Obesity: Cushing or No Cushing?
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ABSTRACT: Silent corticotroph adenomas (SCAs) are rare pituitary tumours immunoreactive for ACTH, but without clinical evidence of Cushing's disease. We characterized SCAs based on clinical, hormonal and molecular data, and compared the characteristics of these tumours with those of macro (MCA)- and micro (mCA)-ACTH adenomas with Cushing's disease. Fifty ACTH adenomas (14 SCAs, 15 MCAs and 21 mCAs) with complete corresponding clinical, radiological and biochemical data were selected. Histological corticotroph differentiation; immunostaining for ACTH, beta-endorphin and beta-LPH; and mRNA expression levels of TPIT, POMC, GRalpha, prohormone convertase 1/3 (PC1/3) and galectin-3 were compared in 21 representative tumours. Despite the absence of clinical hypercortisolism in patients with SCA, elevated plasma ACTH levels that were similar to those associated with mCA were observed. The cortisol/ACTH ratio was similar between SCA and MCA groups and lower than that found with mCA (P<0.05). This dissociation could be explained by lower expression of PC1/3 in SCA and MCA than in mCA (P<0.05). After an i.v. dexamethasone suppression test, ACTH levels were significantly higher in patients with MCA than in those with mCA (P<0.05). Cytological and immunocytochemical analyses as well as mRNA expression levels of TPIT, POMC and GRalpha confirmed corticotroph differentiation in both mCAs and MCAs and in half of the SCAs, with a strong correlation between TPIT and POMC mRNA expression levels in SCAs (R(2)=0.72; P<0.01) and in MCAs (R(2)=0.65; P<0.05). Despite the absence of hypercortisolism, SCAs exhibit histological, biochemical and molecular corticotroph differentiation. SCA and MCA show hormonal and molecular similarities differentiating them from mCA.European Journal of Endocrinology 04/2010; 163(1):35-43. · 3.69 Impact Factor
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ABSTRACT: Several endocrine abnormalities, including hypothyroidism and Cushing's syndrome (CS), are considered as causative factors of obesity. The aim of this study was to evaluate the prevalence of endocrine disorders and obesity-associated co-morbidities, as well as the impact of substantial weight loss. Screening was performed in 433 consecutive morbidly obese patients (age 41 ± 12 years; BMI 47 ± 6.9 kg/m(2); women 76%). A 1-mg dexamethasone suppression test (1-mg DST) was conducted to exclude CS, and thyrotropin (TSH) was measured to exclude hypothyroidism. Insulin sensitivity was estimated from oral glucose tolerance tests employing the Clamp-like index. Examinations were carried out at baseline, as well as at 6 and 12 months postoperatively. The prevalence of CS was below 0.6%. Before surgery, TSH was elevated compared to an age- and sex-matched normal weight control group (2.4 ± 1.2 vs. 1.5 ± 0.7 μU/ml; p < 0.001). The NCEP criteria of metabolic syndrome (MetS) were fulfilled by 39.5% of the patients. Impaired glucose tolerance and diabetes mellitus were observed in 23.5% and 22.6%, respectively. Seventy-two percent were insulin resistant. During follow-up, weight (BMI 47 ± 6.9 vs. 36 ± 6.4 vs. 32 ± 6.6 kg/m(2); p < 0.001) and TSH decreased significantly (2.4 ± 1.2 vs. 1.8 ± 1.0 vs. 1.8 ± 1.0 μU/ml; p < 0.001). Serum cortisol was higher in the MetS(+)-group compared to the MetS(-)-group (15.0 ± 6.3 vs. 13.5 ± 6.3 μg/dl; p = 0.003). CS appears to be a rare cause of morbid obesity. Normalization of slightly elevated thyrotropin after weight loss suggests that obesity causes TSH elevation rather than the reverse.Obesity Surgery 11/2011; 22(1):62-9. · 3.74 Impact Factor
- Neurosurgery 10/2012; · 3.03 Impact Factor
2. Horvath E, Kovacs K, Killinger DW, Smyth HS, Platts ME, Singer W. Silent
corticotroph adenomas of the human pituitary gland: a histologic, immunocytologic,
and ultrastructural study. Am J Pathol. 1980;98(3):617-638.
