Hyperparathyroidism in patients with overt and mild primary aldosteronism.

INTRODUCTION: Increased prevalence of hyperparathyroidism (HP) has been observed in primary aldosteronism (PA) patients. However, HP prevalence in milder forms of PA has not to date been evaluated. OBJECTIVES: The objectives of this study were to assess the prevalence of primary and secondary HP in overt and milder misdiagnosed cases of PA and to investigate the effect of treatment on parathormone (PTH) secretion. PATIENTS AND METHODS: Seventy PA patients with normal renal function were included prospectively. Specifically, patients with biochemically overt PA (increased basal aldosterone/renin ratio (ARR) and a positive diagnostic suppression test (DCVT)) and patients with mild PA (normal basal ARR and a positive DCVT) were analyzed. Mean blood pressure and mineral metabolism were evaluated at diagnosis and after treatment. RESULTS: Primary and secondary HP were found in 4.3% (3/70) and 51.4% (36/70) of patients, respectively, and biochemically overt and mild PA in 47.1% (33/70) and 52.9% (37/70) of patients, respectively. Sixty-three PA patients were followed up after treatment without receiving calcium or vitamin D. There was a decrease of mean blood pressure (p < 0.001), PTH (p < 0.001), and 24-h urinary calcium (p < 0.001), and an increase of serum potassium (p < 0.001) and calcium (p = 0.018) levels in secondary HP patients. There was no significant difference between biochemically overt and mild PA patients as concerned serum PTH, calcium, and 25-hydroxyvitamin-D levels either before or after treatment. Aldosterone levels before treatment were positively correlated with serum PTH levels. CONCLUSIONS: HP prevalence was high in both overt and mild PA patients, whereas the effect of treatment on serum and urinary calcium and PTH levels was similar in both groups.

Salt intake in mineralocorticoid receptor antagonist-treated primary aldosteronism: foe or ally?

Mild hyperkalemia is a common side effect of mineralocorticoid receptor antagonist (MRA) treatment of patients with primary aldosteronism (PA), which can be worsened by instructions to minimize salt intake. Our objective was to evaluate the effect of salt consumption on serum potassium levels and mean, mean minimal, and mean maximal systolic and diastolic blood pressure (BP) in MRA-treated hyperkalemic PA patients under relative salt restriction. Seventeen consecutive mildly hyperkalemic MRA-treated PA patients aged 66.3 ± 8.37 years were recruited. Body mass index (BMI) and BP were assessed, and serum and 24-h urinary sodium and potassium levels, plasma renin, and serum aldosterone were measured, while patients followed a relatively salt-restricted diet, after 1 month of controlled salt supplementation (usual salt-restricted diet plus 4 g salt/day) and after 6 months on instructions for free dietary salt consumption. Baseline salt consumption was additionally evaluated in two more patient groups (normotensive subjects and normokalemic MRA-treated PA patients). One month of controlled salt supplementation (24-h urine sodium (median, min, max): 195.2 (120.30-275.20) vs 110.13 (34.30-139.20) mEq/day, p < 0.001) resulted in increased kaliuresis (62.25 (40.69-97.0) vs 54.0 (23.28-79.60) mEq/day, p = 0.001) and a decrease of serum potassium (5.2 (5-5.70) vs 4.6 (3.8-5.1) mEq/L, p < 0.001), while serum sodium (139 (133-141) vs 1 39 (135-144) mEq/L) and mean systolic (130 (105-141 vs. 130 (106-141) mmHg) and diastolic (76 (53-85) vs75 (53-84) mmHg) BP remained stable. These findings were unchanged after 6 months of free salt consumption. BMI remained constant, while plasma renin and serum aldosterone decreased following salt repletion. Adequate salt consumption attenuates MRA-induced hyperkalemia in relatively salt-restricted PA patients without affecting BP or BMI.

Identification of a novel mutation of the PRKAR1A gene in a patient with Carney complex with significant osteoporosis and recurrent fractures.

OBJECTIVE: Carney complex (CNC) is a rare autosomal dominant multiple neoplasia syndrome characterized by the presence of endocrine and non-endocrine tumors. More than 125 different germline mutations of the protein Kinase A type 1-α regulatory subunit (PRKAR1A) gene have been reported. We present a novel PRKAR1A gene germline mutation in a patient with severe osteoporosis and recurrent vertebral fractures. DESIGN: Clinical case report. CASE REPORT: A 53-year-old male with a medical history of surgically removed recurrent cardiac myxomas was evaluated for repeated low-pressure vertebral fractures and severe osteoporosis. Physical examination revealed spotty skin pigmentation of the lower extremities and papules in the nuchal and thoracic region. The presence of hypercortisolism due to micronodular adrenal disease and the history of cardiac myxomas suggested the diagnosis of CNC; the patient underwent detailed imaging investigation and genetic testing. METHODS: Standard imaging and clinical testing; DNA was sequenced by the Sanger method. RESULTS: Sequence analysis from peripheral lymphocytes DNA revealed a novel heterozygous point mutation at codon 172 of exon 2 (c.172G>T) of the PRKAR1A gene, resulting in early termination of the PRKAR1A transcript [p.Glu58Ter (E58X)]. CONCLUSION: We report a novel point mutation of the PRKAR1A gene in a patient with CNC who presented with significant osteoporosis and fractures. Low bone mineral density along with recurrent myxomas should point to the diagnosis of CNC.