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Biomedical subjects

Mark E Molitch

Publications and source records attributed to Mark E Molitch.

31 records · Page 2Linked to original sources
PubMed2003

Pituitary tumors and pregnancy.

Tumors vary in how they affect pregnancy depending upon the hormone secreted. Some hormone oversecretion syndromes must be controlled to allow pregnancy to proceed without undue maternal and fetal morbidity (Cushing's disease and hyperthyroidism) whereas treatment during pregnancy for other tumors is not necessary. Surveillance for tumor growth during pregnancy is necessary primarily for prolactinomas. A literature search was conducted to identify the effects of pregnancy on pre-existing pituitary tumors and the effects on the outcome of pregnancy due to hormone oversecretion by pituitary tumors. Results show that hyperprolactinemia and Cushing's disease may interfere with fertility and usually need to be controlled to allow for conception. Cushing's syndrome, acromegaly and hyperthyroidism secondary to hypersecretion of thyroid-stimulating hormone (TSH) may increase maternal morbidity (gestational diabetes, hypertension) and fetal morbidity and mortality. Intervention is warranted to remove a tumor that secretes adrenocorticotropic hormone (ACTH) during pregnancy to reduce the risk of fetal loss and to control hyperthyroidism. In contrast, surgery or medical therapy for adenomas that secrete growth hormone (GH) and for clinically nonfunctioning adenomas is not indicated during pregnancy. Pregnancy may cause an increase in the size of tumors that secrete prolactin (PRL), especially macroadenomas, so close surveillance is indicated and re-institution of bromocriptine therapy may be necessary to treat such an increase in tumor size. An increase in the size of other types of tumors during pregnancy is very rare.

Adenoma↗
PubMed2003

Dopamine resistance of prolactinomas.

Resistance to dopamine agonists can be defined with respect to failure to normalize PRL levels and failure to decrease tumor size by > or = 50%. Using these definitions, failure to normalize PRL levels is seen in 24% of those treated with bromocriptine, 13% of those treated with pergolide and 11% of those treated with 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. Studies of in vitro cell preparations show that the D2 receptors of resistant tumors are decreased in number but have normal affinity. Treatment approaches for resistant patients include switching to another dopamine agonist and raising the dose of the drug as long as there is continued response to the dose increases and no adverse effects. Transsphenoidal surgery can also be done. If fertility is desired, clomiphene, gonadotropins, and GnRH are also options. If fertility is not desired, 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. However, in many cases modest or even no reduction may be acceptable long-term 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↗
PubMed2003

Men with acquired hypogonadotropic hypogonadism treated with testosterone may be fertile.

Men with acquired hypogonadotropic hypogonadism treated with testosterone are generally assumed to be infertile. The finding of two such patients with unexpected fertility and normal sperm counts prompted an evaluation of spermatogenesis in additional men with this condition. Case records were initially searched and one similar case with fertility was found. Subsequently, 12 consecutive men with acquired hypogonadotropic hypogonadism were evaluated for gonadal function and sperm production while receiving testosterone. In five of the cases with proven spermatogenesis, exon 10 of the FSH receptor was sequenced to look for activating mutations. The original three cases and four of the subsequent 12 men had sperm concentrations > or = 15 million/ml. Two additional men had concentrations of 1 million/ml and six were azoospermic. Residual LH and FSH levels were slightly higher in those with maintained spermatogenesis prior to testosterone replacement. No activating mutations were found in exon 10 of the FSH receptor in the five cases studied. We conclude that men with acquired hypogonadotropic hypogonadism being treated with testosterone should not be assumed to be sterile, as we have found that more than half have been shown to have persistent spermatogenesis with more than one-third having sperm concentrations > or = 15 million/ml. This may be related to fact that gonadotropin levels in such patients are present, albeit low. Semen analyses in such men should be routinely carried out so that they can be appropriately counseled regarding potential fertility.

Acromegaly↗
PubMed2003

The diabetes prevention program and its global implications.

Type 2 diabetes affects over 150 million adults worldwide and this figure is expected to double over the next 25 yr. This increase will be accompanied by a marked increase in the number of patients with ESRD due to diabetes. We hypothesized that a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes We randomly assigned 3234 nondiabetic persons with elevated fasting and postload plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7% weight loss and at least 150 min of physical activity per week. The mean age of the participants was 51 yr, and the mean body mass index was 34.0 kg/m(2); 68% were women, and 45% were members of non-Caucasian racial/ethnic groups. The average follow-up was 2.8 yr. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence of diabetes by 58% (95% CI: 48 to 66%) and metformin by 31% (95% CI: 17 to 43%), compared with placebo; the lifestyle intervention was significantly more effective than metformin. In conclusion, lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk and the lifestyle intervention was more effective than metformin. Because the lifestyle changes worked equally in all racial/ethnic groups in the Diabetes Prevention Program, they should be applicable to high-risk populations worldwide and may be able to reduce the projected progressive rise in the incidence of diabetes and the expected increase in ESRD.

