Aldosterone and Parathyroid Hormone: A Complex and Clinically Relevant Relationship

Disclosure: N.E. Fretes Oviedo: None. M. Ortega Abad: None. L.Z. Khan: None. R. Correa: None. A. Mehdi: None. P. Rao: None. Introduction: Primary aldosteronism (PA) and primary hyperparathyroidism (HPT) are two common endocrine conditions. The Parathyroid hormone (PTH) and the renin-angiotensin-aldosterone system (RAAS) exhibit a bidirectional relationship. It is thought that PA could lead to secondary HPT. Aldosterone-induced hypercalciuria and subsequent hypocalcemia are hypothesized to trigger PTH secretion to maintain calcium homeostasis. These effects may resolve once aldosterone excess is treated. Evidence suggests that patients with aldosterone-producing adenomas (APA) might have higher PTH levels, leading to greater complications compared to those with bilateral adrenal disease. The aim of this study is to evaluate PTH levels and their potential impact on bone mineral disorders and/or kidney stones in patients with PA, with and without adrenal nodules. Methods: A single-center, retrospective observational study was conducted using an IRB-approved database that included 164 patients with a diagnosis of PA (ICD codes) and PTH levels checked from 2018 to 2023, excluding those with secondary causes of HPT. The PTH level analyzed was the one closest to the time of PA diagnosis. Patients with confirmed PA and adrenal imaging were included. Prevalence and central tendency measures were obtained and compared between groups. Results: A total of 110 patients were included with a diagnosis of PA, of whom 50 had image-confirmed adrenal nodules. Age, sex, race, and comorbidities were similarly distributed between both groups. Not surprisingly, patients with adrenal nodules had significantly higher surgery rates (p<0.001). Higher levels of PTH were noted in those with adrenal nodules compared to those without (median: 79 mg/dL vs. 46 mg/dL; P = 0.004). Regarding clinical manifestations of HPT, the prevalence of kidney stones was similar in both groups (28.3% vs. 28%), while bone mineral disorders were less frequent in the group with adrenal nodules (16% vs. 20%). Levels of calcium, albumin, phosphorus, and vitamin D were similarly distributed in both groups. Notably, a DXA scan was ordered in only 33 patients. Additionally, only 23 out of 50 patients underwent adrenal venous sampling (46%), and 15 out of 23 (65%) lateralized to the adenoma. Discussion: Similar to other studies, our data suggests that patients with PA and adrenal nodules have higher PTH levels compared to those without adrenal nodules. Interestingly, the degree of PTH elevation did not clinically correlate with a higher prevalence of bone mineral disorders or kidney stones in these patients, although the number of patients screened for these potential complications was low (30%). Conclusion: Future research is needed to further elucidate the mechanisms and gain a deeper understanding of the connection between aldosterone excess and PTH levels. This will enable more prompt screening for the deleterious effects of HPT in patients with PA. Presentation: Monday, July 14, 2025

Obstructive sleep apnea syndrome (OSAS) is a common health problem, and associated with obesity, metabolic syndrome (MetS), and diabetes. Growing evidence shows that 25-hydroxyvitamin-D3 (25-OH-D) insufficiency and high parathyroid hormone (PTH) levels may be correlated to glucose intolerance, MetS, obesity, and cardiovascular abnormalities similar to OSAS. Bisphenol A (BPA) is an endocrine disruptor agent which exerts a wide variety of metabolic effects. It has estrogenic activity and its exposure may contribute to weight gain, obesity, impaired glucose metabolism, and the development of diabetes, also similar to OSAS. The aim of this study is to investigate the relationships between OSAS and serum BPA, 25-OH-D, and PTH levels. This study enrolled 128 subjects, with all of the OSAS patients having been diagnosed by polysomnography. The 128 subjects were divided into three groups: a control (n=43), a moderate OSAS (n=23) (AHI=15-30), and a severe OSAS groups (n=62) (AHI>30). The serum BPA, 25-OH-D, and PTH levels for each subject were analyzed. 25-OH-D was lower in both OSAS groups, and PTH was higher in the OSAS groups than in the control subjects. The BPA levels were higher in the severe OSAS group than the moderate OSAS and control. There was a positive correlation between the BPA and body mass index, and a negative correlation between the 25-OH-D and BPA levels in all of the individuals. OSAS is related to high BPA and PTH levels, and low vitamin D levels. There is a positive association between BPA levels and OSAS, and the severity of OSAS. These results suggest that the BPA levels may have a role in the pathogenesis of OSAS.

