Congenital Adrenal Hyperplasia in Adults

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder affecting adrenal steroid synthesis. More than 95% of CAH cases are caused by reduced 21-hydroxylase function leading to variable extent of cortisol and aldosterone deficiency in addition to androgen excess. The foundation of CAH treatment is the use of glucocorticoids. However, overtreatment leads to Cushing s syndrome and undertreatment to hyperandrogenism and Addisonian crisis. The aims of this thesis has been to evaluate the impact of CAH and its treatment on some factors that could lead to a reduced quality of life and increased morbidity or mortality during adult life. In total 93 patients (32 males) with CAH and 93 (32 males) age- and sex-matched controls were studied. Subgroups of different ages (<30 years or older), phenotypes and the three most common genotype groups (null, I2 splice and I172N) were studied. Focus was on cardiovascular and metabolic risk, bone health in females and fertility in males. Cardiovascular and metabolic risk: Younger female and male patients and controls had similar waist/hip ratio, lean and fat mass and insulin values. Older females had higher waist/hip ratio, lean mass and insulin values than controls. Fat mass was similar to controls but higher than in younger patients. Lipid profiles were slightly more favourable in older patients than in controls. Gestational diabetes was more common in patients. Few older female patients had hypertension, cardiovascular disease or diabetes. Despite moderate glucocorticoid doses, most patients had suppressed androgens. Serum liver enzymes were elevated in patients compared to controls. In patients, liver enzymes were correlated with waist circumference and with total body and trunk fat. Liver enzymes were increased even in non-obese patients mainly attributed to the patients ≥30 years who also demonstrated elevated insulin levels and HOMA-indices. In older males, waist/hip ratio, fat mass, and gamma-glutamyl transpeptidase were higher and heart rate faster than in controls. Insulin levels were increased during oral glucose tolerance test in all and older patients. Homocysteine was lower in all and in younger male patients which may be cardioprotective. Adverse cardiovascular profiles were mainly found in the mild genotype I172N. This group had normal urinary epinephrine concentrations whereas the more severe genotypes null and I2 splice had low levels. Few old male patients had cardiovascular disease and no patient had diabetes. Bone health in females: Patients had lower bone mineral density (BMD) than controls at all measured sites. In patients ≥30 years old 73% were osteopenic or osteoporotic vs 21% in controls. BMD was similar in the two classic forms and had no obvious relationship to genotypes. More fractures were reported in patients than controls. Fertility in males: Compared to national data the fertility was impaired in CAH males. The lifetime number of partners was smaller in all patients, in older patients and in the null group. Testicular tumours (TARTs) were found in 86% and 47% had pathological semen. Those with pathological semen had increased total and truncal fat mass, fat/lean mass ratio and heart rate. FSH was elevated and correlated negatively with sperm count and concentration. Conclusions: Adult CAH females and males have a number of issues due to the disease and to corticoid supplementation. However, the findings in this thesis are more positive than many of the previous reports on CAH. Many parameters studied in our CAH individuals <30 years were not different from age- and sex-matched controls. This is likely to reflect improvements in management

Adrenal Crisis

Glucocorticoid replacement therapy, available since the 1950s, has prolonged the survival of patients with adrenal insufficiency. However, adrenal crises, which are life-threatening medical emergencies, still develop in many affected patients. Adrenal crisis appears to be increasing in frequency, despite the availability of effective preventive strategies. This review examines the definitions, pathophysiology, epidemiology, and treatment of adrenal crises

Adrenal insufficiency due to bilateral adrenal metastases - A systematic review and meta-analysis

