Primary hyperparathyroidism: role of the preoperative oral calcium loading test in the differential diagnosis between adenoma and hyperplasia.

Whereas the sensitivity of the membrane calcium receptors is decreased in parathyroid adenoma, extracellular calcium may reduce parathyroid hormone (PTH) secretion through the protein kinase C pathway in parathyroid hyperplasia. The aim of this study was to determine the role of a preoperative oral calcium loading test in the differential diagnosis between adenoma and hyperplasia. Twenty-two subjects with adenoma (group A, age +/- standard error 56 +/-2 years, female/male 15/7), 10 individuals with hyperplasia (group H, age 54 +/-3, female/male 8/2), and 32 age and gender pair-matched controls (group C) underwent the test. Calcium and PTH were measured before and 60, 120, and 180 min after oral administration of 1 g of calcium (as gluconolactate). Product P was defined as minimal PTH concentration (pg/mL) x maximal calcium concentration (mg/dL) during the test. Ratio R was defined as relative PTH decline/relative calcium increase. The PTH decline during the test in group H was comparable to that of the controls. PTH decline <30%, Product P > 1,100, and Ratio R < 4 diagnosed adenoma with specificity of 100%, 90%, and 100%, respectively. PTH decline >60% diagnosed hyperplasia with specificity of 100%. The total accuracy of the test (65%) was comparable to that of technetium-99 m sestamibi scintigraphy (66%) and better than that of ultrasonography (58%). The test may discriminate patients with sporadic diffuse hyperplasia from individuals with solitary adenoma in cases of primary hyperparathyroidism with an indication for surgery.

Diagnosis of normocalcemic hyperparathyroidism by oral calcium loading test.

We evaluated the oral calcium-loading test (OCLT) in diagnosing normocalcemic primary hyperparathyroidism. Calcium and PTH levels were measured before, 60, 120 and 180 min after oral 1 g of calcium gluconolactate administration in 102 consecutive females with high circulating PTH levels, and 25 controls. Patients were classified as follows: Group A, patients with a parathyroid adenoma identified by two imaging modalities. Sub-Group AO, hyperparathyroid patients [no.=13, mean age 59 yr (SD=10)] evaluated prior to parathyroidectomy. Sub-Group AH, non-operated hypercalcemic patients [no.=29, age 63 yr (SD=11)]. Sub-Group AN, normocalcemic non-operated women [no.=14, age 59 yr (SD=8)]. Group B, normocalcemic individuals [no.=46, age 58 yr (SD=11)] with negative parathyroid imaging. Group C, control patients [no.= 25, age 56 yr (SD=12)]. The concentrations of calcium and PTH overlapped in the normocalcemic groups during the OCLT. Product P, defined as circulating PTH nadir (pg/ml) x peak calcium concentration (mg/dl), better discriminated Sub-Group AN from Group B, AUC=0.98 (95% CI 0.95, 1.00) than did Ratio R, defined as relative PTH decline/relative calcium increment, AUC= 0.86 (95%CI 0.73, 0.99). Assuming normal threshold of Product P and Ratio R at 260 and 17 respectively, the combined parameters diagnose normocalcemic hyperparathyroid patients with 100% sensitivity and 87% specificity.

[Quick intraoperative parathormone monitoring].

Successful parathyroidectomy for primary hyperparathyroidism has traditionally consisted of bilateral neck exploration with identification of all parathyroid glands and excision of grossly abnormal glands. Recently it has been reported that preoperative localization combined with intraoperative monitoring of parathyroid hormone enables performing directed unilateral cervical explorations while maintaining similar cure rates. This new surgical approach, feasible under local anesthesia as an outpatient procedure, decreases operative time, improves cosmetic results and may reduce morbidity. We report preliminary results of our experience in implementing this method.

Androgen suppression and clinical improvement with dopamine agonists in hyperandrogenic-hyperprolactinemic women.

