Hyperprolactinemia has been associated with impaired metabolism, including insulin resistance. However, the metabolic effects of elevated prolactin (PRL) levels are not completely clarified. The aim ...of this study was to obtain more insights of metabolic consequences in hyperprolactinemia patients. Fourteen consecutive patients, eight women and six men, aged 39.7 (±13.7) years with prolactinomas (median PRL 72 49–131 μg/L in women and 1,260 123–9,600 μg/L in men) were included. Anthropometric data and metabolic values were studied before and after 2 and 6 months on DA agonists (Bromocriptine 5.7 (±3.9) mg/day,
n
= 13 or Cabergoline 0.5 mg/week,
n
= 1). Euglycemic hyperinsulinemic clamps were studied in six patients before and after 6 months of treatment. PRL normalized in all patients. Anthropometric data changed only in males with a significant decrease of median body weight (95.6 80.7–110.1 to 83.4 77.8–99.1 kg,
P
= 0.046), waist circumference and fat percentage after 6 months. LDL cholesterol was positively correlated to PRL at diagnosis (
r
= 0.62,
P
= 0.025) and decreased within 2 months (3.4 ±0.9 to 2.9 ±0.6 mmol/L,
P
= 0.003). Insulin, IGFBP-1 and total adiponectin levels did not change. Insulin sensitivity tended to improve after 6 months; M-value from 5.7 (±1.8) to 7.8 (±2.6) mg/kg/min,
P
= 0.083 and per cent improvement in M-value was correlated to per cent reduction in PRL levels (
r
= −0.85,
P
= 0.034). In conclusion, beneficial metabolic changes were seen in prolactinoma patients after treatment with DA agonists, underscoring the importance of an active treatment approach and to consider the metabolic profile in the clinical management of hyperprolactinemia patients.
Abstract
Context:
Studies of the clinical and immunological features of autoimmune Addison disease (AAD) are needed to understand the disease burden and increased mortality.
Objective:
To provide ...upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles, and cardiovascular risk factors.
Design, Setting, and Participants:
A cross-sectional, population-based study that included 660 AAD patients from the Swedish Addison Registry (2008–2014). When analyzing the cardiovascular risk factors, 3594 individuals from the population-based survey in Northern Sweden, MONICA (monitoring of trends and determinants of cardiovascular disease), served as controls.
Main Outcome Measures:
The endpoints were the prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.
Results:
The proportion of 21-hydroxylase autoantibody-positive patients was 83%, and 62% of patients had ≥1 associated autoimmune diseases, more frequently coexisting in females (P < 0.0001). AAD patients had a lower body mass index (P < 0.0001) and prevalence of hypertension (P = 0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of the patients, with a mean dose of 28.1 ± 8.5 mg/d. The mean hydrocortisone equivalent dose normalized to the body surface was 14.8 ± 4.4 mg/m2/d. A greater hydrocortisone equivalent dose was associated with a greater incidence of hypertension (P = 0.046).
Conclusions:
Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients did not have an increased prevalence of overweight, hypertension, type 2 diabetes mellitus, or hyperlipidemia. However, high glucocorticoid replacement doses could be a risk factor for hypertension.
Upgraded data regarding autoimmune comorbidities, autoantibody profiles, replacement therapy and cardiovascular risk factors revealing a need to carefully monitor AAD patients.
Experimental evidence indicates that prolactin might play a role in tumorigenesis of several human cancers, but data on cancer risk in hyperprolactinemia patients are sparse. The aim of this study ...was to investigate cancer risk in hyperprolactinemia patients. Design A population-based matched cohort study in Sweden.
The hyperprolactinemia cohort consisted of patients hospitalized for hyperprolactinemia from 1987 to 1995 identified in the National Patient Register (n=585) and a hospital cohort of prolactinoma patients at Karolinska University Hospital (n=384). For each patient, ten matched individuals were identified via the Register of Population. Cancer occurrence was ascertained via the Swedish Cancer Registry. Hazard ratios (HRs) were estimated by Cox proportional hazards regression.
Seventy-three malignant tumors were identified in the hyperprolactinemia patients and 660 tumors in the comparison group (HR 1.31; 95% confidence interval (CI): 1.02-1.68), mainly attributed to an increased risk of upper gastrointestinal cancer in both males and females (HR 3.69; 95% CI: 1.70-8.03) and hematopoietic cancer in females (HR 3.51; 95% CI: 1.06-11.6). Twelve breast cancers occurred in the female patients, corresponding to an HR of 1.09 (95% CI: 0.60-1.99). Prostate cancer risk in hyperprolactinemia men was reduced (HR 0.40; 95% CI: 0.16-0.99).