Postmenopausal women with osteoporosis have a high prevalence of secondary metabolic disturbances that affect the severity of bone loss and the response to treatment. Conditions discussed in the Barcelona Study include vitamin D deficiency, high parathyroid hormone (PTH) levels (with and without hypercalcemia), and idiopathic hypercalciuria. Ninety percent of the patients with high PTH levels did not have primary hyperparathyroidism. A normocalcemic group with the highest PTH values had low calcium excretion, implying low calcium intake or deficient calcium absorption. This study emphasizes the importance of performing a metabolic evaluation for menopausal patients with low bone mass, which will uncover patients with idiopathic hypercalciuria and any who are not getting enough calcium.

Primary hyperparathyroidism

The discovery of fibroblast growth factor-23 (FGF-23) and the elucidation of its function as a phosphaturic and 1,25(OH)2VitD counter-regulatory hormone provides a new conceptual framework for the understanding of the pathogenesis of secondary hyperparathyroidism. This study aims to elucidate the complex associations between FGF-23, parathyroid hormone (PTH), 1,25(OH)2D, and phosphate in patients with early-stage chronic kidney disease (CKD) and to provide clinical evidence in favor of the new phosphate-centric paradigm for the pathogenesis of secondary hyperparathyroidism. Serum biointact PTH and FGF-23, 25(OH)D, 1,25(OH)2D, calcium, phosphate, 24-hour urine excretion of phosphate and calcium, and urinary fractional excretion of phosphate were determined in a cross-sectional study including 125 patients with CKD stages 1 to 3. Serum phosphate levels showed an inverse association with estimated GFR (eGFR), but were within the normal range in all but one patient. FGF-23 and PTH were inversely associated with eGFR, even in the subgroup of patients with CKD stages 1 and 2. High FGF-23 levels were significantly more prevalent than high PTH levels. The urinary fractional excretion of phosphate was highest in patients with both a high serum FGF-23 and PTH level. Increased FGF-23 and phosphate and decreased 25(OH)D were independently associated with decreased 1,25(OH)2D. Our data are in favor of the new paradigm for the pathogenesis of secondary hyperparathyroidism according to which a reduced phosphate excretion capacity is the principal abnormality that initiates secondary hyperparathyroidism.

End-stage renal disease (ESRD) patients frequently develop structural cardiac abnormalities, particularly left ventricular hypertrophy (LVH). The mechanisms involved in these processes are not completely understood. In the present study, we evaluated a possible association between parathyroid hormone (PTH) levels and left ventricular mass (LVM) in patients with ESRD. Stable uremic patients on intermittent hemodialysis treatment were evaluated by standard two-dimensional echocardiography and their sera were analyzed for intact PTH. Forty-one patients (mean age 45 years, range 18 to 61 years), 61% males, who had been on hemodialysis for 3 to 186 months, were evaluated. Patients were stratified into 3 groups according to serum PTH: low levels (< 100 pg/ml; group I = 10 patients), intermediate levels (100 to 280 pg/ml; group II = 10 patients) and high levels (> 280 pg/ml; group III = 21 patients). A positive statistically significant association between LVM index and PTH was identified (r = 0.34; P = 0.03, Pearson's correlation coefficient) in the sample as a whole. In subgroup analyses, we did not observe significant associations in the low and intermediate PTH groups; nevertheless, PTH and LVM index were correlated in patients with high PTH levels (r = 0.62; P = 0.003). LVM index was also inversely associated with hemoglobin (r = -0.34; P = 0.03). In multivariate analysis, after adjustment for age, hemoglobin, body mass index, and blood pressure, the only independent predictor of LVM index was PTH level. Therefore, PTH is an independent predictor of LVH in patients undergoing chronic hemodialysis. Secondary hyperparathyroidism may contribute to the elevated cardiovascular morbidity associated with LVH in ESRD.

