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Biomedical subjects

M E Molitch

Publications and source records attributed to M E Molitch.

At least 37 records · Page 2Linked to original sources
PubMed1995

Clinical review 65. Evaluation and treatment of the patient with a pituitary incidentaloma.

Incidental pituitary adenomas are being found commonly with our improved neuroradiological imaging procedures. Screening for hormone oversecretion by these tumors appears to be warranted. For patients with macroadenomas, patients should also be screened for hypopituitarism. In the absence of visual field abnormalities or hypothalamic/stalk compression, it may be appropriate to observe such patients carefully with repeated CT or MRI scans. A limited amount of data suggests that significant tumor enlargement will occur in less than 15% of patients with microadenomas (7). However, all macroadenomas must start out as microadenomas, so periodic follow-up is indicated to assess this possibility. Macroadenomas, by their very existence at the time of detection, have already indicated a propensity for growth. Over the limited period of follow-up in the two series reported, significant growth occurred in almost one third of patients with macroadenomas (7, 8). Hemorrhage into such tumors is uncommon, but anticoagulation may predispose to this complication. When there is no evidence of visual field deficits, an attempt at medical therapy with a dopamine agonist is reasonable, realizing that only about 10% of such patients will respond with a decrease in tumor size. Surgery is indicated if there is evidence of tumor enlargement, especially when such growth is accompanied by compression of the optic chiasm, cavernous sinus invasion, or the development of pituitary hormone deficiencies.

Adenoma↗
PubMed1995

Safety and efficacy of long-term octreotide therapy of acromegaly: results of a multicenter trial in 103 patients--a clinical research center study.

One hundred and three acromegalic patients from 14 medical centers were enrolled in this study to determine the efficacy and safety of the somatostatin analog, octreotide acetate, during long term treatment. Seventy percent of the patients had undergone previous surgery or radiation treatment. Octreotide was initiated at a dose of 100 micrograms, sc, every 8 h and gradually increased to a maximum of 1500 micrograms daily depending upon the individual patient's clinical and biochemical response [GH and insulin-like growth factor I (IGF-I) reduction]. The mean duration of treatment was 24 months (range, 3-30 months). However, most patients were treated for a mean of 30 months, because this study took place after an initial 6-month study previously reported. Mean serum GH fell from 30.9 micrograms/L (range, 2.7-350) to 5.7 micrograms/L (range, 0.6-59) at the 3 months visit and remained suppressed (P < 0.001). Plasma IGF-I concentrations were also significantly reduced and remained in the normal range for at least half of the treatment visits in 56 of 87 patients (64%) treated for 12-30 months. Patients with higher initial GH concentrations were less likely to normalize IGF-I concentrations during treatment (P < 0.001). There was no evidence of drug tachyphylaxis in those patients who continued taking stable doses of medication. With some exceptions, dose increments above 800 micrograms daily in 31 patients did not provide additional benefit in terms of GH and IGF-I reduction. Headache, excessive perspiration, fatigue, and joint pain were ameliorated in 83-95% of patients. Mean finger circumference was decreased significantly at the 12 month visit (P < 0.05). The most common adverse events reported were diarrhea, abdominal discomfort, loose stools, and nausea; these symptoms usually disappeared within 3 months of treatment. Five patients discontinued octreotide because of adverse events. Of 102 patients with normal baseline ultrasound examinations of the gallbladder, 24 patients (23.5%) developed gallstones (usually during the first year of treatment), and 21 patients developed sludge alone. Gallstone formation was not related to the dose of octreotide. Most patients with cholelithiasis were asymptomatic, and none developed cholecystitis. These observations suggest that octreotide is a valuable long term medical treatment for acromegaly.

Acromegaly↗
PubMed1993

Effect of human prolactin administration on gonadotropin and thyrotropin secretion in normal men.

