Operated by the Kyoto University Bioinformatics Center, “GenomeNet is a Japanese network of database and computational services for genome research and related research areas in biomedical sciences.” Here you can find KEGG Pathway Maps which demonstrate each of the “heterozygous mutations in at least five genes encoding transcription factors” known to cause MODY.

What is Maturity-onset Diabetes of the Young?

For their “October Special Edition” the editors of Diabetes In Control chose to focus on “Uncommon Diabetes Diagnoses” including monogenic diabetes, neonatal diabetes mellitus, and MODY. The section that covers MODY is short, but explains the genetic origins of the disease, incidence and the risk of inheritance, and why, though it may be confused with type 1 and type 2 diabetes, MODY is not the same as either.

MODY: A Rare Form of "Type 1.5" That is Often Misdiagnosed

Janet Ruhl was diagnosed with type 2 diabetes in 1998, but, “after losing 30 pounds with a low carb diet” and exercising “daily for a year,” found her blood sugar levels to be worse than at the time of diagnosis. Frustrated, she began to question her diagnosis and discovered that she may have MODY, which she claims she is able to keep under control through a low carbohydrate diet (her “latest A1C in October of 2010 was 5.7%). In this article (“MODY — It’s Not Type 1 and Not Type 2, but Something Else”) she compiles all of her research on MODY which is interspersed with information from her personal experience dealing with the condition. Ms. Ruhl is careful to note that her site should not substitute for the care or advice of a physician, but nonetheless, it remains a comprehensive resource for patients looking to gain a better understanding of this lesser-known form of diabetes.

Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-onset Diabetes of the Young

If you want to direct your patients to a more official patient-focused resource than that of Janet Ruhl, you can’t get much more stamp-of-authenticity than the National Diabetes Information Clearinghouse. This guide explains both MODY and neonatal diabetes mellitus, what a patient should know about genetic testing and counseling, and provides links and contact information for related organizations. Also helpful is a chart that lists all of the subtypes of monogenic forms of diabetes, how common they are, the usual age of onset, the type of inheritance or mutation, treatment, and more.

This Harvard Health Publications-authored resource is housed at SparkPeople.com and covers all of the basic information that any patient could want to know about MODY including symptoms, diagnosis, expected duration, prevention and treatment strategies, prognosis, and recommendations on when to call a doctor.

Genetics: Maturity Onset Diabetes of the Young

Recognizing that “there are rarer forms of [diabetes] which do not follow simple categorization”, Harvard Medical School has developed this course to help practitioners distinguish MODY from type 1 and type 2 diabetes. The activity explores clinical presentation, diagnostic approaches, therapeutic strategies, and whether “recent genetic discoveries” indicate a need to reclassify monogenic diabetes syndromes “according to a molecular etiology framework;”

Assessment of High-Sensitivity C-Reactive Protein Levels as Diagnostic Discriminator of Maturity-Onset Diabetes of the Young Due to HNF1A Mutations

 Owen K, Thanabalasingham G, James T, et al

 Though genetic testing is currently the only means to diagnose MODY, “restricted access…leaves many patients with undiagnosed diabetes.” To remedy this, researchers tested the hypothesis that “serum levels of high-sensitivity C-reactive protein (hs-CRP) could represent a clinically useful biomarker for the identification of 

 mutations causing maturity-onset diabetes of the young.” 

 The authors found that “serum hs-CRP levels are markedly lower in HNF1A-MODY than in other forms of diabetes,” making this a potential target for a “widely-available, cost-effective screening test to support more precise targeting of MODY diagnostic screening.”

Maturity-onset Diabetes of the Young: How Many Cases Are we Missing? 

 Because only genetic testing can confirm a diagnosis of MODY, which “is frequently misdiagnosed as type 1 or type 2 diabetes,” researchers “aimed to compare the regional distribution of confirmed MODY cases in the UK and to estimate the minimum prevalence.”

 The authors looked at “UK referrals for genetic testing in 2,072 probands and 1,280 relatives between 1996 and 2009” and found that “MODY was confirmed in 1,177 (35%) patients, with 

mutations (32%) being most frequent in probands with MODY.” Because “referral rates and confirmed cases were highly correlated,” the authors conclude that “marked regional variation in prevalence of confirmed MODY directly results from differences in referral rates.” In order to remedy this, “increased referral for diagnostic testing is required if the majority of MODY patients are to have the genetic diagnosis necessary for optimal treatment.”

The Role of Noise and Positive Feedback in the Onset of Autosomal Dominant Diseases

 Bosl and Rong sought to “explore the possible contribution to the onset of autosomal dominant diseases from intrinsic factors, such as those determined by the structure of the molecular networks governing normal cellular physiology.”