An increased overall cancer risk was found in hyperprolactinemia patients, but no increased risk of breast cancer in women and a reduced risk of prostate cancer in men. These findings warrant further investigations and to be confirmed in larger studies but may indicate the importance of an active treatment strategy and follow-up of hyperprolactinemia patients.
Summary
Context
Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. ...The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI).
Objective
The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice‐daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD.
Design and setting
An open, randomized, two‐period, 12‐week crossover multicentre trial in Norway and Sweden.
Patients
Ten Norwegian patients were admitted for 24‐h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic‐hyperinsulinaemic clamp.
Intervention
Thrice‐daily regimen of oral hydrocortisone (OHC) and CSHI treatment.
Main outcome measure
We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin‐like growth factor‐1, (IGF‐1), IGF‐binding protein‐3 (IGFBP‐3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic‐hyperinsulinaemic clamp was used to assess insulin sensitivity.
Results
Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late‐night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms.
Conclusion
Continuous subcutaneous hydrocortisone infusion replacement re‐established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night‐time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night‐time cortisol levels might be advantageous for patients with AD.
In this article, we review published studies covering epidemiology, natural course and mortality in primary adrenal insufficiency (PAI) or Addison's disease. Autoimmune PAI is a rare disease with a ...prevalence of 100-220 per million inhabitants. It occurs as part of an autoimmune polyendocrine syndrome in more than half of the cases. The patients experience impaired quality of life, reduced parity and increased risk of preterm delivery. Following a conventional glucocorticoid replacement regimen leads to a reduction in bone mineral density and an increase in the prevalence of fractures. Registry studies indicate increased mortality, especially evident in patients diagnosed with PAI at a young age and in patients with the rare disease autoimmune polyendocrine syndrome type-1. Most notably, unnecessary deaths still occur because of adrenal crises. All these data imply the need to improve the therapy and care of patients with PAI.
Context:
Conventional glucocorticoid replacement therapy fails to mimic the physiological cortisol rhythm, which may have implications for morbidity and mortality in patients with Addison's disease.
...Objective:
The objective of the study was to compare the effects of continuous sc hydrocortisone infusion (CSHI) with conventional oral hydrocortisone (OHC) replacement therapy.
Design, Patients, and Interventions:
This was a prospective crossover, randomized, multicenter clinical trial comparing 3 months of treatment with thrice-daily OHC vs CSHI. From Norway and Sweden, 33 patients were enrolled from registries and clinics. All patients were assessed at baseline and after 8 and 12 weeks in each treatment arm.
Main Outcome Measures:
The morning ACTH level was the primary outcome measure. Secondary outcome measures were effects on metabolism, health-related quality of life (HRQoL), sleep, and safety.
Results:
CSHI yielded normalization of morning ACTH and cortisol levels, and 24-hour salivary cortisol curves resembled the normal circadian variation. Urinary concentrations of glucocorticoid metabolites displayed a normal pattern with CSHI but were clearly altered with OHC. Several HRQoL indices in the vitality domain improved over time with CSHI. No benefit was found for either treatments for any subjective (Pittsburgh Sleep Quality Index questionnaire) or objective (actigraphy) sleep parameters.
Conclusion:
CSHI safely brought ACTH and cortisol toward normal circadian levels without adversely affecting glucocorticoid metabolism in the way that OHC did. Positive effects on HRQoL were noted with CSHI, indicating that physiological glucocorticoid replacement therapy may be beneficial and that CSHI might become a treatment option for patients poorly controlled on conventional therapy.
Background
Surgical treatment of pituitary lesions causing hormonal overproduction or mass effect is standard procedure. There are few reports on the results and complications related to these ...surgeries from Northern Europe. Our aim was to evaluate the outcome and complications of a single tertiary surgical center over more than a decade.
Methods
This was a retrospective study on all patients that underwent pituitary surgery from 1st of January 2005 to 31st of December 2017. The analysis included type of lesion, surgical method, pre- and postoperative need for hormonal substitution, hormonal outcome, complications to surgery, survival, need for revision surgery, or stereotactic radiation. Appropriate statistical analyses were made to evaluate surgical results, complications, and survival.
Results
Five hundred seventy-eight patients were included in the study. Remission was achieved in 58% of patients with GH-producing and 94% of ACTH-releasing adenomas. Sixty-six percent had no preoperative hormonal substitution compared to 39% postoperatively. Rhinosinusitis (10%) was the most commonly reported postoperative complication followed by leakage of cerebrospinal fluid (8%) and meningitis (4%). Standardized mortality rate for the study population was higher (
p
= 0.18) when compared to the general population.
