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

Abstract

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 microg 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.

• Authors: N M Albiger, G Occhi, B Mariniello, M Iacobone, G Favia, A Fassina, D Faggian, F Mantero, C Scaroni
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 157 Issue 6 Pg. 771-8 (Dec 2007) ISSN: 1479-683X [Electronic] England
• PMID: 18057385 (Publication Type: Case Reports, Journal Article)

Chemical References

• RNA, Messenger
• Receptors, Gastrointestinal Hormone
• Receptors, LH
• Gonadotropin-Releasing Hormone
• Gastric Inhibitory Polypeptide
• Thyrotropin-Releasing Hormone
• gastric inhibitory polypeptide receptor
• Hydrocortisone

Topics

• Adrenal Glands (pathology)
• Adrenalectomy
• Adult
• Cushing Syndrome (etiology, pathology, therapy)
• Female
• Food
• Gastric Inhibitory Polypeptide (blood)
• Glucose Tolerance Test
• Gonadotropin-Releasing Hormone
• Humans
• Hydrocortisone (blood)
• Immunohistochemistry
• RNA, Messenger (metabolism)
• Receptors, Gastrointestinal Hormone (analysis)
• Receptors, LH (analysis)
• Reverse Transcriptase Polymerase Chain Reaction
• Thyrotropin-Releasing Hormone