adrenomedullin and Hyperparathyroidism

Adrenomedullin (AM) is a recently discovered potent vasodilatory peptide, originally isolated in extracts of human pheochromocytoma, with activities including maintenance of cardiovascular and renal homeostasis through vasodilatation, diuresis and natriuresis. Human AM consists of 52 amino acids with a 6-member ring structure linked by a disulfide bond and amidated COOH terminal, which belongs to calcitonin gene-related peptide (CGRP) and amylin. The main sites of AM production are the lungs, vascular tissues (both endothelial and smooth muscle cells), heart, kidney, adrenal glands, pancreatic islets, placenta, anterior pituitary gland and gastrointestinal neuroendocrine system. Intravenous injection of AM increases blood flow predominantly in the tissues with the highest AM expression, suggesting that AM functions primarily as a paracrine/autocrine hormone, but it is also important as circulating hormone. The objective of this review is to analyze the evidence that AM may play a role in some endocrine disorders.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adrenomedullin; Amino Acid Sequence; Cushing Syndrome; Diabetes Mellitus; Endocrine System Diseases; Female; Humans; Hyperaldosteronism; Hyperparathyroidism; Hyperthyroidism; Insulinoma; Male; Menstrual Cycle; Molecular Sequence Data; Molecular Structure; Paraneoplastic Endocrine Syndromes; Peptides; Pheochromocytoma; Pregnancy

Adrenomedullin (ADM) is a new potent vasorelaxant peptide identified originally in extracts of pheochromocytoma, and is widely distributed within the tissue. Although histopathological studies have demonstrated the presence of ADM-immunoreactivity (ir-ADM) in some human neuroendocrine tumors (such as insulinoma, pituitary adenoma, and gastrointestinal neuroendocrine tumors), data on the presence of ADM in normal and pathological parathyroid gland are not available. Plasma AM concentrations were recently reported to be elevated in patients with PHP (primary hyperparathyroidism). The aim of our study was to determine tissue distribution of ir-AM in 34 patients with PHP (27 female and 7 male, mean age 50 +/- 6 years) undergoing surgery. Six normal parathyroid samples incidentally found during thyroidectomy for neoplastic diseases and ten sections of human rectus abdominis muscle tissue were used as controls (C). Adenomatous parathyroids were found in 22 PHP and hyperplastic parathyroids in twelve PHP patients. Four hyperplastic parathyroids were found in three PHP patients and three parathyroids in 10 PHP patients. Eight parathyroids revealed a prevalent diffuse growth pattern and four showed a prevalent nodular growth pattern. Immunohistochemical ADM expression was seen in seven of twelve (58.3 %) hyperplastic parathyroids and in fourteen of twenty-two (66.6 %) adenomatous glands. Parathyroid chief cells showed strong cytoplasmatic staining, whereas oncocytic cells showed a faintly aspecific cytoplasmatic staining. Normal parathyroids were negative for ir-ADM. In conclusion, we found the presence of ADM in parathyroid chief cells of PHP patients using immunohistochemistry in our study.

Topics: Adenoma; Adrenomedullin; Adult; Female; Humans; Hyperparathyroidism; Hyperplasia; Immunohistochemistry; Male; Middle Aged; Parathyroid Glands; Parathyroid Neoplasms; Peptides; Tissue Distribution

The aim of the study was to evaluate plasma adrenomedullin (AM) concentration in primary hyperparathyroidism (PHP) and its effect on the regulation of blood pressure. Forty-one patients with PHP (25 normotensive and 16 hypertensive), and 31 healthy subjects (HS) were included in the study. As expected the total and ionized calcium and i-PTH serum levels were significantly higher in patients with PHP than in HS (P <.001). No significant difference was found in calcium-phosphorus metabolism parameters between normotensive and hypertensive PHP patients. Serum i-PTH levels correlated positively with systolic blood pressure (SBP) (r = 0.510; P <.02), diastolic blood pressure (DBP) (r = 0.586; P <.01) and heart rate (HR) (r = 0.486; P <.043) only in hypertensive PHP patients. Overall, mean plasma AM concentrations were significantly higher in PHP patients (16.1 +/- 7.9 pg/mL) than in HS (11.3 +/- 4.8 pg/mL) (P <.003) and correlated with i-PTH (r = 0.430; P <.005). However, in hypertensive PHP patients plasma AM levels (22.5 +/- 4.7 pg/mL) were higher than in normotensive PHP patients (11.6 +/- 1.8 pg/mL) (P <.001) and correlated with DBP (r = 0.902, P <.0029). In HS no correlation was found between plasma AM values and biohumoral, hormonal, or hemodynamic parameters. In conclusion, we demonstrated that in patients with PHP, plasma AM concentrations are increased and correlate with i-PTH and blood pressure values. We suggest that increased AM levels could be a compensatory factor in the defence mechanism against further blood pressure elevation.

Topics: Adolescent; Adrenomedullin; Adult; Aged; Blood Pressure; Calcium; Female; Heart Rate; Humans; Hyperparathyroidism; Hypertension; Male; Middle Aged; Osmolar Concentration; Parathyroid Hormone; Peptides; Reference Values