Objective: Bilateral adrenal metastases may cause adrenal insufficiency (AI) but it is unclear if screening for AI in patients with bilateral adrenal metastases is justified, despite the potential for adrenal crises. Method: A search using PubMed/Medline, ScienceDirect and Cochrane Reviews was performed to collect all original research articles and all case reports from the past 50 years that describe AI in bilateral adrenal metastases. Results: Twenty studies were included with 6 original research articles, 13 case reports and one case series. The quality was generally poor. The prevalence of AI was 3–8%. Of all cases of AI (n ¼ 25) the mean pooled baseline cortisol was 318 237 nmol/L and stimulated 423 238 nmol/L. Hypotension was present in 69%, hyponatremia in 9% and hyperkalemia in 100%. Lung cancer was the cause in 35%, colorectal 20%, breast cancer 15% and lymphoma 10%. The size of the adrenal metastases was 5.5 2.8 cm (left) and 5.5 3.1 cm (right), respectively. There was no correlation between basal cortisol, stimulated cortisol concentration or ACTH with the size of adrenal metastases. The median time to death was 5.0 months (IQR 0.6–6.5). However, two cases were alive after 12–24 months. Conclusion: The prevalence of AI in patients with bilateral adrenal metastases was low. Prognosis was very poor. Due to the low prevalence of AI, screening is likely only indicated in patients with symptoms and signs suggestive of hypocortisolism

Factors underlying a disproportionate increase in hospital admissions for adrenal insufficiency in women aged 20-29 years

Since the year 2000, admissions for adrenal insufficiency (AI) and adrenal crises (AC) have shown a particular increase in young adult females. We examined data on acute non-surgical hospitalisations for AI/AC from New South Wales, Australia, to determine relevant factors that may have contributed to this increase. Data were analysed to ascertain associations between various comorbid psychosocial issues, identified by relevant ICD-10-AM codes in each record, and ACs. From 2005 to 2021. There were 877 admissions for an acute non-surgical illness in this age group. The average admission rate for females [63.5/million/year] was almost twice that for males [34.0/million/year] (p&lt;0.01), as was the average female AC admission rate [14.7/million/year] relative to that in males [6.75/million/year] (p=NS). Infection was present in 41.6% (n=365) of the admissions and Type 1 diabetes mellitus was present in 12.2% (n=107). Overall, psychosocial factors were considered by the senior clinician to have contributed to the illness episode in 22.1% of all admissions and 29.0% of AC admissions. Having one or more psychosocial problems was associated with an AC in females (37.4%, n=49, in those having an AC, p&lt;0.001) but not males. Females with an AC also had a higher mean composite psychosocial, psychiatric and drug/alcohol score [0.47 (0.67)] than females without an AC [0.32 (0.62) p&lt;0.05]. No comparable associations were found in male patients. An increase in the rates of hospitalisations that included a code for at least one psychosocial problem was highly correlated with increases in admission rates for both ACs (r=0.82, p&lt;0.001) and all AI (r=0.98, p&lt;0.001) in females but there was no such relationship in males. This new evidence suggests that psychosocial factors may play an important role in ongoing rates of ACs in treated AI (incidence approximately 6-8 ACs/100PY) particularly in young adult females. In order to minimize AC episodes, all barriers to self-management need exploration on an individual patient basis and with regard to the patient population as a whole

Lower extremity amputations and long-term outcomes in diabetic foot ulcers: a systematic review

Background: Diabetes mellitus causes a large majority of non-traumatic major and minor amputations globally. Patients with diabetes are clinically complex with a multifactorial association between diabetic foot ulcers (DFU) and subsequent lower extremity amputations (LEA). Few studies show the long-term outcomes within the cohort of DFU-associated LEA. Aim: To highlight the long-term outcomes of LEA as a result of DFU. Methods: PubMed/MEDLINE and Google Scholar were searched for key terms, "diabetes", "foot ulcers", "amputations" and "outcomes". Outcomes such as mortality, re-amputation, re-ulceration and functional impact were recorded. Peer-reviewed studies with adult patients who had DFU, subsequent amputation and follow up of at least 1 year were included. Non-English language articles or studies involving children were excluded. Results: A total of 22 publications with a total of 2334 patients were selected against the inclusion criteria for review. The weighted mean of re-amputation was 20.14%, 29.63% and 45.72% at 1, 3 and 5 years respectively. The weighted mean of mortality at 1, 3 and 5 years were 13.62%, 30.25% and 50.55% respectively with significantly higher rates associated with major amputation, re-amputation and ischemic cardiomyopathy. Conclusion: Previous LEA, level of the LEA and patient comorbidities were significant risk factors contributing to re-ulceration, re-amputation, mortality and depreciated functional status

