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AACE Annual Scientific and Clinical Congress

Paul W. Ladenson, MD, John Eager Howard Professor of Endocrinology and Metabolism, Professor of Medicine, Pathology, Oncology, and Radiology & Radiological Sciences, Director, Division of Endocrinology and Metabolism, Johns Hopkins Medicine, discusses differential diagnosis for cytologically indeterminate thyroid nodules.

	Currently, about 1 in 5 biopsies lead to diagnoses of indeterminacy, and about one-third of those patients prove to have thyroid cancer. Without further diagnostic certainty, many such patients are being advised to have surgery.

	Two molecular diagnostic strategies are currently being explored. The first is a thyroid cancer candidate gene approach, in which clinicians can look for a set of genes known to be associated with thyroid cancer, such as BRAF, RET, PTC rearrangements, and RAS mutations. In the absence of such mutations, the physician can feel more confident that the nodule is benign. This approach has a theoretical limit of achieving a negative predictive value in the 85% range.

	The second molecular approach being explored is gene expression analysis. The approach began with the profiling of almost 250,000 mRNA transcripts in nodules that were benign and malignant. This transcription helped to identify genes that were over- and under-expressed in benign nodules. With this technique, the 142 genes that were ultimately selected as informative and their profiles are employed in indeterminate nodule biopsy material in order to determine if it is benign. The negative predictive value of this testing appears to be 95% to 96%, akin to getting a benign cytologic diagnosis.

	Ladenson says that, as these molecular tests now enter clinical practice, fewer patients with indeterminate nodules will have unnecessary surgeries.

Dr. Paul W. Ladenson, from Johns Hopkins Medicine, on Diagnosis of Thyroid Nodules

Dr. Ladenson on Diagnosis of Thyroid Nodules

 The authors of a case study presented at the 21st Annual Congress of the American Association of Clinical Endocrinologists noted that multiple endocrine neoplasia (MEN) type 2 is “a syndrome of familial cancers with autosomal dominant inheritance basically characterized by Medullary Thyroid Cancer (MTC).” The MEN 2A subtype, which makes up around 90% of cases of MEN, is caused by mutations in the 

 protooncogene, most commonly resulting in “the substitution of one of six cysteine residues in exon 10 and 11;” MEN 2A is “most frequently caused by activating mutations of the extracellular codon 34.”

Patients with MEN 2A often develop cutaneous lichen amyloidosis, primary hyperparathyroidism (about 15-30% of cases), pheochromocytoma (about 50%), and MTC (about 95%). MEN 2A may be indicated when patients develop bilateral or multifocal MTC, or when MTC presents at an early age (younger than 3-5 years). Diagnosis relies on clinical findings, family history, and genetic testing of the 

In “Multiple Endocrine Neoplasia Type 2A: Study of a Family of Three Generations with Pedigree Analysis of the RET Protooncogene,” Galesanu and colleagues reported on the results of genetic screening of the 

 protooncogene for mutation exons 10 and 11, codons 609, 611, 618, 629, 630, and 634, in three generations of a family in which the first patient (proband) presented with “bilateral pheochromocytoma associated with MTC.”

Out of nine family members screened, six (proband, three daughters, and two male grandchildren) were found to have the 

 protooncogene mutation codon 634 (Cys 634 Trp) in exon 11. The proband and one daughter had bilateral pheochromocytoma and MTC, two daughters had unilateral pheochromocytoma (one with confirmed MTC, one with nodular goiter and increased serum calcitonin), and one of the male grandchildren also has increased serum calcitonin.

The authors noted that risk-reducing thyroidectomy is a preventive option for all subtypes of MEN, and is recommended in many cases by the American Thyroid Association. The case findings presented here confirm that “genetic screening for germline 

 protooncogene mutation in hereditary medullary thyroid cancer is accurate,” enabling patients who are carriers of the mutation to opt for early prophylactic surgery. However, this can be a difficult decision for parents of young children to make—in this case study, although the two grandchildren carry the 

 mutation, their parents opted against total thyroidectomy, underscoring the need for further study of “the psychosocial impact of genetic testing for MEN 2” and the challenges of accepting surgical treatment and lifelong follow-up surveillance.

Results of a multi-generational case study strengthen the case for genetic screening in cases of hereditary thyroid cancer.

