Prevalence of Primary Aldosteronism Across the Stages of Hypertension Based on a New Combined Overnight Test.

Primary aldosteronism (PA) is the most common endocrine cause of arterial hypertension. Despite the increasing incidence of hypertension worldwide, the true prevalence of PA in hypertension was only recently recognized. The objective of the work was to estimate the prevalence of PA in patients at different stages of hypertension based on a newly developed screening-diagnostic overnight test. This is a prospective study with hypertensive patients (n=265) at stage I (n=100), II (n=88), and III (n=77) of hypertension. A group of 103 patients with essential hypertension without PA was used as controls. PA diagnosis was based on a combined screening-diagnostic overnight test, the Dexamethasone-Captopril-Valsartan Test (DCVT) that evaluates aldosterone secretion after pharmaceutical blockade of angiotensin-II and adrenocorticotropic hormone. DCVT was performed in all participants independently of the basal aldosterone to renin ratio (ARR). The calculated upper normal limits for post-DCVT aldosterone levels [3 ng/dl (85 pmol/l)] and post-DCVT ARR [0.32 ng/dl/µU/ml (9 pmol/IU)] from controls, were applied together to establish PA diagnosis. Using these criteria PA was confirmed in 80 of 265 (30%) hypertensives. The prevalence of PA was: 21% (21/100) in stage I, 33% (29/88) in stage II, and 39% (30/77) in stage III. Serum K+ levels were negatively correlated and urinary K+ was positively correlated in PA patients with post-DCVT ARR (r=-0.349, p <0.01, and r=0.27, p <0.05 respectively). In conclusion, DCVT revealed that PA is a highly prevalent cause of hypertension. DCVT could be employed as a diagnostic tool in all subjects with arterial hypertension of unknown cause.

Effectiveness of intramuscular ergocalciferol treatment in a patient with osteomalacia and insufficiency fractures due to severe vitamin D deficiency after bariatric surgery.

Vitamin D (vitD) deficiency and bone loss may occur after bariatric surgery and hence, supplementation with high oral doses of vitD may be required. Alternatively, intramuscular depot ergocalciferol, which slowly releases vitD and bypasses the gastrointestinal tract, could be administrated. We present a case of severe vitD deficiency-osteomalacia after gastric bypass operation for morbid obesity, treated with ergocalciferol intramuscularly. A 45-year-old woman was presented with hip pain and muscle weakness, which led ultimately to immobilization in a wheelchair. Fifteen years ago, she underwent roux-en-Y gastric by-pass for morbid obesity. Occasionally, she was treated with multivitamin supplements. On admission, iron deficiency anaemia, vitD deficiency (25OHD: 3.7 ng/ml) and secondary hyperparathyroidism were revealed. Bone turnover markers (BTM) were elevated. Radiological evaluation demonstrated insufficiency fractures on the pubic and left femur and reduced BMD. Osteomalacia due to vitD deficiency and calcium malabsorption were diagnosed. Calcium citrate 500 mg qid and intramuscular ergocalciferol 600,000 IU every 20 days were initiated. One month later, musculoskeletal pain and weakness were resolved and the patient was mobilized. Few months later, vitD, BTM and BMD showed substantial improvement. Intramuscular ergocalciferol administration can improve the clinical and biochemical status and thus, is suggested to prevent and/or treat osteomalacia in such patients.

Concomitant alterations of metabolic parameters, cardiovascular risk factors and altered cortisol secretion in patients with adrenal incidentalomas during prolonged follow-up.

OBJECTIVE: Adrenal incidentalomas (AI) are associated with metabolic and hormonal abnormalities, most commonly autonomous cortisol secretion (ACS). Data regarding alterations of insulin resistance (IR) and ACS after prolonged follow-up are limited. We investigated the evolution of IR, cortisol secretion and ACS development in patients with AI during prolonged follow-up. DESIGN: Prospective study in a tertiary hospital. PATIENTS AND MEASUREMENTS: Seventy-one patients with AI [51 nonfunctioning (NFAI) and 20 ACS] and 5·54 ± 1·7 years follow-up underwent testing for ACS and oral glucose tolerance test to determine IR indices and adrenal imaging. RESULTS: At follow-up, 16/51 (31%) NFAI patients converted to ACS, while two with previous ACS reverted to NFAI; 21% (7/33) of patients who did not covert to ACS exhibited high urinary-free cortisol (H-UFC) levels. All AI patients developed deterioration of IR irrespective of their cortisol secretory status. Eight patients developed newly diagnosed type 2 diabetes (9·8% NFAI and 15% ACS, respectively) and 14 IR (17·6% NFAI and 25% ACS, respectively). Adenoma size increased from 2·1 ± 0·8 to 2·3 ± 0·8 cm, whereas IR correlated with postdexamethasone cortisol level and adenoma size increase. IR showed an incremental continuum trend from normal UFC (Ν-UFC), to H-UFC, C-ACS and ACS patients. CONCLUSIONS: New-onset ACS developed in 31% patients with NFAI, whereas 21% of NFAI patients had H-UFC levels. All AI patients as a group and the subgroups of N-UFC, H-UFC, C-ACS and ACS patients developed deterioration of metabolic parameters during follow-up that was more prominent in ACS patients.

