Vijay Jayagopal

Paradoxical Changes in Cystatin C and Serum Creatinine in Patients with Hypo- and Hyperthyroidism

In the ongoing search for improved serum markers of impaired renal function (1), the low-molecular-weight protein cystatin C has been advocated as a promising and probably superior alternative to creatinine when used to assess glomerular filtration rate (GFR) (2)(3). Cystatin C possesses most of the properties of an ideal GFR test in that it is produced by all nucleated cells at an apparently constant rate, is freely filtered at the glomerulus, and is then fully destroyed in the proximal renal tubule (4). Its rate of production is not influenced by inflammation or malignancy and, unlike creatinine, is unaffected by the muscle mass, sex, or age of a patient (5). Indeed, studies to date would seem to confirm the potential of the marker in many clinical situations in which an accurate estimate of GFR is required in both adults (5)(6)(7) and children (8)(9).nnBefore cystatin C measurement became widespread, another low-molecular-weight protein, β2-microglobulin, was promoted as a marker of GFR for similar reasons (10)(11)(12), but in contrast to cystatin C, its usefulness was subsequently found to be limited by the increased serum values found in inflammatory and neoplastic conditions (13). Thyroid disease …

The LH/FSH ratio has little use in diagnosing polycystic ovarian syndrome

Background: The luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio is often requested to help diagnose polycystic ovarian syndrome (PCOS) despite a recent consensus recommending against its use. This study aimed to compare the variability of the LH/FSH ratio in PCOS with that of normal menstruating women over a full cycle in order to establish the diagnostic utility, or otherwise, of the test. Methods: Twelve women with PCOS and 11 matched controls had blood collected at four-day intervals on 10 consecutive occasions over a complete menstrual cycle. Results: The median LH/FSH ratio for individual subjects did not differ significantly between the PCOS and the non-affected group (1.6 versus 1.2, P=0.14). Only 7.6% of samples from PCOS patients had an LH/FSH ratio above three, compared with 15.6% of samples from normal subjects. Conclusion: This study confirms that measurement of the LH/FSH ratio is of limited use in the diagnosis of PCOS.

Biological variation of total testosterone, free androgen index and bioavailable testosterone in polycystic ovarian syndrome: implications for identifying hyperandrogenaemia.

Objectiveu2003 Hyperandrogenaemia is one of the three Rotterdam consensus diagnostic criteria for polycystic ovarian syndrome (PCOS) and may be measured by estimation of total testosterone, free androgen index (FAI) or bioavailable testosterone (BioT). The aim of this study was to compare the biological variability of total testosterone with that of the biological variability of both the FAI and BioT, to determine the least variable measurement for clinical practice.

Roux-en-Y Gastric Bypass Could Slow Progression of Retinopathy in Type 2 Diabetes: A Pilot Study

BackgroundType 2 diabetes mellitus (T2DM) is a well-recognised complication of obesity. One of the microvascular complications of T2DM is diabetic retinopathy (DR). Bariatric surgery has been shown to effectively treat obesity and can induce remission of T2DM. It is not known what effect this improvement may have on pre-existing DR. We aimed to investigate this.MethodA dual-centre, observer-blinded, case-control study investigated the progression of DR in patients who received Roux-en-Y gastric bypass (treatment group (TG)), compared with controls who received medical therapy (control group (CG)) for their T2DM. Retinal images were taken pre-operatively and approximately 2xa0years post-operatively for the TG and over a 2-year interval for the CG. Data were collected for confounding variables, including glycaemic control (HbA1c) and BMI.ResultsForty-five patients were recruited (TGu2009=u200921, CGu2009=u200924). Groups were significantly heterogeneous. DR showed significant progression for those in the CG (pu2009=u20090.03) but not in TG (pu2009=u20090.135), no significant difference was found when adjusting for confounding variables (pu2009=u20090.480). There was a significant trend in favour of surgery in improvement of glycaemic control (pu2009=u20090.017).ConclusionThe trends within these pilot data may represent a real difference in the progression of DR in patients who have received surgery, compared with medical treatment alone. Due to heterogeneity of group characteristics, further work needs to be done to validate these results. Should there be a true difference, there will be potential cost savings for the National Health Service (NHS) along with a reduced burden of disease for patients.

