Sex steroid levels in women with hypopituitarism: A case-controlled observational study.

CONTEXT: Women with hypopituitarism remain at increased risk of morbidity and mortality. Insufficient replacement of sex steroids has been suggested as a contributing factor, but sex steroid levels in women with hypopituitarism have not been comprehensively mapped. OBJECTIVE: To quantify sex steroids in women with hypopituitarism by a high-sensitivity assay. METHODS: Using a combination of clinical and biochemical criteria, women with hypopituitarism (n = 104) who started growth hormone replacement 1995-2014 at a single center were categorized as eugonadal or having hypogonadotropic hypogonadism (HH). A population-based cohort of women (n = 288) served as controls. Eugonadal women and controls were categorized as pre-/postmenopausal and HH women as younger/older (≤ or >52 years). Dehydroepiandrosterone (DHEA), androstenedione, testosterone, dihydrotestosterone, progesterone, 17αOH-progesterone, estradiol and estrone were analyzed by a validated liquid chromatography-tandem mass spectrometry assay. RESULTS: Among both premenopausal/younger and postmenopausal/older women, women with HH had lower levels of sex steroid precursors (DHEA, androstenedione) and androgens (testosterone and dihydrotestosterone) than controls. Progesterone, 17αOH-progesterone, estrone and estradiol showed similar patterns. Women with HH and adrenocorticotropic hormone (ACTH) deficiency had markedly lower concentrations of all sex hormones than those without ACTH deficiency. CONCLUSION: This study demonstrates for the first time a broad and severe sex steroid deficiency in both younger and older women with HH, particularly in those with combined gonadotropin and ACTH deficiency. The health impact of low sex steroid levels in women with hypopituitarism requires further study and women with combined gonadotropin and ACTH deficiency should be a prioritized group for intervention studies with sex hormone replacement.

The influence of insulin-induced hypoglycemia on copeptin concentrations.

Plasma copeptin is a biomarker that reflects arginine vasopressin (AVP) secretion. In this study we measured copeptin during insulin tolerance test (ITT) in 65 patients referred to our department for evaluation of anterior pituitary function. Plasma for measurements of copeptin were collected at the start of the test and regurarly up to 120 minutes thereafter. Of 60 patients who developed significant hypoglycemia and were included in the analyses, 13 (22%) had corticotropic deficiency, 11 (18%) had thyreotropic deficiency, 33 (55%) had growth hormone deficiency and 4 (6%) had AVP deficieny (AVPD). Thirty-seven (62%) patients had at least one anterior pituitary deficiency. In patients without AVPD, median (range) copeptin increased from 4.5 pmol/L (1.3-33.0) to a maximum of 6.2 pmol/L (2.0-34.4; p<0.001). Baseline copeptin was similar in men and women, but maximal copeptin during ITT was higher in men. Copeptin concentrations were not affected by age, BMI, somatotropic, or corticotropic function. Copeptin concentrations were lower in patients with AVPD than patiets without AVPD, and in patients with thyrotropic deficiency, compared to patients with intact thyrotropic function, both at baseline and during ITT. In conclusion, copeptin increases significantly during insulin induced hypoglycemia but is of limited value in predicting anterior pituitary hormonal function.

Undiagnosed adrenal insufficiency as a cause of premature death in glucocorticoid users.

Objective: It is unknown whether glucocorticoid (GC)-induced adrenal insufficiency may cause premature mortality in GC users. We conducted a retrospective cohort study to investigate if undiagnosed and undertreated GC-induced adrenal insufficiency is a contributor to premature death in GC users. Methods: Information on dispensed prescriptions in West Sweden from 2007 to 2014 was obtained from the Swedish Prescribed Drug Register. Cause of death was collected from the Swedish Cause of Death Register. Of 223,211 patients who received oral GC prescriptions, 665 died from sepsis within 6 months of their last prescription. Three hundred of these patients who had died in hospital were randomly selected for further investigation. Medical records were initially reviewed by one investigator. Furthermore, two additional investigators reviewed the medical records of patients whose deaths were suspected to be caused by GC-induced adrenal insufficiency. Results: Of 300 patients (121 females, 40%), 212 (75%) were prescribed GC treatment at admission. The mean age was 76 ± 11 years (range 30-99). Undiagnosed or undertreated GC-induced adrenal insufficiency was considered a probable contributor to death by at least two investigators in 11 (3.7%) patients. In five of these 11 cases, long-term GC therapy was abruptly discontinued during hospitalization. Undiagnosed or undertreated GC-induced adrenal insufficiency was considered a possible contributing factor to death in a further 36 (12%) patients. Conclusion: GC-induced adrenal insufficiency is an important contributor to premature death in GC users. Awareness of the disorder during intercurrent illness and following cessation of GC treatment is essential.

Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: The Multi-Ethnic Study of Atherosclerosis.

Information on the associations of testosterone levels with abdominal muscle volume and quality in men is limited, while the role of estradiol and SHBG on these muscle characteristics are unclear. To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. After adjustment, higher levels of both total testosterone and estradiol were associated with higher abdominal muscle area (1.79, 0.1-3.4, & 1.79, 0.4-3.2, respectively). In the final analyses, levels of total testosterone showed a positive association, while an inverse relationship was observed for SHBG with abdominal muscle radiodensity (0.3, 0.0-0.6, & -0.34, -0.6 - -0.1, respectively). Our results indicate a complex association between sex hormones and abdominal muscle characteristics in men. Specifically, total testosterone and estradiol were associated with abdominal muscle area, while only total testosterone was associated with muscle radiodensity and SHBG was inversely associated with muscle radiodensity.

Accidental Cushing Syndrome.

We present a patient with Cushing syndrome secondary to accidental intake of corticosteroid tablets-a 66-year-old woman with a history of well-controlled hypertension, who over the course of a few weeks developed full-blown Cushing syndrome with uncontrolled blood pressure, typical central fat accumulation, and easy bruising. The clinical features further worsened upon increase of the dosage of her antihypertensive medication because of rising blood pressure. Biochemical analyses showed low cortisol and ACTH concentrations. Inspection of the patient's medications revealed that she had accidentally been taking corticosteroids tablets, prescribed for her husband, instead of antihypertensives, ie, dexamethasone 4 mg and then 8 mg, instead of candesartan at the same dose. This case highlights the necessity of a thorough review of the medications taken by patients suspected to have exogenous Cushing syndrome, including inspection of the original packaging, and not just relying on information from the patient and electronic health records. This case also highlights the need of special labeling on the packaging for the easy identification of corticosteroid-containing medications given their widespread availability.

The diagnostic performance of copeptin in clinical practice: A prospective study.

OBJECTIVE: Plasma copeptin is a relatively new biomarker for evaluation of arginine vasopressin (AVP) secretion. The aim of this study was to test the diagnostic performance of copeptin in patients with polyuria-polydipsia syndrome. DESIGN, PATIENTS AND MEASUREMENTS: This was a prospective study where 88 patients with polyuria-polydipsia syndrome were evaluated with a water deprivation test (WDT). Weight, urine osmolality, urine specific gravity, and plasma copeptin were collected at baseline, after 8 h, and at termination of the WDT when one of the following had been reached: (i) >3% weight reduction, (ii) urine specific gravity >1.017 or urine osmolality >600 mOsm/kg, or (iii) intolerable adverse symptoms. RESULTS: Of 88 patients (57 women), 21 (24%) were diagnosed with central diabetes insipidus (cDI), 5 (6%) with nephrogenic DI (nDI), and 62 (71%) with primary polydipsia (PP). Median (interquartile range) copeptin at baseline was 1.7 (1.4-2.5) pmol/L in cDI, 22 (18-65) pmol/L in nDI, and 2.7 (2-4) pmol/L in PP. After 8 h of WDT, the highest copeptin in patients with cDI was 4.0 pmol/L. In patients with PP: (i) 41 had urine osmolality <600 mOsm/kg, 7 (17%) of these had copeptin >4.0 pmol/L, (ii) 21 had urine osmolality ≥600 mOsm/kg, 14 (67%) of these had copeptin >4.0 pmol/L. CONCLUSIONS: Copeptin >4.0 pmol/L after an overnight WDT can be used to rule out cDI and copeptin ≥21 pmol/L at baseline to diagnose nDI. The diagnostic performance of copeptin in the context of the WDT is otherwise limited in the diagnostic work-up of patients with polyuria-polydipsia syndrome.