Congenital adrenal hyperplasia is a very rare cause of adrenal incidentalomas in Sweden

BackgroundUndiagnosed congenital adrenal hyperplasia (CAH) can cause adrenal incidentalomas, but the frequency is unclear.ObjectivesThis study aimed to investigate the prevalence of CAH in a population with adrenal incidentalomas and report the clinical characterization.Material and methodsThis was a prospective study performed at a regional hospital from 2016 to 2021. Patients with adrenal incidentalomas were investigated with an adrenocorticotropic hormone (ACTH)-stimulation test in addition to hormonal workup. Serum cortisol and 17-hydroxyprogesterone (17OHP) were analyzed. Individuals with a basal or stimulated 17OHP ≥30 nmol/L were classified as suspicious non-classic CAH, and a CYP21A2-gene analysis was performed in these subjects.ResultsIn total, 320 individuals with adrenal incidentalomas were referred to the center, and of these individuals, an ACTH-stimulation test was performed in 222 (median age, 67 (24–87) years; 58.6% women; and 11.7% with bilateral lesions). None of the individuals presented a basal 17OHP ≥30 nmol/L, but there were 8 (3.6%) who did after ACTH stimulation. Four of these subjects (50%) presented bilateral lesions, and the tumor size was larger compared to that of the individuals with a stimulated 17OHP &lt;30 nmol/L (median, 38 (19–66) vs. 19 (11–85) mm, p=0.001). A CYP21A2 variation (p.Val282Leu) was detected in one of the eight subjects with a stimulated 17OHP ≥30 nmol/L, i.e., the patient was a heterozygotic carrier. None of the eight subjects presented with cortisol insufficiency or clinical signs of hyperandrogenism.ConclusionsThe prevalence of non-classic CAH in an adrenal incidentaloma cohort was 3.6% based on stimulated 17OHP and 0% based on gene analysis. CAH should be considered in AI management in selected cases and confirmed by genetic analysis

Lactation Ketoacidosis: A case series

Lactation ketoacidosis is an extremely rare type of high anion gap metabolic acidosis. We report two lactating women who were diagnosed with lactation ketoacidosis. The first patient presented to the Emergency Department at Royal Darwin Hospital, Darwin, Australia, in 2018 with lethargy, nausea and abdominal pain after she commenced a new diet regimen based on three meals of protein per day and free of glucose, gluten and dairy products. The second patient presented to the Emergency Department at Sultan Qaboos University Hospital, Muscat, Oman, in 2018 with headache, severe malaise, epigastric pain and worsening of gastroesophageal symptoms. Blood investigation results showed that both patients had high anion gap metabolic acidosis, ketosis and hypoglycaemia. The patients responded well to intravenous dextrose and resumption of a balanced diet. Both patients were able to continue breastfeeding and remained well on follow-up.Keywords: Breastfeeding; Starvation; Hypoglycemia; Ketosis; Acid-Base Imbalance; Metabolic Diseases; Ketone Bodies; Fasting; Case Series; Australia; Oman

Hospital admission patterns in children with CAH: admission rates and adrenal crises decline with age

