scholarly journals Acute development of Cushing syndrome in an HIV-infected child on atazanavir/ritonavir based antiretroviral therapy

2017 ◽  
Vol 2017 ◽  
Author(s):  
Gueorgui Dubrocq ◽  
Andrea Estrada ◽  
Shannon Kelly ◽  
Natella Rakhmanina
Keyword(s):  
Drug Interaction ◽  
Weight Gain ◽  
Hpa Axis ◽  
Cortisol Level ◽  
Half Life ◽  
Cushing Syndrome ◽  
Stimulation Test ◽  
List Type ◽  
Free Cortisol ◽  
Triamcinolone Injection

Summary An 11-year-old male with perinatally acquired human immune deficiency virus (HIV) infection on antiretroviral regimen, which included abacavir plus lamivudine (Epzicom), didanosine, ritonavir and atazanavir presented with bilateral axillary striae, increased appetite, fatigue, facial swelling and acute weight gain. Two months prior to presentation, the patient had received a diagnostic and therapeutic intra-articular triamcinolone injection in the knee for pain relief and subsequently became progressively swollen in the face, developed striae bilaterally at the axillae, experienced increased appetite, fatigue and an 8 pound weight gain. During the endocrine workup, suspicion for adrenal insufficiency prompted 24-h urine collection for free cortisol, which was found to be undetectable (below LLQ of 1.0 µg/L). This prompted further evaluation of the hypothalamic–pituitary axis (HPA) by standard dose adrenocorticotropic hormone (ACTH) stimulation test. A 250 µg cosyntropin stimulation test was performed and confirmed HPA axis suppression. Baseline cortisol level was <1 µg/dL and stimulated cortisol level at 30 min was 3.8 µg/dL. The patient was diagnosed with iatrogenic Cushing syndrome and suppression of HPA axis secondary to the drug interaction between ritonavir (RTV) and intra-articular triamcinolone injection. Following endocrine evaluation and workup, the patient was admitted for planned orthopaedic procedure including elective left hamstring lengthening, distal femoral osteotomy and patellar tendon advancement. Taking into consideration the diagnosis of iatrogenic Cushing syndrome, at the start of the surgical procedure, 100 mg IV stress dose of hydrocortisone followed by 50 mg hydrocortisone every 8 h for 24 h was administered. Stress dosing was discontinued 24 h after the procedure. Throughout the hospitalization and upon discharge, the patient continued his ART. From initial presentation, patient has remained clinically stable throughout surgery and postoperative period. Learning points: Drug–drug interaction between ritonavir and triamcinolone can cause Cushing syndrome. Although triamcinolone has a half-life of 3 h, an intra-articular injection may be systematically absorbed for 3 weeks after injection, and adrenal suppression may last as long as 30 days. Co-administration of ritonavir and corticosteroids may result in an increase of plasma levels of corticosteroids levels, as they are both eliminated by CYP3A metabolism, and this interaction has the potential to prolong the half-life of triamcinolone several fold. No specific guidelines are available for the management of iatrogenic Cushing syndrome secondary to ritonavir and corticosteroids. One treatment option includes replacing ritonavir with a non-protease inhibitor-based regimen. Initiating hydrocortisone replacement therapy to prevent an adrenal crisis is also an alternate option.

scholarly journals Fluconazole treatment in severe ectopic Cushing syndrome

2019 ◽  
Vol 2019 ◽  
Author(s):  
Teresa M Canteros ◽  
Valeria De Miguel ◽  
Patricia Fainstein-Day
Keyword(s):  
Liver Metastases ◽  
Alternative Treatment ◽  
Cushing Syndrome ◽  
Serum Cortisol ◽  
Bilateral Adrenalectomy ◽  
Ectopic Acth Syndrome ◽  
List Type ◽  
Ectopic Acth ◽  
Free Cortisol ◽  
Cortisol Levels