Autoimmune Disease in Turner Syndrome in Sweden: An up to 25 Years' Controlled Follow-up Study.

CONTEXT: Turner syndrome (TS) is the most common chromosomal aberration in women; it is the result of structural or numeric abnormalities in the X chromosome. Autoimmune hypothyroidism has been recognized as one of the more prominent disorders associated with TS. OBJECTIVE: This work aimed to study the prevalence of autoimmune diseases in TS. METHODS: A cross-sectional, longitudinal, 25-year follow-up study was conducted of patients from adult Turner centers at the University Hospitals, Sweden. During 1994 to 2020, a total of 503 women aged 16 to 71 years with TS were evaluated consecutively every fifth year according to national guidelines. A random population sample of women, n = 401, aged 25 to 44 years, from the World Health Organization Monitoring of Trends and Determinants for Cardiovascular Disease (MONICA) project served as controls. Serum thyrotropin, free thyroxine, vitamin B12, antithyroid peroxidase (anti-TPO), and antitransglutaminase antibodies were measured. RESULTS: Mean follow-up time (years) was 16 ± 7 for patients and 13 ± 1 for controls. From study start, the prevalence increased in TS for hypothyroidism 40% to 58%, vitamin B12 deficiency 5% to 12%, celiac disease 4% to 7%, positive anti-TPO 26% to 41%, and antitransglutaminase antibodies 6% to 8% (P < .0001 vs controls). Type 1 diabetes and Addison disease were rare. The only interrelationship was between hypothyroidism and vitamin B12 deficiency, both in TS and controls. No association between autoimmune disease and karyotype, antecedent growth hormone treatment, or ongoing estrogen hormone replacement, was seen in TS. CONCLUSION: In women with TS up to older than 80 years, more than half developed hypothyroidism, mainly autoimmune, during follow-up. Awareness of vitamin B12 deficiency and celiac disease throughout life is also recommended in women with TS.

Effects of medical and surgical treatment on vitamin D levels in obesity.

INTRODUCTION: Persons living with obesity treated with bariatric surgery are at a high risk of developing nutritional deficiencies. The primary aim of this observational cohort study was to compare vitamin D levels in patients two years after bariatric surgery (Roux-en-Y gastric bypass/RYGB and sleeve gastrectomy/SG) with a very low-energy diet (VLED). The same subjects were also compared with a population sample from the same region at baseline. The primary hypothesis was that surgery, especially RYGB, would lead to an increased prevalence of vitamin D deficiency compared to subjects treated with VLED. 971 individuals eligible for surgical, RYGB (n = 388), SG (n = 201), and medical treatment (n = 382), in routine care, were included consecutively between 2015 and 2017. A random population sample from the WHO-MONICA project was used as a reference, (n = 414). S-calcium, S-25(OH)D (vitamin D), and S-PTH (parathyroid hormone) were measured in all persons with obesity at baseline and two years after treatment (n = 713). Self-reported use of vitamin D and calcium supplementation was registered. RESULTS: Vitamin D deficiency (S-25(OH)D <25mmol/l) was found in 5.2% of the persons with obesity at baseline versus 1.7% of the general population (SMD>0.1). S-25(OH)D increased for all treatment groups but was higher in RYGB and SG (SMD>0.1, standardized mean difference). Thirteen subjects (1.8%) had vitamin D deficiency after obesity treatment. CONCLUSION: Surgical intervention for obesity followed by vitamin D supplementation was not associated with a higher risk for vitamin D deficiency, irrespective of surgery type, compared to individuals on medical treatment. However, persons living with obesity seeking weight loss treatment are more likely to have deficient vitamin D levels compared to the general population.

