Standards of care for hypoparathyroidism in adults: a Canadian and International Consensus.

PURPOSE: To provide practice recommendations for the diagnosis and management of hypoparathyroidism in adults. METHODS: Key questions pertaining to the diagnosis and management of hypoparathyroidism were addressed following a literature review. We searched PubMed, MEDLINE, EMBASE and Cochrane databases from January 2000 to March 2018 using keywords 'hypoparathyroidism, diagnosis, treatment, calcium, PTH, calcidiol, calcitriol, hydrochlorothiazide and pregnancy'. Only English language papers involving humans were included. We excluded letters, reviews and editorials. The quality of evidence was evaluated based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. These standards of care for hypoparathyroidism have been endorsed by the Canadian Society of Endocrinology and Metabolism. RESULTS: Hypoparathyroidism is a rare disease characterized by hypocalcemia, hyperphosphatemia and a low or inappropriately normal serum parathyroid hormone level (PTH). The majority of cases are post-surgical (75%) with nonsurgical causes accounting for the remaining 25% of cases. A careful review is required to determine the etiology of the hypoparathyroidism in individuals with nonsurgical disease. Hypoparathyroidism is associated with significant morbidity and poor quality of life. Treatment requires close monitoring as well as patient education. Conventional therapy with calcium supplements and active vitamin D analogs is effective in improving serum calcium as well as in controlling the symptoms of hypocalcemia. PTH replacement is of value in lowering the doses of calcium and active vitamin D analogs required and may be of value in lowering long-term complications of hypoparathyroidism. This manuscript addresses acute and chronic management of hypoparathyroidism in adults. MAIN CONCLUSIONS: Hypoparathyroidism requires careful evaluation and pharmacologic intervention in order to improve serum calcium and control the symptoms of hypocalcemia. Frequent laboratory monitoring of the biochemical profile and patient education is essential to achieving optimal control of serum calcium.

Mechanism of lipid enhancement of alpha1-adrenoceptor pressor sensitivity in hypertension.

OBJECTIVE AND DESIGN: Plasma lipids enhance alpha1-adrenoceptor pressor sensitivity, impair baroreflex function, and correlate with increased blood pressure. This clinical study was designed to determine whether the enhanced alpha1-pressor sensitivity induced by acute hyperlipidemia is primarily mediated by increased vascular alpha1 responsiveness, reduced baroreflex sensitivity (BRS) or both. METHOD: Regional alpha1-adrenoceptor vasoreactivity was measured using a graded brachial artery infusion of the alpha1 agonist, phenylephrine, in seven subjects with stage 1 hypertension. Forearm blood flow was estimated from venous occlusion plethysmography. The phenylephrine dose-forearm blood flow response curve was used to determine alpha1-vascular reactivity (slope of the dose-response curve) and sensitivity, EC50 (phenylephrine dose inducing 50% maximal response). BRS (ms/mmHg) was measured as the slope of the progressive rise in systolic blood pressure and the resultant lengthening in the subsequent R-R interval after systemic intravenous boluses of phenylephrine. Subsequently, plasma lipids were raised with a 1-h systemic co-infusion of intralipid and heparin, after which measurements of regional vasoreactivity and BRS were repeated. RESULTS: Mean arterial pressure was 109 +/- 4 versus 110 +/- 3 (P = NS), vasoreactivity was -0.71 +/- 0.10 versus -0.82 +/- 0.10 (P = NS) and log EC50 was 1.47 +/- 0.29 versus 1.52 +/- 0.34 nmol/l (P = NS) before and after raising non-esterified fatty acids, respectively. In contrast, mean BRS was acutely reduced from 8.2 +/- 2.1 to 6.2 +/- 1.8 ms/mmHg (P = 0.02) after the lipid infusion. CONCLUSIONS: These findings suggest that in hypertensive patients, the primary mechanism for short-term alpha1-pressor hypersensitivity in response to hyperlipidemia is via the acute impairment of BRS.

Lipids enhance alpha1-adrenoceptor pressor sensitivity in patients with chronic kidney disease.

