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.

Hip fractures in patients with primary aldosteronism - a Swedish nationwide study.

In this large population-based matched cohort study, patients with primary aldosteronism were at increased risk of hip fracture, particularly subgroups traditionally considered at higher risk of osteoporosis such as women, patients older than 56 years at diagnosis, patients with established cardiovascular disease at diagnosis, and patients treated with MRA. PURPOSE: Previous studies suggest that primary aldosteronism (PA) is associated with dysregulated bone homeostasis. The aim of this study was to evaluate the incidence of hip fractures in patients with PA. METHODS: We studied a nationwide cohort of 2419 patients with PA (1997-2019) and 24 187 age and sex matched controls from the general population. Hip fractures were identified by ICD codes in the Swedish National Patient Register. We estimated hazard ratios (HRs) for incident hip fractures, adjusted for prior fractures, socioeconomic factors, diabetes, osteoporosis, hyperparathyroidism, and cardiovascular disease (CVD). Pairwise subgroup comparisons were performed by age (18-56 and > 56 years), sex, CVD at baseline, and treatment for PA. RESULTS: During a mean follow up of 8 ± 5 years, 64 (2.6%) patients had a hip fracture after being diagnosed with PA, compared to 401 (1.7%) controls. After adjustments, PA was associated with a 55% increased risk of hip fracture compared to controls (HR 1.55 [1.18-2.03]). HRs were increased in women (HR 1.76 [95% CI 1.24-2.52]), patients aged > 56 years (HR 1.62 [95% CI 1.21-2.17]), and patients with CVD at diagnosis (HR 2.15 [95% CI 1.37-3.37]). PA patients treated with adrenalectomy did not have higher risk than controls (HR 0.84 [95% CI 0.35-2.0]), while patients treated with mineralocorticoid receptor antagonists (MRA) retained a greater risk (HR 1.84 [95% CI 1.20-2.83]). CONCLUSION: PA is associated with increased hip fracture risk, especially in women, patients diagnosed after the age of 56 years and patients with established CVD at diagnosis. Also, patients treated with MRA seem to have an increased risk of hip fractures, while adrenalectomy may be protective.

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.

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.

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.

Health-related quality of life in hypothyroidism-A population-based study, the WHO MONICA Project.

OBJECTIVE: To explore health-related quality of life (HRQoL) among subjects with hypothyroidism compared to subjects without hypothyroidism in the general population. HRQoL is important in clinical practice. Hypothyroidism is prevalent, mainly found in women, and increasing with age. DESIGN: Cohort study of random population sample. PATIENTS: Women and men, n = 414 (39-78 years) from the WHO MONICA project, Gothenburg, Sweden, participated. Hypothyroidism was defined as subjects having levothyroxine supplementation or serum thyroid-stimulating hormone (S-TSH) >4.2 mU/L. MEASUREMENTS: Health-related quality of life was measured with Psychological General Well-Being Index (PGWB), Nottingham Health Profile (NHP), Short Form 36 Health Survey (SF-36) and a single item self-rated health scale (0-100), and stress was rated 1-6. The results were adjusted for age, sex and comorbidity using analysis of covariance (ANCOVA). RESULTS: Hypothyroidism was found in 70 subjects (17%). They scored worse HRQoL than controls regarding Sleep (p < .001), Social isolation (p = .01) and Total NHP (p < .05), and had more medication in general 2.7 ± 2.5 vs. 1.8 ± 2.1, p < .05. Subjects with levothyroxine (n = 40) showed similar results as the total hypothyroid group. Subjects unaware of their newly detected elevated STSH (n = 30) showed lower HRQoL in Sleep (p < .01) and Pain (p < .05) in NHP. HRQoL was similar in subjects with and without positive thyroperoxidase antibodies (TPO-Ab) either in those with hypothyroidism (44% TPO-Ab) or controls (9% TPO-Ab). CONCLUSION: Men and women with hypothyroidism in the general population reported having more issues with Sleep and Social isolation than those without hypothyroidism irrespective of TPO-Ab. Scores were similar in all of the other HRQoL domains measuredAQ5.