Summary Severe Cushing syndrome (SCS) is considered an emergency that requires immediate treatment to lower serum cortisol levels. Fluconazole may be considered an alternative treatment in Cushing syndrome when ketoconazole is not tolerated or unavailable. We report a 39-year-old woman with a history of partial pancreaticoduodenectomy due to a periampullary neuroendocrine tumor with locoregional extension. Three years after surgery, she developed liver metastases and was started on 120 mg of lanreotide/month, despite which, liver metastases progressed in the following 6 months. The patient showed extreme fatigue, muscle weakness, delirium, moon face, hirsutism and severe proximal weakness. Laboratory tests showed anemia, hyperglycemia and severe hypokalemia. 24-h urinary free cortisol: 2152 nmol/day (reference range (RR): <276), morning serum cortisol 4883.4 nmol/L (RR: 138–690), ACTH 127.3 pmol/L (RR: 2.2–10). She was diagnosed with ectopic ACTH syndrome (EAS). On admission, she presented with acute upper gastrointestinal tract bleeding and hemodynamic instability. Intravenous fluconazole 400 mg/day was started. After 48 h, her mental state improved and morning cortisol decreased by 25%. The dose was titrated to 600 mg/day which resulted in a 55% decrease in cortisol levels in 1 week, but then had to be decreased to 400 mg/day because transaminase levels increased over 3 times the upper normal level. After 18 days of treatment, hemodynamic stability, lower cortisol levels and better overall clinical status enabled successful bilateral adrenalectomy. This case report shows that intravenous fluconazole effectively decreased cortisol levels in SCS due to EAS. Learning points: Severe Cushing syndrome can be effectively treated with fluconazole to achieve a significant improvement of hypercortisolism prior to bilateral adrenalectomy. Intravenous fluconazole is an alternative treatment when ketoconazole is not tolerated and etomidate is not available. Fluconazole is well tolerated with mild side effects. Hepatotoxicity is usually mild and resolves after drug discontinuation.

scholarly journals Stereotactic radiosurgery for Cushing disease

2004 ◽  
Vol 16 (4) ◽  
pp. 1-7 ◽  
Author(s):  
Stephen J. Hentschel ◽  
Ian E. McCutcheon
Keyword(s):  
Stereotactic Radiosurgery ◽  
Cortisol Level ◽  
Cushing Syndrome ◽  
Latency Period ◽  
Serum Cortisol ◽  
Serum Cortisol Level ◽  
Cushing Disease ◽  
Fractionated Radiotherapy ◽  
Free Cortisol ◽  
Microsurgical Resection

The most common cause of Cushing syndrome is Cushing disease, in which hypercortisolism is produced by a functional adrenocorticotropic hormone–producing adenoma of the anterior pituitary gland. The common therapies available include microsurgical resection, conventional fractionated radiotherapy, and stereotactic radiosurgery (SRS). In this article the authors review the indications, results, and complications associated with SRS in the treatment of Cushing disease. In as many as 90% of patients SRS results in disease remission, which is defined as a normal 24-hour urinary free cortisol level and a normal or subnormal morning serum cortisol level. Although in most patients who are subsequently cured a marked decrease in the serum cortisol level is demonstrated within 3 months after treatment, a biochemical cure may be delayed up to 3 years in some cases. Complications following SRS for pituitary adenomas are uncommon, particularly in patients with microadenomas, which are most commonly seen in Cushing disease. The most common complication is hypopituitarism, which occurs in up to 50% of patients with a mean latency period of 5 years. Radiation-induced optic neuropathy has been reported in less than 2% of cases and induction of a secondary neoplasm in less than 1% of cases. For patients with Cushing disease, the rate of endocrinological cure following SRS appears to be similar to that attained using microsurgical resection. In contrast to surgery, SRS has the benefit of being noninvasive and associated with a very low incidence of diabetes insipidus, although hypopituitarism may be more common with SRS. With continued follow-up patient reviews and additional experience with SRS, it may become possible to make more definitive statements regarding SRS as the initial treatment for patients with Cushing disease.

scholarly journals Exogenous Cushing’s Syndrome, Hypogonadism and Diabetes Secondary to Megestrol Acetate

