Monique Nakayama Ohe

Changes in clinical and laboratory findings at the time of diagnosis of primary hyperparathyroidism in a University Hospital in São Paulo from 1985 to 2002

In contrast to most developed countries, most patients with primary hyperparathyroidism in Brazil are still symptomatic at diagnosis. However, we have been observing a change in this pattern, especially in the last few years. We evaluated 104 patients, 77 females and 27 males aged 11-79 years (mean: 54.4 years), diagnosed between 1985 and 2002 at a University Hospital. Diagnosis was made on the basis of clinical findings and of high total and/or ionized calcium levels, high or inappropriate levels of intact parathyroid hormone and of surgical findings in 80 patients. Patients were divided into three groups, i.e., patients diagnosed from 1985 to 1989, patients diagnosed from 1990 to 1994, and patients diagnosed from 1995 to 2002. The number of new cases diagnosed/year increased from 1.8/year in the first group to 6.0/year in the second group and 8.1/year in the third group. The first group comprised 9 patients (mean serum calcium +/- SD, 13.6 +/- 1.6 mg/dl), 8 of them (88.8%) defined as symptomatic. The second group comprised 30 patients (mean calcium +/- SD, 12.2 +/- 1.63 mg/dl), 22 of them defined as symptomatic (73.3%). The third group contained 65 patients (mean calcium 11.7 +/- 1.1 mg/dl), 34 of them symptomatic (52.3%). Patients from the first group tended to be younger (mean +/- SD, 43.0 +/- 15 vs 55.1 +/- 14.4 and 55.7 +/- 17.3 years, respectively) and their mean serum calcium was significantly higher (P < 0.05). All of symptomatic patients independent of group had higher serum calcium levels (12.4 +/- 1.53 mg/dl, N = 64) than asymptomatic patients (11.4 +/- 1.0 mg/dl, N = 40). Our data showed an increase in the percentage of asymptomatic patients over the years in the number of primary hyperparathyroidism cases diagnosed. This finding may be due to an increased availability of diagnostic methods and/or to an increased awareness about the disease.

Total Parathyroidectomy with Presternal Intramuscular Autotransplantation in Renal Patients: A Prospective Study of 66 Patients

Surgical treatment of secondary (SHPT) and tertiary hyperparathyroidism (THPT) may involve various surgical approaches. The aim of this paper was to evaluate presternal intramuscular autotransplantation of parathyroid tissue as a surgical option in SHPT and THPT treatment. 66 patients with renal chronic disease underwent surgery from April 2000 to April 2005 at Universidade Federal São Paulo, Brazil. There were 38 SHPT patients (24 women/14 men), mean age of 39.yrs (range: 14–58), and 28 THPT patients (14 women/14 men), mean age of 43.4 yrs (range: 24–62). Postoperative average followup was 42.9 months (range: 12–96). Postoperative intact PTH increased throughout followup from 73.5 pg/mL to 133 pg/mL on average from 1st to the 5th year, respectively, in SHPT and from 54.9 pg/mL to 94.7 pg/mL on average from 1st to 5th year, respectively, in THPT group. Definitive hypoparathyroidism was observed in 4 (6.06%) patients and graft-dependent recurrence in 6 (9.09%). Presternal intramuscular autotransplantation of parathyroid tissue is a feasible and safe surgical option in SHPT and THPT treatment.

Analysis of the diagnostic presentation profile, parathyroidectomy indication and bone mineral density follow-up of Brazilian patients with primary hyperparathyroidism

Primary hyperparathyroidism is an endocrine disorder with variable clinical expression, frequently presenting as asymptomatic hypercalcemia in Western countries but still predominantly as a symptomatic disease in developing countries. The objective of this retrospective study was to describe the diagnostic presentation profile, parathyroidectomy indication and post-surgical bone mineral density follow-up of patients with primary hyperparathyroidism seen at a university hospital. We found 115 patients (92 women, median age 56 years) with primary hyperparathyroidism diagnosed during the last 20 years. We defined symptomatic patients based on the presence of any classical symptom affecting bone, kidney or the neuromuscular system. Surgical criteria followed the guidelines of the National Institutes of Health regarding asymptomatic primary hyperparathyroidism. Symptomatic patients and patients meeting surgical criteria for parathyroidectomy were 66 and 93% of the sample, respectively. Median calcium and parathyroid hormone values were 11.9 mg/dL and 189 pg/mL, respectively. After surgical treatment, 97% of patients were cured, with increases in bone mineral density of 19.4% in the lumbar spine and 15.7% in the femoral neck 3 years after surgery. Greater bone mass increases were detected in pre-menopausal women, men, and in symptomatic and younger patients, both in the lumbar spine and femoral neck. Our results support the previous findings of a predominantly symptomatic disease with a presentation profile that could be mainly related to a delayed diagnosis. Nevertheless, genetic and racial backgrounds, and nutritional factors such as calcium and vitamin D deficiency may play a role in the clinical presentation of primary hyperparathyroidism of Brazilian patients.

