Time-dependent association between omeprazole and esomeprazole and hospitalization due to hyponatremia.

PURPOSE: The aim of this study was to explore the time-course of hospitalization due to hyponatremia associated with omeprazole and esomeprazole. METHODS: In this register-based case-control study, we compared patients hospitalized with a main diagnosis of hyponatremia (n = 11,213) to matched controls (n = 44,801). We used multiple regression to investigate time-related associations between omeprazole and esomeprazole and hospitalization because of hyponatremia. RESULTS: The overall adjusted OR (aOR) between proton pump inhibitor (PPI) exposure, regardless of treatment duration and hospitalization with a main diagnosis of hyponatremia, was 1.23 (95% confidence interval CI 1.15-1.32). Exposure to PPIs was associated with a prompt increase in risk of hospitalization for hyponatremia from the first week (aOR 6.87; 95% CI 4.83-9.86). The risk then gradually declined, reaching an aOR of 1.64 (0.96-2.75) the fifth week. The aOR of ongoing PPI treatment was 1.10 (1.03-1.18). CONCLUSION: The present study shows a marked association between omeprazole and esomeprazole and hyponatremia related to recently initiated treatment. Consequently, newly initiated PPIs should be considered a potential culprit in any patient suffering from hyponatremia. However, if the patient has had this treatment for a longer time, the PPI should be considered a less likely cause.

Ambulatory fludrocortisone suppression test in the diagnosis of primary aldosteronism: Safety, accuracy and cost-effectiveness.

OBJECTIVE: The aims of this study were to explore if the ambulatory fludrocortisone suppression test (FST) was safe, accurate and cost-effective. CONTEXT: The diagnosis of primary aldosteronism (PA) remains time-consuming and complex. The FST is used to confirm PA, but it is an in-patient test due to potentially serious complications such as hypokalemia. In Stockholm, FST has been performed since 2005 as an ambulatory procedure. DESIGN: This is a retrospective study including all patients investigated with FST in four hospitals in Stockholm, Sweden, during 2005-2019. PATIENTS/MEASUREMENTS: In total, 156 cases of ambulatory FST (FSTamb) and 15 cases of in-patient FST (FSTin) were included. FSTamb and FSTin were compared regarding health costs, clinical characteristics and laboratory results. RESULTS: No difference was found in the outcomes of FSTamb and FSTin. No severe complications were reported in FSTamb patients. No difference was found in the median value for plasma potassium on Day 5 between the two groups. Only three patients (1.9%) in the FSTamb had to repeat the test due to incomplete intake of medications. FSTamb and FSTin were equally accurate. The cost of performing FSTamb was at least 50% lower compared with FSTin ($2400 vs. $5200 per patient). The time needed for FSTamb was 60 min of physician's time and 150 min of nurse's time which were lower than the 5 days in FSTin. CONCLUSIONS: Ambulatory FST is safe and accurate and can be performed with significantly less healthcare costs compared to FSTin.

Non-thiazide diuretics and hospitalization due to hyponatraemia: A population-based case-control study.

OBJECTIVE: Diuretics are often implicated in hyponatraemia. While thiazides constitute one of the most common causes of hyponatraemia, data on loop diuretics and potassium-sparing agents are limited and partly conflicting. The objective of this investigation was to study the association between use of different types of non-thiazide diuretics and hospitalization due to hyponatraemia. DESIGN, PATIENTS AND MEASUREMENTS: This was a register-based case-control study on the adult Swedish population. By linking national registers, patients hospitalized with a principal diagnosis of hyponatraemia (n = 11,213) from 1 October 2005 through 31 December 2014 were compared with matched controls (n = 44,801). Multivariable logistic regression, adjusted for multiple confounders, was used to analyse the association between use of diuretics and hyponatraemia. In addition, newly initiated use (≤90 days) and ongoing use were examined separately. RESULTS: Adjusted odds ratios (aORs) (95% CI) were 0.61 (0.57-0.66) for the use of furosemide, 1.69 (1.54-1.86) for the use of amiloride and 1.96 (1.78-2.18) for the use of spironolactone and hospitalization due to hyponatraemia. For newly initiated therapy, aORs ranged from 1.23 (1.04-1.47) for furosemide to 3.55 (2.75-4.61) for spironolactone. The aORs for ongoing use were 0.52 (0.47-0.57) for furosemide, 1.62 (1.47-1.79) for amiloride and 1.75 (1.56-1.98) for spironolactone. CONCLUSIONS: Ongoing use of furosemide was inversely correlated with hospitalization due to hyponatraemia, suggesting a protective effect. Consequently, if treatment with furosemide precedes the development of hyponatraemia by some time, other causes of hyponatraemia should be sought. Spironolactone and amiloride may both contribute to hyponatraemia; this effect is most prominent early in treatment.

