Food-dependent Cushing's syndrome: from molecular characterization to therapeutical results

被引:34
作者
Albiger, N. M.
Occhi, G.
Mariniello, B.
Iacobone, M. [1 ,2 ,3 ]
Favia, G. [1 ,2 ,3 ]
Fassina, A.
Faggian, D.
Mantero, F.
Scaroni, C.
机构
[1] Univ Padua, Dept Endocrine Surg, I-35128 Padua, Italy
[2] Univ Padua, Dept Pathol, I-35128 Padua, Italy
[3] Univ Padua, Media Lab, I-35128 Padua, Italy
关键词
D O I
10.1530/EJE-07-0253
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Cortisol secretion in ACTH-independent macronodular adrenal hyperplasia (AIMAH) may be regulated by the aberrant expression of several G-protein-coupled receptors. Bilateral adrenalectomy is the treatment of choice in most cases. We searched for aberrant receptor expression in a patient with AIMAH and evaluated the response to medical and surgical treatment. Patient: A 35-year-old woman with amenorrhea, hirsutism, and hypertension presented ACTH-independent cortisol secretion with high androgen levels. Abdominal computed tomography showed bilateral adrenal macronodules (4.5 cm right and 1.0 cm left). Scintigraphy with I-131-norcholesterol showed bilateral uptake, prevalent on the right side. Several in vivo stimulation tests were assessed before and after treatment and in vitro studies were performed after unilateral adrenalectomy. Results: Plasma cortisol increased after a standard meal test (60%) and oral glucose loading (147%), and the response was blunted by pretreatment with 100 mu g s.c. octreotide. The therapy with long-acting release octreotide (octreotide-LAR) showed an improvement in urinary free cortisol (UFC) levels. Unilateral adrenalectomy was performed and histopathology revealed macronodular AIMAH. Cortisol and androgens increased after perifusion of tumoral tissue with glucose-dependent insulinotropic polypeptide (GIP), and GIP and LH-receptor overexpression was found in both the adrenal nodules and the adjacent cortex. After surgery, UFC and androgen levels normalized followed by clinical improvement. Conclusions: GIP and LH-receptor expression may coexist in AIMAH, influencing the functional and morphological phenotype. Aberrant hormone receptor expression enables specific pharmacological treatment, but long-term studies are needed to evaluate its real efficacy. Unilateral adrenalectomy may be a safe initial option, particularly for asymmetric bilateral adrenal enlargements.
引用
收藏
页码:771 / 778
页数:8
相关论文
共 39 条
[1]   Analysis of the putative regulatory region of the gastric inhibitory polypeptide receptor gene in food-dependent Cushing's syndrome [J].
Antonini, SR ;
N'Diaye, N ;
Baldacchino, V ;
Hamet, P ;
Tremblay, J ;
Lacroix, A .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2004, 91 (03) :171-177
[2]   In vivo and in vitro screening for illegitimate receptors in adrenocorticotropin-independent macronodular adrenal hyperplasia causing Cushing's syndrome:: Identification of two cases of gonadotropin/gastric inhibitory polypeptide-dependent hypercortisolism [J].
Bertherat, J ;
Contesse, V ;
Louiset, E ;
Barrande, G ;
Duparc, C ;
Groussin, L ;
Émy, P ;
Bertagna, X ;
Kuhn, JM ;
Vaudry, H ;
Lefebvre, H .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2005, 90 (03) :1302-1310
[3]   VIRILIZING ADRENOCORTICAL ADENOMA RESPONSIVE TO GONADOTROPIN [J].
BLICHERTTOFT, M ;
VEJLSTED, H ;
KEHLET, H ;
ALBRECHTSEN, R .
ACTA ENDOCRINOLOGICA, 1975, 78 (01) :77-85
[4]   Cushing's syndrome due to a gastric inhibitory polypeptide-dependent adrenal adenoma: Insights into hormonal control of adrenocortical tumorigenesis [J].
Chabre, O ;
Liakos, P ;
Vivier, J ;
Chaffanjon, P ;
Labat-Moleur, F ;
Martinie, M ;
Bottari, SP ;
Bachelot, I ;
Chambaz, EM ;
Defaye, G ;
Feige, JJ .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (09) :3134-3143
[5]   Clinical and subclinical ACTH-independent macronodular adrenal hyperplasia and aberrant hormone receptors [J].
Christopoulos, S ;
Bourdeau, I ;
Lacroix, A .
HORMONE RESEARCH, 2005, 64 (03) :119-131
[6]   GIP-dependent adrenal Cushing's syndrome with incomplete suppression of ACTH [J].
Croughs, RJM ;
Zelissen, PMJ ;
van Vroonhoven, TJMV ;
Hofland, LJ ;
N'diaye, N ;
Lacroix, A ;
de Herder, WW ;
Zelissen, MJ .
CLINICAL ENDOCRINOLOGY, 2000, 52 (02) :235-240
[7]   Androgen-secreting adrenal adenomas [J].
Danilowicz, K ;
Albiger, N ;
Vanegas, M ;
Gómez, RM ;
Cross, G ;
Bruno, OD .
OBSTETRICS AND GYNECOLOGY, 2002, 100 (05) :1099-1102
[8]   Food-dependent Cushing's syndrome resulting from abundant expression of gastric inhibitory polypeptide receptors in adrenal adenoma cells [J].
deHerder, WW ;
Hofland, LJ ;
Usdin, TB ;
deJong, FH ;
Uitterlinden, P ;
vanKoetsveld, P ;
Mezey, E ;
Bonner, TI ;
Bonjer, HJ ;
Lamberts, SWJ .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1996, 81 (09) :3168-3172
[9]   GONADOTROPIN RESPONSIVE TESTOSTERONE PRODUCING ADRENOCORTICAL ADENOMA AND HIGH GONADOTROPIN-LEVELS IN AN ELDERLY WOMAN [J].
DELANGE, WE ;
PRATT, JJ ;
DOORENBOS, H .
CLINICAL ENDOCRINOLOGY, 1980, 12 (01) :21-28
[10]   CLINICAL ASSESSMENT OF BODY HAIR GROWTH IN WOMEN [J].
FERRIMAN, D ;
GALLWEY, JD .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1961, 21 (11) :1440-+