To test the hypothesis that PRL is able to feedback negatively on its own secretion (short-loop feedback) in humans via augmentation of the turnover of tuberoinfundibular dopamine (TIDA), the effects of the administration of purified hPRL on endogenous LH, FSH and TSH were assessed. Purified hPRL, given in an i.v. loading dose of 90 micrograms followed by a continuous infusion of 1.39 micrograms/min to 4 normal male volunteers resulted in a tripling of PRL levels (10.5 +/- 1.9 micrograms/L increasing to 30.9 +/- 3.6 micrograms/L) at the end of 90 min. There were no changes in LH, FSH or TSH levels, however, during or following the infusion. Purified hPRL was also given in 1 and 8 micrograms/kg doses IM to 5 normal male volunteers. Although PRL levels did not rise significantly with the 1 microgram/kg dose, levels almost doubled with the 8 micrograms/kg dose (9.5 +/- 2.2 micrograms/L increasing to 17.4 +/- 1.5 micrograms/L). Again, LH, FSH and TSH levels did not change significantly over the three hour period of sampling with either dose. In conclusion, in this study we found that a 2-3 fold increase of circulating PRL levels maintained for 1.5-3 h exerted no apparent effects on the secretion of endogenous LH, FSH and TSH. This study provides direct evidence against the existence of a short-loop feedback occurring via TIDA activation in humans over this time interval but does not rule out the possibility that such feedback may occur with more prolonged states of hyperprolactinemia or via other mechanisms or the possibility of an effect on the hypothalamic pulse generator.

Adult↗
PubMed1993

Baseline analysis of renal function in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group [corrected].

To determine whether there are relationships between nephropathy, retinopathy and putative risk factors at points very early in the development of long-term complications of IDDM, we have analyzed baseline data pertinent to nephropathy in the 726 subjects in the primary prevention cohort and the 715 subjects in the secondary intervention cohort of the DCCT. AER correlated positively with CCr and HbA1c in both cohorts and with degree of retinopathy and duration of IDDM in the secondary cohort. Within the secondary cohort only mean BP and HbA1c levels were significantly increased (P < 0.005) in the 73 subjects with AER > or = 28 micrograms/24 hr compared to the 642 subjects with AER < 28 micrograms/24 hr. Stratification of all subjects in the secondary cohort showed significant associations (P < 0.001) between retinopathy level, AER, duration of diabetes at entry and entry HbA1c. Even very early in the development of retinopathy and nephropathy, there is a relationship between them and with level of metabolic control. The prospective studies of the DCCT are designed to answer the question of whether intensive diabetes treatment will affect the development and/or progression of retinopathy, and, possibly, of nephropathy.

Adolescent↗
PubMed1993

Incidental pituitary adenomas.

Because adenomas of the pituitary are present in 10% to 20% of healthy individuals, the finding of incidental sellar lesions on computed tomography scanning or magnetic resonance imaging has become relatively common. Hyperfunctioning of such lesions can be excluded clinically and by hormonal screening. Hypopituitarism must be excluded only in lesions more than 10 mm in diameter. Although most such lesions are pituitary adenomas, other lesions such as craniopharyngiomas, meningiomas, and metastatic disease also must be considered. In the absence of visual field defects or hypothalamic/stalk compression, it may be appropriate to follow these patients with repeat imaging. If tumors enlarge, surgery is indicated.

Adenoma↗
PubMed1993

New technique for quantitation of pituitary adenoma size: use in evaluating treatment of gonadotroph adenomas with a gonadotropin-releasing hormone antagonist.

