Three-dimensional cytomorphology in fine needle aspiration biopsy of parathyroid lesions

OBJECTIVE: To elucidate three-dimensional (3-D) cytomorphology in fine needle aspiration biopsy (FNAB) of parathyroid lesions. STUDY DESIGN: Ultrasound-guided FNAB was performed on parathyroid lesions from 10 patients with hyperparathyroidism. The aspirates were stained and observed under a light microscope (LM). The aspirates were also fixed, dehydrated, critical point dried, spattered with gold ions and observed with a scanning electron microscope (SEM). Findings under SEM were correlated with the appearances under LM as well as with serum parathyroid hormone (PTH) concentrations. RESULTS: Under LM, nine cases displayed isokaryosis and one case, anisokaryosis. These appearances corresponded to isocytosis or anisocytosis under SEM. Under SEM, 3-D cytomorphology of parathyroid lesions displayed isocytotic, scattered cells in five cases, uniform cellular arrangements in four cases and anisocytotic, scattered cells in one case. The cell surface was rather smooth in five cases. The other five cases had significant granules on the cell surfaces; these all had serum PTH concentrations > or = 268 pg/mL. CONCLUSION: 3-D cytomorphology in FNAB of parathyroid lesions was a rather smooth cell surface in cases with low serum PTH and a granular cell surface in cases with significantly increased serum PTH. These characteristics and the absence of microvilli might be helpful in the differential diagnosis between parathyroid and follicular thyroid lesions.     

Ultrasound-guided fine needle aspiration cytology of parathyroid lesions. A review of 72 cases

OBJECTIVE: To elucidate the specific cytomorphologic patterns and diagnostic pitfalls in fine needle aspiration cytology (FNAC) of parathyroid lesions. STUDY DESIGN: Seventy-two cases of surgically excised and pathologically verified hyperparathyroidism (20 cases of parathyroid hyperplasia, 51 of parathyroid adenoma and one of parathyroid carcinoma) received preoperative, ultrasound-guided FNAC examination for enlarged parathyroid glands. The smears were reviewed and analyzed. RESULTS: Parathyroid lesions were diagnosed cytologically in 60 cases (83.3%). The presence of colloidlike substance, macrophages or follicular structures in smears led to six cases (8.3%) being misinterpreted as thyroid lesions. The cellularity of the smears was insufficient for interpretation in six cases (8.3%); however, two of these cases were diagnosed by determination of parathyroid hormone (PTH) levels in the fluid. Parathyroid hyperplasia had more tightly cohesive cell clusters with monomorphism, while parathyroid adenoma had more dispersed or loosely cohesive cells with pleomorphism and anisokaryosis. High PTH concentration in an aspirate was noted in all four cases of cystic lesions.     

The use of toluidine blue in locating abnormal parathyroid tissue at operation

The use of toluidine blue solution infused intraoperatively in order to stain selectively abnormal parathyroid tissue was assessed in nine patients with the clinical diagnosis of hyperparathyroidism. There was one case of hyperplasia, one of carcinoma and seven of solitary adenoma. In all cases abnormal parathyroid tissue could be distinguished from adjacent neck tissue. Staining was of particular benefit in the cases of parathyroid tissue in ectopic sites. Dye infusion was tolerated well and all patients had an uncomplicated postoperative course. No cardiotoxicity was apparent. In five patients who had undergone radioimmunoassay studies of parathyroid hormone the use of toluidine blue was also found to be of assistance.     

Fine needle aspiration cytology in the preoperative diagnosis of ultrasonically enlarged parathyroid glands

The value of fine needle aspiration (FNA) cytology in the diagnosis of ultrasonically suspected parathyroid gland enlargements was reviewed for a six-year series of cases. In 146 patients, 277 FNA biopsies under ultrasound guidance were performed on suspected enlarged parathyroid glands. Smears were routinely stained by the Pappenheim (May-Grünwald-Giemsa) method, and the Grimelius silver stain was used to demonstrate argyrophilic granules in the cytoplasm of parathyroid cells. Diagnostic material was obtained by FNA from 121 (83%) patients, whereas the aspirates were considered inadequate for cytologic diagnosis in 25 (17%) patients. For the 121 cases with adequate FNA samples, cytology diagnosed a parathyroid origin in 80 (55%) of the 146 total patients) and a thyroid origin in 41 (28%). The cytologic-histologic correlation available for 36 patients showed a cytologic sensitivity of 86%. Parathyroid lesions are frequently treated preoperatively as a disease of the thyroid; the results of this study suggest that cytomorphologic analysis of FNA samples can demonstrate the parathyroid origin of such samples, especially when a silver stain is used in addition to the routine stain.     

