scholarly journals Paediatric Cushing’s disease: Epidemiology, pathogenesis, clinical management and outcome

2021 ◽  
Author(s):  
Rosario Ferrigno ◽  
Valeria Hasenmajer ◽  
Silvana Caiulo ◽  
Marianna Minnetti ◽  
Paola Mazzotta ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Growth Failure ◽  
Surgical Care ◽  
Pituitary Surgery ◽  
Cushing's Disease ◽  
Pituitary Hormone ◽  
Psychological Disturbance ◽  
Steroid Synthesis ◽  
Adrenal Steroid ◽  
Diagnosis And Therapy

AbstractCushing’s disease (CD) is rare in paediatric practice but requires prompt investigation, diagnosis and therapy to prevent long-term complications. Key presenting features are a change in facial appearance, weight gain, growth failure, virilization, disturbed puberty and psychological disturbance. Close consultation with an adult endocrinology department is recommended regarding diagnosis and therapy. The incidence of CD, a form of ACTH-dependent Cushing’s syndrome (CS), is equal to approximately 5% of that seen in adults. The majority of ACTH-secreting adenomas are monoclonal and sporadic, although recent studies of pituitary tumours have shown links to several deubiquitination gene defects. Diagnosis requires confirmation of hypercortisolism followed by demonstration of ACTH-dependence. Identification of the corticotroph adenoma by pituitary MRI and/or bilateral inferior petrosal sampling for ACTH may contribute to localisation before pituitary surgery. Transsphenoidal surgery (TSS) with selective microadenomectomy is first-line therapy, followed by external pituitary irradiation if surgery is not curative. Medical therapy to suppress adrenal steroid synthesis is effective in the short-term and bilateral adrenalectomy should be considered in cases unfit for TSS or radiotherapy or when urgent remission is needed after unsuccessful surgery. TSS induces remission of hypercortisolism and improvement of symptoms in 70–100% of cases, particularly when performed by a surgeon with experience in children. Post-TSS complications include pituitary hormone deficiencies, sub-optimal catch-up growth, and persisting excess of BMI. Recurrence of hypercortisolism following remission is recognised but infrequent, being less common than in adult CD patients. With experienced specialist medical and surgical care, the overall prognosis is good. Early referral to an experienced endocrine centre is advised.

Sinonasal Outcomes after Pituitary Surgery in Patient's with Cushing's Disease

2020 ◽  
Author(s):  
Nadeem R. Kolia ◽  
Paul A. Gardner ◽  
Carl H. Snyderman ◽  
Eric W. Wang
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Surgery ◽  
Cushing's Disease

ULTRADIAN adrenal steroid metabolodynamics successfully discriminates pituitary Cushing's disease from healthy normal variation

2019 ◽  
Author(s):  
Thomas Upton ◽  
Eder Zavala ◽  
Diane Fraser ◽  
Paal Methlie ◽  
Georgina Russell ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Cushing's Disease ◽  
Normal Variation ◽  
Adrenal Steroid

scholarly journals P34 Characteristics, diagnosis and management of Cushing’s disease - A systematic review and meta-analysis

BJS Open ◽  
2021 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Chan Hee Koh ◽  
Danyal Z Khan ◽  
Ronneil Digpal ◽  
Hugo Layard Horsfall ◽  
Hani J Marcus ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cushing’S Disease ◽  
Meta Analysis ◽  
A Priori ◽  
Pituitary Surgery ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Diagnosis And Management ◽  
Over Time

Abstract Introduction The clinical practice and research in the diagnosis and management of Cushing’s disease remains heterogeneous and challenging to this day. We sought to establish the characteristics of Cushing’s disease, and the trends in diagnosis, management and reporting in this field. Methods Searches of PubMed and Embase were conducted. Study protocol was registered a-priori. Random-effects analyses were conducted to establish numerical estimates. Results Our screening returned 159 papers. The average age of adult patients with Cushing’s disease was 39.3, and 13.6 for children. The male:female ratio was 1:3. 8% of patients had undergone previous transsphenoidal resection. The ratio of macroadenomas: microadenomas:imaging-undetectable adenomas was 18:53:29. The most commonly reported preoperative biochemical investigations were serum cortisol (average 26.4µg/dL) and ACTH (77.5pg/dL). Postoperative cortisol was most frequently used to define remission (74.8%), most commonly with threshold of 5µg/dL (44.8%). Average remission rates were 77.8% with recurrence rate of 13.9%. Median follow-up was 38 months. Majority of papers reported age (81.9%) and sex (79.4%). Only 56.6% reported whether their patients had previous pituitary surgery. 45.3% reported whether their adenomas were macroadenoma, microadenoma or undetectable. Only 24.1% reported preoperative cortisol, and this did not improve over time. 60.4% reported numerical thresholds for cortisol in defining remission, and this improved significantly over time (p = 0.004). Visual inspection of bubbleplots showed increasing preference for threshold of 5µg/dL. 70.4% reported the length of follow up. Conclusion We quantified the characteristics of Cushing’s disease, and analysed the trends in investigation and reporting. This review may help to inform future efforts in forming guidelines for research and clinical practice.

