Janet A. Schlechte

Guidelines for acromegaly management: An update

OBJECTIVE The Acromegaly Consensus Group reconvened in November 2007 to update guidelines for acromegaly management. PARTICIPANTS The meeting participants comprised 68 pituitary specialists, including neurosurgeons and endocrinologists with extensive experience treating patients with acromegaly. EVIDENCE/CONSENSUS PROCESS: Goals of treatment and the appropriate imaging and biochemical and clinical monitoring of patients with acromegaly were enunciated, based on the available published evidence. CONCLUSIONS The group developed a consensus on the approach to managing acromegaly including appropriate roles for neurosurgery, medical therapy, and radiation therapy in the management of these patients.

Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline

OBJECTIVE The aim was to formulate practice guidelines for the diagnosis and treatment of hyperprolactinemia. PARTICIPANTS The Task Force consisted of Endocrine Society-appointed experts, a methodologist, and a medical writer. EVIDENCE This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society, The European Society of Endocrinology, and The Pituitary Society reviewed and commented on preliminary drafts of these guidelines. CONCLUSIONS Practice guidelines are presented for diagnosis and treatment of patients with elevated prolactin levels. These include evidence-based approaches to assessing the cause of hyperprolactinemia, treating drug-induced hyperprolactinemia, and managing prolactinomas in nonpregnant and pregnant subjects. Indications and side effects of therapeutic agents for treating prolactinomas are also presented.

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.

Controlled prospective study of postpartum mood disorders: psychological, environmental, and hormonal variables.

Demographic, psychiatric, social, cognitive, and life stress variables were used to determine the etiology of depression in childbearing (CB; n = 182) and nonchildbearing (NCB; n = 179) women. Hormonal variables in postpartum depression were also evaluated. In the CB group predictors of depression diagnosis were previous depression, depression during pregnancy, and a Vulnerability (V) x Life Stress (LS) interaction; predictors of depressive symptomatology were previous depression, depressive symptoms during pregnancy, life events, and V x LS. Only estradiol was associated with postpartum depression diagnosis. In the NCB group V X LS was the only predictor of depression diagnosis; depressive symptoms during pregnancy and life events were predictors of depressive symptomatology. Previous findings about depression vulnerability were replicated. The significant V x LS interactions support the vulnerability-stress model of postpartum depression.

Regulation of the glucocorticoid receptor in human lymphocytes

The presence of a glucocorticoid receptor in human lymphocytes is well established, but factors affecting its regulation have not been described. Using a competitive binding whole cell assay, we have examined the binding of [3H]-dexamethasone at 24 and 37 degrees C in untreated normal subjects and in healthy subjects taking various glucocorticoid preparations. At 24 degrees C normal human lymphocytes had 6000 binding sites/cell and a dissociation constant of 4 x 10(-9) M. The administration of 1 mg of dexamethasone, 5 mg of prednisone, and 37.5 mg of cortisone acetate resulted in a 30% decrease in binding sites after 1 week with no change in binding affinity. No changes in the number of binding sites was noted before 1 week and the diminished number persisted for 1 week after discontinuation of glucocorticoid treatment. Lymphocytes from hospitalized patients taking 40-60 mg of dexamethasone daily demonstrated the same change in number of binding sites that was seen in normal subjects taking 1 mg of dexamethasone. When binding assays were carried out at physiologic temperature there was the same decrease in number of binding sites after dexamethasone administration, and in addition, there was a two-fold increase in binding affinity. Glucocorticoid administration results in a time-dependent decrease in the number of lymphocyte glucocorticoid binding sites that is independent of the type of glucocorticoid administered. This is the first in vivo demonstration that glucocorticoids modulate their own receptors in man.

Differences in plasma ACTH and cortisol between depressed patients and normal controls

Although studies have repeatedly demonstrated that depressed patients average higher baseline and postdexamethasone serum cortisol than normal controls, studies examining similar trends in adrenocorticotrophic hormone (ACTH) have produced conflicting results. The current study uniquely employs 48 hr of every 20-min serum sampling: the first 24 hr prior to dexamethasone administration and the second 24 hr subsequent. The depressed patients showed higher baseline cortisol levels than normal controls, with the greatest differences between 2 AM and 6 AM. After an 11 PM dose of dexamethasone, the difference was greatest between the hours of 8 AM and 4 PM. Among the depressed patients, those who reported recent weight loss had significantly higher plasma ACTH and cortisol levels than those without weight loss. Depressed patients without weight loss had higher baseline plasma ACTH than normal controls, and the differences reached significance during some time periods.

