2007 Nov. 17(11):2804-9. Luster M, Karges W, Zeich K, Pauls S, Verburg FA, Dralle H, et al. Approximately 10% occur in children. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. In 1852, Nelson was the first to report having viewed spermatic particles in ascaris ovum: "the present research appears to be the first in which the fact of the penetration of the spermatozoid in the ovum has been clearly seen and established" (Nelson, 1852). Although the biological sciences have unarguably demonstrated that the development of a new human being begins with fertilization, several countries have questioned that the life of an embryo before implantation be considered that of a new human being, deserving of respect as such. 1997, Fiddler et al. (2011). Either there are different types of homosexuality. 324, Throsby, K, Gill, R 2004, '"it's different for men": masculinity and IVF', LSE Research Online, Men and Masculinities, vol. In 1827, the embryologist Kart Ernst Von Baer discovered the ovum, first of a dog and then in other mammals. [25] Although pheochromocytomas are rare, making the diagnosis is critical because the malignancy rate is 10%, pheochromocytomas may be associated with a familial syndrome, they may precipitate life-threatening hypertension, and the patient may be cured completely with their removal. [87] On the other hand, growth hormone or aspirin as adjunctive medication in IVF have no evidence of overall benefit.[32]. Gonadectomy does not influence orientation nor does adult treatment with androgens and estrogens. This site also contains a predictor tool.[15]. Sex steroids (testosterone, estradiol, progesterone) are present in the human plasma in concentrations similar to those observed in other mammals. [QxMD MEDLINE Link]. is obviously more difficult to answer for a variety of reasons, such as the intrinsic difficulties in assessing in a reliable manner the sexual orientation of a subject, the long latency between embryonic endocrine events potentially controlling sexual orientation and its overt manifestation in adulthood, and finally, the complete impossibility for ethical reasons of manipulating the process. J Clin Endocrinol Metab. Differential stress induced c-Fos expression and identification of region-specific miRNA-mRNA networks in the dorsal raphe and amygdala of high-responder/low-responder rats. [Links], GADELLA BM, EVANS JP (2011) Membrane fusions during Mammalian fertilization. Drugs and medications are not covered under this Program, along with psychologist or social worker counselling, storage and shipping of eggs, sperm or embryos, and the purchase of donor sperm or eggs. [QxMD MEDLINE Link]. The invention of the microscope by Zacharias Jansen at the end of the 16th century was decisive for the advance of knowledge about the process of reproduction. The phylogenetic perspective was thus a central assumption, more or less implicit. J Clin Endocrinol Metab. [111][112] Indeed, there are serious concerns about the overuse of treatments, for instance Dr Sami David, a fertility specialist, has expressed disappointment over the current state of the industry, and said many procedures are unnecessary; he said: "It's being the first choice of treatment rather than the last choice. Then I discuss to what extent these principles could also determine sexual differentiation of brain and behavior in humans and finally review evidence derived from epidemiological and clinical studies, suggesting that sexual orientation is a sexually differentiated behavioral feature that is most likely influenced, like other sexually differentiated features, by the prenatal hormonal environment. play behavior) and that this in turn could condition the development of sexual orientation (75, 76). pp:270. These processes depend on the activity of several epigenetic enzymes, among which DNA methyltransferases (DNMTs) and TETs are prominent. Wild Duck Review Vol. Join Jose in exploring these excellent and helpful maps. 1983 Dec. 58(12):802-4. Hum. Approximately 10% of pheochromocytomas and 35% of extra-adrenal pheochromocytomas are malignant. 37(3):484-93. The initial focus of these studies was on the hypothalamicpituitaryadrenal (HPA) axis, for several reasons. There are also private clinics that offer the treatment for a fee. This vision fits very well with the hylemorphic theory of the four causes (final, efficient, formal and material), which explains movement. Monday, November 7 at 7PM MST January 18, 2013. The discovery of the nucleus, of chromosomes, the works of Mendel on the inheritance of maternal and paternal characteristics and the fact that all the cells of a species have the same number of chromosomes were central milestones in the history of genetics. In some cases, these symptoms were associated with altered levels of DNA methylation 60 years later (Heijmans et al., 2008). Eisenhofer et al found that pheochromocytomas associated with VHL typically produce norepinephrine only, while