Long-Term Progression-Free Survival of a Pre-Treated Patient with Metastatic Colorectal Cancer Receiving Trifluridine/Tipiracil.

Trifluridine/tipiracil is approved for the use in later or last-line setting in previously treated metastatic colorectal cancer (mCRC) patients who progressed on standard anti-tumor drugs including 5-fluorouracil (5-FU), irinotecan, oxaliplatin, anti-VEGF and anti-EGFR antibodies, or who are not considered candidates for those standard therapies. In this report, we describe a 67-year-old male patient with KRAS-mutated mCRC and metachronous liver and lung metastasis who failed prior 5-FU- and irinotecan-containing regimens, but then showed long-term disease control for 31 months on single-agent trifluridine/tipiracil given as second-line treatment. According to our experience, trifluridine/tipiracil is a feasible and effective treatment option in earlier but not necessarily last-line therapy in mCRC patients who are not considered candidates for doublet or triplet chemotherapy. Besides its efficacy, it is associated with maintained quality of life and a manageable toxicity profile. Considering increasing age of mCRC patients and their wish for maintaining an independent lifestyle, further research on the use of trifluridine/tipiracil in earlier lines of systemic mCRC therapy is warranted.

Primary presentation and clinical course of pediatric and adolescent patients with differentiated thyroid carcinoma after radioiodine therapy.

Introduction: Differentiated thyroid carcinoma (DTC) in childhood and during adolescence is extremely rare. Pediatric DTC commonly presents with advanced disease at diagnosis including a high prevalence of cervical lymph node metastases and pulmonary metastases. Studies in children with DTC are limited. Therefore, we aimed to evaluate the initial presentation, effectiveness of radioiodine therapy (RIT), and long-term outcome of prepubertal in comparison to pubertal/postpubertal patients. Methods: Eighty-five pediatric and young patients aged 6.4 to 21.9 years with histopathologically confirmed DTC were retrospectively included. They all underwent total thyroidectomy followed by RIT. Initial presentation and outcome of prepubertal and pubertal/postpubertal patients were compared 1 year after RIT, during follow-up, and at the last visit of follow-up. Results: Prepubertal patients presented with significantly higher T and M stages. One year after RIT, 42/81 (52%) patients still presented with evidence of disease (ED). During follow-up of a median of 7.9 years, prepubertal patients were less often in complete remission (58% vs. 82% in pubertal patients). At the last visit of follow-up, 19/80 (24%) patients still had ED without statistical differences between the two groups (42% prepubertal vs. 18% pubertal/postpubertal, p-value 0.06). None of our patients died disease-related over the observed period. Conclusion: Prepubertal children with DTC presented with a more advanced tumor stage at the initial presentation. During follow-up, they present more often with ED. However, at the end of our study, we did not observe statistically relevant differences in patient outcomes between the prepubertal and pubertal/postpubertal groups.

[Osteoporosis: diagnostics and treatment]. / Osteoporose: Diagnostik und Behandlung.

Osteoporosis is the most common systemic skeletal disease worldwide. Its consequences have a substantial impact on the quality of life of patients and increases the overall morbidity and mortality. Standardized diagnostic procedures and treatment recommendations have been available for years as German and international (S3) guidelines. Nevertheless, there is a considerable gap in the diagnosis and adequate treatment of osteoporosis, especially in Germany. The aim is to detect the disease at an early stage and to establish a specific and consistent treatment of osteoporosis. In this way the quality of life and independence of those affected can be maintained over a long period. In the acute and permanent treatment of manifest osteoporosis, surgeons, orthopedic and trauma surgeons play a key role.

Thyroidal Angiotensin-Converting Enzyme 2 Protein Expression and Thyroid Function Tests in Patients with COVID-19: Results from a Retrospective Case Series and a Prospective Cohort Study.

