Increased risk of hospitalization, intensive care and death due to COVID-19 in patients with adrenal insufficiency: A Swedish nationwide study.

BACKGROUND: Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown. METHODS: In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis. RESULTS: We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59-2.43), intensive care admission (2.76, 1.49-5.09) and death (2.29, 1.60-3.28). CONCLUSION: Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.

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.

Diagnostic challenges in patients with reninomas and extrarenal renin-producing tumours.

Renin-secreting tumours are rare causes of secondary hypertension and hypokalaemia. They are usually surgically curable, hence proper diagnostic work-up and tumour localisation is essential. In this paper, we present three Swedish patients recently diagnosed with renin secreting tumours, two with reninomas and one with an extrarenal renin-producing tumour, to illustrate diagnostic challenges. We also discuss the biochemical work-up, the pros and cons of different imaging techniques (computer tomography [CT], magnetic resonance imaging and [18F]fluorodeoxyglucose-positron emission tomography-CT), as well as how renal vein sampling (RVC) may contribute to localisation of the tumour.

Acromegaly management in the Nordic countries: A Delphi consensus survey.

OBJECTIVE: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries. METHODS: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale. RESULTS: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists. CONCLUSION: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.

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.

Androgen deficiency in hypopituitary women: its consequences and management.

Women with hypopituitarism have various degrees of androgen deficiency, which is marked among those with combined hypogonadotrophic hypogonadism and secondary adrenal insufficiency. The consequences of androgen deficiency and the effects of androgen replacement therapy have not been fully elucidated. While an impact of androgen deficiency on outcomes such as bone mineral density, quality of life, and sexual function is plausible, the available evidence is limited. There is currently no consensus on the definition of androgen deficiency in women and it is still controversial whether androgen substitution should be used in women with hypopituitarism and coexisting androgen deficiency. Some studies suggest beneficial clinical effects of androgen replacement but data on long-term benefits and risk are not available. Transdermal testosterone replacement therapy in hypopituitary women has shown some positive effects on bone metabolism and body composition. Studies of treatment with oral dehydroepiandrosterone have yielded mixed results, with some studies suggesting improvements in quality of life and sexual function. Further research is required to elucidate the impact of androgen deficiency and its replacement treatment on long-term outcomes in women with hypopituitarism. The lack of transdermal androgens for replacement in this patient population and limited outcome data limit its use. A cautious and personalized treatment approach in the clinical management of androgen deficiency in women with hypopituitarism is recommended while awaiting more efficacy and safety data.

Headache in patients with non-functioning pituitary adenoma before and after transsphenoidal surgery - a prospective study.

PURPOSE: To study the long-term effect of transsphenoidal surgery (TSS) on headache in patients with non-functioning pituitary adenoma (NFPA) and identify factors predicting headache relief following TSS. METHODS: We evaluated headache in 101 consecutive patients with NFPA who underwent TSS from September 2015 to December 2021, preoperatively and 12-months post-surgery, by using the Migraine Disability Assessment (MIDAS) questionnaire. Health-related quality of life (QoL) was assessed using the EQ-5D visual analogue scale (EQ-VAS). RESULTS: Of 101 patients, 27 (27%) experienced disabling preoperative headache. Among these, the median total MIDAS score improved from 60 (interquartile range (IQR): 19-140) to 10 (IQR: 0-49) (P = 0.004). Additionally, headache frequency over a 90-day period decreased from 45 (IQR: 25-83) to 6 (IQR: 3-36) days (P = 0.002), and headache intensity decreased from 5 (IQR: 4-7) to 4 (IQR: 2-7) (P = 0.016) at 12-months post-surgery. At 12 months post-surgery, 18 (67%) of 27 patients with preoperatively disabling headache showed clinically relevant improvement of their headache, 4 (15%) showed deterioration, and 5 (19%) remained unchanged. In patients with clinically relevant improvement of their headache, the EQ-VAS score improved from 50 (IQR: 30 - 7) to 80 (IQR: 65-86) (P < 0.001). Of the 74 patients with no preoperative headache, 11 (15%) developed postoperative headache. We identified no clinical factors predicting postoperative headache relief. CONCLUSION: The study supports that clinically significant and long-lasting improvements of disabling headache and QoL can be achieved with TSS in a substantial number of patients with NFPA.

