c-peptide and Hypothyroidism

As a rare condition characterized by inflammation of the pituitary gland, hypophysitis usually results in hypopituitarism and pituitary enlargement. The most critical outcome of hypopituitarism is caused by secondary adrenal insufficiency. Glucocorticoid deficiency is a life-threatening condition, and patients who develop this deficiency require prompt diagnosis and treatment. However, a delayed diagnosis of hypopituitarism may occur due to its non-specific clinical manifestations. A common presenting sign of glucocorticoid deficiency is hypoglycemia. The amelioration of hyperglycemia has been observed in diabetic patients with adrenal insufficiency. We report the case of a 70-year-old Japanese woman who had suffered from fatigue and anorexia for several months; she was admitted based on refractory hyponatremia (sodium 125-128 mEq/L) and hypoglycemia (glucose 58-75 mg/dL). Laboratory findings and magnetic resonance imaging findings led to the diagnosis of panhypopituitarism caused by autoimmune hypophysitis. After receiving 10 mg/day of hydrocortisone, the patient developed severe hyperglycemia (glucose >500 mg/dL). Undetectable C-peptide levels and positive results of both insulinoma-associated antigen-2 antibodies and insulin autoantibodies indicated that she had experienced a recent onset of type 1 diabetes. The pathophysiological process indicated that overt hyperglycemia could be masked by the deficient action of glucocorticoids even in a diabetic patient with endogenous insulin deficiency. This uncommon case reinforces the importance of the prompt diagnosis and treatment of hypopituitarism. Clinicians should remain aware of the possibility of hidden diabetes when treating hypoglycemia in patients with adrenal insufficiency.

Topics: Adrenal Insufficiency; Aged; Autoantibodies; Autoimmune Hypophysitis; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Female; Glucocorticoids; Glycated Hemoglobin; Humans; Hydrocortisone; Hypoglycemic Agents; Hyponatremia; Hypopituitarism; Hypothyroidism; Insulin; Thyroxine

Immunoassays are susceptible to analytical interferences including from endogenous immunoglobulin antibodies at a rate of ∼0.4% to 4%. Hundreds of millions of immunoassay tests (>10 millions in the UK alone) are performed yearly worldwide for measurements of an array of large and small moieties such as proteins, hormones, tumour markers, rheumatoid factor, troponin, small peptides, steroids and drugs.. Interference in these tests can lead to false results which when suspected, or surmised, can be analytically confirmed in most cases. Suspecting false laboratory data in the first place is not difficult when results are gross and without clinical correlates. However, when false results are subtle and/or plausible, it can be difficult to suspect with adverse clinical sequelae. This problem can be ameliorated by using a probabilistic Bayesian reasoning to flag up potentially suspect results even when laboratory data appear "not-unreasonable".. Essentially, in disorders with low prevalence, the majority of positive results caused by analytical interference are likely to be false positives. On the other hand, when the disease prevalence is high, false negative results increase and become more significant. To illustrate the scope and utility of this approach, six different examples covering wide range of analytes are given, each highlighting specific aspect/nature of interference and suggested options to reduce it.. Bayesian reasoning would allow laboratorians and/or clinicians to extract information about potentially false results, thus seeking follow-up confirmatory tests prior to the initiation of more expensive/invasive procedures or concluding a potentially wrong diagnosis.

Topics: Acute Coronary Syndrome; Aged; Bayes Theorem; C-Peptide; Chorionic Gonadotropin; Data Interpretation, Statistical; False Positive Reactions; Female; Humans; Hyperglycemia; Hypothyroidism; Immunoassay; Insulin; Myocardial Infarction; Proinsulin; Prostate-Specific Antigen; Rheumatoid Factor; Thyrotropin; Troponin

