Exophthalmos and Cushing's Syndrome

A woman experienced red, irritated and bulging eyes. She saw an ophthalmologist who strongly suspected Graves’ ophthalmopathy. However, the patient did not have and never had hyperthyroidism.

Indeed, she had primary hypothyroidism optimally treated with levothyroxine. Her thyroid stimulating hormone level was 1.197 uIU/mL.

An MRI of the orbits showed normal extraocular muscles without thickening, but there was mild proptosis and somewhat increased intraorbital fat content. Both thyroid-stimulating immunoglobulins as well as thyrotropin receptor antibodies were negative.

The patient presented to her primary care physician a few months later. She had experienced a 40-lb weight gain over only a few months and also had difficult-to-control blood pressure.

After failing to respond to several antihypertensive medications, her primary care physician astutely decided to evaluate for secondary causes of hypertension. A renal ultrasound was ordered to evaluate for renal artery stenosis, and the imaging identified an incidental right-sided adrenal mass. A CT confirmed a 3.4-cm right-sided adrenal mass. Her morning cortisol was slightly high at 24.7 ug/dL (4.3 – 22.4) and her adrenocorticotropic hormone was slightly low at 5 pg/mL (10-60).

At this point I saw the patient in consultation. She definitely had many of the expected clinical exam findings of Cushing’s syndrome, including increased fat deposition to her abdomen, neck, and supraclavicular areas, as well as striae. Her 24-hour urine cortisol was markedly elevated at 358 mcg/24hrs (< 45) confirming our suspicions.

She asked me, “Do you think that my eye problem could be related to this?”

“I’ve not heard of it before,” I replied, “but that doesn’t mean there can’t be a connection. Wouldn’t it be wonderful if your eyes got better after surgery?”

The patient underwent surgery to remove what fortunately turned out to be a benign adrenal adenoma.

When we saw her in follow-up 2 weeks later, her blood pressures were normal off medication and her eye symptoms had improved. I had a medical student rotating with me, so I suggested that we do a PubMed literature search.

The first article to come up was a case report titled “Exophthalmos: A Forgotten Clinical Sign of Cushing’s Syndrome.” Indeed, not only did Harvey Cushing describe this clinical finding in his original case series in 1932, but others have reported that up to 45% of patients with active Cushing’s syndrome have exophthalmos.

The cause is uncertain but is theorized to be due to increased intraorbital fat deposition. Unlike exophthalmos due to thyroid disease, the orbital muscles are relatively normal — just as they were with our patient.

Some of you may have seen exophthalmos in your Cushing’s patients; however, this was the first time I had seen it. Just because one has not heard of something, does not mean it could never happen; no one knows everything. “When in doubt, look it up” is a good habit for both attending physicians and their students.

For more information:

Giugni AS, et al. Case Rep Endocrinol. 2013; 2013: 205208.

From http://www.healio.com/endocrinology/adrenal/news/blogs/%7B779bf3e5-e1da-459e-af27-955c9b4274a5%7D/thomas-b-repas-do-facp-face-cde/exophthalmos-and-cushings-syndrome

Single-Incision Transperitoneal Laparoscopic Left Adrenalectomy

Óscar Vidal, Emiliano Astudillo, Mauro Valentini, Cesar Ginestà, Juan C. García-Valdecasas and Laureano Fernandez-Cruz

 

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Abstract

Background  

Laparoscopic adrenalectomy via three or four trocars is a well-established procedure. This report describes the initial experience with single-incision laparoscopic surgery (SILS) using the transperitoneal approach for left adrenalectomy.

Methods  

Between April 2010 and August 2011, all consecutive patients with adrenal masses, including Conn’s syndrome, Cushing’s adenoma, and nonfunctional adrenal tumors, who agreed to undergo SILS adrenalectomy were included in a prospective study. The left 2.5-cm subcostal incision was the sole point of entry. Data of patients who underwent SILS adrenalectomy were compared with those from an uncontrolled group of patients who underwent conventional laparoscopic adrenalectomy during the same study period.

Results  

There were 20 patients in each study group (20 men, 20 women; mean age [SD] = 50 [6.5] years). SILS was successfully performed and none of the patients required conversion to an open procedure. In one case of SILS procedure, an additional lateral 5-mm port was needed for retraction of the kidney. The mean (SD) duration of the operation was 95 (20) min in the SILS group and 80 (8) min in the conventional laparoscopic adrenalectomy group (p = 0.052). There were no intraoperative or postoperative complications. There were no differences between the two study groups with respect to postoperative pain, number of patients who resumed oral intake within the first 24 h, final pathologic diagnosis, and length of hospital stay.

Conclusion  

SILS left adrenalectomy is a technically feasible and safe procedure in carefully selected patients. The definitive clinical, aesthetic and functional advantages of this technique require further analysis.

 

 

 

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From http://www.springerlink.com/content/h60075322750m0x0/

 

Subclinical Cushings syndrome: definition and management

Subclinical Cushing's syndrome is an ill-defined endocrine disorder that may be observed in patients bearing an incidentally found adrenal adenoma. The concept of subclinical Cushing's syndrome stands on the presence of ACTH-independent cortisol secretion by an adrenal adenoma, that is not fully restrained by pituitary feed-back. A hypercortisolemic state of usually minimal intensity may ensue and eventually cause harm to the patients in terms of metabolic and vascular diseases, and bone fractures.

However, the natural history of subclinical Cushing's syndrome remains largely unknown. The present review illustrates the currently used methods to ascertain the presence of subclinical Cushing's syndrome and the surrounding controversy. The management of subclinical Cushing's syndrome, that remains a highly debated issue, is also addressed and discussed.

Most of the recommendations made in this chapter reflects the view and the clinical experience of the Authors and are not based on solid evidence.

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2265.2011.04253.x

Affiliations: 1: Internal Medicine I, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy

Buy the article at http://www.ingentaconnect.com/content/bsc/cend/2012/00000076/00000001/art00003

Cushing’s Syndrome Clinical Analysis of 77 Cases

OBJECTIVE To analyze the cause of Cushing’s syndrome classification, the major clinical manifestations and laboratory features of frequency of occurrence, and the efficiency of various diagnostic methods to evaluate the clinical doctors to improve diagnosis and treatment of disease, improve patient prognosis.

METHODS from 2004 to 2009 in our hospital by clinical or pathological diagnosis of Cushing’s syndrome in patients with clinical data, of which 57 cases of females, 20 males. For the 77 cases of clinical manifestations, laboratory examination, imaging studies, clinical diagnostic tests, pathological characteristics and with the results of literature analysis and summary of them were analyzed retrospectively.

RESULTS 1. From 2004 to 2009 were diagnosed 77 cases of Cushing’s syndrome, of which 20 males, female 57 cases, male: female = 2:2.85, adrenal adenoma 80% of female patients of childbearing age women.

2. In Cushing’s disease causes the most common (35 cases), followed by adrenal cortical adenoma (30 cases, the left side of 21 cases), there is a growing trend in the latter. Cushing’s disease course and age of onset of adrenal adenomas were higher than those, the difference was statistically significant (P <0.05), the shortest duration of adrenal carcinoma.

3. Clinical performance, the performance of the diversity of its starter, Hypertension and central obesity were the most frequently occur in 75%, and 79.22% suffering from hypertension, Hypertension 1 11.48%, Hypertension 2 62.30%, Hypertension 3 grade 26.23%, and the incidence of abnormal glucose metabolism and hyperlipidemia, respectively 41% and 68%, of which the proportion of diabetes by 30%, 65% of patients had hypokalemia, mostly mild to moderate, adrenal cortex carcinoma 100% of patients with a low potassium, and is of moderate to severe hypokalemia. Cushing’s disease and adrenal adenoma in serum potassium, blood pressure and gender showed no significant difference.