Mortality in Patients With Primary Aldosteronism: A Swedish Nationwide Study.

BACKGROUND: Primary aldosteronism (PA) is associated with increased mortality. The extent to which this phenomenon is affected by sex, age, comorbidities at diagnosis, and different treatment modalities is largely unknown. The objective was to determine all-cause and cause-specific mortality in a population-based cohort of patients with PA and the impact of age at diagnosis, sex, comorbidities, and treatment modalities. METHODS: We used national registers to identify patients diagnosed with PA between 1997 and 2019 (n=2419) and controls (n=24 187) from the general population, matched for sex, age, and county of residence. We obtained mortality data from the Cause-of-Death Register. We used Cox regression models, adjusted for socioeconomic factors and diabetes, to estimate adjusted hazard ratios (HRs [95% CI]). RESULTS: Overall, 346 (14.3%) patients with PA and 2736 (11.3%) controls died during a median follow-up time of 8.1 years. PA was associated with increased risk from all-cause mortality (HR, 1.23 [95% CI, 1.10-1.38]), death from cardiovascular disease (HR, 1.57 [95% CI, 1.30-1.89]), and stroke (HR, 1.85 [95% CI, 1.16-2.93]). Patients with cardiovascular disease at diagnosis (HR, 1.53 [1.26-1.85]), age >56 years (HR, 1.28 [95% CI, 1.13-1.45]), patients treated with a low dose of a mineralocorticoid receptor antagonist (HR, 1.30 [95% CI, 1.02-1.66]), and untreated patients (HR, 2.51 [95% CI, 1.72-3.67]) had excess mortality. CONCLUSIONS: Mortality, mainly due to cardiovascular disease, is increased in patients with PA compared with controls from the general population, particularly in patients aged >56 years, patients with preexisting cardiovascular comorbidities, and patients receiving low dose of a mineralocorticoid receptor antagonist.

Intermittent high-dose glucocorticoid treatment does not cause adrenal insufficiency in patients with diffuse large B-cell lymphoma - a prospective study.

Glucocorticoid (GC) treatment suppresses the hypothalamic-pituitary-adrenal axis and can cause GC-induced adrenal insufficiency. In this study we investigated the incidence of GC-induced adrenal insufficiency in patients receiving intermittent short-term high-dose oral GC treatment for newly diagnosed diffuse large B-cell lymphoma. Cosyntropin stimulation test was used to assess adrenal function at study entry (baseline), at 2 months (before the 5th cycle), and 6 months from baseline (3 months after the last cycle). Ten patients were included (40% women). Mean age was 61 years. The mean (range) plasma morning cortisol was 407 (320-530) nmol/L at baseline, 373 (260-610) nmol/L at 2 months, and 372 (230-520) nmol/L 6 months from baseline. All patients had normal response to cosyntropin stimulation at baseline as well as 2 and 6 months from baseline. Thus, none of the patients developed biochemically verified adrenal insufficiency. Therefore, short-term high-dose GC therapy, a commonly used adjuvant treatment in patients with malignant hematological diseases, does not seem to down-regulate the hypothalamic-pituitary-adrenal axis.

The Association between Inflammation, Testosterone and SHBG in men: A cross-sectional Multi-Ethnic Study of Atherosclerosis.

