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Biomedical subjects

Mark E Molitch

Publications and source records attributed to Mark E Molitch.

At least 19 recordsLinked to original sources
PubMed2007

Reduction of surgical mortality and morbidity in diabetic patients undergoing cardiac surgery with a combined intravenous and subcutaneous insulin glucose management strategy.

OBJECTIVE: To determine if glucose management in postcardiothoracic surgery patients with a combined intravenous (IV) and subcutaneous (SC) insulin regimen reduces mortality and morbidity in patients with diabetes and stress-induced hyperglycemia. RESEARCH DESIGN AND METHODS: Retrospective review of 614 consecutive patients who underwent cardiothoracic (CT) surgery in 2005 was performed to evaluate the incidence and treatment of postoperative hyperglycemia and operative morbidity and mortality. Hyperglycemic patients (glucose >6.05 mmol/l) were treated with IV insulin in the intensive care unit (ICU) followed by SC insulin (outside ICU). Subgroup analysis was performed on 159 coronary artery bypass grafting (CABG)-only patients. RESULTS: Among all CT surgeries, patients with a preoperative diagnosis of diabetes had higher rates of postoperative mortality (7.3 vs. 3.3%; P = 0.03) and pulmonary complications (19.5 vs. 11.6%; P = 0.02) but had similar rates of infections and cardiac, renal, and neurological complications on univariate analysis. However, on multivariate analysis, a preoperative diagnosis of diabetes was not a significant factor in postoperative mortality or pulmonary complications. In CABG-only patients, no significant differences were seen in outcomes between diabetic and nondiabetic patients. Independent of diabetic status, glucose > or =11 mmol/l on ICU admission was predictive of higher rates of mortality and renal, pulmonary, and cardiac postoperative complications. CONCLUSIONS: A combination of IV insulin (in the ICU) and SC insulin (outside the ICU), a less costly and less nursing-intensive therapy than 3 days of IV insulin postoperatively, results in a reduction of the increased surgical morbidity and mortality in diabetic patients after CT surgery.

Aged↗
PubMed2006

Advances in the treatment of prolactinomas.

Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future.

Adolescent↗
PubMed2006

Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline.

OBJECTIVE: The objective is to provide guidelines for the evaluation and treatment of adults with GH deficiency (GHD). PARTICIPANTS: The chair of the Task Force was selected by the Clinical Guidelines Subcommittee of The Endocrine Society (TES). The chair selected five other endocrinologists and a medical writer, who were approved by the Council. One closed meeting of the group was held. There was no corporate funding, and members of the group received no remuneration. EVIDENCE: Only fully published, peer-reviewed literature was reviewed. The Grades of Evidence used are outlined in the Appendix. CONSENSUS PROCESS: Consensus was achieved through one group meeting and e-mailing of drafts that were written by the group with grammatical/style help from the medical writer. Drafts were reviewed successively by the Clinical Guidelines Subcommittee, the Clinical Affairs Committee, and TES Council, and a version was placed on the TES web site for comments. At each level, the writing group incorporated needed changes. CONCLUSIONS: GHD can persist from childhood or be newly acquired. Confirmation through stimulation testing is usually required unless there is a proven genetic/structural lesion persistent from childhood. GH therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures and is most likely to benefit those patients who have more severe GHD. The risks of GH treatment are low. GH dosing regimens should be individualized. The final decision to treat adults with GHD requires thoughtful clinical judgment with a careful evaluation of the benefits and risks specific to the individual.

Adult↗
PubMed2006

Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas.

In June 2005, an ad hoc Expert Committee formed by the Pituitary Society convened during the 9th International Pituitary Congress in San Diego, California. Members of this committee consisted of invited international experts in the field, and included endocrinologists and neurosurgeons with recognized expertise in the management of prolactinomas. Discussions were held that included all interested participants to the Congress and resulted in formulation of these guidelines, which represent the current recommendations on the diagnosis and management of prolactinomas based upon comprehensive analysis and synthesis of all available data.