4. In the diagnosis of Cushing’s syndrome test, blood cortisol circadian rhythm disappeared (98.65%), elevated midnight serum cortisol (98.55%), 4Pm serum cortisol increased (97.14%), low-dose dexamethasone suppression test (94.59%), 24hUFC increased (91.22%), morning serum cortisol increased (71.62%). Low-dose dexamethasone suppression of serum cortisol in the morning the next day the basis of 8:00 of serum cortisol of 50% and 275,200,138,50 nmol/Lthe sensitivity of the cut-off point were 94.6%, 95.9%, 97.3% , 97.3% and 100%.

5. Patients with Cushing’s syndrome in the differential diagnosis, 80% of Cushing’s patients can be high-dose dexamethasone suppression, while more than 95% of patients with adrenal cortical adenoma can not be high-dose dexamethasone suppression. Cushing’s patients compared with blood cortisol and ACTH levels were significantly higher in patients with adrenal tumors, while the latter’s rhythmic performance is worse, the differences were statistically significant (P<0.05). Both urinary free cortisol showed no significant difference.6. imaging examination, pituitary MRI can detect 88% of Cushing’s disease there is pituitary adenoma, while the adrenal CT 100% can find out the adrenal tumors, adrenal CT of adrenal tumors and hyperplasia pathology consistent rate of 97.5%.

CONCLUSION 1. The present study in Cushing’s disease and adrenal cortical adenoma is still the most common cause of this group a high proportion of cases of adrenal adenoma, left more common. Cushing’s syndrome more common in women of childbearing age women, more common adrenal adenoma, Hypertension is the most common symptoms, mostly moderate to severe hypertension, diabetes, low potassium, high incidence of dyslipidemia.

2. Diagnostic tests in the CS, the morning cortisol increase the sensitivity of the worst, and serum cortisol circadian rhythm disappeared, midnight serum cortisol increased, 4PM cortisol rise, low-dose dexamethasone suppression test, 24hUFC elevated. There was no significant difference。

3. Patients with Cushing’s disease course, age of onset, blood cortisol and ACTH levels were higher than the adrenal adenoma, the latter comparison rhythm of blood cortisol rhythm performance is worse. The serum potassium, blood pressure and no significant difference in gender.

4. High-dose dexamethasone suppression test is to identify Cushing’s disease and adrenal cortical adenoma of the most appropriate method, CT of the adrenal lesion positive rate and help confirm the diagnosis and localization, B super-positive rate was significantly lower than CT, head MRI in Cushing’s disease positive rate.

From http://www.tumorres.com/tumor-metastasis/15968.htm

Effects of Hormone Stimulation on Brain Scans for Cushing's Disease

This study is currently recruiting participants.

Verified on August 2011 by National Institutes of Health Clinical Center (CC)

First Received on October 21, 2011.   No Changes Posted

Sponsor:	National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT01459237

  Purpose

Background:

• Cushing's disease can be caused by a tumor of the pituitary gland, a small gland about the size of a pea located at the base of the brain. These tumors produce high levels of hormones, which cause obesity, diabetes, and growth problems. The cure for this type of Cushing's disease is to have surgery that removes the tumor but leaves the pituitary gland alone. Currently, magnetic resonance imaging scans are the best way to find these tumors. However, many of these tumors do not show up on the scan.
• Positron emission tomography (PET) scans use radioactive chemicals to light up parts of the body that are more active, such as tumors. Researchers want to try to make the small Cushing's disease tumors more active to help them show up on the scans. A special hormone will be given before the scan to make the tumors more active.

Objectives:

- To test the use of hormone stimulation to improve brain scans for Cushing's disease tumors.

Eligibility:

- Individuals at least 8 years of age who will be having surgery to remove Cushing's disease tumors.

Design:

• Participants will be screened with a medical history, physical exam, blood and urine tests, and imaging studies.
• They will have three brain scans before surgery. The first scan is a magnetic resonance imaging scan to show a full picture of the brain. The second and third scans are PET scans.
• The first PET scan will be given without the special hormone. The second PET scan will be done more than 24 hours but less than 14 days after the first PET scan. The second PET scan will be given with the special hormone.
• Participants will have tumor removal surgery through another study protocol....

Condition
Pituitary Neoplasm

Study Type:	Observational
Official Title:	Prospective Evaluation of the Effect of Corticotropin-Releasing Hormone Stimulation on 18F-Fludeoxyglucose High-Resolution Positron-Emission Tomography in Cushing's Disease

Resource links provided by NLM:

MedlinePlus related topics: Cancer Cushing's Syndrome Nuclear Scans Pituitary Tumors

Drug Information available for: Corticotropin Corticotropin-releasing hormone

U.S. FDA Resources 

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment:	30
Study Start Date:	October 2011

Detailed Description:

Objective

Preoperative imaging identification and localization of adrenocorticotropin hormone (ACTH)-secreting pituitary adenomas is critical for the accurate diagnosis and the successful surgical treatment of Cushing's disease (CD). Unfortunately, over 40 percent of CD patients do not have a visible pituitary adenoma on magnetic resonance (MR)-imaging (the most sensitive imaging modality for ACTH-positive adenoma detection and localization). Lack of MR-imaging for diagnosis and to guide surgical resection results in significantly higher rates of surgical failure compared to cases associated with adenomas visible on MR-imaging. Because ACTH-adenomas are metabolically active compared to the surrounding pituitary gland, (18)F-fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)-imaging in CD patients could be used to detect adenomas not detectable on MR-imaging. Moreover, corticotropin-releasing hormone (CRH) can be given to selectively increase the metabolic activity of ACTH-secreting pituitary adenomas to increase the likelihood of their detection and localization by (18)F -FDG PET-imaging. To determine the effect of CRH stimulation on (18)F-FDG uptake using PET-imaging in CD, we will perform (18)F-FDG high-resolution PET-imaging (with and without CRH stimulation) in CD patients.

Study Population

Thirty male and female CD patients 8 years and older will participate in this study.

Study Design

This is a single center trial to determine the effect of CRH stimulation on (18)F-FDG uptake in high-resolution PET-imaging of ACTH-adenomas in CD patients. CD patients will undergo (18)F-FDG high-resolution PET-imaging without CRH stimulation and (18)F-FDG high-resolution PET-imaging with intravenous CRH stimulation. The order of the PET scans will be randomized and the second PET scan will occur greater than 24 hours but less than 14 days after initial PET-imaging. For (18)F-FDG PET-imaging with CRH stimulation, intravenous (18)F-FDG will be given just before CRH administration. The PET images will be read by radiologists who are blinded to the administration of CRH. Within 12 weeks after completion of the last (18)F-FDG high-resolution PET-imaging scan, patients will undergo surgical resection of the pituitary adenoma. Surgical and histological confirmation of adenoma location will be used to assess the diagnostic and localization accuracy of PET-imaging and to compare to preoperative MR-imaging results in CD patients. Inferior petrosal sinus sampling (IPSS) results will be compared with imaging results and with surgical and histological findings.