Salivary cortisol and cortisone in diagnosis of Cushing's syndrome - a comparison of six different analytical methods.

OBJECTIVES: Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushing's syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS. METHODS: Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves. RESULTS: URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4-3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7-1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5-16.6 nmol/L at 23:00 h and 3.0-3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs ≥0.96. CONCLUSIONS: We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.

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.

The importance of personal documentation for patients living with long-term illness symptoms after pituitary surgery: A Constructivist Grounded Theory study.

INTRODUCTION: Despite surgical treatment, pituitary adenomas often cause long-term illness symptoms, that profoundly impact patients' quality of life physically, psychologically and socially. Healthcare professionals often fail to recognize and discuss the ensuing problems. Personal documentation, such as symptom monitoring, reflective writing or even posts on social media, may help this patient group to manage their daily life and support communication of their care needs. Documentation strategies and the role of documentation for people with long-term symptoms after pituitary adenoma surgery are currently unknown. AIM: To examine the effects and strategies of documenting symptoms, activities and physical and emotional well-being among people living with long-term pituitary adenoma. METHODS: In this Constructivist Grounded Theory study, 12 individuals living with long-term illness symptoms after pituitary adenoma surgery described their documentation strategies in in-depth interviews using teleconferencing and photo-elicitation between August and October 2020. RESULTS: Strategies for documentation included analogue and digital media. One core category (Exercising autonomy) and three categories describing processes (Gaining insight, Striving for control and Sharing) emerged from the analysis. These three interrelated processes become an expression of autonomy to manage life and make sense of chronic illness. Personal documentation is a flexible tool that is used more extensively in times of ill health and less in times of relative well-being. Sharing documentation with healthcare professionals facilitated care planning and sharing with friends and family fostered emotional well-being. CONCLUSION: Personal documentation is a valuable resource for managing life after pituitary adenoma surgery. The current findings may be relevant to other chronic illnesses. Further research exploring potential tools for personal documentation is needed. PATIENT OR PUBLIC CONTRIBUTION: We deliberately chose a Constructivist Grounded Theory approach for this interview study. Using Constructivist Grounded Theory, we gave people living with long-term symptoms a voice, allowing them to freely speak about managing their illness in connection with personal documentation. The theoretical sampling approach enabled us to invite participants that could provide a broad overview of the landscape of personal documentation.

Natural history and surgical outcome of Rathke's cleft cysts-A study from the Swedish Pituitary Registry.

OBJECTIVE: Rathke's cleft cysts are benign, embryological remnants in the pituitary gland. The majority of them are small and asymptomatic but a few may become large, and cause mass effects, pituitary hormone deficiencies and visual impairment. Recommendations for the follow-up of Rathke's cleft cysts vary since data on the natural history are sparse. PATIENTS AND DESIGN: Data at diagnosis and at 1, 5 and 10 years for patients with a Rathke's cleft cyst (434 at diagnosis, 317 females) were retrieved from the Swedish Pituitary Registry. Cysts ≤3 mm in diameter were excluded from the study. MEASUREMENTS: Data included demographics, cyst size, pituitary function, visual defects and surgery. RESULTS: The mean age at diagnosis was 45 years. In patients with cysts <10 mm in diameter (n = 204) 2.9% had pituitary hormone deficiencies and 2% had visual field impairments. Cyst size did not progress during the 5 years. Cysts with a diameter of ≥10 mm that were not operated (n = 174) decreased in size over the years (p < .01). Pituitary hormone deficiencies and visual impairments were more frequent (18% and 5.7%, respectively) but were stable over time. Transphenoidal surgery was performed in 56 patients of whom 51 underwent surgery before the 1-year follow-up. The mean cyst diameter at diagnosis was 18 mm (range: 9─30 mm), 36% had pituitary hormone deficiency, 45% had visual field defects and 20% had impaired visual acuity. One year after surgery 60% had no cyst remnants, 50% had a pituitary deficiency, 26% had visual field defects and 12% had impaired visual acuity. No major changes were observed after 5 years. Twelve of the operated patients had a follow-up at 10 years, in eight the cyst remnants or recurrences increased in size over time (p < .05). CONCLUSIONS: Rathke's cleft cysts with a size less than 10 mm rarely grow and our results indicate that radiological follow-up can be restricted to 5 years. In contrast, progression of postoperative remnants or recurrent cysts is more likely and require long-term follow-up.