The mean and the biological variation of insulin resistance does not differ between polycystic ovary syndrome and type 2 diabetes

Background There is an assumption that the mean and biological variation of insulin resistance (IR) is less in polycystic ovary syndrome (PCOS), and intuitively higher in type 2 diabetes (T2DM). To test this hypothesis we compared the mean and biological variation in IR in PCOS to that of T2DM and to age- and weight-matched controls. Methods Twelve PCOS, 11 matched healthy women; 12 postmenopausal diet-controlled T2DM and 11 matched healthy postmenopausal women were recruited. Blood samples were collected at 4-d intervals on 10 consecutive occasions. The biological variability of IR was derived on duplicate samples. Results Mean and biological variability of HOMA-IR for PCOS did not differ from T2DM. Both measures were higher than the matched controls. There was no difference in insulin or IR measures between the body mass index matched pre- and postmenopausal women. Percentage β cell function were 208.8%, 62.3%, 106.5% and 111.9%, respectively, in PCOS, postmenopausal women with T2DM, healthy premenopausal and healthy postmenopausal women. Conclusions The progression from PCOS to the development of T2DM is unlikely to be due to a further increase in IR (or variability), but rather the progressive failure of pancreatic beta cells with a decrease in insulin production. The clinical trial registration number for this study is ISRCTN65353256.

Insulin Resistance Variability in Women with Anovulatory and Ovulatory Polycystic Ovary Syndrome, and Normal Controls

Women with polycystic ovary syndrome (PCOS) were found to have a higher biological variability in insulin resistance (IR) compared to controls, but it is unknown whether this variability in IR differs between PCOS who are anovulatory compared to those who have an ovulatory cycle. The primary aim of this study was to compare and contrast the variability of IR in women with ovulatory and anovulatory PCOS, in comparison to normal subjects. 53 Caucasian women with PCOS and 22 normal ovulating women were recruited. Fasting blood was collected each day on 10 consecutive occasions at 3-4 day intervals for analysis of insulin, glucose, progesterone, and testosterone. Analysis of progesterone levels showed 22 of 53 women with PCOS to have had an ovulatory cycle. Insulin resistance was calculated by HOMA method. Women with anovulatory PCOS had higher mean and variability of IR compared to those having an ovulatory cycle, and both were significantly higher than controls (mean ± SEM; HOMA-IR 4.14 ± 0.14 vs. 3.65 ± 0.15 vs. 2.21 ± 0.16, respectively) after adjustment or BMI. The mean BMI for individual PCOS patients correlated with mean HOMA-IR (p=0.009). Insulin resistance in women with anovulatory PCOS is both higher and more variable than in ovulatory PCOS. Since anovulatory PCOS therefore mimics the IR features of type 2 diabetes more closely, anovulation may be particularly associated with a higher cardiovascular risk compared to PCOS patients who ovulate.

Atrial fibrillation associated with a thyroid stimulating hormone-secreting adenoma of the pituitary gland leading to a presentation of acute cardiac decompensation: A case report

IntroductionHyperthyroidism is a well established cause of atrial fibrillation (AF). Thyroid Stimulating Hormone-secreting pituitary tumours are rare causes of pituitary hyperthyroidism. Whilst pituitary causes of hyperthyroidism are much less common than primary thyroid pathology, establishing a clear aetiology is critical in minimising complications and providing appropriate treatment. Measuring Thyroid Stimulating Hormone (TSH) alone to screen for hyperthyroidism may be insufficient to appropriately evaluate the thyroid status in such cases.Case presentationA 63-year-old Caucasian man, previously fit and well, presented with a five-day history of shortness of breath associated with wheeze and dry cough. He denied symptoms of hyperthyroidism and his family, social and past history were unremarkable. Initial investigation was in keeping with a diagnosis of atrial fibrillation (AF) with fast ventricular response leading to cardiac decompensation.TSH 6.2 (Normal Range = 0.40 – 4.00 mU/L), Free T3 of 12.5 (4.00 – 6.8 pmol/L) and Free T4 51(10–30 pmol/L). Heterophilic antibodies were ruled out. Testosterone was elevated at 43.10 (Normal range: 10.00 – 31.00 nmol/L) with an elevated FSH, 18.1 (1.0–7.0 U/L) and elevated LH, 12.4 (1.0–8.0 U/L). Growth Hormone, IGF-1 and prolactin were normal. MRI showed a 2.4 cm pituitary macroadenoma. Visual field tests showed a right inferotemporal defect.While awaiting neurosurgical removal of the tumour, the patient was commenced on antithyroid medication (carbimazole) and maintained on this until successful trans-sphenoidal excision of the macroadenoma had been performed. AF persisted post-operatively, but was electrically cardioverted subsequently and he remains in sinus rhythm at twelve months follow-up off all treatment.ConclusionThis case reiterates the need to evaluate thyroid function in all patients presenting with atrial fibrillation. TSH-secreting pituitary adenomas must be considered when evaluating the cause of hyperthyroidism. Early diagnosis and treatment of such adenomas is critical in reducing neurological and endocrine complications.