Outcome Measures

The primary objective of this study is to determine the effect of CRH stimulation on (18)F-FDG uptake in high-resolution PET-imaging for CD. To assess and compare (18)F-FDG uptake without and with CRH stimulation, we will compare (18)F-FDG standardized uptake values (SUVs) in the region of interest (pituitary gland and pituitary adenoma). Secondary objectives include determining if CRH stimulation enhances detection of ACTH-adenomas as demonstrated on (18)F-FDG high-resolution PET-imaging and assessing the accuracy and sensitivity of (18)F-FDG high-resolution PET-imaging detection of ACTH-adenomas compared to MR-imaging. Measures to assess for these secondary objectives include comparing (18)F-FDG high-resolution PET-imaging (with and without CRH stimulation) detection to (1) MR-imaging detection of adenomas, (2) IPSS results, and (3) actual tumor location confirmed by histological findings to location predicted by PET- and MR-imaging within patients.

  Eligibility

Ages Eligible for Study:	8 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

• INCLUSION CRITERIA:

To be eligible for entry into the study, patients must meet all the following criteria:

1. Be 8 years of age or older and able to undergo PET-imaging without needing general anesthesia.
2. Able to provide informed consent (or guardian is able to provide consent in case of minor).
3. Clinical diagnosis of CD based on medical records.
4. Medically able to undergo resection of pituitary adenoma and planning to undergo surgical resection of adenoma within 12 weeks of PET-imaging.
5. Normal liver enzymes: tests should be completed within 14 days before injection of the radiopharmaceutical; SGOT, SGPT less than or equal to 5 times ULN; bilirubin less than or equal to 2 times ULN.

EXCLUSION CRITERIA:

Candidates will be excluded if they meet any of the following criteria:

1. Pregnant or nursing women.
2. Contraindication to MR-scanning, including pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or shrapnel fragments
3. Severe chronic renal insufficiency (glomerular filtration rate < 30 mL/min/1.73 m(2)), hepatorenal syndrome or post-liver transplantation.
4. Elevated blood glucose level above 200 mg/dL on the day of the scan prior to (18)F-FDG administration.

  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01459237

Contacts

Contact: Patient Recruitment and Public Liaison Office	(800) 411-1222	prpl@mail.cc.nih.gov
Contact: TTY	1-866-411-1010

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

  More Information

Additional Information:

NIH Clinical Center Detailed Web Page  

Publications:

Alzahrani AS, Farhat R, Al-Arifi A, Al-Kahtani N, Kanaan I, Abouzied M. The diagnostic value of fused positron emission tomography/computed tomography in the localization of adrenocorticotropin-secreting pituitary adenoma in Cushing's disease. Pituitary. 2009;12(4):309-14. Epub 2009 Apr 22.

Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, Fava GA, Findling JW, Gaillard RC, Grossman AB, Kola B, Lacroix A, Mancini T, Mantero F, Newell-Price J, Nieman LK, Sonino N, Vance ML, Giustina A, Boscaro M. Diagnosis and complications of Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab. 2003 Dec;88(12):5593-602. Review.

Batista D, Gennari M, Riar J, Chang R, Keil MF, Oldfield EH, Stratakis CA. An assessment of petrosal sinus sampling for localization of pituitary microadenomas in children with Cushing disease. J Clin Endocrinol Metab. 2006 Jan;91(1):221-4. Epub 2005 Oct 11.

Selective inferior petrosal sinus sampling without venous outflow diversion in the detection of a pituitary adenoma in Cushing’s syndrome

Lukas Andereggen, Gerhard Schroth, Jan Gralla, Rolf Seiler, Luigi Mariani, Jürgen Beck, Hans-Rudolf Widmer, Robert H. Andres, Emanuel Christ and Christoph Ozdoba

Neuroradiology

DOI: 10.1007/s00234-011-0915-6

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Abstract

Introduction  

Conventional MRI may still be an inaccurate method for the non-invasive detection of a microadenoma in adrenocorticotropin (ACTH)-dependent Cushing’s syndrome (CS). Bilateral inferior petrosal sinus sampling (BIPSS) with ovine corticotropin-releasing hormone (oCRH) stimulation is an invasive, but accurate, intervention in the diagnostic armamentarium surrounding CS. Until now, there is a continuous controversial debate regarding lateralization data in detecting a microadenoma. Using BIPSS, we evaluated whether a highly selective placement of microcatheters without diversion of venous outflow might improve detection of pituitary microadenoma.

Methods  

We performed BIPSS in 23 patients that met clinical and biochemical criteria of CS and with equivocal MRI findings. For BIPSS, the femoral veins were catheterized bilaterally with a 6-F catheter and the inferior petrosal sinus bilaterally with a 2.7-F microcatheter. A third catheter was placed in the right femoral vein. Blood samples were collected from each catheter to determine ACTH blood concentration before and after oCRH stimulation.

Results  

In 21 patients, a central-to-peripheral ACTH gradient was found and the affected side determined. In 18 of 20 patients where transsphenoidal partial hypophysectomy was performed based on BIPSS findings, microadenoma was histologically confirmed. BIPSS had a sensitivity of 94% and a specificity of 67% after oCRH stimulation in detecting a microadenoma. Correct localization of the adenoma was achieved in all Cushing’s disease patients.

Conclusion  

BIPSS remains the gold standard in the detection of a microadenoma in CS. Our findings show that the selective placement of microcatheters without venous outflow diversion might further enhance better recognition to localize the pituitary tumor.

Keywords  Angiography, Digital subtraction – Cushing disease – Petrosal sinus sampling – Pituitary gland – Magnetic resonance imaging

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From http://www.springerlink.com/content/l487284736173002/

Glucocorticoid- and Androgen-Secreting Black Adrenocortical Adenomas: Unique Cause of Corticotropin-Independent Cushing Sydrome

	Glucocorticoid- and Androgen-Secreting Black Adrenocortical Adenomas: Unique Cause of Corticotropin-Independent Cushing Sydrome Journal Endocrine Practice Publisher American Association of Clinical Endocrinologists ISSN 1530-891X (Print) 1934-2403 (Online) Subject Health Services, Medical Sciences and Endocrinology Issue Volume 17, Number 3 / May-June 2011 Pages e73-e78 Online Date Thursday, June 23, 2011

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Authors

Satoshi Tanaka, MD, PhD¹, Akiyo Tanabe, MD, PhD¹, Motohiko Aiba, MD, PhD², Naomi Hizuka, MD, PhD¹, Kazue Takano, MD, PhD¹, Jun Zhang, MD³, William F. Young, MD, MSc, Jr.⁴

¹Department of Medicine, Tokyo Women's Medical University, Tokyto, Japan
²Department of Clinical Pathology, Tokyo Women's Medical University Medical Center East, Tokyo, Japan
³Department of Anatomic and Clinical Pathology, Mayo Clinic, Rochester, Minnesota
⁴Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota

Abstract

Objective: To describe the unique association of corticotropin-independent Cushing syndrome caused by cortisol- and androgen-secreting black adrenal cortical adenomas with myelolipomatous change.

Methods: We report the clinical, laboratory, radiologic, and pathologic findings from 2 patients who presented with androgen excess and typical signs and symptoms of Cushing syndrome.

Results: Endocrine investigations showed high serum cortisol concentrations that lacked diurnal rhythm, undetectable plasma corticotropin concentrations, and absence of serum cortisol suppression after overnight dexamethasone suppression tests. Serum levels of adrenal androgens were elevated. Computed tomography of the abdomen revealed unilateral adrenal masses (largest lesional diameters 4.0 and 3.1 cm). On the basis of the plurihormonal hypersecretion and the imaging characteristics, adrenocortical carcinoma was considered as a possible diagnosis. However, histopathologic analysis in both patients revealed black adrenal cortical adenomas with myelolipomatous change. After surgery, adrenal androgens normalized, and the signs and symptoms of Cushing syndrome and androgen excess resolved. There was no evidence of recurrent disease at last follow-up.

