HIV infections and AIDS cases in Poland in 2021 year. / Zakazenia HIV i zachorowania na AIDS w Polsce w 2021 roku.

BACKGROUND: Despite a temporary decrease in the number of newly HIV infections in Poland in 2020, a return to the growing number of new infections was observed in 2021 in the surveillance. OBJECTIVE: The aim of the study was to assess the epidemiological situation of newly HIV infections and AIDS cases and death among AIDS cases in Poland in 2021 in comparison to the changes in preceding years. MATERIAL AND METHODS: Analysis of the epidemiological situation was based on reports of newly detected HIV cases and AIDS cases received from doctors and laboratories and the results of the annual survey of HIV testing conducted by laboratories throughout the country. A dataset on clients from Voluntary Testing and Counselling, coordinated by the National AIDS Center, which anonymously collects epidemiological and behaviour data on tested people was used. RESULTS: In 2021 there were 1 367 HIV cases newly diagnosed in Poland (diagnosis rate 3.58 per 100,000), including 236 among non-Polish citizens. The number of HIV infections increased by 43.3% compared to the previous year and was higher by 3.8% compared to the median in 2015-2019 years. Similarly, among VCT clients, number of HIV increased by 45%, from 309 in 2020 to 448 in 2021 year. The total number of AIDS cases reported to surveillance was 62 (incidence 0.16 per 100,000). The HIV infection was most often detected in the age group 30-39 year (35.8%) and among men (82.1%). Among cases with known transmission route, 68.7% concerned among MSM. The percentage of AIDS cases diagnosed at the same time with HIV increased by more than 30 percent points (from 63.5% to 95.1% of all AIDS cases). CONCLUSIONS: In 2021 the number of newly detected HIV infections increased compared to the previous year, probably due to a reduction in restrictions related to the COVID-19 pandemic and increased in HIV testing rate.

Tall stature and gigantism in adult patients with acromegaly.

OBJECTIVES: Increased height in patients with acromegaly could be a manifestation of growth hormone (GH) excess before epiphysis closure. The aim of this study was to evaluate the relationship between the height of adult patients with GH excess related to mid-parental height (MPH) and population mean and to find whether taller patients with acromegaly come from tall families. METHODS: This is a single-centre, observational study involving 135 consecutive patients with acromegaly diagnosed as adults and no family history of GH excess. We established three categories for height for patients with acromegaly: normal stature, tall stature (TS, height above the 97th percentile (1.88 standard deviations (SD)) to <3 SD for gender- and country-specific data or as a height which was greater than 1.5 SD but less than 2 SD above the MPH) and gigantism (height which was greater than 3 SD) above the gender- and country-specific mean or greater than 2 SD above MPH). RESULTS: Thirteen percent (17/135) of patients (53% females) met the criteria for gigantism, 10% (14/135) fulfilled the criteria for TS (57% females). Parents and adult siblings were not taller than the population mean. CONCLUSION: In a group of 135 consecutive adult patients with acromegaly, 23% had increased height based on country-specific and MPH data: 13% presented with gigantism while 10% had TS. The frequency of gigantism and TS in patients diagnosed with GH excess as adults is not higher in males than in females. Patients with acromegaly come from normal-stature families.

Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 1, general recommendations.

Tumours of the anterior part of the pituitary gland represent just 1% of all childhood (aged <15 years) intracranial neoplasms, yet they can confer high morbidity and little evidence and guidance is in place for their management. Between 2014 and 2022, a multidisciplinary expert group systematically developed the first comprehensive clinical practice consensus guideline for children and young people under the age 19 years (hereafter referred to as CYP) presenting with a suspected pituitary adenoma to inform specialist care and improve health outcomes. Through robust literature searches and a Delphi consensus exercise with an international Delphi consensus panel of experts, the available scientific evidence and expert opinions were consolidated into 74 recommendations. Part 1 of this consensus guideline includes 17 pragmatic management recommendations related to clinical care, neuroimaging, visual assessment, histopathology, genetics, pituitary surgery and radiotherapy. While in many aspects the care for CYP is similar to that of adults, key differences exist, particularly in aetiology and presentation. CYP with suspected pituitary adenomas require careful clinical examination, appropriate hormonal work-up, dedicated pituitary imaging and visual assessment. Consideration should be given to the potential for syndromic disease and genetic assessment. Multidisciplinary discussion at both the local and national levels can be key for management. Surgery should be performed in specialist centres. The collection of outcome data on novel modalities of medical treatment, surgical intervention and radiotherapy is essential for optimal future treatment.

Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 2, specific diseases.

Pituitary adenomas are rare in children and young people under the age of 19 (hereafter referred to as CYP) but they pose some different diagnostic and management challenges in this age group than in adults. These rare neoplasms can disrupt maturational, visual, intellectual and developmental processes and, in CYP, they tend to have more occult presentation, aggressive behaviour and are more likely to have a genetic basis than in adults. Through standardized AGREE II methodology, literature review and Delphi consensus, a multidisciplinary expert group developed 74 pragmatic management recommendations aimed at optimizing care for CYP in the first-ever comprehensive consensus guideline to cover the care of CYP with pituitary adenoma. Part 2 of this consensus guideline details 57 recommendations for paediatric patients with prolactinomas, Cushing disease, growth hormone excess causing gigantism and acromegaly, clinically non-functioning adenomas, and the rare TSHomas. Compared with adult patients with pituitary adenomas, we highlight that, in the CYP group, there is a greater proportion of functioning tumours, including macroprolactinomas, greater likelihood of underlying genetic disease, more corticotrophinomas in boys aged under 10 years than in girls and difficulty of peri-pubertal diagnosis of growth hormone excess. Collaboration with pituitary specialists caring for adult patients, as part of commissioned and centralized multidisciplinary teams, is key for optimizing management, transition and lifelong care and facilitates the collection of health-related quality of survival outcomes of novel medical, surgical and radiotherapeutic treatments, which are currently largely missing.

Differences in clinical characteristics, treatment, and outcomes of sporadic and MEN-1-related insulinomas.

INTRODUCTION: Although in most cases insulinomas are small, benign, sporadic tumours, they can also be associated with hereditary syndromes, most commonly multiple endocrine neoplasia type 1 (MEN-1). Such a diagnosis significantly affects patient management. The objective was to elucidate the clinical differences between sporadic and MEN-1-linked insulinoma. MATERIAL AND METHODS: Comparison of clinical and histopathological characteristics, types of surgery, and outcomes of patients with sporadic and MEN-1-related insulinoma diagnosed between 2015 and 2022. RESULTS: There were 17 cases of insulinomas that underwent MEN-1 genetic testing (10 women and 7 men). In 7 cases, the mutation in the menin gene was confirmed. The median age at the time of diagnosis of sporadic insulinoma related to MEN-1 was 69 years (range 29-87) and 31.5 years (16-47), respectively. Primary hyperparathyroidism (PHP) was found in 6 of 7 patients with MEN-1-related insulinoma, while in none of the patients without MEN-1 mutations. Multifocal pancreatic NETs were found in 3 patients with MEN-1 syndrome, while in all sporadic cases there was a single pancreatic tumour. Two patients with insulinoma related to MEN-1 had a positive familial history of MEN-1-related diseases, while none with sporadic form. Dissemination at diagnosis was found in 4 cases, including 3 patients with insulinoma related to MEN-1-related insulinoma. Patients with sporadic and MEN-1-related insulinoma did not differ in tumour size, Ki-67 proliferation index, and outcome. CONCLUSIONS: Of all the features evaluated, only the multifocal nature of pancreatic neuroendocrine tumour (PanNET) lesions and a positive family history differentiated between patients with sporadic and MEN-1-related insulinomas. An age of insulinoma diagnosis of less than 30 years may be a strong indicator of an increased risk of MEN-1 syndrome.

COVID-19 infection in a patient with Cushing's disease on osilodrostat treatment.

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Individualized medical treatment options in Cushing disease.

Cushing disease (CD) is caused by a pituitary tumor which oversecretes adrenocorticotropic hormone (ACTH). It is a serious endocrine disease associated with increased mortality and impaired quality of life. The management of CD remains challenging. Although transsphenoidal surgery is the treatment of choice in most cases, in approximately half of CD patients, second or third-line treatment options are needed. Currently, new medical therapies are available which target adrenal steroidogenesis, pituitary somatostatin and dopamine receptors, and glucocorticoid receptors. Selection of which medication to use should be individualized and is determined by many factors including severity of the disease, possible side effects, patients preferences and local availability. The aim of this article is to describe currently available medical therapy to help clinicians individualize the treatment options in the context of recently updated Pituitary Society recommendations.

