scholarly journals Fluticasone furoate induced iatrogenic Cushing syndrome in a pediatric patient receiving anti-retroviral therapy

Author(s):  
S A A van den Berg ◽  
N E van ‘t Veer ◽  
J M A Emmen ◽  
R H T van Beek

Summary We present a case of iatrogenic Cushing’s syndrome, induced by treatment with fluticasone furoate (1–2 dd, 27.5 µg in each nostril) in a pediatric patient treated for congenital HIV. The pediatric patient described in this case report is a young girl of African descent, treated for congenital HIV with a combination therapy of Lopinavir/Ritonavir (1 dd 320/80 mg), Lamivudine (1 dd 160 mg) and Abacavir (1 dd 320 mg). Our pediatric patient presented with typical Cushingoid features (i.e. striae of the upper legs, full moon face, increased body and facial hair) within weeks after starting fluticasone furoate therapy, which was exacerbated after increasing the dose to 2 dd because of complaints of unresolved rhinitis. Biochemical analysis fitted iatrogenic Cushing’s syndrome, with a repeatedly low cortisol (<0.03 µM, ref 0.14–0.60 µM) and low ACTH (9 pg/mL, ref 9–52 pg/mL) without signs of adrenal insufficiency. No other biochemical abnormalities that could point to adrenal or pituitary dysfunction were detected; electrolytes, thyroid and gonadal function, and IGF-1 were within the normal range. Pharmacogenetic analysis revealed that the pediatric patient carried the CYP3A4 *1B/*1G and CYP3A5 *3/*3 genotype (associated with a partial and complete loss of enzyme activity, respectively) which is associated with the development of iatrogenic Cushing’s syndrome in patients treated for HIV due to the strong inhibition of CYP3 enzymes by Ritonavir. Upon discontinuation of fluticasone treatment, the pediatric patient improved both clinically and biochemically with normalisation of cortisol and ACTH within a couple of weeks. Learning points: Fluticasone therapy may induce iatrogenic Cushing’s syndrome in a patient treated with anti-retroviral therapy. Pharmacogenetic analysis, in particular CYP3A genotyping, provides useful information in patients treated for HIV with respect to possible future steroid treatment. Fluticasone furoate is not detected in the Siemens Immulite cortisol binding assay.

2020 ◽  
Vol 31 (1) ◽  
pp. 18-21
Author(s):  
Tamanna Bahar ◽  
Shaila Rahman ◽  
Lilian Catherene Gomes ◽  
Mohammad Murad Hossain ◽  
Zulfia Zinat Chowdhury ◽  
...  

Background: Cushing’s syndrome is caused by excessive activation of glucocorticoid receptor. Iatrogenic Cushing syndrome is the prevalent one world -wide .Patients with Cushing’s syndrome has a high prevalence of osteoporosis. Objective: To see the prevalence of osteoporosis in Iatrogenic Cushing’s syndrome patient. Method: This descriptive cross-sectional study included 211 diagnosed case of Cushing’s syndrome during the time period of December 2013 to December 2018 in outpatient department of Dhaka Medical College and Health and Hope Hospital. Final diagnosis was done on the basis of clinical feature, serum basal cortical level and BMD. We found male were prevalent one (56%).80.56% showed biochemical evidence of Cushing’s syndrome. BMD was done in 113 patients compared with a reference population by means of T score, 17.69% patient in osteoporotic range. Conclusion: The prevalence of osteoporosis and osteopenia is age and sex independent. Judicial use of steroid and co administration with calcium, bisphosphonate can prevent osteoporosis. Treatment with bisphosphonates should be considered in all patients (irrespective of age) with Cushing’s syndrome with a low BMD to reduce fracture. Bangladesh J Medicine Jan 2020; 31(1) : 18-21