Carriers of Mutation Responsible for Multiple Endocrine Neoplasia Can Face Difficult Choices

Study results presented by Guerrero and colleagues at the 21st Annual Congress of the American Association of Clinical Endocrinologists showed that where a patient lives when he or she is diagnosed with thyroid cancer can have an effect on the stage at which the cancer is diagnosed and on cancer-free survival (CFS) rates.

Using information from the Surveillance Epidemiology and End Results (SEER) database, the authors identified more than 87,000 individuals diagnosed with thyroid cancer between 1973 and 2008, assessing for historical stage of diagnosis and CFS according to geographic region. The data were stratified by thyroid cancer type, race/ethnicity of the patient, age, year of diagnosis, and registry site. Data were excluded for Hawaii and Alaska natives, patients with cancer stage 0 or unknown stage at diagnosis, patients who had been previously diagnosed with tumors, patients whose age was unknown at diagnosis, and patients for whom survival information was missing.

The four geographic regions for this study were: West (including data from San Francisco-Oakland, New Mexico, Seattle, Utah, San Jose, Los Angeles, and other locales), South (Atlanta and rural Georgia, Kentucky, and Louisiana), East (Connecticut and New Jersey), and Midwest (Detroit and Iowa). Fifty-five percent of individuals analyzed were from the West, 12% were from the South, 18% were from the East, and 15% were from the Midwest.

The authors reported that 60% of patients presented with localized disease, 34% with regional metastasis, and 5.6% with distant metastasis. Papillary thyroid cancer was the most prevalent diagnosis across regions and ethnicities (West: 85%, South: 82%, East: 83%, Midwest: 79%), followed by follicular thyroid cancer (West: 7.3%, South: 9%, East: 7.7%, Midwest: 10.7%). Median age at diagnosis was consistent across regions (roughly 46-48 years of age).

Regional differences in thyroid cancer stage and survival included:

		Patients in the West region had a higher risk of presenting with regional and distant metastases

		Patients in the East with follicular cancer were more likely to have local disease 

The large majority of patients in this study were female (at least 75% of the patient population in each region) and non-Hispanic white (66-87% of the population in each region, with the highest concentration in the South and Midwest). The authors reported “no significant difference in CFS by geographic region for non-Hispanic white or Hispanic white individuals,” but did find that “blacks from the West had significantly better CFS than blacks from the South.”

The authors concluded that “there are differences in the stage of presentation and survival of individuals with thyroid cancer according to geographic region.” They identified socioeconomic factors, access to healthcare, and cultural beliefs as potential contributing factors.

The data in this study were also used to determine “if there were any differences in treatment before and after the publication of the 2006 American Thyroid Association management guidelines for thyroid nodules and thyroid cancer.” The authors determined that “more patients received a sub-total, near-total, or total thyroidectomy, and more patients had lymph node dissections” after publication of the guidelines. They reported that “stage of presentation and use of radioactive iodine ablation did not change” after the guidelines were published.

Patients are more likely to present with regional or distant metastases and experience lower rates of cancer-free survival depending on where they live.

Researchers Find Regional Differences in Stage of Presentation and Survival of Individuals With Thyroid Cancer

According to study results presented at the 21st Annual Congress of the American Association of Clinical Endocrinologists, overexpression of pituitary tumor transforming gene 1 (

) is associated with low survival rates in patients with adrenocortical carcinoma (ACC). However, treatment with vorinostat, which decreases 

 expression, may be suitable for targeted treatment of ACC.

Researchers extracted RNA from 100 mg samples from 19 flash-frozen ACC tumors, along with RNA from four normal adrenal glands. Sixty-three percent of the patients from whom the tumors were extracted were female, with an average age of 47.6 years. Median survival was 5.9 years. The average tumor size was 9.7 cm and 351 g.

Using gene expression profiling, the authors examined the samples and “identified marked dysregulation of the cell cycle control, focused on sister chromatid adhesion and cytokinesis in the G2/M transition.” In particular, they reported potential alterations in activity of the tumor suppressor gene 

, noting that “genes that are normally repressed by 

 were overexpressed, and those that are normally promoted had decreased expression.”