Association between lipid-lowering agents and severe hyponatremia: a population-based case-control study.

PURPOSE: Drug-induced hyponatremia is common, with medications from many drug-classes implicated. Lipid-lowering agents are among the most prescribed drugs. Limited evidence suggests an inverse association between statins and hyponatremia, while data on other lipid-lowering agents is absent. The objective of this investigation was to study the association between lipid-lowering drugs and hospitalization due to hyponatremia. METHODS: This was a register-based case-control study of the general Swedish population. Those hospitalized with a main diagnosis of hyponatremia (n = 11,213) were compared with matched controls (n = 44,801). Multivariable logistic regression adjusting for co-medication, diseases, previous hospitalizations, and socioeconomic factors was used to explore the association between severe hyponatremia and the use of lipid-lowering drugs. RESULTS: Unadjusted ORs (95% CI) for hospitalization due to hyponatremia were 1.28 (1.22-1.35) for statins, 1.09 (0.79-1.47) for ezetimibe, 1.38 (0.88-2.12) for fibrates, and 2.12 (1.31-3.35) for resins. After adjustment for confounding factors the adjusted odds ratios (95% CI) compared with controls were 0.69 (0.64-0.74) for statins, 0.60 (0.41-0.86) for ezetimibe, 0.87 (0.51-1.42) for fibrates, and 1.21 (0.69-2.06) for resins. CONCLUSIONS: Use of statins and ezetimibe was inversely correlated with severe hyponatremia. Consequently, these drugs are unlikely culprits in patients with hyponatremia, and they appear safe to initiate in hyponatremic patients. A potential protective effect warrants further studies on how statins and other lipid-lowering drugs are linked to dysnatremias.

Association between newly initiated thiazide diuretics and hospitalization due to hyponatremia.

PURPOSE: Thiazide diuretics are the most common origin of drug-induced hyponatremia. However, population-based studies on clinical outcomes are lacking. We therefore explored the time course and absolute risk of thiazide-associated hospitalization due to hyponatremia in Sweden. METHODS: Population-based case-control study including patients hospitalized with a principal diagnosis of hyponatremia (n = 11,213) compared with controls (n = 44,801). Linkage of registers was used to acquire data. Multivariable regression was applied to explore time-dependent associations between thiazide diuretics and hospitalization due to hyponatremia. Attributable risks were calculated assessing the disease burden attributable to thiazides. RESULTS: Individuals initiating thiazide treatment were exposed to an immediate increase in risk for hospitalization with adjusted odds ratio (aOR) (95% CI) of 48 (28-89). The associations gradually declined reaching an aOR of 2.9 (2.7-3.1) for individuals treated for longer than 13 weeks. The attributable risk of hyponatremia-associated hospitalization due to thiazides of any treatment length was 27% (3095/11,213). Among 806 patients initiating treatment < 90 days before hospitalization, hyponatremia could be attributed to thiazides in 754. Based on nationwide data, 616,678 individuals were initiated on thiazides during the 8-year study period suggesting an absolute risk of 0.12% (754/661,678) for subsequent hospitalization with a main diagnosis of hyponatremia. CONCLUSIONS: Thiazide diuretics attributed to more than one in four individuals hospitalized due to hyponatremia. The risk increase was very pronounced during the first month of treatment and then gradually declined, without returning to normal. However, the absolute risk for the development of hyponatremia demanding hospitalization may for most individuals be modest.

Highly proliferative anal neuroendocrine carcinoma: molecular and clinical features of a rare, recurrent case in complete remission.

