Elena Livadariu

Cabergoline and the risk of valvular lesions in endocrine disease

AIMS The cardiac valvular risk associated with lower exposure to cabergoline in common endocrine conditions such as hyperprolactinemia is unknown. METHODS AND RESULTS We performed a cross-sectional, case-control echocardiographic study to assess the valvular status in 102 subjects receiving cabergoline for endocrine disorders and 51 matched control subjects. Cabergoline treatment ranged from 12 to 228 months, with a cumulative dose of 18-1718 mg. Valvular regurgitation was equally prevalent in both groups and was almost exclusively mild. Two cabergoline-treated subjects had moderate mitral regurgitation; there was no relationship between cabergoline dose and the presence or severity of mitral valve regurgitation (P=NS). Mitral valve tenting area was significantly greater in the cabergoline group when compared with the control subjects (P=0.03). Mitral valve leaflet thickening was observed in 5.9% of cabergoline-treated subjects; no relationship with the cumulative cabergoline dose was found. No patient had aortic or tricuspid valvular restriction. CONCLUSION No significantly increased risk of clinically relevant cardiac valve disorders was found in subjects treated with long-term cabergoline therapy at the doses used in endocrine practice. While exposure to cabergoline appears to be safe during low-dose long-term therapy, an association with subclinical changes in mitral valve geometry cannot be completely excluded.

The Epidemiology and Management of Pituitary Incidentalomas

Prevalence:The prevalence of pituitary tumors has been a topic of controversy for many years. Autopsy and radiological series show that pituitary incidentalomas may be present in one of six people. Recent epidemiological data suggest that clinically apparent pituitary adenomas have a prevalence of approximately one in 1,000 people in the general population. The disconnect between these two prevalence rates underlines the common clinical quandary of how to manage pituitary incidentalomas, particularly those lacking clinical signs/symptoms or hormonal abnormalities. Management:The natural history of incidentalomas suggests that periodic hormonal, clinical and radiological follow-up is the optimal approach. In the absence of tumor growth or relevant symptoms, screening can be continued intermittently or curtailed based on the clinical judgment of the physician. In the presence of hormonal hypersecretion, the management of pituitary incidentalomas, whether they are micro- or macroadenomas, should follow accepted clinical guidelines. For incidental pituitary macroadenomas without hormonal hypersecretion, clinical management should also include assessments for visual field impairment or hypopituitarism. In such cases, regular radiological and hormonal follow-up is required to identify tumor growth or the appearance of new symptoms. In the presence of tumor growth or new hormonal abnormalities, surgical options should be considered and discussed with the patient.

Mutations of calcium-sensing receptor gene: two novel mutations and overview of impact on calcium homeostasis

OBJECTIVE Genetic disorders of calcium metabolism arise in a familial or sporadic setting. The calcium-sensing receptor (CASR) plays a key role in maintaining calcium homeostasis and study of the CASR gene can be clinically useful in determining etiology and appropriate therapeutic approaches. We report two cases of novel CASR gene mutations that illustrate the varying clinical presentations and discuss these in terms of the current understanding of CASR function. PATIENTS AND METHODS A 16-year-old patient had mild hypercalcemia associated with low-normal urinary calcium excretion and normal-to-high parathyroid hormone (PTH) levels. Because of negative family history, familial hypocalciuric hypercalcemia was originally excluded. The second patient was a 54-year-old man with symptomatic hypocalcemia, hyperphosphatemia, low PTH, and mild hypercalciuria. Familial investigation revealed the same phenotype in the patients sister. The coding region of the CASR gene was sequenced in both probands and their available first-degree relatives. RESULTS The first patient had a novel heterozygous inactivating CASR mutation in exon 4, which predicted a p.A423K change; genetic analysis was negative in the parents. The second patient had a novel heterozygous activating CASR mutation in exon 6, which predicted a p.E556K change; the affected sister of the proband was also positive. CONCLUSIONS We reported two novel heterozygous mutations of the CASR gene, an inactivating mutation in exon 4 and the first activating mutation reported to date in exon 6. These cases illustrate the importance of genetic testing of CASR gene to aid correct diagnosis and to assist in clinical management.