BACKGROUND: Dyslipidemia in patients with chronic kidney disease (CKD) may contribute to hypertension (HT) by altering neurocirculatory control. To test this notion, we quantified the effects of acutely increasing levels of nonesterified fatty acids (NEFAs) and triglycerides on alpha1-adrenergic pressor sensitivity and baroreflex sensitivity (BRS) in subjects without diabetes with CKD. METHODS: Alpha1 pressor sensitivity was determined before and after increasing NEFA and triglyceride levels with a fat emulsion and heparin infusion in 8 subjects with stage 2 to 3 CKD (glomerular filtration rate, 56 +/- 6 mL/min by 125 I-iothalamate clearance). Seven subjects with HT and 8 normotensive control (CO) subjects with normal renal function and matched to patients with CKD also were studied. RESULTS: Fasting NEFA levels were greater in patients with CKD than in CO subjects (585 +/- 98 versus 321 +/- 32 micromol/L; P < 0.01), but not different from those in subjects with HT (501 +/- 68 micromol/L). Alpha1 pressor sensitivity, defined as the phenylephrine dose that increased mean blood pressure (BP) by 20 mm Hg, was greatest (lowest dose) in subjects with CKD (0.83 +/- 0.11 microg x kg(-1) x min(-1)), followed by those with HT (1.08 +/- 0.19 microg x kg(-1) x min(-1)) and CO subjects (1.34 +/- 0.19 microg x kg(-1) x min(-1); P < 0.05 versus CKD group). BRS, measured as the ratio of change in R-R interval to change in systolic BP during the phenylephrine infusion, was lowest, intermediate, and highest in the CKD, HT, and CO groups, respectively. Increasing NEFA and triglyceride levels significantly enhanced alpha1 pressor sensitivity in all 3 groups and reduced BRS in the CKD and CO groups. CONCLUSION: These observations suggest that the dyslipidemia prevalent in patients with stage 2 to 3 CKD may contribute to HT by enhancing alpha1 pressor sensitivity and impairing baroreflex function.

Hemodynamic effects of chronic hemodialysis therapy assessed by pulse waveform analysis.

Cardiovascular responses to hemodialysis have been characterized by invasive monitoring techniques. These techniques are not feasible for evaluation of hemodynamic status during dialysis in the outpatient setting. In this study, we used pulse waveform analysis (PWA), a noninvasive tool designed for the ambulatory setting, to assess hemodynamic responses of dialysis treatments in 27 stable subjects with end-stage renal disease receiving chronic hemodialysis. In our population, systolic, diastolic, and pulse pressures were unaffected by dialysis despite the mean fluid removal of 3.0 +/- 0.2 kg. However, using PWA, we observed that stroke volume and cardiac output progressively declined by 17% to 19% (P <.001) with a concomitant increase in systemic vascular resistance by 22% from 1654 +/- 88 to 2020 +/- 121 dynes. sec. cm(-5) (P <.001). Also, we observed a significant reduction in small artery compliance from 4.7 +/- 0.5 to 3.3 +/- 0.4 mL. mm Hg(-1). 100 (P =.01), whereas large artery elasticity was unaffected. These findings suggest that changes in small artery vascular compliance contribute to the elevation in systemic vascular resistance during dialysis. This study confirms that hemodynamic adaptations to the dialysis procedure can be detected using PWA and are consistent with data obtained by invasive monitoring techniques. Furthermore, the observed reduction in vascular compliance in response to dialysis may contribute to the high cardiovascular risk in patients undergoing chronic hemodialysis therapy.

Glomerular filtration rate can be accurately predicted using lean mass measured by dual-energy X-ray absorptiometry.

BACKGROUND: Accurate assessment of renal function is important in the management of patients with kidney disease yet is often difficult to obtain. Formulae, designed for clinical use, have been developed to predict glomerular filtration rate (GFR) utilizing serum creatinine (Scr). Additional parameters are included in these formulae to account for variations in Scr due to differences in total body lean mass in kg (LM). Therefore, the purpose of this study was to derive a simple formula to predict GFR based on Scr and direct quantification of LM. METHODS: Ten subjects with a wide range of renal function had GFRs determined by [125I]iothalamate clearance and LM determined by dual-energy X-ray absorptiometry as well as fasting measurements of Scr, serum and 24 h urine urea nitrogen, and albumin. RESULTS: The following formula was derived using LM (kg) and Scr (mg/dl): predicted GFR=(2.4xLM)-(0.75xLMxScr). The correlation coefficient for this formula was 0.97, when compared with [125I]iothalamate clearances, and similar to the MDRD formulae (R=0.87-0.95). CONCLUSION: Although further validation is necessary, these findings suggest that total body non-invasive measurement of LM along with Scr can be used to accurately predict GFR.