Rhoda H. Cobin

Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline

OBJECTIVE The aim was to update the guidelines for the management of thyroid dysfunction during pregnancy and postpartum published previously in 2007. A summary of changes between the 2007 and 2012 version is identified in the Supplemental Data (published on The Endocrine Societys Journals Online web site at http://jcem.endojournals.org). EVIDENCE This evidence-based guideline was developed according to the U.S. Preventive Service Task Force, grading items level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms) as well as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS The guideline was developed through a series of e-mails, conference calls, and one face-to-face meeting. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocrine Society, Asia and Oceania Thyroid Association, and the Latin American Thyroid Society. A second draft was reviewed and approved by The Endocrine Society Council. At each stage of review, the Task Force received written comments and incorporated substantive changes. CONCLUSIONS Practice guidelines are presented for diagnosis and treatment of patients with thyroid-related medical issues just before and during pregnancy and in the postpartum interval. These include evidence-based approaches to assessing the cause of the condition, treating it, and managing hypothyroidism, hyperthyroidism, gestational hyperthyroidism, thyroid autoimmunity, thyroid tumors, iodine nutrition, postpartum thyroiditis, and screening for thyroid disease. Indications and side effects of therapeutic agents used in treatment are also presented.

American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus.

Acknowledgments We would like to recognize Elliot Sternthal, MD, FACE, and Joseph Vassalotti, MD, for their review of these guidelines and thoughtful comments.

Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association

OBJECTIVE Hypothyroidism has multiple etiologies and manifestations. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions. This paper describes evidence-based clinical guidelines for the clinical management of hypothyroidism in ambulatory patients. METHODS The development of these guidelines was commissioned by the American Association of Clinical Endocrinologists (AACE) in association with American Thyroid Association (ATA). AACE and the ATA assembled a task force of expert clinicians who authored this article. The authors examined relevant literature and took an evidence-based medicine approach that incorporated their knowledge and experience to develop a series of specific recommendations and the rationale for these recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach outlined in the American Association of Clinical Endocrinologists Protocol for Standardized Production of Clinical Guidelines-2010 update. RESULTS Topics addressed include the etiology, epidemiology, clinical and laboratory evaluation, management, and consequences of hypothyroidism. Screening, treatment of subclinical hypothyroidism, pregnancy, and areas for future research are also covered. CONCLUSIONS Fifty-two evidence-based recommendations and subrecommendations were developed to aid in the care of patients with hypothyroidism and to share what the authors believe is current, rational, and optimal medical practice for the diagnosis and care of hypothyroidism. A serum thyrotropin is the single best screening test for primary thyroid dysfunction for the vast majority of outpatient clinical situations. The standard treatment is replacement with L-thyroxine. The decision to treat subclinical hypothyroidism when the serum thyrotropin is less than 10 mIU/L should be tailored to the individual patient.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME--PART 1.