High prescription rate of oral glucocorticoids in children and adults: A retrospective cohort study from Western Sweden.

OBJECTIVE: Glucocorticoids (GCs) are a cornerstone in treating various common and uncommon diseases. The aim of this study was to estimate the prevalence of GC use in terms of doses associated with risk of tertiary adrenal insufficiency in adults and children, and treatment indications. METHODS: This was a retrospective cohort study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. Patients with prescriptions of prednisolone (or equivalent dose of other GCs) ≥5 mg daily for ≥21 days between 2007 and 2014 were included. Information on concurrent diseases was obtained from the Swedish National Patient Register and the Västra Götaland Regional Healthcare Database. RESULTS: Of 1 585 335 inhabitants in Västra Götaland County, 223 211 were included in the study (women 55.6%). Mean age was 48 ± 24 years. Period prevalence of oral GC use during the 8-year study period was 14.1%. The highest prevalence (27.4%) was in men aged 80-89 years and lowest (7.5%) in men 10-19 years of age. The period prevalence in children 0-9 years of age was 10.6%. COPD and asthma were the most common indications for treatment (17.2%) followed by allergy (12.5%) and malignant neoplasms (11.5%). Allergy was the most frequent indication (20.5%) in children and adolescents. CONCLUSION: Between 2007 and 2014, every seventh inhabitant in western Sweden received a GC prescription at doses associated with risk of developing tertiary adrenal insufficiency. These findings illustrate the importance of awareness of the potential development of tertiary adrenal insufficiency in both paediatric and adult patients.

The incidence of endogenous Cushing's syndrome in the modern era.

INTRODUCTION: Epidemiological studies on the incidence of Cushing's syndrome (CS) are few and most often includes only patients with the most common form, that is Cushing's disease (CD). OBJECTIVE: To analyse the incidence of endogenous CS in an unselected cohort of patients from western Sweden between 2002 and 2017. METHODS: Medical records from patients who had received a diagnostic code for CS and adrenocortical carcinoma in the Västra Götaland County between 2002 and 2017 were reviewed. Eighty-two patients had been diagnosed with endogenous CS in the region during the study period and were included in this analysis. RESULTS: Thirty-nine patients (48%) had CD, 21 (26%) had ectopic ACTH-producing tumour, 17 (21%) had a benign adrenal CS, and 5 (6%) had cortisol-producing adrenocortical carcinoma. Nine of 21 (43%) patients with ectopic CS had an ACTH-producing lung tumour, 4 had a neuroendocrine pancreas tumour, and 5 had an occult tumour. The annual incidence of endogenous CS was 3.2 cases per million/y; 1.5 for CD, 0.8 for ectopic CS, 0.7 for benign adrenal CS and 0.2 for adrenocortical carcinoma. CONCLUSIONS: Approximately three new cases of endogenous CS, per one million inhabitants, were diagnosed annually between 2002 and 2017. Compared with previous reports, proportionally more patients had ectopic CS. The reason for this is unclear although increased awareness of hypercortisolism in patients with malignant tumours in the modern era is a possible explanation.

Higher menopausal age but no differences in parity in women with polycystic ovary syndrome compared with controls.

INTRODUCTION: To address the question of whether women with polycystic ovary syndrome (PCOS) reach menopause later than age-matched controls, we conducted a follow-up cohort study of women with well-characterized PCOS that was diagnosed 24 years ago. The hypothesis was that women with PCOS would reach menopause later than non-PCOS women. Parity during these 24 years was also studied. MATERIAL AND METHODS: Twenty-seven women diagnosed with PCOS in 1992 (mean age 29.5 years) were re-examined in 2016 (mean age 52.4 years). Randomly selected women, n = 94 (mean age 52.4 years), from the same geographic area included in the World Health Organization MONICA study, Gothenburg, Sweden, served as controls. RESULTS: The mean menopausal age in women with PCOS was higher than in controls (53.3 ± 2.2 years vs 49.3 ± 3.5 years, P < 0.01). Serum-follicle stimulating hormone levels were lower in the PCOS women than in controls (31.0 ± 28.1 IU/L vs 52.3 ± 37.7 IU/L, P = 0.01). There was no difference in parity between women with PCOS (1.9 ± 1.3 children, range 0-4) and controls (1.7 ± 1.0, range 0-4 children). CONCLUSIONS: Women with PCOS reached menopause 4 years later and had lower serum-follicle stimulating hormone compared with age-matched controls. Neither parity nor nulliparity differed between women with PCOS and controls.

