Hyperplasia In Adults Research Articles

Sudden cardiac death and thymic hyperplasia in adults: myth or reality? A case report

BackgroundSudden cardiac death is a major public health concern. The incidence of sudden cardiac death in young adults remains unclear and is generally underestimated.Case presentationThis is a case report of a 24-year-old man with a silent pathological history, who suddenly collapsed in a restaurant during dinner with his workmates. Autopsy and ancillary examination revealed focal atrioventricular node fibrosis and thymic hyperplasia.ConclusionsThymic hyperplasia has been considered a cause of sudden death in the past century. The mode of death was explained through nosographic entities such as status lymphaticus or thymic asthma, which are currently consigned to history books. Nevertheless, recent studies have sought to determine the relationship between thymic hyperplasia and sudden unexpected deaths in adults. Moreover, isolated fibrosis of the atrioventricular node is a rare condition that can remain undiagnosed even after a full autopsy. This report aims to provide a concise review of the existing literature concerning sudden cardiac death and discuss the so-called “thymic death” theory, which is now considered a myth. Was the finding of thymic hyperplasia and atrioventricular node fibrosis a coincidence? Should the myth surrounding “thymic death” be re-examined?

Singularities of the undertreatment of congenital adrenal hyperplasia in adults

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Manganese‐Induced Central Precocious Puberty (MnPP) Increases Hormone Receptor Expression (HR+) in Proliferating Mammary Epithelial Cells in Adult Female Rats

In the developing mammary gland (MG), hormone receptor expressing (HR+) cells very rarely proliferate. The actions of estrogen (E2) and progesterone (P4) on ductal morphogenesis are paracrine and require mediators to stimulate growth of HR− adjacent cells. However, in premalignant and invasive human breast lesions, proliferating cells are HR+. Thus, a dramatic change occurs in MG cell fate with a suspected increased sensitivity to steroid mediated growth. Studies have theorized that early pubertal onset alters MG cell fate increasing the risk of breast cancer later in life. Yet, it is not known if early puberty can cause this conversion to HR+ proliferating MG cells and if this phenotype is sustained in the adult gland. We previously demonstrated that manganese‐induced precocious puberty (MnPP) accelerates E2‐regulated MG development, resulting in sustained proliferation of MG epithelial cells and adult hyperplasia. In the current study, we characterized the normal distribution of HR+ proliferative cells in the MG of prepubertal and adult female rats, determined if MnPP could increase this population and identify cellular proteins that may be involved. Sprague Dawley female rats were exposed daily to 10mg/kg manganese chloride (MnCl2) or saline (control) via gastric gavage from post‐natal day (PND) 12 to PND 30. MGs were collected on PNDs 30 and 120. Using dual labeling immunofluorescence (IF), only 2% of total MG epithelial cells co‐express HRs (E2 or P4 receptor) and the proliferative marker PCNA in the prepubertal MG. As expected, MnPP significantly (p<0.01) increased the percentage of proliferating (PCNA+) MG cells. The percentage of proliferating cells co‐expressing progesterone receptor (PR+/PCNA+) increased by more than 2‐fold in MnPP females relative to controls at PND30 (p<0.01). The proportion of proliferating HR+ cells (ER+/PCNA+ or PR+/PCNA+) remained elevated in PND120 glands of MnPP females compared to controls (p<0.001). Western blot analysis revealed a significant switch in expression levels of the cell cycle regulator, p27, and the mitotic stimulator EREG in MGs that corroborated changes in PR+ proliferation between PND 30 and 120. Furthermore, histologically normal human breast tissue adjacent to ductal carcinoma in situ (DCIS) from The Human Protein Atlas show ER and PR expression similar to expression levels observed in our MnPP rat MGs at PND120. Collectively, these data show that MnPP results in persistent HR expression in proliferating MG cells. Thereby possibly sensitizing it to the hormonal milieu and making the MG more responsive to steroid mediated growth.Support or Funding InformationThis work was supported by NIEHS grant ESO13143 awarded to WLD and NIGMS grant 1R25GM100866 awarded to RKD.

