c-peptide and Hypopituitarism

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

GH treatment (GHT) can lead to glucose metabolism impairment through decreased insulin sensitivity and impaired pancreatic β-cell function, which are the two key components of the pathogenesis of diabetes. Therefore, in addition to insulin sensitivity, during GHT it is very important to perform a reliable evaluation of insulin secretion. However, conflicting data exist regarding the insulin secretion in children during GHT. C-peptide provides a more reliable estimate of β-cell function than insulin, but few studies evaluated it during GHT. Our aim was to assess the usefulness of C-peptide in the evaluation of insulin secretion in GH deficiency (GHD) children.. In 48 GHD children, at baseline and after 12 and 24months of GHT, and in 56 healthy subjects we evaluated fasting and glucagon-stimulated (AUCCpep) C-peptide levels in addition to other commonly used secretion indexes, such as fasting and oral glucose tolerance test-stimulated insulin levels (AUCINS), Homa-β, and insulinogenic index. The main outcomes were the change in C-peptide during GHT and its correlation with the auxological and hormonal parameters.. At baseline GHD children showed a significant lower AUCCpep (p=0.006), while no difference was found for the other indexes. Both fasting C-peptide (beta 0.307, p=0.016) and AUCCpep (beta 0.379, p=0.002) were independently correlated with IGF-I SDS, while no correlation was found for all other indexes. After 12months an increase in Homa-β (p<0.001), fasting C-peptide (p=0.002) and AUCCpep (p<0.001) was found. At multivariate analysis, only fasting C-peptide (beta 0.783, p=0.001) and AUCCpep (beta 0.880, p<0.001) were independently correlated with IGF-I SDS.. C-peptide, rather than the insulin-derived indexes, has proved to be the most useful marker of insulin secretion correlated to IGF-I levels in GHD children. Therefore, we suggest the use of glucagon test both as diagnostic test for the GH assessment and as a useful tool for the evaluation of insulin secretion during GHT in children.

Topics: Area Under Curve; C-Peptide; Case-Control Studies; Child; Child, Preschool; Fasting; Female; Glucagon; Glucose Tolerance Test; Hormones; Human Growth Hormone; Humans; Hypopituitarism; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Like Growth Factor I; Insulin-Secreting Cells; Male; Prospective Studies

An infant diagnosed as having hypopituitarism and on adequate hydrocortisone replacement therapy was referred to a tertiary endocrine unit at 5 weeks of age with persistent hypoglycemia that required a high rate of intravenous glucose infusion (up to 18 mg/kg•min⁻¹) to maintain euglycemia.. A controlled hypoglycemia screen was performed to measure levels of plasma glucose, insulin, C-peptide and 3-β-hydroxybutyrate concentrations. The pancreas was analyzed by fluorine-18-L-3,4-dihydroxyphenylalanine ((18)F-DOPA) PET scan. Genetic analyses were performed on the peripheral blood leukocytes, and loss of heterozygosity within the resected focal lesion of the pancreas was investigated by microsatellite analysis. A glucagon stimulation test helped determine pituitary function, and an MRI of the brain and pituitary gland was performed to define the anatomy of the intracranial structures and the pituitary gland.. Focal form of congenital hyperinsulinism localized to the head of the pancreas, septo-optic dysplasia and pituitary hormone deficiencies.. Resection of the focal lesion from the head of the pancreas and hormonal replacement therapy for hypopituitarism.

Topics: 3-Hydroxybutyric Acid; Blood Glucose; C-Peptide; Congenital Hyperinsulinism; Glucagon; Glucose; Humans; Hydrocortisone; Hypopituitarism; Infant; Insulin; Loss of Heterozygosity; Male; Pancreas; Pituitary Hormones; Septo-Optic Dysplasia