Because administration for 1 week of the GnRH antagonist Nal-Glu GnRH had been shown to decrease FSH secretion from supranormal to normal in men with gonadotroph adenomas, we investigated the effect of prolonged administration of Nal-Glu on the size of gonadotroph adenomas. To quantitate the effect of Nal-Glu GnRH on gonadotroph adenoma size, we first developed a technique for calculating adenoma volume. The technique involved collecting magnetic resonance (MR) imaging data from each adenoma at 1-mm slice intervals in the coronal, axial, and sagittal views and using the Softvu computer program to calculate adenoma volume from the MR data. The precision of this technique, as judged by the coefficients of variation of the calculations of the same view of the same study three times, was 1.7%, 1.0%, and 1.0% for each of three studies. When Nal-Glu GnRH (5 mg, sc, every 12 h) was self-administered for 3-12 months to five men with gonadotroph adenomas and supra-normal serum FSH concentrations, the serum FSH concentrations decreased to normal or below normal for the entire treatment period. Adenoma size, however, did not change during treatment in any of the five men. We conclude that calculating pituitary adenoma volume from MR data using the Softvu computer program is a highly reproducible technique, but that Nal-Glu GnRH is not an effective treatment for reducing gonadotroph adenoma size. The failure of Nal-Glu to reduce adenoma size despite its success in reducing FSH secretion suggests that FSH secretion from gonadotroph adenomas is dependent on endogenous GnRH, but growth of gonadotroph adenomas is not.

Adenoma↗
PubMed1993

Glomerular filtration rate measurements in clinical trials. Modification of Diet in Renal Disease Study Group and the Diabetes Control and Complications Trial Research Group.

To assess the utility and precision of GFR measurements in multicenter trials, the test performance and variability of GFR were analyzed in 2,250 patients enrolled in 44 clinical centers participating in either the Modification of Diet in Renal Disease (MDRD) Study or the Diabetes Control and Complications Trial (DCCT). GRF was measured as the renal clearance of [125I]iothalamate after an sc injection without epinephrine. The studies used similar protocols for obtaining blood and urine, training clinical center staff, and processing specimens in central laboratories. The performance of GFR measurements, assessed from adherence to protocol and quality control analyses, was excellent. The variability among the four clearance periods (intratest coefficient of variation [CV]) was acceptable; the median intratest CV for GFR was 9.4% in the MDRD Study and 11.7% in the DCCT. The pattern of decline in serum counts was better approximated by an exponential rather than a linear relationship. The cause of the intratest variability in GFR measurements was explored by univariate and multivariate analysis. The intratest CV was highest at the extremes of GFR. Among patients with a high GFR (> 90 mL/min per 1.73 m2), most of whom were participants in the DCCT, the higher intratest GFR was due, in part, to a systematic decline in GFR during the test. Among patients with a very low GFR (< 13 mL/min per 1.73 m2), technical difficulties in urine collections contributed substantially to the higher intratest CV. Other patient characteristics, including age, gender, weight, serum glucose, renal diagnosis, and use of diuretics, were not strongly correlated with the intratest CV. The precision of GFR measurements was assessed from the variability from measurement to measurement (interest CV). Among MDRD Study subjects, in whom two measurements of GFR were performed over a 3-month interval, the median interest CV was relatively low (6.3%) and was only weakly related to the intratest CV. Thus, GFR measurements are reasonably precise, even if the intratest CV is high. Given the relatively high intratest CV that is characteristic of GFR measurements, the estimate of GFR in an individual is more precise if multiple clearance periods, rather than a single period, are included. Similarly, the estimate of mean GFR for a population is also more precise if multiple clearance periods are included. In conclusion, by the use of standardized methods, an acceptable precision of GFR results can be obtained in multicenter trials. The same methods can be applied in clinical practice.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Endocrine problems of adolescent pregnancy.

A number of changes in renal and endocrine physiology occur during pregnancy that alter hormone levels and affect a number of disease processes. Increased glomerular filtration causes an increase in hormone and substrate clearance. Increased placental steroid production causes an increase in hormone-binding globulin production, insulin resistance, and prolactinoma growth. Production of peptide hormones may cause changes in normal physiology and alter dynamic hormone testing. Placental vasopressinase increases vasopressin clearance. A number of diseases of hormone overproduction and underproduction affect pregnancy outcome and must be treated promptly by therapeutic modalities that also may affect the fetus.

Adolescent↗
PubMed1992

Octreotide treatment of acromegaly. A randomized, multicenter study.