Polycystic Ovary Syndrome (PCOS) is recognized as the most common endocrine disorder of reproductive-aged women around the world. This document, produced by the collaboration of the American Association of Clinical Endocrinologists (AACE) and the Androgen Excess and PCOS Society (AES) aims to highlight the most important clinical issues confronting physicians and their patients with PCOS. It is a summary of current best practices in 2015. PCOS has been defined using various criteria, including menstrual irregularity, hyperandrogenism, and polycystic ovary morphology (PCOM). General agreement exists among specialty society guidelines that the diagnosis of PCOS must be based on the presence of at least two of the following three criteria: chronic anovulation, hyperandrogenism (clinical or biological) and polycystic ovaries. There is need for careful clinical assessment of womens history, physical examination, and laboratory evaluation, emphasizing the accuracy and validity of the methodology used for both biochemical measurements and ovarian imaging. Free testosterone (T) levels are more sensitive than the measurement of total T for establishing the existence of androgen excess and should be ideally determined through equilibrium dialysis techniques. Value of measuring levels of androgens other than T in patients with PCOS is relatively low. New ultrasound machines allow diagnosis of PCOM in patients having at least 25 small follicles (2 to 9 mm) in the whole ovary. Ovarian size at 10 mL remains the threshold between normal and increased ovary size. Serum 17-hydroxyprogesterone and anti-Müllerian hormone are useful for determining a diagnosis of PCOS. Correct diagnosis of PCOS impacts on the likelihood of associated metabolic and cardiovascular risks and leads to appropriate intervention, depending upon the womans age, reproductive status, and her own concerns. The management of women with PCOS should include reproductive function, as well as the care of hirsutism, alopecia, and acne. Cycle length >35 days suggests chronic anovulation, but cycle length slightly longer than normal (32 to 35 days) or slightly irregular (32 to 35-36 days) needs assessment for ovulatory dysfunction. Ovulatory dysfunction is associated with increased prevalence of endometrial hyperplasia and endometrial cancer, in addition to infertility. In PCOS, hirsutism develops gradually and intensifies with weight gain. In the neoplastic virilizing states, hirsutism is of rapid onset, usually associated with clitoromegaly and oligomenorrhea. Girls with severe acne or acne resistant to oral and topical agents, including isotretinoin (Accutane), may have a 40% likelihood of developing PCOS. Hair loss patterns are variable in women with hyperandrogenemia, typically the vertex, crown or diffuse pattern, whereas women with more severe hyperandrogenemia may see bitemporal hair loss and loss of the frontal hairline. Oral contraceptives (OCPs) can effectively lower androgens and block the effect of androgens via suppression of ovarian androgen production and by increasing sex hormone-binding globulin. Physiologic doses of dexamethasone or prednisone can directly lower adrenal androgen output. Anti-androgens can be used to block the effects of androgen in the pilosebaceous unit or in the hair follicle. Anti-androgen therapy works through competitive antagonism of the androgen receptor (spironolactone, cyproterone acetate, flutamide) or inhibition of 5α-reductase (finasteride) to prevent the conversion of T to its more potent form, 5α-dihydrotestosterone. The choice of antiandrogen therapy is guided by symptoms. The diagnosis of PCOS in adolescents is particularly challenging given significant age and developmental issues in this group. Management of infertility in women with PCOS requires an understanding of the pathophysiology of anovulation as well as currently available treatments. Many features of PCOS, including acne, menstrual irregularities, and hyperinsulinemia, are common in normal puberty. Menstrual irregularities with anovulatory cycles and varied cycle length are common due to the immaturity of the hypothalamic-pituitary-ovarian axis in the 2- to 3-year time period post-menarche. Persistent oligomenorrhea 2 to 3 years beyond menarche predicts ongoing menstrual irregularities and greater likelihood of underlying ovarian or adrenal dysfunction. In adolescent girls, large, multicystic ovaries are a common finding, so ultrasound is not a first-line investigation in women <17 years of age. Ovarian dysfunction in adolescents should be based on oligomenorrhea and/or biochemical evidence of oligo/anovulation, but there are major limitations to the sensitivity of T assays in ranges applicable to young girls. Metformin is commonly used in young girls and adolescents with PCOS as first-line monotherapy or in combination with OCPs and anti-androgen medications. In lean adolescent girls, a dose as low as 850 mg daily may be effective at reducing PCOS symptoms; in overweight and obese adolescents, dose escalation to 1.5 to 2.5 g daily is likely required. Anti-androgen therapy in adolescents could affect bone mass, although available short-term data suggest no effect on bone loss.

Management of recurrent and persistent metastatic lymph nodes in well-differentiated thyroid cancer: A multifactorial decision-making guide for the thyroid cancer care collaborative

Well‐differentiated thyroid cancer (WDTC) recurs in up to 30% of patients. Guidelines from the American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN) provide valuable parameters for the management of recurrent disease, but fail to guide the clinician as to the multitude of factors that should be taken into account. The Thyroid Cancer Care Collaborative (TCCC) is a web‐based repository of a patients clinical information. Ten clinical decision‐making modules (CDMMs) process this information and display individualized treatment recommendations.

ACTIVE SURVEILLANCE FOR PAPILLARY THYROID MICROCARCINOMA: NEW CHALLENGES AND OPPORTUNITIES FOR THE HEALTH CARE SYSTEM.