BACKGROUND: Poorly differentiated anal neuroendocrine carcinomas (ANECs) are rare lesions with poor prognosis, and the molecular etiology is only partially understood. CASE PRESENTATION: At our institution, we have treated and followed a patient with such a rare ANEC. He had primarily surgery followed by three rounds of repeated surgery for loco-regional recurrences. He also received three different combinations of chemotherapy and external beam radiation. At last follow-up 13 years since the primary diagnosis, the patient had been in complete remission for nine years. The patient's medical files were re-examined, including laboratory, radiology and clinical examinations. Histopathology was re-assessed, and expanded immunohistochemistry was performed from tissue specimens from the four surgical procedures. In addition, the molecular genetic status was evaluated through next-generation sequencing. The initial tumor was consistent with a 59 mm small cell neuroendocrine cancer with a Ki-67 index of 80%. Regional lymph node metastases were evident, and immunohistochemistry supported a neuroendocrine origin. A PCR screening detected human papilloma virus type 45 DNA (high-risk subtype), and focused next-generation sequencing found a missense mutation in the Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) gene. In tissues representing subsequent recurrences, the Chromogranin A expression was lost, and the Ki-67 index increased to 90%. CONCLUSIONS: For the first time, we report the detection of HPV45 in a case of ANEC. To our belief, PIK3CA mutations have also not been previously demonstrated in this tumor entity. In highly malignant ANECs, cure can in rare cases be achieved. Although speculative, expression of HPV45 and/or the PIK3CA mutation may have contributed to the favorable outcome.

Factors of importance for discontinuation of thiazides associated with hyponatremia in Sweden: A population-based register study.

PURPOSE: In a patient with clinically significant hyponatremia without other clear causes, thiazide treatment should be replaced with another drug. Data describing to which extent this is being done are scarce. The aim of this study was to investigate sociodemographic and socioeconomic factors that may be of importance for the withdrawal of thiazide diuretics in patients hospitalized due to hyponatremia. METHODS: The study population was sampled from a case-control study investigating individuals hospitalized with a main diagnosis of hyponatremia. For every case, four matched controls were included. In the present study, cases (n = 5204) and controls (n = 7425) that had been dispensed a thiazide diuretic prior to index date were identified and followed onward regarding further dispensations. To investigate the influence of socioeconomic and sociodemographic factors, multiple logistic regression was used. RESULTS: The crude prevalence of thiazide withdrawal for cases and controls was 71.9% and 10.8%, respectively. Thiazide diuretics were more often withdrawn in medium-sized towns (adjusted OR, 1.52; 95% CI, 1.21-1.90) and rural areas (aOR, 1.81; 95% CI, 1.40-2.34) compared with metropolitan areas and less so among divorced (aOR, 0.72; 95% CI, 0.53-0.97). However, education, employment status, income, age, country of birth, and gender did not influence withdrawal of thiazides among patients with hyponatremia. CONCLUSIONS: Thiazide diuretics were discontinued in almost three out of four patients hospitalized due to hyponatremia. Educational, income, gender, and most other sociodemographic and socioeconomic factors were not associated with withdrawal of thiazides.

To Treat or Not to Treat Subclinical Hypothyroidism, What Is the Evidence?

OBJECTIVE: levothyroxine prescriptions have increased remarkably during the last decade, and it is most likely to be prescribed in subclinical hypothyroidism. The aim of this review was to present data on when levothyroxine treatment should be initiated, and the effects of treatment in subclinical hypothyroidism on symptoms such as weight, quality of life, vitality, cognition, and cardiovascular disease. We also discuss evidence for different thyroid-hormone medications. In addition, the option to withhold medication when there is uncertain diagnosis or lack of clinical improvement is discussed. METHODS: a literature search in PubMed on the term "treatment of subclinical hypothyroidism" in combination with "quality of life", "weight", "cognition", and "cerebrovascular disease". RESULTS: current research supports that levothyroxine should be initiated in patients with a thyroid stimulating hormone (TSH) >10 mIU/L. Treatment for hypothyroidism is becoming more frequent. Symptoms related to vitality, weight, and quality of life in subclinical disease often persist with levothyroxine treatment, and other causes should be explored. Patients with cardiovascular-risk factors may benefit from treatment, especially younger patients. Caution is necessary when treating elderly subjects with levothyroxine. CONCLUSION: lifelong treatment with levothyroxine should normally only be considered in manifest hypothyroidism. However, in subclinical hypothyroidism with a TSH >10 mIU/L, therapy is indicated. In milder subclinical forms, a wait-and-see strategy is advocated to see if normalization occurs. Subgroups with cardiovascular risk and subclinical hypothyroidism may benefit from levothyroxine therapy.

