A Case of Congenital Adrenal Hyperplasia due to 11beta-Hydroxylase Deficiency / 대한내분비학회지

Congenital adrenal hyperplasia refers to a group of autosomal recessive disorders that is defective in the synthesis of cortisol. The enzymes most often affected are 21-hydroxylase and 11beta hydroxylase. The low levels of cortisol stimulate the pituitary gland to release ACTH. Chronic elevation of the ACTH level causes bilateral adrenal hyperplasia and a secondary increase in androgen formation. We examined a 19 year-old woman presented with clitoral hypertrophy and vaginal spotting. The subjects basal level of serum cortisol was low, but the serum levels of ACTH, 17a-hydroxyprogesterone, deoxy-corticosterone were elevated. The urinary excretions of 17-ketosteroids and 17-hydroxycorticosteroids were also increased. The karyotyping study and transrectal ultrasonography showed normal findings. The patient underwent clitoris reduction surgery and received hydrocortisone. To the best of our knowledge, this is the first case of 11beta-Hydroxylase deficiency in Korea.

Clinical Features of Adrenocortical Neoplasms

PURPOSE: Adrenocortical tumors are uncommon in children and comprise only a small proportion of primary adrenal neoplasms. The biologic behavior of these tumors may be very difficult to predict, and their rarity has hindered identification of clinical characteristics. Patients with functioning tumors have excessive steroid hormone production, and the clinical manifestation depends on the predominant hormone produced. The detection of nonfunctioning tumors is not easy and the diagnosis may be delayed. Benign tumors can be cured by complete surgical excision, but malignant cases have poor response to treatment and worse prognosis. Early diagnosis and proper management are very important because of the large proportion of functioning malignant tumors in children. We report clinical features of adrenocortical tumors in children that may be of help in the early detection, proper management, and assessment of prognosis of patients. METHODS: We reviewed the clinical characteristics of 14 cases of adrenocortical tumors, among 85 children diagnosed with adrenal tumors, who visited the Severance Hospital, College of Medicine, Yonsei University, from January 1970 to July 1996. RESULTS: 85 Patients were diagnosed with adrenal tumors. Among them, 71 cases 83.5%) were tumors of the adrenal medulla, neuroblastoma and pheochromocytoma, and 14 cases (16.5%) were adrenocortical tumors, consisting of 5 cases of adenoma, 7 cases of carcinoma, and 2 cases unspecified. The age distribution ranged from 16 months to 14 years of age, and the mean was 5 years & 11 months (median 4 years & 2 months). Sex distribution revealed a male to female ratio of 1:1.33. The left to right ratio was 3.7:1, showing a left side predominance. 13 Cases (92.9%) were functioning tumors: 12 cases (92.3%) had clinical evidence of androgen excess, among which 6 cases (46.2%) were associated with Cushing's syndrome, and 1 case was compatible with primary aldosteronism. Serum cortisol, urinary 17-ketosteroids and 17-hydroxycorticosteroids concentrations were measured in 11 cases and urinary concentrations of 17-ketosteroids were elevated in all 11 cases (100%), while 17-hydroxycorticosteroids were elevated in 4 cases (36.4%). Abnormalities of serum cortisol were found in all cases except 1: serum cortisol concentrations were abnormally elevated in 5 cases (45.5%), and the remainder (5 cases, 45.5%) showed loss of diurnal variation. Dexamethasone suppression test was performed in 9 cases, and all (100%) showed no suppression. Preoperative radiologic studies included abdominal sonograms, CT or MRI scans, and angiography. Histology showed carcinomas to be bigger and heavier than adenomas, and microscopically carcinomas had necrosis, calcifications, and invasions of vessels. Distant metastases were found in 4 cases (12.7%). Adrenalectomy with complete surgical excision was performed in 12 cases. Long-term follow-up was possible in 10 patients after operation: 3 patients initially diagnosed with adenoma survived without tumor recurrence over a year, and among 6 carcinoma patients, 4 expired within a year, and 2 survived, with one patient currently undergoing postoperative chemotherapy. Of the 10 patients currently under going follow-up, one patient was initially diagnosed with a histologically unspecified tumor, and has survived 4 years after operation. CONCLUSIONS: When adrenocortical neoplasms are suspected by clinical symptoms and laboratory findings, abdominal ultrasonogram, CT or MRI scans must be performed immediately. Early detection and proper management are important for better prognosis, but are often delayed in the majority of cases. Ultimately, pediatricians need to be familiar with clinical characteristics and laboratory findings of adrenocortical tumors, bearing in mind the possibility of diagnosis in children.

Preliminary study of androgen, thyroid & adrenal status in alcoholic men during deaddiction.

To evaluate the status of the testes, thyroid, and adrenals in male alcoholics during the period of voluntary abstinence and therapy, chronic male drinkers undergoing a 4 wk inpatient deaddiction programme in a social hospital were recruited. Levels of a few serum and urinary hormones/metabolites viz., serum testosterone, total triiodothyronine (T3) and thyroxine (T4) and urinary total 17-ketosteroids (17-KS), estrone, estradiol, and 17-hydroxy corticosteroids (17-OHCS) were assessed in alcoholics thrice during the treatment programme at hospital i.e., on the zero (day of admission), 10th, and 20th day and compared to those of non-alcoholic controls. Alcoholics registered elevated serum total T3, and reduced total T4 and testosterone levels at admission, which persisted even after 20 days of the rehabilitative programme. Markedly high urinary levels of total 17-KS, estrone, and 17-OHCS were observed on zero day of admission. Urinary estrone and 17-OHCS, unlike total 17-KS, showed a trend to return to the normal range during the 20 days period. Urinary estradiol levels, however, recorded no significant alteration. The results of this preliminary study are suggestive of alcohol-induced perturbations on the functional integrity of the testes, thyroid, and adrenal in male alcohol addicts, wherein 20 days period of total alcohol abstinence and rehabilitative programme failed to reverse alcohol-induced hypoandrogenization and altered thyroidal status, but only partially restored certain biochemical events associated with the excretion of steroid metabolites.