The researchers identified overexpression of 

, which encodes the antibody securin, “a negative regulator of 

 and a protein involved in the G2/M transition,” as a marker of poor survival. Patients with tumors expressing high levels of 

 levels had a median survival of 1.2 years, whereas patients with tumors expressing lower levels of 

Treating two ACC cell lines (SW-13 and H295R) with the histone deacytlase inhibitor vorinostat “decreased securin levels in both cell lines and inhibited cell growth with IC50 values of 1.69 uM and 0.891 uM, for SW-13 and H295R, respectively.”

This may be a potentially promising development because, as the authors noted, ACC “is an aggressive malignancy with poor overall five-year survival (16-22%).” Complete surgical excision is the only current treatment with the potential to cure ACC. However, up to 70% of patients have metastases at the time of diagnosis, ruling out surgery. Current chemotherapy options are limited for ACC—the antineoplastic drug mitotane has only a 25% response rate. In the recently concluded FIRM-ACT study, patients with ACC treated with a regimen of etoposide, doxorubicin, cisplatin, and mitotane had a median overall survival of 14.8 months. The response rate for this regimen was only 24%.

The authors noted that limited options currently available to patients with ACC underscore the “continued need to understand the underlying molecular pathogenesis of ACC and develop new therapies.” Further study of the effect of overexpression of 

 on survival in ACC and the potential of vorinostat to inhibit cell growth is warranted.

Researchers find that overexpression of a specific gene is associated with poor survival in patients with adrenocortical carcinoma.

Genetic Data Points to Potential New Therapeutic Target for Adrenocortical Carcinoma

A growing number of health care professionals are considering the use of medical tattoos as a permanent method of letting emergency workers know valuable information about certain medical conditions that require special management.

This area of interest was discussed by Saleh Aldasouqi, MD, an endocrinologist with the Michigan State University Health Team, on Thursday at the American Association of Clinical Endocrinologists 21st Annual Scientific and Clinical Congress.

Aldasouqi noted that many patients with chronic conditions opt to get a tattoo to denote their condition in case they require emergency treatment. These tattoos allow first responders to avoid possible complications by knowing how to properly manage patients given the conditions they may have. For example, many diabetic patients get a tattoo on their wrist or forearm. By knowing this, first responders can test the patient’s blood sugar and, if the levels are found to be low, treat the patient with glucose. Other medical tattoos denote conditions such as allergies, high blood pressure, and heart disease.

Prior to the advent of medical tattoos, patients have traditionally looked to forms of jewelry, such as necklaces or bracelets, to indicate a particular medical condition.  However, Aldasouqi said that there is a lack of data, standards, and regulations associated with them.

“The medical community, and particularly endocrinologists as diabetes experts, should establish guidelines regarding medical tattoos,” Aldasouqi said. “Specifically, patients who want a medical tattoo need guidance on how to get it safely, where it should be located on their body and what it should look like.”

In the cases of diabetic patients, their blood glucose and A1C levels should be in a normal range prior to getting a tattoo in order to reduce the risk of poor healing or developing infections.

Additionally, Aldasouqi said that certain medical tattoos should appear on certain visible locations of the body. This would enable emergency personnel to locate the information quickly when responding. Since no guidelines currently exist, patients opt for several different locations on their body to denote similar conditions.

“Each minute and each second will count, as far as survival is concerned, for a patient in a diabetic coma,” Aldasouqi said. “Accordingly, the medical community must take seriously the opportunity and responsibility to establish medical tattoo guidelines.”

Another presentation at the AACE meeting on Thursday featured Dr. Saleh Aldasouqi, FACE, ECNU, discussing a topic that is not heard about too often in the medical world: tattoos.

Why Medical Tattoos Shouldn't Be Taboo

Patients who live far from medical facilities benefit from having “virtual” conversations with their doctors and are comfortable with that arrangement, according to a study presented this morning during the American Association of Clinical Endocrinologists 21st Annual Scientific and Clinical Congress.

The results were discussed by Rabia Rehman, MD, endocrinology fellow at the University of Tennessee Health Science Center, in a presentation titled “Tele-Endocrinology: Bridging the Gap in Endocrine Care Via Telemedicine.

