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Non-FDG radionuclide imaging and targeted therapies
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Luigi Aloj, Ferdia A Gallagher
Characterization of adrenal lesions is often a diagnostic dilemma in radiology, particularly if they are small. It is important to be able to distinguish benign disease from both primary adrenal malignancy and metastases (77). Cortisol and steroid hormone metabolism is specific to the adrenal cortex and gonads. Labelled precursors of steroid hormones have long been utilized to image and characterize adrenal masses to identify the tissue of origin. 131I-labelled cholesterol derivatives have been utilized since the 1970s for this purpose, using standard gamma camera imaging (78). 11ß-hydroxylase is an essential enzyme in the biosynthesis of cortisol and aldosterone, which is overexpressed in adrenocortical adenomas. Metomidate is an inhibitor of the enzyme 11β hydroxylase, and several metomidate derivatives have been used to identify and characterize adrenocortical lesions. Iodo-metomidate tracers have shown promise for the diagnosis and management of adrenocortical carcinoma (79), and increasingly, 11C-metomidate PET-CT has been shown to have a role in primary hyperaldosteronism or Conn's syndrome, where it can replace the need for invasive adrenal vein sampling (80,81). While such studies can only be performed in a specialized centre, it demonstrates the potential for these highly selective tracers in stratified patient populations. An example of the use of 11C-metomidate is given in Figure 44.8.
Nutrition Therapy of Inborn Errors of Metabolism
Published in Fima Lifshitz, Childhood Nutrition, 2020
Kimberlee Michals-Matalon, Reuben Matalon
The biochemical findings on patients with untreated PKU include elevated levels of phenylalanine in blood, urine, and spinal fluid. A normal concentration of blood phenylalanine is 1–2 mg/dl. Patients with untreated PKU have levels of phenylalanine that often exceed 20 mg/dl. Once an infant with an elevated phenylalanine blood level is identified by newborn screening, confirmatory diagnostic studies must be completed. Blood should be analyzed for quantitative amino acids to document that the phenylalanine is indeed greater than 6 mg/dl and that the tyrosine blood level is normal. The urine should show elevated phenylalanine and phenylalanine metabolites. Phenylalanine hydroxylase requires the cofactor te-trahydrobiopterin (BH4) for the conversion of phenylalanine to tyrosine. The co-factor, BH4, is also utilized in the hydroxylation of tyrosine to dopamine and tryptophan to serotonin. Approximately 2% of infants with hyperphenylalani-nemia have BH4 deficiency. Therefore, this must be ruled out since the treatment for BH4 deficiency is totally different than that for PKU.7
Biogenic amines
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Tyrosine hydroxylase catalyzes the rate-limiting step in the formation of the catecholamines, dopamine, norepinephrine, and epinephrine (see Figure 17.1). Deficient activity of the enzyme leads to diagnostic decrease in CSF concentrations of the metabolic catecholamine degradation products, HVA and MPHG (see Table 17.1). The gene TH contains 14 exons and has an open reading frame of 1491 bp [31]. It was mapped to chromosome 11p.15.5, the most distant end of 11p [32].
A novel homozygous CYP17A1 mutation causes partial 17 α-hydroxylase/17,20-lyase deficiency in 46,XX: a case report and literature review
Published in Blood Pressure, 2023
Heye Chen, Yingting Chen, Hongxian Mao, Huaying Huang, Xueyong Lou
17 α-Hydroxylase/17,20-lyase deficiency (17-OHD) is an extremely rare autosomal recessive disorder caused by mutations in the CYP17A1 gene, which encodes the P450c17 enzyme. This enzyme plays a critical role in the production of both glucocorticoids and sex steroids, specifically by regulating the activities of 17 α-hydroxylase and 17,20-lyase, respectively [1,2]. The deficiency of 17 α-hydroxylase and 17,20-lyase has a significant impact on the patient’s health. The 17-hydroxylase deficiency results in decreased cortisol levels, which compensatively stimulates the secretion of adrenocorticotropic hormone (ACTH). It also increases the production of mineralocorticoid precursors, corticosterone, and 11-deoxycorticosterone (DOC), ultimately resulting in hypertension and hypokalaemia. In contrast, the 17,20-lyase deficiency leads to decreased sex steroid production, which compensatively stimulates Follicle-Stimulating Hormone (FSH) and luteinizing hormone (LH), resulting in primary amenorrhoea and a lack of secondary sex characteristics [3]. Overall, patients with 17-OHD typically present with hypertension, hypokalaemia, primary amenorrhoea, and a lack of secondary sex characteristics.
Sex differences in the hypothalamic-pituitary-adrenal axis response following a single or multiple days of sleep restriction
Published in Stress, 2020
Katelyn N. Buban, Elizabeth A. Shupe, Stephen W. Rothwell, T. John Wu
Relative expression of 11β-hydroxylase, which is an enzyme involved in the biosynthesis of CORT via the conversion of deoxycorticosterone to the active corticosterone (White, Pascoe, Curnow, Tannin, & Rösler, 1992), was measured in the adrenal glands to assess for adrenal insufficiency following PSD. Adrenal insufficiency is a form of adrenal fatigue or exhaustion believed to be caused by a period of overactivation of the adrenal glands, whereby the adrenals are unable to produce CORT due to either a change in local enzymatic activity, or due to a disruption in higher level systems involved in CORT release (Guilliams & Edwards, 2010). 11β-hydroxylase expression, was increased in males but not females following both one and three days of sleep deprivation. While, females showed greater 11β-hydroxylase expression overall compared to their male counterparts. These findings suggests that it is not adrenal insufficiency caused by changes in enzymes that is responsible for the dysregulation in HPA axis reactivity, and that there might be sex-specific differences in baseline enzymatic activity that might contribute to overall sex differences in the HPA axis reported in the literature (Rao & Androulakis, 2017). Therefore, the alterations seen at the level of the adrenal glands might be due to changes in higher-order systems such as the adrenal-sympathetic system or they might be sex-specific strategies employed by the adrenals to combat disruptions elsewhere in the HPA axis.
A report of congenital adrenal hyperplasia due to 17α-hydroxylase deficiency in two 46,XX sisters
Published in Gynecological Endocrinology, 2020
Fernando Espinosa-Herrera, Estefanía Espín, Ana M. Tito-Álvarez, Leonardo-J Beltrán, Diego Gómez-Correa, German Burgos, Arianne Llamos, Camilo Zurita, Samantha Rojas, Iván Dueñas-Espín, Kenny Cueva-Ludeña, Jorge Salazar-Vega, Jorge Pinto-Basto
The 17α-hydroxylase enzyme, which is expressed in gonads and adrenals, acts at two levels: (i) it catalyzes the 17α-hydroxylation of pregnenolone and progesterone, and (ii) its lyase activity cleaves their products at 17,20 side chain [2,3]. 17α-Hydroxylase, also known as P450c17, is a 508 amino acids protein, encoded by the CYP17A1 gene, which is located on chromosome 10 (10q24.32-q25) and is composed of eight exons [3]. Approximately, 120 different mutations of CYP17A1 have been reported [2,3,5]. These mutations impair the enzyme activity partially or completely, resulting in adrenal and gonadal sex steroid deficiency [3,4]. 17OHD causes cortisol synthesis blockage; that leads to adrenocorticotropic hormone (ACTH) accumulation and further activation of the 17-deoxy pathway of the zona fasciculata producing overstimulation of this pathway and increasing progesterone, corticosterone and deoxycorticosterone (DOC) synthesis [3]. Importantly, the excessive mineralocorticoid activity reduces renin activity and decreases aldosterone levels [2].