Conclusions: A unique form of corticotropin-independent Cushing syndrome is described: cortisol- and androgen-secreting black adrenal cortical adenomas with myelolipomatous change. Although most patients with corticotropin-independent Cushing syndrome associated with androgen excess prove to have adrenocortical carcinoma, the clinician should be aware of the possibility of benign, black adrenal adenomas in this clinical setting.

Show References

From http://aace.metapress.com/content/yg61xw4671161wg6/

Paternal deprivation prior to adolescence and vulnerability to pituitary adenomas

L. G. Sobrinho, J. S. Duarte, I. Paiva, L. Gomes, V. Vicente and P. Aguiar

Pituitary

DOI: 10.1007/s11102-011-0324-1

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It has been reported that women with prolactinoma were exposed, early in life, to an environment characterized by an absent or violent father.

The present study was designed to evaluate whether paternal absence or violent paternal behavior were more prevalent in patients with pituitary adenomas (prolactinoma, acromegaly, non-secreting adenoma and Cushing’s disease) compared to a control population.

We conducted an observational case–control multicenter study. We interviewed 395 patients with prolactinoma (296 females and 99 males), 130 with acromegaly (87 females and 43 males), 237 with non-secreting adenoma (144 females and 93 males) and 68 with Cushing’s disease (61 females and 7 males) and 365 patients from the same clinics with nodular thyroid disease or lymphocytic thyroiditis with euthyroidism as controls.

Violent or absent fathers were significantly more prevalent in patients with prolactinoma or acromegaly than in controls (P = 0.001 and P = 0.002, respectively) but not in patients with non-secreting adenoma or corticotrophinoma.

Absent fathers in prolactinoma and acromegaly versus controls: P = 0.001 and P = 0.119. Violent fathers in prolactinoma and acromegaly versus controls: P = 0.069 and P = 0.001. The prevalence of absent or violent fathers was also significantly higher in prolactinoma and acromegaly when compared to non-secreting adenoma (P = 0.039 and P = 0.033, respectively).

Paternal deprivation before adolescence may be a risk factor for prolactinoma and acromegaly but not for non-secreting pituitary adenomas or Cushing’s disease.

Keywords  Acromegaly – Paternal deprivation – Pituitary adenomas – Prolactinoma

This study is conducted for the Grupo de Estudos de Tumores da Hipófise (GETH).

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From http://www.springerlink.com/content/38j3u73175427473/

Familial Pituitary Tumor Syndromes

Journal	Endocrine Practice
Publisher	American Association of Clinical Endocrinologists
ISSN	1530-891X (Print) 1934-2403 (Online)
Subject	Health Services, Medical Sciences and Endocrinology
Pages	1-16
DOI	10.4158/EP11064.RA
Online Date	Wednesday, May 25, 2011

 

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Authors

Vladimir Vasilev, MD^{1, 2}, Adrian F. Daly, MB, BCh, MSc¹, Patrick Petrossians, MD¹, Sabina Zacharieva, MD, PhD², Albert Beckers, MD, PhD¹

¹Department of Endocrinology, University of Liège, Belgium
²Clinical Center of Endocrinology and Gerontology, Medical University, Sofia, Bulgaria

Abstract

Objective: To summarize current knowledge on the clinical and genetic characteristics of familial pituitary tumor syndromes.

Methods: This review is based on comprehensive literature search through the English-language literature using "familial", "pituitary" "adenomas" and "tumors" as search terms.

Results: Familial pituitary tumors are rare and comprise approximately 5 % of all pituitary adenomas. Currently, there are four recognized inherited syndromes that involve pituitary tumorigenesis - multiple endocrine neoplasia type 1 (MEN 1) and type 4 (MEN 4), Carney complex and familial isolated pituitary adenomas (FIPA). MEN 1 and CNC have been known for several decades and their clinical and molecular characteristics have been comprehensively studied. Many familial cases of pituitary adenomas can be attributed to mutations in MEN1 and PRKAR1A genes. The recently defined MEN 4 is extremely rare. Familial pituitary tumors that are not associated with MEN 1 and CNC have been united under a new term introduced in the 1990's: FIPA. About 15-25% of FIPA patients harbor mutations in the AIP gene.

Conclusion: Although rare, familial pituitary tumors present an opportunity to study inherited molecular and genetic mechanisms of pituitary tumorigenesis. A comprehensive understanding of their characteristics may provide basis for better diagnosis and management of affected patients.

Keywords

pituitary adenoma, multiple endocrine neoplasia type 1, Carney complex, familial isolated pituitary adenomas, FIPA

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From http://aace.metapress.com/content/l870r1j66r371206/

Bilateral adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1 (MEN1) and a novel mutation in the MEN1 gene

The incidence of adrenal involvement in MEN1 syndrome has been reported between 9 and 45%, while the incidence of adrenocortical carcinoma (ACC) in MEN1 patients has been reported between 2.6 and 6%. In the literature data only unilateral development of ACCs in MEN1 patients has been reported.

We report a 31 years-old female MEN1-patient, in whom hyperplasia of the parathyroid glands, prolactinoma, non functioning pancreatic endocrine carcinoma and functioning bilateral adrenal carcinomas were diagnosed. Interestingly, a not previously described in the literature data, novel germline mutation (p.E45V) in exon 2 of MEN1 gene, was detected.

The association of exon 2 mutation of the MEN1 gene with bilateral adrenal carcinomas in MEN1 syndrome, should be further investigated.

Author: John Griniatsos, Nikoletta Dimitriou, Athanassios Zilos, Stavroula Sakellariou, Konstantinos Evangelou, Smaragda Kamakari, Penelope Korkolopoulou, Gregory Kaltsas
Credits/Source: World Journal of Surgical Oncology 2011, 9:6

Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please make sure to read our disclaimer prior to contacting 7thSpace Interactive. To contact our editors, visit our online helpdesk. If you wish submit your own press release, click here.

From http://7thspace.com/headlines/370698/bilateral_adrenocortical_carcinoma_in_a_patient_with_multiple_endocrine_neoplasia_type_1_men1_and_a_novel_mutation_in_the_men1_gene.html

Successful treatment of Lt. Adrenocortical Tumor or Cushing's syndrome

Successful treatment of Lt. Adrenocortical Tumor or Cushing's syndrome (+ Enlarge)

Mohini Nayak the two year old female child was brought to Apollo Hospital with H/O gaining excessive weight and became obese since 1 yr. She was treated by different doctors in multiple hospitals in Bhubaneswar and Cuttack. After investigation in S.C.B. Medical College, Cuttack, it was found that the baby is suffering from Lt. Adrenocortical Tumour. Cushing Syndrome in Pediatric age group, particularly less than 2 years old child is a very rare condition, the incidence being 0.3 – 0.4 in one million child below 15yrs of age. Cushing’s syndrome may occur either due to Pituitary tumor or Adreno cortical tumor, said Dr. B N Mishra, Sr. Pediatric Surgeon, Apollo Hosipitals, Bhubaneswar. The baby had adreno cortical; tumor on left side, informed Dr. Mishra. Adrenal glands are present in our body just above and adjacent (Superiorly) to kidneys on both sides.

She had a very large tumor of left adrenal gland of size 10x6x3 cm size and such type of large tumors is usually malignant and rarely seen. However the biopsy does not show features of malignancy, but needs to be observed for a long time. Dr. Mishra informed that, her obesity will take time to reduce, may be six months to one year. Mohini got admitted on 12th November 2010.