The Evaluation of Banana Flower Stamens Extract on Prevention of Benign Prostatic Hyperplasia in Adults

The Evaluation of Banana Flower Stamens Extract on Prevention of Benign Prostatic Hyperplasia in Adults

ЧИ Є ВРОДЖЕНА ГІПЕРПЛАЗІЯ НАДНИРНИКІВ ЧЕРЕЗ 21-ГИДРОКСИЛАЗНУ НЕДОСТАТНІСТЬ ОМАНЛИВОГО ЗАХВОРЮВАННЯ? УПРАВЛІННЯ ТА ДИФЕРЕНЦІЮВАННЯ СИНДРОМУ У ДОРОСЛИХ

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase defi ciency is one of the most common autosomal recessive hereditary diseases. The lack of cortisol synthesis leads to excessive stimulation of the adrenal glands by adrenocorticotropic hormone (ACTH). Moreover the impairment of cortisol synthesis results in adrenal hyperplasia and excessive androgen synthesis. Congenital adrenal hyperplasia is characterised by a considerable correlation between the genotype and the phenotype with the type of CYP21A2 gene mutation affecting the severity of 21-hydroxylase defi ciency. The clinical manifestations of congenital adrenal hyperplasia in adults result from adrenocortical insuffi ciency, hyperandrogenism, and the adverse effects of glucocorticosteroids, which are used for the treatment of the syndrome. Non-classic congenital adrenal hyperplasia may sometimes be asymptomatic. Patients with classic congenital adrenal experience a wide variety of symptoms, including obesity, hyperinsulinaemia, insulin resistance, and hyperleptinaemia. These abnormalities promote the development of metabolic syndrome and its sequelae, including endothelial dysfunction, and cardiovascular disease. The symptoms are more often seen in patients suffering from congenital adrenal hyperplasia syndrome than in the general population. Long-term glucocorticosteroid treatment is also a known risk factor for many diseases, for instance osteoporosis. Patients with congenital adrenal hyperplasia require constant monitoring of biochemical parameters (17a-hydroxyprogesterone [17-OHP] and androstenedione), clinical parameters (Body Mass Index, waist circumference, blood pressure, glucose, and lipids), and bone mineral density by densitometry. Appropriate treatment of congenital adrenal hyperplasia is extremely important. The principal goal of treatment in adults with CAH is to improve quality of life, ensure that they remain fertile, reduce the manifestations of hyperandrogenisation in females. Furthermore it is key to reduce the adverse effects of medicaments used for therapy of the CAH syndrome. Patients with classic congenital adrenal hyperplasia require treatment with glucocorticosteroids and, in cases of salt wasting, also with a mineralocorticosteroid. Radical measures, such as bilateral adrenalectomy, are very rarely needed. Asymptomatic patients with non-classic congenital adrenal hyperplasia require monitoring; treatment is not always necessary. Medical care for patients suffering from congenital adrenal hyperplasia should be provided by reference centres, as the management of such patients requires collaboration between an endocrinologist, diabetologist, gynaecologist, andrologist, urologist, and psychologist.

A model for measuring the health burden of classic congenital adrenal hyperplasia in adults.

Patients with classic congenital adrenal hyperplasia (CAH) have poor health outcomes. In the absence of a comprehensive observational study, this manuscript provides a model to estimate the lifetime disease burden of adults with classic CAH. The model, built in Excel, comprises subdomains addressing the health consequences of CAH and synthesises evidence from clinical and epidemiological studies on health outcomes. The model estimates that adults with classic CAH will implement 'sick day rules' (doubling or tripling glucocorticoid and/or use of parenteral therapy) 171 times over their lifetime and attend hospital for adrenal crisis on 11 occasions. In a population of 1000, over 200 will die of a condition complicated by adrenal crisis resulting, on average, in a loss of 7 years of life. Patients with CAH may also suffer from excess CVD events. Treatment with glucocorticoids almost doubles the risk of bone fractures in patients with CAH compared to the general population, leading on average to an additional 0·8 fractures per patient with CAH over their lifetime. The disease burden model highlights gaps in evidence, particularly regarding intensity of care and adrenal crisis, and the relationship between control of CAH and risks of CVD, osteoporosis, diabetes and infertility. The model can be used for research on the impact of new clinical pathways and therapeutic interventions in terms of clinical events and cost.

