Elsevier

Endocrine Practice

Volume 19, Issue 3, May–June 2013, Pages e77-e82
Endocrine Practice

Case Report
Adrenocorticotropic Hormone Independent Macronodular Adrenal Hyperplasia due to Aberrant Receptor Expression: Is Medical Treatment Always an Option?

https://doi.org/10.4158/EP12346.CRGet rights and content

ABSTRACT

Objective

To investigate the efficacy of medical treatment as an alternative option to bilateral adrenalectomy in patients with cortisol excess due to adrenocorticotropic hormone (ACTH) independent macronodular adrenal hyperplasia (AIMAH).

Methods

We focused on the efficacy of somatostatin analogues in a patient with food-dependent AIMAH and of leuprolide acetate in a patient with AIMAH due to aberrant LH/hCG receptor expression.

Results

Two female patients with bilateral macronodular adrenal hyperplasia and cortisol excess were evaluated for the presence of aberrant cortisol responses. One patient demonstrated an aberrant response to mixed meal and the other, a menopausal female, to luteinizing hormonereleasing hormone (LHRH) and human chorionic gonadotropin (hCG) administration. In the first patient, subcutaneous octreotide was administered prior to mixed meal and completely abolished food-induced cortisol secretion. Thus, the patient was treated with the long-acting somatostatin analogue octreotide long-acting release (LAR) for 3 months. There was no control of cortisol excess upon reevaluation and acute subcutaneous octreotide administration prior to meal was no longer effective in blocking food-induced cortisol secretion. The second patient successfully responded to leuprolide acetate and, for 40 months, her cortisol excess remains in long-term control.

Conclusion

A luteinizing hormone/human chorionic gonadotropin (LH/hCG) responsive patient with AIMAH sustained long-term control of cortisol excess on leuprolide acetate. In contrast, in a meal-responsive patient with apparent gastric inhibitory polypeptide (GIP) dependent AIMAH, did not achieve remission under somatostatin analogues. (Endocr Pract. 2013;19:e77-e82)

Section snippets

INTRODUCTION

Adrenocorticotropic hormone (ACTH) independent macronodular adrenal hyperplasia (AIMAH) is a rare form of Cushing’s syndrome where ACTH-independent hypercortisolism is under the control of aberrant receptors such as those for gastric inhibitory polypeptide (GIP), P-adrenergic receptors, vasopressin, serotonin, angiotensin II, and luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor (1). Most receptors belong to the superfamily of G-protein coupled receptors (GPCR) and their

DISCUSSION

AIMAH represents a rare albeit challenging to diagnose and treat form of adrenal Cushing syndrome (2). So far, pharmaceutical intervention of aberrantly expressed adrenal receptors has been attempted in only few cases with conflicting results. In this report, we have presented two AIMAH patients, one with food-dependent cortisol secretion and another with aberrant LH/hCG receptor expression. Only the latter patient had a long-lasting control of cortisol excess following medical intervention.

CONCLUSIONS

We reported two cases of AIMAH where cortisol production was under control of different illegitimate membrane receptors; GIP receptor in the first and LH/hCG in the second case. In the latter case, we suggest that pharmacological therapy with leuprolide can be the first line treatment, whereas in food-dependent Cushing syndrome somatostatin analogue effect is transient probably due to downregulation of somatostatin receptors.

DISCLOSURE

Dr. Stylianos Tsagarakis, and Dr. Marinella Tzanela, received research, and travel grants from Novartis. The other authors have no multiplicity of interest to disclose.

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