Mohini comes from a very low socio-economic status. The child is the youngest of the three siblings and her parents in spite of their poverty tried their limited resources to provide the best medical treatment. Hopeless slum dwellers finally had a smile. Victory of life over death prevailed. Ashok Naik a low paid sweeper and his wife Jyotsna a domestic help sacrificed what ever little earning they did to save their youngest girl child of 2 years old, Mohini.

The girl became about 20kg within 1 year 2months. Finally parents lost all hope. Some couple of weeks back the heart touching story of the girl and her parents, featured in a local daily. The story dragged few social activists of Lions Club Bhubaneswar met the parent and resolved to take an attempt. After initial checkup, Apollo decided for operation with financial assistance from corporate houses and government of odisha.

It was risky and expensive. A group of expert doctors led by Dr. B.N. Mishra successfully operated the massive tumor after a long operation of three hours. The baby is now free of danger.

From http://www.odisha360.com/news/720/successful-treatment-of-lt-adrenocortical-tumor-or-cushings-syndrome

Unilateral adrenalectomy improves urinary protein excretion but does not abolish its relationship to sodium excretion in patients with aldosterone-producing adenoma

E Pimenta, R D Gordon, A H Ahmed, D Cowley, D Robson, C Kogovsek and M Stowasser

 

Abstract

Experimental and human data suggest that adverse cardiovascular (CV) and renal effects of aldosterone excess are dependent on concomitant dietary salt intake.

Increased urinary protein (Uprot) is an early sign of nephropathy independently associated with CV risk. We have previously reported a positive association between Uprot and urinary sodium (UNa) in patients with hyperaldosteronism, but not in patients with normal aldosterone levels.

 

We aimed to determine whether Uprot is related to UNa in patients with aldosterone-producing adenoma (APA) and whether the degree of Uprot and strength of this relationship is reduced following correction of hyperaldosteronism. Subjects with APA (n=24) underwent measurement of 24 h Uprot and UNa before and after unilateral adrenalectomy (follow-up 15.0±11.9 months).

 

Following surgery, mean clinic systolic blood pressure fell (150.4±18.2 vs 134.5±14.5 mm Hg, P=0.0008), despite a reduction in number of antihypertensive medications, and Uprot (211.2±101.6 vs 106.0±41.8 mg per day, P<0.0001) decreased. There was a positive correlation between Uprot and UNa both before (r=0.5477, P=0.0056) and after (r=0.5097, P=0.0109) adrenalectomy. Changes in UNa independently predicted Uprot reduction (P=0.0189).

 

These findings suggest that both aldosterone levels and dietary salt contribute to renal damage, and that once glomerular damage occurs it is not completely resolved following correction of hyperaldosteronism. Our study suggests that treatment strategies based on reduction of aldosterone effects, by adrenalectomy or mineralocorticoid receptor blockade, in conjunction with low-salt diet would provide additional target-organ protection in patients with primary aldosteronism.

 

From http://www.nature.com/jhh/journal/vaop/ncurrent/full/jhh2010102a.html

Adrenal Disorders: Cushing's Disease & Cushing's Syndrome

The production of cortisol by the adrenal glands is stimulated by ACTH (Adrenal Cortical Tropic Hormone), which is produced by the pituitary gland in the brain. Thus, overproduction of cortisol can be caused by either a tumor in the pituitary gland (Cushing's disease), or in the adrenal glands (Cushing's syndrome). Less commonly, a tumor producing too much ACTH may be found outside of the pituitary gland. In patients with Cushing's disease, the blood levels of both ACTH and cortisol are elevated. In patients with Cushing's syndrome, the blood level of cortisol is increased in the setting of a low level of ACTH. Rarely, adrenocortical cancers may cause Cushing's syndrome.

Diagnosis

There is a great deal of variability throughout the day in the amounts of cortisol produced by the adrenal glands. For this reason, the most sensitive test measures the amount of cortisol excreted in the urine over a 24-hour period. A 24 hour free cortisol level greater than 100 µg is diagnostic of Cushing's syndrome. Patients suspected of having Cushing's syndrome will also undergo a dexamethasone suppression test which helps to determine the cause of the increased cortisol production. A CT or MRI scan is used to determine the location of the tumor.

Treatment

Patients with Cushing's disease typically have benign tumors of the pituitary gland in the brain. These patients are referred to a neurosurgeon for removal of the tumors. If removal of the pituitary tumor and medications fail to control Cushing's disease, removing both adrenal glands may be indicated. In patients with Cushing's syndrome, an adrenalectomy—surgical removal of the adrenal gland—is curative. This operation is usually performed laparoscopically, through several very small incisions.

From http://www.columbiasurgery.org/pat/adrenal/cushing.html

Laparoscopic Resection is Inappropriate in Patients with Known or Suspected Adrenocortical Carcinoma

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Laparoscopic Resection is Inappropriate in Patients with Known or Suspected Adrenocortical Carcinoma

B. S. Miller¹ , J. B. Ammori¹, P. G. Gauger¹, J. T. Broome³, G. D. Hammer² and G. M. Doherty¹

(1)	Division of Endocrine Surgery, University of Michigan, 2920F Taubman Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA

(2)	Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, USA

(3)	Division of Surgical Oncology and Endocrine Surgery, Vanderbilt University, Nashville, TN, USA

Published online: 7 April 2010

Abstract

Background

Complete surgical resection is the mainstay of treatment for patients with adrenocortical cancer (ACC). Use of laparoscopy has been questioned in patients with ACC. This study compares the outcomes of patients undergoing laparoscopic versus open resection (OR) for ACC.

 

Methods

A retrospective review (2003–2008) of patients with ACC was performed. Data were collected for demographics, operative and pathologic data, adjuvant therapy, and outcome. Chi-square analysis was performed.

 

Results

Eighty-eight patients (66% women; median age, 47 (range, 18–81) years) were identified. Seventeen patients underwent laparoscopic adrenalectomy (LA). Median tumor size of those who underwent LA was 7.0 (range, 4–14) cm versus 12.3 (range, 5–27) cm for OR. Recurrent disease in the laparoscopic group occurred in 63% versus 65% in the open group. Mean time to first recurrence for those who underwent LA was 9.6 months (±14) versus 19.2 months (±37.5) in the open group (p < 0.005). Fifty percent of patients who underwent LA had positive margins or notation of intraoperative tumor spill versus 18% of those who underwent OR (p = 0.01). Local recurrence occurred in 25% of the laparoscopic group versus 20% in the open group (p = 0.23). Mean follow-up was 36.5 months (±43.6).

 

Conclusions

ACC continues to be a deadly disease, and little to no progress has been made from a treatment standpoint in the past 20 years. Careful and complete surgical resection is of the utmost importance. Although feasible in many cases and tempting, laparoscopic resection should not be attempted in patients with tumors suspicious for or known to be adrenocortical carcinoma.

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B. S. Miller Email: barbram@umich.edu

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Trends in adrenalectomy: a recent national review

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Trends in adrenalectomy: a recent national review

Melissa M. Murphy¹ , Elan R. Witkowski¹, Sing Chau Ng¹, Theodore P. McDade¹, Joshua S. Hill¹, Anne C. Larkin¹, Giles F. Whalen¹, Demetrius E. Litwin¹ and Jennifer F. Tseng¹

(1)
Department of Surgery, Surgical Outcomes Analysis and Research (SOAR), University of Massachusetts Medical School, 55 Lake Avenue North, Suite S3-752, Worcester, MA 01655, USA

Received: 20 May 2009  Accepted: 26 February 2010  Published online: 25 March 2010

Abstract

Background

Adrenalectomy remains the definitive therapy for most adrenal neoplasms. Introduced in the 1990s, laparoscopic adrenalectomy is reported to have lower associated morbidity and mortality. This study aimed to evaluate national adrenalectomy trends, including major postoperative complications and perioperative mortality.