Primary aldosteronism in hypertensive patients: clinical implications and target therapy.

BACKGROUND: The prevalence of primary aldosteronism (PA) in hypertensive patients varies according to diagnostic testing and ascertained normal cut-offs. The aim of this case-control study was to confirm the high prevalence of PA in a large hypertensive population and evaluate the antihypertensive effect of mineralocorticoid receptor antagonists (MRA) treatment. MATERIAL AND METHODS: We investigated 327 hypertensive and 90 matched normotensive subjects with normal adrenal imaging. Serum aldosterone (ALD), active renin (REN) levels and aldosterone/active renin (ALD/REN) ratio were measured before and after a combined sodium chloride, fludrocortisone and dexamethasone suppression test (FDST). Post-FDST values were compared to cut-offs obtained from controls (post-FDST ALD 2·96 ng/dL and post-FDST ALD/REN 0·93 ng/dL/µU/mL). PA patients received MRA treatment. RESULTS: By applying the combination of post-FDST ALD levels and ALD/REN ratio, 28·7% of the hypertensive patients had PA. There was a positive, albeit weak, correlation between systolic (SBP) and diastolic blood pressure (DBP) and ALD levels and/or ALD/REN ratio after the FDST (P < 0·0001). SBP was associated with a post-FDST ALD of 3·24 ng/dL and ALD/REN ratio of 0·90 ng/dL/µU/mL, whereas post-FDST ALD had an inverse association at serum K+ values of less than 3·9 mEq/L. MRA treatment in 69 PA patients, resulted in a significant reduction in the maximum SBP and DBP values (28 ± 15 and 14 ± 7 mmHg, respectively, P < 0·0001). CONCLUSIONS: Using the FDST, an increased prevalence of PA in hypertensives was observed. Α significant blood pressure lowering effect was obtained with MRA treatment, implying that these agents may be beneficial in a significant number of hypertensive patients.

Nonalcoholic fatty liver disease in subjects with adrenal incidentaloma.

BACKGROUND: Adrenal incidentalomas (AI) are associated with several parameters of the metabolic syndrome (MS). Although nonalcoholic fatty liver disease (NAFLD) is considered a cardiometabolic risk factor, no data exist on its prevalence and clinical relevance in AI. The aim was to investigate the presence of MS and NAFLD in AI subjects. PATIENTS AND METHODS: Fifty-six AI subjects and 30 age-, sex- and body mass index (BMI)-matched controls were evaluated. All subjects underwent abdominal computerized tomography scan and hepatic and spleen attenuation measurements. The presence of NAFLD was defined as a mean hepatic minus mean spleen attenuation difference (ΔL-ΔS) <-10HU. Anthropometric variables [BMI and waist-to-hip ratio (W/H)] were recorded, and biochemical parameters were measured. An oral glucose tolerance test was performed, and several insulin resistance (IR) indices were determined. All subjects underwent testing to reveal autonomous cortisol and/or aldosterone (ALD) secretion, while the diagnosis of pheochromocytoma was ruled out. RESULTS: Adrenal incidentaloma subjects' mean age (± standard deviation) was 59.64 (± 8.68) years, BMI 29.84 (± 5.85) kg/m(2) and W/H 0.90 (± 0.07). Twelve subjects with AI had subtle autonomous cortisol, five autonomous ALD and three combined cortisol and ALD secretion. AI subjects exhibited higher IR indices than controls. NAFLD was present in three AI subjects and two controls. In the multiple regression analysis, W/H and triglycerides were independently associated with a low ΔL-ΔS and, hence, degree of hepatic steatosis. CONCLUSIONS: There was no significant difference in the presence of NAFLD between AI patients and controls. ΔL-ΔS, an inverse index of NAFLD, was independently associated with abdominal obesity and increased triglycerides.