CONTEXT: Earlier studies have investigated the role of obesity-related inflammation and endogenous sex hormones in men. The role of interleukin-6 (IL-6) and C-reactive protein (CRP) with testosterone and sex hormone binding globulin (SHBG) levels in men is still debated. OBJECTIVE: To investigate the independent association between levels of high sensitivity CRP (hsCRP) and IL-6 with endogenous sex hormones in men. DESIGN: Cross-sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. PATIENTS OR OTHER PARTICIPANTS: A community-based sample of 3212 men aged 45-84 years was included. After exclusions, 3041 men remained for the analyses. MAIN OUTCOME MEASURE(S): Serum concentrations of testosterone, SHBG, hsCRP, IL-6, and sTNFR were measured from the baseline exam. Multivariable linear regressions were used to examine the association of inflammatory markers with sex hormones. RESULTS: An inverse association was found between levels of hsCRP and levels of testosterone and SHBG, even after adjustment for confounders and IL-6 (Total Testosterone; B = -0.14, Bioavailable Testosterone; B = -0.06, and SHBG; B = -0.66). Similar results were found for IL-6, although a positive association was found for SHBG (B = 0.95). Notably, an inverse association was found for IL-6 with bioavailable testosterone in African Americans and Hispanic Americans aged 45-54 years. No associations were found for sTNFR and endogenous sex hormones. CONCLUSION: Our results indicate that inflammatory markers have independent associations with levels of testosterone (total and bioavailable) and furthermore, appear to associate differently with SHBG levels.

Topical clobetasol treatment for oral lichen planus can cause adrenal insufficiency.

OBJECTIVE: Glucocorticoids suppress the hypothalamic-pituitary-adrenal axis, which may lead to glucocorticoid-induced adrenal insufficiency. The study aimed to investigate the prevalence of this state in patients with oral lichen planus treated with topical clobetasol propionate. METHODS: In this cross-sectional study, 30 patients with oral lichen planus receiving long-term (>6 weeks) clobetasol propionate gel 0.025% were invited to participate. Adrenal function was assessed by measuring morning plasma cortisol after a 48-h withdrawal of clobetasol treatment. In patients with plasma cortisol <280 nmol/L, a cosyntropin stimulation test was performed. RESULTS: Twenty-seven patients were included. Twenty-one (78%) patients presented with plasma cortisol ≥280 nmol/L (range 280-570 nmol/L), and six (22%) <280 nmol/L (range 13-260 nmol/L). Five of these six patients underwent cosyntropin stimulation that revealed severe adrenal insufficiency in two patients (cortisol peak 150 nmol/L and 210 nmol/L) and mild adrenal insufficiency in three patients (cortisol peak 350-388 nmol/L). CONCLUSION: In this study, approximately 20% of patients receiving intermittent topical glucocorticoid treatment for oral lichen planus had glucocorticoid-induced adrenal insufficiency. It is essential for clinicians to be aware of this risk and to inform patients about the potential need for glucocorticoid stress doses during intercurrent illness.

Teriparatide treatment in severe osteoporosis - a controlled 10-year follow-up study.

BACKGROUND: Teriparatide was the first anabolic agent recommended for the treatment of osteoporosis. Long-term real-world, controlled studies are not available. The purpose was to evaluate the long-term effects of treatment with teriparatide on fractures and Health Related Quality of Life in subjects with established osteoporosis in comparison with placebo treated patients with osteoporosis and the general population. METHODS: A 10-year follow-up was performed after a prospective, open-labelled study with teriparatide 20 µg given subcutaneously daily for a mean of 18 months (range 14-24 months) in 40 women, mean age 69 years, with osteoporosis and vertebral compression. Placebo treated women, n = 25, mean age 60 years, from a randomized, double-blind, placebo-controlled growth hormone trial with daily subcutaneous injections for 18 months, with osteoporosis were used as controls. Dual energy x-ray absorptiometry and questionnaires were performed at start, after 18 months, after 36 months and after 10 years. Women, n = 233, of similar age from a random population sample, also served as controls and were followed in parallel. All fractures were X-ray verified. RESULTS: Fractures decreased from 100 to 35% in the teriparatide treated patients (p < 0.0001) to similar levels as in the population sample, 25 to 28% at start and after 10 years, respectively. Bone mineral density increased on teriparatide but returned to levels at treatment start after 10 years. Health Related Quality of Life was lower in the teriparatide group than in the population (p < 0.001) before and, after treatment and at 10 years. CONCLUSIONS: Anabolic hormonal treatment with teriparatide reduced fracture prevalence to similar levels as in the general population at 10 years' follow-up. Health Related Quality of Life was low in osteoporosis and unaffected by bone specific treatment.

Comorbidity and quality of life in obesity-a comparative study with the general population in Gothenburg, Sweden.

