1/5. Cyclic Cushing's syndrome: an overview.Cyclic Cushing's syndrome (CS) involves rhythmic fluctuations in ACTH secretion resulting in a cyclic variation of adrenal steroid production. In the majority of cases, cyclic CS is caused by an acth-secreting pituitary adenoma, but it can also be due to ectopic ACTH production or an adrenal adenoma. This condition should be strongly suspected in patients with symptoms or signs of hypercortisolism but normal cortisol levels and paradoxical responses to the dexamethasone test, that may reflect an increasing or decreasing endogenous hormone activity. Dynamic tests are best interpreted if they are performed during a sustained period of hypercortisolism. Sometimes, it is necessary to confirm the diagnosis over lengthy periods of observation. Responses to treatment must be closely monitored, interpreted and evaluated with caution because of the potential variations in steroidogenesis. An original case report of a cyclic Cushing's syndrome is presented in this review. ( info) |
2/5. The Nelson's syndrome... revisited.adrenalectomy is a radical therapeutic approach to control hypercortisolism in some patients with Cushing's disease. However it may be complicated by the Nelson's syndrome, defined by the association of a pituitary macroadenoma and high ACTH secretion after adrenalectomy. This definition has not changed since the end of the fifties. Today the Nelson's syndrome must be revisited with new to criteria using more sensitive diagnostic tools, especially the pituitary magnetic resonance imaging. In this paper we will review the pathophysiological aspects of corticotroph tumor growth, with reference to the impact of adrenalectomy. The main epidemiological data on the Nelson's syndrome will be presented. More importantly, we will propose a new pathophysiological and practical approach to this question which attempts to evaluate the Corticotroph Tumor Progression after adrenalectomy, rather than to diagnose the Nelson's syndrome. We will discuss the consequences for the management of Cushing's disease patients after adrenalectomy, and will also draw some perspectives. ( info) |
3/5. 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. ( info) |
4/5. A patient with recurrent hypercortisolism after removal of an acth-secreting pituitary adenoma due to an adrenal macronodule.A 41-yr-old female was referred for signs and symptoms of Cushing's syndrome. Cortisol was not suppressed by 1 mg dexamethasone (0.41 micromol/l). Midnight cortisol and ACTH were 0.44 micromol/l and 18 pmol/l, respectively. Urinary cortisol excretion was 250 nmol/24 h (normal between 30 and 150 nmol/24 h). A magnetic resonance imaging (MRI) revealed a pituitary lesion of 7 mm. ACTH and cortisol levels were unaltered by administration of human CRH and high-dose dexamethasone. Inferior sinus petrosus sampling showed CRH-stimulated ACTH levels of 128.4 (left sinus) vs a peripheral level of 19.2 pmol/l, indicating Cushing's disease. After 4 months of pre-treatment with metyrapone and dexamethasone, endoscopic transsphenoidal resection of an ACTH-positive pituitary adenoma was performed. ACTH levels decreased to 2.6 pmol/l and fasting cortisol was 0.35 micromol/l. Despite clinical regression of Cushing's syndrome and normalization of urinary cortisol, cortisol was not suppressed by 1 mg dexamethasone (0.30 micromol/l). Ten months post-operatively, signs and symptoms of Cushing's syndrome reoccurred. A high dose dexamethasone test according to Liddle resulted in undetectable ACTH, but no suppression of cortisol levels, pointing towards adrenal-dependent Cushing's syndrome. Computed tomography (CT)-scanning showed a left-sided adrenal macronodule. Laparoscopic left adrenalectomy revealed a cortical macronodule (3.5 cm) surrounded by micronodular hyperplasia. fasting cortisol had decreased to 0.02 micromol/l. Glucocorticoid suppletion was started and tapered over 12 months. Symptoms and signs of hypercortisolism gradually disappeared. This case illustrates, that longstanding ACTH stimulation by a pituitary adenoma can induce unilateral macronodular adrenal hyperplasia with autonomous cortisol production. ( info) |
5/5. Menstrual abnormalities in a woman with ACTH-dependent pituitary macroadenoma mimicking polycystic ovary syndrome.OBJECTIVE: Here, we present a case of ACTH-dependent pituitary macroadenoma (Cushing's disease) resulting in secondary amenorrhea mimicking polycystic ovary syndrome (PCOS). CASE REPORT: A 20-year-old nulligravid woman had been suffering from oligomenorrhea, amenorrhea, and moderate hirsutism since the age of 18 years. She visited a gynecologic clinic where PCOS was impressed according to the clinical manifestation and ultrasound finding. The patient responded to medication in the 1st year, but gradually failed to induce menses. She was advised to visit the endocrinology department for secondary amenorrhea and endocrine survey. physical examination revealed central obesity, supraclavicle fatpad, abdominal striae, and myopathy of four limbs. Endocrine studies revealed: serum prolactin 21 ng/mL (3.0-20 ng/mL), FSH 5.69 mIU/mL (3.4-10.0 mIU/mL), LH 1.01 mIU/mL (1.1-11.6 mIU/mL), E2 < 20 pg/mL (follicular phase 53-258 pg/mL), ACTH 110 pg/mL (0-46.0 pg/mL), cortisol 26.7 microg/dL at 8 a.m. (5.0-25 microg/dL), cortisol 21.3 microg/dL at 11 p.m. (half of normal morning value). Right pituitary macroadenoma was diagnosed through a series of dexamethasone tests and MRI. The patient received staging surgery including transsphenoidal adenomectomy and right frontotemporal craniotomy. As a result, the patient's physical condition gradually improved, and her menstrual cycle became regular with medication after the operation in the outpatient follow-up. CONCLUSION: PCOS is a common disease resulting in secondary amenorrhea. However, Cushing's syndrome resulting from pituitary macroadenoma should also be considered. Therefore, a careful history, observation, physical examination, and endocrine studies can differentiate between patients with PCOS and Cushing's disease. ( info) |