Pattern of adrenal morphology and function in patients with acromegaly.

BACKGROUND: Acromegaly is well known to induce hypertrophic and hyperplastic changes in various organs and is commonly accompanied by arterial hypertension. In our study, we assess the adrenal morphology and function in a series of patients with acromegaly and possible associations with the activity of the disease and arterial hypertension. MATERIALS AND METHODS: Sixty patients with acromegaly, admitted to two endocrinology departments in the time period 2005-2010, were studied prospectively. Basal IGF-1 and growth hormone levels after oral glucose tolerance test were used to assess the disease activity. All subjects underwent adrenal CT scan, basal adrenal hormonal investigation and evaluation with 24-h urinary free cortisol and cortisol levels following low-dose dexamethasone suppression test. In 33 acromegalics, the 'modified' saline infusion test (MSI), i.e. saline infusion after dexamethasone administration, was performed to identify autonomous aldosterone (ALD) secretion. RESULTS: Abnormal adrenal morphology was present in 48% of our patients, and a significant association was found between the presence of arterial hypertension and adrenal morphology. Among patients with adrenal morphological changes, 55% exhibited no adrenal secretory hyperactivity, 34% autonomous cortisol, 7% ALD and 4% combined autonomous cortisol and ALD secretion, when applying recently proposed modified cut-off levels compared to widely used criteria. An increased prevalence of autonomous ALD secretion was shown among the subgroup of patients with acromegaly tested with MSI. CONCLUSIONS: This study provides evidence of an increased prevalence of anatomic and functional adrenal alterations in patients with acromegaly; further studies will clarify the importance of evaluating these subjects with baseline hormonal investigation along with dynamic testing and modified cut-offs.

Thyroid Paraganglioma With Medullary Carcinoma: A Unique Combination in a Patient in Association With Multiple Endocrine Neoplasia Type 2B Syndrome With Prolonged Survival.

Head and neck paragangliomas (PGLs) most commonly derive from the carotid body, jugulotympanic, vagal, and laryngeal paraganglia. Thyroid PGLs originate in the inferior laryngeal paraganglion, which may lie inside the thyroid parenchyma. Intrathyroid PGLs are rare with approximately 75 cases reported to date, mostly as solitary lesions. The coexistence of thyroid PGL with medullary thyroid carcinoma (MTC) has not been reported. Here, we report a unique case of intrathyroid PGL concomitant with MTC in the context of multiple endocrine neoplasia type 2B syndrome. Interestingly, the patient showed a prolonged survival with good clinical response to tyrosine kinase inhibitors, despite her advanced metastatic MTC. We discuss the challenges in pathology, differential diagnosis, and genetic background for the development of these thyroid lesions.

Juxtaglomerular cell tumour of the kidney: a rare cause of resistant hypertension.

SUMMARY: Juxtaglomerular cell tumour (JGCT) is an unusually encountered clinical entity. A 33-year-old man with severe long-standing hypertension and hypokalaemia is described. The patient also suffered from polyuria, polydipsia, nocturia and severe headaches. On admission, laboratory investigation revealed hypokalaemia, kaliuresis, high aldosterone and renin levels, and the abdomen CT identified a mass of 4 cm at the right kidney. Kidney function was normal. Following nephrectomy, the histological investigation revealed the presence of a JGCT. Immunostaining was positive for CD34 as well as for smooth muscle actin and vimentin. Following surgery, a marked control of his hypertension with calcium channel blockers and normalization of the serum potassium, renin or aldosterone levels were reached. According to our findings, JGCT could be included in the differential diagnosis of secondary hypertension as it consists of a curable cause. The association of JGCT with hypertension and hypokalaemia focusing on the clinical presentation, diagnostic evaluation and management is herein discussed and a brief review of the existing literature is provided. LEARNING POINTS: Juxtaglomerular cell tumours (JGCT), despite their rarity, should be included in the differential diagnosis of secondary hypertension as they consist of a curable cause of hypertension. JGCT could be presented with resistant hypertension along with hypokalaemia, kaliuresis and metabolic alkalosis. Early recognition and management can help to prevent cardiovascular complications. Imaging (enhanced CT scans) may be considered as the primary diagnostic tool for the detection of renal or JGCT. For the confirmation of the diagnosis, a histopathologic examination is needed.

Enhanced performance of a modified diagnostic test of primary aldosteronism in patients with adrenal adenomas.

