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MaryO posted a topic in News Items and ResearchA man with Cushing’s disease — caused by an adrenocorticotrophic hormone (ACTH)-secreting pituitary adenoma — who later developed metastases in the central nervous system without Cushing’s recurrence, was successfully treated over eight years with radiation and chemotherapy, according to a case report. The report, “Long-term survival following transformation of an adrenocorticotropic hormone secreting pituitary macroadenoma to a silent corticotroph pituitary carcinoma: Case report,” was published in the journal World Neurosurgery. Pituitary carcinomas make up only 0.1-0.2% of all pituitary tumors and are characterized by a primary pituitary tumor that metastasizes into cranial, spinal, or systemic locations. Fewer than 200 cases have been reported in the literature. Most of these carcinomas secrete hormones, with ACTH being the most common. Though the majority of ACTH-secreting carcinomas present with Cushing’s disease, about one-third do not show symptoms of the condition and have normal serum cortisol and ACTH levels. These are called silent corticotroph adenomas and are considered more aggressive. A research team at the University of Alabama at Birmingham presented the case of a 51-year-old Caucasian man with ACTH-dependent Cushing’s disease. He had undergone an incomplete transsphenoidal (through the nose) resection of an ACTH-secreting pituitary macroadenoma – larger than 10 mm in size – and radiation therapy the year before. At referral in August 1997, the patient had persistent high cortisol levels and partial hypopituitarism, or pituitary insufficiency. He exhibited Cushing’s symptoms, including facial reddening, moon facies, weight gain above the collarbone, “buffalo hump,” and abdominal stretch marks. About two years later, the man was weaned off ketoconazole — a medication used to lower cortisol levels — and his cortisol levels had been effectively reduced. He also had no physical manifestations of Cushing’s apart from facial reddening. In May 2010, the patient reported two episodes of partial seizures, describing two spells of right arm tingling, followed by impaired peripheral vision. Imaging showed a 2.1-by-1-cm mass with an associated cyst within the brain’s right posterior temporal lobe, as well as a 1.8-by-1.2-cm mass at the cervicomedullary junction, which is the region where the brainstem continues as the spinal cord. His right temporal cystic mass was then removed by craniotomy. A histopathologic analysis was consistent with pituitary carcinoma. Cell morphology was generally similar to the primary pituitary tumor, but cell proliferation was higher. Physical exams showed no recurrence of Cushing’s disease and 24-hour free urinary cortisol was within the normal range. His cervicomedullary metastasis was treated with radiation therapy in July 2010. He took the oral chemotherapy temozolomide until August 2011, and Avastin (bevacizumab, by Genentech) was administered from September 2010 to November 2012. At present, the patient continues to undergo annual imaging and laboratory draws. He receives treatment with hydrocortisone, levothyroxine — synthetic thyroid hormone — and testosterone replacement with androgel. His most recent exam showed no progression over eight years of a small residual right temporal cyst, a residual mass along the pituitary stalk — the connection between the hypothalamus and the pituitary gland — and a small residual mass at the cervicomedullary junction. Lab results continue to show no Cushing’s recurrence. “Our case is the first to document a patient who initially presented with an endocrinologically active ACTH secreting pituitary adenoma and Cushing’s disease who later developed cranial and spinal metastases without recurrence of Cushing’s disease and transformation to a silent corticotroph pituitary carcinoma,” the scientists wrote. They added that the report is also the first documenting “8 years of progression-free survival in a patient with pituitary carcinoma treated with radiotherapy, [temozolomide] and bevacizumab.” Adapted from https://cushingsdiseasenews.com/2019/01/03/successful-treatment-pituitary-carcinoma-radiation-chemo-case-report/