OBJECTIVE: To examine the effect of dopamine agonist (DA) treatment on clinical and biochemical features in hirsute, hyperprolactinemic (HPRL) women and the relationship between prolactin (PRL) and androgens. STUDY DESIGN: We evaluated 80 hirsute HPRL women (age, 27 +/- 1 years [mean +/- SE]) with neuroleptic treatment, prolactinoma and idiopathic HPRL (12, 13 and 55, respectively). DA, mainly bromocriptine, was administered for 11 +/- 1 months. Response indicators were Ferriman-Gallwey hirsutism (FGS) and Leeds acne (LAS) scores, circulating PRL, dehydroepiandrosterone sulfate (DHEAS), free and total testosterone, and androstenedione. RESULTS: Baseline PRL correlated positively with DHEAS (r = .23, P = .03) and free testosterone (r = .36, P < .001). In all women, FGS, LAS, PRL, free testosterone, DHEAS and androstenedione decreased by 40-85% during DA treatment (P < .001). The decline in free testosterone was higher when PRL was > or = 65 ng/mL than when PRL was < 65 (P = .03) and correlated positively with basal DHEAS (r = .40, P < .001). CONCLUSION: Our data suggest a modulation by PRL of adrenal androgen production. DA treatment reduces PRL and serum androgens. It results in a significant clinical improvement in acne and hirsutism. Therefore, DA is recommended as monotherapy for hyperandrogenic.

Early postmenopausal bone loss in hyperthyroidism.

OBJECTIVES: To evaluate the effect of hyperthyroidism on bone in relation to the menopausal state. METHODS: Fifty-nine hyperthyroid (HYPER), 40 hypothyroid (HYPO), and 51 control euthyroid (EUTH) women were studied. Bone mineral density (BMD) was assessed by dual X-rays absorptiometry (DXA) at the lumbar spine, and at the femoral neck. A multi-site QUS device evaluated speed of sound (SOS) at the radius (RAD), tibia (TIB), metatarsus (MTR), and phalanx (PLX). Bone markers used were serum bone specific alkaline phosphatase (BSAP) and urinary deoxypyridinoline (DPD). RESULTS: At all sites, SOS was lower in HYPER than in EUTH (RAD P<0.05, TIB P<0.01, MTR P<0.05, PLX P=0.01). The low SOS was only noted at the early postmenopausal period. BMD at the femoral neck but not at the lumbar spine was lower in HYPER as compared to EUTH (P<0.05). Both femoral neck and tibia were the sites with the highest odds ratio for being hyperthyroid (2.3 and 2.04, respectively). There was no correlation between BMD or SOS and FT(4), TT(3) or duration of hyperthyroidism. BSAP and DPD positively correlated with FT(4) and TT(3) (P<0.05). CONCLUSIONS: This study suggests that hyperthyroidism affects bone mineralization especially during the early postmenopausal period, and the effect is mainly at the cortical bone.

[Epidemiological characteristics and I-131 scintigraphic of patients with papillary thyriod carcinoma with distant metastases].

One hundred and twenty-nine patients with papillary thyroid carcinoma were treated with radioiodine (I-131) and followed up in our department between the years 1992 and 2000. Thirty-three patients (25.6%) had distant metastases (mean follow-up time was 3.12 +/- 2.9 years). The incidence of distant metastases among patients with papillary carcinoma was higher in our group in comparison with most published studies. The most common sites for distant metastases were the lungs and mediastinum. In 32 of the 33 patients distant metastases were found in those sites. We characterized two main patterns of I-131 uptake in lung metastases: in the first there was diffuse lung uptake and in the second there were focal lesions. Bone metastases were only found in one patient. Distant metastases were found in 38.7% of males as compared to 21.4% of females. The age of the male patients with distant metastases was significantly higher than the age of the other patients (mean age 52.8 years, p = 0.099). There was no significant association between distant metastases and advanced age. Most cases of distant metastases in females (81%) were diagnosed at the time of the primary diagnosis as compared to less than half (42%) in males. Sixteen patients with distant metastases underwent cervical lymph node dissection. In 15 patients (94%) cervical lymph node metastases were found. It was found that 39.4% of the patients with distant metastases were born in Israel and 30.3% were born in the Soviet Union. The percentage of the patients with distant metastases, who came to Israel from the Soviet Union after the nuclear accident in Chernobyl (1986), was found to be significantly higher then their relative number in the Israeli population and higher then their relative number in the hospitalized patient population in the years of the study (24.2% as compared to 9% and 8.1% respectively). The survival rate of patients with distant metastases was 97% and for patients without metastases the rate was 100%.