Síndrome de Cushing: Estudo comparativo de métodos diagnósticos / Cushing's syndrome: A comparative study of diagnostic methods

Comparamos as respostas dos corticosteróides urinários:17-hidroxicorticosteróides (17-OHCS), 17-cetosteróides (17-KS) e cortisol livre (FC) à supressäo com dexametasona (baixa dose - 2 mg e alta dose - 8mg) em 71 pacientes com síndrome de Cushing (45 com doença de Cushing, 12 com carcinoma adrenal, oito com adenoma adrenocortical e seis com hiperplasia nodular da córtex adrenal). Os pacientes com doença de Cushing e hiperplasia nodular da córtex adrenal näo apresentam supressäo suficiente com 2 mg de dexametasona,porém o fazem com 8 mg. Os tumores adrenais näo demonstram supressäo adequada. A resposta hiperativa dos 17-OHCS, 17-KS e FC ao hormônio adrenocorticotrópico (ACTH) exógeno foi comparada na doença de Cushing. Concluimos que a determinaçäo urinária dos 17-OHCS, 17-KS e FC säo parâmetros diagnósticos úteis, embora a dosagem do FC mostrou ser um índice mais sensível da hiperfunçäo adrenocortical

Effect of bone injury on circadian periodicity of plasma 17-hydroxy corticosteroids (17-OHCS) in rabbits.

Bone injury inflicted at varying time intervals during 24 hr day-night cycle caused significant varying increase in plasma 17-OHCS levels in all traumatized animals and the levels remained elevated up to 24 hr after trauma. The level of plasma 17-OHCS was found to be aberrated in all the traumatized animals. Thus, adequate adrenocortical response to trauma and aberration in the adrenocortical secretory activity appears inevitable irrespective of the time at which the trauma is produced. However, the degree of response depends on the particular time at which the trauma is inflicted.

Funçäo pituitária e gravidez a termo na síndrome de Sheehan / Pituitary function and term pregnancy in Sheehan's syndrome

Uma paciente com síndrome de Sheehan (necrose pituitária pós-parto) desenvolveu gravidez a termo, quatro anos após a instalaçäo do hipopituitarismo, na vigência de reposiçäp hormonal tiroidiana e corticosteróide. Testes de estímulo da pituitária demonstraram claramente que o setor gonadotrófico era responsivo, sugerindo que possivelmente as células gonadotróficas teriam sido poupadas, pelo menos parcialmente, o suficiente para que houvesse ovulaçäo espontânea.

Problemas en el tratamiento de la enfermedad de Cushing / Problems in the management of Cushing's disease

Los resultados del tratamiento de la enfermedad de Cushing siguen siendo muy variables, lo cual indica que aún no se conoce su fisiopatogenia. La revisión de 12 casos en los que el diagnóstico se estableció mediante pruebas hormonales y tomografia craneal computada y se sometieron a microcirugía hipofisaria, reveló que el índice de curación fue bajo (42 por ciento) después del primer tratamiento y que el resto falleció (tres pacientes) o requirió de otro tratamiento. Se puede concluir que aunque en la actualidad no hay dificultad para establecer el diagnóstico, su tratamiento debe individualizarse. En caso de microadenoma el tratamiento de elección es operación transesfenoidal y, cuando se presenta persistencia, el siguiente recurso puede ser radioterapia ordinaria auxiliada por fármacos en forma temporal para disminuir los efectos del cortisol elevado en la sangre. En caso de macradenoma, que es índice de mal pronóstico, se debe hacer hipofisectomía y seguirse de radiación ordinaria. La adrenolectomía debe reservarse para los casos en que haya contraindicación absoluta para la operación hipofisaria

Septum and adrenocortical function.

Dorsal septum is an intermediary centre in between the hippocampus and hypothalamus and it has got inhibitory influence over the hypothalamo-pituitary-adrenal axis. Stimulation of the dorsal septum manifested with fall in adrenocortical output whereas its lesion has opposite response. Ventral septum is a facilitatory area regarding activation of the hypothalamo-pituitary-adrenal axis. It is a balancing centre lying in between the higher central nervous system structures and the hypothalamus. Stimulation and lesion of the ventral septum led to rise and fall in adrenal venous 17-OHCS output respectively. Adrenocortical response to stress of burn was not blocked or inhibited following lesion of the dorsal as well as ventall septum.

Experimental Studies on the Release of 17-Hydroxycorticosteroids from Soaked Soft Contact Lenses

The therapeutic application of the soft contact lenses are popular in ophthalmic use recently. Drug effects of greater magnitude and duration may be achieved by using a soft contact lens soaked with drugs. Using mycon-soft lenses, with different diameter (14.5mm, 12.0mm) and thickness (0.2mm, 0.1mm), soaked in 2.5% hydrocortisone acetate or 2.5% hydrocortisone succinate for 15 minutes and 30 minutes according to the protocol, and elution studies were performed. Elution rate were not influenced by the thickness of contact lens and soaked time in drugs, but it was influenced by the size of contact lens. It showed that increased elution rate in larger contact lens than smaller one. It was suggested that neither hydrocortisone acetate nor hydrocortisone succinate were absorbed by the soft contact lens but were adhered to the lens surface and released from it gradually.