The conventional dosage of hydrocortisone, used for many years in the management of hypopituitarism (30 mg per day), has now been shown to be more than is physiologically necessary. On this conventional corticosteroid therapy studies have demonstrated an increased prevalence of diabetes and impaired glucose tolerance, which may contribute to the increased vascular morbidity and mortality reported in the condition. In these studies no information is available on oral glucose tolerance test (OGTT) timing in relation to administration of oral steroid and variable hydrocortisone doses were employed.. In order to assess glucose tolerance in patients treated with lower, more physiological doses, we performed a 75-g OGTT at least 1 month after hydrocortisone therapy was adjusted to 15 mg at 0800 h and 5 mg at 1700 h in 45 adult onset hypopituitary patients (30 M, 15 F). Mean (+/- SD) duration of hypopituitarism was 12 +/- 10 years, mean age 52 +/- 14 years and BMI 29.3 +/- 5.1 kg/m2. All were on hydrocortisone, 43 on thyroxine, 31 on sex steroids, 9 on desmopressin and 33 had documented growth hormone deficiency. Hydrocortisone 15 mg was taken at 0800 and the OGTT commenced at 0900.. Using standard WHO criteria 36 patients (80%) had normal glucose tolerance, 1 (2%) had newly diagnosed diabetes and 8 (18%) had impaired glucose tolerance. Using the recently announced American Diabetes Association criteria for diagnosis 96% had normal glucose tolerance, 2% had diabetes and 2% impaired fasting glucose.. The markedly reduced prevalence of diabetes and impaired glucose tolerance on lower hydrocortisone replacement doses in our series of patients with hypopituitarism, not previously known to be diabetic, is of great interest. This lower prevalence may eventually result in reduced vascular complication rates.

Topics: Adult; Aged; Aged, 80 and over; C-Peptide; Diabetes Mellitus; Drug Administration Schedule; Female; Glucose Tolerance Test; Humans; Hydrocortisone; Hypopituitarism; Insulin; Male; Middle Aged; Statistics, Nonparametric

At present, the duration of the effect of recombinant human growth hormone (rhGH) on the rates of protein synthesis and lipolysis in GH deficient (GHD) adults is unknown. This study was designed to establish the frequency of rhGH administration necessary to provide the beneficial metabolic effects of the hormone in GHD adults.. Two different studies (A and B) were performed in two groups of five GHD men. In study A, whole body protein and lipid kinetics was determined in the basal state (Bas), 12 (GH12h) and 36 (GH36h) h after the last of seven injections of rhGH (3.3 microg/kg), given at bedtime on alternate days. In study B, the same parameters were determined in the basal state (Bas), 60 (GH60h) and 84 (GH84h) h after the last of seven injections of rhGH (3.3 microg/kg), given at bedtime at 3 day intervals.. The rates of protein metabolism were estimated by infusing [1-13C]leucine, and those of lipolysis by infusing [1,1,2,3, 3-D5]glycerol.. Leucine oxidation decreased (P < 0.01) by approximately 30% after GH12h and GH36h but did not change after GH60h and GH84h. Non-oxidative leucine disposal increased after GH12h and GH36h by approximately 13% (P < 0.05) whereas it did not change after GH60h and GH84h. Glycerol appearance increased (P < 0. 01) by approximately 45% after GH12h and GH36h but did not change after GH60h and GH84h.. The effects on protein and lipid metabolism following the injection of rhGH last longer than 36 and less than 60 h. In fact, rhGH administration on alternate days induced a sustained increase in the rates of protein synthesis and lipolysis of GHD adults, whereas a longer interval of administration (3 days) had no effect by 60 h.

Topics: Adult; Analysis of Variance; Blood Glucose; C-Peptide; Drug Administration Schedule; Glycerol; Growth Hormone; Humans; Hypopituitarism; Insulin; Insulin-Like Growth Factor I; Leucine; Lipid Metabolism; Lipolysis; Male; Protein Biosynthesis; Time Factors