Reference database for bone speed of sound measurement by a novel quantitative multi-site ultrasound device.

The nonuniform skeletal involvement in osteoporosis argues for multi-site evaluation. The Sunlight Omnisense (Sunlight Ultrasound Technologies, Israel) is a multi-site device that measures speed of sound (SOS) at the appendicular skeleton. We report the reference database for SOS at the radius (RAD), tibia (TIB), metatarsus (MTR) and phalanx (PLX). The database was obtained from 1521 healthy Israeli women (age 20-90 years) out of 2051 respondents. SOS was determined in 97.6% of the participants at the PLX, 96.4% at the TIB, 93.6% at the RAD and 85.1% at the MTR; it was not measurable in 0.5%. Short-term coefficient of variation was lowest at the RAD and always less than 1%. Maximal SOS was noted at 35-45 years of age in three of the sites (RAD 4169 m/s, MTR 3663 m/s, PLX 4047 m/s, respectively) but 10 years earlier at the TIB (3939 m/s). In the perimenopausal period (age 46-55 years), SOS was always lower in post- as compared with premenopausal women (p<0.05). Immediately following the menopause, SOS annually declined close to the short-term CV: 16, 34, 37 and 13 m/s at the RAD, PLX, MTR and TIB, respectively. The average age-stratified SOS values at various measurement sites were highly correlated at the population level (0.96-0.99), but less so at the individual level (0.40-0.57). Therefore, multi-site SOS measurements are better than single-site assessment. After 79 years of age, the average T-score at the RAD and PLX was <--2.5. This is similar to that of dual-energy X-ray absorptiometry (DXA)-determined spine bone mineral density (BMD) and somewhat lower than hip BMD. Equivalent T-score curves obtained by percentile adjustment of SOS at various sites to that of the RAD (at age group 60-69 years) reveal convergence and indicate that 52-68% of women older than 79 years are osteoporotic. In conclusion, multi-site peripheral SOS measurements reveal age-dependent bone changes with a high degree of measurement precision and indicate a prevalence of osteoporosis similar to that obtained by DXA.

Effect of estrogen replacement therapy on speed of sound at multiple skeletal sites.

OBJECTIVES: To evaluate the effect of estrogen replacement therapy (ERT) on postmenopausal bone loss by multi-site ultrasound measurement. METHODS: A cross-sectional comparison of postmenopausal women, ERT users and non-users. The two study groups were enrolled for the reference database collection for the Sunlight Omnisense (Omnisense) and were matched by years since menopause. Speed of sound (SOS) was measured at the distal radius (RAD), mid-shaft tibia (TIB), fifth metatarsus (MTR) and proximal phalanx (PLX). RESULTS: 143 ERT users for 5.2+/-3.6 years were compared with 139 ERT non-users (age: 57.0+/-5.3 and 57.5+/-5.5, respectively). Both groups were 7.1+/-5.0 years since menopause. SOS, expressed in T-score units, was higher at the RAD in ERT users as compared to ERT non-users (-0.55+/-1.30 and -1.36+/-1.60, respectively, P<0.0001), and at the TIB (-0.73+/-1.34 and -1.28+/-1.45, respectively, P=0. 003). Same trend was observed at the MTR and PLX, but not statistically significant because of fewer observations. In early post menopause period, the ERT-non users RAD data shows an annual SOS decrease of 0.17 versus annual increase of 0.12 T-score units (P=0.037). Similar effect is observed at the TIB, though not statistically significant (non-users decrease of 0.20 vs. users increase of 0.08 T-score units/year, P=0.086). CONCLUSIONS: SOS measurements by Omnisense at multiple skeletal sites support the ERT protective effect on bone.