Objective: To examine patterns of hospitalisation for acute medical conditions in children with congenital adrenal hyperplasia (CAH). Design: A retrospective study of hospitalisation using administrative data. Setting. All hospitals in NSW, Australia. Patients: All patients admitted with CAH and a random sample of admissions in patients aged 0 to 18 years without adrenal insufficiency (AI). Main Outcome Measures: Admissions and comorbidities by age and sex. Results: Of 573 admissions for medical problems in CAH children, 286 (49.9%) were in males, and 236 (41.2%) had a principal diagnosis of CAH or had an adrenal crisis (AC). 37 (6.5%) ACs were recorded. An infection was found in 43.5% ( = 249) of the CAH patient admissions and 51.7% ( = 1613) of the non-AI group, \u3c 0.001. Children aged up to one year had the highest number of admissions ( = 149) and six ACs (four in males).There were 21 ACs recorded for children aged 1–5 years. Older CAH children had fewer admissions and fewer ACs. No in-hospital deaths were recorded. Conclusions. Admission for medical problems in CAH children declines with age. An AC was recorded in 6.5% of the admissions, with the majority of ACs occurring in the 1 to 5 years age group and there were no deaths

Increased cardiovascular and metabolic morbidity in patients with 21-hydroxylase deficiency : a Swedish population-based national cohort study

CONTEXT: Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms if not treated with glucocorticoids. However, glucocorticoids may increase the risk of cardiovascular and metabolic morbidity. OBJECTIVE: This study aimed to study cardiovascular and metabolic morbidity in CAH. DESIGN, SETTING, AND PARTICIPANTS: Patients with CAH due to 21-hydroxylase deficiency (n = 588; >80% with known CYP21A2 mutations) were compared with controls matched for sex, year, and place of birth (n = 58 800). Data were obtained by linking national population-based registers. Subgroup analyses were performed regarding sex, clinical severity (salt wasting, simple virilizing, nonclassic), CYP21A2 genotype (null, I2 splice, I172N, P30L), and stratified by the introduction of neonatal screening, age groups, and nonobesity. MAIN OUTCOME MEASURES: To study cardiovascular and metabolic morbidity in CAH. RESULTS: In CAH, both any cardiovascular and metabolic disorders (OR [odds ratio], 3.9; 95% CI [confidence interval], 3.1-5.0), and cardiovascular disease (OR, 2.7; 95% CI, 1.9-3.9) were increased. Separate analyses of the individual diseases showed higher frequencies in CAH of hypertension, hyperlipidemia, atrial fibrillation, venous thromboembolism, obesity, diabetes (mainly type 2), obstructive sleep disorder, thyrotoxicosis, and hypothyroidism. Similar results were seen in the stratified groups. On the subgroup level, females were generally more affected (especially I172N and the nonclassic group), as were males with the null genotype. CONCLUSIONS: CAH was associated with excess cardiovascular and metabolic morbidity but the mechanism is not certain as the glucocorticoids were not assessed. Hypothyroidism and obesity may be an effect of close observation. However, more severe conditions were presumably detected equally in patients and controls. Screening for diabetes and other metabolic disorders that increase cardiovascular risk is important.Magn. Bergvalls FoundationKarolinska InstitutetStockholm County CouncilSwedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences, SIMSAM 340-2013-5867Manuscrip

Magnesium and Human Health: Perspectives and Research Directions

Copyright © 2018 Abdullah M. Al Alawi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Magnesium is the fourth most abundant cation in the body. It has several functions in the human body including its role as a cofactor for more than 300 enzymatic reactions. Several studies have shown that hypomagnesemia is a common electrolyte derangement in clinical setting especially in patients admitted to intensive care unit where it has been found to be associated with increase mortality and hospital stay. Hypomagnesemia can be caused by a wide range of inherited and acquired diseases. It can also be a side effect of several medications. Many studies have reported that reduced levels of magnesium are associated with a wide range of chronic diseases. Magnesium can play important therapeutic and preventive role in several conditions such as diabetes, osteoporosis, bronchial asthma, preeclampsia, migraine, and cardiovascular diseases. This review is aimed at comprehensively collating the current available published evidence and clinical correlates of magnesium disorders