Abnormal Muscle and Hematopoietic Gene Expression May be Important for Clinical Morbidity in Primary Hyperparathyroidism

Abstract

Primary hyperparathyroidism (PHTP) is characterized by overproduction of parathyroid hormone and an increase in the level of serum ionized calcium. The most common cause of excess hormone production is the development of a benign tumor (adenoma) in one of the parathyroid glands.Adenoma accounts for 80-90% percent of all patients with PHTP. Muscular fatigue, constipation ,weakness, lethargy, neuropsychiatric, neuromuscular and cardiovascular manifestations, renal stones, osteoporosis, ostopenia, peptic ulcers, pancreatitis and gallstones are some of the symptoms of PHTP. Nowadays many patients with PHTP are discovered in their asymptomatic phase, especially in Western Europe and North Amerika(2) probably by routine screening This project was aimed to characterize changes in muscle and hematopoietic gene expression in patients with reversible mild PHPT during illness and after parathyroidectomy and possibly link molecular pathology to the symptoms. The transcriptional activity was analysed in biopsies obtained before and one year after parathyroidectomy in 7 patients with mild PHTP comparing bone marrow and muscle genes. My task was to quantify the distribution of PTH receptors (PTHR1 and PTHR2) using real time RT-PCR in unrelated persons to define PTH target tissues and quantify PTH receptors in prathyroidectomized patients. These studies showed that PTHR1 and PTHR2 were more abundantly expressed in muscle and brain than in hematopoietic cells. It is possible that sustained stimulation of PTH receptors in brain,muscle, heart and hematopoietic cells because of elevated serum levels of PTH lead to alterations in gene expression and gives rise to symptoms like muscle fatigue, weakness, cardiovascular pathology and neuropsychiatric manifestations.