CONTEXT: Obesity is considered to have a detrimental impact on health-related quality of life (HRQoL). OBJECTIVE: To compare HRQoL in a well-defined group of people with obesity with a population-based control group from the general public. DESIGN: Observational cross-sectional cohort study with a reference population. SETTING: The Regional Obesity Center at the Department of Medicine at Sahlgrenska University Hospital, Gothenburg, Sweden. PARTICIPANTS: People with obesity (n = 1122) eligible for surgical and non-surgical obesity treatment in routine care were included consecutively between 2015 and 2017 into the BASUN study. Men and women from the WHO-MONICA-GOT project were used as a reference population (n = 414). MAIN OUTCOME MEASURES: HRQoL was measured with the RAND-36/Short Form-36 questionnaire (SF-36) and a Visual Analogue Scale (VAS) for self-related health (SRH). Prescription drugs for hypertension, diabetes mellitus, depression, and anxiety were taken as a proxy for these conditions. RESULTS: People with obesity rated their overall HRQoL lower than the reference population according to the SRH-VAS. Lower scores were reported on physical and social functioning, vitality, general and mental health after adjustment for age and use of prescription drugs (considered a proxy for burden of disease, or comorbidities) using the RAND-36/SF-36 questionnaire. Use of some psychopharmacological agents was more common in patients with obesity. CONCLUSION: People with obesity seeking help with weight reduction are more likely to have lower physical and mental self-reported HRQoL than the general population.

High Mortality Rate in Oral Glucocorticoid Users: A Population-Based Matched Cohort Study.

Objective: The aim of the study was to investigate all-cause and disease-specific mortality in a large population-based cohort of oral glucocorticoid (GC) users. Methods: This was a retrospective, matched cohort study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. The cause of death was obtained from the Swedish Cause-of-Death Registry. Patients receiving prednisolone ≥5 mg/day (or equivalent dose of other GC) for ≥21 days between 2007-2014 were included. For each patient, one control subject matched for age and sex was included. The study period was divided into 3-month periods and patients were divided into groups according to a defined daily dose (DDD) of GC used per day. The groups were: Non-users (0 DDD per day), low-dose users (>0 but <0.5 DDD per day), medium-dose users (0.5-1.5 DDD per day) and high-dose users (>1.5 DDD per day). Hazard ratios (HRs), unadjusted and adjusted for age, sex and comorbidities, were calculated using a time-dependent Cox proportional hazard model. Results: Cases (n=223 211) had significantly higher all-cause mortality compared to controls (HR adjusted for age, sex and comorbidities 2.08, 95% confidence interval 2.04 to 2.13). After dividing the cases into subgroups, adjusted HR was 1.31 (1.28 to 1.34) in non-users, 3.64 (3.51 to 3.77) in low-dose users, 5.43 (5.27 to 5.60) in medium-dose users and, 5.12 (4.84 to 5.42) in high-dose users. The highest adjusted hazard ratio was observed in high-dose users for deaths from sepsis 6.71 (5.12 to 8.81) and pulmonary embolism 7.83 (5.71 to 10.74). Conclusion: Oral GC users have an increased mortality rate compared to the background population, even after adjustment for comorbidities. High-dose users have an increased risk of dying from sepsis, and pulmonary embolism compared to controls. Whether the relationship between GC exposure and the excess mortality is causal remains to be elucidated.

Long-Term Outcomes and Complications from Endoscopic Versus Microscopic Transsphenoidal Surgery for Cushing's Disease: A 15-Year Single-Center Study.