those associated with MEN 2 and NF1 typically produce both epinephrine and norepinephrine. Among mice exposed to stress during early, mid and late gestation, male F1 with early gestation prenatal stress exposure demonstrated behavioral indicators of stress responsivity and anhedonia, as well as alterations in GR and corticotrophinreleasing factor (CRF) expression and increased HPA axis responsivity, with corresponding alteration in CRF and nr3c1 gene methylation159. As women get older, they are more likely to develop conditions such as gestational diabetes and pre-eclampsia. Some countries have banned or otherwise regulate the availability of IVF treatment, giving rise to fertility tourism. Butz JJ, Weingarten TN, Cavalcante AN, et al. Manipulacin gentica de seres humanos. The results remain incomplete and sometimes conflicting, perhaps because only one route of transmission is usually considered at a time (e.g., maternal stress during pregnancy, paternal stress before mating). Measurements of plasma methoxytyramine, normetanephrine, and metanephrine as discriminators of different hereditary forms of pheochromocytoma. Ann. [QxMD MEDLINE Link]. Nabu Press. [QxMD MEDLINE Link]. Furthermore, a clustering analysis of clinical selfreport scales revealed that maternal and paternal PTSD were associated with different clinical indicators as well. 35:457-462. New York, ", "Of course a deaf couple want a deaf child", "Winston: IVF clinics corrupt and greedy", "Is In Vitro Fertilization Being Overused? Monday - Friday US MT, Telephone: 505-982-8732 )", "Tennessee Seeking To Ban IVF For Unmarried Individuals", "Russell D. Knight, Frozen Embryos and Divorce in Illinois", "Reproductive Rights and Access to Reproductive Services for Women with Disabilities", 10.1001/journalofethics.2016.18.4.msoc1-1604, "Fertility and disability - the additional challenges faced during IVF", "Considering Decision Making and Sexuality in Menstrual Suppression of Teens and Young Adults with Intellectual Disabilities", 10.1001/journalofethics.2016.18.4.ecas2-1604, "Should older women be offered in vitro fertilisation? 2003 Sep. 21(9):1703-7. This model is consistent with the growing body of literature above (see Yeshurun and Hannan, 2018 for an exhaustive review). The expression patterns of microRNAs (miRNAs), for example, have been studied in correlation with neuro- and psychopathologies, such as Alzheimers disease, Parkinsons disease, Huntingtons disease, multiple sclerosis, schizophrenia, addiction, autism, bipolar disorder and especially anxiety and depression (Baltimore et al., 2015; OConnor et al., 2016). Many subsequent studies have ratified our findings, in a way that has left me very satisfied to have contributed a grain of sand to this new knowledge at the world level". From in vitro fertilization (IVF) to fostering. (2014). [QxMD MEDLINE Link]. First, the DNA in paternal pronuclei undergoes rapid, active demethylation that is mediated by TET3 proteins, which spare only imprinting control regions (ICRs) and certain retrotransposons, such as intracisternal A particles. This idea was plausible, since the HPA axis is subject to early developmental programming50, 51. Piwi proteins and piRNAs in mammalian oocytes and early embryos. [47] When looking at long-term studies comparing women who received or did not receive IVF, there seems to be no correlation with increased risk of cardiac events. Much more is known today about the genetic and epigenetic processes in fertilization at the functional and molecular levels (Hemberger et al, 2009). The process involves monitoring and stimulating a woman's ovulatory process, removing an ovum or ova (egg or eggs) from her ovaries and letting sperm fertilise them in a culture medium in a laboratory. [5] A 2019 study that explores 10 adjuncts with IVF (screening hysteroscopy, DHEA, testosterone, GH, aspirin, heparin, antioxidants in males and females, seminal plasma, and PRP) suggests that until more evidence is done to show that these adjuncts are safe and effective, they should be avoided.[6]. Today, the scientific term "in vitro" is used to refer to any biological procedure that is performed outside the organism in which it would normally have occurred, to distinguish it from an in vivo procedure (such as in vivo fertilisation), where the tissue remains inside the living organism in which it is normally found. Stress, burnout and depression: a systematic review on DNA methylation mechanisms. Multivariate correction did not remove the significance of the association of birth defects and ICSI (corrected odds ratio 1.57), although the authors speculate that underlying male infertility factors (which would be associated with the use of ICSI) may contribute to this observation and were not able to correct for these confounders. Boston: Springer, 1998:25776, Transgenerational transmission of warrelated trauma. Finally, researchers from the laboratory of Roger Gorski (who had identified the