 

Methods

The Nationwide Inpatient Sample was queried to identify all adrenalectomies performed during 1998–2006. Univariate and multivariate logistic regression were performed, with adjustments for patient age, sex, comorbidities, indication, year of surgery, laparoscopy, hospital teaching status, and hospital volume. Annual incidence, major in-hospital postoperative complications, and in-hospital mortality were evaluated.

 

Results

Using weighted national estimate, 40,363 patients with a mean age of 54 years were identified. Men made up 40% of these patients, and 77% of the patients were white. The majority of adrenalectomies (83%) were performed for benign disease. The annual volume of adrenalectomies increased from 3,241 in 1998 to 5,323 in 2006 (p < 0.0001, trend analysis). The overall in-hospital mortality was 1.1%, with no significant change. Advanced age (<45 years as the referent; ≥65 years: adjusted odds ratio [AOR], 4.10; 95%; confidence Interval [CI], 1.66–10.10) and patient comorbidities (Charlson score 0 as the referent; Charlson score ≥2: AOR, 4.33; 96% CI, 2.34–8.02) were independent predictors of in-hospital mortality. Indication, year, hospital teaching status, and hospital volume did not independently affect perioperative mortality. Major postoperative in-hospital complications occurred in 7.2% of the cohort, with a significant increasing trend (1998–2000 [5.9%] vs 2004–2006 [8.1%]; p < 0.0001, trend analysis). Patient comorbidities (Charlson score 0 as the referent; Charlson score ≥2: AOR, 4.77; 95% CI, 3.71–6.14), recent year of surgery (1998–2000 as the referent; 2004–2006: AOR, 1.40; 95% CI, 1.09–1.78), and benign disease (malignant disease as the referent; benign disease: AOR, 1.98; 95% CI, 1.55–2.53) were predictive of major postoperative complications at multivariable analyses, whereas laparoscopy was protective (no laparoscopy as the referent; laparoscopy: AOR, 0.62; 95% CI, 0.47–0.82).

 

Conclusion

Adrenalectomy is increasingly performed nationwide for both benign and malignant indications. In this study, whereas perioperative mortality remained low, major postoperative complications increased significantly.

Keywords Adrenalectomy - Complications - Mortality - Nationwide inpatient sample

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Melissa M. Murphy
Email: melissa.murphy-smith@umassmemorial.org

Jennifer F. Tseng (Corresponding author)
Email: Jennifer.Tseng@umassmemorial.org

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From http://www.springerlink.com/content/h2j69247138788u8/

Incidentally-discovered Adrenal Masses

Author: Milton D Gross

Specialty: Radiology, Nuclear Medicine, Endocrinology
Institution: Division of Nuclear Medicine, Department of Radiology, University of Michigan
City: Ann Arbor; State/Province: Michigan; Postal Code: 48105; Country: United States

Author: Melvyn Korobkin

Specialty: Radiology
Institution: Division of Abdominal Imaging, Department of Radiology, University of Michigan Medical Center
City: Ann Arbor; State/Province: Michigan; Country: United States

 

Author: Wessam Bou-Assaly

Specialty: Radiology
Institution: Department of Radiology, University of Michigan Medical Center
City: Ann Arbor; State/Province: Michigan; Country: United States
Institution: Radiology Service, Department of Veterans Affairs Health System
City: Ann Arbor; State/Province: Michigan; Country: United States

Author: Domenico Rubello

Specialty: Radiology
Institution: Department of Nuclear Medicine, PET Center, and Medical Physics and Radiology, Santa Maria della Misericordia Hospital
City: Rovigo; Country: Italy

 

Abstract: Unanticipated adrenal masses are frequently encountered in modern, high resolution diagnostic imaging. Most often, these masses are benign adrenal adenomas, but when detected they necessitate a clinical evaluation sufficient to exclude subclinical endocrine disease, primary adrenal cancer, and remote metastases to the adrenal glands from other malignancies. These "incidentally-discovered" adrenal masses or so-called "adrenal incidentalomas" can be further evaluated with CT, MRI, and nuclear medicine imaging techniques. A substantial literature supports the use of each of these modalities to non-invasively characterize these neoplasms that have been considered by some as a 'disease' by modern imaging technology.

 

Introduction

Over the last 3 decades the more widespread use of high-resolution CT and MRI have seen the frequent, “incidental” discovery of clinically unsuspected masses of the adrenal glands. Detection of these masses raises the specter of malignancy and forces further diagnostic evaluation to determine their etiology and to distinguish benign masses from those that would substantially change the clinical approach to the patient.

 

In patients undergoing CT for reasons other than adrenal disease, adrenal masses are incidentally discovered in 0.4-4.5% (Kloos et al., 1995). The majority of adrenal masses, ranging from 7% to 94%, are benign and hormonally non-functional, while in patients with malignancy the incidence of unsuspected adrenal masses ranges from 7% to 68% (Kloos et al., 1995). Metastases from other cancers to the adrenal occur in up to 20% of patients without previously diagnosed cancers and in almost 75 % of patients harboring non-adrenal primary malignancies (Kloos et al., 1995) (Table 1).

 

The incidence of clinically unsuspected adrenal masses increases with age greater than 30 years, regardless of gender. Clinically silent, hormonally active adrenal masses include tumors that produce hormones from all of the functional zones of the adrenal cortex and the adrenal medulla. As a result it is important that once discovered, and prior to any further imaging, a biochemical evaluation sufficient to exclude pheochromocytoma, normokalemic primary aldosteronism, and subclinical hypercortisolism be done as these conditions are optimally managed by surgical removal of the offending tumor (Young, 2007).

 

Methods of Adrenal Gland Imaging

Computed tomography is the most common imaging modality that identifies unsuspected adrenal masses in the evaluation of the chest and upper abdomen for diseases unrelated to the adrenal glands (Gross at al., 2005). Both CT and MRI can be used to differentiate normal from abnormal adrenal glands and MRI has been used to characterize incidentally discovered adrenal masses in clinical situations where CT is non-diagnostic (Gross et al., 2009) (Table 2).

 

Computed tomography and magnetic resonance imaging

 

Contemporary CT scanners using slice thicknesses of 3-5 mm will reliably depict the adrenal glands in virtually all patients. Comparison of non-contrast to contrast-enhanced CT can be used to distinguish adrenal masses and for evaluating retention and patterns of contrast washout as a means to differentiate adenomas from other adrenal neoplasms (Boland et al., 2008). MRI can be used to advantage in the evaluation of normal adrenal glands and adrenal masses. Gradient-echo, chemical shift MRI with in- and opposed-phrase imaging, and dynamic contrast-enhanced MRI detect lipid content in adrenal adenomas and, when combined with chemical shift ratios, depict the adrenal glands with an efficacy similar to CT (Dunnick et al., 2002). Hybrid scanners marrying CT, and perhaps in the near future MRI, with positron emission tomography (PET) and single photon emission tomography (SPECT) employing radiopharmaceuticals designed to target unique aspects of adrenal gland function(s) offer direct combination of anatomic and functional information that enhances diagnosis and differentiation of benign from malignant adrenal lesions (Gross et al., 2009).

