Understanding and Managing Primary Hyperparathyroidism –Anything New?

Understanding and Managing Primary Hyperparathyroidism -Anything New?' Classic Primary HyperparathyroidismPrimary hyperparathyroidism (PHPT) is an endocrine disorder characterised by inappropriately high serum levels of parathyroid hormone (PTH) accompanied by hypercalcaemia.PHPT occurs as a direct (primary) consequence of underlying pathologies, e.g.single benign parathyroid adenoma (approximately 80% of cases), hyperplasia (~15-20%) or carcinoma (<1%) of the parathyroid glands. 1 The incidence, up to one in 1,000 individuals, is highest in post-menopausal women and increases with age in both sexes.1-3 PHPT is a leading cause of hypercalcaemia in the general population. 1 In more severely affected individuals, PHPT is linked to a variety of complications, such as: cardiovascular calcification, bone disease and pathological fractures, kidney stones and damage, gastrointestinal and central nervous system disturbances.1,4 Modern Primary Hyperparathyroidism Once described as a disease of 'bones, stones and psychic groans', PHPT today frequently presents as hypercalcaemia without overt symptoms.5,6 'Asymptomatic' PHPT is most often diagnosed through biochemical screening.5,7-9 Although earlier diagnosis and treatment could be expected to slow PHPT progression, studies on the natural history of the disease suggest that even patients diagnosed and monitored without intervention for a decade or more rarely go on to develop the 'classic' symptoms.6 This suggests the emergence of a novel PHPT disorder with similar end-organ involvement but different, yet recognisable, manifestations.6 While PHPT is most frequently diagnosed in the context of asymptomatic hypercalcaemia, it is important to recognise that classic symptomatic PHPT is still prevalent in some parts of the world.6 Bilezikian et al. described this classic symptomatic presentation in a study comparing two large PHPT-patient cohorts in New York and Beijing.9 The Beijing patients were younger and much more symptomatic (mean age 37 years, 97% with bone/stone symptoms) than the US subjects (mean age 55 years; 18.4% with bone/stone symptoms).Mean biochemical parameters were far beyond the normal range in the Beijing patients (see Table 1), who were also severely vitamin D depleted, aggravating their PHPT symptoms since this leads to even higher PTH levels.9 Non-traditional Features of Mild Asymptomatic Primary Hyperparathyroidism and Impact on Quality of LifeAlthough the 'modern' PHPT phenotype is termed asymptomatic to AbstractThe endocrine disorder primary hyperparathyroidism (PHPT) is characterised by increased parathyroid hormone (PTH) in association with elevated serum calcium levels.Over the past 30 years, there has been a shift in the clinical presentation of PHPT in the most developed Western countries from a disorder associated with overt skeletal and renal disease, to an asymptomatic form.The latter form has hypercalcaemia and elevated PTH levels, often only detected through routine biochemical screening, sometimes inadvertently.Despite exhibiting few 'traditional' symptoms, some studies suggest that the quality of life of these PHPT patients may be reduced.Subtle neuropsychological and cardiovascular concerns in PHPT, even prior to diagnosis, have a significant impact both on the patients themselves and on the economy through increased time off work.Although asymptomatic, PHPT may remain stable for at least 10 years without intervention.Parathyroidectomy offers the only definitive solution in the longer term.Successful surgery improves bone mineral density and the neurological and psychological symptoms of PHPT; however, it is not always clinically indicated.Medical management is seen as a viable alternative for interim treatment prior to surgery, or for patients unsuitable for, or unwilling to undergo, surgery.Vitamin D supplements, antiresorptives and calcimimetics redress the biochemical imbalances of PHPT -stabilising bone turnover, serum calcium and PTH levels.Targeted pharmacological therapy increases quality of life in patients under non-surgical follow-up and improves general disease management.

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