Utilidade da medida de PTH intra-operatório no tratamento cirúrgico do hiperparatiroidismo primário e secundário: análise de 109 casos

INTRODUCAO: A medida de PTH intra-operatorio (PTH-IO) foi inicialmente descrita em 1988, sendo potencialmente util na definicao de sucesso apos a paratiroidectomia. OBJETIVOS: Avaliar prospectivamente perfil de decaimento do PTH-IO e sua capacidade de prever sucesso cirurgico no hiperparatiroidismo primario (HPP) e secundario a insuficiencia renal (HPS). PACIENTES E METODOS: 109 pacientes operados entre 06/2000 e 12/2004, sendo 33 HPP, 76 HPS (52 em dialise, 24 transplantados renais). PTH-IO: metodo imunometrico rapido (Elecsys-PTH/Immunoassay-Roche); tempo para resultado: 10 minutos. Coletas de sangue periferico nos tempos basal, 10 e 20 minutos pos-paratiroidectomia. RESULTADOS: HPP: queda media de PTH de 79,2% aos 10 minutos. HPS: queda media de PTH de 85,8% e 87,6% aos 10 minutos nos pacientes dialise e transplantados respectivamente. A cirurgia foi bem sucedida em todos, exceto em 2 pacientes (1 HPP, 1 HPS). Em ambos nao houve queda PTH-IO, sendo constatado adenoma duplo no HPP e paratiroide ectopica no HPS. CONCLUSAO: Medida PTH-IO fornece resultados confiaveis em tempo rapido, sendo capaz de discriminar persistencia da doenca se mantidos niveis elevados.

Usefulness of a rapid immunometric assay for intraoperative parathyroid hormone measurements

Intraoperative parathyroid hormone (IO-PTH) measurements have been proposed to improve operative success rates in primary, secondary and tertiary hyperparathyroidism (PHP, SHP and THP). Thirty-one patients requiring parathyroidectomy were evaluated retrospectively from June 2000 to January 2002. Sixteen had PHP, 7 SHP and 8 THP. Serum samples were taken at times 0 (before resection), 10, 20 and 30 min after resection of each abnormal parathyroid gland. Samples from 28 patients were frozen at -70 C for subsequent tests, whereas samples from three patients were tested while surgery was being performed. IO-PTH was measured using the Elecsys immunochemiluminometric assay (Roche, Mannheim, Germany). The time necessary to perform the assay was 9 min. All samples had a second measurement taken by a conventional immunofluorimetric method. We considered as cured patients who presented normocalcemia in PHP and THP, and normal levels of PTH in SHP one month after surgery and who remained in this condition throughout the follow-up of 1 to 20 months. When rapid PTH assay was compared with a routine immunofluorimetric assay, excellent correlation was observed (r = 0.959, P < 0.0001). IO-PTH measurement showed a rapid average decline of 78.8% in PTH 10 min after adenoma resection in PHP and all patients were cured. SHP patients had an average IO-PTH decrease of 89% 30 min after total parathyroidectomy and cure was observed in 85.7%. THP showed an average IO-PTH decrease of 91.9%, and cure was obtained in 87.5% of patients. IO-PTH can be a useful tool that might improve the rate of successful treatment of PHP, SHP and THP.

Parathyroid hormone: an early predictor of symptomatic hypocalcemia after total thyroidectomy

OBJECTIVE The purpose of this study was to evaluate if the measurement of peri-operative parathyroid hormone (PTH) is able to identify patients with increased risk of developing symptoms of hypocalcemia. SUBJECTS AND METHODS Forty patients who underwent total thyroidectomy were studied prospectively. Ionized serum calcium and PTH were measured after induction of anesthesia, one hour (PTH1) and one day after surgery (PTH24). Patients were evaluated for symptoms of hypocalcemia and treated with calcium and vitamin D supplementation as necessary. RESULTS Symptomatic hypocalcemia developed in 16 patients. Symptomatic patients had significant lower PTH1 and greater drops in PTH levels. The selection of 12.1 ng/L as PTH1 level cutoff level divided patients with and without symptoms with 93.7% sensitivity and 91.6% specificity. The selection of 73.5% as the cutoff value for PTH decrease resulted in 91.6% sensitivity and 87.5% specificity. CONCLUSION PTH1 levels and the drop in PTH levels are reliable predictors of developing symptomatic hypocalcemia after total thyroidectomy.