 Bosl and Rong simulated “model pathways for two autosomal dominant disease, AD polycystic kidney disease and mature onset diabetes of youth.” The “simulations demonstrate that some of the primary disease characteristics are consistent with the positive feedback — stochastic variation theory presented here. This has implications for new drug targets to control these diseases by blocking the positive feedback loop in the relevant pathways.”

 Tablet; 2.5 mg, 5 mg, 10 mg (oral administration)

 Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

 Tablet; 1.25 mg, 2.5 mg, 5 mg (oral administration)

 Tablet; 1 mg, 2 mg, 4 mg (oral administration)

Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Articles

Net Guide

Maturity-onset Diabetes of the Young (MODY)

Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Acromegaly

Though these guidelines have not been updated in six years, they are the American Association of Clinical Endocrinology’s standard resource for physicians looking for guidance on how best to manage the patient with acromegaly. Among other topics, the guidelines cover the roles of surgical treatment, medical treatment, and radiation therapy in acromegaly management.

Guidelines for Acromegaly Management: An Update

If you’re looking for more recent guidelines than the AACE provides, follow this link and peruse the recommendations of the Acromegaly Consensus Group from their November 2007 meeting, sponsored by the Pituitary Society and the European Neuroendocrine Association.

This expired CME webcast comprises three presentations made “at the live CMES ancillary symposium entitled ‘Management of Pituitary Adenomas,’ held in conjunction with The Endocrine Society's 90th Annual Meeting on June 16, 2008 in San Francisco, CA”: Treatment Options for Acromegaly, Uncertainties in the Treatment of Prolactinomas, and Pharmacologic Therapy for Cushing’s: The Old and the New. Though you will not obtain credit for viewing any of this, the activity can still serve as a relevant refresher.

Sponsored by the Department of Radiology and Radiological Sciences at the Uniformed Services University of the Health Science, this small image library contains 13 acromegaly-related magnetic resonance and x-ray scans illustrating dramatic skull thickening, pituitary macroadenoma, and acromegaly vs. gigantism.

This resource from the Stanford Cancer Center is about as basic a patient primer as it gets. It provides an overview of the disease, explains how it is diagnosed, and therapeutic options available to patients (including information on receiving treatment at Stanford). You can turn this into a two-page patient handout with some quick text size adjustments.

Tanya Angus “is the only known person in the world [whose acromegaly] can not be treated successfully with surgery or drugs.” This heart-breaking reality was reinforced recently when a hoped-for procedure to remove her pituitary tumor was cancelled because the surgeon ultimately deemed it too risky. For recently diagnosed patients, reading her words and about her life will hopefully inspire and comfort.

This ABC News story on Tanya Angus will help patients get a better idea of what life with acromegaly can potentially be like.

Pure Endoscopic Transsphenoidal Surgery for Treatment of Acromegaly

 Gondim J, Almeida J, de Albuquerque L, et al

 “The authors discuss the advantages, outcome, complications, and factors related to the success of the endoscopic approach in cases of GHsecreting adenomas” in a population “of patients with acromegaly who were operated on by a pituitary specialist surgeon.”

 The procedure had a high rate of success (“disease control was obtained in” 74.6% of cases; “the rate of treatment success was higher in patients with microadenomas…12 of 14 cases”) and a low incidence of complications (“epistaxis (6.0%), transitory diabetes insipidus (4.5%), and 1 case of seizure (1.5%)”). “Lesion size, suprasellar/parasellar extension, and the degree of sella floor erosion” are important factors related to success. The authors indicate that this procedure is an effective treatment option, however, they found that “there is no conclusive evidence that endoscopy is superior to microsurgery in treatment of GH-secreting adenomas.”

Biochemical Acromegaly in Patients with Prolactinoma during Treatment with Dopaminergic Agonists

Arquivos Brasileiros de Endocrinologia & Metabologia

 The authors studied “one hundred twenty one patients without a phenotype suggestive of acromegaly” in order to “evaluate the frequency of sublinical acromegaly (in the absence of clinical phenotype but biochemically uncontrolled).”

 “Initially, the laboratory diagnosis of acromegaly was unequivocal” and a repetition of testing “6 months after withdrawal of the dopaminergic agonist confirmed the diagnosis of sublinical acromegaly.” The authors recommend that “n patients with prolactinomas, acromegaly should be investigated not only in cases with a clinical phenotype.”

Approach to the Patient with Persistent Acromegaly after Pituitary Surgery

“In the acromegaly patient with persistent disease after surgery, therapeutic options including medical therapies allow disease control in the majority of patients.” This activity discusses those options which include “medical therapy, utilizing somatostatin analogs, dopamine agonists, and pegvisomant;” and radiation therapy. Situations in which repeat surgery is called for are also covered.