Growth hormone deficiency in adults with hypopituitarism-What are the risks and can they be eliminated by therapy?

Growth hormone (GH) deficiency develops early in patients with hypothalamic-pituitary disorders and is therefore common among these patients. GH deficiency in adults is associated with increased morbidity, increased body fat mass, abdominal obesity, dyslipidaemia, reduced exercise capacity, impaired cardiac function as well as reduced self-reported well-being and impaired quality of life. Since recombinant human GH became available as replacement therapy more than 25 years ago, randomised controlled trials and long-term studies, together with meta-analyses, have shown improved outcomes in adult patients with hypopituitarism receiving GH. Many of the features associated with GH deficiency in adults improve, or even normalize, and the safety profile is reassuring. The increased interest in GH deficiency in adults with hypothalamic-pituitary disorders has also contributed to the identification of other factors of importance for an outcome such as the replacement of other pituitary hormone deficiencies, and the management of the underlying hypothalamic-pituitary disease, most commonly a pituitary tumour. In this narrative review, we summarize the burden of GH deficiency in adults with hypopituitarism, the impact of GH replacement on the outcome, as well as safety. Based on currently available data, GH replacement should be considered routine management of adults with hypopituitarism.

Pre- and postoperative 68 Ga-DOTATOC positron emission tomography for hormone-secreting pituitary neuroendocrine tumours.

OBJECTIVES: Somatostatin receptors (SSTRs) are potential targets for detecting pituitary neuroendocrine tumours (PitNETs) that can be visualized effectively with 68 Ga-labelled PET tracers. With this study, we have evaluated the diagnostic properties of such a tracer, 68 Ga-DOTATOC, in patients with hormone-producing PitNETs before and after surgery. DESIGN/METHODS: This prospective case-control study presents preoperative positron emission tomography (PET) and histopathological data in 18 patients with somatotroph (n = 8), corticotroph (n = 7) and thyrotroph (n = 3) PitNETs. Patients were scanned pre- and postoperatively with 68 Ga-DOTATOC PET. For the postoperative part of the study, patients with gonadotroph tumours (n = 7) were also included. Fifteen pituitary healthy controls underwent the same protocol once. The maximum standard uptake value (SUVmax ) was analysed in manually outlined regions around the tumour in patients and around the pituitary gland in controls. specimens were collected during surgery in subjects for assessment of adenohypophyseal tumour cell type and the SSTR expression. RESULTS: Thyrotroph tumours showed higher uptake (median SUVmax 41.1; IQR 37.4-60.0) and corticotroph tumours lower uptake (SUVmax 6.8; 2.6-9.3) than normal pituitary gland (SUVmax 13.8; 12.1-15.5). The uptake in somatotroph tumours (SUVmax 15.9; 11.6-19.7) was similar to the uptake in the pituitary gland. There was a strong correlation between SUVmax and SSTR2 expression (r = .75 (P < .01)). In the postoperative evaluation, PET was able to correlate tracer uptake with biochemical cure and noncure in patients with an abnormal postoperative magnetic resonance image and a preoperative tumour uptake SUVmax  > 13.8. CONCLUSIONS: 68 Ga-DOTATOC PET can be used to detect thyrotroph tumours in the pre- and postoperative imaging assessment. Corticotroph tumours had a significantly lower uptake compared to the pituitary gland but without a distinct increased tumour uptake the clinical postoperative value is limited.

Prevalence of Nelson's syndrome after bilateral adrenalectomy in patients with cushing's disease: a systematic review and meta-analysis.

PURPOSE: Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development. DATA SOURCES: Systematic literature search in four databases. STUDY SELECTION: Observational studies reporting the prevalence of NS after BA in adult patients with CD. DATA EXTRACTION: Data extraction and risk of bias assessment were performed by three independent investigators. DATA SYNTHESIS: Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)]. CONCLUSIONS: Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.

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.

Lower 68 Ga-DOTATOC uptake in nonfunctioning pituitary neuroendocrine tumours compared to normal pituitary gland-A proof-of-concept study.

