Hyperdynamic right heart function in Graves' hyperthyroidism measured by echocardiography normalises on restoration of euthyroidism

Graves' hyperthyroidism commonly causes tachycardia and may result in pulmonary hypertension and high output cardiac failure. There is limited information regarding the effect of treatment on cardiac function measured using modern echocardiographic techniques.Eight individuals with Graves' hyperthyroidism, aged 22-64 years, underwent comprehensive transthoracic echocardiography at three time points: before treatment, two weeks after commencement of carbimazole, and at six months or more when euthyroid. Exercise capacity was assessed using the 6-minute-walk-distance (6MWT), and quality of life was assessed by Medical Outcome Study 36-item Short-Form Health Status Survey.All individuals were rendered euthyroid by final assessment. At presentation, there was evidence of hyperdynamic right ventricular function as measured by peak systolic velocity of the free wall of the tricuspid annulus, tricuspid annular plane systolic excursion and right ventricular ejection fraction, which normalised after resolution of thyrotoxicosis. Baseline heart rate correlated significantly with severity of the thyrotoxicosis for either free T4 (r = 0.91, p=0.01) or free T3 (r=0.94, p=0.001). No individual had measurable pulmonary hypertension. Cardiac output was significantly lower in the euthyroid compared to the thyrotoxic state (p=0.03). A higher baseline TSH-receptor antibody titre corresponded to a greater improvement in exercise capacity (r=0.76,

Impulse control disorders in dopamine agonist-treated hyperprolactinemia: Prevalence and risk factors

Context: There are growing reports of dopamine agonist (DA)-induced impulse control disorders (ICDs) in hyperprolactinemic patients. However, the magnitude of this risk and predictive factors remain uncertain. Objective: To determine ICD prevalence and risk factors in DA-treated hyperprolactinemic patients compared to community controls. Design, Setting and Participants: Multicenter cross-sectional analysis of 113 patients and 99 healthy controls. Main Outcome Measures: Participants completed a neuropsychological questionnaire consisting of the Depression Anxiety Stress Scale (DASS21), Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s disease (QUIP-S), Hypersexual Behavior Inventory (HBI), Hypersexual Behavior Consequences Scale and Social Desirability Response Set Scale. Demographic and clinical data were collated to determine ICD risk factors. Patients testing positive for an ICD were offered a semi-structured psychological interview. Results: Patients were more likely than controls to test positive by QUIP-S for any ICD (61.1 vs 42.4%, P=0.01), hypersexuality (22.1 vs 8.1%, P=0.009), compulsive buying (15.9 vs 6.1%, P=0.041) and punding (18.6 vs 6.1%, P=0.012), and by HBI for hypersexuality (8.0 vs 0.0%, P=0.004). Independent risk factors were male sex (OR 13.85), eugonadism (OR 7.85), Hardy’s tumor score, and psychiatric comorbidity (OR 6.86) for hypersexuality; and age (OR 0.95) for compulsive buying. DASS21 subset scores were higher in patients vs controls, and in patients with vs without different ICDs. Only 19/51 (37.3%) interviewed patients were aware of the relationship between DAs and ICDs before the study. Conclusions: DA therapy poses a high, previously underestimated risk of ICDs, especially in the form of hypersexuality in eugonadal men

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Long-acting porcine sequence ACTH in the diagnosis of adrenal insufficiency: a cost-effective alternative to the ACTH(1-24) test

While the ACTH(1-24) test has some well-documented shortcomings, it is the most widely used test to diagnose primary and secondary adrenal insufficiency. However, this synthetic ACTH preparation is not readily available in some countries. Research from India has demonstrated that using a long-acting porcine sequence ACTH has similar diagnostic performance to ACTH(1-24) at around 25% of the cost. This may allow access to a robust test for adrenal insufficiency to developing countries and potentially allow thousands of patients to be identified and appropriately treated

Measurement of salivary cortisol in 2012 – laboratory techniques and clinical indications

The utility of measuring salivary cortisol has become increasingly appreciated since the early 1980s. Salivary cortisol is a measure of active free cortisol and follows the diurnal rhythm of serum or plasma cortisol. The saliva sample may be collected by drooling or through the use of absorbent swabs which are placed into the mouth until saturated. Salivary cortisol is therefore convenient for patients and research participants to collect non-invasively on an outpatient basis. Several assay techniques have been used to measure salivary cortisol including radioimmunoassay and more recently liquid chromatography-tandem mass spectrometry. The analytical sensitivity varies between these assay methods, as does the potential for cross reactivity with other steroids. The interpretation of salivary cortisol levels relies on rigorous standardization of sampling equipment, sampling protocols and assay technology with establishment of a local reference range. Clinically, the commonest use for salivary cortisol is measuring late night salivary cortisol as a screening test for Cushing's syndrome. Several studies have shown diagnostic sensitivities and specificities of over 90%, which compares very favourably with other screening tests for Cushing's syndrome such as the 24 hour urinary free cortisol and the 1mg overnight dexamethasone suppression test. There are emerging roles for the use of salivary cortisol in diagnosing adrenal insufficiency, particularly in conditions associated with low cortisol binding globulin levels, and in the monitoring of glucocorticoid replacement. Finally, salivary cortisol has been used extensively as a biomarker of stress in a research setting, especially in studies examining psychological stress with repeated measurements

The need for annual echocardiography to detect cabergoline-associated valvulopathy in patients with prolactinoma: a systematic review and additional clinical data

Present recommendations by the US Food and Drug Administration advise that patients with prolactinoma treated with cabergoline should have an annual echocardiogram to screen for valvular heart disease. Here, we present new clinical data and a systematic review of the scientific literature showing that the prevalence of cabergoline-associated valvulopathy is very low. We prospectively assessed 40 patients with prolactinoma taking cabergoline. Cardiovascular examination before echocardiography detected an audible systolic murmur in 10% of cases (all were functional murmurs), and no clinically significant valvular lesion was shown on echocardiogram in the 90% of patients without a murmur. Our systematic review identified 21 studies that assessed the presence of valvular abnormalities in patients with prolactinoma treated with cabergoline. Including our new clinical data, only two (0·11%) of 1811 patients were confirmed to have cabergoline-associated valvulopathy (three [0·17%] if possible cases were included). The probability of clinically significant valvular heart disease is low in the absence of a murmur. On the basis of these findings, we challenge the present recommendations to do routine echocardiography in all patients taking cabergoline for prolactinoma every 12 months. We propose that such patients should be screened by a clinical cardiovascular examination and that echocardiogram should be reserved for those patients with an audible murmur, those treated for more than 5 years at a dose of more than 3 mg per week, or those who maintain cabergoline treatment after the age of 50 years