 

Adrenal scintigraphy

The radiocholesterol analogs, ¹³¹I-6β-iodomethyl-19-norcholesterol (NP-59) and selenium-75-6β-iodomethyl-19-norcholesterol (Scintadren®) were some of the first successful radiopharmaceuticals used to image the adrenal cortex (Gross et al., 2007). Radiolabeled inhibitors of enzymes responsible for adrenal steroid hormone biosynthesis like the 11β-hydroxylase inhibitor, carbon-11-metomidate (¹¹C-MTO), can also be used to image neoplasms of adrenocortical origin. Other radiolabeled substrates depict metabolic processes such as the radio-fluorine-labeled ¹⁸F-fluorodeoxyglucose (FDG) to identify primary adrenal neoplasms and metastases to the adrenals, while ¹¹C-labeled acetate and ¹¹C- and ¹⁸F-labeled choline have been used to depict adrenal adenomas (Gross et al., 2007).

Radiolabeled metaiodobenzylguanidine (MIBG) has been used to identify the adrenal medulla and localize neoplasms of adrenomedullary origin by exploiting norepinephrine-re-uptake mechanisms into the catecholamine storage vesicles of adrenergic tissues.

 

Hydroxyephedrine, an analog of norepinephrine, can be labeled with ¹¹C or ¹⁸F, and is transported into adrenergic nerve terminals by these same mechanisms. The list of catecholamine-based PET radiopharmaceuticals used to image the adrenal medulla, related tissues, and tumors of sympathomedullary origin now includes ¹¹C-epinephrine, ¹¹C- or ¹⁸F-hydroxyepinephrine, ¹⁸F-fluorodopamine (FDA), and ¹⁸F-fluorodihydroxyphenylalanine (¹⁸F-DOPA) (Shulkin et al., 2006). Alternatively, somatostatin receptor uptake of specific imaging agents can be used to image tissues that express somatostatin receptors, like the adrenal medulla and many other tissues and neoplasms. Octreotide, a long-acting somatostatin antagonist labeled with a variety of radioisotopes (¹¹¹Indium, ¹²³Iodine, ^99mTechnetium for SPECT, and ⁶⁸Gallium for PET imaging) can be used to accurately localize and stage primary and metastatic sympathomedullary tumors (Gross et al., 2007).

 

Imaging Incidentally-discovered Adrenal Masses

The differential diagnostic list of incidentally-discovered adrenal masses is long and a description of all but the most common is outside the scope of this short review. An extensive medical literature is available that describes the imaging characteristics of adrenal masses (Gross et al., 2005).

 

Adrenal adenoma

Adrenal adenomas are depicted on CT with density values expressed as Hounsfield units (HU) that are similar to normal adrenal tissues and depending upon their lipid content may express HU values similar to tissue water density (Korobkin et al., 1996). Furthermore, adenomas demonstrate increasing density, so-called “enhancement,” after intravenous CT contrast with more rapid loss of contrast — “washout” as compared to adrenal metastases (Korobkin et al., 1998). Like CT, MRI characteristics of adenomas are also similar to normal adrenal tissues. Signal intensity of adenomas is low on T2-weighted MR imaging sequences, but there is overlap (20-30%) with the signal intensity of metastases to the adrenal. Chemical-shift imaging is useful to depict tissue lipid content and is often employed to differentiate adenomas from metastases to the adrenal (Dunnick et al., 2002).

 

Pheochromocytoma

Pheochromocytomas are often clinically silent and present on high resolution anatomic imaging as incidentally-discovered adrenal masses. These neoplasms show enhancement with intravenous contrast agents in a fashion similar to malignant adrenal masses and occasionally may mimic contrast washout characteristics of benign adrenal adenomas. The imaging uncertainty posed by pheochromocytomas demands a biochemical evaluation sufficient to exclude catecholamine hypersecretion in suspect patients. Concerns over the potential of intravenous contrast-induction of hypertensive crisis have recently been allayed with nonionic contrast agents. Like CT, pheochromocytomas are usually hyperintense on T2-weighted imaging; however, there is overlap and about 30% are hypointense on T2-weighted imaging sequences (Blake et al., 2004).

 

Adrenal carcinoma

Adrenal carcinoma is a rare neoplasm (~ 2/10⁶ patients) that usually presents late in the course of disease. Adrenal carcinoma is often imaged as a large, heterogeneous abdominal mass with central necrosis, calcification, and tumor venous extension on contrast enhanced CT (Gross et al., 2009). On MRI these neoplasms are hyperintense on both T1- and T2-weighted imaging sequences from intra-tumor hemorrhage and central necrosis.

 

Adrenal metastases

Adrenal glands are common sites of remote metastases from cancers of the lung, breast, and melanoma. Adrenal metastases can be unilateral, bilateral, and variable in size. CT and MRI are nonspecific. Small metastases are often homogeneous on contrast CT or MRI, while large metastases are heterogeneous as a result of intra-metastasis necrosis and hemorrhage.

 

Distinguishing benign from malignant adrenal masses

Figure 1. An adrenal mass (arrow) is identified on CT (panel A) with characteristics of an adenoma with a non-contrast CT density (panel B) of 9.8 HU.

 

CT can be used to distinguish adrenal adenomas from metastases since most adenomas demonstrate non-contrast densities that are lower than metastases to the adrenal. The highest diagnostic efficacy for diagnosis of adrenal adenomas is obtained by selecting a threshold density value of 10 HU on non-contrast CT, as HU values for adenomas and adrenal hyperplasia are typically lower than those of metastases to the adrenal and pheochromocytomas (Figures 1 and 2).

 

Chemical-shift MRI also differentiates adrenal adenomas from metastases. By exploiting the different resonant frequencies of hydrogen in tissue water and lipid molecules, chemical-shift MRI detects a loss of signal intensity of tissues with high lipid and water content. Using gradient-echo imaging techniques, signal intensity loss on opposed-phase as compared to in-phase images differentiates tissues that contain lipids with high sensitivity and specificity. As lipids are common components of adrenal adenomas that are usually absent in metastases, this difference in lipid content can be exploited for the differentiation of adenomas vs. metastases to the adrenals (Figures 3 and 4).

Figure 2. Abdominal CT of bilateral adrenal masses (arrows) shows persistent enhancement of the right adrenal gland after intravenous contrast at 1.5 (panel B) and 5 min (panel C) after contrast injection in a pattern compatible with metastases to the adrenals.

 

In a combined histological CT and MRI study of adrenal adenomas there was an inverse relationship between lipid-containing cells and unenhanced CT, and a positive correlation with the relative change in signal intensity on opposed-phase MRI confirming that non-contrast CT and chemical-shift MRI might not necessarily complement each other in the evaluation of adrenal adenomas (Outwater et al., 1996). Contrast-enhanced CT images of the adrenals are obtained about 1 minute after a bolus intravenous injection of contrast and at this time point the attenuation values of adenomas and metastases are nearly identical (Figure 2B and Figure 5C). However, over time adenomas demonstrate loss of contrast enhancement and attenuation values on contrast enhanced CT of < 30-40 HU at 10-15 minutes post contrast injection can be used to distinguish, with few exceptions, adenomas from other adrenal masses (Gross el al., 2009).

 

Figure 3. MRI of a right adrenal nodule (arrows) demonstrates post-contrast enhancement on T1-weighted imaging (panel C) and displays loss of signal on out-of-phase (panel B) compared to in-phase imaging (panel A) confirming the mass as an adrenal adenoma.