Comorbidity and health-related quality of life in Somali women living in Sweden.

Objective: To explore the relationship between low serum vitamin D levels and comorbidity in Somali women, immigrants to Sweden. Design and setting: Cohort study in a Primary Health Care Center and a University Hospital. Subjects: Somali women skin type V, n = 114, aged 18-56 years, from latitude 0-10○ N, living in Sweden, latitude 57○ N > 2 years were compared with women from a population sample, skin type II-III, n = 69, aged 38-56 years, the WHO MONICA study, Gothenburg, Sweden. Main outcome measures: Serum (S)-25(OH)D, S-parathyroid hormone (PTH), comorbidity and Health-Related Quality of Life (HRQoL) using the Short Form-36 (SF-36) and part of the EQ-5D questionnaires. All calculations were corrected for age. Results: Vitamin D deficiency (S-25(OH)D < 25 nmol/l) was found in 73% of the Somali women and in 1% of the controls (p < .0001). S-PTH was elevated (>6.9 pmol/l) in 26% and 9%, respectively (p < .004). Somali women used less medication, 16% vs. 55%, p < .0001) but more allergy medication, 11% vs. 7% (p = .006), had fewer fractures, 2% vs. 28% (p < .0001) and lower HRQoL in 7 out of 9 scales (p < .05-.001), than native controls. There were no differences in the prevalence of diabetes mellitus, hypothyroidism, positive thyroid peroxidase antibodies, vitamin B12 deficiency, celiac disease or hypertension. Conclusions: Vitamin D deficiency was common in Somali women living in Sweden, 73%, but comorbidity was low. Both mental, and especially physical HRQoL scores were lower in the Somali women. The effects of long-lasting deficiency are unknown. Key points The aim was to explore the relationship between vitamin D deficiency (S-25(OH)D < 25 nmol/l) and comorbidity in immigrants. Vitamin D deficiency was common in Somali women living in Sweden, 73%, but comorbidity of hypothyroidism, diabetes mellitus, hypertension, fractures and use of medications was low. Both mental, and especially physical, Health-Related Quality of Life were lower in the Somali women than in native Swedish women. The effects of long-lasting deficiency are unknown.

Pituitary dysfunction in granulomatosis with polyangiitis.

PURPOSE: Granulomatosis with polyangiitis (GPA) is a multisystem disease, characterized by necrotizing small-vessel vasculitis, which mainly affects the respiratory tract and the kidneys. Pituitary involvement in GPA is rare, present in about 1% of all cases of GPA. To date, only case reports or small case series have been published. Herein we report clinical features, imaging findings, treatment and outcomes in three patients with GPA-related pituitary dysfunction (PD). METHODS: A retrospective analysis of three cases of GPA-related PD was conducted, followed by systematic review of the English medical literature using PubMed. RESULTS: The three cases include three women aged between 32 and 37 years. PD was the presenting feature in one and two developed PD in the course of the disease. All patients had a pituitary lesion on MRI. Conventional treatment with high doses of glucocorticoids and cyclophosphamide led to resolution or improvement of the MRI abnormalities, whereas it was not effective in restoring PD. A systematic review identified 51 additional patients, showing that GPA can lead to partial or global PD, either at onset or, during the course of the disease. Secondary hypogonadism is the predominant manifestation, followed by diabetes insipidus (DI). Sellar mass with central cystic lesion is the most frequent radiological finding. CONCLUSION: GPA should be carefully considered in patients with a sellar mass and unusual clinical presentation with DI and systemic disease. Although conventional induction-remission treatment improves systemic symptoms and radiological pituitary abnormalities, hormonal deficiencies persist in most of the patients. Therefore, follow-up should include both imaging and pituitary function assessment.