BACKGROUND: Endoscopic endonasal surgery is the main transsphenoidal approach for pituitary surgery in many centers; however, few studies compare the endoscopic and microscopic surgical approaches with regard to long-term follow-up. This single-center study aimed to compare the 2 techniques over 15 years. METHODS: Medical records and magnetic resonance images from 40 patients with primary transsphenoidal surgery for Cushing's disease at Sahlgrenska University Hospital between 2003 and 2018 were reviewed. 14 patients who underwent microscopic surgery and 26 patients who underwent endoscopic surgery were included in this study. RESULTS: In the microscopic group, 12 of 14 patients achieved endocrine remission, compared to 19 of 26 patients in the endoscopic group (n. s.). Three patients in each group developed a late recurrence. Complications were seen in 5 patients in the microscopic group and in 8 patients in the endoscopic group (n. s.). No serious complications, such as carotid artery damage, cerebrovascular fluid leakage, epistaxis, or meningitis, occurred in any group. The postoperative hospital stay was shorter in the endoscopic than in the microscopic group. CONCLUSIONS: Endoscopic endonasal surgery for Cushing's disease showed no difference in remission, recurrence, and complication rates compared to the microscopic approach. The endoscopic group had a shorter postoperative hospital stay than the microscopic group, which in part may be due to the minimal invasiveness of the endoscopic approach.

Low health-related quality of life in hypoparathyroidism and need for PTH analog.

Objective: Hypoparathyroidism (HypoPT) is a rare endocrine disorder in which insufficient levels of parathyroid hormone (PTH) lead to low serum calcium (S-Ca) levels and muscular cramps. The aim was to study the health-related quality of life (HRQoL) and comorbidities in patients with HypoPT compared with the general population and to estimate the need of treatment with PTH analog. Design: Patients with HypoPT were identified and compared with a population sample. Short Form-36 (SF-36) and EuroQol-5 Dimensions Visual Analogue Scale questionnaires were used. All patients were followed up at the Sahlgrenska University Hospital outpatient clinic. Methods: From the medical records between 2007 and 2020, 203 patients with HypoPT were identified and compared with a population sample (n = 414) from the World Health Organization's (WHO) MONICA project, Gothenburg, Sweden. Of the 203 patients who met the diagnostic criteria, 164 were alive and 65% answered the HRQoL questionnaires. Results: Patients with HypoPT, 80% postsurgical, and controls had similar age (60 years) and sex distribution (80% women). Patients had lower SF-36 summary component scores for physical (40.0 (interquartile range (IQR): 21) vs 51.2 (IQR: 14.6); P < 0.001) and mental (43.1 (IQR:17.4) vs 56.1(IQR:13.3); P < 0.001) well-being, irrespective of etiology or calcium levels. Individuals with HypoPT had more medications and lower renal function but not higher mortality than controls. Low HRQoL together with low calcium was present in 23% of individuals with HypoPT. Conclusion: HRQoL was markedly lower in patients with HypoPT than in controls and independent of S-Ca levels. Treatment with PTH analog could be considered at least among patients with both low HRQoL and low calcium levels.

Increasing Incidence of Primary Aldosteronism in Western Sweden During 3 Decades - Yet An Underdiagnosed Disorder.

CONTEXT: Primary aldosteronism (PA) is the most common cause of secondary hypertension. Yet, the incidence of PA in the general population has not been studied. OBJECTIVE: To estimate the incidence of PA in the general population. DESIGN AND METHODS: Patients who had received a diagnostic code for PA between 1987 and 2016 were identified in the Swedish National Patient Registry. Assessment of clinical and biochemical data was used to validate the diagnosis. The annual incidence of PA was calculated by using the number of inhabitants in the Västra Götaland County as a reference. RESULTS: Of 570 identified patients, 473 (83%) had confirmed PA. Eligible for the incidence analysis were 416 patients, 248 (60%) men and 168 (40%) women, diagnosed with PA between 1987 and 2016. The mean (± standard deviation) age at diagnosis was 56 ±â€…12 years. The median (interquartile range) annual incidence was 2 (1-2) cases per million between 1987 and 1996, 6 (4-9) cases per million between 1997 and 2006 and 17 (12-24) cases per million between 2007 and 2016. At the end of the study (December 31, 2016), 386 patients with confirmed PA were alive and living in the Västra Götaland County, giving a prevalence of 231 cases per million (0.022%). CONCLUSIONS: Despite increasing incidence, the proportion of patients identified with PA is lower than expected. Given the serious consequences of untreated PA, the noticeably low prevalence at the end of the study stresses the need to increase the awareness of PA among health care providers.