Fine needle aspiration cytology of cystic parathyroid lesions. A cytomorphologic overlap with cystic lesions of the thyroid

Three cases of palpable cystic parathyroid nodules examined by fine needle aspiration (FNA) cytology are reported. Two of the three aspirates were incorrectly identified as thyroid neoplasms due to the presence of papillary clusters or microfollicles and grossly golden-brown cyst fluid. Histologic examination of these two nodules revealed partially cystic parathyroid adenomas. Aspirated material from the third patient yielded clear watery fluid, which was correctly identified as consistent with a parathyroid cyst. The diagnostic difficulties in the differentiation of parathyroid adenoma from thyroid carcinoma or adenoma are discussed, as is the utilization of assays for parathyroid hormone in making the FNA diagnosis of parathyroid lesions.     

Relationship of parathyroid adenoma volume and biochemical function

We retrospectively studied data of 24 patients with surgically proven hyperparathyroidism to determine whether biochemical function correlated with the calculated volume of parathyroid adenoma. Carboxyl-terminal parathyroid hormone (C-PTH), amino-terminal parathyroid hormone (N-PTH), nephrogenous cyclic AMP (N-CAMP), and other markers of calcium metabolism were measured with standard techniques. Tumors were divided into small (less than 1.0 cm3) or large (greater than or equal to 1.0 cm3) sizes. N-PTH and C-PTH measurements were increased in 10% and 30% of patients with small tumors and in 71 and 78% of patients with large tumors. Serum calcium, N-CAMP, C-PTH and N-PTH tended to be greater with large tumors, but only C-PTH was significant. We concluded that the size of parathyroid adenoma influenced biochemical measurements of its activity and that the measurements of PTH in patients with small tumors are not as sensitive as those in patients with large tumors.     

Eleven cases of nonfunctioning parathyroid cyst--significance of needle aspiration in diagnosis and management

Eleven cases of nonfunctioning parathyroid cyst are reported. Ultrasonography revealed the cystic nature of the asymptomatic lump in the neck. Clear watery fluid obtained by needle aspiration and the increased parathyroid hormone concentration in the fluid established the diagnosis. Five patients, in four of whom the cysts reappeared after one (3 cases) or seven (1 case) needle aspirations, underwent surgical resection of the cysts. Six other patients were followed conservatively after the aspiration maneuver. In four patients with enough follow-up time for evaluation, the cyst fluid has not reaccumulated 5, 2 and 2 years after only one aspiration, and 1 year after two aspirations. In one patient, the cyst reappeared 9 months after the initial aspiration. Simple percutaneous aspiration may be curative in some cases of nonfunctioning parathyroid cysts.     

A case report: Giant cystic parathyroid adenoma presenting with parathyroid crisis after Vitamin D replacement

ABSTRACT: BACKGROUND: Parathyroid adenoma with cystic degeneration is a rare cause of primary hyperparathyroidism. The clinical and biochemical presentation may mimic parathyroid carcinoma. Case Presentation: We report the case of a 55 year old lady, who had longstanding history of depression and acid peptic disease. Serum calcium eight months prior to presentation was slightly high, but she was never worked up. She was found to be Vitamin D deficient while being investigated for generalized body aches. A month after she was replaced with Vitamin D, she presented to us with parathyroid crisis. Her corrected serum calcium was 23.0 mg/dL. She had severe gastrointestinal symptoms and acute kidney injury. She had unexplained consistent hypokalemia until surgery. Neck ultrasound and CT scan revealed giant parathyroid cyst extending into the mediastinum. After initial medical management for parathyroid crisis, parathyroid cystic adenoma was surgically excised. Her serum calcium, intact parathyroid hormone, creatinine and potassium levels normalized after surgery. CONCLUSION: This case of parathyroid crisis, with very high serum calcium and parathyroid hormone levels, is a rare presentation of parathyroid adenoma with cystic degeneration. This case also highlights that Vitamin D replacement may unmask subclinical hyperparathyroidism. Consistent hypokalemia until surgery merits research into its association with hypercalcemia.     

Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial

ABSTRACT: BACKGROUND: Increasing evidence suggests the bidirectional interplay between parathyroid hormone and aldosterone as an important mechanism behind the increased risk of cardiovascular damage and bone disease observed in primary hyperparathyroidism. Our primary object is to assess the efficacy of the mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone secretion in patients with parathyroid hormone excess. Methods/design Overall, 110 adult male and female patients with primary hyperparathyroidism will be randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50 mg once daily after dose titration] or placebo, over eight weeks. Each participant will undergo detailed clinical assessment, including anthropometric evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography, kidney function and detailed laboratory determination of biomarkers of bone metabolism and cardiovascular disease. The study comprises the following exploratory endpoints: mean change from baseline to week eight in (1) parathyroid hormone(1--84) as the primary endpoint and (2) 24-hour systolic and diastolic ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24 hours urinary protein/albumin excretion and echocardiographic parameters reflecting systolic and diastolic function as well as cardiac dimensions, as secondary endpoints. DISCUSSION: In view of the reciprocal interaction between aldosterone and parathyroid hormone and the potentially ensuing target organ damage, the EPATH trial is designed to determine whether eplerenone, compared to placebo, will effectively impact on parathyroid hormone secretion and improve cardiovascular and bone health in patients with primary hyperparathyroidism. Trial registration ISRCTN33941607.     

A vasopressor factor partially purified from human parathyroid glands.

Recently, a parathyroid hypertensive factor was postulated to play a role in the pathogenesis of hypertension in genetically hypertensive rats. Therefore it was examined, whether in human parathyroid glands a vasopressor substance can be detected. For this purpose, homogenates of hyperplastic parathyroid glands from 20 patients with tertiary hyperparathyroidism were deproteinized and fractionated by gel chromatography. The fractions obtained were tested for vasopressor activity in isolated perfused rat kidneys. A vasopressor fraction containing substances of 0.6-2.5 kDa was identified in the parathyroid glands. The responsible product was heat sensitive, peptidase-, trypsin- and carboxypeptidase y- sensitive and hydrophilic, as it did not bind to hydrophobic reversed-phase gel. These results suggest that parathyroid glands contain a hydrophilic peptide-like vasopressor substance different from the parathyroid hormone.     

Three large, functioning cystic parathyroid adenomas

ObjectiveTo report a very rare case of 3 large, functioning cystic parathyroid adenomas causing primary hyperparathyroidism.MethodsWe present the history, clinical findings, laboratory test results, radiologic findings, endocrine workup results, intraoperative surgical challenges, and surgical pathology report of the study patient. We review the literature and discuss the importance of intraoperative parathyroid hormone (PTH) measurement in such cases.ResultsA 79-year-old woman presented with primary hyperparathyroidism and elevated levels of calcium and PTH. Localization studies confirmed the presence of a large right upper parathyroid adenoma. On exploration, a very large cystic parathyroid gland was identified at that location. Because intraoperative PTH levels remained elevated, further exploration was pursued, which revealed 2 more large cystic glands on the left side that were resected. This resulted in an adequate but slow PTH drop. The right lower gland appeared normal. On follow-up 4 days and 6 weeks after surgery, the calcium and PTH levels had normalized.ConclusionThis case highlights the aspects of intraoperative PTH use and underscores the need to exclude multigland disease even in the setting of a very large parathyroid cyst with concordant localization studies. (Endocr Pract. 2012;18:e14-e16)     