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A700-A700
Author(s):  
Merilyn Baby ◽  
Deepa Badrinath Murthy ◽  
Melissa Kaori Litao ◽  
Gail Shust ◽  
Bina Cherryl Shah
Keyword(s):  
Weight Gain ◽  
Hpa Axis ◽  
Cortisol Level ◽  
Cushing's Syndrome ◽  
Megestrol Acetate ◽  
Acth Level ◽  
Hpg Axis ◽  
Perinatal Hiv ◽  
Regular Menses ◽  
Hiv Aids

Abstract Introduction: Megestrol acetate (MA) is a synthetic progestin that is often prescribed for anorexic patients with HIV due to its effects on weight gain and appetite stimulation. It can cause several endocrine/metabolic abnormalities. Chronic use of MA can cause exogenous Cushing’s Syndrome (ECS) and iatrogenic adrenal insufficiency (AI) due to its stronger affinity for the glucocorticoid receptor (GR). It can also cause gonadotropin suppression, diabetes and hyperprolactinemia. We present a case of a young woman with perinatal HIV/AIDS that developed ECS secondary to MA treatment in the setting of fatigue, rapid weight gain and irregular menses. Case: A 19 year old female with perinatal HIV/AIDS (CD4&lt;200) was treated with MA (200mg/day for 5 months) for anorexia and weight loss. On exam she was pre-hypertensive (BP 138/62), obese (BMI 43.07, SDS +2.25; weight 114kg, SDS +2.34) with increased fat deposition over upper back and abdominal striae, excessive weight gain (21.5 kg in 5 months) suggestive of ECS. She had menarche at 13 years of age and had regular menses until starting MA, upon which she developed oligomenorrhea. A random serum cortisol level was &lt;0.5ug/dl at 1pm with a low ACTH &lt;1.5pg/ml and DHEAS of 13.4ug/dl. Her FSH was 3.4 mIU/L and LH 0.82 mIU/L, estradiol was &lt;2pg/dl and total testosterone &lt;2.5ng/dl consistent with secondary hypogonadism. Liver/kidney function, prolactin and lipid profile were normal. HbA1c increased from 5.3 to 6.4% in 8 months so she was started on metformin. ECS with AI, central hypogonadism and diabetes were all attributed to MA therapy. MA was discontinued gradually over two weeks. Stress dosing of glucocorticoids were advised as needed. Results: Gradual recovery of HPA axis was noted after discontinuation of MA. Two months after taper, serum ACTH level rose to 2.5pg/ml but AM cortisol level remained low at &lt;0.5ug.dl. Her HPA axis showed partial recovery by 5 months with ACTH level of 53.2pg/ml and AM cortisol level of 5.5ug/dl. By 8 months after discontinuing MA therapy, AM cortisol was 9.3ug/dl, suggesting complete HPA axis recovery. Her HPG axis also normalized by 8 months with FSH 6.6 mIU/L and LH of 14.6 mIU/L, estradiol 32pg/dl with regular menses. Metformin was discontinued at 4 months due to hypoglycemia and HbA1C of 5.7%. Subsequently, euglycemia was achieved (HbA1C of 5.4%) within 9 months. BMI was stable (BMI 43.07, SDS +2.25; weight 114kg, SDS +2.34). Conclusion: Multiple endocrine abnormalities may occur due to MA therapy due to its affinity to bind with glucocorticoid and progesterone/androgen receptors. ECS and AI are known to occur with various forms of glucocorticoid use, but rarely can be seen with MA therapy. HPA axis, HPG axis and metabolic parameters should be evaluated and monitored carefully during MA therapy.

URINARY EXCRETION OF FREE CORTISOL IN HYPERCALCAEMIA

1973 ◽  
Vol 74 (1) ◽  
pp. 122-126 ◽  
Author(s):  
F. Schønau Jorgensen ◽  
H. Kehlet
Keyword(s):  
Urinary Excretion ◽  
Hpa Axis ◽  
Animal Studies ◽  
Urinary Cortisol ◽  
Free Cortisol ◽  
Free Urinary Cortisol ◽  
Urinary Cortisol Excretion ◽  
Cortisol Excretion

ABSTRACT Human and animal studies have uniformly demonstrated increased hypothalamic-pituitary-adrenocortical (HPA) activity during acute hypercalcaemia. The HPA-activity during chronic hypercalcaemia was investigated by means of free urinary cortisol excretion. No difference in HPA activity could be demonstrated between a hyperparathyroid hypercalcaemic and a normocalcaemic group of patients. Based on these results it is suggested that during chronic hypercalcaemia, the HPA feed back mechanism overcomes the influence of hypercalcaemia on the HPA-axis.

