Adiponectin level may serve as predictor of subclinical Cushing’s syndrome

Posted on September 13, 2016 by MaryO

Unal AD, et al. Int J Endocrinol. 2016;doi:10.1155/2016/8519362.

 

In adults with adrenal incidentaloma, adiponectin levels may help predict the presence of subclinical Cushing’s disease, according to recent findings.

Asli Dogruk Unal, MD, of the department of endocrinology and metabolism at Memorial Atasehir Hospital in Istanbul, and colleagues analyzed data from 40 patients with adrenal incidentaloma (24 women; mean age, 61 years) and 30 metabolically healthy adults without adrenal adenomas or hyperplasia (22 women; mean age, 26 years). All patients with type 2 diabetes were newly diagnosed and not on any antidiabetic therapies; included patients were not using statin therapy for about 12 weeks.

Participants provided blood samples

Among patients with adrenal incidentaloma, eight (20%) were diagnosed with subclinical Cushing’s syndrome; median adenoma diameter in these patients was 3.05 cm. The remaining patients were classified as nonfunctional adrenal incidentaloma. Compared with patients who had nonfunctional adrenal incidentaloma, patients with subclinical Cushing’s syndrome had a higher median midnight cortisol level (9.15 µg/dL vs. 5.1 µg/dL; P = .004) and urinary free cortisol level (249 µg per 24 hours vs. 170 µg per 24 hours; P = .007).

In two group comparisons, researchers found that only adiponectin level was lower in the subclinical Cushing’s syndrome group vs. the nonfunctional adrenal incidentaloma group (P = .007); there were no observed between-group differences for age, BMI, waist circumference, insulin levels, homeostasis model assessment for insulin resistance (HOMA-IR) or lipid profiles.

Adiponectin level was negatively associated with insulin level, HOMA-IR, triglyceride level and midnight cortisol level, and was positively associated with body fat percentage, HDL and adrenocorticotropic hormone levels. In linear regression analysis, age was found to be an increasing factor, whereas sex, HOMA-IR, LDL, waist circumference and presence of subclinical Cushing’s syndrome were decreasing factors.

In evaluating the receiver operating characteristic analysis, researchers found that adiponectin level had a predictive value in determining the presence of subclinical Cushing’s syndrome (area under the curve: 0.81; 95% CI, 0.67-0.96). Sensitivity and specificity for an adiponectin value of 13 ng/mL or less in predicting the presence of subclinical Cushing’s syndrome were 87.5% and 77.4%, respectively; positive predictive value and negative predictive value were 50% and 96%, respectively.

“Presence of [subclinical Cushing’s syndrome] should be considered in case of an adiponectin level of 13 ng/mL in [adrenal incidentaloma] patients,” the researchers wrote. “Low adiponectin levels in [subclinical Cushing’s syndrome] patients may be important in treatment decision due to the known relation between adiponectin and cardiovascular events. In order to increase the evidences on this subject, further prospective follow-up studies with larger number of subjects are needed.” – by Regina Schaffer

Disclosure: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B81c38f07-b378-4ca1-806b-d5c17bea064c%7D/adiponectin-level-may-serve-as-predictor-of-subclinical-cushings-syndrome

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Primary hyperaldosteronism: a case of unilateral adrenal hyperplasia with contralateral incidentaloma

Posted on July 16, 2016 by MaryO
BMJ Case Reports 2016; doi:10.1136/bcr-2016-216209
  • CASE REPORT
  1. Sujit Vakkalanka1,
  2. Andrew Zhao1,
  3. Mohammed Samannodi2

+Author Affiliations


  1. 1University at Buffalo, Buffalo, New York, USA

  2. 2Department of Medicine, Buffalo, New York, USA
  1. Correspondence toDr Mohammed Samannodi, samannodi@gmail.com
  • Accepted 28 June 2016
  • Published 14 July 2016

Summary

Primary hyperaldosteronism is one of the most common causes of secondary hypertension but clear differentiation between its various subtypes can be a clinical challenge.

We report the case of a 37-year-old African-American woman with refractory hypertension who was admitted to our hospital for palpitations, shortness of breath and headache. Her laboratory results showed hypokalaemia and an elevated aldosterone/renin ratio. An abdominal CT scan showed a nodule in the left adrenal gland but adrenal venous sampling showed elevated aldosterone/renin ratio from the right adrenal vein. The patient began a new medical regimen but declined any surgical options.

We recommend clinicians to maintain a high level of suspicion to consider the less common subtypes of primary hyperaldosteronism, especially given the fact that the management greatly varies.

From http://casereports.bmj.com/content/2016/bcr-2016-216209.short?rss=1

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What Is Adrenal Hyperplasia? – Yahoo News UK

Posted on March 31, 2015 by MaryO

Adrenal hyperplasia is a rare genetic condition that involves the adrenal glands, which lie just above the kidneys.

It results in a blockage in the assembly line that makes the stress hormone cortisol from its chemical precursors.

People with the condition have low levels of cortisol, which helps to regulate blood sugar levels. If they fall too low, it can result in a coma.

But in some cases, the blockage can also reduce the production of aldosterone, a hormone involved in the regulation of salt in the bloodstream.

If salt levels fall too low it can lead to dehydration, vomiting and death.

Regular treatment with steroid medicines can help to maintain normal hormone levels and although the condition is lifelong, the outlook is generally good.

via Missing Boy: What Is Adrenal Hyperplasia? – Yahoo News UK.

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PRKACA mutations in cortisol-producing adenomas and adrenal hyperplasia

Posted on March 31, 2015 by MaryO
Eur J Endocrinol. 2015 Mar 6. pii: EJE-14-1113. [Epub ahead of print]

PRKACA mutations in cortisol-producing adenomas and adrenal hyperplasia – a single-center study of 60 cases.