Acute suppurative thyroiditis with thyroid abscess in adults: clinical presentation, treatment and outcomes.

BACKGROUND: Abscess in the thyroid gland is a rare but severe infectious disease. The condition can have anatomic or iatrogenic underlying causes. If untreated it could be fatal. Pathogens vary considerably. Treatment is intravenous antibiotics, drainage, and sometimes surgery. METHODS: The electronic medical records of all adult patients with acute thyroiditis 2003-2017 treated at the Karolinska University Hospital (catchment area 2 million) in Sweden were systematically reviewed. RESULTS: Five patients were found in the catchment area. One patient from another region but known to us was also included. Thus, six patients (aged 28-73 years) were included in the study. Median length of hospital stay was 7.5 days (4-79 days). All were treated with antibiotics (intravenous n = 5, oral n = 1). Total antibiotic treatment duration was 13.5 days (10-41 days). Blood cultures were positive in three (streptococcus pneumonia, streptococci sanguineous, pepto streptococci), deep tissue culture in three (Escherichia coli, Candida, Hemophilic influenza) and no positive culture at all in two. Drainage was used in three patients. All patients recovered without recurrences. Surgery was performed twice in the acute phase in one. There was no recurrence during 7 years (3-12) of follow-up, but one patient died after three years (severe heart failure and pneumonia). CONCLUSION: Thyroid abscess in adults is extremely rare nowadays in the developed world. With prompt antibiotic therapy, drainage and in some cases thyroidectomy the prognosis seems favourable.

Adrenocortical cancer: mortality, hormone secretion, proliferation and urine steroids - experience from a single centre spanning three decades.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignant disease with a poor prognosis. Our aims were to study survival and to explore prognostic markers. METHODS: We retrospectively investigated the medical records of all 50 ACC patients at a single centre diagnosed between 1985 and 2012 and followed them up until 31/12/2014. RESULTS: Of this cohort, twenty six (52 %) were females. Adrenalectomy was performed in 48 patients (96 %), and twenty seven (54 %) were treated with adjuvant cytotoxic agents. The tumor sizes ranged from 6 to 20 cm. Overall survival time was 5.5 years (0.3-19.8), the two and five-year survival was 64 and 40 %, respectively. In ENSAT stage II 25/48 patients had a median survival of 7.0 years (0.7-15.5), in stage III 8/48 this was 1.9 (0.4 - 19.8), and in stage IV 15/48 it was 1.2 (0.3-3.6) years. Seventeen patients (34 %) were still alive at the end of 2014. The total follow-up time was 8.4 (0.3-19.8) years. Cell proliferation measured with Ki-67 had a median value of 15 % (2-80) and the urinary steroid profile was clearly pathologic in 29 of 43 (67 %) tested patients. The proliferation index did not significantly predict mortality (Ki-67 ≤ 10 vs. >10 %, 9.0 vs. 3.2 years, P = 0.0833), but resection margins did (R1 vs. R2, P = 0.0066; R0 vs. R2, P < 0.0001). The urinary steroid profile did not predict mortality (normal vs. pathologic urine profile: median survival 6.6 vs. 3.3 years, P = 0.261). CONCLUSIONS: The prognosis was generally poor and macroscopically positive resection margins resulted in a worse prognosis. However, some patients were still alive many years following primary surgery with no sign of residual disease.

Primary aldosteronism: functional histopathology and long-term follow-up after unilateral adrenalectomy.

OBJECTIVES: To investigate the long-term outcome after unilateral adrenalectomy in patients with primary aldosteronism (PA) and to establish the role of functional pathology for the final diagnosis of aldosterone-producing adenoma (APA) or hyperplasia. DESIGN: A single-centre, retrospective cohort study in a hospital setting. PATIENTS: Consecutive patients with PA, n = 120, who underwent unilateral adrenalectomy between 1985 and 2010. Preoperative and postoperative data were analysed. To indicate the site of aldosterone secretion in the resected adrenal, we added functional methods to routine histopathology, using in situ hybridization and immunohistochemistry to detect the presence of enzymes needed for aldosterone (CYP11B2) and cortisol (CYP11B1, CYP17A1) synthesis. RESULTS: The median follow-up was 5 years and the cure rate of PA 91%. Hypertension was improved in 97% and normalized in 38%. Functional histopathology changed the final diagnosis from APA to hyperplasia in 6 cases (7%). Five of these had no expression of or staining for aldosterone synthase in the adenoma, but only in nodules in the adjacent cortex. All except one APA patient were cured of PA. They had lower preoperative serum potassium and higher 24-h urinary aldosterone than patients with hyperplasia. Among patients with hyperplasia 16 of 26 were cured. CONCLUSIONS: Most patients were cured of PA by unilateral adrenalectomy. Almost all noncured benefitted from the operation as the blood pressure improved. Functional histopathology proved helpful in the distinction between APA and hyperplasia, and we recommend that functional histopathology should be added to routine histopathology to improve the diagnostic evaluation and aid in tailoring the follow-up.