Adult↗
PubMed2002

The relationship between glucose control and the development and progression of diabetic nephropathy.

Diabetic nephropathy is a major cause of morbidity and mortality in patients with diabetes; it occurs in about one third of such patients. The course of nephropathy is better defined and similar for both type 1 and type 2 diabetes. Patients initially develop microalbuminuria (albumin excretion rates [AERs] between 20 and 200 micrograms/min), then overt nephropathy (AER > or = 200 micrograms/min), and finally a decline in glomerular filtration rate (GFR) eventuating in end-stage renal disease. Although metabolic control has long been hypothesized as a contributor to the development of nephropathy, it is only in recent years that this hypothesis has been proven. A number of observational studies have shown correlations between glycemic control and the development of various levels of albuminuria and also declines in GFR. However, large long-term prospective, randomized, interventional studies have now definitely proven that improved metabolic control that achieves near-normoglycemia can significantly decrease the development and progression of diabetic nephropathy as well as other long-term complications of diabetes, including retinopathy and neuropathy. It is now conceivable that the achievement of near-normoglycemia, plus medications that inhibit the renin-angiotensin system if microalbuminuria develops, may greatly decrease the numbers of patients eventually requiring renal replacement therapy.

Blood Glucose↗
PubMed2002

Medical management of prolactin-secreting pituitary adenomas.

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 TSH, imaging with MRI or CT will delineate the size and extent of the tumor. Medical therapy is the initial treatment of choice. When infertility is the primary indication for treatment, bromocriptine use has an extensive safety experience and is preferred. 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.

Dopamine Agonists↗
PubMed2002

The novel use of very high doses of cabergoline and a combination of testosterone and an aromatase inhibitor in the treatment of a giant prolactinoma.

Most prolactinomas respond rapidly to low doses of dopamine agonists. Occasionally, stepwise increases in doses of these agents are needed to achieve gradual prolactin (PRL) reductions. Approximately 50% of treated men remain hypogonadal, yet testosterone replacement may stimulate hyperprolactinemia. A 34-yr-old male with a pituitary macroadenoma was found to have a PRL level of 10,362 micro g/liter and testosterone level of 3.5 nmol/liter. Eleven months of dopamine agonist therapy at standard doses lowered PRL levels to 299 micro g/liter. Subsequent stepwise increases in cabergoline (3 mg daily) further lowered PRL levels to 71 micro g/liter, but hypogonadism persisted. Initiation of testosterone replacement resulted in a rise and discontinuation in a fall of PRL levels. Aromatization of exogenous testosterone to estradiol and subsequent estrogen-stimulated PRL release was suspected. Concomitant use of cabergoline with the aromatase inhibitor anastrozole after resuming testosterone replacement resulted in the maintenance of testosterone levels and restoration of normal sexual function, without increasing PRL. Ultimately, further reduction in PRL on this therapy permitted endogenous testosterone production. Thus, novel pharmacological maneuvers may permit successful medical treatment of some patients with invasive macroprolactinomas.

Adult↗
PubMed2001

Rise in albuminuria and blood pressure in patients who progressed to diabetic nephropathy in the Diabetes Control and Complications Trial.

The Diabetes Control and Complications Trial (DCCT) enrolled 1441 participants to address the role of intensive therapy for type 1 diabetes mellitus on the onset and progression of microvascular complications. To examine the timing of elevated systolic BP (SBP) and diastolic BP (DBP) and increased albumin excretion rate (AER) in the progression to clinical diabetic nephropathy (AER > 300 mg/24 h on two consecutive visits from a baseline of <100 mg/24 h) and, importantly, to control for initial values of hemoglobin A(1c), a retrospective case-control study was assembled from the records of the publicly released DCCT data. Participants who progressed to clinical diabetic nephropathy-progressors-were matched with participants of the same gender and treatment group who had similar baseline values for DBP, SBP, AER AER and hemoglobin A(1c), but who did not progress to clinical diabetic nephropathy-matched controls. In the conventional treatment group, the 21 progressors exhibited a significant rise in mean AER (above their own baseline levels and above values in the matched controls) at year 2 of the DCCT. In contrast, the progressors' mean DBP and SBP were not significantly higher than baseline until year 3 (DBP) or year 4 (SBP) and not significantly higher than the matched controls until year 4 (both DBP and SBP). On the individual level, 19 of 21 (90%) progressors reached clinical diabetic nephropathy before the diagnosis of hypertension (140/90 mmHg). In the intensive treatment group, however, the rise in DBP preceded the rise in AER by 1 to 2 yr among the six progressors. Both intensively treated progressors who experienced hypertension reached this before AER > 300 mg/24 h. These results underline the early and prognostic rise in AER in diabetic patients, but only in those who received conventional treatment. The evolution of diabetic renal disease may follow a different course in patients who receive intensive diabetic treatment.

