Coexistence of a parathyroid adenoma and parathyroid cyst causing primary hyperparathyroidism

The association of a functional parathyroid cyst with a parathyroid adenoma is an uncommon finding. In this report we describe the clinical history of a 60-yr-old man, presenting with the following findings: hypercalcemia (18.9 mg/dl), elevated serum parathormone levels (1320 pg/dl), hypercalciuria (228 mg/dl), and hyperphosphaturia (155 mg/dl). Neck ultrasound, magnetic resonance imaging (MRI) and 99Tc Sestamibi scintigraphy led to the identification of a left parathyroid adenoma, located at the lower pole of the left thyroid gland lobe, associated with a parathyroid cyst, located at the upper extremity of the same thyroid lobe. Parathyroidectomy was performed and the histological examination confirmed the diagnosis of a parathyroid adenoma with aspects of cystic degeneration and an upper parathyroid cyst. Analysis of the crystal clear intracystic fluid showed elevated parathyroid hormone (PTH) levels (137.000 pg/ml). The patient is normocalcemic at 2 yr after surgery without signs of recurrent parathyroid enlargements. Aetiology, diagnosis and management of parathyroid cyst will be discussed.     

Spontaneous short-term remission of primary hyperparathyroidism from infarction of a parathyroid adenoma

We report a 39-yr-old woman with spontaneous short-term remission of primary hyperparathyroidism (PHPT). She was referred to our Department for PHPT with bilateral kidney stones diagnosed elsewhere; at the time of our observation she had developed anterior neck pain associated with swelling and tenderness. Biochemical data (serum ionized calcium and PTH) suggested a remission of the PHPT. The local symptoms gradually improved and disappeared over the next several days without therapy. Serum ionized calcium and PTH levels remained normal for up to 11 months. Subsequently, the patient had a recurrence of PHPT with mild hypercalcemia and elevated PTH levels. The patient underwent surgery and pathological examination revealing a 1.0 x 1.2 cm parathyroid adenoma with areas of necrosis with hemosiderinladen macrophages. In conclusion, we describe a case of spontaneous short-term remission of PHPT due to infarction of parathyroid adenoma.     

Ultrasonographic features of parathyroid carcinoma.

Although several authors have reported single cases illustrative of some ultrasonographic characteristic of parathyroid carcinoma, the value of ultrasonography for diagnosing this entity remains to be determined. The purpose of our study was to investigate the ultrasonographic features of parathyroid carcinoma in a large number of cases. We assessed the shape, contour, echogenicity, and depth-width (DW) ratio of 16 parathyroid carcinomas and 61 parathyroid adenomas. Ultrasonography showed that parathyroid carcinomas tend to be large, inhomogeneous, hypoechoic masses with lobulated contours. In contrast, parathyroid adenomas were small, homogeneous, hypoechoic masses with smooth borders. The mean (range) DW ratios for parathyroid carcinomas were 1.21 (0.91-2.5) and 0.64 (0.33-1.47) for adenomas; the difference was statistically significant (p<0.0001). The DW ratio was > or =1 in 15 (94%) of the 16 cases of carcinoma, whereas only 3 (5%) of the 61 adenomas had a similar ratio. Ultrasonographic examination is useful not only for preoperative localization but also for differentiating parathyroid carcinoma from adenoma. Parathyroid tumors with irregular margins, inhomogeneous echogenicity, and a DW ratio > or =1 are likely to be malignant.     

