Primärer Hyperparathyreoidismus: sporadisch, Lithium-induziert und bei Multipler Endokriner Neoplasie

The present work deals with the disease of primary Hyperparathyroidism (pHPT), its clinical manifestation and therapeutic outcome. The study aimed to collect information on the frequencies of lithium-induced and sporadic pHPT as well as pHPT associated with Multiple Endocrine Neoplasia (MEN). Furthermore, its objective was to point out and compare clinical features and particularities of sporadic, lithium- and MEN-associated pHPT, especially regarding rates of multiple gland disease, persistence, recurrence and associated endocrine diseases. While nowadays pHPT mostly presents itself with asymptomatic hypercalcaemia, it may also cause severe clinical manifestations affecting the gastro-intestinal tract, kidneys or skeleton (Chapter 2). Several authors claimed that pHPT in MEN- and lithium-induced pHPT are associated with multiple gland disease, persistence and recurrence. Therefore, bilateral neck exploration has often been recommended as the treatment of choice against MEN- and lithium-associated pHPT. The study data was collected retrospectively considering all medical records of patients with pHPT who attended the University Hospital of Marburg between 01-01-2004 and 30-06-2013. 682 patients were admitted (491 female, 191 male). The patients were sent a questionnaire asking about their history of lithium medication, MEN syndrome, addi-tionally affected endocrine disorders and clinical features of pHPT. The patients were divided into three groups, based on the results of 280 completed questionnaires and 682 medical reports: Patients with sporadic pHPT, lithium-induced pHPT and pHPT in MEN. The present study revealed an underlying MEN syndrome in 9.8% and a history of lithi-um medication in 1 % of all patients (s. Chapter 2). The remaining 89.2% were defined to have sporadic pHPT. Renal and skeletal manifestations were common among pa-tients with pHPT. In the completed questionnaires, patients with sporadic and lithium-induced pHPT often stated to have an accompanying thyroid disease. Pancreatic affec-tions were rare among patients with sporadic pHPT, while they were common among those with MEN1. Patients with MEN2a had medullary thyroid cancer in 100% of all cases. Preoperative laboratory findings showed similar results in all groups. There was no significant difference in preoperative calcium and PTH levels between the three groups. The cure rate was 97.4% in primary surgery and 87% in resurgery. The rates for persistent and recurrent disease neither depended on the type of pHPT (sporadic/MEN/lithium-associated) nor on the selected surgical method (unilateral/bilateral approach). Primary surgery revealed singular adenomas in 92.4%, double adenomas in 2.9% and hyperplasia in 3.4% of all cases. Patients with sporadic disease mostly had singular adenomas (95%). Most of the patients with MEN1 had multiple gland hyperplasia (82.35% of MEN1 patients, 0% of MEN2a patients). One out of five patients with lithium-associated pHPT that underwent primary surgery at the University Hospital Marburg suffered from multiple gland hyperplasia (20%). Thus, multiple gland disease was significantly more common in patients with MEN, while a significant difference between patients with spo-radic and lithium-associated disease could not be shown. The evaluation of preoperative imaging methods (ultrasound and sestamibi scintigraphy) revealed low sensitivity when dealing with multiglandular diseases (25 respectively 26.5%), while sensitivity was at around 70% among patients with only one gland being affected. The discussion (chapter 5) pointed out, that the present study was the first to investigate lithium-induced/associated pHPT in a collection of patients with pHPT in Germany. It revealed that there were only very few patients with a history of lithium medication. These results go in line with the results from other countries that have also revealed small percentages of patients with a history of lithium medication in groups with pHPT. Contrary to most of the studies dealing with lithium-induced pHPT, the present study could not show a significantly higher rate of multiple gland, persistent or recurrent diseases compared to sporadic pHPT. Instead, the study could prove that sporadic pHPT and pHPT in MEN2a are mostly caused by a singular adenoma, while singular adeno-mas are uncommon in MEN1. Problems and deficits of the study were mostly due to its retrospective design, the frequently short follow-up periods, and the big variety of group sizes with only a small number of patients with lithium-associated pHPT. It could deliver important information con-cerning the frequency of lithium-induced, MEN-associated and sporadic pHPT. Especially for a more conclusive evaluation of lithium-associated pHPT, bigger study groups seem to be necessary. As the retrospective study revealed that there were only very few patients with a history of lithium medication in the examined group, a systematic inclu-sion of patients with positive lithium anamnesis into prospective studies with regularly performed follow-ups can be recommended