Lectin-binding sites in human parathyroid tissue

The aim of this study was to demonstrate several lectin-binding sites in human parathyroid tissue and to correlate these results with functional activity. The following lectins were tested for binding sites with certain carbohydrates (in parentheses): Arachis hypogea (PNA) (galactose), Ulex europaeus I (UEA) (fucose) and concanavalin A (ConA) (mannose). In addition to normal parathyroids used as controls (13 cases), we examined adenomas associated with a clinical picture of primary hyperparathyroidism of differing severity (31 cases), atrophic glands contralateral to a hyperfunctioning adenoma (7 cases), and secondary (renal) hyperplasia (12 cases). Use of PNA (with and without neuraminidase treatment) and UEA yielded negative staining in normal glands, a wide variety of reactions in adenomas, and frequent dense precipitates in atrophic parathyroids, whereas ConA yielded positive staining in all kinds of parathyroid tissue. Assessment of functional activity of adenomas by clinical parameters (pre-operative serum levels of calcium and parathormone) displayed a significant correlation with the semiquantitative grading of the histochemical reactions after PNA and UEA. Lectin-binding sites in parathyroid chief cells of adenomas are believed to indicate some of the cell structures or products directly involved in the secretory process, including degradation. Although ConA may recognize constituent parathyroid glycoproteins, the binding sites for PNA and UEA are thought to be partially associated with secretory glycoprotein (SP-I), as is known from animal experiments. The positive reaction of the atrophic gland may result from degradation enforced by exposure of primarily non-terminal carbohydrate components.     

Fine needle aspiration of parathyroid lesions

OBJECTIVE: To assess the cytologic features of parathyroid lesions and to determine if it is possible to differentiate between parathyroid hyperplasia (PH) and parathyroid adenoma (PA) based on fine needle aspiration (FNA). STUDY DESIGN: FNAs of 14 parathyroid lesions were performed during intraoperative consultation. Alcohol-fixed, Papanicolaou-stained smears and air-dried Diff-Quik-stained smears were prepared in each case. Cytologic features were evaluated. RESULTS: All cases, PA and PH, showed numerous bare nuclei in the background. Ninety percent of PA contained microfollicular groups in addition to sheets and syncytia, while PH was arranged primarily in sheets and syncytia without microfollicles. Nuclear pleomorphism was seen in 33% of PA and absent from PH. CONCLUSION: Careful evaluation of cytologic features might help to differentiate between PA and PH on FNA.     

Functioning parathyroid lipoadenoma--report of four cases: clinicopathological and ultrasonographic features

Functioning parathyroid lipoadenoma (hamartoma) composed of abundant adipose or myxomatous stroma and epithelial cell nests is an unusual cause of primary hyperparathyroidism. We report herein four new cases. None of them belongs in the category of multiple endocrine neoplasia or familial hyperparathyroidism. The clinical manifestations and the laboratory findings are indistinguishable from those of the usual forms of primary hyperparathyroidism. Ultrasonography of the neck demonstrated an enlarged parathyroid gland as a hyperechoic mass in the two patients tested. At operation in each case, a single enlarged gland was found and resected, the weight being 3, 0.3, 0.45 and 1 g, respectively. The patients are normocalcemic 1 to 10 years after surgery. Pathological examination disclosed that the lesions were consistent with lipoadenoma or its variants. On reviewing 20 cases of functioning lipoadenoma which were reported in the literature, including the present cases, we found that the size of the tumors varied and a functioning lipoadenoma is hence by no means unusually large as previously reported. Without knowledge of this specific clinicopathologic entity, the lesion may be overlooked at the preoperative localization study and misdiagnosed as a normal or hyperplastic parathyroid.     

Significance of Elevated Parathyroid Hormone After Parathyroidectomy

ObjectiveTo review the prevalence of parathyroid hormone elevation after parathyroidectomy for primary hyperparathyroidism and to discuss possible mechanisms.MethodsA Medline search of the English-language literature published between 1990 and 2009 was performed using the search terms “elevated PTH after parathyroidectomy.” All of the identified articles reported either prospective or retrospective studies without control groups. Studies that included patients with secondary or tertiary hyperparathyroidism were not reviewed.ResultsWithin 1 week to 5 years after parathyroidectomy, 9% to 62% of patients with a normal serum calcium concentration are reported to have an elevated parathyroid hormone concentration. No evidence suggests that postoperative normocalcemic parathyroid hormone elevation is an indication of surgical failure and recurrent hypercalcemia. Preoperative findings in patients with postoperative parathyroid hormone elevation include lower vitamin D concentration, higher concentrations of bone turnover markers, and higher parathyroid hormone concentration. Potential mechanisms for parathyroid hormone elevation in the setting of normocalcemia include vitamin D deficiency, hungry bone syndrome, and parathyroid hormone resistance. Study findings suggest a possible benefit of postoperative calcium and vitamin D supplementation, but no randomized trials have been done.ConclusionElevation of parathyroid hormone commonly occurs after parathyroidectomy for primary hyperparathyroidism, although the underlying mechanism remains unclear. (Endocr Pract. 2010;16:112-117)     