Background: Infection with SARS-CoV-2 has initially been known as a respiratory disease but in the course of the pandemic the understanding has emerged that severity is owing to fatal inflammatory responses apart from lung injury. In this context, endocrine disorders such as thyroiditis as well as pituitary dysfunction in addition to nonthyroidal illness syndrome have been described. Furthermore, angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 cell receptor, has been detected in most endocrine tissues, including the thyroid gland. Objective: To evaluate histopathologic changes and compare thyroidal ACE2 protein expression in thyroid tissue from patients who died from severe COVID-19 with thyroid tissue from patients without SARS-CoV-2 infection in a retrospective case series. Furthermore, to assess and compare alterations in thyroid function tests (TFTs) between patients with or without SARS-CoV-2 infection as well as association of TFTs with the severity of the disease in a prospective cohort study. Methods: Thyroid tissue of deceased COVID-19 patients (n = 23) was analyzed for histopathology and ACE2 expression by immunohistochemical staining. A total of 153 patients with confirmed SARS-CoV-2 were evaluated regarding TFTs and divided into a severe (intubation, intensive care treatment) and an intermediate group. Results: Thyroidal ACE2 expression was detected in 87% of the deceased COVID-19 patients. Normal thyroid tissue from patients without SARS-CoV-2 infection showed no ACE2 protein expression. Half of the severely ill COVID-19 patients had low free triiodothyronine (fT3) levels. Combination of low fT3 and thyrotropin (TSH) was associated significantly with deadly disease. Conclusion: The high percentage of positive ACE2 immunostaining in deceased patients compared with normal thyroid tissue of patients without SARS-CoV-2 infection suggests involvement of the thyroid in COVID-19, although further research will have to show the pathogenic role of thyroidal ACE2 in COVID-19. Abnormal fT3 and a TSH of ≤0.5 mU/L were associated with a fatal outcome in our severely ill SARS-CoV-2 patient cohort. Therefore, assessment of TFTs is crucial in the treatment of severely ill COVID-19 patients. Trial Registration: COVID-19 Registry of the LMU University Hospital Munich (CORKUM), WHO trial ID DRKS00021225.

[Osteoporosis: diagnostics and treatment]. / Osteoporose: Diagnostik und Behandlung.

Osteoporosis is the most common systemic skeletal disease worldwide. Its consequences have a substantial impact on the quality of life of patients and increases the overall morbidity and mortality. Standardized diagnostic procedures and treatment recommendations have been available for years as German and international (S3) guidelines. Nevertheless, there is a considerable gap in the diagnosis and adequate treatment of osteoporosis, especially in Germany. The aim is to detect the disease at an early stage and to establish a specific and consistent treatment of osteoporosis. In this way the quality of life and independence of those affected can be maintained over a long period. In the acute and permanent treatment of manifest osteoporosis, surgeons, orthopedic and trauma surgeons play a key role.

Influence of cortisol cosecretion on non-ACTH-stimulated adrenal venous sampling in primary aldosteronism: a retrospective cohort study.