HIV infections and AIDS in Poland in 2020.

PURPOSE: The aim of the study was to assess the epidemiological situation of newly diagnosed HIV infections and AIDS cases and death among AIDS cases in Poland in 2020 in comparison to the changes in preceding years. MATERIAL AND METHODS: Analysis of the epidemiological situation was based on reports of newly detected HIV cases and AIDS cases received from doctors and laboratories and the results of the annual survey of HIV testing conducted among the laboratories throughout the country. A dataset on clients from anonymous Voluntary Testing and Counselling (VCT) network was also used. The activities of the VCT are coordinated by the National AIDS Center, which anonymously collects epidemiological and behavior data on people who come for testing. RESULTS: In 2020 there were 934 HIV cases newly diagnosed in Poland (diagnosis rate 2.44 per 100,000), including 100 among non-Polish citizens. The number of newly detected HIV infections decreased by 39.9% compared to the previous year and was lower by 26.9% compared to the median in 2014-2018 years. Similarly, among VCT clients, number of HIV diagnoses decreased by 42%, from 536 in 2019 to 308 in 2020 year, what was connected with 44% decreased in number of HIV tests. The total number of AIDS cases was 50 (incidence 0.13 per 100,000). The HIV infection was most often detected in the age group between 30 and 39 (35.7%) and among men (83.5%). Among cases with known transmission route, 68.5% concerned among men who had sexual contact with men (MSM). The percentage of AIDS cases diagnosed at the same time with HIV diagnosis decreased by almost 14 percent points in comparison to 2019 (from 75.8% to 62% of all incident AIDS cases). CONCLUSION: In 2020, the number of newly detected HIV infections decreased compared to the previous year, however, this is not only due to a decrease in the number of infections, but rather to a lack of continuity in the diagnostic and reporting system during the COVID-19 pandemic, as indicated by a smaller number of tests and greater delays in data reporting. Due to the chronic course of HIV infection, a full assessment of the impact of the COVID-19 pandemic will be possible in the future.

Changes in HIV testing trends in Poland during COVID-19 pandemic.

INTRODUCTION: At the beginning of COVID-19 pandemic, due to lockdown, limited mobility, as well as changes in the activity profile of some laboratories, the restriction also applied to access to various screening tests, including HIV screening tests. AIM: The aim of the study was to assess HIV testing trend during COVID-19 pandemic in laboratories in Poland and its comparison to the preceding years, with special focus on testing in the network of Voluntary Testing and Counselling (VCT) sites serving population with higher behavior risk, which increase the possibility of HIV infection. MATERIAL AND METHODS: Analysis of the changes in HIV tests number was based on the results of the annual survey of HIV tests conducted among the laboratories throughout the country. The questionnaire included data on screening and positive tests by testing site type, age group and gender. In addition, we extracted data collected in comprehensive National AIDS Centre database, based on epidemiological and behavior data collected by VCT on people who come for testing. RESULTS: There are approximately 400,000 HIV tests annually run in general population in last years. COVID-19 pandemic, which occurred in beginning of 2020 did not have a huge impact on HIV test number among these population, because there was observed 1% decreased. Pandemic COVID-19, due to few lockdown reduced the HIV tests number among VCT clients - population with higher HIV risk infection. Tests number decreased by 44% compare to previous year, due to temporal closed of these centres. Data analysis shows that due to the pandemic, the structure of the surveyed people changed, especially in terms of age and gender, and the place where the study was performed. CONCLUSION: We confirmed low HIV testing rates in general population and low positivity rate over the studied period. The positivity rate was higher in the testing site network targeting individuals engaging in high risk behaviors. Changes observed in HIV testing trends in recent years have been affected by the COVID-19 pandemic.

Sex and age differences among patients with acromegaly.