SDN-POA of rats) at the University of California, Los Angeles (Los Angeles, CA) discovered in the human POA a nucleus they called interstitial nucleus of the anterior hypothalamus number 3 (INAH3) (a member of four cellular condensations of the POA) that was significantly larger in men than in women (44). Considering the panorama of human development, we add to the statement of Lodish and colleagues that this is not only an amazing feat, but also a wonderful and complex one. 2004. [Links], BURGESS J. Enhanced cognitive stimulation and physical activity reduce the response to adult stress, but only recently have the transgenerational effects of enrichment of the paternal environment on the offspring been evaluated. The concept of fetal programming refers to all of the adaptations to the intrauterine and maternal environment that shape the developing individual structurally and functionally (Swanson et al., 2009). In adulthood, the handled rats had altered basal and stressinduced corticosterone levels as well as higher GR sensitivity on the lowdose DST and greater GR number in the hippocampus77, 78, 79. More 'designer' options. [Links], AUSTRIACO N (2006). In rats and sheep, the size of a potentially homologous nucleus located in the same part of the POA (SDN-POA in rat, oSDN in sheep) is irreversibly determined by embryonic sex steroids. Strict limits on the number of embryos that may be transferred have been enacted in some countries (e.g. The SART summarised 20089 success rates for US clinics for fresh embryo cycles that did not involve donor eggs and gave live birth rates by the age of the prospective mother, with a peak at 41.3% per cycle started and 47.3% per embryo transfer for patients under 35 years of age. 2009 Feb. 192(2):450-4. The Constitution in Chile protects all human beings without discrimination, including the unborn. These cells are then evaluated for normality. Endocrine Society first to address rare adrenal-tumor care. St. Louis: Mosby. The moral case or ANT-derived plutipotent stem cell lines. Van Beneden and Boveri showed that for this to occur there had to be an equal contribution of chromosomes on the part of the ovum and the sperm and that each had to contribute half of the nucleus so that the new nucleus of the zygote maintained the number of chromosomes (Bovari, 1890; Van Beneden, 1883). Please confirm that you would like to log out of Medscape. Zucker KJ, Bradley SJ, Oliver G, Blake J, Fleming S, Hood J. [QxMD MEDLINE Link]. Endocrine Society (ENDO) Annual Meeting. A first, active demethylation takes place in parental gametes, right after fertilization. Within indirect epigenetics (WIE) encompasses all of the epigenetic changes that act synchronously on the developing individual. Multiple epidemiological studies have demonstrated a correlation between concordance of sexual orientation and genetic relatedness. JAMA. The decisions that we take with respect to human beings in development, particularly in relation to intervention against human embryos are today the subject of debate. The work of these developmental biologists established the genetic mechanisms that regulate the first stages of the development of the embryo of the fruit fly, but as the official announcement for the awarding of the Nobel Prize in 1995 indicated "the principles found in the fruit fly apply also to higher organisms, including man" http://nobelprize.org/medicine/laureates/1995/press.html. Neverthelessand for this same reasonthe epigenetic mechanisms that determine the womb cannot be neglected if they are demonstrated to mediate the transmission of information on the genetic expression of the developing organism (as discussed below). [Guideline] Lenders JW, Duh QY, Eisenhofer G, et al. [QxMD MEDLINE Link]. Stewart et al. Further, the prevalence of maternal and paternal contributions could depend on environmental conditions that could bring about, for example, paternal prevalence when the father is stressed or the predominance of maternal contribution under baseline conditions. Handling clutter in your physical space may help set the tone for decluttering emotional and mental spaces. [32], For women, intake of antioxidants (such as N-acetyl-cysteine, melatonin, vitamin A, vitamin C, vitamin E, folic acid, myo-inositol, zinc or selenium) has not been associated with a significantly increased live birth rate or clinical pregnancy rate in IVF according to Cochrane reviews. Direct proof of transgenerational epigenetic inheritance in humans remains lacking (van Otterdijk and Michels, 2016). The fertilised egg is passed to a special growth medium and left for about 48 hours until the egg consists of six to eight cells. [207], Individuals with disabilities are just as entitled to equitable access to fertility treatment such as IVF as individuals without disabilities. The ovine sexually dimorphic nucleus of the medial preoptic area is organized prenatally by testosterone. It is clear, however, that