section during thyroid lobectomy. However, the focal distribution of key diagnostic features of malignancy contributes to a high rate of noninformative frozen sections. METHODS: The series comprised 68 consecutive patients with a solitary thyroid nodule in whom fine-needle aspiration showed a follicular neoplasm. Patients were excluded for bilateral or nodal disease, extrathyroidal extension, or a definitive fine-needle aspiration diagnosis. Final pathologic findings were compared with frozen sections, and cost analyses were performed. RESULTS: Sixty-one patients met the inclusion criteria. Twenty-nine were randomized to the frozen-section group and 32 to the non-frozen-section group. In the non-frozen-section group, one patient was excluded when gross examination of the specimen was suggestive of malignancy and a directed frozen section was diagnostic of follicular carcinoma. Frozen-section analysis rendered a definitive diagnosis of malignancy in 1 of 29 (3.4%) patients, who then underwent a one-stage total thyroidectomy. In the remaining 28 patients, frozen section showed a "follicular or Hürthle cell neoplasm." Permanent histology demonstrated well-differentiated thyroid cancer in 6 of these 28 patients (21%). Of the 31 patients in the non-frozen-section group, 3 (10%) showed well-differentiated thyroid carcinoma on permanent histology. Complications were limited to one transient unilateral vocal cord dysfunction. All but one patient had a 1-day hospital stay. There were no significant differences between the groups in surgical time or total hospital charges; however, the charge per informative frozen section was approximately $12,470. CONCLUSIONS: For the vast majority of patients (96.4%) with follicular neoplasms of the thyroid, frozen section is neither informative nor cost-effective.

Primary hyperparathyroidism.

Treatment of primary hyperparathyroidism depends on a clear diagnosis based on biochemical confirmation. Most patients have an elevated serum total or ionized calcium level in association with an elevated or inappropriate serum intact parathyroid hormone level. The serum calcium level can be lowered by hydration and by a variety of pharmacologic agents. However, none of these agents is effective in the long-term management of primary hyperparathyroidism. The extraordinarily high success rate of surgery, combined with its low morbidity and the ever-increasing acceptance of minimally invasive techniques, makes surgical resection the recommended treatment for virtually all patients.

Intraperitoneal delivery of insulin via mechanical pump: surgical implications.

Between November 1986 and January 2000, 28 patients with insulin-dependent diabetes mellitus were enrolled in the implanted insulin pump study at Johns Hopkins Hospital. An additional two patients underwent pump implantation under compassionate use guidelines due to apparent resistance to subcutaneously administered insulin uptake. The mean patient age was 44 +/- 10.5 years. Eleven patients (39%) were female and the mean duration of diabetes was 25.7 +/- 8.9 years. Diabetic retinopathy, neuropathy, and nephropathy were present in 43%, 25% and 11 % of patients, respectively. The insulin pumps functioned safely for a total of 189 patient years. Mean pump life was 26 +/- 1.2 months. There was no mortality. Morbidity was limited to pump-site infections [n=y (4%) of all pumps placed], one case of pump migration and skin erosion, and one small bowel obstruction associated with the pump catheter. Mean serum hemoglobin AIC levels before and after pump placement were 9.0 +/- 2.9% and 7.5 +/- 0.7% (P=0.0023), respectively. Correspondingly, the mean daily blood glucose levels decreased from l61 +/- 40 mg/dl before placement to 141 +/- 27 mg/dl after pump placement (P=0.0063). Intraperitoneal delivery of insulin by a mechanical pump appears to be an attractive alternative for the treatment of insulin-dependent diabetes mellitus.

Intraoperative parathyroid hormone analysis: A study of 200 consecutive cases.