Objective: Cortisol measurements are essential for the interpretation of adrenal venous samplings (AVS) in primary aldosteronism (PA). Cortisol cosecretion may influence AVS indices. We aimed to investigate whether cortisol cosecretion affects non-adrenocorticotrophic hormone (ACTH)-stimulated AVS results. Design: Retrospective cohort study at a tertiary referral center. Methods: We analyzed 278 PA patients who underwent non-ACTH-stimulated AVS and had undergone at least a 1-mg dexamethasone suppression test (DST). Subsets underwent additional late-night salivary cortisol (LSC) and/or 24-h urinary free cortisol (UFC) measurements. Patients were studied from 2013 to 2020 with follow-up data of 6 months following adrenalectomy or mineralocorticoid antagonist therapy initiation. We analyzed AVS parameters including adrenal vein aldosterone/cortisol ratios, selectivity, lateralization (LI) and contralateral suppression indices and post-operative ACTH-stimulation. We classified outcomes according to the primary aldosteronism surgical outcome (PASO) criteria. Results: Among the patients, 18.9% had a pathological DST result (1.9-5 µg/dL: n = 44 (15.8%); >5 µg/dL: n = 8 (2.9%)). Comparison of AVS results stratified according to the 1-mg DST (≤1.8 vs >1.8 µg/dL: P = 0.499; ≤1.8 vs 1.8 ≤ 5 vs >5 µg/dL: P = 0.811) showed no difference. Lateralized cases with post DST serum cortisol values > 5 µg/dL had lower LI (≤1.8 µg/dL: 11.11 (5.36; 26.76) vs 1.9-5 µg/dL: 11.76 (4.9; 31.88) vs >5 µg/dL: 2.58 (1.67; 3.3); P = 0.008). PASO outcome was not different according to cortisol cosecretion. Conclusions: Marked cortisol cosecretion has the potential to influence non-ACTH-stimulated AVS results. While this could result in falsely classified lateralized cases as bilateral, further analysis of substitutes for cortisol are required to unmask effects on clinical outcome.

A cervical compartment syndrome impairs cerebral circulation in post-thyroidectomy hemorrhage: data from an animal model.

Background: Post thyroidectomy hemorrhage is a potentially life-threatening complication. As the mechanism leading to hypoxemic brain damage and death is still unknown, our aim was to examine the underlaying pathophysiology in an animal model. Methods: A series of experiments was performed in our established model for post thyroidectomy hemorrhage in 6 pigs. First, post thyroidectomy hemorrhage was simulated with an artificial increase of cervical compartment pressure. Second, spontaneous bleeding into the cervical compartment was initiated. Primary outcome measure is the correlation between cerebral oxygenation and cervical compartment pressure. Results: With an increase in cervical compartment pressure apnea could be detected in all experiments. A significant 24.2% (9.5-34.4%) decrease of cerebral oxygenation at time of apnea (47.0%; 38.0-65.0%) compared to baseline values (63.5%; 56.0-74.0%; P=0.043) occurred due increase of cervical compartment pressure concurrent with an impaired cerebral perfusion. Apnea occurred about 200 sec after a 10% decrease of cerebral oxygenation, but 35 sec before a 10% decrease of peripheral oxygenation. Spontaneous bleeding into the cervical compartment causes an increase of cervical compartment pressure reaching levels of the mean arterial blood pressure 56.0 (35.0-72.0) mmHg. Conclusions: Peripheral hypoxemia occurs with relevant delay in time after decrease of cerebral perfusion and cerebral hypoxemia, therefore cerebral hypoxemia seems to be causal for a central apnea. With this evidence of impaired cerebral perfusion and cerebral hypoxemia due to an increased cervical compartment pressure we can disprove the historic theory of tracheal collapse due to a compressive hematoma in post thyroidectomy hemorrhage. A cervical compartment syndrome seems to be causal, not only for brain hypoxemia but also an additional laryngo-pharyngeal mucosal edema.

Preoperative Imaging with [18F]-Fluorocholine PET/CT in Primary Hyperparathyroidism.

Primary hyperparathyroidism (pHPT) is a common endocrine disorder due to hyperfunctioning parathyroid glands. To date, the only curing therapy is surgical removal of the dysfunctional gland, making correct detection and localization crucial in order to perform a minimally invasive parathyroidectomy. 18F-Fluorocholine positron emission tomography/computed tomography (18F-FCH PET/CT) has shown promising results for the detection of pHPT, suggesting superiority over conventional imaging with ultrasounds or scintigraphy. A total of 33 patients with pHPT who had negative or equivocal findings in conventional imaging received 18F-FCH PET/CT preoperatively and were retrospectively included. A pathological hyperfunctional parathyroid gland was diagnosed in 24 cases (positive PET, 72.7%), 4 cases showed equivocal choline uptake (equivocal PET, 12.1%), and in 5 cases, no enhanced choline uptake was evident (negative PET, 15.2%). Twelve of the twenty-four detected adenoma patients underwent surgery, and in all cases, a pathological parathyroid adenoma was resected at the site detected by PET/CT. Two of the six patients without pathological choline uptake who received a parathyroidectomy revealed no evidence of parathyroid adenoma tissue in the histopathological evaluation. This retrospective study analyzes 18F-FCH PET/CT in a challenging patient cohort with pHPT and negative or equivocal conventional imaging results and supports the use of 18F-FCH for the diagnosis of hyperfunctional parathyroid tissue, especially in this patient setting, with a 100% true positive and true negative detection rate. Our study further demonstrates the importance of 18F-FCH PET/CT for successful surgical guidance.