Chronic iodine deficiency (ID) increases thyrotropin (TSH) concentrations and produces a thyroid hormone pattern consistent with subclinical hypothyroidism (ScH). ScH may be associated with cardiovascular disease risk factors. Thus, the study aim was to determine if iodine treatment of children with elevated TSH concentrations due to ID would affect their lipid profile, insulin (C-peptide) levels, and/or subclinical inflammation.. In controlled intervention trials of oral iodized oil or iodized salt, 5-14-year-old children from Morocco, Albania, and South Africa with TSH concentrations > or = 2.5 mU/L (n = 262) received 400 mg iodine as oral iodized oil or household distribution of iodized salt containing 25 microg iodine/g salt. At baseline and after 5 or 6 months, urinary iodine (UI) and blood concentrations of total thyroxine, TSH, C-reactive protein (CRP), C-peptide, and lipids were measured.. Median (range) UI at baseline was 46 (2-601) microg/L. Compared to the control group, iodine treatment significantly increased UI and total thyroxine and decreased TSH, C-peptide, and total and low-density lipoprotein cholesterol. The mean low-density lipoprotein/high-density lipoprotein cholesterol ratio fell from 3.3 to 2.4 after iodine treatment (p < 0.001). Iodine treatment had no significant effect on concentrations of high-density lipoprotein cholesterol, triglycerides, or C-reactive protein.. Correction of ID-associated ScH improves the insulin and lipid profile and may thereby reduce risk for cardiovascular disease. This previously unrecognized benefit of iodine prophylaxis may be important because ID remains common in rapidly developing countries with increasing rates of obesity and cardiovascular disease.

Topics: Adolescent; C-Peptide; Cardiovascular Diseases; Child; Child, Preschool; Female; Humans; Hypothyroidism; Inflammation; Insulin; Iodine; Lipids; Male; Risk Factors; Thyrotropin; Thyroxine

A 61-year-old overweight woman had been diagnosed with diabetes mellitus, hypertension and hypothyreosis. Treatment with antidiabetic and antihypertensive medication and thyroxine had been started. Blood sugar had been increasing despite medication and she had started using insulin. In 2003 she used 150 IE insulin per day. She tried hard to adhere to a recommended diet, but gradually became fatter, maximum weight was 120 kg. She started on a low carbohydrate diet on her own and lost 14 kg during 5 months. She had some hypoglycemic episodes and sought advice at Dr. Fedon Lindberg's Clinic. Her low carbohydrate diet was continued, endurance exercise was included, medication with metformin was started and during 8 months she was off insulin and showed much lower blood sugar values than before. She lost 14 kg during this period. She was motivated for loosing more weight and starter on a VLCD (very low caloric diet). She lost another 9 kg on this diet. She than started regular resistance training and her weight stabilized on 80 kg. Her HbA1c value has been reduced from 8.9 to 5.4% and her total/HDL cholesterol ratio has been reduced from 5.4 to 1.7. Her C-peptide value increased in the period when insulin was reduced, but is now reduced to 700 pmol/L. Micro-CRP has been reduced from 9.0 mg/L to 0.4 mg/L. With a low carbohydrate diet and exercise this woman no longer has diabetes or severe overweight. It is our opinion that many patients with type 2 diabetes can manage without medication (especially insulin) by reducing the intake of carbohydrates considerably.

Topics: C-Peptide; Caloric Restriction; Diabetes Mellitus, Type 2; Diet, Carbohydrate-Restricted; Exercise Therapy; Female; Humans; Hypertension; Hypoglycemic Agents; Hypothyroidism; Insulin; Metformin; Middle Aged; Overweight; Weight Loss

We examined insulin sensitivity and secretion, together with the levels of selected glucoregulatory hormones, in 15 female patients with severe hypothyroidism (H) and during subsequent thyroid hormone replacement therapy (HRT) using the euglycaemic hyperinsulinaemic clamp technique. Insulin action, as evaluated by glucose disposal, the insulin sensitivity index, and fasting post-hepatic insulin delivery rate were established. The basal levels of insulin, C-peptide and counter-regulatory hormones were measured in basal condition. In H, glucose disposal (p<0.01), the insulin sensitivity index (p<0.01) and post-hepatic insulin delivery rate (p<0.05) were significantly lower than during HRT. No significant changes in the levels of fasting insulin and C-peptide were observed. The levels of counter-regulatory hormones in patients with H were significantly higher than during HRT (glucagon, p<0.05; epinephrine, p<0.01; cortisol, p<0.05; growth hormone, p<0.05). In H, an inverse correlation between insulin sensitivity and insulin secretion was observed (p<0.05). Cortisol was the most important factor affecting the variability of insulin sensitivity values, regardless of thyroid function (p=0.0012). In conclusion, H altered both insulin sensitivity and the levels of selected counter-regulatory hormones. The situation was restored by HRT, as manifested not only by normalisation of insulin sensitivity, secretion and levels of glucoregulatory hormones, but also by improvement of their relationships.

