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Macronodular adrenocortical hyperplasia in a postmenopausal woman.

This case report describes the diagnosis of Cushing's syndrome due to macronodular adrenal hyperplasia in an elderly woman who presented with fatigue, muscle weakness and oedema, and recent excessive bruising. Long-standing disease and comorbidity precluded adrenalectomy. Despite treatment with metyrapone and diuretics, the patient died after two months hospitalisation. Postmortal examination revealed overexpression of luteinising hormone (LH) receptors in the adrenal glands, suggesting that the postmenopausal rise in LH may have a role in adrenal hyperplasia and hypercortisolism.

Adrenal Cortex↗

[Cushing disease resistent to conventional therapy: role of bilateral laparoscopic adrenalectomy].

Cushing's disease is the most frequent form of endogenous hypercortisolism in the adult. It is a rare disease, whose natural history is not well known, and has a tremendous impact on patients' quality of life. Trans-sphenoidal surgery is the first therapeutic option in the management of these patients, but it is associated with a 25% long-term recurrence rate. Based on the observation of two patients, the Authors discuss the multidisciplinary approach, the indications and the timing of treatment by bilateral adrenalectomy. Also, the peculiar aspects of the laparoscopic surgical technique are outlined.

Adolescent↗

[Syndrome of inappropriate ADH secretion (SIADH) induced by pramipexole in a patient with Parkinson's disease].

An 85-year-old woman with Parkinson's disease was admitted to our hospital to conduct a further work-up for progressive gait disturbance. She had been on medications for the disease for more than a decade prior to admission. In order to improve her condition, she was newly administered pramipexole, a dopamine agonist, from day 3 in addition to the preceding anti-Parkinson's therapy. However, on day 10, her consciousness level was rapidly deteriorated into delirium(JCS II-10), which was not accompanied by neurological signs and symptoms. Laboratory tests showed severe hyponatoremia with relatively increased urinary sodium excretion, and severe low serum osmolarity with an increased urinary osmolarity. Brain CT and brain MRI showed no specific abnormalities except for those related to aging. Blood concentration of ADH measured at the onset was substantially higher(39.5 pg/ml) than normal (0.3-3.5 pg/ml under normal osmolarity). Diseases causing hyponatremia, such as liver cirrhosis, congestive heart failure, hypotonic dehydration, and malignancy-associated inappropriate ADH secretion (SIADH), were all excluded. Under the suspicion of SIADH due to pramipexole, the drug was discontinued and as a result, her consciousness level improved rapidly together with a prompt reduction in ADH level (9.2 pg/ml). To the best of our knowledge, the present case is the first that demonstrates pramipexole-induced SIADH. Since pramipexole is classified as a dopaminergic receptor agonist, this case may provide new insight into a link between ADH and the dopaminergic receptor in the central nervous system.

Aged↗

[Melatonin].

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Aging↗

[ACTH-dependent Cushing's syndrome: a revision of 43 cases].

AIM: To evaluate the characteristics and outcomes of the patients diagnosed as ACTH-dependent Cushing syndrome, registered in the department. MATERIAL AND METHODS: We reviewed the files of forty-three patients followed from 1974 to 2002. RESULTS: A progressive rise in the number of patients diagnosed was found, being 80% females. Clinical suspicion was based mostly on the typical fat distribution; hirsutism and amenorrhoea were important in women. The more reliable diagnostic tests were: 11 pm cortisol, day curve of ACTH and cortisol, and dexamethasone suppression tests. The ACTH response to CRH during inferior petrosal sinus sampling permitted the diagnosis of ectopic source. In thirty-seven patients a pituitary adenoma was diagnosed. The three patients diagnosed before 1985 went for bilateral adrenalectomy (Nelson's syndrome in two); the others were submitted to transsphenoidal pituitary adenomectomy, obtaining remission in twenty six at the first operation and in two others at the second. Three patients had a recidive. Of the six patients with persistent disease (all treated with metyrapone or ketoconazole), three were submitted to radiotherapy, two to bilateral adrenalectomy, and one was waiting for surgery. Four patients had a bronchial carcinoid, successfully removed in three. One patient was lost to follow-up and another was still being evaluated. CONCLUSIONS: We found a positive evolution in the capacity to diagnose and treat these patients. Neurosurgical ability to achieve remission was 80% in the operated cases. More effective technical methods and drugs, as well as a multidisciplinary and dedicated medical team, lead to long lasting remissions in most of the patients.

Adolescent↗

[Pharmacological therapy of Cushing's disease].