Psoriasis is associated with an increased risk of cardiovascular disease although the mechanism remains unclear. Recent studies have shown that such patients have a high prevalence of vitamin D (vit-D) deficiency and elevated parathyroid hormone (PTH) level. We hypothesized that vit-D deficiency and/or elevated PTH in psoriasis may contribute to left ventricular (LV) dysfunction. Seventy-four patients with severe psoriasis with no known cardiovascular disease and 53 age- and gender-matched controls were recruited. All patients underwent detailed transthoracic echocardiography, including speckle tracking derived strains, and plasma levels of 25-hydoxyvitamin D (25-OHD), PTH and cardiac biomarkers including high sensitive C-reactive protein (hs-CRP), high sensitive troponin I (hs-TNI) and brain natriuretic peptide (BNP) were measured. Despite similar systolic and diastolic LV function, patients with severe psoriasis had impaired LV global longitudinal (-18.1 ± 2.6 vs.-19.6 ± 2.9%, P < 0.01) and circumferential strain (-18.7 ± 3.6 vs. -20.8 ± 4.3%, P < 0.01) compared with controls. Patients with severe psoriasis also had a significantly higher PTH (49.9 ± 18.0 vs. 40.5 ± 15.4 pmol/mL, P < 0.01) and hs-CRP (5.7 ± 6.9 vs. 1.9 ± 2.5 pg/mL, P < 0.01), but similar levels of 25-OHD, hs-TNI and BNP (all P > 0.05) compared with controls. Importantly, PTH level was negatively correlated with LV global longitudinal strain (R = -0.30, P < 0.01); and higher PTH level was independently associated with impaired global LV longitudinal strain (R = -0.33, P = 0.04), independent of cardiovascular risk factors, vit-D status and serum biomarkers. Severe psoriasis patients had an elevated PTH level and suffered from subclinical LV systolic dysfunction as detected by impaired global LV longitudinal strain. Importantly, a higher PTH level was independently associated with impaired global LV longitudinal strain.

Elevated Fibroblast Growth Factor 23 Levels As a Cause of Early Post–Renal Transplantation Hypophosphatemia

Recently, normocalcemic (NC) and normohormonal (NH) variants of primary hyperparathyroidism (pHPT) have been described, with distinct biochemical profiles from the typical high serum calcium and parathyroid hormone (PTH) levels. Here, we investigate whether biochemical profile affects cure rate, as well as the kinetics of intraoperative PTH (IOPTH). This is a single-center, retrospective study of pHPT patients undergoing parathyroidectomy. Patients were grouped based on preoperative calcium and PTH levels into typical, NC (normal calcium, elevated PTH, no evidence of secondary hyperparathyroidism), and NH (elevated calcium, unsuppressed PTH) biochemical profiles. All patients had IOPTH monitoring and ≥6-month post-op serum studies to confirm surgical cure. Patient variables were analyzed with Kruskal-Wallis test and Chi-square analysis. IOPTH kinetic curves were analyzed using a linear mixed model. From June 2006 to October 2014, 646 patients met inclusion criteria. Biochemical profile was typical in 460 patients (71%), NC in 101 (16%), and NH in 85 (13%). IOPTH levels were higher at all time points in typical patients, p < 0.001. Surgical cure rates were significantly lower for NC patients (90.1%) than for typical (98.5%) or NH patients (97.7%), p < 0.001, although a stricter criteria for cure was used in this group(normal calcium AND normal PTH). In a multivariable linear mixed model, NC patients had a significantly slower rate of IOPTH decline (p < 0.001 at 10min). Here, we better characterize the atypical variants of pHPT. Using a stricter definition of cure in the NC variant, these patients have a lower surgical cure rate than typical or NH variants in pHPT. The IOPTH curve is affected by biochemical profile, with both NC and NH patients having lower absolute values and NC patients having a slower decline.