Topics: Adult; Blood Glucose; C-Peptide; Epinephrine; Female; Glucagon; Glucose Clamp Technique; Hormones; Human Growth Hormone; Humans; Hydrocortisone; Hypothyroidism; Insulin; Insulin Resistance; Insulin Secretion; Thyroid Hormones

We report a case of chronic hepatitis C presenting insulin-dependent diabetes mellitus (IDDM) associated with various autoantibodies including possible anti-insulin receptor antibody (AIRA) during interferon (IFN) therapy. A 57-year-old man having chronic hepatitis C virus (HCV) infection with chronic thyroiditis received IFN therapy. The thyroid function was well-controlled by administration of thyroid hormone, although thyroid autoantibodies were positive. At 15 weeks after starting IFN (reaching 530 million units of total dose), marked thirst happened, with increased fasting plasma glucose level (488 mg/dl) and decreased daily urinary C peptide immunoreactivity level (less than 4.2 microg/day). IDDM occurred with anti-nuclear antibody (ANA), anti-DNA antibody and possible AIRA, and thyroid autoantibodies titers increased, but without pancreatic islet cell antibody and anti-glutamic acid decarboxylase antibody. Administration of IFN was stopped and insulin treatment was started, but plasma glucose level was not controlled well. AIRA became negative 2 months later, however, insulin antibody (IA) was positive when tested after 18 months. Serum HCV RNA has been negative, and a normal level of serum transaminase has been observed since IFN therapy. It is likely that IFN therapy induced the immunological disturbance and resulted in occurrence of various autoantibodies and IDDM in the patient.

Topics: Antibodies, Antinuclear; Antiviral Agents; Autoantibodies; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Glutamate Decarboxylase; Glycated Hemoglobin; Hepatitis C, Chronic; Humans; Hypothyroidism; Insulin; Insulin Antibodies; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Receptor, Insulin; Recombinant Proteins; Thyroid Hormones; Transfusion Reaction

Plasma leptin is considered to play a role in maintenance of energy balance and body weight by neuroendocrine mechanisms. Thyroid hormones are permissive for adrenergic activation, which in turn has been shown to decrease leptin expression. This study was therefore designed to test the hypothesis that hyperthyroidism results in lower leptin concentrations, whereas hypothyroidism leads to higher plasma leptin concentrations. In addition, the effects of normalization of thyroid function on plasma leptin were investigated.. Fasting plasma leptin concentrations and body fat mass (total body electrical conductivity) were measured in patients with overt hypothyroidism and hyperthyroidism before and after successful treatment. Plasma leptin, glucose, insulin and free fatty acid concentrations were monitored during an oral glucose tolerance test (OGTT 75 g).. Fasting plasma leptin concentrations were similar in lean patients, independently of their thyroid function (hyperthyroid 12.5 +/- 2 ng mL-1, hypothyroid 10.2 +/- ng mL-1, euthyroid 12.7 +/- 3 ng mL-1). In obese hypothyroid patients, plasma leptin was threefold higher (P < 0.0005) than in lean hypothyroid patients, twofold higher (P < 0.005) than in obese hyperthyroid patients matched for fat mass and 30% increased (P < 0.01) compared with obese euthyroid subjects. There were no differences between fasting and post-prandial (OGTT) leptin concentrations in any group. Normalization of thyroid function did not affect plasma leptin, which remained elevated (P < 0.005) in formerly obese hypothyroid patients. Plasma leptin was not associated with serum thyroid hormones but highly correlated with body mass index and body fat mass in all patients (r = 0.85, P < 0.001). Plasma leptin correlated with plasma insulin concentration only in hyperthyroid patients (P < 0.01, r = 0.64), who presented with blunted stimulation of insulin release and higher plasma glucose (P < 0.05) than hypothyroid subjects.. The results indicate that (a) the correlation of leptin with body fat mass is preserved in thyroid dysfunction, (b) plasma leptin is markedly increased in obese hypothyroid hyperinsulinaemic patients and (c) plasma leptin is not affected by oral glucose loading.