Nutrition interventions in people with severe mental illness: Novel strategies for addressing physical health co-morbidity in a high-risk population

2016 ◽  
Vol 33 (S1) ◽  
pp. S620-S620 ◽  
Author(s):  
S. Teasdale ◽  
P. Ward ◽  
K. Samaras ◽  
S. Rosenbaum ◽  
J. Curtis ◽  
...  
Keyword(s):  
Mental Illness ◽  
Weight Gain ◽  
Severe Mental Illness ◽  
Meta Analysis ◽  
Nutrition Intervention ◽  
High Risk Population ◽  
List Type ◽  
Nutrition Interventions ◽  
Glucose Levels ◽  
Co Morbidity

IntroductionNutrition interventions are critical for weight management and cardiometabolic risk reduction in people experiencing severe mental illness (SMI). As mental health teams evolve to incorporate nutrition interventions, evidence needs to guide clinical practice.AimsA systematic review and meta-analysis was performed to assess whether nutrition interventions improve:– anthropometric and biochemical measures,– nutritional intake of people experiencing SMI.To evaluate the effectiveness of a dietician-led nutrition intervention, as part of a broader lifestyle intervention, in the early stages of antipsychotic prescription.MethodAn electronic database search was conducted to identify all trials with nutritional components. Included trials were pooled for meta-analysis. Meta-regression analyses were run on potential anthropometric moderators. Weekly individualised dietetic consultations plus group cooking classes were then offered to clients attending a Community Early Psychosis Programme, who had recently commenced antipsychotics for a 12-week period.ResultsFrom pooled trials, nutrition interventions resulted in significant weight loss (19 studies, g = –0.39, P < 0.001), reduced BMI (17 studies, g = –0.40, P < 0.001), decreased waist circumference (10 studies, g = –0.27, P < 0.001) and lower blood glucose levels (5 studies, g = –0.37, P = 0.02). Dietician-led interventions (g = –0.90) and trials focussing on preventing weight gain (g = –0.61) were the most effective. The 12-week nutrition intervention resulted in a 47% reduction in discretionary (junk) food intake (P < 0.001) and reductions in daily energy (–24%, P < 0.001) and sodium intakes (–26%, P < 0.001), while improving diet quality (P < 0.05).ConclusionEvidence supports the inclusion of nutrition interventions as part of standard care for preventing weight gain and metabolic deterioration among people with SMI.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Glucocorticoid Signaling in Stress-Related Psychiatric Disorders Uncovered by Dexamethasone-Induced Gene Expression

2017 ◽  
Author(s):  
Andreas Menke
Keyword(s):  
Gene Expression ◽  
Major Depressive Disorder ◽  
Major Depression ◽  
Depressive Disorder ◽  
Glucocorticoid Receptor ◽  
Psychiatric Disorders ◽  
Hpa Axis ◽  
Stimulation Test ◽  
Major Depressive ◽  
Depressed Patients