Pathogenesis of prolactin-secreting pituitary adenomas.

42 women with amenorrhoea and hyperprolactinaemia had trans-sphenoidal surgery and resection of histologically verified pituitary adenomas. 74% of these patients developed amenorrhoea and/or galactorrhoea in immediate association with the use or discontinuation of oral contraceptives or post partum. There was enough adenomatous tissue for immunocytochemical studies in 35 specimens and specific localisation of prolactin was possible in 31. There is evidence that about 10% of the population have small pituitary tumours, and the majority of these tumours, though asymptomatic, are potentially prolactin-secreting. It is suggested that oestrogens, which are known to modulate prolactin secretion in normal human beings and in animals, can induce the growth and expression of otherwise silent pituitary lesions and that this should be considered a risk of oral-contraceptive use.

Weight Gain and Metabolic Abnormalities During Extended Risperidone Treatment in Children and Adolescents

OBJECTIVE The aim of this study was to investigate the prevalence of clinical and laboratory metabolic abnormalities during long-term risperidone treatment in children and adolescents. METHODS Medically healthy 7- to 17-year-old children chronically treated, in a naturalistic setting, with risperidone were recruited through child psychiatry clinics. Anthropometric measurements and laboratory testing were conducted. Developmental and medication histories were obtained from medical records. RESULTS In 99 patients treated with risperidone for an average of 2.9 years, a significant increase in age- and gender-adjusted weight and body mass index (BMI) (i.e., z-scores) was observed. Concomitant treatment with psychostimulants did not attenuate this weight gain. Risperidone-associated weight gain was negatively correlated with the BMI z-score obtained at the onset of risperidone treatment. Compared to lean children, overweight and obese children had higher odds of metabolic abnormalities, including increased waist circumference, hypertriglyceridemia, and low high-density lipoprotein cholesterol (HDL-C). They also tended to have a higher insulin level and homeostasis model assessment insulin resistance (HOMA-IR) index. As a result, upon recruitment in the study, children with excessive weight were 12 times more likely to have at least one laboratory metabolic abnormality and seven times more likely to have at least one criterion of the metabolic syndrome compared to lean subjects. In contrast to excessive weight status, gaining > or =0.5 BMI z-score point during risperidone treatment was not associated with a significantly higher occurrence of metabolic disturbances. CONCLUSIONS The long-term use of risperidone, especially when weight is above normal, is associated with a number of metabolic abnormalities but a low prevalence of the metabolic syndrome phenotype. Future studies should evaluate the stability of these abnormalities over time.

Influence of age on the cortisol response to dexamethasone.

Controversy exists regarding the association of age with postdexamethasone serum cortisol levels. We evaluated this relationship in 95 patients with major depressive disorder and 49 healthy controls. Age and 8 a.m. postdexamethasone cortisol levels were not correlated among the healthy controls, but were positively associated among the depressives. There was also a trend for age and 4 p.m. postdexamethasone cortisol levels to be positively associated in depressives. Multiple linear regression analyses revealed that these associations could not be explained by other variables such as sex, psychotic features, or familial subtype of depression. Several hypotheses that might account for these associations are examined.

Cushing's syndrome

Cushings syndrome results from prolonged exposure to excess glucocorticoids. Patients with Cushings syndrome may develop multiple metabolic problems including obesity, hyperglycemia, hypertension, depression, low bone mass, muscle atrophy, and hypogonadism. Cutaneous manifestations of hypercortisolism include skin atrophy, excessive bruising, purple striations, poor wound healing, facial plethora, vellous hypertrichosis and hirsutism. Diagnostic tests used to screen for Cushings syndrome include 24-hour urine cortisol, the 1 mg dexamethasone suppresion test, and late night salivary cortisol. A normal screening test excludes the diagnosis of Cushings. Patients with an abnormal screening test should be referred to an endocrinologist for complete evaluation of the pituitary-adrenal axis.