[Osteoporosis: diagnostics and treatment]. / Osteoporose: Diagnostik und Behandlung.

Osteoporosis is the most common systemic skeletal disease worldwide. Its consequences have a substantial impact on the quality of life of patients and increases the overall morbidity and mortality. Standardized diagnostic procedures and treatment recommendations have been available for years as German and international (S3) guidelines. Nevertheless, there is a considerable gap in the diagnosis and adequate treatment of osteoporosis, especially in Germany. The aim is to detect the disease at an early stage and to establish a specific and consistent treatment of osteoporosis. In this way the quality of life and independence of those affected can be maintained over a long period. In the acute and permanent treatment of manifest osteoporosis, surgeons, orthopedic and trauma surgeons play a key role.

The role of adrenal venous sampling (AVS) in primary bilateral macronodular adrenocortical hyperplasia (PBMAH): a study of 16 patients.

OBJECTIVE: Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a rare cause of ACTH-independent Cushing's syndrome. Current guidelines recommend bilateral adrenalectomy for PBMAH, but several studies showed clinical effectiveness of unilateral adrenalectomy despite bilateral disease in selected patients. Our aim was to evaluate the gain of information which can be obtained through adrenal venous sampling (AVS) based cortisol lateralization ratios for guidance of unilateral adrenalectomy. DESIGN: We performed a retrospective analysis of 16 patients with PBMAH and clinical overt cortisol secretion in three centers METHODS: Selectivity of adrenal vein sampling during AVS was defined as a gradient of cortisol or a reference adrenal hormone ≥2.0 between adrenal and peripheral vein. Lateralization was assumed if the dominant to non-dominant ratio of cortisol to reference hormone was ≥4.0. RESULTS: AVS was technically successful in all patients based on absolute cortisol levels and in 13 of 16 patients (81%) based on reference hormone levels. Lateralization was documented in 8 of 16 patients. In patients with lateralization, in 5 of 8 cases this occurred toward morphologically larger adrenals, while in 3 patients lateralization was present in bilaterally identical adrenals. The combined volume of adrenals correlated positively with urinary free cortisol, suggesting that adrenal size is the dominant determinant of cortisol secretion. CONCLUSIONS: In this study the gain of information through AVS for unilateral adrenalectomy was limited in patients with PBMAH and marked adrenal asymmetry.

Personalized drug testing in human pheochromocytoma/paraganglioma primary cultures.

Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular targeting is being increasingly considered, but with variable results. This study investigates established and novel molecular-targeted drugs and chemotherapeutic agents for the treatment of PPGLs in human primary cultures and murine cell line spheroids. In PPGLs from 33 patients, including 7 metastatic PPGLs, we identified germline or somatic driver mutations in 79% of cases, allowing us to assess potential differences in drug responsivity between pseudohypoxia-associated cluster 1-related (n = 10) and kinase signaling-associated cluster 2-related (n = 14) PPGL primary cultures. Single anti-cancer drugs were either more effective in cluster 1 (cabozantinib, selpercatinib, and 5-FU) or similarly effective in both clusters (everolimus, sunitinib, alpelisib, trametinib, niraparib, entinostat, gemcitabine, AR-A014418, and high-dose zoledronic acid). High-dose estrogen and low-dose zoledronic acid were the only single substances more effective in cluster 2. Neither cluster 1- nor cluster 2-related patient primary cultures responded to HIF-2a inhibitors, temozolomide, dabrafenib, or octreotide. We showed particular efficacy of targeted combination treatments (cabozantinib/everolimus, alpelisib/everolimus, alpelisib/trametinib) in both clusters, with higher efficacy of some targeted combinations in cluster 2 and overall synergistic effects (cabozantinib/everolimus, alpelisib/trametinib) or synergistic effects in cluster 2 (alpelisib/everolimus). Cabozantinib/everolimus combination therapy, gemcitabine, and high-dose zoledronic acid appear to be promising treatment options with particularly high efficacy in SDHB-mutant and metastatic tumors. In conclusion, only minor differences regarding drug responsivity were found between cluster 1 and cluster 2: some single anti-cancer drugs were more effective in cluster 1 and some targeted combination treatments were more effective in cluster 2.

Renin, a marker for left ventricular hypertrophy, in primary aldosteronism: a cohort study.

CONTEXT: Primary aldosteronism (PA) causes left ventricular hypertrophy (LVH) via hemodynamic factors and directly by aldosterone effects. Specific treatment by mineralocorticoid receptor antagonists (MRA) or adrenalectomy (ADX) has been reported to improve LVH. However, the cardiovascular benefit could depend on plasma renin concentration (PRC) in patients on MRA. PATIENTS AND OBJECTIVE: We analyzed data from 184 patients from the Munich center of the German Conn's Registry, who underwent echocardiography at the time of diagnosis and 1 year after treatment. To assess the effect of PRC on cardiac recovery, we stratified patients on MRA according to suppression (n = 46) or non-suppression of PRC (n = 59) at follow-up and compared them to PA patients after ADX (n = 79). RESULTS: At baseline, patients treated by ADX or MRA had comparable left ventricular mass index (LVMI, 61.7 vs 58.9 g/m2.7, P = 0.591). Likewise, patients on MRA had similar LVMI at baseline, when stratified into treatment groups with suppressed and unsuppressed PRC during follow-up (60.0 vs 58.1 g/m2.7, P = 0.576). In all three groups, we observed a significant reduction in LVMI following treatment (P < 0.001). However, patients with suppressed PRC had no decrease in pro-BNP levels, and the reduction of LVMI was less intense than in patients with unsuppressed PRC (4.1 vs 8.2 g/m2.7, P = 0.033) or after ADX (9.3 g/m2.7, P = 0.019). Similarly, in multivariate analysis, higher PRC was correlated with the regression of LVH. CONCLUSION: PA patients with suppressed PRC on MRA show impaired regression of LVH. Therefore, dosing of MRA according to PRC could improve their cardiovascular benefit.

Single-Center Prospective Cohort Study on the Histopathology, Genotype, and Postsurgical Outcomes of Patients With Primary Aldosteronism.

[Figure: see text].

Influence of insufflated carbon dioxide on abdominal temperature compared to oesophageal temperature during laparoscopic surgery.

