Medical Therapies in Cushing’s Syndrome

Posted on December 4, 2016 by MaryO
Chapter

The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease

pp 165-179

Date: 03 December 2016

Medical Therapies in Cushing’s Syndrome

Abstract

Medical therapy has an important, albeit secondary, role in patients with Cushing’s syndrome. While medications are not currently used as definitive therapy of this condition, they can be very effective in controlling hypercortisolism in patients who fail surgery, those who are not surgical candidates, or those whose tumor location is unknown. Medical therapies can be particularly helpful to control hypercortisolism in patients with Cushing’s disease who underwent radiation therapy and are awaiting its salutary effects.

Currently available treatment options include several steroidogenesis inhibitors (ketoconazole, metyrapone, mitotane, etomidate), which block one or several steps in cortisol synthesis in the adrenal glands, centrally acting agents (cabergoline, pasireotide), which decrease ACTH secretion, and glucocorticoid receptor antagonists, which are represented by a single agent (mifepristone). With the exception of pasireotide and mifepristone, available agents are used “off-label” to manage hypercortisolism. Several other medications are at various stages of development and may offer additional options for the management of this serious condition.

As more potential molecular targets become known and our understanding of the pathogenesis of Cushing’s syndrome improves, it is anticipated that novel, rationally designed medical therapies may emerge. Clinical trials are needed to further investigate the relative risks and benefits of currently available and novel medical therapies and examine the potential role of combination therapy in the management of Cushing’s syndrome.

Keywords

Cabergoline, Etomidate, Ketoconazole, Levoketoconazole, Metyrapone, Mifepristone, Mitotane, Osilodrostat, Pasireotide, Pituitary adenoma

From http://link.springer.com/chapter/10.1007/978-3-319-45950-9_9

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Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and Subclinical Cushing Syndrome

Posted on August 16, 2016 by MaryO

Eur J Endocrinol. 2016 Jul 22. pii: EJE-16-0465. [Epub ahead of print]

Bancos I1, Alahdab F2, Crowley RK3, Chortis V4, Delivanis D5, Erickson D6, Natt N7, Terzolo M8, Arlt W9, Young W10, Murad MH11.

Author information

Abstract

OBJECTIVE:

Beneficial effects of adrenalectomy on cardiovascular risk factors in patients with Subclinical Cushing Syndrome (SCS) are uncertain. We sought to conduct a systematic review and meta-analysis with the following objectives: 1) determine the effect of adrenalectomy compared to conservative management on cardiovascular risk factors in patients with SCS and 2) compare the effect of adrenalectomy on cardiovascular risk factors in patients with SCS versus those with a non-functioning (NF) adrenal tumor.

METHODS:

Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial were searched on November 17th, 2015. Reviewers extracted data and assessed methodological quality in duplicate.

RESULTS:

We included 26 studies reporting on 584 patients with SCS and 457 patients with NF adrenal tumors. Studies used different definitions of SCS. Patients with SCS undergoing adrenalectomy demonstrated an overall improvement in cardiovascular risk factors (61% for hypertension, 52% for diabetes mellitus, 45% for obesity and 24% for dyslipidemia). When compared to conservative management, patients with SCS undergoing adrenalectomy experienced improvement in hypertension (RR 11, 95% CI 4.3 – 27.8) and diabetes mellitus (RR 3.9, 95%CI 1.5- 9.9), but not dyslipidemia (RR 2.6, 95%CI 0.97 -7.2) or obesity (RR 3.4 (95%CI 0.95-12)). Patients with NF adrenal tumors experienced improvement in hypertension (21/54 patients), however, insufficient data exist for comparison to patients with SCS.

CONCLUSIONS:

Available low to moderate quality evidence from heterogeneous studies suggests a beneficial effect of adrenalectomy on cardiovascular risk factors in patients with SCS overall and as compared to conservative management.

PMID:
27450696
DOI:
10.1530/EJE-16-0465
[PubMed – as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/27450696

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New Diagnostic Criteria for Subclinical Hypercortisolism using Postsurgical Hypocortisolism

Posted on August 12, 2016 by MaryO

Clin Endocrinol (Oxf). 2016 Jun 24. doi: 10.1111/cen.13145. [Epub ahead of print]

 

Abstract

OBJECTIVE:

There is no consensus on the biochemical diagnostic criteria for subclinical hypercortisolism (SH). Using parameters related to the hypothalamic-pituitary-adrenal axis, we aimed to develop a diagnostic model of SH for predicting postsurgical hypocortisolism and metabolic complications.

DESIGN:

Prospective and cross-sectional, observational, multicentre study in Korea.

METHODS:

After exclusion of overt Cushing’s syndrome, adrenal incidentaloma (AI) patients who underwent unilateral adrenalectomy (n = 99) and AI patients (n = 843) were included. Primary outcome was defined as the presence of postsurgical hypocortisolism; secondary outcome was the presence of ≥4 complications (components of the metabolic syndrome and low bone mass). Postsurgical hypocortisolism was determined on the fifth postsurgery day using the ACTH stimulation test.