Although the prevalence of obesity in 2000 was lower than it is
now, the proportion of patients with Cushing syndrome (CS) has
not changed in parallel.1CS was present in , 0.6% of 433
morbidly obese subjects. Interestingly, bariatric surgery in these
patients normalized slightly elevated preoperative thyrotropin
levels.2Screening for CS, including a 1-mg dexamethasone
suppression test, in 150 obese patients identified CS in 9%
(14 patients), whereas elevated levels of 24-hour urinary free
cortisol were recorded in 24% (37 patients).3Similarly, the
observed prevalence rates of CS in patients with type 2 diabetes
mellitus vary and range from 0% to 9%,4underscoring that the
cons surpass the pros for screening for CS at present.5Biochemical
evaluation should take into account the limitations of assays
including heterophil antibodies.6In obese patients with type 2
diabetes mellitus without clinical features of CS, ruling in
cortisol of 90%, and 1-mg dexamethasone suppression test of
72%.7In our patient,8initial early-morning serum cortisol was
15.7 mg/dL (433 nmol/L), in line with findings in the literature on
silent corticotroph pituitary adenomas (343 6 112 nmol/L) and
(790 nmol/L) or micro-ACTHomas (653 nmol/L).9
Dr Koch has received consulting fees from Corcept and Ipsen.
Christian A. Koch
1. Koch CA. Endocrine hypertension: what is new? Rev Port Endocrinol Diabetes.
2. Jankovic D, Wolf P, Anderwald CH, et al. Prevalence of endocrine disorders in
morbidly obese patients and the effects of bariatric surgery on endocrine and
metabolic parameters. Obes Surg. 2012;22(1):62-69.
3. Tiryakioglu O, Ugurlu S, Yalin S, et al. Screening for Cushing’s syndrome in obese
patients. Clin (Sao Paulo). 2010;65(1):9-13.
4. Krarup T, Hagen C. Do patients with type 2 diabetes mellitus have an increased
prevalence of Cushing’s syndrome? Diabetes Metab Res Rev. 2012;28(3):219-227.
5. Tabarin A, Perez P. Pros and cons of screening for occult Cushing syndrome. Nat
Rev Endocrinol. 2011;7(8):445-455.
6. Melcescu E, Ng KK, Grebe SK, et al. False positive ACTH caused by heterophil
antibody in an obese patient considered for possible Cushing’s syndrome. Endocr
7. Ellis E, Chin PK, Hunt PJ, et al. Is late-night salivary cortisol a better screening test
for possible cortisol excess than standard screening tests in obese patients with type 2
diabetes? N Z Med J. 2012;125(1353):47-58.
8. Melcescu E, Gannon AW, Parent AD, et al. Silent or subclinical corticotroph
pituitary macroadenoma transforming into Cushing disease: 11-year follow-up.
9. Raverot G, Wierinchx A, Jouanneau E, et al. Clinical, hormonal and molecular
characterization of pituitary ACTH adenomas without (silent corticotroph
adenomas) and with Cushing’s disease. Eur J Endocrinol. 2010;163(1):35-43.
Intracranial Aneurysms With Small Basal Outpouching
To the Editor:
IfoundthearticlebyParketal1very interesting. We know that
procedure-related ruptures are one of the most significant
complications of coiling, and very small aneurysms are found
to be associated with a higher risk of rupture. This study showed
that the basal outpouching was identified as the rupture point in
31% of the aneurysm cases with basal outpouchings, and
endovascular coiling carried high risk of intraprocedural rebleed-
ing in this group of patients.
However, I have some comments regarding to this article. First of
first angiographic evaluation of the patient. When I reviewed the
article, I saw that the basal outpouching was evaluated based on 3-
dimensional reconstruction digital subtraction angiographic images
respectively. I could not find any information about which of these 2
is obvious that this information is reliable only in surgical cases if you
compare the preoperative angiographic findings with operative
findings. But this information about the superiority of the imaging
patients with ruptured aneurysms in planning further management.
One of the comments given in the article had emphasized the
importance of the high-quality imaging by rotational angiography.
My second comment about this article is related to the planning
team.Ideally,the managementstrategy fortheruptured aneurysms
endovascular teams. In the planning the approach, catheter
angiography is seen to be more feasible and suitable for both
groups, but the decision regarding the approach depends on the
procedure to the endovascular team if the hospital has equally
experienced both microsurgical and endovascular teams. On the
other hand, microvascular surgeons will become more confident
when they are recommending surgery to their patients. But all
around the world, because of the lack of the experienced microvas-
cularsurgeons,itwouldnot affectthe planningofthemanagement
of the treatment in most hospitals. I hope that the development of
the new coiling technologies will solve this problem and provide
a safer approach to the treatment of this kind of aneurysm in near
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