OBJECTIVE: Primary aldosteronism (PA) is the commonest cause of endocrine hypertension ranging from 4.6 to 16.6% according to the diagnostic tests employed. The aim of this study was to compare the traditional saline infusion test (SIT) with the modified post-dexamethasone saline infusion test (DSIT) by applying both tests on the same subjects. METHODS: We studied 68 patients (72% hypertensives) with single adrenal adenoma and 55 normotensive controls with normal adrenal imaging. Serum cortisol, aldosterone, and plasma renin concentration (PRC) were measured and the aldosterone-to-renin ratio (ARR) was calculated. Using the mean ± 2 s.d. values from the controls, we defined the upper normal limits for cortisol, aldosterone, and PRC for both the SIT and DSIT. RESULTS: In the controls, the post-DSIT aldosterone levels and the ARR were approximately two-fold and three-fold lower, respectively, than the corresponding post-SIT values (all P = 0.001) leading to lower cut-offs of aldosterone suppression. Applying these cut-offs to patients with adrenal adenomas, the prevalence of PA was 13.2% following the SIT and 29.4% following the DSIT, respectively. In addition, 54.5% of patients with PA had concomitant autonomous cortisol secretion (ACS). Targeted treatment of PA resulted in resolution of hypertension and restoration of normal secretory aldosterone dynamics. CONCLUSIONS: The DSIT improves the diagnostic accuracy of PA, allowing for the detection of milder forms of PA in patients with adrenal adenomas. This is of particular importance as such patients may be at an increased risk of developing cardiovascular and renal morbidity that could be enhanced in the presence of concomitant ACS.

A very rare case of extranodal B-cell non-Hodgkin lymphoma presenting with adrenal and heart involvement.

We report an extremely rare case of extranodal B-cell NHL: DLBCL (diffuse large B-cell non-Hodgkin lymphoma), stage IVE, presenting with heart and bilateral adrenal involvement. On admission, adrenal and thorax imaging identified large bilateral adrenal masses and a 4.6 cm mass in the right atrium wall. An adrenal biopsy revealed the presence of a DLBCL, with triple expression of bcl2, bcl6, C-MYC(+70%). Following six cycles of systemic immunochemotherapy with R-DA-EPOCH, and high methotrexate dose for CNS prophylaxis a marked decrease of lymphoma infiltration was observed. The selection of the appropriate treatment modality can lead to profound response and improve patient's outcome.

Pre- and peri-operative characteristics, complications and outcomes of patients with biochemically silent pheochromocytomas; a case series.

PURPOSE: Pheochromocytomas are rare tumors and biochemically silent ones with normal catecholamine levels are even rarer. Up to date, biochemically inactive pheochromocytomas are poorly investigated. We aimed to systematically assess the pre- and peri-operative characteristics and the outcomes of patients with these tumors who had been treated and followed-up in 2 tertiary centers. METHODS: Clinical, laboratory and imaging data, treatment outcomes and follow-up of biochemically silent pheochromocytoma patients were recorded. RESULTS: Ten patients (5 men) [median age at diagnosis 52.5 years (24-72)] were included. Adrenal masses were incidentally discovered in all patients except from one who presented with pheochromocytoma-related manifestations. Twenty-four-hour urine metanephrine and normetanephrine levels were in the low-normal, normal and high-normal range in 4, 4 and 2 patients and in 1, 6 and 3 patients, respectively. Tumors were unilateral [median size 46 mm (17-125)] and high density on pre-contrast CT imaging or high signal intensity on T2-weighted MRI scans were found in all cases. Pre-operatively, 5 patients were treated with phenoxybenzamine [median total daily dose 70 mg (20-100)]. Intra-operatively, 4 patients developed hypertension requiring vasodilator administration and 8 developed hypotension; vasoconstrictors were required in 5 cases. One patient, not pre-operatively treated with phenoxybenzamine, developed Takotsubo cardiomyopathy. During a median 24-month (12-88) follow-up period, one patient had disease progression. CONCLUSIONS: The majority (90%) of patients with biochemically silent pheochromocytomas developed hemodynamic instability during adrenal surgery. In patients with biochemically silent adrenal lesions and a high suspicion index for pheochromocytoma based on tumor imaging characteristics, pre-operative alpha-blockade treatment may be advisable.