scholarly journals Endoscopic transsphenoidal pituitary surgery: a good and safe primary treatment option for Cushing's disease, even in case of macroadenomas or invasive adenomas

2013 ◽  
Vol 169 (3) ◽  
pp. 329-337 ◽  
Author(s):  
M A E M Wagenmakers ◽  
H D Boogaarts ◽  
S H P P Roerink ◽  
H J L M Timmers ◽  
N M M L Stikkelbroeck ◽  
...  
Keyword(s):  
Treatment Option ◽  
Cushing’S Disease ◽  
Remission Rate ◽  
Pituitary Surgery ◽  
Primary Treatment ◽  
Endoscopic Technique ◽  
Cushing's Disease ◽  
Recurrence Rates ◽  
Transsphenoidal Pituitary Surgery

ContextAlthough the endoscopic technique of transsphenoidal pituitary surgery (TS) has been widely adopted, reports on its results in Cushing's disease (CD) are still scarce and no studies have investigated long-term recurrence rates. This is the largest endoscopic series published till now.ObjectiveTo gain insight into the role of endoscopic TS as a primary treatment option for CD, especially in patients with magnetic resonance imaging (MRI)-negative CD and (invasive) macroadenomas.DesignRetrospective cohort study.Patients and methodsThe medical records of 86 patients with CD who underwent endoscopic TS were examined. Data on preoperative and postoperative evaluation, perioperative complications, and follow-up were collected. Remission was defined as disappearance of clinical symptoms with a fasting plasma cortisol level ≤50 nmol/l either basal or after 1 mg dexamethasone.ResultsThe remission rate in different adenoma subclasses varied significantly: 60% in MRI-negative CD (n=20), 83% in microadenomas (n=35), 94% in noninvasive macroadenomas (n=16), and 40% in macroadenomas that invaded the cavernous sinus (n=15). The recurrence rate was 16% after 71±39 months of follow-up (mean±s.d., range 10–165 months).ConclusionsEndoscopic TS is a safe and effective treatment for all patients with CD. Recurrence rates after endoscopic TS are comparable with those reported for microscopic TS. Our data suggest that in patients with noninvasive and invasive macroadenomas, the endoscopic technique of TS should be the treatment of choice as remission rates seem to be higher than those reported for microscopic TS, although no comparative study has been performed.

scholarly journals Endogenous ACTH Concentration-Cortisol Secretion Dose Analysis Unmasks Decreased ACTH Potency in Cushing's Disease with Restoration after Successful Pituitary Adenomectomy

2011 ◽  
Vol 96 (12) ◽  
pp. 3768-3774 ◽  
Author(s):  
Ferdinand Roelfsema ◽  
Daniel M. Keenan ◽  
Johannes D. Veldhuis
Keyword(s):  
Surgical Treatment ◽  
Cushing’S Disease ◽  
Pituitary Surgery ◽  
Pulse Frequency ◽  
Cushing's Disease ◽  
P Value ◽  
Cortisol Secretion ◽  
Acth Concentration ◽  
Active Disease