INTRODUCTION: Acromegaly is a chronic, slowly progressive disorder caused mostly by growth hormone (GH)-producing pituitary neuroendocrine tumors (PitNETs). Recently, the associations between sex and age at the time of diagnosis and the course of acromegaly have been a focus of debate. OBJECTIVES: The aim of our study was to evaluate the association between sex and age at the time of diagnosis of acromegaly and the clinical features, biochemical status, severity of the disease, and comorbidities. PATIENTS AND METHODS: This was a single­center study conducted in a group of consecutive patients with acromegaly and no family history of PitNETs. The participants were divded into 2 subgroups according to sex (male, female) and 3 subgroups according to age at the time of diagnosis: i) younger (≤40 years), ii) middle­aged (41-59 years), and iii) elderly patients (≥60 years). RESULTS: Our study included 101 patients (41 men, 60 women) who met the eligibility criteria. The mean (SD) age at the time of diagnosis was 47.3 (14.1) years and the median diagnostic delay was 5 years (interquartile range, 3-10). Age at the time of diagnosis and diagnostic delay were not statistically different in men and women. Levels of insulin­like growth factor 1 (IGF­1) above the upper limit of age­adjusted normal range (%ULN IGF­1) were greater in men than in women (mean [SD], 174.8% [98.9%] vs 109.4% [66.6%]; P = 0.002), while there was no significant difference in terms of %ULN IGF­1 between the age groups. Median basal and nadir GH levels did not differ between the sexes. Men presented with hypogonadism more frequently than women (54% vs 26%; P = 0.005). Hyperprolactinemia, hypogonadism, and macroadenoma were more frequently observed in the younger patients than in the middle­aged and elderly individuals (all P <0.05). CONCLUSIONS: According to our results, hypogonadism and greater IGF­1 values were more frequently observed in men with acromegaly. Hyperprolactinemia, hypogonadism, and macroadenoma were more frequent in patients with acromegaly aged 40 years or younger.

Metabolic Disorders/Obesity Is a Primary Risk Factor in Hidradenitis Suppurativa: An Immunohistochemical Real-World Approach.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory, potentially scarring disease of the hair follicle, affecting the apocrine gland-bearing skin areas. The major comorbid disorders associated with the occurrence or the aggravation of the disease are obesity and smoking. Numerous efforts to dissociate these factors led to controversial results. OBJECTIVES: To assess the importance of metabolic disorders/obesity, smoking/environmental toxins, and inflammation in HS by utilizing the differential expression of major relevant protein markers in lesional skin of obese/smoking versus non-obese/non-smoking HS patients. METHODS: Lesional skin specimens deriving from two groups of HS patients (BMI >30 and smokers, n = 12 vs. BMI <30 and non-smokers, n = 10) were stained with antibodies raised against irisin, PPARγ, and IGF-1R, which correlate with metabolic disorders/obesity, EGFR and AhR, associated with smoking, and IL-17, IL-17R, and S100A8, as markers of inflammation. RESULTS: Metabolic disorders/obesity-related markers exhibited marked differential expression between the two groups, while smoking-associated markers a limited one. IL-17R expression was stronger in obese/smokers, and S100A8 staining exhibited intense strong immunoreactivity in both groups without significant difference. CONCLUSIONS: The notion that obesity plays a role in HS development appears to be supported by the prominent regulation of the associated lesional biomarkers. Tobacco smoking might contribute less to HS than previously suspected.

Hyperinsulinemic Hypoglycemia in Three Generations of a Family with Glucokinase Activating Mutation, c.295T>C (p.Trp99Arg).

Familial Hyperinsulinemic Hypoglycemia (FHH) is a very rare disease with heterogeneous clinical manifestations. There are only a few reports of heterozygous activating mutations of glucokinase (GCK) attributable to FHH, with no reports describing effects in the course in pregnancy with affected mother/affected child. A large kindred with FHH and GCK:c.295T>C (p.Trp99Arg) pathogenic variant was identified in which four family members from three generations were affected. The clinical follow up in one clinical center lasted up to 30 years, with different times of diagnosis ranging from neonate period to adulthood. The severity of hypoglycemia was mild/severe and fasting was the trigger for hypoglycemia. Response to diazoxide varied from good, in the neonate, to moderate/poor, in childhood/adulthood; however, this was biased by poor compliance. Treatment with somatostatin analogues was discontinued due to side effects. Over time, patients developed clinical adaptation to very low glucose levels. During pregnancy, episodes of severe hypoglycemia in the first trimester were observed, which responded very well to steroids. The clinical course of the GCK:c.295T>C (p.Trp99Arg) mutation varied in the same family, with the development of clinical adaptation to very low glucose levels over time. Treatment with steroids might prevent hypoglycemia during pregnancy in an affected mother.