Thiel A1, Reis AC2, Haase M3, Goh G4, Schott M5, Willenberg HS6, Scholl UI7.

Author information

Abstract

Objective: Cortisol excess due to adrenal adenomas or hyperplasia causes Cushing’s syndrome. Recent genetic studies have identified a somatic PRKACAL206R mutation as a cause of cortisol-producing adenomas.

We aimed to compare the clinical features of lesions with PRKACA mutations to those with CTNNB1 mutations and to search for similar mutations in unilateral hyperplasia or tumors co-secreting aldosterone.

Design, patients and methods: 60 patients with cortisol excess who had adrenalectomies at our institution between 1992 and 2013 were assessed, and somatic mutations were determined by Sanger sequencing. 36 patients had overt Cushing’s syndrome, the remainder were subclinical. 59 cases were adenomas (three bilateral), one was classified as hyperplasia. Four tumors had proven co-secretion of aldosterone.

Results: Among cortisol-secreting unilateral lesions without evidence of co-secretion (n=52), we identified somatic mutations in PRKACA (L206R) in 23.1%, CTNNB1 (S45P, S45F) in 23.1%, GNAS (R201C) in 5.8% and CTNNB1 plus GNAS (S45P, R201H) in 1.9%. PRKACA and GNAS mutations were mutually exclusive. Of the co-secreting tumors, two (50%) had mutations in KCNJ5 (G151R and L168R). The hyperplastic gland showed a PRKACAL206R mutation, while patients with bilateral adenomas did not have known somatic mutations. PRKACA-mutant lesions were associated with younger age, overt Cushing’s syndrome and higher cortisol levels versus non-PRKACA-mutant or CTNNB1-mutant lesions. CTNNB1 mutations were more significantly associated with right than left lesions.

Conclusions: PRKACAL206R is present not only in adenomas, but also in unilateral hyperplasia and is associated with more severe autonomous cortisol secretion. Bilateral adenomas may be caused by yet-unknown germline mutations.

PMID:
25750087
[PubMed – as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/25750087

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Mutations in PKA catalytic subunit associated with Cushing’s syndrome

Posted on March 18, 2014 by MaryO

1. Somatic mutations resulting in constitutive activation of PRKACA, which encodes the catalytic subunit of protein kinase A, were found in 37% of patients with Cushing’s syndrome due to an adrenal adenoma. 

2. Germline duplications of PRKACA were detected in patients with bilateral adrenal hyperplasia and overt Cushing’s syndrome. 

Study Rundown: This study found that 37% of patients with overt Cushing’s syndrome due to an adrenal adenoma have a somatic mutation in PRKACA, which encodes the catalytic subunit of cyclic AMP-dependent protein kinase A (PKA), present in their tumor cells. The most commonly identified variant, Leu206Arg, results in impaired interaction between the catalytic and regulatory subunits of PKA, thereby causing constitutive activation of PKA. Additionally, a subset of patients with cortisol-producing bilateral adrenal hyperplasia harbored germline duplications of PRKACA.

This is the first study to identify an association between genetic alterations of the catalytic subunit of PKA and Cushing’s syndrome. It is significant that 37% of patients with overt Cushing’s syndrome were found to have tumors with PRKACA mutations; previous research had revealed only very rare mutations. Of note, this study did not find PRKACA mutations in any patients with subclinical Cushing’s syndrome or inactive adenomas. This suggests that Cushing’s syndrome and subclinical Cushing’s are distinct entities. Patients involved in this study were recruited from only three centers; the frequency of PRKACA mutations in Cushing’s syndrome may be different in other study populations. Further research will be needed to identify biochemical causes of overt Cushing’s syndrome in patients without PRKACA mutations.

Relevant Reading: Abnormalities of cAMP signaling are present in adrenocortical lesions associated with ACTH-independent Cushing’s syndrome despite the absence of mutations in known genes

In-Depth: In this study, exome sequencing of tumor specimens from 10 patients with unilateral cortisol-producing adenomas and overt Cushing’s syndrome was performed. Eight of 10 adenomas had somatic mutations in PRKACA; 7 of these patients had the same mutation (p.Leu206Arg). Subsequently, PRKACA was sequenced in 129 additional patients with adrenal adenomas. Patients were classified as having overt Cushing’s syndrome (at least three abnormal biochemical tests or catabolic features plus two abnormal tests), subclinical Cushing’s (at least one abnormal biochemical test without catabolic signs) or as having an inactive adenoma. The Leu206Arg variant was identified in tumor tissue of 14/129 patients and all 14 had overt Cushing’s syndrome. Overall, 37% (22/59) of patients with overt Cushing’s syndrome due to an adenoma had a PRKACA mutation; in contrast, PRKACA mutations were not found in any patients with subclinical Cushing’s or an inactive adenoma. Of 35 patients with overt Cushing’s syndrome due to cortisol-secreting bilateral adrenal hyperplasia, 5 patients had copy-number gains of a region on chromosome 19p that contains PRKACA.

Analysis of holoenzyme structure revealed that the Leu206Arg mutation is located in the active-site cleft of the catalytic subunit of PKA. To evaluate the functional consequences of this mutation, cells were transfected with either nonmutant or variant C-alpha, which encodes the catalytic subunit of PKA. Investigators determined that the mutation causes constitutive activation of the catalytic subunit by impairing interaction with the regulatory subunit of PKA.

From http://www.2minutemedicine.com/mutations-in-pka-catalytic-subunit-associated-with-cushings-syndrome/

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