Background: Previous research has established a link between high blood levels of parathyroid hormone (PTH) levels and hyperglycemia, as well as early mortality. However, the extent of this relationship and the predictive value of PTH for mortality risk in hyperglycemic populations have been minimally explored. Methods: The National Health and Nutrition Examination Survey study conducted from 2003 to 2006 identified 932 adults with diabetes and 1645 adults with prediabetes. A weighted multivariate logistic regression analysis was utilized to examine the association between PTH levels and hyperglycemia. Furthermore, Cox proportional hazards regression models were employed to examine the correlation between PTH levels and both cardiovascular and overall mortality within the hyperglycemia cohort. Results: (1) The research findings revealed a negative association between PTH levels (per 10-pg/mL increase) and diabetes status (OR, 0.79; 95% confidence interval (CI), 0.73–0.86). (2) There was a significant correlation between the risk of all-cause mortality (hazard ratios (HR), 1.13; 95% CI, 1.01–1.29) and cardiovascular disease mortality (HR, 1.39; 95% CI, 1.05–1.84) among individuals with diabetes for every 10-pg/mL increase in PTH levels. Conclusion: The current research shows that individuals with elevated PTH spectrum within the normal range are less likely to have diabetes, while those with higher PTH levels in adults with diabetes are linked to worse outcomes, particularly cardiovascular mortality.

Calcium carbonate (CaCO3) is an effective phosphate (PO4) binder in uremics, and its use reduces aluminum (Al) intake. By maintaining high serum Ca2+, it decreases serum parathyroid hormone (PTH) levels. Hypercalcemia, however, often limits the dosage. In order to evaluate the effects of a low-Ca peritoneal dialysis solution (PDS) (1.25 mmol/L) on Ca metabolism, we studied the following in 12 continuous ambulatory peritoneal dialysis (CAPD) patients with hypercalcemia (6 with low PTH levels, low-turnover bone disease, group 1, and 6 with high PTH levels, high-turnover bone disease, group 2, documented by bone biopsies): serum Ca2+; serum PTH; bone morphology. The follow-up was 12 months. Results show that in both groups within the third month there was a decrease in serum Ca2+. In group 1 serum PTH increased, reaching the norm, and in group 2 it further increased exceeding the norm. Because in both groups serum Ca2+ was normal, it was possible to increase oral CaCO3 (10.5 +/- 2.5 g/day) to control PO4 levels and to stop Al gels. In group 2, in order to avoid the further rise of serum PTH, the low-Ca PDS was supplemented with 2 micrograms/day of 1,25(OH)2D3 (vitamin D3); this was followed by a reduction in serum PTH with no increase in Ca2+ and PO4. The use of low-Ca PDS may be useful in preventing hypercalcemia in CAPD patients treated with high oral doses of CaCO3 and in improving low-turnover bone disease, while low-Ca PDS supplemented with vitamin D3 improves high-turnover bone disease.