Adenoma↗
PubMed2006

Prolactin-secreting tumors: what's new?

Prolactinomas are a common cause of reproductive/sexual dysfunction. Once other causes of hyperprolactinemia have been excluded with a careful history and physical examination, routine chemistries, a pregnancy test and a thyroid-stimulating hormone, imaging with magnetic resonance imaging or computed tomography will delineate the size and extent of the tumor. Medical therapy with cabergoline or bromocriptine is the initial treatment of choice. When infertility is the primary indication for treatment, bromocriptine use has an extensive safety experience and is preferred by some clinicians. However, for other indications, cabergoline appears to be more efficacious and better tolerated. Transsphenoidal surgery remains an option, especially for patients with microadenomas, when medical therapy is ineffective or not tolerated.

Animals↗
PubMed2006

Higher levels of HDL cholesterol are associated with a decreased likelihood of albuminuria in patients with long-standing type 1 diabetes.

OBJECTIVE: The objective of this study was to determine whether high levels of HDL cholesterol are associated with a lower prevalence of albuminuria RESEARCH DESIGN AND METHODS: We analyzed the lipid profiles of patients with type 1 diabetes of > or = 20 years duration in 42 patients with albuminuria (28 microalbuminuria and 14 macroalbuminuria) and 65 patients without increased albumin excretion before any interventions with either statins or ACE inhibitors. RESULTS: Several characteristics were similar in the two groups: sex, age, duration of diabetes, total cholesterol, LDL cholesterol, and triglycerides. By univariate analysis, significant differences (P < 0.01) were found in HDL cholesterol (albuminuria 1.42 mg/dl, no albuminuria 1.71 mg/dl, P < 0.01), HbA1c (A1C) (albuminuria 8.5%, no albuminuria 7.5%), and proportions with no, background, and proliferative retinopathy (albuminuria 2.4, 16.7, and 81%; no albuminuria 24.6, 52.3, and 23.1%, respectively). When adjusted for age and sex, a 0.26-mmol/l (10-mg/dl) increase in HDL cholesterol is associated with an odds ratio (OR) of 0.70 (95% CI 0.54-0.90) for having albuminuria. In a multivariate model that adjusted for age, sex, diabetes duration, and A1C, for every 0.54-mmol/l (21-mg/dl) increase in HDL cholesterol, patients are approximately half (OR 0.51 [95% CI 0.30-0.86]) as likely to have albuminuria, even after controlling for A1C. CONCLUSIONS: Higher HDL cholesterol levels may be protective against the development of albuminuria in patients with type 1 diabetes. Whether this is due to the HDL cholesterol levels or whether they serve as a marker for some other mechanism remains to be determined.

Adult↗
PubMed2006

The association among autonomic nervous system function, incident diabetes, and intervention arm in the Diabetes Prevention Program.

OBJECTIVE: Autonomic nervous system dysfunction, a correlate of obesity and poor cardiorespiratory fitness, is associated with the development of diabetes. We tested whether estimates of autonomic nervous system function improved in the intensive lifestyle versus metformin or placebo arms of the Diabetes Prevention Program (DPP) and whether baseline or a change in autonomic nervous system function was associated with the development of diabetes over 3.2 years. RESEARCH DESIGN AND METHODS: In 2,980 DPP participants, 12-lead electrocardiograms were measured at baseline and annually. Heart rate, heart rate variability (HRV), and QT duration were used to estimate fitness and autonomic nervous system function. RESULTS: In the lifestyle arm, heart rate and QT indexes decreased, and HRV increased over time. The magnitude of decline in heart rate and QT duration was substantially smaller in the other arms, whereas HRV did not increase. Baseline heart rate was the only index significantly (P < 0.05) associated with incident diabetes after adjustment for demographics and weight change (hazard ratio for lifestyle and metformin arms = 1.19 and 1.17 per 10.6 beats/min, respectively). Decreases in heart rate and QT indexes and increases in HRV over time were associated with a lower risk of developing diabetes. The protective association between decreased heart rate and incident diabetes in the lifestyle arm remained significant after accounting for change in weight and physical activity. CONCLUSIONS: Indexes that reflect autonomic function and fitness improved (i.e., heart rate decreased and HRV increased) in the lifestyle modification arm of the DPP. Improvements in these indexes are inversely associated with the development of diabetes independent of weight change.