Adult↗
PubMedDate not supplied

Inpatient management of hyperglycemia: the Northwestern experience.

OBJECTIVE: To describe a novel method of safe and effective intensive management of inpatient hyperglycemia with use of cost-effective protocols directed by a glucose management service (GMS). METHODS: An intravenous insulin protocol was designed to achieve a glycemic target of 80 to 110 mg/dL. When stable inpatients were transferred from the intravenous protocol to a subcutaneous insulin protocol, which consisted of basal long-acting and prandial and supplemental rapid-acting insulins, the blood glucose target was 80 to 150 mg/dL. Glucose levels were reviewed by the GMS at least daily for protocol adjustments, when necessary. RESULTS: The intravenous insulin protocol was used in 276 patients, and 4,058 capillary blood glucose levels were recorded. Glycemic target levels (80 to 110 mg/dL) were achieved, on average, 10.6 +/- 5.2 hours after initiation of insulin drip therapy. The mean capillary blood glucose level during the study interval was 135.3 +/- 49.9 mg/dL. Hypoglycemia (< or = 60 mg/dL) was recorded in 1.5% of glucose values, and hyperglycemia (> or = 400 mg/dL) was recorded in only 0.06%. The subcutaneous insulin protocol was used in 922 patients, and 18,067 capillary glucose levels were documented. The mean blood glucose level was 145.6 +/- 55.8 mg/dL during the study period. The blood glucose target of 80 to 150 mg/dL was achieved in 58.6%, whereas 74.3% of glycemic values were in the clinically acceptable range (80 to 180 mg/dL). Hypoglycemia (< or = 60 mg/dL) occurred in 1.3% of capillary blood glucose values, and hyperglycemia (> or = 400 mg/dL) occurred in 0.4% of values. CONCLUSION: Validated protocols dedicated to the achievement of strict glycemic goals were implemented by a GMS and resulted in substantial improvements in glycemic control on the surgical inpatient services, with a reduced frequency of hypoglycemia. The protocols and the GMS have been well received by the inpatient nursing and surgical staff members, and all of this has been done in a cost-effective manner.

Aged↗
PubMedDate not supplied

Conversion of intravenous insulin infusions to subcutaneously administered insulin glargine in patients with hyperglycemia.

OBJECTIVE: To determine the optimal dose of insulin glargine needed to maintain glycemic control in patients undergoing conversion from intravenous regular insulin infusions to a subcutaneous insulin regimen. METHODS: Seventy-five hospitalized patients receiving continuous insulin infusions were randomized to receive 40%, 60%, or 80% of their total daily insulin requirement, calculated from the rate during the final 6 hours of the infusion, as insulin glargine at the time of conversion to a subcutaneous regimen. Prandial insulin aspart was added to the subcutaneous regimen when patients began oral intake, and the dosage was left to clinical judgment. Capillary blood glucose monitoring (CBGM) was performed before every meal and at bedtime. All CBGM values for the 24-hour period after conversion were collected. RESULTS: Three hundred ninety-two CBGM values were recorded and analyzed. The mean for all CBGM values during the 24-hour period after conversion to the subcutaneous insulin regimen was 151.9 +/- 42.5 mg/dL in the 40% group, 164.0 +/- 41.6 mg/dL in the 60% group, and 153.2 +/- 66.2 mg/dL in the 80% group (P = 0.66). The percentage of CBGM values in the predefined study target range (80 to 140 mg/dL) was 43.2%, 34.8%, and 48% in the 40%, 60%, and 80% groups, respectively (P = 0.09). Secondary analysis with use of a glycemic target of 80 to 150 mg/dL and removal of outliers resulted in CBGM values within that range in 58.7%, 44.4%, and 67.6% for the 40%, 60%, and 80% groups, respectively (overall, P = 0.001; 40% group versus the 60% group, P = 0.03; 60% group versus the 80% group, P = 0.0004; and 40% group versus the 80% group, P = 0.18). CONCLUSION: Conversion from continuous insulin infusion to subcutaneously administered insulin glargine at a dose equal to 80% of the total daily insulin requirements resulted in the highest percentage of CBGM values in the glycemic target range of 80 to 150 mg/dL within the first 24 hours after regimen conversion in comparison with conversion at 40% and 60%, albeit the difference between the 40% and 80% groups was not statistically significant.

Aged↗