OBJECTIVE The dramatic increase in papillary thyroid carcinoma (PTC) is primarily a result of early diagnosis of small cancers. Active surveillance is a promising management strategy for papillary thyroid microcarcinomas (PTMCs). However, as this management strategy gains traction in the U.S., it is imperative that patients and clinicians be properly educated, patients be followed for life, and appropriate tools be identified to implement the strategy. METHODS We review previous active surveillance studies and the parameters used to identify patients who are good candidates for active surveillance. We also review some of the challenges to implementing active surveillance protocols in the U.S. and discuss how these might be addressed. RESULTS Trials of active surveillance support nonsurgical management as a viable and safe management strategy. However, numerous challenges exist, including the need for adherence to protocols, education of patients and physicians, and awareness of the impact of this strategy on patient psychology and quality of life. The Thyroid Cancer Care Collaborative (TCCC) is a portable record keeping system that can manage a mobile patient population undergoing active surveillance. CONCLUSION With proper patient selection, organization, and patient support, active surveillance has the potential to be a long-term management strategy for select patients with PTMC. In order to address the challenges and opportunities for this approach to be successfully implemented in the U.S., it will be necessary to consider psychological and quality of life, cultural differences, and the patients clinical status.

Cardiovascular and metabolic risks associated with PCOS

Polycystic ovary syndrome, the most common endocrine disorder of reproductive age women, is often associated with insulin resistance and associated disorders. The frequency of type 2 diabetes, hyperlipidemia, cardiac risk markers, structural vascular disease, and clinical disease events are increased in this population of women. PCOS, however, represents a broad spectrum of clinical presentations, as defined by different criteria proposed in Europe and the United States. The role of insulin resistance and hence the risk of cardiometabolic disorders may in part be determined by the definition of PCOS used. Epidemiologic studies and clinical trials support the need to identify women with PCOS to determine their risk of cardiometabolic disorders to prevent and/or treat their serious consequences.

Database and registry research in thyroid cancer: Striving for a new and improved national thyroid cancer database

BACKGROUND Health registries have become extremely powerful tools for cancer research. Unfortunately, certain details and the ability to adapt to new information are necessarily limited in current registries, and they cannot address many controversial issues in cancer management. This is of particular concern in differentiated thyroid cancer, which is rapidly increasing in incidence and has many unknowns related to optimal treatment and surveillance recommendations. SUMMARY In this study, we review different types of health registries used in cancer research in the United States, with a focus on their advantages and disadvantages as related to the study of thyroid cancer. This analysis includes population-based cancer registries, health systems-based cancer registries, and patient-based disease registries. It is important that clinicians understand the way data are collected in, as well as the composition of, these different registries in order to more critically interpret the clinical research that is conducted using that data. In an attempt to address shortcoming of current databases for thyroid cancer, we present the potential of an innovative web-based disease management tool for thyroid cancer called the Thyroid Cancer Care Collaborative (TCCC) to become a patient-based registry that can be used to evaluate and improve the quality of care delivered to patients with thyroid cancer as well as to answer questions that we have not been able to address with current databases and registries. CONCLUSION A cancer registry that follows a specific patient, is integrated into physician workflow, and collects data across different treatment sites and different payers does not exist in the current fragmented system of healthcare in the United States. The TCCC offers physicians who treat thyroid cancer numerous time-saving and quality improvement services, and could significantly improve patient care. With rapid adoption across the nation, the TCCC could become a new paradigm for database research in thyroid cancer to improve our understanding of thyroid cancer management.

Hypothalamic-pituitary axis dysfunction in critically ill patients with a low free thyroxine index

The purpose of this study is to investigate the association of hypothalamic-pituitary axis abnormalities with the free thyroxine index (FTI) in critically ill patients. Fourteen critically ill patients and twenty healthy volunteers were studied using combined anterior pituitary gland testing with CRF, GHRH, TRH, and GnRH. The subjects were grouped as follows: I — healthy volunteers; II — sick/normal FTI; and III — sick/low FTI. Serial measurements of hormones were performed over a two-hour interval and the following parameters were measured: baseline level, response amplitude and time to maximal response. Response velocities and area-under-the-curves (integrated responses) were also computed. Group III had a longer mean ICU duration prior to testing than group II. Urinary cortisol, serum cortisol and serum PRL levels were elevated in groups II and III. However, group III had lower baseline ACTH levels, slower ACTH and TSH response velocities and decreased PRL integrated responses. Cortisol response parameters were similar between groups II and III. There were no differences in LH, FSH or GH response velocities or integrated responses among the 3 groups. These data confirm that critically ill patients develop hyperprolactinemia and hypothalamic-pituitary-adrenal axis activation but when a low FTI exists, a plurality of changes occur reflected by attenuated PRL, TSH and ACTH responses despite unaffected adrenal cortisol output.

Improving the adoption of thyroid cancer clinical practice guidelines

To present an overview of the barriers to the implementation of clinical practice guidelines (CPGs) in thyroid cancer management and to introduce a computer‐based clinical support system.