Autonomic Nervous System↗
PubMed2005

Pharmacologic resistance in prolactinoma patients.

Pharmacologic resistance to dopamine agonists is defined here as failure to normalize PRL levels and failure to decrease macroprolactinoma size by >or=50%. Failure to normalize PRL levels is found in about one-quarter of patients treated with bromocriptine and 10-15% of those treated with pergolide or cabergoline. Failure to achieve at least a 50% reduction in tumor size occurs in about one-third of those treated with bromocriptine and 10-15% of those treated with pergolide or cabergoline. The cause of dopamine resistance is primarily a decrease in D(2) receptors but the receptors have normal affinity for dopamine. Treatment approaches for patients resistant to dopamine agonists include changing to another dopamine agonist and increasing the dose of the drug as long as there is continued response to the dose increases and no adverse effects with higher doses. Transsphenoidal surgery is also an option. Clomiphene, gonadotropins, and GnRH can be used if fertility is desired. For those not desiring fertility, estrogen replacement may be used unless there is a macroadenoma, in which case control of tumor growth is also an issue and dopamine agonists are generally necessary. In many patients modest or even no reduction in tumor size may be acceptable as long as there is not tumor growth. Hormone replacement (estrogen or testosterone) may cause a decrease in efficacy of the dopamine agonist so that it must be carried out cautiously. Reduction of endogenous estrogen, use of selective estrogen receptor modulators, and aromatase inhibitors are potential experimental approaches.

Bromocriptine↗
PubMed2005

The incidence of Sheehan's syndrome after obstetric hemorrhage.

OBJECTIVE: To estimate the incidence of Sheehan's syndrome in a well-described cohort of patients with obstetric hemorrhage. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENT(S): Two hundred patients. INTERVENTION(S): Questionnaires were sent to study and comparison patients asking about menstrual dysfunction, lactation difficulty, cold intolerance, fatigue, axillary and pubic hair loss, and secondary infertility. MAIN OUTCOME MEASURE(S): Women who experienced two or more symptoms were referred for hormone testing of insulin-like growth factor 1 (IGF-1), T4, PRL, and early morning cortisol (F) levels. RESULT(S): A total of 109 patients responded to the survey, a 55% response rate. Fourteen of 55 (25%) patients in the hemorrhage group identified themselves as suffering from two or more symptoms on the questionnaire. Eight of the 14 patients were tested, but none had hormonal evidence of hypopituitarism. Four of 54 (7%) comparison patients also identified themselves as suffering from two or more symptoms, but neither of the two tested had hormonal evidence of hypopituitarism. CONCLUSION(S): Among women with postpartum hemorrhage, subsequent development of clinical symptoms does not correlate well with laboratory evidence of hypopituitarism. Clinically significant Sheehan syndrome is an uncommon consequence of obstetric hemorrhage in today's environment.

Adult↗
PubMed2005

Medication-induced hyperprolactinemia.