Author(s):  
Adrienne Dow ◽  
Run Yu ◽  
John Carmichael

Summary To report the puzzling, rare occurrence of coexisting adrenal insufficiency and Cushing's syndrome from chronic, intermittent use of intranasal betamethasone spray. A 62-year-old male was referred to our endocrinology clinic for management of adrenal insufficiency. This previously healthy individual began to experience chronic sinus symptoms in 2007, was treated with multiple ensuing sinus surgeries, and received oral glucocorticoid for 6 months. In the following 5 years, he suffered severe fatigue and was diagnosed with secondary adrenal insufficiency. He could not be weaned from corticosteroid and developed clear cushingoid features. In our clinic, careful inquiry on medications revealed chronic, intermittent use of high-dose intranasal betamethasone since 2008, which was not apparent to his other treating physicians. His cushingoid features significantly improved after holding intranasal betamethasone. Learning points Chronic, intermittent intranasal betamethasone can cause secondary adrenal insufficiency and iatrogenic Cushing's syndrome when used in excess. Topical corticosteroid use should be considered in the differential diagnosis of adrenal insufficiency or Cushing's syndrome.


Author(s):  
Sophie Comte-Perret ◽  
Anne Zanchi ◽  
Fulgencio Gomez

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.


Author(s):  
Hiroaki Iwasaki

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.


Author(s):  
Ziadoon Faisal ◽  
Miguel Debono

Summary In this case report, we describe the management of a patient who was admitted with an ectopic ACTH syndrome during the COVID pandemic with new-onset type 2 diabetes, neutrophilia and unexplained hypokalaemia. These three findings when combined should alert physicians to the potential presence of Cushing’s syndrome (CS). On admission, a quick diagnosis of CS was made based on clinical and biochemical features and the patient was treated urgently using high dose oral metyrapone thus allowing delays in surgery and rapidly improving the patient’s clinical condition. This resulted in the treatment of hyperglycaemia, hypokalaemia and hypertension reducing cardiovascular risk and likely risk for infection. Observing COVID-19 pandemic international guidelines to treat patients with CS has shown to be effective and offers endocrinologists an option to manage these patients adequately in difficult times. Learning points This case report highlights the importance of having a low threshold for suspicion and investigation for Cushing’s syndrome in a patient with neutrophilia and hypokalaemia, recently diagnosed with type 2 diabetes especially in someone with catabolic features of the disease irrespective of losing weight. It also supports the use of alternative methods of approaching the diagnosis and treatment of Cushing’s syndrome during a pandemic as indicated by international protocols designed specifically for managing this condition during Covid-19.


2019 ◽  
Vol 92 (3) ◽  
pp. 196-202
Author(s):  
Prapai Dejkhamron ◽  
Chupong Ittiwut ◽  
Hataitip TangNgam ◽  
Kanokkarn Sunkonkit ◽  
Rungrote Natesirinilkul ◽  
...  

Infantile Cushing’s syndrome is potentially found as part of McCune-Albright syndrome (MAS) which is caused by postzygotic somatic mutations of the GNAS gene. MAS is typically characterized by a triad of polyostotic fibrous dysplasia, café-au-lait skin pigmentation, and precocious puberty or other endocrine hyperfunction. Here, we describe a 2-month-old female infant with features of Cushing’s syndrome without café au lait spots, polyostotic fibrous dysplasia, and clinical evidence of other endocrine hyperfunction. Investigations demonstrated adrenocorticotropic hormone-independent Cushing’s syndrome with bilateral adrenal gland enlargement. Whole-exome sequencing of leukocytes identified a de novo heterozygous novel missense mutation (c.521G>A, p.Cys174Tyr) in the GNAS gene. The patient experienced clinical improvement of Cushing’s syndrome during ketoconazole treatment. Her clinical course was complicated by Pneumocystis jiroveci pneumonia. She also had shortened activated partial thromboplastin time indicating a hypercoagulable state and resulting in pulmonary embolism. She eventually manifested gonadotropin-independent precocious puberty at the age of 13 months after ketoco­nazole was discontinued. This patient demonstrated that Cushing syndrome can be the presenting sign of MAS in infancy. A high index of suspicion followed by genetic analysis is essential in order to establish a diagnosis.


2020 ◽  
Vol 2020 ◽  
pp. 1-3
Author(s):  
Ricardo Álvarez Martínez ◽  
Rosa María Tomé Rodríguez ◽  
María Álvarez Ariza ◽  
Carlos Spuch ◽  
Jose M. Olivares

This is a case of a patient affected by Cushing syndrome that was admitted at the hospital due to hormonal problems. He had presented psychiatric symptoms that were mistakenly considered not directly connected to the pathology causing the clinical condition, but a mere psychological reaction to it.


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