Ketoconazole/octreotide/potassium

Abstract

Liver damage and lack of efficacy: 2 case reports In a case report of 3 patients, a 23-year-old woman and a 28-year-old man were described, of whom the man developed liver damage during treatment with ketoconazole, and the woman exhibited lack of efficacy while receiving treatment with potassium and octreotide [not all dosages and routes stated; duration of treatment to reaction onset and outcome not stated]. Case 1: A 23-year-old woman exhibited lack of efficacy while receiving treatment with potassium for hypokalaemia and octreotide for hypercortisolism. The woman was admitted with one-month history of acne, hirsutism and general fatigue. On admission, hypokalaemia was evident. Therefore, she received oral and IV potassium supplementation. However, hypokalaemia could not be normalised until spironolactone therapy was added. Thus, lack of efficacy with potassium was considered. The woman’s therapy with potassium was stopped. The further laboratory test suggested osteopenia, loss of circadian rhythm, elevated 24-h urinary free cortisol levels and failure to suppress cortisol with classical low dose dexamethasone suppression test. Additionally, she had elevated plasma adrenocorticotropic hormone (ACTH) level, favoring ACTH-dependent Cushing’s syndrome. Desmopressin stimulation resulted in ACTH increase by about 700%. However, cortisol level was not decreased after high dose of dexamethasone. Thereafter, a diagnosis of ectopic ACTH syndrome (EAS) was made. The further evaluation failed to identify the source of ACTH secretion; however, only bilateral adrenal hyperplasia was observed. She then received octreotide injection for hypercortisolism. Despite treatment, the cortisol level remained unchangeable, indicating lack of efficacy with octreotide therapy. The woman underwent bilateral adrenalectomy for rapid control of hypercortisolism. Post-surgery, she received hydrocortisone. The level of serum potassium was subsequently normalised without any supplementation. Three months after the surgery, ACTH level significantly decreased, indicating adrenal glands to be the origin of excess ACTH. Subsequently, the histopathological imaging revealed a thickened adrenal medulla, which met the criteria of adrenal medulla hyperplasia. Case 2: A 28-year-old man developed liver damage during treatment with ketoconazole. The man presented with a six-month history of acne and three-month history of general fatigue, moon face and hypertension. He displayed overt cushingoid features with central obesity, abdominal striae, dorsocervical and supraclavicular fat pads, acne, skin bruises and facial plethora. The laboratory examination revealed severe hypokalaemia, diabetes mellitus, severe osteoporosis, hyperglycaemia, severe hypercortisolism with loss of circadian rhythm and elevated 24h urinary cortisol levels. Additionally, plasma adrenocorticotropic hormone (ACTH) level was significantly elevated, confirming ACTH-dependent Cushing’s syndrome. Due to elevated ACTH level, ectopic ACTH syndrome (EAS) was considered. The further laboratory examination revealed hyperplasia of the right adrenal gland. Additionally, a mass in the left nasal cavity and left ethmoidal sinus was observed with intense metabolic activity of the mass. Based on the clinical presentation and laboratory findings, a diagnosis of olfactory neuroblastoma was considered. On admission, ketoconazole was available. Therefore, he received antifungal treatment with ketoconazole 800 mg/day, which resulted in the decrease of serum cortisol level. However, he developed liver damage with ALT level reaching 300 U/L. The liver damage was attributed to the ketoconazole therapy. Therefore, the man’s therapy with ketoconazole was stopped and bilateral adrenalectomy was performed. Post-surgery, cushingoid features gradually disappeared. His blood glucose, BP and potassium levels returned to normal ranges without medication. He then required prednisone acetate daily. Three months after the surgery, the ACTH level decreased. He then underwent transnasal endoscopic resection of the tumour mass. Subsequently, the histopathological imaging revealed increased adrenal medullary cell mass and diffuse hyperplasia of the medullary cells in both adrenal glands, indicating adrenal medulla hyperplasia. He was currently under regular follow-up and remained well for 7 years.