Topics: Adult; Blood Glucose; C-Peptide; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Hydrocortisone; Hyperinsulinism; Hyperthyroidism; Hypothyroidism; Insulin; Leptin; Male; Middle Aged; Obesity; Proteins

We report 34 patients (aged 5-18 years) with acute (n = 26) or chronic (n = 1) leukemia, non-Hodgkin's lymphoma (n = 3) or severe aplastic anemia (n = 4) evaluated for pancreatic beta-cell function 9 months to 10.2 years after autologous (n = 19) or allogeneic (n = 15) BMT. Before BMT, all patients received cytotoxic drugs, combined with total body irradiation (TBI) in 24 cases or thoracoabdominal irradiation (TAI) in 4 children. Patients were investigated for fasting blood glucose (FBG), HbA1C, anti-insulin (IAA) and islet cell antibodies (ICA), first-phase insulin response (FPIR) and insulinemia/glycemia (I/G) ratio on i.v. glucose tolerance test (GTT) and C-peptide response after glucagon 1 mg i.v. Results were compared with those obtained in 21 age- and sex-matched controls. None of the patients or controls had IAA and/or ICA. FBG and HbA1C were normal in all children. In the patients, glycemia on i.v. GTT was similar to controls whereas insulin levels I/G ratio and FPIR were significantly higher in patients than in controls, as well as C-peptide levels. We divided the patients on the basis of the radiotherapy into group I with TBI (n = 18), group II with TAI (n = 4) and group III who were not irradiated (n = 4). The I/G ratio, FPIR on i.v. GTT and C-peptide response were significantly higher in group I compared with the other two groups and controls. The increased insulin and C-peptide levels in our patients with normal glycemia might be interpreted as a state of insulin resistance, more evident in patients who received TBL.

Topics: Adolescent; Anemia, Aplastic; Antineoplastic Combined Chemotherapy Protocols; Autoantibodies; Blood Glucose; Bone Marrow Transplantation; C-Peptide; Child; Child, Preschool; Female; Glucagon; Glycated Hemoglobin; Growth Hormone; Humans; Hypogonadism; Hypothyroidism; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Leukemia; Lymphoma, Non-Hodgkin; Male; Prospective Studies; Radiation Injuries; Radioisotope Teletherapy; Whole-Body Irradiation

The response of circulating somatostatin-like immunoactivity (SLI) to oral glucose and its relation to other pancreatic islet cell hormones were studied in 10 hypothyroid subjects before and after treatment. None of the patients suffered from diabetes mellitus or obesity. Compared with normal controls, the hypothyroid subjects had higher fasting and stimulated SLI levels but lower fasting pancreatic glucagon levels. Integrated glucose and insulin responses following glucose ingestion were normal, but the peak insulin response was delayed to 120 min suggesting impaired pancreatic beta-cell response to oral glucose. On the other hand, the peak response of plasma C-peptide was higher probably because of a reduction in metabolic clearance. In both hypothyroid subjects and controls, a significant correlation was found between the maximal increment of SLI and the maximal decrement of glucagon following oral glucose. In conclusion, plasma SLI is increased in hypothyroidism. The changes in SLI may be due to either an increased hormonal secretion or a reduced metabolic clearance in hypothyroidism. This elevated SLI might contribute to the slower gastrointestinal motility observed in hypothyroidism. Our data also suggest that the reduction in glucagon secretion may be secondary to the increase in circulating SLI.

Topics: Adult; Aged; C-Peptide; China; Glucagon; Glucose; Glucose Tolerance Test; Humans; Hypothyroidism; Insulin; Male; Middle Aged; Somatostatin; Thyrotropin; Thyroxine; Triiodothyronine

C-peptide and proinsulin levels were studied in hyper and hypothyroidism both pre and post-treatment and in comparison to matched normals. Fasting C-peptide was reduced in untreated hyperthyroidism (0.4 +/- 0.2 (mean +/- SEM) vs 0.7 +/- 0.2 nmol/l, P less than 0.05) but returned to normal levels following treatment. Fasting proinsulin was elevated in untreated hyperthyroidism (3.6 +/- 0.7 vs 2.4 +/- 0.5 pmol/l, P less than 0.05) also returning to normal after treatment. A similar pattern was seen after oral glucose. The increased proinsulin and reduced C-peptide suggest there may be a defect of proinsulin processing in hyperthyroidism. Fasting C-peptide was reduced in untreated hypothyroidism (0.4 +/- 0.1 vs 0.7 +/- 0.1 nmol/l, P less than 0.05) and also returned to normal after treatment. Fasting proinsulin did not differ significantly from controls. However, proinsulin was reduced after oral glucose (4.7 +/- 0.7 vs. 7.9 +/- 2.0 pmol/l, P less than 0.05) as was C-peptide (0.9 +/- 0.2 vs 2.6 +/- 0.3 nmol/l, P less than 0.05). Both returned to normal after treatment. These findings suggest there are abnormalities of proinsulin and C-peptide levels in both hyper and hypothyroidism.