Ultrasound-guided laser thermal ablation for parathyroid adenomas: analysis of three cases with a three-year follow-up

BACKGROUND: In patients with primary hyperparathyroidism (pHPT) the therapeutical choice is surgery. In patients with high surgical and anesthetic risks, ultrasound-guided laser ablation (LTA) of parathyroid adenoma has been reported to reduce parathyroid hormone (PTH) hypersecretion without relevant side effects. No data are available from patients followed for >6 months. We report our 3-year follow-up experience with LTA in 3 patients affected by pHPT due to a parathyroid tumor. METHODS: LTA was performed under color-Doppler ultrasound guidance with a continuous pulse at 2 W (total treatment duration: 300 s in each session; total energy: 1,200 J in two sessions). RESULTS: In the first patient who refused to undergo the second LTA session, calcium, PTH levels and parathyroid lesion volume showed a slight reduction, returning to baseline values in a month. In the second patient, no modification of parathyroid lesion was obtained even if calcium levels temporarily normalized. In the third patient, LTA led to normalization of calcium and PTH levels and to a 99% reduction of parathyroid volume. CONCLUSION: After LTA procedures the long-term disease remission of pHPT is achievable in a minority of patients. Data from larger samples are needed to verify the usefulness of this procedure.     

Normal responsiveness of serum parathyroid hormone to beta-adrenergic blockade in patients with secondary hyperparathyroidism

Infusion of calcium gluconate (15 mg Ca++/kg body weight in 4 h) to 6 patients with secondary hyperparathyroidism (due to mild renal insufficiency) decreased serum parathyroid hormone (PTH) levels to the same degree (on a percent basis) as in normal subjects. Serum PTH values at 4 h were 60 +/- 4.5 (SEM)% of baseline in the patients and 59 +/- 2.9% of baseline in the normal subjects. Infusion of propranolol (1 mg i.v. bolus followed by an infusion of 60 micrograms/min for 2 h) to 7 additional patients with secondary hyperparathyroidism also decreased serum PTH to the same degree as in normal subjects. Serum PTH values at 2 h were 68 +/- 10.4% of baseline in the patients and 68 +/- 3.3% of baseline in the normal subjects. The studies indicate normal responsiveness of serum PTH to calcium or beta-adrenergic blockade in secondary hyperparathyroidism due to mild renal insufficiency.     

西那卡塞治疗血液透析患者继发性甲状旁腺功能亢进症的临床研究

通过研究两个相同随机、双盲、安慰剂对照试验,本研究评估了拟钙剂盐酸西那卡塞治疗血液透析患者继发性甲状旁腺功能亢进症的临床效果。将接受血液透析及进行标准治疗仍控制不佳的继发性甲状旁腺功能亢进患者随机分配接受西那卡塞(80名患者)或安慰剂(80名患者)治疗26周。每日一次的剂量从30 mg增加到180 mg,以达到患者体内每毫升250 mg或更少的完整甲状旁腺激素水平。主要终点是进行为期14周的疗效评估阶段的患者在该范围内的值的百分比。西那卡塞组有43%的患者达到主要终点,而安慰剂组仅为5%(p<0.001)。总体而言,接受西那卡塞治疗的患者平均甲状旁腺激素水平下降43%,而安慰剂组平均甲状旁腺激素水平下降9%(p<0.001)。西那卡塞组患者体内血清钙磷乘积下降15%,安慰剂组则维持不变(p<0.001)。西那卡塞可有效降低甲状旁腺激素水平,而不依赖于疾病严重程度或维生素D甾醇剂量的变化。西那卡塞可降低接受血液透析的不受控制继发性甲状旁腺功能亢进症患者体内的甲状旁腺激素水平,提高钙磷稳态。     

Fine needle aspiration cytology of parathyroid adenoma. A review of seven cases

The value of fine needle aspiration (FNA) cytology in the diagnosis of parathyroid adenomas was demonstrated by a cytohistologic review of seven cases. The cytologic patterns, which were characterized by numerous, mostly isolated epithelial cells and naked nuclei showing anisokaryosis and multiple nucleoli, were consistent with the histologic findings in this neoplasm, which should be considered in the differential (FNA) diagnosis of masses in the neck region. The only diagnostic problem is its differentiation from follicular thyroid neoplasms.