Childbearing and the risk of parathyroid adenoma – a dominant cause for primary hyperparathyroidism

OBJECTIVES: To explore possible associations between the reproductive history amongst women and the risk of parathyroid adenoma (PA). DESIGN: Two nationwide Swedish registries. The Fertility Register included data on more than 3.4 million livebirths between 1943 and 1992 amongst Swedish females born 1925-72. The Cancer Register encompasses more than 1800 women with a diagnosis of PA 1960 until 1992. SETTING: All women resident in Sweden 1960-92. SUBJECTS: Cases were all 1800 women born 1925-72 reported to the Swedish Cancer Registry with a histopathological diagnosis of PA. Five controls were selected at random for each case by matching for the month and year of birth. Conditional logistic regression was used to estimate relative risks of PA. MAIN OUTCOMES: Parathyroid adenoma. RESULTS: High parity (four or more live births) was associated with an increased risk of PA. Amongst women with a diagnosis of PA before menopause (i.e. the age of 50 years) there was an increased risk of PA with younger age at first childbirth. Nulliparous women were at increased risk for PA before menopause, and at decreased risk after menopause. CONCLUSIONS: There is an association between childbearing and the risk of PA, which has not previously been demonstrated, but the underlying biological mechanisms remain to be determined.     

Hypocalcemia due to spontaneous infarction of parathyroid adenoma and osteomalacia in a patient with primary hyperparathyroidism.

A 49 year-old Japanese woman had subjected enlargement of a cervical tumor, and also suffered two bone fractures in 2 years. The cervical tumor had enlarged further in the month prior to admission, becoming warm and tender. Endocrinological examination revealed that the serum intact PTH concentration was remarkably high at 400 pg/mL despite the low serum calcium concentration, and that the serum vitamin Ds concentration was decreased. Bone roentgenograms revealed severe osteolytic changes compatible with osteitis fibrosa cystica and a pathologic fracture of the humerus. Under a diagnosis of primary hyperparathyroidism, parathyroidectomy was performed, followed by fixation surgery for the pathologic fracture. Histologically, the cervical tumor was a parathyroid chief-cell adenoma with massive necrosis, and the bone pathology by iliac bone biopsy revealed the existence of osteomalacia. She was treated with calcium, vitamins D and K2 and calcitonin after the surgery. This case is a rare condition manifesting hypocalcemia with catastrophic osteoporosis under the coexistence of spontaneous infarction of parathyroid adenoma with osteomalacia, suggesting that the clinical features of hyperparathyroidism are modified by both the autoparathyroidiectomy and the existence of osteomalacia due to vitamin D deficiency.     

Vitamin D status, seasonal variations, parathyroid adenoma weight and bone mineral density in primary hyperparathyroidism

BACKGROUND: Primary hyperparathyroidism (PHPT) and vitamin D insufficiency are common conditions that can occur in combination. However, low plasma 25-hydroxyvitamin D (25OHD) may also enhance the risk of PHPT or modify disease severity. AIM: To compare the risk of vitamin D insufficiency and deficiency stratified by age, sex and season between PHPT patients and controls and to assess associations between plasma 25OHD and adenoma weight, biochemical variables, bone mineral density (BMD) and clinical complications. DESIGN: Cross-sectional study. MATERIAL: A total of 289 consecutive Caucasian patients with PHPT aged 65.9 (24-92) years, 289 sex-, age- and season-matched normocalcaemic controls and 187 healthy adult blood donors. PHPT diagnosis was confirmed in 214 by neck exploration. RESULTS: Vitamin D insufficiency (plasma 25OHD < 50 nmol/l) was observed in 81% of PHPT patients compared with 60% of sex- and age-matched controls (P < 0.001) and 35% of blood donors (P < 0.001). During summer, 77%vs. 53% (P < 0.001) and 4% (P < 0.001), respectively, had vitamin D insufficiency. Average plasma 25OHD was 41 (range 9-87) nmol/l among 27 PHPT patients compared with 87 (21-173) nmol/l (P < 0.001) among aged-matched blood donors. During winter, 86%vs. 66% (P < 0.001) and 71% (P < 0.05), respectively, had vitamin D insufficiency. Vitamin D deficiency (plasma 25OHD < 25 nmol/l) was observed in 33% of PHPT patients compared with 20% of age- and sex-matched controls (P < 0.001) and 13% of blood donors (P < 0.001). Both PHPT patients and controls showed seasonal variations in 25OHD related to the average number of sun hours, but values were lower in PHPT patients at all calendar months. In PHPT patients low plasma 25OHD was associated with higher plasma levels of calcium, PTH and alkaline phosphatase and with lower renal calcium excretion, femoral neck and forearm BMD. No association was found between plasma 25OHD and adenoma weight (total or divided into tertiles). There was a trend towards increased risk of osteoporotic fractures (P < 0.08) with low plasma 25OHD. CONCLUSION: Vitamin D insufficiency and deficiency are common findings in PHPT and occur more often than in a sex- and age-matched control group referred from general practice and in normal blood donors irrespective of season. Low plasma 25OHD levels are associated with an aggravated clinical presentation of PHPT but do not affect adenoma size.     

