Thesis (Ph. D.)--University of Wisconsin--Madison, 1955. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Bibliography: leaves 62-70.

Thesis (Ph.D.)--Boston University. / The literature concerning the physiology of the mammalian adrenal cortex is voluminous. However, little has been reported on the physiology of the adrenal cortex of the hamster, Mesocricetus auratus. The present investigation of the effects of adrenalectomy in the hamster was initiated in order that fundamental data such as survival time, electrolyte levels, and changes in estrus cycle of the female could be determined. Since the golden hamster is being used more and more as a laboratory animal, this data would serve as a basis for further investigation. All results obtained in the study of the hamster are compared and contrated to those reported for the rat, the most commonly used laboratory animal in endocrinological investigation. A great many phenomena have been observed by endocrinologists which have demonstrated an apparent interrelationship between the adrenal cortices and gonads of mammals. These phenomena are so numerous that Parkes (1945) was forced to adopt an artificial classification of these interrelationships in orer to review the field with some order and clarity. The effects of adrenalectomy in the hamster were such that it was felt that in this study greater emphasis should be placed on the interrelationships between the gonads and the adrenal cortices than on any other aspect of the adrenal cortical physiology of the animals. It was hoped thereby that the mechanisms involved in these interrelationships would be further elucidated. [Truncated]

A Hiperplasia Adrenal Congênita (HAC) compreende um grupo de doenças autossômicas recessivas causadas por um defeito em uma das enzimas envolvidas na biossíntese do cortisol. Em 90% dos casos, a HAC é devido a deficiência na enzima 21-hidroxilase. Programas de triagem de recém-nascidos detectam a HAC através do teste bioquímico do hormônio 17-hidroxiprogesterona (17OHP), substrato da 21-HIDROXILASE, realizado em uma amostra de sangue seco em papel filtro. Entretanto, os valores do 17OHP podem variar devido a diferentes fatores, causando resultado falso positivos ou falso negativos. Com o intuito de elucidar esses casos, ensaios de biologia molecular têm sido empregados. Sendo assim, o presente trabalho teve como objetivo empregar metodologias moleculares para a análise de crianças com suspeita de HAC no Estado do Rio Grande do Sul. Três testes moleculares, minisequenciamento multiplex, sequenciamento e multiplex ligation-dependent probe amplification (MLPA) foram padronizados e/ou validados. Essas metodologias foram aplicadas para determinar o genótipo de 166 crianças com suspeita de HAC. A técnica de minisequenciamento multiplex foi utilizada para detectar doze mutações (p.Gln318Ter, p.Arg356Trp, p.Leu306PhefsX6, p.Val237Glu, IVS2-13A/C>G, p.Ile172Ans, p.Pro30Leu, p.Pro453Ser, p.Val281Leu, p.Gly110ValfsX21 e p.His62Leu) e o sequenciamento foi empregado quando necessária a análise de outras mutações pontuais. A identificação de grandes deleções, rearranjos e conversões foi realizada através do kit de MLPA. Como resultado, foi possível identificar 84 alelos patogênicos em 48 pacientes, sendo que as mutações mais frequentes encontradas foram p.Val281Leu (27,1%) e IVS2-13A/C>G (20,8%). Portanto, as metodologias empregadas neste trabalho foram eficientes para detectar as mutações mais frequentes descritas no Brasil e podem ser utilizadas em programas de triagem de recém-nascidos para ajudar a distinguir entre doentes e casos falsos positivos. / Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by a defect in one of the enzymes involved in cortisol biosynthesis. In 90% of cases, CAH is due to steroid 21-hydroxylase deficiency. Newborn screening program detect CAH through 17-hydroxyprogesterone (17OHP) biochemistry test done in dried blood spotted on filter paper, which is the 21-hydroxylase substrate. However, the levels of 17OHP can vary due to different factors, causing false positives or false negatives results. To clarify and assist these cases, molecular biology assays have been used. Therefore, this work aimed to employ molecular assays to detect mutations in CYP21A2 gene of children suspected of CAH from Rio Grande do Sul state. Three molecular tests, multiplex minisequencing, direct sequencing and multiplex ligation-dependent probe amplification (MLPA) were standardized and/or validated. These assays were used to determine the genotype of 166 children suspected CAH. Multiplex minisequencing technique was performed to detect twelve point mutations (p.Gln318Ter, p.Arg356Trp, p.Leu306PhefsX6, p.Val237Glu, IVS2-13A/C>G, p.Ile172Ans, p.Pro30Leu, p.Pro453Ser, p.Val281Leu, p.Gly110ValfsX21 and p.His62Leu) and the direct sequencing was used when other point mutations needed to be analyzed. Large deletions, rearrangements and conversions was investigated by MLPA assay. As a result, it we were able to identify 84 pathogenic alleles in 48 patients, being p.Val281Leu (27.1%) and IVS2-13A/C>G (20.8%) the most frequent mutations. In conclusion, the methods used in this work were efficient to detect the most frequently mutations described in Brazil and can be used in newborn screening program to help distinguishing between affected and false positive cases.