High Prevalence of Primary Aldosteronism in Patients with Type 2 Diabetes Mellitus and Hypertension.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. The prevalence of hypertension is higher in patients with diabetes mellitus-2 (DM-2). Following the limited existing data, we prospectively investigated the prevalence of aldosterone excess either as autonomous secretion (PA) or as a hyper-response to stress in hypertensive patients with DM-2 (HDM-2). A total of 137 HDM-2 patients and 61 non-diabetics with essential hypertension who served as controls (EH-C) underwent a combined, overnight diagnostic test, the Dexamethasone-captopril-valsartan test (DCVT) used for the diagnosis of PA and an ultralow dose (0.3 µg) ACTH stimulation test to identify an exaggerated aldosterone response to ACTH stimulation. Twenty-three normotensive individuals served as controls (NC) to define the normal response of aldosterone (ALD) and aldosterone-to-renin ratio (ARR) to the ultralow dose ACTH test. Using post-DCVTALD and ARR from the EH-C, and post-ACTH peak ALD and ARR from the NC, 47 (34.3%) HDM-2 patients were found to have PA, whereas 6 (10.4%) HDM-2 patients without PA (DCVT-negative) exhibited an exaggerated aldosterone response to stress-a prevalence much higher than ever reported. Treatment with mineralocorticoid receptor antagonists (MRAs) induced a significant and permanent reduction of BP in all HDM-2 patients. Early diagnosis and targeted treatment of PA is crucial to prevent any aggravating effect on chronic diabetic complications.

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.

Diabetic ketoacidosis in patients treated with SGLT2 inhibitors: experience at a tertiary hospital.

PURPOSE: Diabetic ketoacidosis (DKA) is a rare and life-threatening complication in patients with diabetes. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have rarely been associated with ketoacidosis. The aim of this retrospective study was to investigate DKA episodes occurring after SGLT2i treatment and to compare them to DKA episodes due to other causes. METHODS: The medical records of the years 2018-2020 related to clinical and biochemical characteristics and to treatment of six patients with DKA due to SGLT2i were reviewed. They were compared to those of 12 patients with DKA due to other causes. RESULTS: On admission, the most common symptom was abdominal pain. Glucose levels (median, min-max) were lower in patients with SGLT2i-induced DKA compared to those with DKA due to other causes (229 (150-481) vs. 458.5 (332-695) mg/dl, p = 0.007), whereas no statistical difference was observed in HbA1c and in the severity of DKA (pH, HCO3, CO2, and anion gap). The duration of insulin infusion (41 (33-124) vs. 21.50 (11-32) h, p < 0.001) and the time required until DKA resolution (39 (31-120) vs. 19 (9-28) h, p < 0.001) were higher in patients with SGLT2i-induced DKA than those with DKA due to other causes. In addition, there were increased fluid requirements (14 (8-22.75) vs. 5.5 (2-24) L, p = 0.013) and longer hospitalization time (11 (6-22) vs. 5.5 (2-14) days, p = 0.024) in patients with SGLT2i-induced DKA. No statistically significant differences were observed in total intravenous insulin and potassium administration until DKA resolution. CONCLUSIONS: Patients with SGLT2i-induced DKA had lower serum glucose levels on admission and required increased fluid administration and longer time to recover from acidosis compared to patients with DKA from other causes.

Surgical treatment outcome of primary aldosteronism assessed using new modified diagnostic tests.

PURPOSE: Primary aldosteronism (PA) is the most frequent type of endocrine hypertension. In our previous studies, we introduced two modified diagnostic tests for PA, the post-dexamethasone saline infusion test (DSIT) and the overnight dexamethasone, captopril, and valsartan test (DCVT). In this study, we aimed to validate both tests in respect to the biochemical and clinical response of a cohort of hypertensive patients in pre- and post-surgical setting. METHODS: We retrospectively studied 41 hypertensive patients (16 males), with a median (IQR, range) age of 50 (16, 35-74) years and positive histology for adrenal adenoma. Preoperatively, all patients had a single adenoma on CT and a diagnosis of PA with either DSIT or DCVT. The defined daily dose (DDD) of hypertensive drugs was assessed pre- and postoperatively. DSIT or DCVT and basal ARR were reassessed postoperatively. RESULTS: Two of the 41 patients failed to suppress aldosterone post-surgery, leading to a post-adrenalectomy biochemical cure rate of 95%, while blood pressure was improved in 36 patients, leading to a clinical cure rate of 88% as assessed by the DDD methodology. CONCLUSIONS: The present study was a proof-of-concept process to validate two modified diagnostic tests for PA in clinical practice. These tests, used to diagnose a group of patients with PA, successfully assessed their biochemical cure post-adrenalectomy at rates similar to those reported in the literature.