Rheumatic manifestations of primary hyperparathyroidism and parathyroid hormone therapy

A frequent manifestation of severe primary hyperparathyroidism was the bone disease osteitis fibrosa cystica. Rarely, excess parathyroid hormone (PTH) was associated with gout and calcium pyrophosphate crystal deposition disease. Surgical cure of primary hyperparathyroidism was occasionally associated with pseudogout. Today, primary hyperparathyroidism is generally asymptomatic. Clinically overt rheumatologic and skeletal effects are mainly of historical interest. Skeletal disease is still detectable by more sensitive techniques. In certain circumstances, PTH may be protective and anabolic for the skeleton.     

Non-autonomy of parathyroid hormone secretion in acute primary hyperparathyroidism

A patient with acute primary hyperparathyroidism treated with mithramycin preoperatively, underwent neck exploration and two enlarged parathyroid glands were excised: one huge adenoma (6g) and another smaller gland. Mithramycin was administered preoperatively to lower life-threatening hypercalcaemia, and parathyroid slices from the huge adenoma removed at surgery were submitted in vitro to various calcium concentrations in the media to determine the influence of calcium on parathyroid adenoma secretory pattern in acute primary hyperparathyroidism. Mithramycin induced a significant decline in calcium levels and significant elevations of calciotrophic hormones (intact PTH, mid-region specific PTH, calcitonin and calcitriol). Significant suppression in PTH output in vitro was achieved by increasing calcium levels in the media. These results exclude autonomous PTH secretion (non-calcium dependent) as a possible aetiology of acute primary hyperparathyroidism. We suggest that a sudden increase in the set-point of the diseased parathyroid cells in the presence of a huge cell mass accounts, in large part, for both the marked hypercalcaemia and elevated PTH levels in this patient.     

Multimodality imaging of the parathyroid glands in primary hyperparathyroidism

Primary hyperparathyroidism is a common endocrine disorder, affecting approximately 1 in 500 women and 1 in 2,000 men. Surgical removal of the hyperfunctioning parathyroid gland is the primary curative treatment. The last decade has witnessed the development of minimally invasive parathyroidectomy, which is based on the fact that the vast majority of cases are caused by single adenomas. However, the success of this technique relies on accurate preoperative localisation of the parathyroid lesions. The imaging modalities used vary at different institutions according to local expertise and availability, but include high resolution ultrasound, radionuclide studies, computed tomography (CT) and magnetic resonance imaging (MRI). Ultrasound and 99mTc sestamibi scintigraphy, particularly when complemented by single photon emission computed tomography (SPECT), are currently the imaging techniques of choice for preoperative localisation of parathyroid adenomas; a combination of the two methods further improves the sensitivity and accuracy of detection. CT is less commonly used for preoperative localisation and usually reserved for cases of failed parathyroidectomy, for the detection of suspected ectopic glands. MRI appears to be useful in patients with persistent or recurrent hyperparathyroidism, who have previously undergone surgery. Cross-sectional imaging is also useful in cases where the findings at sonography and scintigraphy are discordant. SPECT/CT appears promising, but further studies are needed to evaluate its role in preoperative localisation.     