MaryO posted a topic in News Items and ResearchTreatment with fluconazole after cabergoline eased symptoms and normalized cortisol levels in a patient with recurrent Cushing’s disease who failed to respond to ketoconazole, a case study reports. The case report, “Fluconazole as a Safe and Effective Alternative to Ketoconazole in Controlling Hypercortisolism of Recurrent Cushing’s Disease: A Case Report,” was published in the International Journal of Endocrinology Metabolism. Ketoconazole, (brand name Nizoral, among others) is an anti-fungal treatment used off-label for Cushing’s disease to prevent excess cortisol production, a distinct symptom of the disease. However, severe side effects associated with its use often result in treatment discontinuation and have led to its unavailability or restriction in many countries. Consequently, there is a need for alternative medications that help manage disease activity and clinical symptoms without causing adverse reactions, and that could be given to patients who do not respond to ketoconazole treatment. In this case report, researchers in Malaysia reported on a 50-year-old woman who fared well with fluconazole treatment after experiencing severe side effects with ketoconazole. The woman had been in remission for 16 years after a transsphenoidal surgery — a minimally invasive brain surgery to remove a pituitary tumor — but went to the clinic with a three-year history of high blood pressure and gradual weight gain. She also showed classic symptoms of Cushing’s disease: moon face, fragile skin that bruised easily, and purple stretch marks on her thighs. Blood and urine analysis confirmed high cortisol levels, consistent with a relapse of the pituitary tumor. Accordingly, magnetic resonance imaging (MRI) of her brain showed the presence of a small tumor on the right side of the pituitary gland, confirming the diagnosis of recurrent Cushing’s disease. Doctors performed another transsphenoidal surgery to remove the tumor, and a brain MRI then confirmed the success of the surgery. However, her blood and urine cortisol levels remained markedly high, indicating persistent disease activity. The patient refused radiation therapy or adrenal gland removal surgery, and was thus prescribed ketoconazole twice daily for managing the disease. But after one month on ketoconazole, she experienced low cortisol levels. Hydrocortisone — a synthetic cortisol hormone — was administered to maintain steady cortisol levels. However, she developed severe skin itching and peeling, which are known side effects of ketoconazole. She also suffered a brain bleeding episode, for which she had to have a craniotomy to remove the blood clot. Since she experienced adverse effects on ketoconazole, which also hadn’t decreased her disease activity, the doctors switched her to cabergoline. Cabergoline (marketed as Dostinex, among others) is a dopamine receptor agonist that has been shown to be effective in managing Cushing’s disease. But cabergoline treatment also did not lower the disease activity, and her symptoms persisted. The doctors then added fluconazole (marketed as Diflucan, among others), an anti-fungal medication, based on studies that showed promising results in managing Cushing’s syndrome. Three months after the addition of fluconazole to her treatment plan, the patient’s clinical symptoms and cortisol levels had responded favorably. At her next clinical visit 15 months later, her condition remained stable with no adverse events. “This case demonstrates the long-term efficacy of fluconazole in tandem with cabergoline for the control of recurrent Cushing’s disease,” the researchers wrote. The favorable outcome in this case also “supports the notion that fluconazole is a viable substitute for ketoconazole in the medical management of this rare but serious condition,” they concluded. From https://cushingsdiseasenews.com/2018/09/27/fluconazole-safe-effective-alternative-recurrent-cushings-patient-case-report/
Have questions about the new Korlym? How about Korlym vs ketoconazole? About medical vs surgical treatment for Cushing's. Ask Dr. Theodore F.. Theodore C. F., M.D., Ph.D. has opened a private practice, specializing in treating patients with adrenal, pituitary, thyroid and fatigue disorders. Dr. F. has privileges at Cedars-Sinai Medical Center and Martin Luther King Medical Center. His practice includes detecting and treating hormone imbalances, including hormone replacement therapy. Dr. F. is also an expert in diagnosing and treating pituitary disorders, including Cushings disease and syndrome. Dr. F.'s career reflects his ongoing quest to better understand and treat endocrine problems. With both medical and research doctoral degrees, he has conducted studies and cared for patients at some of the country's most prestigious institutions, including the University of Michigan, the National Institutes of Health, Cedars-Sinai Medical Center, and UCLA's Charles Drew University of Medicine and Science. Read Dr. F.'s First Guest Chat, November 11, 2003. Read Dr. F.'s Second Guest Chat, March 2, 2004. Listen to Dr. F. First Live Voice Interview, January 29, 2009. Listen to Dr. F. Second Live Voice Interview, March 12, 2009. Listen to Dr. F. Third Live Voice Interview, February 13, 2011. Listen live at http://www.blogtalkradio.com/cushingshelp/2012/03/13/questions-about-medical-therapies-for-cushings Call in to ask your question at (646) 200-0162 This interview will be archived afterwards at the same link and on iTunes Cushie Podcasts This post has been promoted to an article