Major depressive disorder (MDD) is a common, serious and in some cases life‐threatening condition and affects approximately 350 million people globally (Otte et al., 2016). The magnitude of the clinical burden reflects the limited effectiveness of current available therapies. The current prescribed antidepressants are based on modulating monoaminergic neurotransmission, i.e. they improve central availability of serotonin, norepinephrine and dopamine. However, they are associated with a high rate of partial or non-response, delayed response onset and limited duration. Actually more than 50% of the patients fail to respond to their first antidepressant they receive. Therefore there is a need of new treatment approaches targeting other systems than the monoaminergic pathway. One of the most robust findings in biological psychiatry is a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in major depression (Holsboer, 2000). Many studies observed an increased production of the corticotropin-releasing hormone (CRH) in the hypothalamus, leading to an increased release of adrenocorticotropic hormone (ACTH) from the pituitary and subsequently to an enhanced production of cortisol in the adrenal cortex. Due to an impaired sensitivity of the glucocorticoid receptor (GR) the negative feedback mechanisms usually restoring homeostasis after a stress triggered cortisol release are not functioning properly (Holsboer, 2000, Pariante and Miller, 2001). However, treatment strategies targeting the GR or the CRH receptors have not been successful for a general patient population. Selecting the right patients for these treatment alternatives may improve therapy outcome, since a dysregulation of the HPA axis affects only 40-60 % of the depressed patients. Thus, patients with a dysregulated HPA axis have first to be identified and then allocated to a specific treatment regime. Tests like the dexamethasone-suppression-test (DST) or the dex-CRH test have been shown to uncover GR sensitivity deficits, but are not routinely applied in the clinical setting. Recently, the dexamethasone-induced gene expression could uncover GR alterations in participants suffering from major depression and job-related exhaustion (Menke et al., 2012, Menke et al., 2013, Menke et al., 2014, Menke et al., 2016). Actually, by applying the dexamethasone-stimulation test we found a GR hyposensitivity in depressed patients (Menke et al., 2012) and a GR hypersensitivity in subjects with job-related exhaustion (Menke et al., 2014). These alterations normalized after clinical recovery (Menke et al., 2014). Interestingly, the dexamethasone-stimulation test also uncovered FKBP5 genotype dependent alterations in FKBP5 mRNA expression in depressed patients and healthy controls (Menke et al., 2013). FKBP5 is a co-chaperone which modulates the sensitivity of the GR (Binder, 2009). In addition, the dexamethasone-stimulation test provided evidence of common genetic variants that modulate the immediate transcriptional response to GR activation in peripheral human blood cells and increase the risk for depression and co-heritable psychiatric disorders (Arloth et al., 2015). In conclusion, the molecular dexamethasone-stimulation test may thus help to characterize subgroups of subjects suffering from stress-related conditions and in the long-run may be helpful to guide treatment regime as well as prevention strategies.   References: Arloth J, Bogdan R, Weber P, Frishman G, Menke A, Wagner KV, Balsevich G, Schmidt MV, Karbalai N, Czamara D, Altmann A, Trumbach D, Wurst W, Mehta D, Uhr M, Klengel T, Erhardt A, Carey CE, Conley ED, Major Depressive Disorder Working Group of the Psychiatric Genomics C, Ruepp A, Muller-Myhsok B, Hariri AR, Binder EB, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium PGC (2015) Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders. Neuron 86:1189-1202. Binder EB (2009) The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology 34 Suppl 1:S186-195. Holsboer F (2000) The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 23:477-501. Menke A, Arloth J, Best J, Namendorf C, Gerlach T, Czamara D, Lucae S, Dunlop BW, Crowe TM, Garlow SJ, Nemeroff CB, Ritchie JC, Craighead WE, Mayberg HS, Rex-Haffner M, Binder EB, Uhr M (2016) Time-dependent effects of dexamethasone plasma concentrations on glucocorticoid receptor challenge tests. Psychoneuroendocrinology 69:161-171. Menke A, Arloth J, Gerber M, Rex-Haffner M, Uhr M, Holsboer F, Binder EB, Holsboer-Trachsler E, Beck J (2014) Dexamethasone stimulated gene expression in peripheral blood indicates glucocorticoid-receptor hypersensitivity in job-related exhaustion. Psychoneuroendocrinology 44:35-46. Menke A, Arloth J, Putz B, Weber P, Klengel T, Mehta D, Gonik M, Rex-Haffner M, Rubel J, Uhr M, Lucae S, Deussing JM, Muller-Myhsok B, Holsboer F, Binder EB (2012) Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients. Neuropsychopharmacology 37:1455-1464. Menke A, Klengel T, Rubel J, Bruckl T, Pfister H, Lucae S, Uhr M, Holsboer F, Binder EB (2013) Genetic variation in FKBP5 associated with the extent of stress hormone dysregulation in major depression. Genes Brain Behav  12:289-296. Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, Mohr DC, Schatzberg AF (2016) Major depressive disorder. Nature reviews Disease primers 2:16065. Pariante CM, Miller AH (2001) Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment. Biological psychiatry 49:391-404.