While telemedicine is not a new concept, data continues to suggest that such programs are not only clinically effective, but also cost-effective. The topic was of particular interest during the conference because diabetes is approximately 17% more prevalent in rural areas compared to urban centers, the AACE said in a statement.

For their study, Rehman and her colleagues set up a “virtual examination room” in the office of a clinical endocrinologist in an urban center so that the physician would be able to have virtual, face-to-face communications with patients in rural areas. A nurse at the physical location of each patient assisted with communication and physical examinations. A total of 66 patients were examined in this manner over the course of 2.5 years.

According to Rehman, “progress was shown to occur in the condition of a majority of the patients where follow-up data was available, including a significant improvement in the health of Type 2 diabetes patients.” Moreover, 97% of the patients were comfortable with the telemedicine examination and found value in this type of healthcare delivery.

The research team did not collect any data on the cost of setting up a virtual examination room, but Rehman said she believes physicians will find that the cost of equipment such as television monitors, an Internet connect, and audio/video equipment will be “far outweighed by the benefit of reaching many patients who might not otherwise have been seen by a specialist.” In the long term, she said, cost savings are likely to be significant for both patients and providers.

Patients who live far from medical facilities benefit from having "virtual" conversations with their doctors and are comfortable with that arrangement.

Telemedicine a Valuable Way to Deliver Healthcare

Photos taken from the American Association of Clinical Endocrinologists (AACE) 21st Annual Scientific and Clinical Congress held at the Pennsylvania Convention Center, from May 23-27, 2012.

Photos taken from the AACE 21st Annual Scientific and Clinical Congress held at the Pennsylvania Convention Center, from May 23-27, 2012.

AACE 21st Annual Scientific and Clinical Congress Slideshow

Although the 21st Annual Congress of the American Association of Clinical Endocrinologists (AACE) is focused primarily on developments in diabetes, studies relevant to the oncology world were also presented. Two, in particular, were on display as poster presentations.

	“Insular Carcinoma: A New Face of Thyroid Cancer,” was conducted by Rattan et al of Geisinger and featured data on this histologically distinct subset of thyroid cancer, which falls between well-differentiated and anaplastic carcinomas.

	The presentation, a case study of a 79-year-old male, included a summary in which the researchers explained that insular carcinoma is a subtype of thyroid carcinoma “whose criteria for diagnosis is not uniform among pathologists.” They also noted that this subtype exhibits increased aggressiveness and a propensity for both local recurrence and distant metastases. Because of this, the authors concluded that “it is important to identify insular thyroid carcinoma, as it warrants aggressive management with total thyroidectomy followed by radioactive iodine ablation of any remaining thyroid tissue, which leads to better outcomes.”

	The second study on display, “Novel Gene Expression Classifier Raises Pre-Operative Suspicion of Medullary Thyroid Cancer,” was conducted by Kloos et al of Veracyte. Medullary thyroid carcinoma (MTC) is the most aggressive of the well-differentiated thyroid carcinomas.

	The study focused on the use of the Afirma Gene Expression Classifier (GEC), a test that “measures RNA transcript signals from 142 genes and applies an algorithm to classify nodules, with indeterminate fine needle aspiration (FNA) cytology, as either ‘benign’ or ‘suspicious.’”

	The study included more than 10,000 biopsied thyroid nodules and allowed for a combined prospective and retrospective analysis of pre-operative case series of cytologically indeterminate and malignant FNAs. No false positive cases occurred.

	The researchers concluded that “the GEC can raise suspicion for MTC in certain FNA samples,” and that “surgical management is altered to include a minimum of total thyroidectomy and central neck dissection.” The research team also mentioned that “pre-operative RET proto-oncogene status alters management of unintentionally devascularized parathyroid glands.”

A look at two poster presentations from the AACE meeting focusing on insular carcinoma and medullary thyroid cancer.

Oncology Posters Presented at Annual Endocrinology Meeting

Stay tuned for live coverage from the American Association of Clinical Endocrinologists (AACE) 21st Annual Scientific and Clinical Congress held at the Pennsylvania Convention Center, from May 23-27, 2012.

The conference will feature new products and devices as well as cutting edge research.

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Stay tuned for live coverage from the American Association of Clinical Endocrinologists (AACE) 21st Annual Scientific and Clinical Congress.

AACE Annual Scientific and Clinical Congress | Conference