Discrimination of proximal hip fracture by quantitative ultrasound measurement at the radius.

Osteoporosis is a disease that culminates in fragility fractures and, therefore, imposes major burden on the health economy. In dealing with this worldwide condition, it is prudent to use a reliable, inexpensive, portable diagnostic means that does not use ionizing radiation and is capable of measuring bone properties at several sites. Recently, a quantitative ultrasound device (Omnisense) that measures speed of sound (SOS) at multiple skeletal sites was introduced. The Omnisense combines the 'axial transmission' mode and the critical angle concept. Preliminary reports suggested that of the different skeletal sites measured by this device, the distal third of the radius is the preferred measurement site for osteoporosis. In this cross-sectional study, SOS was determined at the radius using Omnisense in 50 hip-fractured elderly women (group F, age 76.1 +/- 6.0 years), 130 elderly controls (group NF, age 71.5 +/- 5.2 years) and 185 young healthy controls (group YH, age 40.6 +/- 3.0 years). Actual SOS was significantly lower in group F compared with group NF (p = 0.0001). Whereas SOS T-scores calculated for each woman and stratified into age subgroups within each of the study groups indicate decline from -2.22 to -3.56 in group F and from -1.56 to -3.17 in group NF, there was an increase from -0.02 to 0.03 in group YH. Age- and BMI-adjusted logistic regression for hip fracture discrimination indicated an area under the receiver operating characteristic curve for hip fracture of 0.79 (95% CI, 0.73-0.86; p = 0.005) and an odds ratio of 1.92 (95% CI, 1.22-3.02; p = 0.005). We conclude that SOS measured at the radius by Omnisense discriminates subjects with hip fracture. from controls. Prospective studies are needed to support the role of Omnisense in assessing the risk of hip fracture.

Diagnosis of polycystic ovary disease in obese women with a 24-hour hormone profile after buserelin stimulation.

OBJECTIVE: To evaluate the 24-hour hormone response to GnRH agonist stimulation in the diagnosis of polycystic ovary disease (PCOD) in obese women. STUDY DESIGN: Forty-three obese PCOD patients and 23 controls were randomized to 1 mg buserelin (BSRL) stimulation (PCOD group P-1, n = 31; control group C-1, n = 12) or 0.1 mg (PCOD group P-0.1, n = 12; control group C-0.1, n = 11). RESULTS: Whereas following 1 mg BSRL administration, serum levels of 17 hydroxyprogesterone (17OHP), delta 4 androstenedione, estradiol (E2) and luteinizing hormone increment (delta LH) as well as the delta LH/delta follicle stimulating hormone ratio were all higher in group P-1 than in group C-1 (P < .001, < .01, < .01, = .08 and < .001, respectively), only 17OHP and E2 serum levels were higher in group P-0.1 than in group C-0.1 (P < .001, and = .01, respectively). Whereas 24-hour LH inversely correlated with body mass index (r = .37, P = .04), 24-hour hormone profile, and basal or glucose-stimulated serum insulin levels did not correlate in group P-1. CONCLUSION: The 1-mg BSRL stimulation test is a convenient diagnostic means in obesity-associated PCOD. The hormone response to BSRL administration is related to obesity, not to insulin resistance.

Role of ultrasound-guided fine-needle aspiration biopsy in evaluation of nonpalpable thyroid nodules.