 

Adrenal gland contrast washout as a percentage of initial enhancement is another parameter that can be used to identify adenomas from other adrenal masses. Adrenal adenomas have characteristic washout percentages of ~ 60% at 15 minutes post contrast administration corresponding to a sensitivity of 88% and a specificity of 96% for diagnosis of adenoma (Korobkin et al., 1998) (Figure 5). Further, so-called “lipid-poor” adenomas with unenhanced CT attenuation of >10 HU have contrast enhancement washout values that are nearly identical to those of lipid-rich adenomas confirming the value of differential washout as a means to identify adrenal adenomas from other adrenal masses (Caoili et al., 2000).

 

Distinguishing adrenal adenoma from carcinoma

Figure 4. MRI of a right adrenal mass demonstrates heterogeneous post-contrast enhancement (panel C) with no signal loss on out-of-phase imaging (panel B) vs. in-phase imaging (panel A) confirming the mass to be an adrenal metastasis.

 

Any adrenal mass larger than 5 to 6 cm in diameter is considered suspicious for an adrenocortical carcinoma. Large, non-secreting pheochromocytomas, adrenal carcinoma, or adrenal metastases may be indistinguishable by CT and MRI. Size criteria for resection of adrenal masses varies widely from 3.5 to 6 cm, and while there is controversy concerning the approach to smaller masses there is general agreement that masses > 6 cm, regardless of their imaging characteristics, should be removed.

 

Scintigraphy of adrenal masses

There are a host of scintigraphic imaging agents, with each targeting a unique characteristic of adrenal gland function that can be used to assess the etiology of incidentally-discovered adrenal masses. Adrenal adenomas can be depicted with iodocholesterol with positive and negative predictive values of 89% and 100%, respectively, and the lateralization of tracer uptake to one gland may be predictive of the development of future functional autonomy.

 

Metaiodbenzylguanidine images masses of adrenomedulla origin with positive and negative predictive values of 83% and 100%, respectively, while ¹⁸F-FDG separated benign from malignant adrenal lesions with 100% sensitivity and specificity (Maurea et al., 2001). As a result, if functional imaging is to be used to evaluate adrenal masses in patients with no history of cancer, radiocholesterol scintigraphy should be the first imaging procedure to identify the most common incidentally-discovered adrenal mass, a benign adrenal adenoma, followed by MIBG to identify clinically silent pheochromocytomas. Should MIBG be non-diagnostic, ¹⁸F-FDG is to be used to identify a potentially malignant adrenal mass or remote metastasis to the adrenal. Conversely, in patients with a prior history of cancer, ¹⁸F-FDG would be the most optimal first imaging study in the search for metastatic disease to the adrenal followed in sequence by iodocholesterol and MIBG.

Figure 5. A left adrenal gland mass (arrow) with a density of 1.5 HU on non-contrast CT (panels A and B) increases after intravenous contrast administration to 50 HU on early post-contrast enhanced images (panel C), and falls to 4 HU on the delayed images (panel D). The calculated washout of 95% is compatible with a lipid rich, adrenal adenoma.

 

¹⁸F-FDG-PET can differentiate benign from malignant adrenal lesions and metastases to the adrenal (Figure 6). In a study of 150 patients with adrenal masses, ¹⁸F-FDG-PET had a sensitivity of 98.5% and a specificity of 92% at a standardized uptake value (SUV) threshold of 3.1 and with the addition of CT to FDG-PET specificity increased to 98% with all masses correctly characterized as benign or malignant (Metser et al., 2006). While in 50 patients with known or suspected malignancy, ¹⁸F-FDG-PET had a sensitivity of 100%, a specificity of 94%, and an accuracy of 96%, and by using the liver as a ‘normal’ comparison tissue it improved the sensitivity of ¹⁸F-FDG for detecting malignant adrenal lesions without sacrificing sensitivity (Yun et al., 2001). More recently ¹⁸F-FDG-PET was shown in a prospective multicenter trial to accurately differentiate adrenocortical adenomas from adrenal carcinomas and in particular a subgroup of masses with indeterminate findings on CT (Groussain et al., 2009).

 

In comparative studies of the 11β-hydroxylase inhibitor, ¹¹C-MTO, and ¹⁸F-FDG in incidentally-discovered masses, ¹¹C-MTO identified lesions of adrenocortical origin with the highest SUV in adrenocortical carcinoma, followed by hypersecretory adrenal cortical adenomas and non-hypersecretory adenomas, although ¹¹C-MTO-PET did not distinguish benign adrenocortical neoplasms from adrenocortical carcinoma (Hennings et al., 2006). ¹⁸F-FDG can be also used to image pheochromocytomas and adrenocortical carcinoma and to differentiate these neoplasms from other non-hypersecreting and most hypersecreting adrenal adenomas.

Figure 6. PET/CT scans of adrenal masses (white arrows). An ¹⁸F-FDG scan (panel A) shows no appreciable tracer accumulation in a left adrenal mass seen on CT (panel B) compatible with an adrenal adenoma. An adrenal metastasis from lung cancer (black arrows) is depicted on an ¹⁸F-FDG scan (panel C) as an intense focus of tracer uptake in a small left adrenal mass on CT (panel D).

 

Pheochromocytomas can be reliably imaged with ¹²³I- or ¹³¹I-MIBG with PET/CT using ¹⁸F-dopamine or ¹⁸F-DOPA (Shulkin et al., 2006) (Figure 7). In a comparison of the efficacy of ¹⁸F-FDA, ¹²³I-MIBG, and ¹¹¹In-octreotide, ¹⁸F-FDA demonstrated the highest sensitivity in the localization of intra-adrenal and metastatic pheochromocytomas, followed by ¹²³I-MIBG and ¹¹¹In-octreotide for intra-adrenal pheochromocytoma, while the efficacy of ¹⁸F-FDA and ¹²³I-MIBG were equivalent (Ilias et al., 2008). If catecholamine analogs are not successful in imaging, the neoplasm may have experienced malignant dedifferentiation, and ¹⁸F-FDG or ¹¹¹In-octreotide can be used to localize metastases and guide subsequent therapy.

 

Summary

Incidentally-discovered adrenal masses are commonly encountered in modern high-resolution imaging. The list of differential diagnostic possibilities of incidentally-discovered adrenal masses is large, but fortunately, most are benign and non-hyperfunctioning adenomas. The first consideration in the evaluation of an incidentally-discovered adrenal mass is its functional status and should include a biochemical evaluation sufficient to exclude clinically-silent endocrine disease. CT, MRI, and scintigraphy can be used to characterize incidentally-discovered adrenal masses and distinguish adrenal adenomas from metastases to the adrenals and other adrenal neoplasms. An understanding of the imaging techniques used to distinguish benign from malignant and other incidentally-discovered adrenal masses speeds diagnosis, optimizes therapy, and decreases costs in the evaluation of these neoplasms.

Figure 7. A small, left adrenal mass (arrow) on CT (panel A) demonstrates intense ¹⁸F-DOPA uptake (panel B) in a patient with hypertension and a prior negative ¹²³I-MIBG scan who was later shown to have elevated catecholamines compatible with a pheochromocytoma.

 

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Dunnick NR and Korobkin M. Imaging of adrenal incidentalomas: current status. Am J Roentgenol 179(3):559-68, 2002.

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Gross MD, Korobkin M, Bou Assaly W, Dwamena B, Djekidel M. Contemporary imaging of incidentally discovered adrenal masses. Nat Rev Urol 6:363-73, 2009.

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[Discovery Medicine, Volume 9, Number 44, January 2010. Pre-published.]

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From http://www.discoverymedicine.com/Milton-D-Gross/2010/01/04/incidentally-discovered-adrenal-masses/