scholarly journals Prolonged half-life of voriconazole in a CYP2C19 homozygous poor metabolizer receiving vincristine chemotherapy: avoiding a serious adverse drug interaction

Mycoses ◽  
2011 ◽  
Vol 54 (6) ◽  
pp. e877-e879 ◽  
Author(s):  
Brad Moriyama ◽  
Oluwaseun Falade-Nwulia ◽  
Janice Leung ◽  
Scott R. Penzak ◽  
Caroline JJingo ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Half Life ◽  
Poor Metabolizer ◽  
Adverse Drug Interaction

scholarly journals Post-surgical hypocortisolism after removal of an adrenal incidentaloma: is it predictable by an accurate endocrinological work-up before surgery?

2010 ◽  
Vol 162 (1) ◽  
pp. 91-99 ◽  
Author(s):  
Cristina Eller-Vainicher ◽  
Valentina Morelli ◽  
Antonio Stefano Salcuni ◽  
Massimo Torlontano ◽  
Francesca Coletti ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Adrenal Incidentaloma ◽  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Tolerance Test ◽  
Surgical Removal ◽  
Acth Stimulation ◽  
Unilateral Adrenalectomy ◽  
Free Cortisol ◽  
Few Data

ObjectiveFew data are available regarding the need of steroid substitutive therapy after unilateral adrenalectomy for adrenal incidentaloma (AI). It is unknown whether, before surgery, the hypothalamic–pituitary–adrenal (HPA) axis secretion parameters can predict post-surgical hypocortisolism.AimThis study aimed to evaluate whether, in AI patients undergoing unilateral adrenalectomy, post-surgical hypocortisolism could be predicted by the parameters of HPA axis function.DesignProspective, multicenter.MethodsA total of 60 patients underwent surgical removal of AI (surgical indication: 29 subclinical hypercortisolism (SH); 31 AI dimension). Before surgery, SH was diagnosed in patients presenting at least three criteria out of urinary free cortisol (UFC) levels>60 μg/24 h, cortisol after 1-mg dexamethasone suppression test (1 mg-DST)>3.0 μg/dl, ACTH levels<10 pg/ml, midnight serum cortisol (MSC)>5.4 μg/dl.Two months after surgery, HPA axis function was assessed by low dose ACTH stimulation test or insulin tolerance test when needed: 39 patients were affected (Group B) and 21 were not affected (Group A) with hypocortisolism. The accuracy in predicting hypocortisolism of pre-surgical HPA axis parameters or their combinations was evaluated.ResultsThe presence of >2 alterations among 1 mg-DST>5.0 μg/dl, ACTH<10 pg/ml, elevated UFC and MSC has the highest odds ratio (OR) for predicting post-surgical hypocortisolism (OR 10.45, 95% confidence interval, CI 2.54–42.95, P=0.001). Post-surgical hypocortisolism was predicted with 100% probability by elevated UFC plus MSC levels, but not ruled out even in the presence of the normality of all HPA axis parameters.ConclusionPost-surgical hypocortisolism cannot be pre-surgically ruled out. A steroid substitutive therapy is indicated after unilateral adrenalectomy for SH or size of the adenoma.

scholarly journals Long-term low-dose ketoconazole treatment in bilateral macronodular adrenal hyperplasia

2014 ◽  
Vol 2014 ◽  
Author(s):  
Sophie Comte-Perret ◽  
Anne Zanchi ◽  
Fulgencio Gomez
Keyword(s):  
Medical Therapy ◽  
Cushing’S Syndrome ◽  
Clinical Signs ◽  
Cushing's Syndrome ◽  
List Type ◽  
Adrenal Hyperplasia ◽  
Benign Condition ◽  
Steroid Secretion ◽  
Free Cortisol