To determine the role of ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in the evaluation of incidentally diagnosed nonpalpable thyroid nodules (NP-TN), we compared the diagnostic yield of US-FNAB in NP-TN larger than 10 mm in diameter, with palpation-guided (P-FNAB) in palpable thyroid nodules (P-TN) in the same hospital setting. Of 108 consecutive patients with NP-TN (female/male: 97/11, age: 55.2 +/- 14.3, mean +/- SD), malignancy was identified in 8 patients (7 with thyroid papillary carcinoma, 4 of which had extrathyroidal spread, and 1 patient had metastasis of pulmonary adenocarcinoma). Male gender was associated with higher prevalence of malignancy (p = 0.09) while calcification and/or cystic degeneration of the nodule did not predict the cytological findings. Malignancy was identified in 16 of 151 consecutive patients with P-TN (female/male: 139/12, age: 44.1 +/- 9.5, mean +/- SD) indicating a similar rate of malignancy in both NP-TN and P-TN. In the P-TN group thyroid cancer was more common in males (p = 0.007), and the US properties of the nodule did not predict its cytological diagnosis. In conclusion, because similar rates of cancer are detected by FNAB in both NP-TN and P-TN, an FNAB is recommended for NP-TN larger than 10 mm.

Role of colestipol in the treatment of hyperthyroidism.

The enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) is higher in thyrotoxicosis. Bile-salt sequestrants bind iodothyronines and thereby increase their fecal excretion. We, therefore, evaluated the effect of colestipol-hydrochloride administration on clinical and biochemical indices of patients with hyperthyroidism. In a prospective, controlled trial, ninety-two adult volunteers with Graves' disease, toxic autonomous nodule or toxic multinodular goiter were randomly assigned into the following treatment protocols: Group 1, 30 mg of methimazole (MMI) and 20 g of colestipol-hydrochloride (COL) daily; Group 2, 30 mg of MMI daily; and Group 3, 15 mg of MMI 20 g of COL daily. The patients were further classified into Group A, severe hyperthyroidism (baseline levels of total T3 (TT3) > or =5 nmol/l) and Group B, mild to moderate thyrotoxicosis (baseline levels of TT-3<5 nmol/l). Crook's clinical index, serum free T4 (FT4), TT3 and thyroid stimulating hormone (TSH) levels were determined before (WO), following one week (W1) and two weeks (W2) of treatment. Serum TT3 level decreased (mean+/-SE) at W1 by 40.8+/-2.6% of WO in Group1 and by 29.2+/-2.4% in Group 2 (p<0.001), and down further to 47.8+/-3.0% at W2 in Group 1, and 40.6+/-2.8% in Group 2 (p=0.01). Serum FT4 level decreased (mean+/-SE) from WO to W1 by 31.7+/-2.7% in Group 1 and by 16.2+/-3.1% in Group 2 (p=0.005), and down to 49.1+/-2.8% of WO at W2 in Group 1 and to 38.7+/-3.5% in Group 2 (p=0.07). In sub groups B COL was not effective in reducing thyroid hormone levels nor in ameliorating the clinical status of the patients. However, in Group A3 COL lowered FT4 (p=0.001) and TT3 (p=0.05) levels as compared to group A2. At W2 the clinical hyperthyroidism score improved faster in Group A1 (p<0.001) and Group A3 (p=0.012) as compared to the control Group A2. In conclusion, COL is an effective and well tolerated adjunctive agent in the treatment of hyperthyroidism. Its main effect is in severe cases of thyrotoxicosis, and in the first phase of treatment. As adjunctive COL treatment in hyperthyroidism allows reducing MMI dosage it may decrease the rate of dose dependent MMI side effects.

A study of the clinical differences between women and men with hyperprolactinemia.

A group of 64 women and 14 men with hyperprolactinemia were followed up in an endocrine service center for a mean of 43 months. The various parameters in each sex were compared. The mean age at first visit was 49 years in the men and 36 years in the women (p < 0.001). The peak prolactin index levels were 13.7 in the men and 5.5 in the women (p < 0.002). Macroprolactinomas were significantly more prevalent in the men (p < 0.002). The women complained significantly more about headache (p < 0.02), malaise (p < 0.02), restlessness (p < 0.03) and fatigue (p < 0.04). These symptoms had no correlation with the prolactin level. Thus, in the men the clinical manifestations of hyperprolactinemia came to attention at an older age and had a connection with a higher prevalence of macroprolactinoma. The possible mechanisms are discussed. Vague complaints, reported more often by the women, do not seem to correlate with the prolactin level.