BACKGROUND: Immunoassays for parathyroid hormone (PTH), with short incubation times and results available in <15 min, have allowed intraoperative monitoring of the success of parathyroid surgery. The purpose of this study was to evaluate the analytical performance of a rapid PTH assay and its clinical performance in a series of 200 patients. METHODS: PTH was measured with a modified immunochemiluminometric assay with a 7-min incubation time (QuiCk-IntraOperative(TM) Intact PTH assay). The rapid assay was compared with results in a central laboratory (immunoradiometric assay) in 44 EDTA-plasma specimens. The rapid assay was used intraoperatively in 200 consecutive cases with specimens analyzed before and 5-10 min after resection of the hypersecreting parathyroid gland(s). RESULTS: Intraassay imprecision was 12% at 28 ng/L and 11% at 278 ng/L. Regression analysis of results of the rapid PTH assay and the IRMA PTH assay in 44 parathyroidectomy patients yielded y = 1.26x - 12 ng/L, S:(y|x) = 26.3 ng/L, r = 0.984, and in 40 of 44 patients with values <200 ng/L, y = 1.02x + 1.9, S:(y|x) = 13.9, r = 0.947. In the 195 cases using intraoperative PTH testing with complete results and defined clinical outcomes, the overall accuracy of the assay in predicting surgical success was 88% using the criterion of a 50% decrease at 5-10 min and 97% including the subset of patients with delayed decreases of PTH. CONCLUSIONS: The rapid PTH assay had excellent analytical performance and excellent agreement with the PTH immunoradiometric assay and predicted the success of parathyroid surgery in this large series of consecutive patients.

One hundred consecutive minimally invasive parathyroid explorations.

OBJECTIVE: To review the outcomes of 100 consecutive minimally invasive parathyroid explorations. SUMMARY BACKGROUND DATA: Minimally invasive parathyroidectomy (MIP) has challenged the traditional approach of bilateral neck exploration for patients with primary hyperparathyroidism. Most patients with primary hyperparathyroidism have a single adenoma that when resected results in cure. It therefore appears logical to perform a directed approach to adenoma extirpation. MIP involves high-quality sestamibi images obtained with single photon emission computed tomography to localize enlarged parathyroid glands in three dimensions, limited exploration after surgeon-administered cervical block anesthesia, rapid intraoperative parathyroid hormone assay to confirm the adequacy of resection, and discharge within 1 to 3 hours of surgery. METHODS: MIP was offered to 100 selected consecutive patients during an 18-month period beginning in March 1998. RESULTS: Ninety-two cases were accomplished under cervical block anesthesia and 89 of these on an ambulatory basis. The cure rate was 100%, and there were no long-term complications. The mean hospital charge for MIP was less than 40% of that associated with traditional exploration. CONCLUSIONS: Outpatient MIP appears to be the procedure of choice for most patients with primary hyperparathyroidism.

Corticotropin-independent Cushing's syndrome caused by an ectopic adrenal adenoma.

Although nonsecreting suprarenal embryonic remnants are frequently found in the urogenital tract, adenomatous transformation resulting in glucocorticoid excess is a rare phenomenon. We report a case of a 63-yr-old woman that presented with new-onset hirsutism, facial plethora, hypertension, centripetal obesity, and a proximal myopathy. The 24-h urinary free cortisol excretion rate was elevated, and the serum ACTH level was suppressed. The patient failed an overnight and low dose dexamethasone suppression test and did not respond to CRH stimulation. In light of the undetectable baseline morning ACTH levels and the blunt response to CRH, the diagnosis of corticotropin-independent Cushing's syndrome was made. Imaging studies revealed normal adrenal glands and enlargement of a left pararenal nodule incidentally observed 4 yr before the onset of symptoms. Dramatic resolution of symptoms was observed after surgical removal of the 3.5-cm mass. Pathological exam confirmed adrenocortical adenoma in ectopic adrenal tissue. The case reported here represents the unusual circumstance in which the development of adenomatous transformation of ectopic adrenal tissue has been prospectively observed with imaging studies. It illustrates the importance of considering ectopic corticosteroid-secreting tumors in the context of corticotropin-independent Cushing's syndrome.

Paraganglioma of the thyroid: two cases that clarify and expand the clinical spectrum.

BACKGROUND: Paragangliomas (PGs) can, on rare occasions, arise within the thyroid parenchyma presumably from displaced laryngeal paraganglia. On the basis of a limited number of reported cases, thyroid PGs invariably affect women, they are always benign, and they are usually mistaken for some other more common thyroid lesion. METHODS: We describe the histopathologic features, immunohistochemical findings, and clinical characteristics of two thyroid PGs. RESULTS: One tumor was incidentally discovered in a 55-year-old man during evaluation of a carotid bruit. The other tumor aggressively invaded the trachea and esophagus of a 52-year-old woman with a presumed long-standing nodular goiter. In both cases, the initial pathologic evaluation suggested medullary thyroid carcinoma. Both patients are alive without recurrent disease after surgical resection. CONCLUSIONS: These cases emphasize the need to consider PG in the differential diagnosis of neuroendocrine thyroid tumors, even in those tumors involving men or behaving in a locally aggressive fashion. Failure to do so carries grave implications regarding patient prognosis and management.