Jorge H. Mestman

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 AND AMERICAN COLLEGE OF ENDOCRINOLOGY - CLINICAL PRACTICE GUIDELINES FOR DEVELOPING A DIABETES MELLITUS COMPREHENSIVE CARE PLAN - 2015

The American Association of Clinical Endocrinologists/American College of Endocrinology Medical Guidelines for Clinical Practice are systematically developed statements to assist healthcare professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances. Abbreviations: A1C = hemoglobin A1c AACE = American Association of Clinical Endocrinologists ACCORD = Action to Control Cardiovascu...

Congenital Malformations in Pregnancies Complicated by NIDDM: Increased risk from poor maternal metabolic control but not from exposure to sulfonylurea drugs

OBJECTIVE To determine whether the use of oral hypoglycemic agents during early pregnancy is associated with a risk of congenital malformations in infants of mothers with non-insulin-dependent diabetes mellitus (NIDDM) independent of maternal metabolic control. RESEARCH DESIGN AND METHODS From a prospectively collected data-base of pregnancies complicated by diabetes at a large urban medical center, we identified 332 consecutive infants born to women with NIDDM who did not participate in a preconceptional diabetes care program. Stepwise logistical regression was used to identify maternal characteristics that were independently associated with risks of major and minor congenital malformations in infants. RESULTS Overall, 56 (16.9%) of the 332 infants were born with congenital anomalies (11.7% major anomalies and 5.1% minor anomalies). Analysis of data from subgroups of women who were treated with diet therapy, exogenous insulin, or sulfonylurea compounds during the first 8 weeks of gestation did not reveal statistically significant differences in major or minor malformation rates among the three groups. Stepwise logistic regression analysis revealed two maternal characteristics that were independently associated with major malformations in infants: maternal HbA1c at initial presentation for care (direct relationship; P = 0.0007) and the maternal age at onset of diabetes (inverse relationship; P = 0.009). The risk of major malformations was unrelated to the mode of antidiabetic therapy during early pregnancy. No relationship was found between maternal glycemia or treatment modality and rates of minor congenital anomalies. CONCLUSIONS These data indicate that, in the absence of special preconceptional care, NIDDM is associated with a risk for major congenital anomalies that is in the range reported for pregnancies complicated by insulin-dependent diabetes mellitus. Moreover, the risk in individual patients appears to be related to maternal glycemic control rather than to the mode of antidiabetic therapy during early pregnancy.

Diabetes and Pregnancy: An Endocrine Society Clinical Practice Guideline

OBJECTIVE Our objective was to formulate a clinical practice guideline for the management of the pregnant woman with diabetes. PARTICIPANTS The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, 5 additional experts, a methodologist, and a medical writer. EVIDENCE This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS One group meeting, several conference calls, and innumerable e-mail communications enabled consensus for all recommendations save one with a majority decision being employed for this single exception. CONCLUSIONS Using an evidence-based approach, this Diabetes and Pregnancy Clinical Practice Guideline addresses important clinical issues in the contemporary management of women with type 1 or type 2 diabetes preconceptionally, during pregnancy, and in the postpartum setting and in the diagnosis and management of women with gestational diabetes during and after pregnancy.

A comparison of propylthiouracil versus methimazole in the treatment of hyperthyroidism in pregnancy

OBJECTIVE Our purpose was to demonstrate that propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism during pregnancy. STUDY DESIGN Between 1974 and 1990 records were available on 185 pregnant patients with a history or diagnosis of hyperthyroidism. Ninety-nine patients were treated with propylthiouracil and 36 with methimazole. The response to therapy was compared with respect to the time to normalization of the free thyroxine index and the incidences of congenital anomalies and hypothyroidism. RESULTS The time to normalization of the free thyroxine index was compared in the two groups by means of survival analysis. The median time to normalization of the free thyroxine index on propylthiouracil and methimazole was 7 and 8 weeks, respectively (p = 0.34, log-rank test). The incidence of major congenital malformations in mothers treated with propylthiouracil and methimazole was 3.0% and 2.7%, respectively. No neonatal scalp defects were seen. One infant was overtly hypothyroid at delivery. CONCLUSION Propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism in pregnancy.

Gestational diabetes mellitus : the prevalence of glucose intolerance and diabetes mellitus in the first two months post partum

To determine the prevalence of abnormal carbohydrate metabolism in the early postpartum period in women with gestational diabetes mellitus, we performed 2-hour oral glucose tolerance tests between 5 and 8 weeks post partum in 246 women with recent gestational diabetes mellitus. Patients were stratified into three study groups based on their fasting serum glucose level during pregnancy: (1) group A1: all fasting serum glucose levels during pregnancy less than 105 mg/dl without insulin therapy; (2) group A2: any fasting serum glucose levels greater than 105 and less than 140 mg/dl before insulin therapy; (3) group B1: any pregnancy with fasting serum glucose levels greater than 140 mg/dl. Overall, 48 (19%) of the patients had an abnormal oral glucose tolerance test in the early postpartum period; 25 (10%) had impaired glucose tolerance and 23 (9%) had diabetes mellitus. The prevalence of postpartum diabetes mellitus (2% in group A1, 9% in group A2 and 44% in group B1) increased in parallel with the degree of maternal metabolic decompensation during pregnancy (p less than 0.05 for A1 versus A2; p less than 0.001 for A2 versus B1). The prevalence of impaired glucose tolerance was likewise greater in the B1 group (26%) than in either the A1 or the A2 group (p less than 0.05). Gestational age less than 24 weeks at diagnosis of gestational diabetes mellitus was an additional risk factor for postpartum glucose intolerance. Our findings support the use of an oral glucose tolerance test in the early puerperium, especially for patients with elevated fasting serum glucose levels during pregnancy.