Increasing integrated testing in community settings through interventions for change, including the Spring European Testing Week.

BACKGROUND: Maximising access to testing by targeting more than one infection is effective in identifying new infections in settings or populations. Within the EU funded Joint Action INTEGRATE, this paper examined the feasibility and impact of expanding integrated testing for HIV, hepatitis C (HCV), chlamydia, gonorrhoea and/or syphilis in four community-based pilots through targeted interventions in Croatia, Italy and Poland and the Spring European Testing Week since community settings are key in detecting new infections and reaching key populations. METHODS: Pilots led by local INTEGRATE partners prioritised testing for other infections or key populations. The Croatian pilot expanded testing for men who have sex with men to syphilis, chlamydia and gonorrhoea. Italian partners implemented a HIV and HCV testing/information event at a migrant centre. A second Italian pilot tested migrants for HIV and HCV through outreach and a low-threshold service for people who use drugs. Polish partners tested for HIV, HCV and syphilis among people who inject drugs in unstable housing via a mobile van. Pilots monitored the number of individuals tested for each infection and reactive results. The pilot Spring European Testing Week from 18 to 25 May 2018 was an INTEGRATE-driven initiative to create more testing awareness and opportunities throughout Europe. RESULTS: The Croatian pilot found a high prevalence for each syphilis, chlamydia and gonorrhoea respectively, 2.1%, 12.4% and 6.7%. The Italian migrant centre pilot found low proportions who were previously tested for HIV (24%) or HCV (11%) and the second Italian pilot found an HCV prevalence of 6.2%, with low proportions previously tested for HIV (33%) or HCV (31%). The Polish pilot found rates of being previously tested for HIV, HCV and syphilis at 39%, 37%, and 38%, respectively. Results from the Spring European Testing Week pilot showed it was acceptable with increased integrated testing, from 50% in 2018 to 71% in 2019 in participants. CONCLUSIONS: Results show that integrated testing is feasible and effective in community settings, in reaching key populations and minimising missed testing opportunities, and the pilots made feasible because of the European collaboration and funding. For sustainability and expansion of integrated community testing across Europe, local government investment in legislation, financial and structural support are crucial.

Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family.

Multiple neuroendocrine neoplasia type 1 (MEN1) is a rare genetic disorder with an autosomal dominant inheritance, predisposing carriers to benign and malignant tumors. The phenotype of MEN1 syndrome varies between patients in terms of tumor localization, age of onset, and clinical aggressiveness, even between affected members within the same family. We describe a heterogenic phenotype of the MEN1 variant c.781C>T (LRG_509t1), which was previously reported only once in a family with isolated hyperparathyroidism. A heterozygous missense variant in exon 4 of the gene was identified in the sequence of the MEN1 gene, i.e., c.781C>T, leading to the amino acid change p.Leu261Phe in a three-generation family. In the screened family, 5/6 affected members had already developed hyperparathyroidism. In the index patient and two other family members, an aggressive course of pancreatic neuroendocrine tumor (insulinoma and non-functioning neuroendocrine tumors) with dissemination was diagnosed. In the index patient, late diagnosis and slow progression of the disseminated neuroendocrine tumor have been observed (24 years of follow-up). The very rare variant of MEN1, LRG_509t1 c.781C>T /p.Leu261Phe (LRG_509p1), diagnosed within a three-generation family has a heterogenic clinical presentation. Further follow-up of the family members should be carried out to confirm the spectrum and exact time of clinical presentation.

Genetics of Acromegaly and Gigantism.