Imaging features of poorly controlled congenital adrenal hyperplasia in adults.

Congenital adrenal hyperplasia (CAH) is a genetic autosomal recessive condition most frequently as a result of a mutation in the 21-hydroxylase enzyme gene. Patients with poorly controlled CAH can manifest characteristic imaging findings as a result of adrenocorticotrophic hormone stimulation or the effects of cortisol precursor excess on various target organs. We present a spectrum of imaging findings encountered in adult patients with poorly treated CAH, with an emphasis on radiological features and their clinical relevance.

Limited Value of 18F-F-DOPA PET to Localize Pancreatic Insulin-Secreting Tumors in Adults with Hyperinsulinemic Hypoglycemia

Fluorine-18-L-dihydroxyphenylalanine positron emission tomography (18F-FDOPA PET) imaging is increasingly used in the workup of neuroendocrine tumors. It has been shown to be an accurate tool in the diagnosis of congenital hyperinsulinism, but limited information is available on its value in adult disease. OBJECTIVE, PATIENTS, AND DESIGN: The objective of this study was to review our experience with 18F-FDOPA PET imaging in six consecutive patients with hyperinsulinemic hypoglycemia (HH) (four solitary insulinomas, one diffuse beta-cell hyperplasia, one malignant insulinoma). 18F-FDOPA uptake was also evaluated in 37 patients (43 procedures) without HH or other pancreatic neuroendocrine tumors, which acted as a control group. Using visual analysis, 18F-FDOPA-PET proved positive in only one case (a multiple endocrine neoplasia type 1 related insulinoma). In diffuse beta-cell hyperplasia, the pancreatic uptake was similar to controls. In the patient with liver metastases, the extent of disease was underestimated. The pancreatic uptake was not statistically different between controls and hyperinsulinemic patients. The main limitation for identifying insulinomas or beta-cell hyperplasia in adults appears to be to the 18F-FDOPA uptake and retention in the whole pancreas. This drawback is potentially circumvented in focal hyperplasia in newborns due to a lower aromatic amino acid decarboxylase expression in the extralesional pancreatic parenchyma. 18F-FDOPA PET is of limited value in localizing pancreatic insulin secreting tumors in adult HH. Our results contrast with the referential study and require further analysis.

A Case of Congenital Cystic Adenomatoid Malformation of the Lng with Atypical Adenomatous Hyperplasia in Adult

Congenital cystic adenomatoid malformation (CCAM), which is classified into five types according to size and bronchial invasion, is a rare type of developmental anomaly of the lung. CCAM is occasionally accompanied by malignancy, such as bronchioloalveolar carcinoma (BAC) or rhabdomyosarcoma. As defined by the WHO, atypical adenomatous hyperplasia (AAH) is a non-invasive spread of atypical epithelial cells in single rows along the alveolar wall, within a lesion that is usually less than 5 mm in diameter. AAH was also regarded as a pre-invasive neoplasia, especially associated with BAC and adenocarcinoma. We report a case of type II CCAM with AAH in adults, with a review of the references.

Premedication With Carbidopa Masks Positive Finding of Insulinoma and β-Cell Hyperplasia in [18F]-Dihydroxy-Phenyl-Alanine Positron Emission Tomography

