Hugues Beauregard

Recurrence of Hyperprolactinemia after Selective Transsphenoidal Adenomectomy in Women with Prolactinoma

To assess the long-term prognosis for women with prolactinoma after selective transsphenoidal adenomectomy, we followed 44 patients for 6.2 +/- 1.5 years. Group 1 (28 patients) had microprolactinomas, and Group 2 (16 patients) had macroprolactinomas. After surgery, normal plasma prolactin levels, resumption of menses, and cessation of galactorrhea were observed in 24 Group 1 patients (85 per cent) and 5 Group 2 patients (31 per cent). Hyperprolactinemia recurred in 12 of the 24 Group 1 patients and in 4 of the 5 Group 2 patients after 4 +/- 1.3 and 2.5 +/- 1.6 years of remission, respectively. There was no radiologic evidence of tumor recurrence in any patient, and no relation was found between the occurrence of pregnancy after surgery and the recurrence of hyperprolactinemia. Clinical and biologic features before surgery could not predict the long-term outcome. However, the immediate postoperative level of plasma prolactin was significantly lower in patients in whom normal prolactinemia (6.4 +/- 1.1 ng per milliliter) was maintained than in those who relapsed (11.7 +/- 1.5 ng per milliliter) (P less than 0.02). We conclude that recurrence of hyperprolactinemia after successful surgery is frequent but delayed. The immediate postoperative level of plasma prolactin may be a predictive risk factor.

The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas

From 1962 to 1987, 126 patients underwent trans‐sphenoidal surgery for primary treatment of pituitary adenomas unassociated with clinical or biochemical evidence of hormonal overproduction. There were 73 male and 53 female patients (mean age, 50 ± 12 years). Before surgery, 56% of the patients (70 of 124) had headaches, 74% (94 of 126) had deterioration of vision, and 12% (15 of 126) had ophthalmoplegia. Endocrine evaluation revealed the presence of hypogonadism in 75% (87 of 115), adrenal insufficiency in 36% (46 of 126), and hypothyroidism in 18% (21 of 122). Plasma prolactin was increased in 65% (56 of 86) with a mean level of 39 ± 14 μg/l (normal, 3 to 20 μg/l). Radiologic enlargement of the sella turcica was documented in all cases: 67% (84 of 126) had enclosed and 33% (42 of 126) had invasive adenomas. After surgery, vision was normalized or improved in 75% (71 of 94) of the patients. Thyroid, adrenal, and gonadal functions were improved in 14% (three of 22), 41% (19 of 46), 11% (ten of 87), were unchanged in 82% (100 of 122), 77% (97 of 126), 89% (102 of 115), and worsened in 15% (19 of 22), 8% (ten of 126), 3% (102 of 115), respectively. Permanent diabetes insipidus occurred in 5% (seven of 126). Two patients died during the immediate postoperative period. The recurrence rate in patients with a mean follow‐up of 6.4 ± 4.2 years was 21% (15 of 71). These data indicate that trans‐sphenoidal microsurgery is an effective and safe initial treatment for patients with nonsecreting pituitary adenoma and may reverse hypopituitarism.

Cabergoline monotherapy in the long-term treatment of Cushing's disease

BACKGROUND Cabergoline is a long-acting dopamine receptor agonist used to treat prolactinomas. Identification of D(2) receptors in corticotroph tumors led to clinical trials of cabergoline therapy in limited cases of Nelsons syndrome, ectopic ACTH-secreting tumors, and recently Cushings disease (CD). OBJECTIVE To evaluate the long-term efficacy of cabergoline monotherapy in patients with CD. METHODS Retrospective analysis of non-randomized clinical therapy with cabergoline in 30 patients with CD treated in academic centers of Buenos Aires and Montreal. Cabergoline was initiated at 0.5-1.0 mg/week and adjusted up to a maximal dose of 6 mg/week based on urinary free cortisol (UFC) levels. Complete response to cabergoline was defined as a sustained normalization of UFC with at least two normal values measured at 1-3 months interval; partial response was defined as a decrease of UFC to <125% of the upper limit of normal, and treatment failure as UFC ≥ 125% of it. RESULTS Within 3-6 months, complete response was achieved in 11 patients (36.6%) and partial response in 4 patients (13.3%). After long-term therapy, nine patients (30%) remain with a complete response after a mean of 37 months (range from 12 to 60 months) with a mean dose of 2.1 mg/week of cabergoline. Two patients escaped after 2 and 5 years of complete response, but one patient transiently renormalized UFC after an increase in cabergoline dosage. No long-term response was maintained in four initial partial responders. CONCLUSIONS Cabergoline monotherapy can provide an effective long-term medical therapy for selected patients with CD, but requires close follow-up for dose adjustments.