Conclusion
Our results regarding remission rates and complications are in comparison with previous studies. Surgery of pituitary lesion can be considered a safe and efficient surgery. We noted lower rates of CSF leakage in the later part of the study period and believe that this, in part, was an effect by the introduction of a multidisciplinary surgical skull base team and increased surgical experience.
Autoimmune Addison's disease (AAD) is characterized by the autoimmune destruction of the adrenal cortex. Low prevalence and complex inheritance have long hindered successful genetic studies. We here ...report the first genome-wide association study on AAD, which identifies nine independent risk loci (P < 5 × 10
). In addition to loci implicated in lymphocyte function and development shared with other autoimmune diseases such as HLA, BACH2, PTPN22 and CTLA4, we associate two protein-coding alterations in Autoimmune Regulator (AIRE) with AAD. The strongest, p.R471C (rs74203920, OR = 3.4 (2.7-4.3), P = 9.0 × 10
) introduces an additional cysteine residue in the zinc-finger motif of the second PHD domain of the AIRE protein. This unbiased elucidation of the genetic contribution to development of AAD points to the importance of central immunological tolerance, and explains 35-41% of heritability (h
).
Background
Hydrocortisone treatment in transsphenoidal pituitary surgery has been debated. Although several publications advocate restrictive treatment, centers around the world administer stress ...doses of hydrocortisone in patients with presumed intact cortisol production. Our aim with this analysis was to compare postoperative hypocortisolism in patients who received three different protocols of hydrocortisone therapy during and after surgery.
Method
This was a retrospective observational study. Based on perioperative hydrocortisone dose given, patients were divided in three groups: high dose (HD), intermediate dose (ID), and low dose (LD). Postoperative evaluation of the pituitary function was performed using S-cortisol at day 4 and short Synacthen test (SST) at 6–8 weeks. Patients with ACTH-producing adenomas or preoperative hydrocortisone treatment were excluded.
Result
There was no difference between the groups regarding failure rate of SST. The rate of failed SST (all groups) was 51/186 (27%), 24/74 (32%) in the HD group and 26/74 (35%) and 11/38 (29%) in the ID and LD groups respectively. There was no significant difference between the ID and LD groups regarding S-cortisol at postoperative day 4 regarding serum cortisol level below 200 nmol/L. There was a significant but weak correlation,
r
s
0.330 (
P
< 0.01) between S-cortisol day 4 and SST at 4–6 weeks.
Conclusions
Peri and postoperative hydrocortisone treatment did not affect SST response 6–8 weeks postoperatively, whereas the rate of patients with S-cortisol below 200 nmol/L at postoperative day 4 did. LD hydrocortisone therapy seems to favor a better endogenous production in the early postoperative phase.
Context:
Patients with Addison's disease (AD) self-report impairment in specific dimensions on well-being questionnaires. An AD-specific quality-of-life questionnaire (AddiQoL) was developed to aid ...evaluation of patients.
Objective:
We aimed to translate and determine construct validity, reliability, and concurrent validity of the AddiQoL questionnaire.
Methods:
After translation, the final versions were tested in AD patients from Norway (n = 107), Sweden (n = 101), Italy (n = 165), Germany (n = 200), and Poland (n = 50). Construct validity was examined by exploratory factor analysis and Rasch analysis, aiming at unidimensionality and fit to the Rasch model. Reliability was determined by Cronbach's coefficient-α and Person separation index. Longitudinal reliability was tested by differential item functioning in stable patient subgroups. Concurrent validity was examined in Norwegian (n = 101) and Swedish (n = 107) patients.
Results:
Exploratory factor analysis and Rasch analysis identified six items with poor psychometric properties. The 30 remaining items fitted the Rasch model and proved unidimensional, supported by appropriate item and person fit residuals and a nonsignificant χ2 probability. Crohnbach's α-coefficient 0.93 and Person separation index 0.86 indicate high reliability. Longitudinal reliability was excellent. Correlation with Short Form-36 and Psychological General Well-Being Index scores was high. A shorter subscale comprising eight items also proved valid and reliable. Testing of AddiQoL-30 in this large patient cohort showed significantly worse scores with increasing age and in women compared with men but no difference between patients with isolated AD and those with concomitant diseases.
Conclusion:
The validation process resulted in a revised 30-item AddiQoL questionnaire and an eight-item AddiQoL short version with good psychometric properties and high reliability.
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