scholarly journals Spontaneous resolution of avascular necrosis of femoral heads following cure of Cushing’s syndrome

2016 ◽  
Vol 2016 ◽  
Author(s):  
A Pazderska ◽  
S Crowther ◽  
P Govender ◽  
K C Conlon ◽  
M Sherlock ◽  
...  
Keyword(s):  
Femoral Head ◽  
Avascular Necrosis ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Leg Pain ◽  
List Type ◽  
Rapid Weight Gain ◽  
Free Cortisol ◽  
Femoral Heads ◽  
Adrenal Disease

Summary Avascular necrosis (AVN) is a rare presenting feature of endogenous hypercortisolism. If left untreated, complete collapse of the femoral head may ensue, necessitating hip replacement in up to 70% of patients. The majority of the described patients with AVN due to endogenous hypercortisolaemia required surgical intervention. A 36-year-old female, investigated for right leg pain, reported rapid weight gain, bruising and secondary amenorrhoea. She had abdominal adiposity with violaceous striae, facial plethora and hirsutism, atrophic skin, ecchymosis and proximal myopathy. Investigations confirmed cortisol excess (cortisol following low-dose 48h dexamethasone suppression test 807nmol/L; 24h urinary free cortisol 1443nmol (normal<290nmol)). Adrenocorticotrophic hormone (ACTH) was <5.0pg/mL. CT demonstrated subtle left adrenal gland hypertrophy. Hypercortisolaemia persisted after left adrenalectomy. Histology revealed primary pigmented micronodular adrenal disease. Post-operatively, right leg pain worsened and left leg pain developed, affecting mobility. MRI showed bilateral femoral head AVN. She underwent right adrenalectomy and steroid replacement was commenced. Four months after surgery, leg pain had resolved and mobility was normal. Repeat MRI showed marked improvement of radiological abnormalities in both femoral heads, consistent with spontaneous healing of AVN. We report a case of Cushing’s syndrome due to primary pigmented nodular adrenocortical disease, presenting with symptomatic AVN of both hips. This was managed conservatively from an orthopaedic perspective. Following cure of hypercortisolaemia, the patient experienced excellent recovery and remains symptom free 4 years after adrenalectomy. This is the first report of a favourable outcome over long-term follow-up of a patient with bilateral AVN of the hip, which reversed with treatment of endogenous hypercortisolaemia. Learning points AVN of femoral head can be a presenting feature of hypercortisolism, both endogenous and exogenous. Rarely, treatment of hypercortisolaemia can reverse AVN without the need for orthopaedic intervention. Primary pigmented nodular adrenal disease is a rare cause of ACTH-independent Cushing’s syndrome.

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.

scholarly journals Vandetanib induces a marked anti-tumor effect and amelioration of ectopic Cushing’s syndrome in a medullary thyroid carcinoma patient

2016 ◽  
Vol 2016 ◽  
Author(s):  
Hashem Bseiso ◽  
Naama Lev-Cohain ◽  
David J Gross ◽  
Simona Grozinsky-Glasberg
Keyword(s):  
Cushing’S Syndrome ◽  
Tumor Size ◽  
Cushing's Syndrome ◽  
Whole Body ◽  
List Type ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Ectopic Cushing’S Syndrome ◽  
Free Cortisol

Summary A 55-year-old woman diagnosed with sporadic MTC underwent total thyroidectomy 20 years ago. After the first surgery, elevated calcitonin levels in parallel with local disease persistence were noted and therefore she underwent repeated neck dissections. During follow-up, multiple foci of metastatic disease were noted in the neck and mediastinal lymph nodes, lungs and bones; however, the disease had an indolent course for a number of years, in parallel with a calcitonin doubling time of more than two years and without significant symptoms. During a routine follow-up visit 2 years ago, findings suggestive of Cushing’s syndrome were observed on physical examination. The biochemical evaluation demonstrated markedly elevated serum calcitonin level, in parallel with lack of cortisol suppression after an overnight 1 mg dexamethasone suppression test, lack of cortisol and ACTH suppression after high-dose IV dexamethasone 8 mg, elevated plasma ACTH up to 79 pg/mL (normal <46 pg/mL) and elevated 24-h urinary free cortisol up to 501 µg/24 h (normal 9–90 µg/24 h). After a negative pituitary MRI, she underwent IPSS, which was compatible with EAS. Whole-body CT demonstrated progressive disease at most of the tumor sites. Treatment with vandetanib at a dosage of 200 mg/day was commenced. The patient showed a significant, rapid and consistent clinical improvement already after two months of treatment, in parallel with biochemical improvement, whereas a decrease in tumor size was demonstrated on follow-up CT. Learning points: Ectopic Cushing’s syndrome due to ectopic ACTH secretion (EAS) by MTC is an uncommon and a poor prognostic event, being associated with significant morbidity and mortality. We demonstrate that vandetanib is effective in controlling the signs and symptoms related to the EAS in patients with advanced progressive MTC. We demonstrate that vandetanib is effective in decreasing tumor size and in inducing tumor control.