A Hiperplasia Adrenal Congênita (HAC) compreende um grupo de doenças autossômicas recessivas causadas por um defeito em uma das enzimas envolvidas na biossíntese do cortisol. Em 90% dos casos, a HAC é devido a deficiência na enzima 21-hidroxilase. Programas de triagem de recém-nascidos detectam a HAC através do teste bioquímico do hormônio 17-hidroxiprogesterona (17OHP), substrato da 21-HIDROXILASE, realizado em uma amostra de sangue seco em papel filtro. Entretanto, os valores do 17OHP podem variar devido a diferentes fatores, causando resultado falso positivos ou falso negativos. Com o intuito de elucidar esses casos, ensaios de biologia molecular têm sido empregados. Sendo assim, o presente trabalho teve como objetivo empregar metodologias moleculares para a análise de crianças com suspeita de HAC no Estado do Rio Grande do Sul. Três testes moleculares, minisequenciamento multiplex, sequenciamento e multiplex ligation-dependent probe amplification (MLPA) foram padronizados e/ou validados. Essas metodologias foram aplicadas para determinar o genótipo de 166 crianças com suspeita de HAC. A técnica de minisequenciamento multiplex foi utilizada para detectar doze mutações (p.Gln318Ter, p.Arg356Trp, p.Leu306PhefsX6, p.Val237Glu, IVS2-13A/C>G, p.Ile172Ans, p.Pro30Leu, p.Pro453Ser, p.Val281Leu, p.Gly110ValfsX21 e p.His62Leu) e o sequenciamento foi empregado quando necessária a análise de outras mutações pontuais. A identificação de grandes deleções, rearranjos e conversões foi realizada através do kit de MLPA. Como resultado, foi possível identificar 84 alelos patogênicos em 48 pacientes, sendo que as mutações mais frequentes encontradas foram p.Val281Leu (27,1%) e IVS2-13A/C>G (20,8%). Portanto, as metodologias empregadas neste trabalho foram eficientes para detectar as mutações mais frequentes descritas no Brasil e podem ser utilizadas em programas de triagem de recém-nascidos para ajudar a distinguir entre doentes e casos falsos positivos. / Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by a defect in one of the enzymes involved in cortisol biosynthesis. In 90% of cases, CAH is due to steroid 21-hydroxylase deficiency. Newborn screening program detect CAH through 17-hydroxyprogesterone (17OHP) biochemistry test done in dried blood spotted on filter paper, which is the 21-hydroxylase substrate. However, the levels of 17OHP can vary due to different factors, causing false positives or false negatives results. To clarify and assist these cases, molecular biology assays have been used. Therefore, this work aimed to employ molecular assays to detect mutations in CYP21A2 gene of children suspected of CAH from Rio Grande do Sul state. Three molecular tests, multiplex minisequencing, direct sequencing and multiplex ligation-dependent probe amplification (MLPA) were standardized and/or validated. These assays were used to determine the genotype of 166 children suspected CAH. Multiplex minisequencing technique was performed to detect twelve point mutations (p.Gln318Ter, p.Arg356Trp, p.Leu306PhefsX6, p.Val237Glu, IVS2-13A/C>G, p.Ile172Ans, p.Pro30Leu, p.Pro453Ser, p.Val281Leu, p.Gly110ValfsX21 and p.His62Leu) and the direct sequencing was used when other point mutations needed to be analyzed. Large deletions, rearrangements and conversions was investigated by MLPA assay. As a result, it we were able to identify 84 pathogenic alleles in 48 patients, being p.Val281Leu (27.1%) and IVS2-13A/C>G (20.8%) the most frequent mutations. In conclusion, the methods used in this work were efficient to detect the most frequently mutations described in Brazil and can be used in newborn screening program to help distinguishing between affected and false positive cases.