TO THE EDITOR: We read with interest the excellent and valuable article by Koopmans and colleagues concerning staging of carcinoid and islet cell tumors with [F]-dihydroxy-phenyl-alanine (FDOPA) and [C]-5-hydroxy-tryptophan (C-5-HTP) positron emission tomography/computed tomography (PET-CT). They reported that PET-CT using C-5-HTP as a tracer is a more sensitive method in the diagnosis of islet cell tumors compared with PET-CT using tracer F-DOPA (96% v 80%). However, we would like to raise concerns regarding that study’s use of carbidopa pretreatment before F-DOPA PET scanning in patients suspected of having islet cell tumor of the pancreas. We and others have recently shown that when studied without carbidopa pretreatment, F-DOPA PET is a highly sensitive method for localization of focal -cell hyperplasia in infants and insulinoma and -cell hyperplasia in adults. We are currently carrying out a prospective study to test the effect of carbidopa on pancreatic FDOPA uptake in patients with suspected islet cell tumor. So far, three consecutive patients have undergone F-DOPA PET-CT, both with and without premedication, and all have histological confirmation of the disease. Characteristics of the patients, the findings of different imaging methods, and histopathological data are shown in Table 1. In two out of three patients, insulinoma and -cell hyperplasia were observed in F-DOPA PET without carbidopa premedication but were fully masked when decarboxylation was prevented by carbidopa (Fig 1). In one study patient with insulinoma, both PET scans showed the lesions. The phenomenon behind this might be explained by the metabolites of F-DOPA. Oral premedication with carbidopa, an inhibitor of amino acid decarboxylase, improves the contrast in PET imaging by increasing the concentration and availability of F-DOPA and 3-Omethyl-6-[F]-fluoro-L-dopa and by reducing urinary radioactivity concentration. It has become a standard procedure in visualization of neuroendocrine tumors (NETs). A few studies have shown that the image quality improves markedly after pretreatment with carbidopa, as a result of equivalent metabolic pathways. In addition to the 6-fluorodopamine metabolite, F-DOPA is also the origin of many other metabolites such as 3-O-methyl-6[F]-fluoro-L-dopa, 6-fluoro-L-3,4-dihydroxyphenylacetic acid, and 6-fluorohomovanillic acid, as well as sulfated conjugates. When the amino acid decarboxylase pathway is blocked with carbidopa, the amount of metabolites changes. So far, the accumulation of these metabolites other than 6-fluorodopamine into various types of NETs is largely unknown. In conclusion, prevention of F-DOPA decarboxylation by means of carbidopa premedication totally prohibited accumulation of radioactivity into the disease focus in two out of three patients with histologically proven insulinoma and -cell hyperplasia. Our report is the first to demonstrate that imaging of islet cell tumors using PET and labeled amino acid precursors differs from imaging of other NETs. Therefore our recommendation is that until larger studies are available, carbidopa should not be given in F-DOPA PET imaging when islet cell tumor is suspected.

Identification of White Adipocyte Progenitor Cells In Vivo

The increased white adipose tissue (WAT) mass associated with obesity is the result of both hyperplasia and hypertrophy of adipocytes. However, the mechanisms controlling adipocyte number are unknown in part because the identity of the physiological adipocyte progenitor cells has not been defined in vivo. In this report, we employ a variety of approaches, including a noninvasive assay for following fat mass reconstitution in vivo, to identify a subpopulation of early adipocyte progenitor cells (Lin(-):CD29(+):CD34(+):Sca-1(+):CD24(+)) resident in adult WAT. When injected into the residual fat pads of A-Zip lipodystrophic mice, these cells reconstitute a normal WAT depot and rescue the diabetic phenotype that develops in these animals. This report provides the identification of an undifferentiated adipocyte precursor subpopulation resident within the adipose tissue stroma that is capable of proliferating and differentiating into an adipose depot in vivo.