Limited value of long-term biochemical follow-up in patients with adrenal incidentalomas-a retrospective cohort study.

BACKGROUND: The prevailing view that advocates long-term hormonal follow-up of adrenal incidentalomas is currently under debate. The purpose of the present study was to examine all adrenal incidentalomas presented during five years to a single centre. We hypothesized that 24-month biochemical follow-up in patients with an initial normal screening would fail to increase the sensitivity in finding hormone producing tumours. METHODS: The present study is a retrospective register based cohort study of 194 patients referred to the Department of Endocrinology at Södersjukhuset between the years 2006-2010. Computerized medical records were used to find and extract information on patients with newly discovered adrenal incidentalomas. The sensitivity, specificity, positive predictive value and negative predictive value were calculated to evaluate the validity of an initial normal screening when used to identify individuals with hormone producing tumours. RESULTS: Of the incidentalomas 94% consisted of benign, non-functioning tumours. Three patients were diagnosed with cortisol hypersecretion and one with pheochromocytoma. The sensitivity, specificity, positive predictive value and negative predictive value of an initial complete negative screening to predict a hormone producing tumour were 100%, 63%, 12% and 100%, respectively. CONCLUSION: Patients with an initially normal hormonal screening may not need further biochemical follow-up.

Surgical outcome after thyroidectomy due to Graves' disease and Lugol iodine treatment: a retrospective register-based cohort study.

PURPOSE: This study aimed to investigate the relationship between Lugol iodine treatment in a rescue setting and surgical outcomes in Graves' disease patients. METHODS: The retrospective register-based cohort study included 813 patients who had undergone primary total thyroidectomy with a primary diagnosis of Graves' disease (ICD-code E05.0) at Karolinska University Hospital in Stockholm, Sweden, between January 2008 and December 2015. Of 813 patients, 33 (4.1%) were given Lugol iodine before surgery and the remaining, the non-Lugol group, did not. The study's primary outcomes were post-operative calcium treatment day 1, calcium and vitamin D supplements at discharge and follow-up. Secondary outcomes were laryngeal nerve damage and bleeding (defined as re-operation). RESULTS: Differences were found between the Lugol and non-Lugol groups in the treatment of calcium day 1 (45.5% vs 26.7%, p = 0.018), at discharge (36.4% vs. 16.2%, p = 0.002) and vitamin D supplements at discharge (36.4% vs. 19.1%, p = 0.015) as surrogate variables for hypocalcemia post-operatively. No differences could be seen at 4-6 weeks and six-months follow-up. There were no differences between the Lugol and non-Lugol groups in terms of operation time, laryngeal nerve damage, and bleeding. CONCLUSION: Patients in our cohort undergoing thyroidectomy due to Graves' disease pre-operatively treated with Lugol iodine as a rescue therapy had a higher risk of experiencing short term post-operative hypocalcemia.

Maternal thyroid function and offspring birth anthropometrics in women with polycystic ovary syndrome.