BACKGROUND: Body core temperature is an important vital parameter during surgery and anaesthesia. It is influenced by several patient-related and surgery-related factors. Laparoscopy is considered beneficial in terms of a variety of parameters, for example, postoperative pain and length of hospital stay. Non-humidified, non-warmed insufflated CO2 applied during laparoscopy is standard of care. This prospective observational trial therefore evaluates the impact of non-humidified CO2 at room temperature on abdominal temperature and its correlation to body core temperature. METHODS: Seventy patients undergoing laparoscopic surgery were included in this prospective observational study. Temperature was measured oesophageal and abdominal before induction of anaesthesia (T1), right before skin incision (T2), 15 min, 30 min and 60 min after skin incision. All patients were treated according to actual guidelines for perioperative temperature measurement. RESULTS: Body core temperature and abdominal temperature correlated moderately (r = 0.6123; p < 0.0001). Bland-Altman plot for comparison of methods showed an average difference of 0.4 °C (bias - 0.3955; 95% agreement of bias from - 2.365 to 1.574). Abdominal temperature further decreased after establishing pneumoperitoneum (T2: 36.2 °C (35.9/36.4) to T5: 36.1 °C (35.6/36.4); p < 0.0001), whereas oesophageal temperature increased (T2: 36.2 °C (35.9/36.4) to 36.4 °C (36.0/36.7); p = 0.0296). Values of oesophageal and abdominal measurement points differed at T4 (36.3 °C (36.0/36.6) vs. 36.1 °C (35.4/36.6); p < 0.0001) and T5 (36.4 °C (36.0/36.7) vs. 36.1 °C (35.6/36.4) p = 0.0003). CONCLUSION: This prospective observational trial shows the influence of insufflated, non-humidified carbon dioxide at room temperature on abdominal temperature during laparoscopic surgery. We show that carbon dioxide applied at these conditions decreases abdominal temperature and therefore might be a risk factor for perioperative hypothermia.

Recurrence after pituitary surgery in adult Cushing's disease: a systematic review on diagnosis and treatment.

PURPOSE: Recurrence after pituitary surgery in Cushing's disease (CD) is a common problem ranging from 5% (minimum) to 50% (maximum) after initially successful surgery, respectively. In this review, we give an overview of the current literature regarding prevalence, diagnosis, and therapeutic options of recurrent CD. METHODS: We systematically screened the literature regarding recurrent and persistent Cushing's disease using the MESH term Cushing's disease and recurrence. Of 717 results in PubMed, all manuscripts in English and German published between 1980 and April 2020 were screened. Case reports, comments, publications focusing on pediatric CD or CD in veterinary disciplines or studies with very small sample size (patient number < 10) were excluded. Also, papers on CD in pregnancy were not included in this review. RESULTS AND CONCLUSIONS: Because of the high incidence of recurrence in CD, annual clinical and biochemical follow-up is paramount. 50% of recurrences occur during the first 50 months after first surgery. In case of recurrence, treatment options include second surgery, pituitary radiation, targeted medical therapy to control hypercortisolism, and bilateral adrenalectomy. Success rates of all these treatment options vary between 25 (some of the medical therapy) and 100% (bilateral adrenalectomy). All treatment options have specific advantages, limitations, and side effects. Therefore, treatment decisions have to be individualized according to the specific needs of the patient.

The Impact of Glucocorticoid Co-Secretion in Primary Aldosteronism on Thyroid Autoantibody Titers During the Course of Disease.

Excess aldosterone is associated with the increased risk of cardio-/cerebrovascular events as well as metabolic comorbidities not only due to its hypertensive effect but also due to its proinflammatory action. Autonomous cortisol secretion (ACS) in the setting of primary aldosteronism (PA) is known to worsen cardiovascular outcome and potentially exhibit immunosuppressive effects. The aim of this study was to determine the impact of ACS status in patients with PA on kinetics of thyroid autoantibodies (anti-TPO, anti-TG) pre and post therapy initiation. Ninety-seven PA patients (43 unilateral, 54 with bilateral PA) from the database of the German Conn's Registry were included. Anti-TPO and anti-TG levels were measured pre and 6-12 months post therapeutic intervention. Patients were assessed for ACS according to their 24- hour urinary cortisol excretion, late night salivary cortisol and low-dose dexamethasone suppression test. Abnormal test results in line with ACS were identified in 74.2% of patients with PA. Following adrenalectomy, significant increases in anti-TPO levels were observed in patients with at least one abnormal test (p = 0.049), adrenalectomized patients with at least two pathological ACS tests (p = 0.015) and adrenalectomized patients with pathologic dexamethasone suppression tests (p = 0.018). No antibody increases were observed in unilateral PA patients without ACS and in patients with bilateral PA receiving mineralocorticoid antagonist therapy (MRA). Our data are in line with an immunosuppressive effect of mild glucocorticoid excess in PA on thyroid autoantibody titers. This effect is uncovered by adrenalectomy, but not by MRA treatment.

