Cushing's disease in a 5-month infant due to a basophilic microadenoma of the pituitary gland.

We report a female patient who developed severe Cushing's disease during the fifth month of life due to a basophilic pituitary adenoma Histological findings showed a basophilic microadenoma of the pituitary gland, leading to the diagnosis of Cushing's disease. The infant died because of untreatable septic shock. The importance of the present report resides in the age of the child at diagnosis, and that it was the necropsy finding of microadenoma which clarified the cause of the Cushing's syndrome, since it was not diagnosed during life. Cushing's disease is most often diagnosed in children older than 7 years, and our patient was only 5 months old when we detected the pituitary adenoma, the earliest case diagnosed so far. Cushing's syndrome in pediatric patients has been rarely reported and most cases are due to functioning adrenal tumors, usually a malignant carcinoma but occasionally a benign adenoma. The present case shows that the pituitary of these patients should be investigated with important implications in terms of therapeutic approaches, such as pituitary radiotherapy, which can cure the patient when treatment is started very soon.

[Cushing's disease]. / Maladie de Cushing.

Patients with Cushing's disease usually present typical clinical and biological features easily leading to the diagnosis. However very atypical presentations of the disease do exist especially in the intermittent forms and several investigations are often necessary to detect pituitary microadenoma wich sometimes is inconspicuous. The course of the disease can be serious and might responsible of definitive sequellas wich can threaten patient's life. Therefore rapid treatment is recommended. Pituitary surgery should be considered as the major therapeutic approach; however, in severe cases or when pituitary-directed treatments or OP'DDD have failed, total bilateral adrenalectomy should be proposed.

Cushing's disease. Therapy of pituitary adenomas.

Treatment of Cushing's disease has evolved over the past 20 years from the era of bilateral adrenalectomy to the current era of pituitary microsurgery. Therapy directed to the pituitary gland is currently the first approach in Cushing's disease and transphenoidal exploration of the sellar contents is the procedure of choice. Tumor localization and pituitary surgery are reviewed. Pituitary radiotherapy, pharmacologic inhibition of ACTH secretion, and Nelson's syndrome are also discussed.

[Unidentified steroid hormone of Cushing's syndrome and disease].

A previously unknown HPLC peak was recently observed in urine samples from patients with Cushing's syndrome and disease. We analysed dansylated derivatives of 17keto steroid glucuronides in urine samples from patients with Cushing's syndrome, Cushing disease and from healthy subjects using high-performance liquid chromatography (HPLC) on reversed-phase Cap Cell PakC8. All urine samples from patients with Cushing's syndrome caused by adrenal adenoma and Cushing's disease showed an unknown large peak at the point between [110HE-G] and [110HA-G] peaks and at a retention time of 25.4 min. The same unknown peak was also observed in urine samples from a patient with asymptomatic cortisol-producing adrenal adenoma and two patients with ectopic ACTH-producing tumor, though the peak height was low for the former and one of the latter but high for the second of the two patients. In contrast, healthy male and female urine only showed a very small peak at the same retention time. Urine samples from a Cushing disease treated with op'DDD and Cushing's syndrome bilaterally adrenalectomized and treating with cortisol showed no such peak. The retention time of this unknown peak is clearly different from that of seven 17keto steroid standard glucuronide conjugates. The structure of this substance may be closely related to [110HE-G] or [110HA-G].

[The treatment of Cushing's disease]. / Le traitement de la maladie de Cushing.

The differential diagnosis of Cushing's disease remains difficult to establish. The selective transsphenoidal adenomectomy is the initial treatment of choice. In a group of 65 patients, 50 (77%) initially responded to surgery with correction of their hypercortisolism. Forty-three out of 51 (84%) patients with small pituitary tumors responded favourably to surgery, but recurrency occurred in 10% of the cases. Medical treatment with steroids inhibitors or antagonists is only an adjuvant treatment. In case of surgery failure or recurrency, bilateral adrenalectomy is usually performed. Conventional radiotherapy may be used after surgery in presence of macroadenomas or invasive adenomas. Correction of the hypercortisolism, after a second surgery, was achieved in 50% of the cases and was always associated with a panhypopituitarism.

A case of ruptured dissecting aneurysm 5 years after pituitary microsurgical treatment of Cushing's disease: autopsy findings in the hypothalamic-pituitary-adrenal axis.

The patient was a 26-year-old man with Cushing's disease who underwent transsphenoidal microscopic surgery for a pituitary microadenoma. His postoperative course was uneventful, but he died suddenly five years after the operation. At autopsy, a ruptured dissecting aneurysm with marked atherosclerosis was observed in the aorta. In the pituitary, a small focus of adrenocorticotropic hormone (ACTH) producing adenoma, possibly residual adenoma, was detected and Crooke's degeneration was observed in the non-tumorous pituitary gland. But immunohistochemical patterns of pituitary hormones in the non-tumorous pituitary gland were normal and the adrenal cortex was unremarkable. In the hypothalamus, corticotropin-releasing hormone immunoreactivity was not detected and arginine vasopressin was sporadically positive. Considering these findings, this patient may have developed subclinical hypercortisolism due to the residual adenoma at the time of autopsy, despite clinical remission. Cushing's syndrome is considered to be a risk factor dissecting aneurysm, and in this case the metabolic changes in Cushing's disease may have influenced the development of the dissecting aneurysm. Periodic cardiovascular re-evaluations should therefore be performed when there is clinical remission of Cushing's syndrome.