OBJECTIVE: To determine the effects of the somatostatin analog, octreotide acetate, in patients with acromegaly. DESIGN: Double-blind, randomized trial. SETTING: Fourteen university-affiliated medical centers. PATIENTS: One hundred fifteen acromegalic patients, 70% of whom had persistent disease after pituitary surgery or radiotherapy. INTERVENTION: Subcutaneous octreotide, 100 micrograms, or placebo every 8 hours for 4 weeks. Four weeks after the end of treatment, patients were randomized to receive 100 or 250 micrograms octreotide subcutaneously every 8 hours for 6 months. RESULTS: After 2 weeks of treatment, a single 100-micrograms injection reduced mean serum growth hormone (GH) to 30% of the pretreatment concentration within 2 hours. The integrated mean GH level was reduced over 8 hours from 39 +/- 11 micrograms/L to 9 +/- 2 micrograms/L (P less than 0.001). Mean plasma insulin-like growth factor-1 (IGF-1) was reduced from 5100 +/- 400 U/L to 2400 +/- 400 U/L (P less than 0.001). After 6 months, the mean GH was reduced from 39 +/- 13 to 15 +/- 4 micrograms/L by 300 micrograms of octreotide and from 29 +/- 5 micrograms/L to 9 +/- 2 micrograms/L by 750 micrograms of octreotide daily. The mean IGF-1 concentration was suppressed to 2100 +/- 300 and 2500 +/- 400 U/L after 300 and 750 micrograms octreotide, respectively. Integrated mean GH levels were reduced to < 5 micrograms/L in 53% (95% CI, 39% to 67%) and 49% (CI, 35% to 63%), and IGF-1 levels were normal in 68% (CI, 54% to 82%) and 55% (CI, 40% to 70%) of patients receiving low- and high-dose octreotide, respectively. A substantial decrease in headache, amount of perspiration, joint pain, and finger circumference occurred in two thirds of the patients. The pituitary size was reduced in 19% (CI, 5% to 33%) and 37% (CI, 22% to 52%) of patients receiving 6 months of low- and high-dose octreotide, respectively. Ten percent and 13% of patients in each treatment group developed transient diarrhea; 10% and 14%, biliary sludge; and 6% and 18%, cholelithiasis, respectively. CONCLUSION: Octreotide effectively decreased GH and IGF-1 concentrations in 53% and 68% of patients, respectively. The higher dose resulted in increased frequency of tumor shrinkage but added no biochemical or clinical benefit.

Acromegaly↗
PubMed1992

Endocrine emergencies in pregnancy.

A number of endocrine conditions and emergencies have unique characteristics when present in the pregnant woman. Often the abnormal endocrine state affects both mother and fetus and the various diagnostic and therapeutic approaches have to be altered to avoid harming the fetus. Furthermore, the pregnant state itself may alter the natural course of the underlying endocrine condition. Prolactinomas may enlarge due to the hormonal milieu of pregnancy, causing mass effects and even apoplexy. Anticipation of this possibility and prompt recognition may prevent disastrous consequences. This stimulatory state may extend to the normal pituitary, resulting in Sheehan's syndrome. An acute form of Sheehan's may go unrecognized, leading to unnecessary maternal deaths. Autoimmune endocrine disorders may sometimes be exacerbated and at other times be ameliorated during pregnancy. Witness the development of lymphocytic hypophysitis during pregnancy, a condition best left alone if it can be diagnosed without surgery. Graves's disease usually improves during pregnancy but it may occasionally flare, resulting in potentially lethal thyroid storm. The various therapeutic alternatives for hyperthyroidism are very much affected by effects on the fetus. Cushing's syndrome has very bad consequences for the fetus and must be diagnosed and treated urgently, if not emergently. Phaeochromocytomas are always endocrine emergencies requiring urgent and sometimes emergent treatment. Hyperparathyroidism is usually mild, but severe hypercalcaemia can be a true endocrine emergency. Recognition of the interactions of these endocrine conditions and their specific treatments with the complicated maternal-fetal unit makes their diagnosis and treatment simultaneously both difficult and extremely rewarding.

