Ariane Godbout

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.

Markers of Recurrence and Long-Term Morbidity in Craniopharyngioma: A Systematic Analysis of 171 Patients

CONTEXT Craniopharyngiomas are often associated with an unfavorable prognosis, but data on their long-term consequences are sparse. OBJECTIVE The aim of the study was to identify markers of recurrence and factors associated with compromised social rehabilitation and altered quality of life in a large cohort of patients with either childhood-onset (CO) or adult-onset craniopharyngioma. METHODS Retrospective analysis was performed for 171 patients treated for craniopharyngioma in two academic centers in France between 1972 and 2009. For each subject, data were collected concerning clinical presentation, imaging features, visual sequelae, endocrine and metabolic impact, treatment modalities (surgery, radiotherapy), recurrence-free survival rate, and social insertion, as well as answers to the WHO-QOL BREF questionnaire. RESULTS A total of 65 CO and 106 adult-onset patients were reviewed. If CO was diagnosed before the age of 10 yr, this was associated with a higher incidence of obesity, blindness, and panhypopituitarism, and only 40.7% of subjects had adequate work or school attendance compared to 72.4% of patients with later disease onset. Initial symptoms of intracranial hypertension (SIHT), pterional surgery, and multiple surgery were associated with obesity and poorer social insertion. No determinant of quality of life was identified. In the subgroup of patients treated in the 1990s and later, the progression rate was 59.4% in patients with residual tumor on magnetic resonance imaging compared with a 19.8% recurrence rate in the group with apparently complete resection. Recurrence/progression correlates significantly with male gender, early onset (before 10 yr), and SIHT, but only SIHT at presentation remained a significant predictor with multivariate analysis. CONCLUSIONS Craniopharyngioma continues to be associated with severe outcomes. Higher morbidity rates are found in patients with early-onset disease (before 10 yr), initial SIHT, or in whom pterional surgery was required. Markers of recurrence are difficult to identify, with SIHT being the most powerful predictor.

Regulation of Aldosterone Secretion by Several Aberrant Receptors Including for Glucose-Dependent Insulinotropic Peptide in a Patient with an Aldosteronoma

CONTEXT Primary adrenal Cushings syndrome can result from the aberrant adrenal expression of several hormone receptors; this mechanism has not been explored in detail in aldosterone-producing tumors. OBJECTIVE The objective of the study was to evaluate a 56-yr-old male patient with an aldosteronoma for the regulation of aldosterone secretion by aberrant hormone receptors. RESULTS Renin-independent stimulation of aldosterone secretion was observed in vivo after a mixed meal, oral glucose, or administration of glucose-dependent insulinotropic peptide (GIP), vasopressin, and tegaserod. The mixed meal-mediated stimulation of aldosterone was not present in five other cases of aldosteronoma. A smaller response of aldosterone after GIP infusion was observed in a normal subject. Aldosterone secretion was stimulated by GIP in primary cultures of this patients aldosteronoma. Increased expression of GIP receptor was found in this aldosteronoma by real-time RT-PCR and immunohistochemistry. The GIP receptor protein was also found at lower levels in zona glomerulosa cells of the normal adjacent adrenal gland. Increased expression of serotonin 4 and ACTH receptors was also present in this aldosteronoma. CONCLUSIONS This case report provides new evidence of the implication of aberrant hormone receptors in the regulation of this aldosteronoma and suggests that further detailed studies of the role of aberrant hormone receptors in this frequent pathology should be undertaken.

Transition from Pediatric to Adult Healthcare: Assessment of Specific Needs of Patients with Chronic Endocrine Conditions

Background/Aim: Transition from pediatric to adult care is a challenging turning point. The aim was to evaluate the transition process and needs expressed by patients with chronic endocrine conditions at transition in order to ensure program optimization. Methods: Prospective assessment of the transition period was conducted through completion of standardized questionnaires given to targeted patients. Two types were created: (1) a general questionnaire (GQ) addressing universal aspects of transition, and (2) a specific questionnaire (SQ) exploring concerns related to each endocrine condition. Three endocrinopathies (congenital adrenal hyperplasia, hypogonadotropic hypogonadism and growth hormone deficiency) were selected for assessment since they present specific challenges requiring characterization. Results: Over the last decade, 244 patients in transition were registered in our department and 153 were included since they presented one of the endocrinopathies selected. A total of 73 subjects completed both the GQ and the SQ. Over 80% of the patients were satisfied with the transition process in terms of organization, accessibility and medical care. The actual age of transition corresponded for most to the age considered by patients as ideal for transition. SQs identified psychosexual issues that must be addressed more systematically. Conclusion: This study identified key elements allowing the creation of an improved transition program tailored for our center and for each endocrine condition studied.