Objectives: Polycystic ovary syndrome (PCOS) and thyroid disorders have both been linked to adverse pregnancy and neonatal outcomes. Even small variations in thyroid function within the normal range may influence fetal growth. Our aim was to investigate whether maternal thyroid function is associated with newborn anthropometrics in PCOS and explore the potential modifying effect of metformin. Methods: Post-hoc analyses of two RCTs in which pregnant women with PCOS were randomized to metformin or placebo, from first trimester to delivery. Maternal serum levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were measured at gestational weeks (gw) 5-12, 19, 32 and 36 in 309 singleton pregnancies. The mean z-scores of birthweight, birth length, and head circumference were estimated in the offspring. Associations of maternal thyroid parameters with offspring anthropometrics and the outcomes large for gestational age (LGA) and small for gestational age (SGA) were studied using linear and logistic regression models, with adjustment for body mass index (BMI) when relevant. Results: Maternal fT4 at baseline was negatively associated with birth length (b= -0.09, p=0.048). Furthermore, ΔfT4 during pregnancy correlated positively to z-score of both birth weight and length (b=0.10, p=0.017 and b=0.10, p=0.047 respectively), independently of treatment group. TSH at baseline and gw19 was inversely associated with LGA (OR 0.47, p=0.012 and OR 0.58, p=0.042), while ΔTSH was positively associated with LGA (OR 1.99, p=0.023). There were inverse associations between TSH at baseline and SGA (OR 0.32, p=0.005) and between ΔfT4 and SGA (OR 0.59, p=0.005) in the metformin group only. There were no associations between maternal thyroid function and head circumference of the newborns. Conclusion: In women with PCOS, a higher maternal fT4 in early pregnancy and a greater decrease in fT4 during pregnancy was associated with a lower offspring birthweight and shorter birth length. Higher TSH by mid-gestation and smaller increase in TSH during pregnancy was associated with less risk of LGA. Subclinical variations in maternal thyroid function might play a role for birth anthropometrics of PCOS offspring.

Genetic variants and down-regulation of CACNA1H in pheochromocytoma.

Pheochromocytoma (PCC) and abdominal paraganglioma (aPGL) (together abbreviated PPGL) frequently present with an underlying genetic event in a PPGL driver gene, and additional susceptibility genes are anticipated. Here we re-analysed whole-exome sequencing data for PCC patients and identified two patients with rare missense variants in the calcium voltage-gated channel subunit 1H gene (CACNA1H). CACNA1H variants were also found in the clinical setting in PCC patients using targeted sequencing and from analysis of The Cancer Genome Atlas database. In total, CACNA1H variants were found in six PCC cases. Three of these were constitutional and two are known to have functional consequences on hormone production and gene expression in primary aldosteronism and aldosterone-producing adrenocortical adenoma. In general, PPGL exhibited reduced CACNA1H mRNA expression as compared to normal adrenal. Immunohistochemistry showed strong CACNA1H (CaV3.2) staining in adrenal medulla while PPGL typically had weak or negative staining. Reduced CACNA1H gene expression was especially pronounced in PCC as compared to aPGL and in PPGL with Cluster 2 kinase signalling phenotype. Furthermore, CACNA1H levels correlated with HIF1A and HIF2A. Moreover, TCGA data revealed a correlation between CACNA1H methylation density and gene expression. Expression of rCacna1h in PC12 cells induced differential protein expression profiles determined by mass spectrometry as well as a shift in the membrane potential where maximum calcium currents were observed as determined by electrophysiology. The findings suggest the involvement of CACNA1H/CaV3.2 in pheochromocytoma development and establish a potential link between the aetiology of adrenomedullary and adrenocortical tumor development.

The dangerous trend of levothyroxine medicalization.

Thyroid hormone replacement is paramount in overt hypothyroidism; recently, however, thyroid hormone substitution is increasingly prescribed to patients with normal thyroid hormone levels. This forum article discusses the complex causes and the possible negative effects of overusing thyroid hormone replacement drugs.

Adrenal cysts: an emerging condition.

Adrenal cysts are rare lesions representing approximately 1-2% of adrenal incidentalomas. The majority of these rare lesions are benign. Rarely, phaeochromocytomas and adrenal malignant masses can present as cystic lesions and can occasionally be difficult to distinguish from benign cysts. Histologically, adrenal cysts are subdivided into pseudocysts, endothelial cysts, epithelial cysts and parasitic cysts. The radiological appearance of an adrenal cyst is generally similar to that of cysts in the kidney. They are thus well demarcated, usually rounded, with a thin wall and homogenous internal structure, low attenuating (<20 Hounsfield Units) on CT, low signalling on T1-weighted MRI sequences and high signalling on T2-weighted MRI sequences, and anechoic or hypoechoic on ultrasonography. Benign adrenal cysts have a slight female predominance and are usually diagnosed between the ages of 40 and 60. Most adrenal cysts are asymptomatic and are detected incidentally, although very large adrenal cysts can lead to mass effect symptoms, with surgery required to alleviate the symptoms. Thus, conservative management is usually recommended for asymptomatic cysts. However, when uncertainty exists regarding the benign nature of the cyst, additional work-up or follow-up is needed. The management of an adrenal cyst should preferably be discussed at an adrenal multidisciplinary team meeting.