biological factors acting during prenatal life play a significant role in the control of sexual orientation and that homosexuality is not, for most people, the result only of postnatal experiences or a free choice. Recent results (Andolina et al., 2018) highlight the molecular mechanisms of this phenomenon, completing this model: when a stressor is encountered, miR-34 levels influence which coping strategy will be implemented through its inhibition of CRFR1 expression in DRN, which in turn regulates the balance in cortico-subcortical 5-HT/GABA activity that ultimately governs motivation and its behavioral output (Puglisi-Allegra and Andolina, 2015). Yehuda R, Schmeidler J, Wainberg M et al. Another key fact to clarify fertilization was the development of cellular theory by Matthias Schleiden (18041881) and Theodor Schwann (1810-1882). Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. On the other hand, the GnRH antagonist protocol has a lower risk of ovarian hyperstimulation syndrome (OHSS), which is a life-threatening complication.[63]. At the current time, the idea that epigenetic mechanisms underlie clinical observations in offspring of trauma survivors represents a hypothesis to be tested. The first studies on epigenetic forms of transmission focused on the effects of maternal care on the early stages of life, later considering nongenetic forms of developmental programming of fetal development during pregnancy. [Links]. [Links], EVANS JP, FLORMAN HM. In other clinical conditions, however, the prenatal endocrine environment may push sexual orientation in a direction opposite to the effects of postnatal social environment. A linkage between DNA markers on the X chromosome and male sexual orientation. Conditional models are preferred when defining the weight of a specific effector in a specific place and time (e.g., during paternal or maternal gametogenesis, zygote formation, the third week of gestation throughout the placenta, right after birth). Araujo-Castro M, Garcia Centeno R, Lopez-Garca MC, et al. High costs keep IVF out of reach for many developing countries, but research by the Genk Institute for Fertility Technology, in Belgium, claim to have found a much lower cost methodology (about 90% reduction) with similar efficacy, which may be suitable for some fertility treatment. [Links], SANTOS, M.J (2006). Many studies have analyzed the potential influence of steroids on human sexual orientation. Ender C., Krek A., Friedlnder M. R., Beitzinger M., Weinmann L., Chen W., et al.. (2008). 2013 Feb. 98(2):581-91. [50], A review in 2013 came to the result that infants resulting from IVF (with or without ICSI) have a relative risk of birth defects of 1.32 (95% confidence interval 1.241.42) compared to naturally conceived infants. Learn how and when to remove this template message, Embryo Ranking Intelligent Classification Assistant, North Coast Women's Care Medical Group v. Superior Court, Religious response to assisted reproductive technology, National Institute for Health and Care Excellence, Human Fertilisation and Embryology Authority, Royal College of Obstetricians and Gynaecologists, Pre-Conception and Pre-Natal Diagnostic Techniques Act, 1994, "Louise Brown: World's first IVF baby's family archive unveiled", "World's first test-tube baby Louise Brown has a child of her own", "After IVF, some couples get pregnant without help", "More than 8 million babies born from IVF since the world's first in 1978", "Clinical adjuncts in in vitro fertilization: a growing list", Fertility: assessment and treatment for people with fertility problems, "How long should we continue clomiphene citrate in anovulatory people? Bierer and M.J. Meaney for their comments and very careful review of this paper, and A. Ropes for assistance with manuscript preparation. Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress. An overview of methylation and demethylation mechanisms is provided in Figure Figure33. Or the effects of different biological factors interact to varying degrees in each individual, and it is only when several of these predisposing factors are combined that an homosexual orientation is observed. And with this, the use and destruction of pre-implantation human embryos has been justified. Does finger fat produce sex differences in second to fourth digit ratios? R. Soc. Maternal care behavior, the first environment for the newborn, effects several epigenetic changes in the offspring. Adrenocortical carcinomas and adrenal pheochromocytomas: mass and enhancement loss evaluation at delayed contrast-enhanced CT. Radiology. Gu Y., Sun J., Groome L. J., Wang Y. Surgery. 215:204-10. This occurs in the fallopian tube and forms the zygote, which is the first stage in the development of a new human being. In moderate cases, ovaries swell and fluid accumulated in the abdominal cavities and may have symptoms of heartburn, gas, nausea or loss of appetite. 