RESULTS:

Thirty-three of the 99 patients developed postsurgical hypocortisolism. Analysis of the presurgery overnight 1-mg dexamethasone suppression test (1-mg DST) showed that all patients with cortisol levels of >138 nmol/l experienced postsurgical hypocortisolism, whereas those with levels of ≤61 nmol/l did not. The models of (i) 1-mg DST >138 nmol/l or (ii) >61 nmol/l with the presence of one among low levels of ACTH and dehydroepiandrosterone-sulphate had the highest accuracy (89·9%, P < 0·001) and odds ratio [OR 111·62, 95% confidence interval (CI) 21·98-566·74, P < 0·001] for predicting postsurgical hypocortisolism. Finally, patients with the same criteria in the 843 AI patients showed the highest risk for having ≥4 complications (OR 3·51, 95% CI 1·84-6·69, P < 0·001), regardless of gender, age, body mass index and bilaterality.

CONCLUSIONS:

Our proposed model is able to accurately predict subtle cortisol excess and its chronic manifestations in AI patients.

© 2016 John Wiley & Sons Ltd.

PMID:
27341314
DOI:
10.1111/cen.13145

From http://www.ncbi.nlm.nih.gov/pubmed/27341314

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Pituitary Gland: Normal Function and Assessment

Posted on July 23, 2016 by MaryO

Abstract

This computer-based, interactive module introduces preclinical medical students to normal pituitary function and outlines its assessment. Solid understanding of these topics is requisite to learning clinical disorders of the pituitary.

Existing resources largely target learners at earlier or later stages of training; thus, we created this resource to address needs of medical students during a first- or second-year endocrine course. A module format was selected to promote interactive, independent learning.

Two cohorts of medical students completed the 40-minute module: 172 second-year students who had completed a year of basic sciences in the traditional curriculum and 180 foundation-phase students in a three-semester combined basic and clinical sciences curriculum (due to a change in the medical school curriculum at our institution). In both instances, the module was completed before start of clinical pituitary content. A static set of PowerPoint slides accompanied the module to facilitate note taking.

Test Your Knowledge slides were inserted to ensure grasp of key terms/concepts before moving to subsequent slides. A short question-and-answer session was held following module completion to clarify points of confusion. Students rated effectiveness of the module as 4.6 out of 5, commenting on its clarity, organization, high-yield nature, and utility in preparing for clinical material.

Faculty noted greater understanding of foundational pituitary principles and more engaging discussions. The percentage of pituitary-related questions answered correctly on the midterm exam increased.

Finally, success of the pituitary module prompted development of adrenal, thyroid, and parathyroid modules that now comprise the Endocrine Organs Introduction Series in our curriculum.

Citation

Kirk D, Smith KW. Pituitary gland: normal function and assessment. MedEdPORTAL Publications. 2016;12:10430. http://dx.doi.org/10.15766/mep_2374-8265.10430

Educational Objectives

After completing this module, the learner will be able to:

  1. Describe the normal function and regulation of the pituitary gland, including names and actions of the anterior and posterior pituitary hormones.
  2. Understand the basic approach to laboratory assessment of the pituitary.
  3. Differentiate between anterior and posterior pituitary origin, function, and regulation.
  4. List the hormones produced by the pituitary gland.
  5. Discuss for each pituitary hormone: hypothalamic stimulating/inhibiting factors and their clinical uses, basic physiologic function, and regulation (feedback loop).
  6. Describe factors that affect growth hormone levels.
  7. Understand the tests for growth hormone excess and deficiency.
  8. Define a primary versus secondary endocrine disorder.

Keywords

  • Endocrine, Endocrinology, Pituitary, Module, Preclinical Medical Education

More information at https://www.mededportal.org/publication/10430

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Six controversial issues on subclinical Cushing’s syndrome

Posted on July 14, 2016 by MaryO

Abstract

Subclinical Cushing’s syndrome is a condition of hypercortisolism in the absence of signs specific of overt cortisol excess, and it is associated with an increased risk of diabetes, hypertension, fragility fractures, cardiovascular events and mortality.

The subclinical Cushing’s syndrome is not rare, being estimated to be between 0.2–2 % in the adult population. Despite the huge number of studies that have been published in the recent years, several issues remain controversial for the subclinical Cushing’s syndrome screening, diagnosis and treatment.

The Altogether to Beat Cushing’s syndrome Group was founded in 2012 for bringing together the leading Italian experts in the hypercortisolism-related diseases. This document represents the Altogether to Beat Cushing’s syndrome viewpoint regarding the following controversial issues on Subclinical Cushing’s syndrome (SCS):

(1) Who has to be screened for subclinical Cushing’s syndrome?
(2) How to screen the populations at risk?
(3) How to diagnose subclinical Cushing’s syndrome in patients with an adrenal incidentaloma?
(4) Which consequence of subclinical Cushing’s syndrome has to be searched for?
(5) How to address the therapy of choice in AI patients with subclinical Cushing’s syndrome?
(6) How to follow-up adrenal incidentaloma patients with subclinical Cushing’s syndrome surgically or conservatively treated?

Notwithstanding the fact that most studies that faced these points may have several biases (e.g., retrospective design, small sample size, different criteria for the subclinical Cushing’s syndrome diagnosis), we believe that the literature evidence is sufficient to affirm that the subclinical Cushing’s syndrome condition is not harmless and that the currently available diagnostic tools are reliable for identifying the majority of individuals with subclinical Cushing’s syndrome.

Keywords

Subclinical hypercortisolism, Adrenal incidentalomas, Hypertension, Diabetes, Osteoporosis

Buy the entire article at http://link.springer.com/article/10.1007/s12020-016-1017-3

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