High androgen levels protect against hypothyroidism.

INTRODUCTION: Hypothyroidism is a common disorder, appearing mainly in women although less frequently found in women with polycystic ovary syndrome (PCOS). The objective was to test the hypothesis that hyperandrogenism might protect against hypothyroidism. MATERIAL AND METHODS: The data from three prospective follow-up studies (up to 21 years) and one register study were compared: women with PCOS (Rotterdam criteria), n = 25, women with Turner syndrome, n = 217, a random population sample of women, n = 315, and men, n = 95 (the WHO MONICA study). Findings were to be verified or rejected in all females, n = 553 716, from the same region. The proportion of hypothyroidism was calculated and thyroid peroxidase antibodies (TPO) in serum were measured. RESULTS: Hypothyroidism at >50 years of age was found in 8% of women with PCOS, 4% in men (PCOS vs. men; ns), 43% of women with Turner syndrome, irrespective of karyotype (p < 0.001 vs. PCOS), and in 17% of postmenopausal women in the population (p < 0.01 vs. PCOS). Elevated TPO were similar in PCOS and women and men in the population but higher in Turner syndrome. Hypothyroidism increased with age in all groups except PCOS women and men. In the register study, hypothyroidism was less common in women with PCOS >25 years (5.5%) than in women without PCOS (6.8%) from the same region (p < 0.01). CONCLUSIONS: Hypothyroidism was less frequently seen in women with PCOS and in men compared with women in the general population and among women with Turner syndrome. This was not explained by altered autoimmunity or the Y-chromosome. Androgens seem to protect against hypothyroidism.

Normocalcaemic, vitamin D-sufficient hyperparathyroidism - high prevalence and low morbidity in the general population: A long-term follow-up study, the WHO MONICA project, Gothenburg, Sweden.

OBJECTIVE: There is limited knowledge about the natural history of normocalcaemic, vitamin D-sufficient hyperparathyroidism (nHPT). The aim was to study the prevalence of nHPT and its relation to morbidity. DESIGN: Cross-sectional and retrospective study at the Sahlgrenska University Hospital, Gothenburg, Sweden. SUBJECTS: A random population of 608 men and women, age 25-64 years, was studied in 1995 as part of the WHO MONICA study and reinvestigated in 2008 (n = 410, of whom 277 were vitamin D sufficient). MEASUREMENTS: A serum intact parathyroid hormone (S-PTH) ≥60 ng/l was considered as HPT, S-calcium 2·15-2·49 mmol/l as normocalcaemia and S-25(OH)D ≥ 50 nmol/l as vitamin D sufficiency. Data on fractures, stroke and myocardial infarction were retrieved until 2013, that is a 17-year follow-up. RESULTS: The prevalence of nHPT was 2·0% in 1995 (age 25-64) and 11·0% in 2008 (age 38-79). S-PTH was positively correlated with age and BMI. After adjustment for these variables, a high S-PTH level (≥60 ng/l) at follow-up was associated with previously low S-25(OH)D, high osteocalcin, S-PTH and both past and presently treated hypertension. No relation was seen with creatinine, cystatin C, malabsorption markers, thyroid function, glucose, insulin, lipids, calcaneal quantitative ultrasound, fractures, myocardial infarction, stroke or death at follow-up. CONCLUSIONS: This small random population study showed that nHPT was common, 11% at follow-up. Only one individual developed mild hypercalcaemia in 13 years. Previous S-PTH was predictive of nHPT and hypertension was prevalent, but no increase in hard end-points was seen over a 17-year period.

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.

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.

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.

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.

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.

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.