Dr. Edward Laws of Brigham and Women’s Hospital interviews Dr. M. Beatriz Lopes of the University of Virginia School of Medicine about “Growth Hormone-secreting Ademonas: Pathology and Cell Biology,” and article authored by Dr. Lopes which was published in the October 2010 issue of the 

(http://hcp.lv/cRCNZt). In the article, Dr. Lopes “reviews the main pathological features of the GH-secreting adenomas and some of the molecular genetics mechanisms involved in their pathogenesis.”

Preoperative Lanreotide Treatment in Acromegalic Patients with Macroadenomas Increases Short-term Postoperative Cure Rates

 Zhi-gang M, Yong-hong Z, Hai-liang T, et al

Researchers tested the hypothesis that a “4-month preoperative lanreotide treatmentwould improve the surgical cure rate of newly diagnosed acromegalicpatients with macroadenomas.”

 Researchers randomly divided 108 patients into two groups, the first receiving a four month preoperative regimen of lanreotide, the other moving directly to transsphenoidal surger. Cure, defined as “fasting IGF1 less than or equal to age-adjusted upper limit of normal,” was “established in 24 of 49 pretreated patients versus 9 of 49 direct surgery patients. Surgical morbidity was similar in both groups.

Somatuline Depot for Acromegaly Post-Marketing Observational Study

Acromegaly

Cancer Management: A Multidisciplinary Approach

 is available free-of-charge to registered members of CancerNetwork.com (registration is also free). Authored by Mimi I. Hu, MD, Peter Ahn, MD , and Jeffrey P. Lamont, MD, this 11-page work covers tumor types (eg, anaplastic carcinoma, follicular thyroid carcinoma), epidemiology, etiology and risk factors, signs and symptoms, imaging modalities, genetic testing, staging and prognosis, and more.

Practice Guideline for Thyroid and Parathyroid Ultrasound

This guideline from the American Institute of Ultrasound in Medicine is short and direct. In three pages, the authors cover indications for ultrasound examination, qualifiations and responsibilities of personnel, the written request for the examination, specifications of the examination, producing adequate documentation, equipment specifications, quality control and improvement, and safety, infection, and patient education concerns.

Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules

Produced jointly by the American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association, this set of guidelines utilizes the “AACE protocol for standardized production of clinical practice guidelines…to rate the evidence level of each reference (on a scale of 1 to 4) and to link the guidelines to the strength of recommendations on the basis of grade designations A (action based on strong evidence) through D (action not based on any evidence of not recommended). Among other topics, the authors discuss, diagnostic imaging studies, thyroid biopsy, radionuclide scanning, and pregnancy and childhood.

Edited by Frederick Singer, MD, Director of the Endocrine/Bone Disease Program at the John Wayne Cancer Institute, 

 is available free-of-charge at EndoText.org. Chapters 5, 6, and 9 cover Primary Hyperparathyroidism, Hyperparathyroidism in Renal Failure, and Hypoparathyroidism and Psuedohypoparathyroidism.

This guide from EndocrineWeb covers the basics of hyperparathyroidism (What Causes Excess Hormone Production?, How Many Parathyroids Are Affected?, Symptoms of Hyperparathyroidism, Potential Dangers of Hyperparathyroidism) and should be a good place for your patients to start their education about the disorder.

This Medline primer, last updated Robert Cooper, MD, Endocinology Specialist and Chief of Medicine at Holyoke Medical Center, explains the causes and symptoms of, and treatment, tests, exams, and outlook for secondary hyperparathyroidism.

This brand new page was “produced by HPTH UK and the HPTH UK Clinical Advisory Team working in conjunction with the Society for Endocrinology” and features a Patient Information Leaflet on hypoparathyroidism that you can distribute in your office. It covers all the basics, however, one cause for concern is the mention of brand name drugs such as Calcichew that are not available in the United States; some quick edits to the document can fix that, though.

Biopsying the Thyroid, Parathyroid, and Cervical Lymph Nodes: How to Do It

This program from the American Institute of Ultrasound Medicine “discusses the number of fine-needle aspirations that are optimal versus the size of the needle used as well as other controversies in the technique, with an emphasis on complications and pitfalls to avoid.” Purchase of the activity comes with five test and evaluation forms, “allow[ing] you and up to 4 colleagues to earn CME credit at no addition charge.”

Advances in Thyroid and Parathyroid Surgery

This activity comprises five presentations: ATA Guidelines for Workup of Thyroid Nodule; FNA Cytopathology — Bethesda System for Reporting; Preoperative Considerations for Thyroid Surgery; Avoiding Surgical Complications in Thyroid Surgery; and Reoperative Thyroid Surgery for Malignancy. Each addresses specific controversies regarding “recommendations for the diagnosis and treatment” of thyroid and parathyroid tumors that have arisen due to advances “in diagnostic modalities and treatment options for thyroid cancer.”