Identification of human glucocorticoid response markers using integrated multi-omic analysis from a randomized crossover trial.

Background: Glucocorticoids are among the most commonly prescribed drugs, but there is no biomarker that can quantify their action. The aim of the study was to identify and validate circulating biomarkers of glucocorticoid action. Methods: In a randomized, crossover, single-blind, discovery study, 10 subjects with primary adrenal insufficiency (and no other endocrinopathies) were admitted at the in-patient clinic and studied during physiological glucocorticoid exposure and withdrawal. A randomization plan before the first intervention was used. Besides mild physical and/or mental fatigue and salt craving, no serious adverse events were observed. The transcriptome in peripheral blood mononuclear cells and adipose tissue, plasma miRNAomic, and serum metabolomics were compared between the interventions using integrated multi-omic analysis. Results: We identified a transcriptomic profile derived from two tissues and a multi-omic cluster, both predictive of glucocorticoid exposure. A microRNA (miR-122-5p) that was correlated with genes and metabolites regulated by glucocorticoid exposure was identified (p=0.009) and replicated in independent studies with varying glucocorticoid exposure (0.01 ≤ p≤0.05). Conclusions: We have generated results that construct the basis for successful discovery of biomarker(s) to measure effects of glucocorticoids, allowing strategies to individualize and optimize glucocorticoid therapy, and shedding light on disease etiology related to unphysiological glucocorticoid exposure, such as in cardiovascular disease and obesity. Funding: The Swedish Research Council (Grant 2015-02561 and 2019-01112); The Swedish federal government under the LUA/ALF agreement (Grant ALFGBG-719531); The Swedish Endocrinology Association; The Gothenburg Medical Society; Wellcome Trust; The Medical Research Council, UK; The Chief Scientist Office, UK; The Eva Madura's Foundation; The Research Foundation of Copenhagen University Hospital; and The Danish Rheumatism Association. Clinical trial number: NCT02152553.

Several diseases, including asthma, arthritis, some skin conditions, and cancer, are treated with medications called glucocorticoids, which are synthetic versions of human hormones. These drugs are also used to treat people with a condition call adrenal insufficiency who do not produce enough of an important hormone called cortisol. Use of glucocorticoids is very common, the proportion of people in a given country taking them can range from 0.5% to 21% of the population depending on the duration of the treatment. But, like any medication, glucocorticoids have both benefits and risks: people who take glucocorticoids for a long time have an increased risk of diabetes, obesity, cardiovascular disease, and death. Because of the risks associated with taking glucocorticoids, it is very important for physicians to tailor the dose to each patient's needs. Doing this can be tricky, because the levels of glucocorticoids in a patient's blood are not a good indicator of the medication's activity in the body. A test that can accurately measure the glucocorticoid activity could help physicians personalize treatment and reduce harmful side effects. As a first step towards developing such a test, Chantzichristos et al. identified a potential way to measure glucocorticoid activity in patient's blood. In the experiments, blood samples were collected from ten patients with adrenal insufficiency both when they were on no medication, and when they were taking a glucocorticoid to replace their missing hormones. Next, the blood samples were analyzed to determine which genes were turned on and off in each patient with and without the medication. They also compared small molecules in the blood called metabolites and tiny pieces of genetic material called microRNAs that turn genes on and off. The experiments revealed networks of genes, metabolites, and microRNAs that are associated with glucocorticoid activity, and one microRNA called miR-122-5p stood out as a potential way to measure glucocorticoid activity. To verify this microRNA's usefulness, Chantzichristos et al. looked at levels of miR-122-5p in people participating in three other studies and confirmed that it was a good indicator of the glucocorticoid activity. More research is needed to confirm Chantzichristos et al.'s findings and to develop a test that can be used by physicians to measure glucocorticoid activity. The microRNA identified, miR-122-5p, has been previously linked to diabetes, so studying it further may also help scientists understand how taking glucocorticoids may increase the risk of developing diabetes and related diseases.