Successful Outcome of Pregnancy in Women with Hypothyroidism

Published data on the influence of hypothyroidism on fertility, gestation, and the offspring are controversial. We studied nine hypothyroid women during 11 pregnancies. Mean serum values for thyroxine, triiodothyronine (T3), resin T3 uptake ratio, and thyroid-stimulating hormone were 2.3 microgram/dL, 82 ng/dL, 0.64, and 105 mU/mL, respectively. Four patients had iatrogenic hypothyroidism (three remote thyroidectomy, one remote 131I therapy), two Hashimotos thyroiditis, and three idiopathic primary hypothyroidism. Seven patients first presented untreated after the 24th week of gestation. Two patients needed cesarean section; seven delivered vaginally. There was one stillborn infant in the only patient with pre-eclampsia. Another infant had Downs syndrome and an ostium primum defect (mothers age, 41 years). The remaining nine infants were normal at birth. All placentas were normal. Follow-up in seven infants up to 2.7 years showed normal thyroid function and somatic development. Infants of hypothyroid mothers may be normal because their hypothalamic-pituitary thyroid axis develops independently from the mother.

Use of the Continuous Glucose Monitoring System to Guide Therapy in Patients With Insulin-Treated Diabetes: A Randomized Controlled Trial

OBJECTIVE To show improved glycemic control in patients with insulin-treated diabetes after adjustments to the diabetes management plan based on either continuous glucose monitoring using the Continuous Glucose Monitoring System (CGMS) or frequent self-monitoring of blood glucose (SMBG) using a home blood glucose meter. PATIENTS AND METHODS From January to September 2000, patients aged 19 to 76 years with insulin-treated diabetes were assigned to insulin therapy adjustments based on either CGMS or SMBG values. At the end of the study, patients in both groups used the CGMS for 3 days; these values were used to calculate measures of hypoglycemia. Repeated-measures analysis of variance with post hoc comparisons were used to test differences in hemoglobin A1c levels and hypoglycemia between the 2 study groups. RESULTS A total of 128 patients were enrolled in the study. Nineteen discontinued study participation, leaving 51 in the CGMS group and 58 in the SMBG group. No significant differences were noted in demographics or baseline characteristics between the 2 groups. There were no significant differences in hemoglobin A1c levels between the CGMS group and the SMBG group at baseline (9.1% +/- 1.1% vs 9.0% +/- 1.0%, P = .70), and both groups showed statistically significant (P < .001) and similar (P = .95) improvement in hemoglobin A1c levels after 12 weeks of study. However, the CGMS group had a significantly shorter duration of hypoglycemia (sensor glucose, < or = 60 mg/dL) at week 12 of the study (49.4 +/- 40.8 vs 81.0 +/- 61.1 minutes per event, P = .009). CONCLUSION Use of the CGMS to guide therapy adjustments in patients with insulin-treated diabetes reduces the duration of hypoglycemia compared with therapy adjustments guided by SMBG values alone.

Thyroid disease in pregnancy.

Thyroid diseases are common in women of childbearing age and it is well known that untreated thyroid disturbances result in an increased rate of adverse events, particularly miscarriage, preterm birth and gestational hypertension. Furthermore, thyroid autoimmunity per se seems to be associated with complications such as miscarriage and preterm delivery. While strong evidence clearly demonstrates that overt dysfunctions (hyper- or hypothyroidism) have deleterious effects on pregnancy, subclinical disease, namely subclinical hypothyroidism, has still to be conclusively defined as a risk factor for adverse outcomes. Additionally, other conditions, such as isolated hypothyroxinemia and thyroid autoimmunity in euthyroidism, are still clouded with uncertainty regarding the need for substitutive treatment.

Calcium/creatinine ratio and microalbuminuria in the prediction of preeclampsia

Eighty-eight normotensive gravid women between 24 and 34 weeks of gestation underwent urine evaluation for the presence of microalbuminuria and urinary calcium excretion (calcium/creatinine ratio). Preeclampsia subsequently developed in 83% of patients with a high level of microalbuminuria (greater than or equal to 11 micrograms/ml) and a low calcium/creatinine ratio (less than or equal to 0.04). Conversely, 94% of women who did not demonstrate high microalbuminuria and a low calcium/creatinine ratio remained normotensive at the time of delivery. These results suggest that changes in renal function are present in gravid women who are otherwise free of symptoms in whom preeclampsia will eventually develop. Testing for microalbuminuria and a calcium/creatinine ratio may be a useful screening tool in predicting the subsequent development of preeclampsia.