scholarly journals SAT-263 A Vicious Cycle of Hypercortisolism - Cyclical Cushing’s Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Bahar Kapoor Force ◽  
Daniel Yoshor ◽  
Sherly Sebastian ◽  
Mas Takashima ◽  
Susan Leanne Samson
Keyword(s):  
Weight Gain ◽  
Cushing’S Syndrome ◽  
Clinical Signs ◽  
Case Series ◽  
Cushing's Syndrome ◽  
Cortisol Secretion ◽  
Diagnostic Challenge ◽  
Rapid Weight Gain ◽  
Free Cortisol ◽  
C 30

Abstract Background: Cyclical Cushing’s syndrome (CS) is described as periods of excess cortisol secretion interspersed with low or normal cortisol. The generally acceptable criteria for diagnosis is demonstration of 3 peaks and 2 troughs in cortisol secretion but, in practice, patterns and duration of cycles are unpredictable and can present a significant diagnostic challenge. Here, we present a case series of three patients who did not meet the published criteria but had pathological confirmation of ACTH-dependent CS. Clinical Case: Two women (A: 30 year-old, B: 40 year-old), and one man (C: 30 year-old) presented to the Pituitary Center for second/third opinions regarding CS. All patients had significant central weight gain. Patient A described cycles of rapid weight gain and loss, fluctuating facial and leg swelling, anxiety and darkening of stretch marks or scars punctuated with episodes of fatigue, lightheadedness and nausea. Patients B and C reported cyclical leg swelling, facial redness and acne. These patients had additional clinical signs of Cushingoid facies, dorsocervical and supraclavicular fat pads. Patient C had violaceous striae. Multiple tests for CS were performed: 1 mg overnight dexamethasone suppression test, two midnight salivary cortisols, and 24h urine free cortisol (UFC). All testing was normal, with a few exceptions. Patient A had an isolated midnight salivary cortisol elevated to 0.426 (&lt;0.112 ug/dL). Patient C had two mildly elevated 24h UFC collections of 1.4 times upper limit of normal corresponding with his cycles of peripheral edema and acne. Patient B had completely negative testing. In all 3 patients, ACTH levels were not suppressed but also not elevated. Random serum DHEA-S levels were elevated in patients A and B. Patients A and C were found to have possible pituitary microadenomas on MRI with dynamic contrast. Patient B’s MRI was negative but inferior petrosal sinus sampling revealed a markedly elevated tumoral level of ACTH of &gt;62,500 pg/mL with CRH stimulation. All 3 patients underwent endoscopic transsphenoidal resection by an expert pituitary surgeon with no post-operative complications in patients A & B, but development of partial diabetes insipidus in patient C. In patients A & C, pathology revealed corticotroph hyperplasia while patient B was found to have a corticotroph adenoma. Patients A & B persisted to have symptoms of hypercortisolism, opted to undergo bilateral adrenalectomy and pathology showed diffuse adrenocortical hyperplasia for both. Conclusion: Cyclical CS is likely underdiagnosed because of difficulty in obtaining biochemical confirmation even with strong clinical suspicion of CS. DHEA-S has a long half-life as well as minimal diurnal variation, and could be an additional clue in patients with suspected pituitary source of cyclical hypercortisolism. Ultimately, clinical concern should drive further diagnostic imaging and management.

scholarly journals Exacerbation of Cushing’s syndrome during pregnancy: stimulation of a cortisol-secreting adrenocortical adenoma by ACTH originating from the foeto-placental unit

2019 ◽  
Vol 2019 ◽  
Author(s):  
Matthieu St-Jean ◽  
Jessica MacKenzie-Feder ◽  
Isabelle Bourdeau ◽  
André Lacroix
Keyword(s):  
Cushing’S Syndrome ◽  
Post Partum ◽  
Adrenal Adenoma ◽  
Cushing's Syndrome ◽  
List Type ◽  
Adrenocortical Adenoma ◽  
Late Night ◽  
Receptor Mrna ◽  
Free Cortisol ◽  
Stimulation Of