Topics: Adult; Blood Glucose; C-Peptide; Fasting; Female; Glucose; Humans; Hyperthyroidism; Hypothyroidism; Immunoradiometric Assay; Middle Aged; Proinsulin

Topics: Adult; Aged; C-Peptide; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Hypothyroidism; Insulin; Middle Aged

Hypothyroidism has been alleged to modulate insulin action and influence the secretion of growth hormone and catecholamines. We recently investigated the influence of hypothyroidism on glucose counter-regulatory capacity and the hormonal responses to insulin-induced hypoglycaemia in 6 patients with primary hypothyroidism (age 32-52 years, TSH-values 66-200 mU/l). Hypoglycaemia was induced in the hypothyroid state and again when the subjects were euthyroid. After an overnight fast a constant rate infusion of insulin (2.4 U/h) was given for 4 h. Glucose was measured every 15 min and insulin. C-peptide, glucagon, epinephrine, norepinephrine, growth hormone and cortisol every 30 min for 5 h. During insulin infusion somewhat higher concentrations of the hormone were obtained in the hypothyroid state and simultaneously glucose levels were 0.5 mmol/l lower. As expected, basal norepinephrine levels were higher in hypothyroidism. However, no increase in circulating norepinephrine during hypoglycaemia was registered in the two experiments. The responses of counterregulatory hormones showed an enhanced response of cortisol, similar responses of growth hormone and epinephrine while the glucagon response was paradoxically impaired. Our findings suggest that hypothyroidism alters insulin metabolism, and that the glucagon response to hypoglycaemia is impaired in this condition.

Topics: Adult; Blood Glucose; Blood Pressure; C-Peptide; Epinephrine; Female; Glucagon; Growth Hormone; Humans; Hydrocortisone; Hypothyroidism; Insulin; Male; Middle Aged; Norepinephrine; Pulse

Immunoreactive insulin (IRI) and C-peptide secretory responses to terbutaline, glucagon, glucose and a standardized meal during continuous blood glucose monitoring were investigated in hyper- and hypothyroid patients before and after treatment. The beta 2-adrenoceptor agonist terbutaline (125 micrograms IV) induced prompt IRI and C-peptide responses in hyperthyroid patients. On the contrary, in the hypothyroid, no insulin or C-peptide responses were seen despite a slight enhancement of blood glucose concentrations. Thyroxine treatment of these patients improved the IRI and C-peptide responses and no blood glucose increment was then seen. Glucagon (250 micrograms IV) induced prominent IRI and C-peptide responses of similar magnitude in hyper- and hypothyroid patients before as well as after treatment. Before treatment, the blood glucose increment was greater in the hypothyroid patients than in the hyperthyroid but after treatment no difference between the 2 groups was seen. After a small load of glucose (6 g IV) no apparent difference in glucose tolerance was seen between hyper- and hypothyroid patients. However, the hyperthyroid patients had greater IRI and C-peptide responses to glucose than the hypothyroid but the differences diminished after treatment. Before treatment, hypothyroid patients had lower blood glucose response to a meal intake than hyperthyroid patients but no differences were seen between the 2 patient groups with regard to IRI- and C-peptide responses. After treatment, no differences between the 2 groups were seen with regard to blood glucose, IRI or C-peptide responses to the meal.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Antithyroid Agents; Blood Glucose; C-Peptide; Eating; Female; Glucagon; Glucose; Humans; Hyperthyroidism; Hypothyroidism; Insulin; Insulin Secretion; Iodine Radioisotopes; Male; Middle Aged; Secretory Rate; Terbutaline; Thyroid Hormones; Thyroxine