The curative treatment of Cushing's disease is surgery, mainly transphenoidal surgery. The cure probability is high and the risks or complications are few. However, pharmacotherapy is necessary while localisation of the secreting tumour is not achieved, when there is persistence of hypercortisolism after surgery, or while waiting for effectiveness of radiotherapy. We review the existing drugs, their characteristics, mechanisms of action, doses and specific indications.

Humans↗

[The role of phosphoinositides, protein kinase C and protein kinase A in the K+ regulatory signal transduction in human adrenocortical cells].

The messenger mechanisms mediating K+ regulatory signals in human adrenocorticocytes were studied. It was shown that potassium ions initiated decay of polyphosphoinositides to inositolphosphates and obviously diacylglycerol. The latter compounds activate protein kinase C as affected by different agonists. Using western blotting method we showed translocation of PKCalpha from cytosol to membranes after adrenal tissue preincubation in the medium with increased K+ content (8.5 mM). Translocation means activation of the enzyme. Activity of PKC increased in the microsomal fraction and did not change in cytosol. Increased concentration of K+ in the incubation medium also activates protein kinase A, although to a lesser extent compared to PKC. Unlike PKC activity of PKA was changed in cytosol as well. The possibility of involvement of several messenger systems in K+ signal transduction in human adrenocortical cells as well as the hypothesis on cross-talk between messenger mechanisms for main physiological agonists controlling aldosterone biosynthesis in the adrenals are discussed.

Adrenal Cortex↗

Pituitary corticotroph hyperplasia preceding adenoma in a patient with Nelson's syndrome.

We report the case of a 42-year-old woman with Cushing's disease and Nelson's syndrome. When she was 17 years old, transsphenoidal surgery was performed. A detailed morphologic study demonstrated nodular hyperplasia of corticotroph cells but no adenoma. Following a long-lasting remission (14 years), Cushing's disease recurred. After an unsuccessful second transsphenoidal surgery, Cushing's disease persisted and both adrenals were removed (at the age of 34). Subsequently the patient developed Nelson's syndrome. The pituitary tumor proved to be a corticotroph adenoma; it was removed by the transsphenoidal approach (at the age of 42). Although in most patients Cushing's disease is due to an ACTH-secreting pituitary corticotroph adenoma which precedes the manifestation of Nelson's syndrome, our case indicates not only that corticotroph hyperplasia may cause Cushing's disease but that it may exist before the development of Nelson's syndrome after the removal of both adrenals. Our study supports the view that protracted stimulation of corticotrophs resulting from the elimination of the negative inhibitory feedback effect by corticosteroids plays a role in adenoma initiation.

ACTH-Secreting Pituitary Adenoma↗

[Diagnosis and therapy of endocrine hypertension].

Once the diagnosis of hypertension is established, secondary forms should be considered. Especially hormonally active adrenal tumors may allow specific treatment. For primary hyperaldosteronism plasma aldosterone to active renin concentration ratio in patients with plasma aldosterone levels > or = 200 ng/l is a reliable screening method under random conditions. A salt loading test may confirm a primary aldosteronism. A unilateral adrenal adenoma has to be separated from bilateral adrenal hyperplasia. To exclude Cushing's syndrome, the dexamethasone challenge is a reliable screening parameter. Patients with Cushing's syndrome may have an elevated urinary free cortisol and the circadian rhythm may be abolished resulting in an elevated 23:00 h serum cortisol. Alternatively, cortisol may be measured in saliva using specific cutoffs. Determinations of 24-h urinary epinephrine and norepinephrine levels are established diagnostic tools for the diagnosis of pheochromocytoma. Metanephrines, which are metabolites of catecholamines, have been suggested as an alternative more sensitive and specific diagnostic tool. In conclusion, recently established biochemical methods are reliable screening parameters for the diagnosis of adrenal hypertension. Endocrine hypertension due to adrenal tumors may be treated by minimally invasive surgery or specific antihypertensive treatment.

Adrenal Gland Neoplasms↗

[The condition and prospects of Russian endocrinology].

The article presents a brief essay dedicated to the development of endocrinology in our country since pre-war time. The article covers the most promising areas of endocrinology, from endemic goiter to the introduction of the newest technologies to endocrinology, and informs the readers about structural and organizational changes in the diabetological service, including the establishment of Institute of Diabetes and Institute of Pediatric Endocrinology, the first ones in Russia, the establishment of diabetological service, including State Registry of Diabetic Patients, a school for adult patients, etc. Another issue is the establishment of Growth Center and the introduction of genetic engineering growth hormone preparations into the practice of treatment of short children. Once again, the authors emphasize the issue of fighting endemic goiter. Many tasks of Russian endocrinology are now considered weighty matters of state.

Adrenal Gland Diseases↗