Fluorine-18-l-Dihydroxyphenylalanine (18F-DOPA) Positron Emission Tomography as a Tool to Localize an Insulinoma or β-Cell Hyperplasia in Adult Patients

Fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET) is a promising method in localizing neuroendocrine tumors. Recently, it has been shown to differentiate focal forms of congenital hyperinsulinism of infancy. The current study was set up to determine the potential of 18F-DOPA PET in identifying the insulin-secreting tumors or beta-cell hyperplasia of the pancreas in adults. We prospectively studied 10 patients with confirmed hyperinsulinemic hypoglycemia and presumed insulin-secreting tumor using 18F-DOPA PET. Anatomical imaging was performed with computed tomography (CT) and magnetic resonance imaging (MRI). All patients were operated on, and histological verification was available in each case. Semiquantitative PET findings in the pancreas using standardized uptake values were compared to standardized uptake values of seven consecutive patients with nonpancreatic neuroendocrine tumors. By visual inspection of 18F-DOPA PET images, it was possible in nine of 10 patients to localize the pancreatic lesion, subsequently confirmed by histological analysis. 18F-DOPA uptake was enhanced in six of seven solid insulinomas and in the malignant insulinoma and its hepatic metastasis. Two patients with beta-cell hyperplasia showed increased focal uptake of 18F-DOPA in the affected areas. As compared to CT or MRI, 18F-DOPA PET was more sensitive in localizing diseased pancreatic tissue. 18F-DOPA PET was useful in most patients with insulinoma and negative CT, MRI, and ultrasound results. In agreement with previous findings in infants, preoperative 18F-DOPA imaging seems to be a method of choice for the detection of beta-cell hyperplasia in adults. It should be considered for the detection of insulinoma or beta-cell hyperplasia in patients with confirmed hyperinsulinemic hypoglycemias when other diagnostic work-up is negative.

Re: “Islet Hyperplasia in Adults: Challenge to Preoperatively Diagnose Non‐insulinoma Pancreatogenic Hypoglycemia Syndrome”

Re: “Islet Hyperplasia in Adults: Challenge to Preoperatively Diagnose Non‐insulinoma Pancreatogenic Hypoglycemia Syndrome”

Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation.

Although glucagon (GLU) plays a pivotal role in glucose homeostasis, its role in the regulation of fetal growth and maturation is poorly understood. These issues were examined in a line of mice with a global deletion of the GLU receptor (Gcgr-/-), which are characterized by lower blood glucose levels and by alpha- and delta-cell hyperplasia in adults. Ablation of Gcgr was deleterious to fetal survival; it delayed beta-cell differentiation and perturbed the proportion of beta- to alpha-cells in embryonic islets. In adults, the mutation inhibited the progression of alpha-cells to maturity, affected the expression of several beta-cell-specific genes, and resulted in an augmentation of the alpha-, beta-, and delta-cell mass. This increase was due to an augmentation in both islet number and in the rate of proliferation of cells expressing GLU or insulin. These findings suggest that GLU participates in a feedback loop that regulates the proportion of the different endocrine cell types in islets, the number of islets per pancreas, and development of the mature alpha-cell phenotype.

Islet Hyperplasia in Adults: Challenge to Preoperatively Diagnose Non‐Insulinoma Pancreatogenic Hypoglycemia Syndrome

Pancreatic hyperfunctional islet hyperplasia in adults has been more and more frequently described in the literature. Postprandial neuroglycopenia, a negative normal fasting test, negative pancreatic imaging results, and positive intra-arterial calcium stimulation of serum insulin are characteristic. In affected patients the term non-insulinoma pancreatogenic hypoglycemia syndrome (NIPHS) was proposed. MATERIALS AND METHODS/PATIENTS: We also encountered fasting hypoglycemia in such patients and therefore evaluated clinical and biochemical data in patients with NIPHS (n = 11), patients with insulinoma (n = 70), and patients in whom hypoglycemia was ruled out (n = 70). Patients with NIPHS were younger (median age: 41 years; range: 18-66) and mostly non-obese (median body mass index/BMI: 22.2 kg/m2; range: 19-39) compared with patients with an insulinoma (median age: 50 years; median: BMI 26.1 kg/m2). During an oral glucose tolerance test (OGTT) followed by a standard fasting test, neuroglycopenia was observed postprandially with a mean minimal blood glucose level of 36 +/- 9 mg/dl in 7 out of 11 patients. Spontaneous hypoglycemia during the fast was 38 +/- 5 mg/dl in 8 out of 11 patients. The corresponding insulin levels were 9.2 +/- 9.8 mU/l (OGTT) and 6.8 +/- 5.4 mU/l (fasting), significantly lower than in patients with insulinoma (P < 0.001), but not different from patients without hypoglycemia (P = 0.05). After pancreatic resection 8 patients (73%) were cured with enduring euglycemia. Pathohistological islet abnormalities with hyperplasia, hypertrophy, and microadenomatosis were confirmed in all patients. In patients with postprandial and/or fasting neuroglycopenia NIPHS may be suspected when insulin levels are low but inadequately suppressed and localization studies failed to show a distinct pancreatic tumor.