Summary Medical therapy for Cushing's syndrome due to bilateral macronodular adrenal hyperplasia (BMAH) is generally administered for a limited time before surgery. Aberrant receptors antagonists show inconsistent efficacy in the long run to prevent adrenalectomy. We present a patient with BMAH, treated for 10 years with low doses of ketoconazole to control cortisol secretion. A 48-year-old woman presented with headaches and hypertension. Investigations showed the following: no clinical signs of Cushing's syndrome; enlarged lobulated adrenals; normal creatinine, potassium, and aldosterone; normal urinary aldosterone and metanephrines; elevated urinary free cortisol and steroid metabolites; and suppressed plasma renin activity and ACTH. A screening protocol for aberrant adrenal receptors failed to show any illegitimate hormone dependence. Ketoconazole caused rapid normalisation of cortisol and ACTH that persists over 10 years on treatment, while adrenals show no change in shape or size. Ketoconazole decreases cortisol in patients with Cushing's syndrome, and may prevent adrenal overgrowth. Steroid secretion in BMAH is inefficient as compared with normal adrenals or secreting tumours and can be controlled with low, well-tolerated doses of ketoconazole, as an alternative to surgery. Learning points Enlarged, macronodular adrenals are often incidentally found during the investigation of hypertension in patients harboring BMAH. Although laboratory findings include low ACTH and elevated cortisol, the majority of patients do not display cushingoid features. Bilateral adrenalectomy, followed by life-long steroid replacement, is the usual treatment of this benign condition, and alternative medical therapy is sought. Therapy based on aberrant adrenal receptors gives disappointing results, and inhibitors of steroidogenesis are not always well tolerated. However, ketoconazole at low, well-tolerated doses appeared appropriate to control adrenal steroid secretion indefinitely, while preventing adrenal overgrowth. This treatment probably constitutes the most convenient long-term alternative to surgery.

scholarly journals Reversible alterations in cardiac morphology and functions in a patient with Cushing's syndrome

2014 ◽  
Vol 2014 ◽  
Author(s):  
Hiroaki Iwasaki
Keyword(s):  
Cushing’S Syndrome ◽  
Interventricular Septum ◽  
Urinary Free Cortisol ◽  
Cushing's Syndrome ◽  
Left Ventricular ◽  
Multidetector Row Computed Tomography ◽  
List Type ◽  
Adrenocortical Adenoma ◽  
Cardiac Morphology ◽  
Free Cortisol

Summary A 45-year-old female was referred for endocrine evaluation of an incidental mass (31×24 mm in diameter) on the right adrenal gland. The patient was normotensive and nondiabetic, and had no history of generalised obesity (body weight, 46 kg at 20 years of age and 51.2 kg on admission); however, her waist-to-hip ratio was 0.97. Elevated urinary free cortisol levels (112–118 μg/day) and other findings indicated adrenocorticotrophic hormone-independent Cushing's syndrome due to right adrenocortical adenoma. Echocardiography before adrenalectomy revealed concentric left ventricular (LV) hypertrophy with a particular increase in interventricular septum thickness leading to impaired systolic and diastolic functions. Upon surgical remission of hypercortisolism, the asymmetric hypertrophy disappeared and the cardiac dysfunctions were considerably ameliorated. Although the mechanism(s) by which excessive cortisol contributes to LV wall thickness remain(s) unclear, serial echocardiography and cardiac multidetector-row computed tomography may support the notion that abnormal fat deposition in the myocardium owing to hypercortisolism appears to be an important factor for the reversible change in the cardiac morphology. Learning points Patients with Cushing's syndrome occasionally exhibit severe LV hypertrophy related to systolic and diastolic dysfunctions although they have neither hypertension nor diabetes mellitus. Biological remission of hypercortisolism can normalise structural and functional cardiac parameters and help in differentiating the cardiac alterations induced by excessive cortisol from those induced by other diseases. Excessive lipid accumulation within the heart before myocardial fibrosis may be implicated in reversible alterations in the cardiac morphology by Cushing's syndrome. Early diagnosis and treatment of Cushing's syndrome appear to be pivotal in preventing irreversible cardiac dysfunctions subsequent to cardiovascular events and heart failure.

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