Transsphenoidal adenomectomy for microprolactinomas: 10 to 20 years of follow-up

BACKGROUND Transsphenoidal adenomectomy is an effective treatment fo r microprolactinomas. However, postoperative recurrence of hyperprolactinemia is not rare. This study was designed to evaluate the long-term outcome of women with microprolactinomas operated on by transsphenoidal approach. METHODS We retrospectively studied 64 women with microprolactinomas who underwent transsphenoidal adenomectomy and were followed for 10 to 20 years. RESULTS Postoperatively, 58 women (90%) had normal plasma prolactin concentrations (<20 microg/L). After a mean of 3.3 years, during which the women were asymptomatic with normoprolactinemia, 25 (43%) had a relapse of hyperprolactinemia (> or = 20 microg/L). However, their evolution varied. Fifteen women had symptomatic hyperprolactinemia. Computed tomography (CT) scans showed recurrent microadenomas in 2 women. The other 10 women had only hyperprolactinemia. Of these women, 5 had transient hyperprolactinemia (29 +/- 4 microg/L) for 5 years, after which prolactin declined to normal 13 +/- 3 microg/L). The remaining five patients had elevated prolactin (31 +/- 3 microg/L) throughout the follow-up period (10 to 20 years). CT scan did not show recurrent adenomas in these women. Thirty-three women remained normoprolactinemic and asymptomatic for a mean period of 12 years (range, 10 to 20 years). CONCLUSIONS In conclusion, most of the patients with late relapse of hyperprolactinemia have slight functional hyperprolactinemia and remain asymptomatic with no evidence of tumor recurrence.

Decreased sensitivity to insulin in women with microprolactinomas

To determine whether there exists an altered sensitivity to insulin in hyperprolactinemia, we studied, in 15 women with microprolactinomas, the insulin effects on glucose, PRL, GH, and cortisol before and after successful adenoma removal. Our results show that in women with microprolactinomas, the sensitivity to insulin is lower in hyperprolactinemia than in normoprolactinemia achieved by selective adenomectomy.

Effects of a Diet Higher in Carbohydrate/ Lower in Fat Versus Lower in Carbohydrate/Higher in Monounsaturated Fat on Postmeal Triglyceride Concentrations and Other Cardiovascular Risk Factors in Type 1 Diabetes

OBJECTIVE To compare the effects of a eucaloric diet higher in carbohydrate/lower in fat versus lower in carbohydrate/higher in monounsaturated fat on postmeal triglyceride (TG) concentrations and other cardiovascular disease risk factors in nonobese subjects with type 1 diabetes and in good glycemic control. RESEARCH DESIGN AND METHODS In a parallel group design study, 30 subjects were randomly assigned and completed one of the two eucaloric diets. Assessments included: BMI, blood pressure, A1C, plasma lipids, and markers of oxidation, thrombosis, and inflammation. At 6 months, subjects were hospitalized for 24 h to measure plasma TG excursions. RESULTS There were no significant differences between groups other than decreased plasminogen activator inhibitor 1 (PAI-1) levels and weight gain in the lower-carbohydrate/higher–monounsaturated fat group. During the 24-h testing, the lower-carbohydrate/higher–monounsaturated fat group had a lower plasma TG profile. CONCLUSIONS A diet lower in carbohydrate/higher in monounsaturated fat could offer an appropriate choice for nonobese type 1 diabetic individuals with good metabolic and weight control.

Iatrogenic Cushing syndrome in patients receiving inhaled budesonide and itraconazole or ritonavir: two cases and literature review.

OBJECTIVE To present two cases of iatrogenic Cushing syndrome caused by the interaction of budesonide, an inhaled glucocorticoid, with ritonavir and itraconazole. METHODS We present the clinical and biochemical data of two patients in whom diagnosis of Cushing syndrome was caused by this interaction. We also reviewed the pertinent literature and management options. RESULTS A 71-year-old man was treated with inhaled budesonide for a chronic obstructive pulmonary disease and itraconazole for a pulmonary aspergillosis. The patient rapidly developed a typical Cushing syndrome complicated by bilateral avascular necrosis of the femoral heads. Serum 8:00 AM cortisol concentrations were suppressed at 0.76 and 0.83 μg/dL on two occasions. The patient died 4 days later of a massive myocardial infarction. The second case is a 46-year-old woman who was treated for several years with inhaled budesonide for asthma. She was put on ritonavir, a retroviral protease inhibitor, for the treatment of human immunodeficiency virus (HIV). In the following months, she developed typical signs of Cushing syndrome. Her morning serum cortisol concentration was 1.92 μg/dL. A cosyntropin stimulation test showed values of serum cortisol of <1.10, 2.65, and 5.36 μg/dL at 0, 30, and 60 minutes, respectively, confirming an adrenal insufficiency. Because the patient was unable to stop budesonide, she was advised to reduce the frequency of its administration and eventually taper the dose until cessation. CONCLUSION Clinicians should be aware of the potential occurrence of iatrogenic Cushing syndrome and secondary adrenal insufficiency due to the association of inhaled corticosteroids with itraconazole or ritonavir.