Reversibility of fibrotic appearance of lungs with thyroxine replacement therapy in patients with severe hypothyroidism.

OBJECTIVEnTo present 2 cases of hypothyroidism with hypoxia associated with computed tomographic (CT) features suggestive of pulmonary fibrosis that resolved with correction of the hypothyroidism.nnnMETHODSnClinical case histories are described, comparative radiologic pulmonary images before and after treatment are provided, and the pertinent literature regarding possible pathologic mechanisms is reviewed.nnnRESULTSnOur first patient, a 68-year-old woman, presented with symptomatic severe hypothyroidism associated with respiratory failure. A CT scan of her lungs showed appearances suggestive of pulmonary fibrosis. Replacement therapy with levothyroxine led to correction of hypoxia and radiologic abnormalities. Our second patient, a 26-year-old man, presented with symptoms suggestive of obstructive sleep apnea that persisted despite use of positive pressure ventilation. Biochemical evaluation revealed severe hypothyroidism, and a CT scan disclosed pulmonary appearances consistent with fibrosis. His symptoms and radiologic abnormalities also improved after correction of hypothyroidism with levothyroxine therapy.nnnCONCLUSIONnRadiologic pulmonary abnormalities suggestive of fibrotic disease are associated with severe hypothyroidism. Invasive investigations such as lung biopsy should be deferred until the clinical and radiologic responses to thyroxine replacement therapy have been assessed.

Alterations in thyroid status do not affect plasma peptide YY (PYY) and ghrelin concentrations

We read with interest the paper by Recasens et al . 1 describing a case of asymptomatic bilateral adrenal pheochromocytoma incidentally discovered during a CT scan, in a patient carrying a germline V804M RET mutation. A multicentric medullary thyroid carcinoma (MCT) was also identified in the index case, while four relatives carrying the same mutation had only MTC or C-cell hyperplasia. This finding confirms and extends previous reports showing that V804M mutation is not exclusively associated to familial MTC (FMTC), but can occasionally display a multiple endocrine neoplasia syndrome 2A (MEN-2A) phenotype. 2,3 This observation is also in keeping with our recent study on a large group of patients with V804M RET mutation, which represents the most prevalent (59%) mutation responsible for FMTC or MEN-2A in Sardinia, an island whose population has been strongly influenced by genetic drift and founder effect. 4 In our series 16/17 (94·1%) V804M carriers displayed a FMTC phenotype; in one case (5·9%) FMTC was associated to primary hyperparathyroidism, while no case of pheochromocytoma has so far been found. Taken together, the above observations support the concept that a life-long, periodic screening for other manifestations of MEN-2A should be advised in all subjects with V804M mutation. Regarding pheochromocytoma, Recasens et al . 1

The effect of thyroid dysfunction on N-terminal pro-B-type natriuretic peptide concentrations

Background: B-type natriuretic peptides and N-terminal pro-B-type natriuretic peptides (NT-proBNP) have been suggested as being useful for the diagnosis of congestive heart failure. We have shown previously that changes in thyroid function are associated with changes in concentrations of other low molecular weight molecules. Therefore, the aim of this study was to assess whether similar changes occurred with NT-proBNP concentrations following treatment of thyroid dysfunction. Methods: Seventeen patients (12 female, 5 male, age range 24-77 years) with newly diagnosed hypothyroidism and 21 patients (16 female, 5 male, age range 21-66 years) with newly diagnosed hyperthyroidism had NT-proBNP measured at baseline and when they subsequently became euthyroid. Results: NT-proBNP levels were not significantly different in the hyperthyroid group from the hypothyroid, either before (P = 0.706) or after treatment to euthyroidism (P = 0.170). The hypothyroid group showed a rise in NT-proBNP after treatment (P < 0.001). There was a marginally significant fall in the NT-proBNP levels in the hyperthyroid group (P = 0.05). However, these changes were within the expected wide range of biological variability of NT-proBNP shown in earlier studies. Conclusions: Hypothyroidism alters NT-proBNP concentrations, but the magnitude of this effect may be lost in the wide biological variability of natriuretic peptides and this statistically significant finding is not likely to be of clinical relevance.