Medication use is a common cause of hyperprolactinemia, and it is important to differentiate this cause from pathologic causes, such as prolactinomas. To ascertain the frequency of this clinical problem and to develop treatment guidelines, the medical literature was searched by using PubMed and the reference lists of other articles dealing with hyperprolactinemia due to specific types of medications. The medications that most commonly cause hyperprolactinemia are antipsychotic agents; however, some newer atypical antipsychotics do not cause this condition. Other classes of medications that cause hyperprolactinemia include antidepressants, antihypertensive agents, and drugs that increase bowel motility. Hyperprolactinemia caused by medications is commonly symptomatic, causing galactorrhea, menstrual disturbance, and impotence. It is Important to ensure that hyperprolactinemia in an Individual patient is due to medication and not to a structural lesion in the hypothalamic/pituitary area; this can be accomplished by (1) stopping the medication temporarily to determine whether prolactin levels return to normal, (2) switching to a medication that does not cause hyperprolactinemia (in consultation with the patient's psychiatrist for psychoactive medications), or (3) performing magnetic resonance imaging or computed tomography of the hypothalamic/pituitary area. If the patient's hyperprolactinemia is symptomatic, treatment strategies include switching to an alternative medication that does not cause hyperprolactinemia, using estrogen or testosterone replacement, or, rarely, cautiously adding a dopamine agonist.

Antidepressive Agents↗
PubMed2004

Cortisol levels and mortality in severe sepsis.

OBJECTIVE: Serum cortisol levels rise in response to the stress of critical illness but the optimal range of serum cortisol in such settings is not clearly defined. The objectives of this study were to determine the range of serum cortisol levels in a group of medical intensive care unit patients with severe sepsis/septic shock using uniform criteria, and to correlate serum cortisol levels to mortality. DESIGN AND PATIENTS: In a prospective observational fashion, 100 medical intensive care unit patients at Northwestern Memorial Hospital in Chicago were enrolled within 48 h of developing severe sepsis/septic shock as defined by the American College of Chest Physicians/Society of Critical Care Medicine. MEASUREMENTS: A serum cortisol level was measured during the morning hours in the first 48 h of developing severe sepsis/septic shock. The severity of critical illness was measured by the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. RESULTS: The average patient age was 63 +/- 17 years, 54 patients were men. The average APACHE II score for all patients was 23 +/- 7. In-hospital and 90-day mortality were 51% and 60%, respectively. Four patient groups were defined a priori based on morning serum cortisol levels and their in-hospital mortalities were as follows: group 1 (cortisol < or = 345 nmol/l), n = 11, mortality 54%; group 2 (cortisol 345-552 nmol/l), n = 19, mortality 53%; group 3 (cortisol 552-1242 nmol/l), n = 54, mortality 41%; and group 4 (cortisol > or = 1242 nmol/l), n = 16, mortality 81% (P < 0.01). CONCLUSIONS: Cortisol levels were elevated in most patients with septic shock. Cortisol levels less than 552 nmol/l occurred in 30% of patients with septic shock but the mortality in these patients was not significantly increased. Serum cortisol levels > or = 1242 nmol/l were associated with significantly higher mortality.

APACHE↗
PubMed2004

Prolactin excess: treatment and toxicity.

Dopamine agonists provide highly effective therapy for the treatment of hyperprolactinemia. As a result of their efficacy and tolerability, these agents are considered to be the initial therapy of choice in children, adolescents and adults with idiopathic hyperprolactinemia and prolactinomas. The four dopamine agonists, bromocriptine, pergolide, cabergoline and quinagolide, share a similar mechanism of action and side effect profile. Although studies of cabergoline have demonstrated the highest treatment efficacy and tolerability, all four of these agents are safe, effective and tolerable in children and adolescents. When fertility is desired, bromocriptine is generally preferable, but cabergoline is also likely safe; pergolide and quinagolide should not be used in this setting.

Adult↗
PubMed2003

Timing and special concerns regarding endocrine surgery during pregnancy.

Pregnancy may occur in the setting of endocrine diseases or be the first time these diseases manifest clinically. Management of pregnancy in these circumstances is challenging and requires a high degree of vigilance on the part of the treating physicians. The best outcome is achieved by a multidisciplinary approach consisting of endocrinology, obstetrics, anesthesiology, and endocrine surgery.

Cushing Syndrome↗