Oral contraceptives and prolactinomas: A case-control study

The increase in the number of newly diagnosed cases of prolactinomas seems to coincide with the use of oral contraceptives during the past two decades. The following retrospective case-control study was undertaken in an attempt to disprove a null hypothesis of relationship between oral contraceptive use and prolactinomas. Each of 70 patients operated upon for removal of a prolactinoma was closely matched for age, gravidity, and year of final diagnosis with one patient in each of three control groups. The control groups selected were constituted, respectively, of patients with secondary amenorrhea and normal prolactin levels, patients with normal ovulatory cycles consulting for infertility, and subjects without medical or gynecologic problems. No statistically significative differences were found in the exposure rates to oral contraceptives among four groups. This study thus failed to reveal a significant association between prolactinomas and oral contraceptives but, given the sample size, a relative risk lower than 3.32 cannot be demonstrated or disproved.

Amenorrhea following the use of oral contraceptives.

Clinical aspects and the incidence of the various underlying etiologic factors were studied in 86 patients with post-oral contraceptive amenorrhea. Patients were divided into two groups according to the presence or absence of detectable galactorrhea. Group I was composed of 55 amenorrheic patients without detectable galactorrhea and group II included 31 patients with amenorrhea associated with galactorrhea. Both groups were comparable for age, gravidity, duration of intake of oral contraceptives, and duration of amenorrhea. The incidence of previous oligomenorrhea and late menarche was high in both groups. The most striking difference between the two groups was in the incidence of pituitary prolactin-secreting tumor--32% among patients with galactorrhea and less than 2% among patients without galactorrhea. Identification of galactorrhea and accurate diagnosis of its causes are mandatory for successful management of postpill amenorrhea.

Impact of a high-monounsaturated-fat diet on lipid profile in subjects with type 1 diabetes

OBJECTIVE Controversy persists regarding the use of a high-monounsaturated-fat diet in people with type 1 diabetes. The purpose of this study was to compare the effects of a high-monounsaturated-fat diet containing 43% to 46% carbohydrates and 37% to 40% fat (17% to 20% monounsaturated fat) with those of a high-carbohydrate diet containing 54% to 57% carbohydrates and 27% to 30% fat (10% to 13% monounsaturated fat) on the quantitative and qualitative lipoprotein profile in type 1 diabetes. DESIGN A randomized crossover study was conducted. Two months before the dietary trial, subjects were monitored on their intensive insulin regimen to normalize glycemic and lipid levels. SUBJECTS Twenty-six individuals followed each diet for 2 months. Eight subjects lost or gained >2 kg, and three had the same dietary intakes during the two diets. For the remaining 15, seven adhered to the two diet prescriptions and eight followed one of the two diets. STATISTICAL ANALYSIS Analysis of variance for crossover design (intent-to-treat group of 26) and Wilcoxon signed rank test (group of seven) were used to assess differences between the two diets. RESULTS For the intent-to-treat group (n=26), low-density lipoprotein cholesterol, although within normal range, was lower by 7% (P=.034) at the end of the high-monounsaturated-fat diet. The other 17 lipid parameters tested were not statistically significant. For those who adhered to the two diets (n= 7), lower plasma total triglycerides by 18% (P=.027), lower very low-density lipoprotein triglycerides by 26% (P=.043), lower very low-density lipoprotein cholesterol by 48% (P=.043), higher apolipoprotein A1 by 7% (P=.018), smaller low-density lipoprotein particle size by 1% (P=.043), and longer low-density lipoprotein oxidation lag time by 25% (P=.043) were found after the high-monounsaturated-fat diet. APPLICATIONS/CONCLUSIONS A high-monounsaturated-fat diet seemed to have a favorable effect on fasting lipoprotein profile in people with type 1 diabetes. Further research is needed with a larger sample to recommend a high-monounsaturated-fat diet as an alternative diet therapy in type 1 diabetes.