Acute Disease↗
PubMed1992

Effects of calcium channel blockade with verapamil on the prolactin responses to TRH, L-dopa, and bromocriptine.

To determine the mechanisms by which calcium channel blockade with verapamil causes hyperprolactinemia, the authors investigated the effects of this blockade on the prolactin (PRL) responses to stimulation by thyrotropin releasing hormone (TRH) and inhibition by dopamine, using L-dopa and bromocriptine. Verapamil, given for 1 week at a dosage of 240 mg orally to eight healthy volunteers, induced a significant elevation of basal PRL levels (17.3 +/- 1.8 ng/ml to 30.9 +/- 4.3 ng/ml, p < 0.005). Verapamil also caused an increase in the PRL response to a TRH (100 micrograms). However, when the increased basal level was considered by calculating the area under the THR response curve and subtracting the basal values, this increase (1763.4 +/- 202.6 ng/ml.min to 2260.6 +/- 223.9 ng/ml.min) was not found to be statistically significant (p > 0.05). Verapamil had no effect on the basal or TRH-stimulated thyroid stimulating hormone levels. In these same volunteers, PRL levels decreased from 13.2 +/- 2.5 ng/ml to a nadir of 5.5 +/- 1.6 ng/ml in response to L-dopa. After 1 week of verapamil 240 mg, basal PRL levels were elevated to 21.5 +/- 3.1 ng/ml, then decreased to 8.2 +/- 1.8 ng/ml with L-dopa. The percentage decreased in PRL in response to L-dopa (60 +/- 5% versus 62 +/- 3%) were not significantly different (p > 0.05). Verapamil had no effect on the basal or L-dopa-stimulated growth hormone levels. Bromocriptine 2.5 mg given to five volunteers twice daily caused PRL levels to fall from 13.3 +/- 1.6 ng/ml to 5.0 +/- 0.9 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Low plasma growth hormone binding protein in IDDM.

Poorly controlled insulin-dependent diabetes mellitus (IDDM) is associated with elevated basal plasma growth hormone (GH), disproportionally low insulin-like growth factor I (IGF-I) levels, and impaired somatic growth. These derangements in the GH-IGF axis imply a state of GH resistance. The mechanism of GH resistance is unknown; it may involve a defect at the level of the GH receptor, unresponsiveness due to a postreceptor defect in GH action, or both. To investigate a potential receptor involvement, we measured plasma high-affinity GH-binding protein (GHBP), which represents a truncated GH receptor and may reflect GH receptor levels in tissues, in patients with IDDM, patients with non-insulin-dependent diabetes (NIDDM), and nondiabetic control subjects. Patients with IDDM had significantly lower plasma GHBP levels than either patients with NIDDM or nondiabetic control subjects (mean value 18.2 vs. 24.6 and 23.8% GH bound/ml plasma, respectively, P less than 0.001). This difference persisted when only lean patients (less than 115% ideal body wt) were included in the analysis. Basal plasma GH levels were significantly elevated in IDDM compared with either patients with NIDDM or nondiabetic control subjects (mean 6.9 vs. 2.1 and 2.0 micrograms/L, respectively, P less than 0.001), whereas IFG-I levels were not significantly different in IDDM and NIDDM. No correlations were found between levels of GHBP and HbA1, duration of diabetes, or plasma GH. GHBP and IGF-I levels were significantly correlated in NIDDM but not in IDDM. We conclude that IDDM is associated with low GHBP levels and that GH resistance found in this disorder may be mediated, at least in part, by a decrease in GH receptor levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Pathologic hyperprolactinemia.