[Pituitary hemorrhage extending into the third ventricle. Case report].

A case of pituitary apoplexy causing pituitary hemorrhage with extension into the third ventricle is reported. The patient was a 73-year-old, obese female admitted with sudden onset of vomiting and impaired consciousness. Neurological examination revealed that she was stuporous, with marked neck stiffness and a dilated left pupil. A plain skull X-ray showed sellar enlargement and destruction of the dorsum sellae. Computed tomography demonstrated a high-density area in the third and lateral ventricles and a round, high-density mass in the suprasellar cistern. The patient died the next day. Autopsy revealed a large tumor in the sellar and suprasellar areas. The tumor and the hematoma within it compressed the floor of the third ventricle and passed through the lamina terminalis and the hypothalamic region. Histological examination disclosed a basophilic adenoma. The pituitary hemorrhage appeared to be the result of ischemia and necrosis within the pituitary adenoma caused by its acute expansion. The extension of the hematoma into the third ventricle was attributable to the large size of the tumor and its close adhesion to the floor of third ventricle.

Cushing's disease in a young woman with anorexia nervosa: pathophysiological implications.

This report describes a 17-year old student who was found to have Cushing's syndrome two years after she had developed anorexia nervosa (AN). The Cushing's syndrome was treated with bilateral resection of enlarged, hyperplastic, non-tumorous adrenal glands. The diagnosis was further confirmed four years later when, two to three years after new symptoms had appeared, an ACTH secreting pituitary adenoma (that is, Cushing's disease) was found on surgery. The possible mechanism for the development of Cushing's disease in a patient with prior anorexia nervosa, a sequence of events reported once previously, is discussed. It is suggested that increased hypothalamic-pituitary corticotroph stimulation in association with the anorexia nervosa, a now well-established endocrine phenomenon, activated an occult, inactive pituitary basophil adenoma in this patient, eventually resulting in autonomous pituitary overproduction of ACTH by the tumor.

Cushing disease presenting as atypical psychosis followed by sudden death.

The authors report a case of Cushing's Disease that first presented as a diagnostically confusing Atypical Psychosis. Sudden death occurred secondary to unexpected gastrointestinal bleed. Pathological findings confirmed the diagnosis. Neurochemical mechanisms for the behavioral aberrations are explored.

A case of pituitary dependent Cushing's disease with clinical and biochemical features of the ectopic ACTH syndrome.

A case of atypical pituitary dependent Cushing's disease is reported. The patient presented with clinical symptoms similar to those of the ectopic ACTH syndrome; notably a marked hypokalaemic alkalosis, widely fluctuating plasma cortisol levels, greatly elevated plasma ACTH levels, and failure to suppress both plasma cortisol and ACTH levels following high dose oral dexamethasone. However, a large aggressive pituitary tumour was detected by skull X-ray and computed tomography. Removal of the pituitary tumour led to full remission of the patient's Cushing's syndrome. Pro-opiomelanocortin (POMC) related peptides in the plasma and tumour tissue extract of this patient have been characterized by gel-filtration and Concanavalin-A Sepharose affinity chromatography, indicating processing of POMC in a manner more usually associated with ectopic tumours.

Cyclical Cushing's disease: two distinct rhythms in a patient with a basophil adenoma.

A 71-yr-old woman with clinical signs of Cushing's syndrome was studied continuously for an extended period after demonstration of a paradoxical response to dexamethasone. She proved to have a corticotroph cell adenoma of the pituitary which caused secretion of ACTH and cortisol in two distinct rhythms. One rhythm consisted of a period of 40 days of excess cortisol production, followed by a period of 60-70 days of normal production. During the period of excess cortisol production there was a second rhythm, consisting of peaks of cortisol production every 3-6 days with intervening troughs of normal cortisol production. Prolonged clinical remission followed transphenoidal surgery, but the pituitary still has the ability to provoke abnormal amounts of cortisol secretion, as occurred during a postoperative dexamethasone suppression test. The long duration of normal cortisol production phases in this patient demonstrates the difficulty in excluding Cushing's syndrome in patients with suggestive clinical symptoms but normal serum and urinary cortisol levels if these tests are measured for a single short phase of several days.

Mania in Cushing's syndrome: case report.

A case is described of recurrent mania without depressive episodes in a patient subsequently diagnosed as having an ACTH-producing basophil adenoma. The difficulties involved in the clinical and laboratory diagnosis of Cushing's syndrome, and the ramifications of neuroendocrinopathies' ability to mimic symptoms of functional psychosis, are discussed.

Cyproheptadine-induced remission of Cushing's disease due to pituitary basophil adenoma.

Serotonin is involved in the control of ACTH secretion, possibly by stimulating corticotropin releasing factor secretion from the hypothalamus. Cushing's disease seems to be due to defective hypothalamic regulation of ACTH release from the pituitary gland. Cyproheptadine is a potent antagonist of serotonin and has been used successfully in some patients with Cushing's disease, although, generally, in women without radiological evidence of pituitary tumors. We report the successful use of cyproheptadine in a 54-year-old man with Cushing's disease due to pituitary basophil adenoma. Significant clinical and biochemical improvement was noted 45 days after treatment began. The results in this patient support our findings that cyproheptadine can be effective in patients with Cushing's disease due to pituitary tumors, as well as in preparing very ill patients for surgery or managing such patients until radiotherapy takes effect.