Background: The relationship between circulating ACTH levels and cortisol secretion in Cushing's disease is not precisely known. Hypothesis: Chronic ACTH hyperstimulation leads to decreased adrenal potency and is restored after normalization of ACTH secretion. Subjects: Subjects included 20 patients with Cushing's disease, eight patients in long-term remission, and 36 healthy controls. Outcomes: ACTH and cortisol secretion rates and analytical dose-response estimates of endogenous ACTH efficacy (maximal cortisol secretion), dynamic ACTH potency, and adrenal sensitivity (slope term) from 24-h ACTH-cortisol profiles were evaluated. Results: Both basal and pulsatile secretion of ACTH and cortisol were increased in patients with active disease but normal in cured patients. ACTH, but not cortisol pulse frequency, was amplified in patients and restored after successful surgical treatment. ACTH EC50, an inverse measure of potency, was higher during pulse onset in Cushing's disease (59 ± 7.4 ng/liter) than in controls (20 ± 3.7 ng/liter) (P < 0.0001) and remitted patients after surgery [15 ± 3.2 ng/liter, P value not significant (NS) vs. controls] and during pulse recovery phases [128 ± 18 (P <0.0001), 70 ± 8.4, and 67 ± 17 ng/liter (NS vs. controls), respectively]. Efficacy was increased in active disease and normalized after surgical treatment [patients, 38 ± 8.3 nmol/liter · min, vs. controls, 21 ± 2.3 nmol/liter · min (P <0.0001), and cured patients, 15 ± 3.2 nmol/liter · min (NS vs. controls)]. Sensitivity to endogenous ACTH did not differ among the three groups. Conclusion: The adrenal gland in Cushing's disease exhibits decreased responsiveness to submaximal ACTH drive and amplified efficacy, with unchanged sensitivity. These target-gland abnormalities are reversible in long-term remission after pituitary surgery.

Long-term remission rates after pituitary surgery for Cushing's disease: the need for long-term surveillance

2005 ◽  
Vol 63 (5) ◽  
pp. 549-559 ◽  
Author(s):  
A. Brew Atkinson ◽  
Adele Kennedy ◽  
M. Ivan Wiggam ◽  
David R. McCance ◽  
Brian Sheridan
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Surgery ◽  
Cushing's Disease ◽  
Remission Rates

Postoperative metyrapone test in the early assessment of outcome of pituitary surgery for Cushing's disease

1997 ◽  
Vol 47 (2) ◽  
pp. 145-149 ◽  
Author(s):  
Maarten O. Van Aken ◽  
Wouter W. De Herder ◽  
Aart-Jan Van Der Lely ◽  
Frank H. De Jong ◽  
Steven W. J. Lamberts
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Surgery ◽  
Cushing's Disease ◽  
Early Assessment

scholarly journals Linear Growth and Final Height after Treatment for Cushing’s Disease in Childhood

2000 ◽  
Vol 85 (9) ◽  
pp. 3262-3265
Author(s):  
Marie-Christine Lebrethon ◽  
Ashley B. Grossman ◽  
Farhad Afshar ◽  
P. Nicholas Plowman ◽  
G. Michael Besser ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Final Height ◽  
Growth Failure ◽  
Height Velocity ◽  
Cushing's Disease ◽  
Childhood And Adolescence ◽  
Target Height ◽  
Gnrh Analog ◽  
The Mean ◽  
The Difference

Abstract Cushing’s disease is associated with growth failure in childhood and adolescence. Growth and final height were analyzed in 10 patients who were cured or in remission after treatment of Cushing’s disease. Seven males and 3 females, aged 6.8–17.6 yr (bone age, 3.3- 15.4 yr), had transsphenoidal surgery, which was combined with pituitary irradiation (4500 cGy in 25 fractions) in 5 patients. At presentation, 5 patients were prepubertal (males), and 5 were pubertal (2 males and 3 females). The mean height sd score was −2.15 ± 1.26 (range, −0.21 to −4.32) compared with mean target height sd score of −0.43 ± 0.58. Height velocity in 6 patients was subnormal (0.9–3.8 cm/yr). After treatment, short-term height velocity, over a mean interval of 0.57 yr, in 8 patients not receiving human GH (hGH) therapy, was variable (range, 0.8–7.6 cm/yr). GH stimulation tests (insulin tolerance test/glucagon) in 9 subjects showed peak GH levels of 0.5–20.9 mU/L. Eight were treated with hGH (14 IU/m2·wk), combined in 2 girls and 1 boy with a GnRH analog. After 1 yr of hGH, the mean height sd score had increased from −2.45 ± 1.0 at initiation of hGH to −2.07± 1.2 (P = 0.01). GH therapy was continued until final height or latest assessment. The mean final height sd score (n = 6) was −1.24 ± 1.38, and at the latest assessment the mean height sd score (n = 4) was− 1.52 ± 1.33. Combining these 2 groups, the mean height sd score was −1.36 ± 1.29. The difference between final or latest height sd score and target height sd score was 0.93 ± 1.13, i.e. less (P = 0.005) than the difference between height and target height sd score of 1.72 ± 1.26 at presentation. In conclusion, catch-up and favorable long-term growth was seen after treatment for Cushing’s disease. Posttreatment GH deficiency was frequent, and early hGH replacement may have contributed to the encouraging outcome.

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