Unlike other pituitary hormones, PRL is under tonic inhibition by the hypothalamus by way of the PRL inhibitory factor, dopamine. GAP and GABA may also be inhibitory. PRL-releasing factors include TRH and VIP and possibly others. Circulating PRL is predominantly monomeric, although some patients with hyperprolactinemia appear to have increased quantities of the less biologically active polymeric forms. PRL is secreted episodically, with an increase in the amplitude of the secretory pulses with sleep. A transitory increase also occurs in response to the protein component of meals. Basal PRL levels increase in response to the hormonal milieu of pregnancy, and suckling postpartum triggers PRL release. Pathologic increases of PRL owing to hypothalamic dysregulation occur with a variety of medications, including the neuroleptics, metoclopramide, antidepressants, methyldopa, reserpine and verapamil, abuse of opiates and cocaine, renal insufficiency, cirrhosis, hypothyroidism, adrenal insufficiency, neurogenic stimulation, and idiopathically. Hyperprolactinemia also may occur from structural lesions of the stalk and hypothalamus, which cause disinhibition with or without maintenance of PRF activity, ectopic neoplasm production, and, most commonly, from prolactinomas. Diagnostic testing consists of routine chemistry and thyroid testing and imaging with MRI or CT. Dopamine agonists are the treatment of choice of prolactinomas of all sizes. Transsphenoidal surgery is an alternative for the patient who does not respond to medical therapy or who wishes definitive tumor removal, realizing that long-term cure is achieved in only 50% to 60% of patients with microadenomas and a much lower number in those with macroadenomas. Radiotherapy is reserved for patients who do respond to either medical or surgical treatment. Patients wishing to become pregnant usually are treated with bromocriptine, although prepregnancy surgical debulking may be advisable for those with large macroadenomas to reduce problems with tumor enlargement.

Bromocriptine↗
PubMed1992

Clinical manifestations of acromegaly.

Acromegaly is an uncommon disorder and may present in a variety of ways, leading to considerable delay in diagnosis. Unlike other pituitary tumors, tumors associated with acromegaly tend to be fairly large in most patients. Thus, symptoms may be commonly due to the tumor mass as well as to hormone oversecretion. Mortality is two- to threefold increased due to cardiovascular, respiratory, and neoplastic causes. An increase in diabetes mellitus and hypertension may contribute to the first of these. Early treatment may reverse the diabetes, soft tissue changes, sleep apnea, cardiovascular disease, and neuromuscular disease. The effect of early treatment on neoplasia is unclear, and patients probably should continue to be screened, especially for colon neoplasia, even after appropriate therapy for the acromegaly. Hypopituitarism may be present initially as a result of tumor mass but may also develop as a result of ablative therapy.

Acromegaly↗
PubMed1990

The pituitary "incidentaloma".

PURPOSE: To review evidence related to sellar masses that might be found incidentally on various radiologic procedures, including their differential diagnosis and recommendations for their evaluation and treatment. DATA IDENTIFICATION: An English-language literature search using bibliographic reviews of textbooks and review articles. STUDY SELECTION: Articles were selected on the basis of providing data on the autopsy prevalence of sellar masses, the radiologic and endocrinologic evaluation of such masses, and the prognostic aspects of pituitary adenomas. DATA EXTRACTION: Twelve studies relating autopsy findings, 6 studies describing radiologic characteristics, and 26 articles reviewing various endocrine aspects of pituitary adenomas were evaluated. RESULTS OF DATA SYNTHESIS: Pituitary adenoma is the most common incidental sellar mass. Scanning techniques are of great importance in differentiating the pituitary adenoma from other mass lesions. Autopsy and radiologic studies suggest that microadenomas (less than 10 mm in diameter) may be present in 10% to 20% of the population but that macroadenomas (greater than 10 mm in diameter) are quite rare. Hormone oversecretion by an adenoma may be asymptomatic but, when present, is very helpful in the differential diagnosis. CONCLUSIONS: For adenomas found to be hypersecreting, therapy is as indicated for that specific tumor type. If there is no evidence of hormone oversecretion from microadenomas, we suggest a conservative approach with repeat scanning done at yearly intervals, initially, and subsequently less frequently. Macroadenomas, because they have already indicated some propensity for growth, should either be surgically removed or, if completely asymptomatic, followed closely with repeat scans at 6- to 12-month intervals.

Adenoma↗