Rare benign adrenal lesions.

While most benign lesions of the adrenal glands represent either an adrenocortical adenoma or a myelolipoma, the advent and frequent use of high-resolution radiological investigations have led to relatively increased incidental discovery of rare adrenal lesions, specifically benign adrenal cysts, adrenal ganglioneuromas, adrenal schwannomas, adrenal hemorrhage, and adrenal calcifications. Radiological characteristics of the different rare benign adrenal lesions could vary from distinct to indeterminate. Though typically nonfunctional, these rare lesions require evaluation for adrenal hormone excess, as they may phenotypically appear similar to pheochromocytoma or adrenocortical carcinoma and could sometimes be associated with or conceal an underlying functional adrenal tumor. In this review, we discuss the various rare benign adrenal lesions, emphasizing a practical perspective.

Long-Term Outcome of Graves' Disease: A Gender Perspective.

Introduction: In gender-skewed conditions such as Graves' disease (GD), the outcome naturally becomes dominated by the majority. This may lead to gender-biased misunderstandings regarding treatment outcomes. This especially holds true when complications, such as depression, are unevenly distributed. We have, therefore, studied the long-term outcome of GD from a gender perspective. Materials and Methods: A cohort of 1186 patients with GD was included in a follow-up 6-10 years after inclusion. Choice of treatment, the feeling of recovery, long-term treatment, comorbidity, and quality of life were investigated with questionnaires. All results were studied sex-divided. Results: We included 973 women and 213 men. There was no difference between men and women in the choice of treatment. At follow-up, women scored significantly worse in the general questionnaire 36-item Short-Form Health Status (SF-36) domain bodily pain and in the thyroid-specific Thyroid-Related Patient-Reported Outcome (ThyPRO) domains depression, impaired sex life, and cosmetic complaints, all p < 0.05. Women were twice as likely (29.5%) to be treated with levothyroxine after successful treatment with antithyroid drugs (ATD) compared with men (14.9%, p < 0.05). Conclusion: After treatment for GD, women were more affected by depression, impaired sex life, cosmetic issues, and bodily pain despite successful cure of hyperthyroidism. The prevalence of hypothyroidism was also doubled in women. Whether these observed gender differences reflect a worse outcome of GD in women or a natural consequence of a higher prevalence of these symptoms and autoimmunity in the female population is difficult to disentangle. Nevertheless, several years after GD, women reveal more persistent symptoms.

Fracture Incidence in Graves' Disease: A Population-Based Study.

Background: Population-based studies have indicated an increase in bone turnover in hyperthyroidism with a subsequent decrease in bone mineral density and an increased risk of fractures, especially in postmenopausal women. However, heterogeneity between studies prevents a definitive conclusion. Graves' disease (GD) is an autoimmune disease, and it is the most common cause of hyperthyroidism. The aim of this study was to investigate fracture risk in patients with GD. Methods: A total of 2134 patients with incident GD and 21,261 age, sex- and county-matched controls were included 16-18 years after diagnosis in a retrospective cohort study. Drug and patient national registries in Sweden were used to assess the risk of developing skeletal complications. Up to 10 years of age, sex- and county-matched controls per patient were selected from databases from the National Board of Health and Welfare and Statistics Sweden. Cox proportional hazards models were fitted to estimate hazard ratios (HR) and confidence intervals [CI]. Results: There were no significant differences in fracture rates between GD and controls but after adjustment for comorbidities, the data showed higher vertebral fracture rates in male GD patients aged >52 years compared to male controls, HR = 2.83 [CI 1.05-7.64]. The rates of osteoporosis treatments as well as treatment with corticosteroids were higher in patients with GD. However, HR for the association between GD and fractures remained largely unchanged after adjustment for osteoporosis treatments and treatments with corticosteroids. Conclusions: There were no significant differences in total fracture rate between GD and the general population. However, men older than 52 years had a higher vertebral fracture rate. This study also shows that patients with treated GD receive more osteoporosis treatments compared to the general population.