Increasing parathyroid hormone concentrations in untreated primary hyperparathyroidism.

Twenty-four patients with mild to moderate primary hyperparathyroidism were followed for an average of 2.45 years with serial determinations of serum ionized calcium and intact parathyroid hormone (PTH). For the entire group serum ionized calcium remained stable, whereas serum PTH increased significantly. Eleven patients (group 1) demonstrated a significant increase in PTH with time. The remaining 13 patients formed group 2. Comparison of the changes (%) in each subgroup showed a small but significant increase in serum ionized calcium of 2.6% with time in group 1, while serum PTH increased by 78%. In group 2 serum ionized calcium remained stable whereas PTH increased modestly by 22%. Serum concentrations of creatinine were stable throughout the follow-up period in both groups. Despite the greater precision of serum ionized calcium, measurements of intact PTH are evidently more sensitive than measurements of serum ionized calcium for the detection of progression in primary hyperparathyroidism.     

A rare case of primary hyperparathyroidism with clear cell adenoma

We report a 52-year-old woman who was noted to have elevated alkaline phosphatase (ALP), hypercalcemia (Ca: 11.7 mg/dL), and intact parathyroid hormone (intact PTH: 643.1 pg/mL), and then referred to our hospital with suspected hyperparathyroidism. Ultrasound examination of the neck and magnetic resonance imaging showed a mass region in the posterior aspect of the left lobe of the thyroid, and Tl-Tc subtraction scintigraphy showed Tl uptake at the same location. Based on laboratory and imaging studies, she was diagnosed with primary hyperparathyroidism. The excised parathyroid was a large mass measuring 6.8 x 2.8 x 1.9 cm in diameter and weighing 15.4 g. It was soft, covered with a thin capsule, did not infiltrate the thyroid parenchyma, and showed no evidence of malignant process. Histopathological examination showed that it was clear cell adenoma. There was no evidence of metastasis from the parathyroid tumor in other organs. The post-operative course was excellent, and serum PTH, Ca, and ALP levels returned to normal. Among parathyroid tumors, large adenomas are commonly considered to be more likely malignant, but in this case it was benign despite measuring more than 6 cm in diameter. The histopathological type of the adenoma was clear cell adenoma, a very rare type. We report a clear cell adenoma of the parathyroid gland, which has not been described previously in Japan.     

Localization of parathyroid tumors using endoscopic ultrasonography in primary hyperparathyroidism

Parathyroid adenomas responsible for primary hyperparathyroidism may be difficult to detect preoperatively. Furthermore parathyroid adenomas may arise behind the (nodular) thyroid gland, in a deep cervical location, and plans should be plane. The purpose of the present prospective study was to evaluate echoendoscopy, and to compare its accuracy to that of non invasive tests. Fourteen consecutive patients with primary hyperparathyroidism were prospectively studied. All patients underwent echoendoscopy, ultrasonography (US), CT scanning or magnetic resonance imaging (MRI) and Tc 99m sestamibi scanning before undergoing initial neck exploration. The parathyroid pathology was a solitary adenoma in 13 patients and a 4 glands hyperplasia in one. All tests were corroborating in 5 cases. Four adenomas were localized to the correc tside (33%), and no test accurately localized all hyperplastic glands. EUS, sestamibi and CT scanning or MRI correctly identified 10 parathyroid tumors in 14 cases (71%). US correctly localized only 5 adenomas (sensitivity 36%). The sensitivity of EUS to detect parathyroid adenomas is superior to US (p<0.05) and comparable to that of other non invasive tests. We conclude that EUS may be an useful tool to localize parathyroid lesions. This method may replace US prior to initial neck exploration with further miniaturization of probes, or find an intermediate place among invasive and noninvasive preoperative localization procedures in patients with persistent or recurrent PHPT.