J Rastad

Normalized dyslipidaemia after parathyroidectomy in mild primary hyperparathyroidism: population‐based study over five years

objective Postmenopausal women are at increased risk of primary hyperparathyroidism (pHPT). Secondary dyslipidaemia in pHPT has attracted little attention, although morbidity and mortality associated with cardiovascular diseases have been reported to be increased in these patients.

Parathyroid hormone and ionized calcium levels are related to the severity of illness and survival in critically ill patients.

The present study explores serum parathyroid hormone (PTH) and blood ionized calcium (Ca2+) levels in relation to the severity of disease and mortality in the intensive care unit (ICU).

Serum levels of parathyroid hormone are related to the mortality and severity of illness in patients in the emergency department

Hypocalcaemia is a common finding in intensive care patients. In addition, raised levels of parathyroid hormone (PTH) have been described. The explanation and clinical importance of these findings are yet to be revealed. To investigate the occurrence of hypocalcaemia and elevated PTH levels and their relationship to morality and the severity of disease, serum levels of PTH, ionized calcium (Ca2+) and the cytokines interleukin 6 (IL‐6) and tumour necrosis factor alpha (TNF‐α) were measured on arrival in the emergency department in a broad spectrum of 140 acutely ill patients patients suffering from common diseases such as stroke, acute abdominal disorders, obstructive lung diseases, heart failure, acute myocardial infarction, angina pectoris, trauma and infectious diseases. A score (APACHE II) was calculated to assess the severity of disease. Elevated PTH levels (> 55 pg mL−1) were seen in 16% of the patients, being most frequent in patients with myocardial infarction (28%) and congestive heart failure (42%). The levels were significantly correlated with the APACHE II score (r = 0.48, P < 0.0001) and with the length of stay in hospital (r = 0.26, P < 0.002). PTH was also significantly (P < 0.03) elevated in non‐survivors compared with survivors and was found to be a stronger predictor of mortality (P < 0.01) than the APACHE II score (P < 0.02) in Coxs proportional hazard analysis. No close relationships were found between the cytokine levels and the indices of calcium metabolism. In conclusion, a rise in serum levels of PTH was common and related to the severity of disease and mortality in a mixed emergency department population.

Interleukin-6 Induced Suppression of Bovine Parathyroid Hormone Secretion

Calcium disturbances in the critically ill coincide with elevations of proinflammatory cytokines. The effects of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) on parathyroid hormone (PTH) secretion were investigated. IL-6 and TNF-α had no acute effect on PTH secretion in extracellular Ca2+ concentrations of 0.5, 1.25 and 3.0 mM. In contrast to TNF-α, cultures for 24 h in the presence of l0 ng/mL of IL-6 showed decreased PTH secretion by 51% and 29% in 0.5 mM and 1.25 mMCa2+ respectively. Neither IL-6 nor TNF-α, affected cytoplasmic Ca2+ of the cells. We conclude that PTH secretion in vitro can be suppressed by IL-6 at clinically relevant concentrations. This suppression may aggravate hypocalcemia of the critically ill and attenuate the conventionally strong stimulation of the PTH release by reduction in serum calcium.

Positive effect of parathyroidectomy on bone mineral density in mild asymptomatic primary hyperparathyroidism

Objectives.  Patients with mild primary hyperparathyroidism (pHPT) often appear asymptomatic, and have previously been regarded as not requiring treatment. However, increased cardiovascular morbidity and dyslipidaemia have also been recognized in mild pHPT, which also seem to be normalized after parathyroidectomy. The present study explores whether postmenopausal women with mild pHPT have decreased bone mineral density (BMD) compared with age‐matched healthy controls, and the effects on BMD of parathyroidectomy.

Parathyroidectomy for asymptomatic primary hyperparathyroidism (PHPT): Is it worth the risk?