123I-meta-iodobenzylguanidine scintigraphy for the detection of neuroblastoma and pheochromocytoma: results of a meta-analysis. If the small size of oSDN in MoR is determined like in females by a relative lack of early exposure to testosterone, it might represent (one of) the cause(s), and not a consequence, of their atypical sexual attraction. Girls exposed in utero to abnormally high levels of androgens not only show masculinization of genital structures and of a variety of behavioral traits (e.g. At the fourth or fifth day the embryo grows and a cavity is generated, producing a blastocyst. will also be available for a limited time. Most of the literature has focused on the paternal role in mediating AIE (see Yeshurun and Hannan, 2018), whereas maternal function has been neglected. At the molecular level, several abnormalities have been observed, such as DNA methylation in the male testis of F1 animals, which impairs spermatogenic capacity (Anway et al., 2005); altered methylation of several imprinting sites in F1 (Stouder and Paoloni-Giacobino, 2010); altered metabolic brain activity, testosterone levels in response to stress, and hippocampal gene expression (Crews et al., 2012); changes in germ cells (Skinner et al., 2013); and diseases of the reproductive organs (Manikkam et al., 2012). To strengthen the therapeutic power of the environment, paradoxically, we must understand the specific mechanisms that are altered by epigenetic adaptations following certain experiences. 2003 Jun. This question can also be partially addressed by considering studies of the effects of mood and anxiety disorders during pregnancy in the absence of trauma exposure. J Law Med Ethics. The above work provided a strong rationale for the examination of the GR promoter methylation in peripheral blood mononuclear cells of Holocaust offspring. An endometrial thickness (EMT) of less than 7mm decreases the pregnancy rate by an odds ratio of approximately 0.4 compared to an EMT of over 7mm. Anxiety is associated with higher levels of global DNA methylation and altered expression of epigenetic and interleukin-6 genes. The tumors most commonly associated with hemihyperplasia are Wilms tumor and hepatoblastoma, but at least one patient has been described with isolated hemihyperplasia and an adrenal pheochromocytoma on the hyperplastic side. Estrogens are often unable to activate female-typical behaviors (e.g. 2229 years (women) Evidence from children of Holocaust survivors, International handbook of multigenerational legacies of trauma, Multigenerational perspectives on coping with the Holocaust experience: an attachment perspective for understanding the developmental sequelae of trauma across generations, Intergenerational transmission of trauma: recent contributions from the literature of family systems approaches to treatment. [153] These costs can be exaggerated by the increasing age of the woman undergoing IVF treatment (particularly those over the age of 40), and the increase costs associated with multiple births. What is surprising is that even at the present time there are individuals who maintain this argument in the framework of current biological knowledge. Although this genetic contribution was identified many years ago, the responsible gene(s) remain(s) unknown. Children born through IVF are commonly called test tube babies. MiR-16 and miR-146 have thus been implicated as responsive mechanisms to cell stress (Morales-Prieto et al., 2014). A genomewide scan of male sexual orientation. Glucocorticoid "programming" and PTSD risk, Epigenetic programming by maternal behavior and pharmacological intervention. In 1853 Newport reported having seen spermatozoids in frogs eggs (Newport, 1853). First-generation epigenetic mechanisms are centered on modifications to chromatin densityi.e., a tuning of transcriptional probability. pp: 131. It is not a trivial matter to determine the location on a gene, or within the genome, that would activate the relevant transcription factors which result in phenotypic change. [14]. However, the actual contribution of genetic influences on environmentallyinduced events has been insufficiently studied. The findings in human brains of abuse victims implied that early developmental traumas such as those perpetrated by primary caretakers might influence the same neurobiological developmental systems as those involved in early maternal care121. It has now been shown that stressful experiences such as adult trauma change methylation of the GR gene in blood cells, whether primed by early experience or not118, 119, 129, 130. This study is noteworthy for examining both male and female F1. 