Neue Therapien bei chronischem Hypoparathyreoidismus

Zusammenfassung

Der chronische Hypoparathyreoidismus (hypoPT) ist geprägt durch einen Mangel an Parathormon (PTH) und als Konsequenz auch an Calcitriol [1, 25 (OH)2 Vitamin D]. Neben der Hypocalcämie kommt es zu einer Reihe biochemischer Veränderungen mit Hyperphosphatämie und Hypercalciurie. Trotz Therapie mit Calcium und aktivem Vitamin D haben Betroffene eine Vielzahl von Beschwerden und eine erhöhte Langzeitmorbidität und -mortalität.

Es kann zu Komplikationen wie Nierenfunktionsstörungen, Nephrocalcinose, Nierensteinen, Basalganglienverkalkungen, Katarakten, zu einem verminderten Knochenumsatz und zu einem erhöhten Infektionsrisiko kommen.

Seit 2017 ist das rekombinante humane Parathormon [rhPTH (1-84)] als Ersatz des beim hypoPT fehlenden PTHs für die Therapie zugelassen. In der initial durchgeführten Zulassungsstudie konnten ca. 40% der Patienten nach 24 Wochen rhPTH (1-84) Therapie auf die orale Einnahme von Calcitriol verzichten und gleichzeitig die Calciumzufuhr reduzieren. Aktuell sind Daten über acht Jahre Therapie mit rhPTH (1-84) vorliegend. Die Therapie wird gut vertragen, es kommt zur Normalisierung des Knochenstoffwechsels sowie zur Verbesserung der Lebensqualität im Vergleich zum Therapiebeginn bei unveränderter Nierenfunktion. Eine Verminderung der Hypercalciurie kann allerdings erst ab dem siebten Jahr der Therapie gezeigt werden.

Aktuell sind weitere Medikamente in Entwicklung, die in der Zukunft neue Therapiemöglichkeiten für Betroffene mit hypoPT eröffnen.

Abstract

During recent years, it has become apparent that chronic hypoparathyroidism (hypoPT) is a complex disease characterized by the deficiency of parathyroid hormone (PTH) and as a consequence calcitriol [1, 25 (OH)₂ vitamine D]. Besides hypocalcemia, hypoPT is associated with additional biochemical disturbances, such as hyperphosphatemia and hypercalciuria. Moreover, patients suffer from impaired quality of life (QoL) and an increased risk of various co-morbidities. These include renal impairment, stones and/or nephrocalcinosis, impaired bone quality, neuropsychiatric diseases, infections and an increased mortality. Lately, different hypoparathyroidism-specific tailored instruments were developed to assess the nature and the degree of symptoms or complaints in hypoPT patients. These instruments highlighted differences compared to control groups as well as a correlation to laboratory values, especially the calcium-phosphate product.

In addition to growing insights into its clinical consequences, in recent years recombinant human parathyroid hormone (1-84) [rhPTH (1-84)] has become available as a replacement of the missing hormone. Data demonstrating efficacy and safety of rhPTH (1-84) in both short-term and long-term studies are now available. Long-term administration of rhPTH (1-84) resulted in sustained, and in some cases, progressive reductions in supplemental calcium and calcitriol requirements. With regard to bone structure, rhPTH (1-84) led to an increase in bone turnover in both the trabecular and cortical compartment and to a restoration of bone metabolism towards a euparathyroid state. Studies that have attempted to quantify QoL in hypoPT with widely used questionnaires such as the Short-Form-36 (SF-36) have revealed large deviations from the general population and improvement during long-term hormone replacement. However, evidence of improvement of QoL with rhPTH (1-84) when compared to placebo-treated control groups is still lacking. Moreover, hypercalciuria is reduced by treatment with rhPTH (1-84) only after the seventh year of treatment.

Currently, a number of other treatment options are being developed offering physicians and patients a wider set of therapeutic options in the future.

Schlüsselwörter

chronischer Hypoparathyreoidismus - Hypocalcämie - Hypercalciurie - rekombinantes humanes Parathormon

Key words

chronic hypoparathyroidism - hypocalcemia - hypercalciuria - renal impairment - human recombinant parathyroid hormone

Publication History

Article published online:
23 November 2020

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