Benefits and Limitations of TKIs in Patients with Medullary Thyroid Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been used in patients with advanced medullary thyroid carcinoma (MTC); however, data on their effectiveness and safety are limited. The aim of this systematic review and meta-analysis was to document clinical response and toxicities of TKIs in advanced MTC. METHODS: We systematically searched major databases for articles or abstracts on TKI use in MTC patients until May 2018. Objective response (OR), defined as the sum of complete + partial response, expressed as percentage, was our primary endpoint, while disease stability, disease progression (DP), median progression-free survival (PFS), and drug discontinuation rate due to adverse events (AEs) were secondary endpoints. Pooled percentages, PFS time, and 95% CIs were reported. RESULTS: Thirty-three publications were finally included in the analysis: 1 phase IV, 2 phase III trials evaluating vandetanib and cabozantinib, respectively, 20 phase I or II studies, and the remaining 10 studies of retrospective-observational nature. OR was documented in 28.6% (95% CI 25.9-31.9) of patients. Stable disease was recorded in 46.2% (95% CI 43.3-49.1). Overall, DP was observed in 22.9% (95% CI 20.4-27.6). Grade 3 or more AEs occurred in 48.5% (95% CI 45.5-51.5) of patients, and drug discontinuation was reported in 44.7% (95% CI 41.7-47.6). In general, use of TKIs conferred a PFS of 23.3 months (95% CI 21.07-25.5). In particular, vandetanib induced an OR in 33.8% (95% CI 29.6-38.0) of patients and cabozantinib in 27.7% (95% CI 22.05-33.4). DP occurred in 23.7% (95% CI 19.9-27.6) with vandetanib use and in 22.6% (95% CI 17.4-27.9) in cabozantinib-treated patients. Sorafenib, the third most frequently studied drug, showed intermediate efficacy, but higher discontinuation rates. CONCLUSION: Treatment with TKIs in MTC patients with progressive disease is associated with a moderate therapeutic benefit, with achievement of either disease stability or partial response in 73%. The toxicity of these drugs is not negligible, but it is, nonetheless, manageable.

Thyrotoxic periodic paralysis as the first manifestation of a thyrotropin-secreting pituitary adenoma.

Thyrotoxic Periodic Paralysis (TPP) is a rare manifestation of hyperthyroidism characterized by muscle weakness and hypokalemia. Thyroid-Stimulating Hormone (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism. Even more rare is the occurrence of TPP as the first manifestation of a TSH-secreting pituitary adenoma. We report a 31-year-old Asian male patient suffering from TPP caused by a TSH-secreting adenoma, who was evaluated for persistent episodes of muscle paralysis. Laboratory investigation revealed hypokalemia as well as elevated levels of both thyroid hormones and TSH. The Magnetic Resonance Imaging (MRI) of the pituitary gland revealed a microadenoma, thus suggesting the presence of a TSH-secreting adenoma. The patient underwent transphenoidal resection and the pathological investigation confirmed the diagnosis of TSH-secreting pituitary adenoma. After the adenomectomy and the restoration of euthyroidism, the patient did not experience any episode of hypokalemic paralysis or weakness. Despite its rarity, TSH-secreting pituitary adenoma should be included in the differential diagnosis of TPP.

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.

Thyroid autoimmunity in the current iodine environment.

Iodine is essential for thyroid function. Thyroid disorders related to iodine deficiency decreased progressively with the continuous iodine prophylaxis and the increased iodine intake. An adverse effect resulting from iodine prophylaxis may be the induction of thyroid autoimmunity. Although experiments performed in animal models suggest that iodine could initiate or exacerbate thyroid autoimmunity, the role of iodine in humans remains controversial. Several observational studies in areas with adequate or high iodine intake suggest that there is an increase in the incidence of thyroid autoimmune disease. Moreover, intervention studies suggest that increased iodine intake may enhance thyroid autoimmunity too. However, not all studies generated the same findings, probably because of genetic, racial, and environmental differences. It seems that autoimmune exacerbation is a transient phenomenon. Studies have shown that in persons presenting thyroid antibodies, the levels of these antibodies progressively decrease when the majority of them react against a nonspecific pattern of thyroglobulin (Tg) epitopes. However, in a small number of these persons, the anti-Tg antibodies are similar to those in patients with patent thyroid autoimmune disease, reacting against specific immunodominant Tg epitopes, and their levels persist. One possible attractive explanation is that enhanced iodine intake increases the antigenicity of Tg through the incorporation of iodine into its molecule and the formation of iodinated Tg epitopes or even the generation of noniodinated pathogenetic Tg epitopes that are normally cryptic.