OBJECTIVES: 68  Ga-DOTATOC PET targets somatostatin receptors (SSTRs) and is well established for the detection of SSTR-expressing tumors, such as gastrointestinal neuroendocrine tumors. Pituitary adenomas, recently designated as pituitary neuroendocrine tumors (PitNETs), also express SSTRs, but there has been no previous evaluations of 68  Ga-DOTATOC PET in PitNET patients. The aim of this pilot study was to evaluate the diagnostic properties of 68  Ga-DOTATOC PET in the most common PitNET, ie non-functioning (NF)-PitNET. DESIGN/PATIENTS: NF-PitNET patients (n = 9) and controls (n = 13) were examined preoperatively with 68  Ga-DOTATOC PET for 45 min after tracer injection in dynamic list mode. Tumor specimens were collected during surgery in patients. MRI and PET images were co-registered using PMOD software. The maximum standard uptake value (SUVmax ) was analyzed in manually outlined regions of interest (ROI) around the tumor in patients and around the pituitary gland in controls. Immunohistochemical analyses were conducted on tumor specimens for assessment of tumor cell type and SSTR expression. RESULTS: Median SUVmax (IQR) was lower in patients than in controls (3.9 [3.4-8.5] vs 14.1 [12.5-15.9]; P < .01]. In ROC analysis, the area under the curve was 0.87 (P < .01) for SUVmax , with 78% sensitivity and 92% specificity. Immunohistochemical analysis showed NF-PitNETs were of gonadotroph (n = 7) and corticotroph (n = 2) origin. SSTR expression was high for SSTR3, low-to-moderate for SSTR2, and low for SSTR1 and SSTR5. CONCLUSIONS: This proof-of-concept study shows that 68 Ga-DOTATOC PET can be used to differentiate between normal pituitary tissue and NF-PitNET.

[Obesity isn't always obesity: Cushing's disease - case report]. / Offita er ekki alltaf offita: Cushing-sjúkdómur, sjúkratilfelli

Woman in her thirties presented to the emergency room with a two-week history of worsening headache and diplopia. For eight years she had suffered from progressive weight gain, diabetes and hypertension that didn't improve with lifestyle modification. A lumbar puncture demonstrated increased intracranial pressure and MRI a pituitary adenoma. Physical examination was consistent with Cushing's syndrome and endocrine workup confirmed Cushing's disease. Treatment was complex, including unsuccessful pituitary surgery and gamma knife radiosurgery, and eventually bilateral adrenalectomy with subsequent development of Nelsons syndrome. This case illustrates the diagnostic delay that many patients with CD suffer from.

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.

Non-functioning pituitary adenomas: indications for pituitary surgery and post-surgical management.

PURPOSE: Non-functioning pituitary adenomas (NFPAs) are associated with impaired well-being, increased comorbidities, and reduced long-term survival. Data on optimal management of NFPAs around surgical treatment are scarce, and postoperative treatment and follow-up strategies have not been evaluated in prospective trials. Here, we review the preoperative, perioperative, and early postoperative management of patients with NFPAs. METHODS: We searched Medline and the Cochrane Library for articles published in English with the following items "Pituitary neoplasms AND Surgery" and "Surgery AND Hypopituitarism". Studies containing detailed analyses of the management of NFPAs in adult patients, including pituitary surgery, endocrine care, imaging, ophthalmologic assessment and long-term outcome were reviewed. RESULTS: Treatment options for NFPAs include active surveillance, surgical resection, and radiotherapy. Pituitary surgery is currently recommended as first-line treatment in patients with visual impairment due to adenomas compressing the optic nerves or chiasma. Radiotherapy is reserved for large tumor remnants or tumor recurrence following one or more surgical attempts. There is no consensus of optimal pre-, peri-, and postoperative management such as timing, frequency, and duration of endocrine, radiologic, and ophthalmologic assessments as well as management of smaller tumor remnants or tumor recurrence. CONCLUSIONS: In clinical practice, there is a great variation in the treatment and follow-up of patients with NFPAs. We have, based on available data, suggested an optimal management strategy for patients with NFPAs in relation to pituitary surgery. Prospective trials oriented at drawing up strategies for the management of NFPAs are needed.