Growth hormone (GH)-secreting pituitary tumours represent the most genetically determined pituitary tumour type. This is true both for germline and somatic mutations. Germline mutations occur in several known genes (AIP, PRKAR1A, GPR101, GNAS, MEN1, CDKN1B, SDHx, MAX) as well as familial cases with currently unknown genes, while somatic mutations in GNAS are present in up to 40% of tumours. If the disease starts before the fusion of the epiphysis, then accelerated growth and increased final height, or gigantism, can develop, where a genetic background can be identified in half of the cases. Hereditary GH-secreting pituitary adenoma (PA) can manifest as isolated tumours, familial isolated pituitary adenoma (FIPA) including cases with AIP mutations or GPR101 duplications (X-linked acrogigantism, XLAG) or can be a part of systemic diseases like multiple endocrine neoplasia type 1 or type 4, McCune-Albright syndrome, Carney complex or phaeochromocytoma/paraganglioma-pituitary adenoma association. Family history and a search for associated syndromic manifestations can help to draw attention to genetic causes; many of these are now tested as part of gene panels. Identifying genetic mutations allows appropriate screening of associated comorbidities as well as finding affected family members before the clinical manifestation of the disease. This review focuses on germline and somatic mutations predisposing to acromegaly and gigantism.

HIV infections and AIDS in Poland in 2019.

AIM OF THE STUDY: The aim of the study was to assess the epidemiological situation of newly diagnosed HIV infections, and AIDS cases, and death among AIDS cases in Poland in 2019 in comparison to the changes in preceding years. MATERIAL AND METHODS: Analysis of the epidemiological situation was based on reports of newly detected HIV cases and AIDS cases received from doctors and laboratories and the results of the annual survey of HIV testing conducted among the laboratories throughout the country. A dataset on clients from anonymous Voluntary Testing and Counselling (VCT) network was also used. The activities of the VCT are coordinated by the National AIDS Center, which collects epidemiological and behaviour data on people who come for testing. RESULTS: In 2019 there were 1,551 HIV cases newly diagnosed in Poland (diagnosis rate was 4.04 per 100,000), including 144 among non-Polish citizens. The frequency of newly detected HIV infections increased by 28.2% compared to the previous year and was higher by 21.4% compared to the median in 2013-2017 years. The total number of AIDS cases was 95 (incidence was 0.25 per 100,000) and 15 people died from AIDS disease (0.04 per 100,000 ). The HIV infection was most often detected in the age group between 30 and 39 (36%) and among men (85,1%). Among cases with known transmission route, 73.6% concerned among men who had sexual contact with men (MSM). The percentage of AIDS cases diagnosed at the same time with HIV diagnosis increased by almost 8 percent points in comparison to 2018 (from 73% to 81.1% of all incident AIDS cases). CONCLUSION: In 2019, the frequency of newly detected HIV infections increased compared to the previous year. All actions should be taken to provide medical care to people with newly detected HIV infection, including foreigners residing in Poland. Also HIV testing action should be promoted among total population. Initiatives should be taken to raise awareness of the risk of HIV infection and to disseminate methods of prevention of infection, especially among key populations. It is also advisable to integrate different data sources, the combination of which will allow to improve their quality, as well as reliable monitoring of key epidemiological indicators.

Acromegaly and late-onset primary hyperparathyroidism in a female with a rare MEN1 gene variant of yet undetermined clinical significance (p.Val167Ala).

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The Skin as a Mirror of Internal Disease: Comorbidities and Epidemiology of Acne Vulgaris and Adult Female Acne - A Cross-sectional Study and Current State of Knowledge.

Acne vulgaris is a common skin condition affecting an increasing number of adults and might be a clue to identifying systemic disease. Objective of this study is assessment of the demographic and clinical characteristic, including comorbidities, of patients with acne with a special focus on adult female acne (AFA). This cross-sectional study analyzed the medical records of 354 patients with acne (323 outpatients and 31 hospitalized). Data concerning patient age, sex, lesions morphology and distribution on body areas, duration of the disease, Body Mass Index, and dermatologic and systemic comorbidities were collected. 61% of all patients were female, 45.37% of women were classified as AFA. The median age of patients with acne was 24 years and 32.5 years for AFA. The face was the most commonly affected area; patients with AFA had lesions on their back than less frequently non-AFA. Predominant eruptions were pustules and papules. 38.7% of patients had concomitant systemic chronic disease, 15.25% had an endocrinologic disorder, and 6.21% had thyroid gland dysfunction. Women with AFA had endocrinologic disorders more frequently (P=0.002), whereas cutaneous signs of hyperandrogenism were observed less frequently than in the non-AFA group (P=0.034). AFA possess distinct clinical features and it should raise suspicion towards possible underlying endocrinologic disturbance.