Localization of ectopic and supernumerary parathyroid glands in patients with secondary and tertiary hyperparathyroidism: surgical description and correlation with preoperative ultrasonography and Tc99m-Sestamibi scintigraphy

INTRODUCTION Hyperparathyroidism is an expected metabolic consequence of chronic kidney disease (CKD). Ectopic and/or supernumerary parathyroid glands (PT) may be the cause of surgical failure in patients undergoing total parathyroidectomy (PTX). AIM To define the locations of ectopic and supernumerary PT in patients with renal hyperparathyroidism and to correlate intraoperative findings with preoperative tests. MATERIALS AND METHODS A retrospective study was conducted with 166 patients submitted to PTX. The location of PT during surgery was recorded and classified as eutopic or ectopic. The preoperative localizations of PT found by ultrasonography (USG) and Tc99m-Sestamibi scintigraphy (MIBI) were subsequently compared with intraoperative findings. RESULTS In the 166 patients studied, 664 PT were found. Five-hundred-seventy-seven (86.4%) glands were classified as eutopic and 91(13.6%) as ectopic. Eight supernumerary PT were found. The most common sites of ectopic PT were in the retroesophageal and thymic regions. Taken together, USG and MIBI did not identify 56 (61.5%) ectopic glands. MIBI was positive for 69,7% of all ectopic glands located in the mediastinal and thymic regions. CONCLUSION The presence of ectopic and supernumerary PT in patients with renal hyperparathyroidism is significant. Although preoperative imaging tests did not locate most of ectopic glands, MIBI may be important for identifying ectopic PT in the mediastinal and thymic regions.

Parathyroid carcinoma and hungry bone syndrome

We hereby report two patients with parathyroid carcinoma presenting extremely high calcium and PTH levels, severe bone disease, and palpable neck mass at diagnosis. They both underwent parathyroidectomy, and one of them evolved to lung metastasis. Important hypocalcemia was observed after surgery in both: after parathyroidectomy in one patient, and only after surgical removal of the metastasis in the other. Both required intravenous calcium replacement, thus revealing hungry bone syndrome (HBS). HBS usually reflects rapid mineralization after correction of hyperparathyroidism. The more severe the bone disease before surgery, the more prone the patient is to HBS after surgery. Despite being an unfavorable outcome, HBS state suggests that surgical removal of hypersecretory parathyroid tissue was accomplished. In this study, HBS was observed in both patients, who presented severe bone disease prior to surgery. HBS would be expected post-operatively in successful parathyroid carcinoma removal.

Heterogeneity of carboxyl-terminal parathyroid hormone circulating forms in patients with hyperparathyroidism due to end stage renal disease

OBJECTIVE To study carboxyl-terminal (COOH) parathyroid hormone (PTH) circulating forms in patients with hyperparathyroidism due to end stage renal disease (ESRD). METHODS An immunometric assay that recognizes both intact and COOH PTH forms was developed. The assay, in conjunction with an intact assay, was used to measure PTH in serum samples obtained from 25 patients with hyperparathyroidism due to ESRD. Samples were also submitted to gel filtration chromatography in a Superdex((R)) 30 1.6 x 60 cm column, and the PTH content in the elution tubes, measured using both assays. RESULTS Values from 39.000 to 232.300 ng/mL (mean +/- sd = 101.680 +/- 45.330 ng/mL) were found using the COOH assay (PTH 39-84 was used as standard). Values obtained by the intact PTH assay ranged from 318 to 3.307 ng/mL (1.769 +/- 693 ng/mL) with a correlation between assays of 0.462 (p = 0.02). The elution profile obtained using the COOH assay showed a preponderance of forms with MW ranging from 8.500 to 4.500 daltons. The profiles obtained from the 25 patients were very similar. CONCLUSIONS In patients with hyperparathyroidism due to ESRD circulating PTH levels contain a broad range of molecular forms including COOH with MW ranging from 8.500 to 4.500 daltons. These forms are not recognized by the standard intact PTH assays. The correlation of these findings to the clinical aspects of bone disease in ESRD patients remains to be studied.

Carcinoma de paratiroide

Carcinoma de paratiroide e uma condicao rara, correspondendo na maior parte das casuisticas a menos de 1% dos casos de hiperparatiroidismo primario (HPP). No entanto, pela sua gravidade, e com o prognostico dependente do diagnostico precoce e de uma conduta agressiva, e fundamental que a suspeita clinica seja feita pre-operatoriamente. As caracteristicas clinicas sao compativeis com um caso de HPP grave, sintomatico, com tumor cervical >1,5cm, podendo ser palpavel. A definicao anatomo-patologica pode ser dificil em muitos casos. Nossa casuistica (1983-2004) compreende 7 casos, todos sintomaticos, com sindrome hipercalcemica e doenca ossea presente na maioria. Em 6/7 o tumor era palpavel, e todos apresentavam quadro bioquimico compativel. Tres pacientes faleceram em quadro de hipercalcemia refrataria. Dados recentes apontam para uma mutacao no gene HRPT2 como base molecular para o desenvolvimento destes tumores. A conduta e cirurgica e deve incluir hemitiroidectomia e exploracao cervical ampliada, procurando focos metastaticos. O pos-operatorio e compativel com a gravidade da alteracao metabolica pre-existente, sendo comum a tendencia a hipocalcemia. O prognostico de longo prazo depende do diagnostico precoce, do sucesso cirurgico e do controle da hipercalcemia. Novas possibilidades terapeuticas, na forma de bisfosfonatos e drogas calcimimeticas, bem como a possibilidade de diagnostico genetico, tendem a melhorar o prognostico desta grave condicao.