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 patient's 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.

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.

[Clinico-functional particularities of cardiac dysfunction in the elderly]. / Particularitati clinico-functionale ale disfunctiei cardiace la vârstnici.

UNLABELLED: Ischaemic left ventricular dysfunction is more frequent at the elderly and has a series of clinical and functional peculiarities. The aim of the paper is to define the clinical, biochemical, and echocardiograph features of the older patients with ischaemic heart disease. METHODS: 189 patients with ischaemic heart disease (old myocardial infarction, angina, ischaemic cardiomiopathy) have been parted, according to age, in Group A (n = 101) over 60 years old and Group B (n = 88) < 60 years old. Symptoms, cardiovascular risk factors, lipid profile, echocardiograph findings, and the exercise testing (at the bicycle) were analyzed. RESULTS: Ischaemic heart dysfunction appears earlier at the male gender, who is dominant at Group B (83%) in comparison with Group A (48%, p = 0.009). Myocardial infarction is more frequent at Group B (61 vs 42%, p = 0.006), and ischaemic cardiomiopathy at Group A (34% vs. 2%, p = 0.004). At Group A, symptomatic heart failure (dyspnoea of III or IV NYHA class) is prevalent (20% vs. 1%, p = 0.002). Arterial hypertension was dominant at Group A (73% vs. 58%, p = 0.02). At the echocardiograph examination, regional and diffuse contractility abnormalities were dominant at Group A, and the ejection fraction was lower (49 +/- 10%) in comparison to Group B (53 +/- 9%, p = 0.005). Diastolic dysfunction was found in 63% at Group A and 36% at Group B (p = 0.001). At the exercise testing there were not reported significant differences concerning the mechanical load according to age (87% of maximum heart rate at Group A and 83% at Group B). CONCLUSIONS: At the old patients with ischaemic left ventricular dysfunction the presence of a myocardial infarction is not so frequent. Systolic and diastolic dysfunction of the left ventricle is more severe, the ejection fraction is lower, but the exercise capacity did not differ significant.

[Is physical training useful for elderly patients with ischemic heart disease?]. / Este antrenamentul fizic util la pacientii vârstnici cu disfunctie cardiaca ischemica?

UNLABELLED: The aim of the paper is the study of the effects of a supervised physical training at old patients with ischaemic heart disease. METHODS: 74 patients with ischaemic left ventricular dysfunction have been followed during a supervised physical training consisting of a daily programme of exercise over a period of 21 +/- 10 days. They were parted in Group A (n = 26) over 60 years old and Group B (n = 48) under this age. The heart rate (HR), systolic and diastolic heart pressure (SHP respectively DHP), the time-tension index (TTI) were registered during the rest, the peak intensity of exercise and the recovery. These parameters were compared in evolution at each group and also between the groups. RESULTS: At Group A, at the end of the period, SHP at the peak intensity decreased (from 146 +/- 19 to 137 +/- 14 mmHg, p = 0.01), also SHP in the recovery period (from 119 +/- 10 to 116 +/- 10 mmHg, p = 0.01) and HR during the recovery time (from 77 +/- 8/min to 73 +/- 6/min, p = 0.03). The total length of the session time increased (from 12 +/- 4 min to 21 +/- 6 min, p = 0.01) and also the duration of the peak exercise time (from 3.6 +/- 1.0 min to 7.7 +/- 2.9 min, p = 0.03), in the condition of maintaining a HR at the peak exercise of about 75-76% of the maximum HR obtained at a previous exercise testing. The improvement of the training parameters was similar with Group B, except the duration of the session, longer at the last group (21 +/- 6 min at Group A vs. 25 +/- 7 min at Group B, p = 0.02) and the duration of the peak intensity (7.7 +/- 1.0 min at Group A vs. 9.1 +/- 2.9 min at Group B, p = 0.02). CONCLUSIONS: Old patients with ischaemic left ventricular dysfunction improve their exercise capacity as well as the younger ones; the benefits of a supervised physical exercise are evident regardless of age.