We have used high-dose oral pulse therapy with 1 alpha-hydroxycholecalciferol (1 alpha-OH-D3) to treat 40 hemodialysis patients suffering form secondary hyperparathyroidism. Forty patients with intact parathyroid hormone (PTH) levels of > 150 pg/ml were treated with 4 micrograms oral 1 alpha-OH-D3 twice weekly for 1 year. The mean PTH level was 515 +/- 50 pg/ml prior to treatment, which fell to 191 +/- 42 pg/ml after 6 months of treatment (p < 0.00001), and to 164 +/- 39 pg/ml after 12 months of treatment. Patients with very high PTH levels (> 800 pg/ml) suppressed less well than patients with lower levels (150-300 pg/ml). The therapeutic end point of PTH < 100 pg/ml was achieved in 23 patients (58%). The main side effect of the treatment was hypercalcemia, but this was symptomatic in only 3 patients, all above the age of 70 years. In summary, oral high-dose pulse therapy with 1 alpha-OH-D3 was highly effective in suppressing PTH levels in hyperparathyroid hemodialysis patients, and side effects were relatively few.

A Structural Approach to Renal Bone Disease

Calciotropic hormones, parathyroid hormone (PTH) and calcitonin are involved in the regulation of bone mineral metabolism and maintenance of calcium and phosphate homeostasis in the body. Therefore, an understanding of environmental and genetic factors influencing PTH and calcitonin levels is crucial. Genetic factors are estimated to account for 60% of variations in PTH levels, while the genetic background of interindividual calcitonin variations has not yet been studied. In this review, we analyzed the literature discussing the influence of environmental factors (lifestyle factors and pollutants) on PTH and calcitonin levels. Among lifestyle factors, smoking, body mass index (BMI), diet, alcohol, and exercise were analyzed; among pollutants, heavy metals and chemicals were analyzed. Lifestyle factors that showed the clearest association with PTH levels were smoking, BMI, exercise, and micronutrients taken from the diet (vitamin D and calcium). Smoking, vitamin D, and calcium intake led to a decrease in PTH levels, while higher BMI and exercise led to an increase in PTH levels. In terms of pollutants, exposure to cadmium led to a decrease in PTH levels, while exposure to lead increased PTH levels. Several studies have investigated the effect of chemicals on PTH levels in humans. Compared to PTH studies, a smaller number of studies analyzed the influence of environmental factors on calcitonin levels, which gives great variability in results. Only a few studies have analyzed the influence of pollutants on calcitonin levels in humans. The lifestyle factor with the clearest relationship with calcitonin was smoking (smokers had increased calcitonin levels). Given the importance of PTH and calcitonin in maintaining calcium and phosphate homeostasis and bone mineral metabolism, additional studies on the influence of environmental factors that could affect PTH and calcitonin levels are crucial.

Background & objectives:Primary hyperparathyroidism (PHPT) is a common endocrine disorder caused by the elevated secretion of the parathormone (PTH). The aim of this study was to evaluate the haematological manifestations of PHPT in patients with normal renal functions who were treated surgically for parathyroid adenomas.Methods:In this retrospective cross-sectional study, 134 patients with normal renal functions who underwent parathyroidectomies for PHPT were included. The haematological manifestations were evaluated in the total study cohort and in the two groups of different calcium (Ca) levels (Group 1 ≤11.2 mg/dl and Group 2 >11.2 mg/dl).Results:The overall prevalence of anaemia, leucopenia and thrombocytopenia was 20.1, 6.7 and 6.0 per cent, respectively. Normocytic anaemia was present in 19 (14.2%) patients. There were no significant differences in the prevalence of anaemia, leucopenia and thrombocytopenia between the two groups. There were no correlations between the PTH levels and the leukocyte, haemoglobin or platelet values. Six to 12 months after the parathyroidectomy (PTX), 35.7 per cent of the patients with anaemia, 85.7 per cent of the patients with leucopenia and 100 per cent of the patients with thrombocytopenia had recovered.Interpretation & conclusions:In the present study, anaemia was seen with a variable frequency in PHPT, but there was no relationship between anaemia and high PTH or Ca levels. The development of anaemia can be seen regardless of the PTH levels in PHPT patients with normal renal functions. High-resolution rates after PTX indicate a possible association between PHPT and thrombocytopenia or leucopenia, although their prevalence is low in PHPT.