Indocyanine green fluorescence imaging during partial adrenalectomy.

BACKGROUND: Indocyanine green (ICG) fluorescence imaging represents an emerging technology that facilitates the assessment of tissue vascularity, tissue distinction, and tumor localization during surgery. The aim of this study was to investigate the potential role of ICG imaging during laparoscopic partial adrenalectomy. METHODS: Indocyanine fluorescence imaging was carried out during laparoscopic partial adrenalectomy for bilateral pheochromocytoma and bilateral Cushing's syndrome. A first bolus of 5 mg ICG was applied intravenously upon exposure of the retroperitoneal plane to identify the adrenal borders. The fluorescence was visualized using a Storz® NIR/ICG endoscopic system. As the camera of this system detects NIR light as a blue signal, the well-vascularized adrenal tissue was expected to show a strong fluorescence in the blue color channel in contrast to the surrounding adipose tissue. Following partial adrenalectomy, a second bolus of 5 mg ICG was applied intravenously to evaluate the vascularity of the remaining adrenal tissue. RESULTS: We investigated six adrenal glands from three patients undergoing bilateral partial adrenalectomy. The indication for surgery was pheochromocytoma in two patients and Cushing's syndrome with bilateral adenomas in one patient. Regarding left adrenalectomies, ICG imaging was helpful in visualizing the adrenal borders and the adrenal vein. Further, it facilitated the identification of the hypofluorescent pheochromocytoma and to resect the entire tumor. On the right side, due to the more apparent anatomy, ICG imaging did not contribute to the conduct of the operation. Four adrenal remnants showed a strong vascularization and two remnants were only reasonably vascularized. CONCLUSION: ICG fluorescence may be helpful in guiding partial adrenalectomy and assessing the vascularity of remaining adrenal tissue.

Primary and Secondary Hyperparathyroidism in Patients with Primary Aldosteronism - Findings From the German Conn's Registry.

CONTEXT: Recent studies support a bidirectional interaction between aldosterone and parathyroid hormone (PTH), possibly increasing the individual cardiovascular risk. Primary aldosteronism (PA) and primary hyperparathyroidism can occur simultaneously. OBJECTIVE: Our aim was to investigate the prevalence of hyperparathyroidism in PA. PATIENTS: We performed a case finding of primary hyperparathyroidism in a retrospective series of 503 patients with PA (cohort 1). We analysed primary and secondary hyperparathyroidism in 141 prospective PA patients who underwent PTH, serum calcium and phosphate measurements at time of diagnosis of PA (cohort 2). RESULTS: The prevalence for primary hyperparathyroidism was 1.2% in cohort 1, and 2.1% in cohort 2. Secondary hyperparathyroidism was found in 54.6% of the patients. Patients with secondary hyperparathyroidism had significantly higher aldosterone and lower potassium levels and took more antihypertensive medications compared to those with normal PTH levels. In multivariate analysis, aldosterone and 25-hydroxyvitamin D levels were significantly correlated with serum PTH levels. There was a nonsignificant trend to a higher cardiovascular morbidity in patients with secondary hyperparathyroidism. Patients with aldosterone producing adenoma had significantly higher PTH levels compared to patients with bilateral adrenal hyperplasia. After treatment, there was a significant decrease of PTH levels in both groups. CONCLUSION: Patients with PA frequently have primary or secondary hyperparathyroidism, which is alleviated by correction of PA by surgical or medical means. Patients affected by secondary hyperparathyroidism seem to have a more severe phenotype of PA and have a trend towards more cardiovascular co-morbidities.