Are There Benefits for Gestational Diabetes Mellitus in Treating Lower Levels of Hyperglycemia Than Standard Recommendations

OBJECTIVES The new International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations for diagnosis of gestational diabetes mellitus (GDM) are generating discussion regarding their universal adoption. Our centre is currently using stricter GDM diagnostic criteria than those proposed by the IADPSG. Evaluation of complication rates and their predictors in our cohort may provide insight for the care of this high-risk population. Therefore, we determined complication rates and identified antepartum maternal predictors of adverse outcomes in our cohort with mild GDM. METHODS A retrospective cohort study was performed between 2005 and 2011. It included women with and without GDM, which was diagnosed if fasting plasma glucose levels were 5.0 or above or 2-hour post 75 gram oral glucose tolerance test (OGTT) were 7.8 mmol/L or higher. RESULTS A total of 3712 women, with and without diabetes, were included. Rates of macrosomia and pre-eclampsia were significantly higher in the group with GDM but were lower than the rates usually reported. Macrosomia, the need for insulin therapy or caesarean section and postpartum glucose intolerance predictors included prepregnancy body mass index, excessive gestational weight gain and OGTT screening results, although no specific threshold was found. CONCLUSIONS This study provides insight into GDM-related complications rates and the benefits of intervention in a large cohort of women with levels of hyperglycemia lower than those currently recommended for diagnosis of GDM. These findings suggest a continuous association between adverse outcomes and maternal hyperglycemia and highlight the important role of maternal risk factors other than glycemic results in the development of pregnancy-related complications. Milder forms of hyperglycemia that would not be identified by IADPSG guidelines may benefit from treatment.

Pituitary apoplexy in pregnancy: A case series and literature review

Background Severe headache during pregnancy is a challenging condition that may rarely imply endocrine disturbances. Rapid recognition of pituitary apoplexy is needed to improve pregnancy outcome. Objective To review and compare maternal and fetal outcomes after pituitary apoplexy. Methods Four cases of pituitary apoplexy during pregnancy in our centre are reported and literature review covering the past 54 years was performed. Results In the four cases presented and the 33 reported in the literature, most women presented with severe headaches and systemic symptoms. Overall, 42% were treated surgically, 31% received bromocriptine or cabergoline and 61% were given hormone replacement. No major obstetrical complication was reported and all babies were healthy. Conclusion Pituitary apoplexy is a rare cause of sudden and severe headache during pregnancy. Rapid identification of this condition with potentially associated endocrine disturbances is important to ensure maternal and fetal well-being. A multidisciplinary team approach seems to reduce morbidity and mortality.

Unusual presentation of pheochromocytoma: thirteen years of anxiety requiring psychiatric treatment

Summary Pheochromocytoma is a rare tumor of the adrenal gland. It often presents with the classic triad of headache, palpitations and generalized sweating. Although not described as a typical symptom of pheochromocytoma, anxiety is the fourth most common symptom reported by patients suffering of pheochromocytoma. We report the case of a 64 year old man who had severe anxiety and panic disorder as presenting symptoms of pheochromocytoma. After 13 years of psychiatric follow-up, the patient was diagnosed with malignant pheochromocytoma. After surgical resection of his pheochromocytoma and his hepatic metastases, the major panic attacks completely disappeared, the anxiety symptoms improved significantly and the psychiatric medications were stopped except for a very low maintenance dose of venlafaxine. We found in our cohort of 160 patients with pheochromocytoma 2 others cases of apparently benign tumors with severe anxiety that resolved after pheochromocytoma resection. These cases highlight that pheochromocytoma should be included in the differential diagnosis of refractory anxiety disorder. Learning points: Anxiety and panic disorder may be the main presenting symptoms of pheochromocytoma. The diagnosis of pheochromocytoma should be excluded in cases of long-term panic disorder refractory to medications since the anxiety may be secondary to a catecholamine-secreting tumor. Surgical treatment of pheochromocytoma leads to significant improvement of anxiety disorders.

A Rare Case of Severe Headache and Sudden-Onset Diabetes Insipidus During Pregnancy: Differential Diagnosis and Management of Lymphocytic Hypophysitis

ABSTRACT Objective: To present a case of lymphocytic hypophysitis (LH) during pregnancy. Methods: Clinical presentation before and after pregnancy and review of the pertinent literature are presented. Results: A 30-year-old woman, G3P2A0, presented at 30 weeks of gestation with headache, polyuria, and hypernatremia (156 mmol/L). Obstetrical history was significant for gestational diabetes mellitus, without previous infertility or autoimmune disorders. Magnetic resonance imaging of the head revealed an enlarged pituitary gland measuring 16 mm with slight compression of the optic chiasm. A clinical diagnosis of LH was made upon laboratory findings of diabetes insipidus, adrenal insufficiency, and central hypothyroidism. The patient was treated with desmopressin, hydrocortisone, and levothyroxine. There was rapid regression of the pituitary enlargement within 10 days. At 38 weeks, the patient gave birth to a healthy baby girl weighing 3,950 g. Post-delivery, she breastfed normally and continued to experience...