There are examples of long-standing controversies on the strategy and the indication for surgery in many common endocrine disorders. The more well known of these seemingly endless debates include lobectomy vs total thyroidectomy in high differentiated papillary thyroid cancer, subtotal resection vs total parathyroidectomy in secondary hyperparathyroidism, and surgery vs radioiodine as definitive treatment of Graves’ disease. The utility of parathyroidectomy in “asymptomatic” primary hyperparathyroidism (PHPT) is another example, which is surprising not least because of the wealth of arguments for operation that have been unveiled during the last decade. The surgical community must accept its responsibility for the situation, since truly few efforts have been made to explore these controversies under controlled circumstances. Another possible reason is that this community has a rather heterogeneous endocrinology counterpart, which today generally consists of experts on bone diseases. Scrutiny of parathyroidectomy in asymptomatic PHPT naturally should span from aspects of the natural disease course and available options for active or passive treatments to cost-benefit estimations and the expected influences on ameliorated symptoms, signs and complications of the disorder. To focus this contribution on the essentials of our current knowledge, it may be adequate to begin by stating that there have been no thorough health economy calculations in treated PHPT. Moreover, neither hormone replacement therapy (estrogen and gestagen) nor calcium receptor-interactive compounds (calciomimetics) have been characterized enough for therapeutic applicability outside of prospective trials. It is consequently pertinent to consider parathyroidectomy and conservative surveillance as the only therapeutic options that are available in asymptomatic PHPT at present.

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

Rastad J, Ekbom A, Hultin H, Wuu J, Lundgren E, Hsieh C‐C, Lambe M (University Hospital Uppsala, Astra Zeneca R & D, Mölndal, Karolinska Institutet, Stockholm, Sweden, Harvard School of Public Health, Boston, University of Massachusetts Medical Center, Worcester, MA, USA). Childbearing and the risk of parathyroid adenoma – a dominant cause for primary hyperparathyroidism. J Intern Med 2001; 250: 43–49.

Different Secretory Actions of Pancreastatin in Bovine and Human Parathyroid Cells

Chromogranin A is an acidic protein that is costored and cosecreted with parathyroid hormone (PTH) from parathyroid cells. Pancreastatin (PST), is derived from chromogranin A, and inhibits secretion from several endocrine/neuroendocrine tissues. Effects of different pancreastatin peptides were investigated on dispersed cells from bovine and human parathyroid glands. Bovine PST(1–47) and bovine PST(32–47) inhibited PTH release from bovine cells in a dose-dependent manner. The former peptide was more potent and suppressed the secretion at 1–100 nM. This inhibition was evident in 0.5 and 1.25 mM, but not in 3.0 mM external Ca2+. Both peptides failed to alter the concentration of cytoplasmic Ca2+([Ca2+]i) of bovine cells. Human PST(1–52) and PST(34–52) did not affect PTH release or [Ca2+]i of parathyroid cells from patients with hyperparathyroidism, nor [Ca2+]i of normal human parathyroid cells. Furthermore, bovine PST(1–47) and bovine PST(32–47) failed to alter the secretion of abnormal human parathyroid cells. The study indicates that PST exerts secretory inhibition on bovine but not human parathyroid cells, and that this action does not involve alterations of [Ca2+]i.

Imaging of Ca2+-induced cytoplasmic Ca2+ responses in normal and pathological parathyroid cells

Ca2+‐induced changes in the cytoplasmic Ca2+ concentration ([Ca2+]i) were studied in bovine and normal and pathological human parathyroid cells using digital image analysis of fura‐2‐loaded cells. When raising external Ca2+ from 0.5 to 3.0 mmol L−1, about 95% of all cells reacted rapidly and simultaneously with sustained elevation of [Ca2+]i. In approximately two out of three bovine parathyroid cells, normal human cells and cells from most patients with hyperparathyroidism (HPT) the sustained phase was preceded by an overshooting [Ca2+]i transient. The proportion of cells with such a transient was decreased in cells from severe cases of uraemic parathyroid hyperplasia only. However, pathological human cells from adenomas and normal‐sized glands associated with adenomas, as well as cells from primary and uraemic hyperplasias, had lower peak and sustained levels than normal human and bovine cells. The results indicate that both normal and pathological parathyroid cells exhibit heterogeneity in their [Ca2+]i responses to elevation of external Ca2+. The Ca2+‐induced [Ca2+]i transients and the sustained elevations are attenuated in pathological human parathyroid cells. However, the presence of the overshooting transient represents physiological variability rather than being a consequence of the pathophysiology associated with HPT.