Summary A 29-year-old G4A3 woman presented at 25 weeks of pregnancy with progressive signs of Cushing’s syndrome (CS), gestational diabetes requiring insulin and hypertension. A 3.4 × 3.3 cm right adrenal adenoma was identified during abdominal ultrasound imaging for nephrolithiasis. Investigation revealed elevated levels of plasma cortisol, 24 h urinary free cortisol (UFC) and late-night salivary cortisol (LNSC). Serum ACTH levels were not fully suppressed (4 and 5 pmol/L (N: 2–11)). One month post-partum, CS regressed, 24-h UFC had normalised while ACTH levels were now less than 2 pmol/L; however, dexamethasone failed to suppress cortisol levels. Tests performed in vivo 6 weeks post-partum to identify aberrant hormone receptors showed no cortisol stimulation by various tests (including 300 IU hLH i.v.) except after administration of 250 µg i.v. Cosyntropin 1–24. Right adrenalectomy demonstrated an adrenocortical adenoma and atrophy of adjacent cortex. Quantitative RT-PCR analysis of the adenoma revealed the presence of ACTH (MC2) receptor mRNA, while LHCG receptor mRNA was almost undetectable. This case reveals that CS exacerbation in the context of pregnancy can result from the placental-derived ACTH stimulation of MC2 receptors on the adrenocortical adenoma. Possible contribution of other placental-derived factors such as oestrogens, CRH or CRH-like peptides cannot be ruled out. Learning points: Diagnosis of Cushing’s syndrome during pregnancy is complicated by several physiological alterations in hypothalamic–pituitary–adrenal axis regulation occurring in normal pregnancy. Cushing’s syndrome (CS) exacerbation during pregnancy can be associated with aberrant expression of LHCG receptor on primary adrenocortical tumour or hyperplasia in some cases, but not in this patient. Placental-derived ACTH, which is not subject to glucocorticoid negative feedback, stimulated cortisol secretion from this adrenal adenoma causing transient CS exacerbation during pregnancy. Following delivery and tumour removal, suppression of HPA axis can require several months to recover and requires glucocorticoid replacement therapy.

How useful is 24 hour Urinary Free Cortisol as a screening tool for Cushing's syndrome?

2018 ◽  
Author(s):  
Ahmed Hanafy ◽  
Chinnadorai Rajeswaran ◽  
Saad Saddiq ◽  
Warren Gillibrand ◽  
John Stephenson
Keyword(s):  
Cushing’S Syndrome ◽  
Screening Tool ◽  
Urinary Free Cortisol ◽  
Cushing's Syndrome ◽  
Free Cortisol

scholarly journals Scalp hair cortisol for diagnosis of Cushing’s syndrome

2017 ◽  
Vol 176 (6) ◽  
pp. 695-703 ◽  
Author(s):  
Vincent L Wester ◽  
Martin Reincke ◽  
Jan W Koper ◽  
Erica L T van den Akker ◽  
Laura Manenschijn ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Scalp Hair ◽  
Geometric Mean ◽  
Disease Onset ◽  
Cushing's Syndrome ◽  
Screening Tests ◽  
Healthy Controls ◽  
Hair Cortisol ◽  
First Line ◽  
Free Cortisol

Objective Current first-line screening tests for Cushing’s syndrome (CS) only measure time-point or short-term cortisol. Hair cortisol content (HCC) offers a non-invasive way to measure long-term cortisol exposure over several months of time. We aimed to evaluate HCC as a screening tool for CS. Design Case-control study in two academic referral centers for CS. Methods Between 2009 and 2016, we collected scalp hair from patients suspected of CS and healthy controls. HCC was measured using ELISA. HCC was available in 43 confirmed CS patients, 35 patients in whom the diagnosis CS was rejected during diagnostic work-up and follow-up (patient controls), and 174 healthy controls. Additionally, we created HCC timelines in two patients with ectopic CS. Results CS patients had higher HCC than patient controls and healthy controls (geometric mean 106.9 vs 12.7 and 8.4 pg/mg respectively, P < 0.001). At a cut-off of 31.1 pg/mg, HCC could differentiate between CS patients and healthy controls with a sensitivity of 93% and a specificity of 90%. With patient controls as a reference, specificity remained the same (91%). Within CS patients, HCC correlated significantly with urinary free cortisol (r = 0.691, P < 0.001). In two ectopic CS patients, HCC timelines indicated that cortisol was increased 3 and 6 months before CS became clinically apparent. Conclusions Analysis of cortisol in a single scalp hair sample offers diagnostic accuracy for CS similar to currently used first-line tests, and can be used to investigate cortisol exposure in CS patients months to years back in time, enabling the estimation of disease onset.

Sign in / Sign up

Export Citation Format

Share Document