The current interest in the secretions of the adrenal cortex is shared by physiologist, physician and pharmacologists alike. such attention is not surprising in the case of a gland which is immediately essential to life, which can produce syndromes as varied as precocious puberty, virilisation; Addison's disease; Cushing's syndrome, and the newly described hyperaldosteronism syndrome of Conn (1955), a gland which has been implicated in the parthenogenesis of diabetes (Hoet and Lukens, 195; Jackson, 1955), hypertension (Sepeika, 1948, 1955), pre-eclampsia, and atherosclerosis, and which profoundly effects so many of the metabolic processes of the body. The need for accurate measurement of adrenocortical function has therefore been accentuated in recent years. The purpose of this study was to find out as direct a method as possible for determining the rate of secretion of this gland and to define with this method the norms and normal variations.

Background: TB was once a common cause of primary adrenal insufficiency, it is now most often autoimmune in the developed world, but there are rarely observed infectious causes, including TB, Fungal, and CMV. The extra-adrenal manifestations typically stem from pulmonary TB. When TB invades the adrenals, imaging of the adrenal glands initially shows hypertrophy, which progresses to fibrosis and calcification in almost half the cases. This adrenal hypertrophy is often a key marker for differentiating tuberculous adrenal insufficiency from autoimmune adrenalitis, in which case adrenals are usually atrophied. Case: A 62 year old woman with a history of CKD, hyperlipidemia, and possible heart failure presented to the hospital with a 3 week history of worsening right knee pain. She was initially hypotensive at 68/48. Her hospital course was complicated by renal failure, persistent hypotension, and hyponatremia. She received approximately 5 liters of fluid with no significant hemodynamic response. Initial labs showed sodium of 125 with normal range 135-145 and a creatinine of 3.63 with sodium levels hovering in the low 130’s throughout the next 8 days while systolic pressure remained less than 110. Endocrinology was consulted to evaluate the ongoing hypotension and hyponatremia 5 days into admission. Infectious disease was also consulted after it was later revealed that the patient had a history of TB with a positive ppd in 2014, treated with Isoniazid but she was unable to confidently state whether she completed treatment. Other lab work was remarkable for a positive ppd test, negative HIV, and random cortisol levels of 1.3 and 1.1. Cosyntropin stimulation test was very abnormal with cortisol results of 1.3 and 1.1 at 30 and 60 minute intervals (normal >18). ACTH on day 6 of admission was greater than 2000, consistent with primary adrenal insufficiency. Abdominal CT without contrast on day 11 showed adrenal fullness with nodal calcifications consistent with post-infectious TB. Blood pressure and sodium improved on hydrocortisone 50 mg three times daily. She was discharged on hydrocortisone 20mg in the AM and 10mg in the PM, fludrocortisone 0.1mg daily and the 4 drug combo for TB; Rifampin, Isoniazid, Pyrazinamide, and Ethambutol. Conclusion: This case of primary adrenal insufficiency highlights an atypical cause that is now rare in the developed world. TB causes adrenal destruction in a gradual manner, targeting the medulla and cortex secondarily as illustrated here by this HIV-negative latent TB patient. Tuberculous adrenal insufficiency typically presents in an insidious manner. This case demonstrates the importance of a thorough history and evaluation coupled with the realization that not all primary adrenal insufficiency is autoimmune.

No description available.

Cultures Y-1 mouse adrenal tumor cells exhibited varying degrees of rounding when treated with ACTH (0.5 U/ml) caused rounding, formation of filopodia and numerous thin microvilli, and stimulated steroidgenesis.

No description available.

No description available.