ABSTRACT
CONTEXT: Women with congenital adrenal hyperplasia (CAH) may present with androgen excess that is difficult to control with conventional suppressive doses of glucocorticoids. Clinical management is challenging, and the woman is at great risk of developing steroid-induced complications. PATIENTS AND METHODS: A 32-year-old woman with salt-wasting CAH due to 21-hydroxylase deficiency underwent right-sided adrenalectomy because of a large myelolipoma. Over the years, androgens became increasingly difficult to suppress on prednisolone 5â +â 0â +â 2.5 mg daily, and at age 39 years the left adrenal with an enlarging myelolipoma was removed. A month later serum testosterone levels had increased from 4.1 preoperatively to 18.3 nmol/L (reference 0.2-1.8 nmol/L), and adrenocorticotropin levels from 32 to 283 pmol/L (reference <â 14 pmol/L). No adrenal parenchyma was visualized on computed tomography (CT). In the further search for the source of the markedly elevated testosterone, positron emission tomography (PET) was performed with 2 different tracers, 18fluorodeoxyglucose (18FDG) reflecting glucose metabolism and 11C-metomidate, an inhibitor of 11-ß-hydroxylase targeting adrenocortical tissue. RESULTS: 18FDG-PET/CT with cosyntropin stimulation showed ovarian/paraovarian hypermetabolism, suggestive of adrenal rest tumors. Further characterization with 11C-metomidate PET/CT showed uptakes localized to the ovaries/adnexa, behind the spleen, and between the right crus diaphragmaticus and inferior vena cava. CONCLUSION: Adrenal rest tumors can give rise to high androgen levels in spite of suppressive supraphysiological glucocorticoid doses. This case illustrates, for the first time, the value of 11C-metomidate PET as a sensitive method in documenting adrenal rest tumors, currently considered rare in women with CAH.
Subject(s)
Adrenal Hyperplasia, Congenital , Adrenal Rest Tumor/diagnosis , Ovarian Neoplasms/diagnosis , Retroperitoneal Neoplasms/diagnosis , Adrenal Hyperplasia, Congenital/complications , Adrenal Hyperplasia, Congenital/diagnosis , Adrenal Hyperplasia, Congenital/metabolism , Adrenal Rest Tumor/complications , Adrenal Rest Tumor/metabolism , Adult , Carbon Radioisotopes , Etomidate/analogs & derivatives , Female , Humans , Neoplasms, Multiple Primary/complications , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/metabolism , Ovarian Neoplasms/complications , Ovarian Neoplasms/metabolism , Positron Emission Tomography Computed Tomography/methods , Retroperitoneal Neoplasms/complications , Retroperitoneal Neoplasms/metabolism , Salts/metabolism , Sweden , Water-Electrolyte Imbalance/complications , Water-Electrolyte Imbalance/metabolismABSTRACT
Context: Studies of the clinical and immunological features of autoimmune Addison disease (AAD) are needed to understand the disease burden and increased mortality. Objective: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles, and cardiovascular risk factors. Design, Setting, and Participants: A cross-sectional, population-based study that included 660 AAD patients from the Swedish Addison Registry (2008-2014). When analyzing the cardiovascular risk factors, 3594 individuals from the population-based survey in Northern Sweden, MONICA (monitoring of trends and determinants of cardiovascular disease), served as controls. Main Outcome Measures: The endpoints were the prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined. Results: The proportion of 21-hydroxylase autoantibody-positive patients was 83%, and 62% of patients had ≥1 associated autoimmune diseases, more frequently coexisting in females (P < 0.0001). AAD patients had a lower body mass index (P < 0.0001) and prevalence of hypertension (P = 0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of the patients, with a mean dose of 28.1 ± 8.5 mg/d. The mean hydrocortisone equivalent dose normalized to the body surface was 14.8 ± 4.4 mg/m2/d. A greater hydrocortisone equivalent dose was associated with a greater incidence of hypertension (P = 0.046). Conclusions: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients did not have an increased prevalence of overweight, hypertension, type 2 diabetes mellitus, or hyperlipidemia. However, high glucocorticoid replacement doses could be a risk factor for hypertension.
Subject(s)
Addison Disease/immunology , Addison Disease/complications , Addison Disease/drug therapy , Addison Disease/epidemiology , Adolescent , Adult , Aged , Autoantibodies/blood , Autoimmune Diseases/epidemiology , Autoimmune Diseases/immunology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Child , Child, Preschool , Comorbidity , Cross-Sectional Studies , Drug Administration Schedule , Female , Hormone Replacement Therapy/methods , Humans , Hydrocortisone/administration & dosage , Hydrocortisone/therapeutic use , Infant , Infant, Newborn , Male , Middle Aged , Registries , Risk Factors , Sweden/epidemiology , Young AdultABSTRACT
Wilson disease (WD) is a recessively inherited copper storage disorder mainly affecting liver and brain. Genotype/phenotype correlations have been report ed but as yet not regarding psychic symptoms. Our aim was to investigate if a correlation might exist between genotype and phenotype concerning psychopathology and/or personality traits in patients with treated WD. Nine homozygous and three compound heterozygous Swedish patients were retrospectively investigated, representing four different mutation settings. Psychopathological symptoms were studied using the Comprehensive Psychopathological Rating Scale (CPRS), personality traits using the Karolinska Scales of Personality (KSP) and mutations were analyzed by manifold sequencing. Psychopathological symptoms: Patients with the Trp779Stop mutation had the lowest scores on the total CPRS, due to less pronounced reported CPRS items, as compared to the other three groups of patients. Compound heterozygotes for the His1069Gln/Arg1319Stop mutation showed the highest total CPRS scores. Personality traits: Patients homozygous for the Trp779Stop and the Thr977Met mutations had high scores on Psychopathy related scales whereas patients with His1069Gln/Arg1319Stop mutations had the lowest scores on these scales. Serum ceruloplasmin levels were undetectable in all patients with the Trp779Stop and Thr977Met mutations. The results show a trend towards a genotype/phenotype correlation regarding psychopathological symptoms and personality traits in treated patients with WD. If replicable, these results might contribute to the elucidation of the possible clinical importance of functionally deleterious gene mutations in WD psychopathology and personality traits.
Subject(s)
Hepatolenticular Degeneration/psychology , Mental Disorders/genetics , Mutation , Personality/genetics , Adult , Female , Hepatolenticular Degeneration/genetics , Heterozygote , Homozygote , Humans , Male , Middle AgedABSTRACT
Parallel, highly specific analysis methods are required to take advantage of the extensive information about DNA sequence variation and of expressed sequences. We present a scalable laboratory technique suitable to analyze numerous target sequences in multiplexed assays. Sets of padlock probes were applied to analyze single nucleotide variation directly in total genomic DNA or cDNA for parallel genotyping or gene expression analysis. All reacted probes were then co-amplified and identified by hybridization to a standard tag oligonucleotide array. The technique was illustrated by analyzing normal and pathogenic variation within the Wilson disease-related ATP7B gene, both at the level of DNA and RNA, using allele-specific padlock probes.