1985. We report only some of the most significant evidence to provide concrete examples of our proposed classification. This idea fits well with the Darwinian concept of adaptation as an all-or-nothing process, which can be recalled easily from the collective imaginary through such terms as survival, reproductive power, and law of large numbers. Those who survive live longer, thus theoretically increasing the probability of finding a mate and reproducing. [Links], AUERBACH L (1874) Zur Charakteristik und Lebensgeschichte der Zellkerne Breslau. [Full Text]. Functionally, methylation levels were associated with salivary cortisol stress responses in the newborns at 3 months, indicating that maternal mood and offspring HPA axis reactivity may be linked through epigenetic processes and sensitive to fetal developmental stage. B., Morgan C. P., Leu N. A., Bale T. L. (2015). Although the true role of the ovum and sperm in reproduction was far from having been elucidated, their discovery led to the emergence of preformist theories, which responded to the ancient question: How can we explain the development of all the parts of an organism from a seed? The offspring is at risk when being born from older mothers, and the risks associated with being conceived through IVF. Ref. Given that this is not a matter of mutation, that is, a change that affects the gene sequence (there is no mutation), this can be reversible. The autism spectrum is a range of neurodevelopmental conditions generally characterized by difficulties in social interactions and communication, repetitive behaviors, intense interests, and unusual responses to sensory stimuli. An interaction of maternal and paternal PTSD on urinary cortisol and the DST demonstrated a decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD. Success rates for older patients were also lower and decrease with age, with 37-year-olds at 27.4% and no live births for those older than 48, the oldest group evaluated. 161(3):157-60. Certainly, they account for the general setting in which the newborn develops, which in turn begets different and complex forms of information about the past that guides ontogenetic and phylogenetic adaptation. Z., Kay M. A. Conradt E., Lester B. M., Appleton A. [Links], WATSON J D, CRICK F (1953b) Genetic implications of the structure of deoxyribonucleic acid. These behaviors were transmitted to the next generation through the male germ line. sense intronic, originating from the introns of coding genes. Developmental origins of health and disease: environmental exposures, Nongenetic inheritance and transgenerational epigenetics. Depending on their view of the embryo's humanity or the chance the couple will want to try to have another child, the couple has multiple options for dealing with these extra embryos. Rice G, Anderson C, Risch N, Ebers G. 1999. The maternal mitochondria contribute their genome to constitute the genome of the zygote. The .gov means its official. Catecholamine secretion in pheochromocytomas is not regulated in the same manner as in healthy adrenal tissue. (http://www.ornl.gov/sci/techresources/Human_Genome/ home.shtml). of his writing, among them notably his famous study on "The Generation of Animals" (Aristotle, 1953). 2010 Aug. 39(6):775-83. However, the biological knowledge and understanding about when and how this event was produced was only acquired with the discoveries described above, which culminated in the description and study of the penetration of the ovum by the spermatozoid, resulting in a new cell, the zygote. [66], Mild IVF[67] is a method where a small dose of ovarian stimulating drugs are used for a short duration during a natural menstrual cycle aimed at producing 27 eggs and creating healthy embryos. In this instance, the epigenetic modification(s) causes the offspring to express the maternal copy of a gene or the paternal copy of a gene, but not both. Such studies often did not account for parental psychopathology, but assumed it on the basis of parental exposure. long intergenic ncRNA (lincRNA), which is encoded from the introns of intergenic regions (macroRNA or vlincRNA). Intermediate forms of attraction also exist, and as early as in 1948, Kinsey et al. 2011 Feb. 18(1):97-111. This transgenerational effect has been attributed to the fact that prenatal exposure directly impacts both the fetus and the fetal germ cells, thus directly exposing the third generation. Sci. 2016 May. When environmental enrichment was applied at weaning until adulthood, the behavioral and methylation effects were no longer observed in the F0 or F1. National Library of Medicine More recent studies demonstrate that similar principles also contribute to determine the sex of the partner that will be the target of these behaviors. Mutations in this gene are known to cause carotid body tumors and paragangliomas and are inherited in an autosomal dominant fashion. VHL disease is associated with the following: One study found that this syndrome was present in nearly 19% of patients with pheochromocytomas. J Clin Endocrinol Metab. In the presence of vertebral fracture, patients with pheochromocytoma had a 58% prevalence of abdominal aortic calcification (AAC), compared with 6% in pheochromocytoma patients without vertebral fracture.
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