Parathyroid Carcinoma: Current Understanding and New Insights into Gene Expression and Intraoperative Parathyroid Hormone Kinetics

After reading the article from which this activity derives its name, participants will take a nine-question quiz to obtain credit for this activity.

Tampa General Hospital has archived the broadcast of this parathyroid surgery on its ORLive.com channel. Visitors can also view seven “Physician Insight” videos in which James Norman, MD, FACS, FACE, the physician performing the procedure, discusses minimally invasive surgery compared to old-style operations, detecting a parathyroid tumor, diagnosis, patient symptoms, and more.

Run jointly by Parathyroid.com and the National Parathyroid Education Foundation, Parathyroid.TV features three types of video: Featured Flicks (“3-10 minute videos with detailed information on many subjects”), Quick Flicks (“short 1-3 minute videos about very specific areas”), and Patient Flicks (“video stories uploaded by patients about their experience with high calcium, being diagnosed, and cured). The bulk of the site content can be found under Featured Flicks (16 videos focusing on such topics as hypercalcemia and sestamibi scans). Quick Flicks and Patient Flicks house a combined total of one video.

Chasing “Shadows”: Discovering the Subtleties of Sestamibi Scans to Facilitate Minimally Invasive Parathyroidectomy

 Though sestamibi scans are now “considered the standard of care for patients with primary hyperthyroidism,” preoperative imaging “can be negative more than 20% of the time.” Because of this, researchers “chose to examine one surgeon’s experience with patients who presented with primary hyperparathyroidism and negative or indeterminate preoperative imaging from July 1993 to September 2009.”

 “A total of 126 patients had a negative or indeterminate sestamibi scan and a negative or no US report,” and “each sestamibi scan had been re-reviewed preoperatively by the surgeon with a nuclear medicine physician.” Researchers found that “with careful preoperative re-review of a negative or indeterminate sestamibi scan and the identification of subtleties in patients with a negative preoperative US scan, a successful MIP can be performed 91% of the time with a 98% cure rate.”

Effects of Smoking on Severity of Disease in Primary Hyperparathyroidism

Amstrup A, Rejnmark L, Vestergaard P, et al

 Though “smoking is associated with lower plasma levels of parathyroid hormone (PTH) and decreased bone mineral density (BMD),” its effects on “PTH, skeletal metabolism, and size/histology of the parathyroid glands in primary hyperparathyroidism (PHPT) is unknown.” Investigators pursued this by examining “removed parathyroid tissue” in 344 subjects, 24% of whom were smokers.

 “After adjustment for body weight, age, sex, and 25OHD levels, smokers had slightly lower BMD at the whole body but not at the spine, hip, or forearm,” while “surgical cure caused a significant increase in BMD at all measurement sites” independent of smoking status. “In contrast to healthy subjects, smoking seems not to decrease BMD in PHPT. Smoking may compromise the correct diagnostic evaluation of borderline hyperparathyroidism. It is unknown to what extent smoking in PHPT affects fracture risk and indication for surgery.”

Efficacy and Safety Study of Cinacalcet for the Treatment of Hypercalcemia in Subjects with PHPT Unable to Undergo Parathyroidectomy

Researchers will be comparing cinacalcet HCl to placebo in order to determine “the efficacy of cinacalcet for normalizing serum calcium” and “reducing corrected total serum calcium and plasma PTH levels.

Evaluation of the Effectiveness of Paricalcitol Versus Cinacalcet With Low-Dose Vitamin D

Participants will receive paricalcitol or cinacalcet with low dose vitamin D therapy over a 28-week period in order to determine “the proportion of subjects that achieve a mean iPTH value between 150 to 300 pg/mL in Weeks 21 to 28” and those “achieving at least 30% reduction from baseline in iPTH as assessed by the mean iPTH obtained in Weeks 21 to 28.”

Cinacalcet Effectively Reduces Parathyroid Hormone Secretion and Gland Volume Regardless of Pretreatment Gland Size in Patients with Secondary Hyperparathyroidism

Clinical Journal of the American Society of Nephrology

 Though “cinacalcet is effective in reducingserum parathyroid hormone in patients with secondary hyperparathyroidism…it has not been proven whether parathyroid gland sizepredicts response to therapy and whether cinacalcet is capableof inducing a reduction in parathyroid volume.”

November 2010

Maturity-onset Diabetes of the Young (MODY)

Acromegaly

Parathyroid Gland Disorders