Congenital adrenal hyperplasia in adults: a review of medical, surgical and psychological issues

Our knowledge of the experience of adults with congenital adrenal hyperplasia (CAH) as they pass through life is only now emerging. In this review we gather medical, surgical and psychological literature pertaining to adults with CAH and consider this alongside practical experience gained from a dedicated adult CAH clinic. There is increasing awareness for the need for multidisciplinary teams who have knowledge of CAH particularly with respect to gynaecological surgery and clinical psychology for women and testicular function in men. Routine management of CAH comprises adjustment of glucocorticoid and mineralocorticoid treatment according to individual needs balancing biochemical markers, compliance and long term risks. Bone density is one such long term concern and is not greatly reduced in most individuals with CAH. More recently, attention has turned to cardiovascular risk factors and catecholamine deficiency in adults with CAH. Women with CAH require access to an experienced gynaecologist, specialised pregnancy care and psychosexual support. The very low fertility rates for women with CAH previously reported appear to be improving with time. Men with CAH are often lost to follow up and therefore miss out on surveillance for hypogonadism either through the effect of adrenal rests of from suppression of gonadotrophins resulting in a high prevalence of oligospermia.

Islet cell hyperplasia in adults – a not so rare cause of pancreatogenic non-insulinoma hypoglycemia

Islet cell hyperplasia in adults has become better understood since Service et al. published such patients (JCEM 1999, Surgery 2000) and proposed the term pancreatogenic non-insulinoma hypoglycemia. Preoperative diagnostic criteria, however, remain to be established. We report 9 patients diagnosed since 1994, in whom an insulinoma was excluded or not found during surgery. Severe mostly postprandial neuroglycopenic attacks within 2–6 hours were evident in 7 female and 2 male patients (age 42 (18–68 years), BMI 22.0 (19.1–39.4kg/m2). The results (median, range) of an extended oral glucose load were compared to 70 patients with a proven insulinoma (* p<0.05).

Focal thymic hyperplasia in an adult: Report of a case

We report herein an unusual case of a 35-year-old Japanese man who underwent thoracotomy for a mass in the mediastinum which was found to be a well circumscribed localized tumor within the thymus. Focal thymic hyperplasia in adults is extremely rare and the clinicopathological features of this case were particularly interesting and posed great difficulty in establishing a diagnosis.

Benign thymic enlargement in adults after chemotherapy: CT demonstration.

Serial computed tomographic (CT) scans of 200 patients with malignant testicular teratomas were reviewed. Of the 200 patients, 120 were treated with chemotherapy for metastatic disease; 80 patients with no evidence of metastases (stage I disease) received no treatment and served as a control group. CT was performed at regular intervals for ongoing follow-up in both groups. Thymic enlargement occurred 3-14 months after initiation of treatment in 14 of the 120 patients (11.6%) who received chemotherapy but in only one patient in the control group. Histologic examination in one patient who received chemotherapy revealed that the thymic enlargement represented true hyperplasia. Thirteen of the 14 patients (93%) with thymic enlargement after chemotherapy were well and disease free on mean follow-up of 45 months, compared with 78% of the group that did not show thymic enlargement after chemotherapy (P less than .02). Rebound thymic hyperplasia in adults after chemotherapy for metastatic testicular teratoma may be a good prognostic feature and should be considered when an anterior mediastinal mass develops after chemotherapy for metastatic malignancy.

Congenital Adrenal Hyperplasia in Adults

Congenital Adrenal Hyperplasia in Adults