c-peptide and Thyrotoxicosis

Autoimmune diseases, including autoimmune endocrine diseases (AIED), are thought to develop following environmental exposure in patients with genetic predisposition. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and vaccines against it could represent new environmental triggers for AIED. We report a patient, with history of vitiligo vulgaris and 8 years of type 2 diabetes, who came to our institution because of fever, weight loss, asthenia and thyrotoxicosis occurred 4 weeks later the administration of BNT162B2 (Pfizer-BioNTech) SARS-CoV-2 vaccine. Clinical, biochemical and instrumental work-up demonstrated Graves' disease and autoimmune diabetes mellitus. The occurrence of these disorders could be explained through different mechanism such as autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome), mRNA "self-adjuvant" effect, molecular mimicry between human and viral proteins and immune disruption from external stimuli. However further studies are needed to better understand the underlying pathogenesis of AIED following SARS-CoV-2 vaccine.

Topics: Adjuvants, Immunologic; Autoantibodies; BNT162 Vaccine; C-Peptide; COVID-19; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycemic Control; Graves Disease; Humans; Male; Middle Aged; Molecular Mimicry; SARS-CoV-2; Thyrotoxicosis; Vitiligo

Increased thyroid hormone concentrations have been reported to have disparate effects on insulin sensitivity in man. We describe a 72-year-old lady who initially presented with episodic hypoglycemia secondary to an insulinoma that was controlled by diazoxide. She re-presented 12 months later with a recurrence of the hypoglycemia following the development of thyrotoxicosis. The diazoxide treatment was maintained and propranolol was introduced, which prevented further episodes of hypoglycemia. This appeared to be due to a direct effect of propranolol on endogenous insulin secretion, while whole body insulin sensitivity remained unchanged as assessed using the hyperinsulinemic-euglycemic clamp technique. She was later rendered biochemically euthyroid with a combination of blocking carbimazole therapy and thyroxine replacement, and this was associated with a marked decrease in insulin sensitivity. Thus, the principal effect of thyroid hormone excess in this patient was an increase in insulin sensitivity that led to the clinical relapse of the insulinoma.

Topics: Aged; C-Peptide; Diazoxide; Female; Humans; Hypoglycemia; Insulin; Insulin Resistance; Insulinoma; Pancreatic Neoplasms; Propranolol; Recurrence; Thyrotoxicosis

Based largely on evidence of increased target tissue beta-adrenergic receptor densities and responsiveness in animal and, to a lesser extent, human tissues, it is often assumed that thyroid hormone excess results in increased sensitivity to catecholamines in vivo, thus explaining several clinical manifestations of thyrotoxicosis. To test the hypothesis that thyrotoxicosis results in increased target tissue beta-adrenergic receptor densities and correspondingly increased metabolic and hemodynamic sensitivity to epinephrine in vivo, we measured these in 10 normal humans before and after administration of triiodothyronine (100 micrograms daily) for 10 d. Thyrotoxicosis increased beta-adrenergic receptor densities in fat (approximately 60%) and skeletal muscle (approximately 30%). Despite increments in beta-adrenergic receptor densities in these and probably other target tissues, metabolic and hemodynamic sensitivity to epinephrine in vivo was unaltered. An apparently adaptive increase in insulin secretion plausibly explains normal glycemic, glycogenolytic/glycolytic, lipolytic, and ketogenic sensitivity to epinephrine in the thyrotoxic state. In view of this striking homeostatic efficiency of the intact individual, the finding of altered adrenergic receptors, even in relevant target tissues, should not be extrapolated to altered sensitivity to catecholamines in vivo in the absence of direct testing of that hypothesis. With respect to the clinical issue, these data suggest that increased sensitivity to catecholamines does not explain clinical manifestations of thyrotoxicosis in humans.

Topics: 3-Hydroxybutyric Acid; Adipose Tissue; Adult; Blood Glucose; Blood Pressure; C-Peptide; Cyclic AMP; Epinephrine; Fatty Acids, Nonesterified; Female; Heart Rate; Homeostasis; Humans; Hydroxybutyrates; Insulin; Insulin Secretion; Lactates; Lactic Acid; Male; Muscles; Pancreatic Polypeptide; Receptors, Adrenergic, beta; Thyrotoxicosis; Triiodothyronine

Topics: Adult; Aged; Blood Glucose; C-Peptide; Fatty Acids, Nonesterified; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Thyrotoxicosis

The responses in plasma glucose, insulin, C-peptide, glucagon and somatostatin to an oral glucose load were studied in 10 thyrotoxic patients and 10 matched euthyroid controls. The thyrotoxic patients had higher mean fasting plasma glucose (P less than 0.05) and responded to oral glucose with an earlier peak at 30 min which was higher than the corresponding glucose level in the controls (P less than 0.05). Impaired glucose tolerance was found in 3 patients. Fasting insulin and C-peptide levels were normal in the thyrotoxic patients when corrected for the higher glucose levels. Following glucose ingestion, there was no significant difference between the areas under the insulin or C-peptide curves in patients and controls, but Seltzer's insulinogenic index was reduced in the patients (P less than 0.01) suggesting an impaired pancreatic B-cell response to oral glucose. Mean basal glucagon was normal in the thyrotoxic patients. However, while in the controls plasma glucagon became suppressed following glucose ingestion (P less than 0.0001), no significant suppression was found in the patients. In the thyrotoxic patients, mean basal somatostatin was normal, but the area under the somatostatin curve following glucose ingestion was significantly increased (P less than 0.02). Our findings suggest that decreased glucagon suppression and impaired insulin response after glucose ingestion are involved in glucose intolerance in thyrotoxicosis. Enhanced somatostatin responses to oral glucose in thyrotoxicosis may have contributed to the observed impairment in pancreatic B-cell responsiveness.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Somatostatin; Thyrotoxicosis