The diagnosis of hypoglycemia caused by hyperinsulinism may be difficult because insulin levels are not uniformly elevated at the time of hypoglycemia. Insulin-like growth factor binding protein-1 (IGFBP-1) is a 28 kd protein whose secretion is acutely inhibited by insulin. We hypothesized that serum levels of IGFBP-1 would be a useful marker of hyperinsulinism. We measured IGFBP-1 levels during the course of standardized fasting studies in hospitalized children; 36 patients became hypoglycemic during the fasting studies, and samples obtained at the point of hypoglycemia were analyzed. On the basis of the currently used diagnostic criteria, 13 children had hyperinsulinism, 16 had ketotic hypoglycemia or no disorder, 3 had hypopituitarism or isolated growth hormone deficiency, 2 had glycogen storage disease type 1 and 2 had fatty acid oxidation disorders. In control subjects (children with ketotic hypoglycemia or no disorder), IGFBP-1 levels rose during fasting to a mean of 343.8 +/- 71.3 ng/ml in the sample drawn at the time of hypoglycemia. Mean IGFBP-1 levels at hypoglycemia for the entire group with hyperinsulinism were 52.4 +/- 11.5 ng/ml, significantly different from levels seen in control subjects (p < 0.0001). In children with moderately controlled hyperinsulinism (fasting tolerance > 4 hours), mean IGFBP-1 levels at the time of hypoglycemia were 71.5 +/- 16.9 ng/ml. IGFBP-1 levels in the children with poorly controlled hyperinsulinism (fasting tolerance < 4 hours) failed to rise during fasting, with a mean of 30.1 +/- 10.4 ng/ml in the final sample. IGFBP-1 levels were inversely correlated with serum insulin and C-peptide levels (r = -0.71 and -0.72, respectively; p < 0.0001). Patients with other endocrinologic or metabolic diseases that result in fasting hypoglycemia demonstrated a rise in IGFBP-1 levels similar to that seen in ketotic hypoglycemia. Low serum levels of IGFBP-1 at the time of hypoglycemia provide an additional marker of insulin action that might help to differentiate hyperinsulinism from other hypoglycemic disorders.

Topics: Adolescent; Biomarkers; C-Peptide; Child; Child, Preschool; Fasting; Fatty Acids; Female; Glycogen Storage Disease Type I; Human Growth Hormone; Humans; Hyperinsulinism; Hypoglycemia; Hypopituitarism; Infant; Infant, Newborn; Insulin; Insulin-Like Growth Factor Binding Protein 1; Ketosis; Lipid Metabolism, Inborn Errors; Male

Hypopituitarism is associated with reduced lean body mass and increased body fat, while in acromegaly the converse is true. Fasting plasma glucose is increased in acromegaly but fasting plasma insulin and C-peptide are increased in both groups. There is a positive association between fat mass and fasting serum insulin in hypopituitarism, suggesting insulin resistance. Hypoglycaemia unresponsiveness, rather than insulin sensitivity, is the feature of growth hormone deficiency. Basal metabolic rate (expressed per kg body weight) is increased in acromegaly and decreased in hypopituitarism but when expressed 'per kg lean body mass', is increased in both groups. There is a close correlation between fat mass and fasting free fatty acid and glycerol levels in obese but not normal weight patients with hypopituitarism; slim patients appear to metabolise and oxidise their fat stores more effectively than those who remain obese. Thus indirect evidence suggests that growth hormone has an important role in maintaining normal body composition and energy stores.

Topics: Acromegaly; Adipose Tissue; Adult; Basal Metabolism; Blood Glucose; Body Composition; Body Weight; C-Peptide; Female; Humans; Hypopituitarism; Insulin; Insulin-Like Growth Factor I; Male

We tested the hypotheses that growth hormone, cortisol, or both are involved in defense against but are not critical to recovery from prolonged hypoglycemia and that the putative roles of these hormones in defense against prolonged hypoglycemia are permissive rather than direct. To do so we studied control subjects (n = 10) and patients with growth hormone and cortisol deficiencies resulting from hypopituitarism both in the untreated state (n = 7) and with prestudy and basal intrastudy growth hormone and cortisol replacement (n = 6). Postabsorptive plasma glucose, insulin, glucagon, and epinephrine concentrations were no different in the untreated patients and controls. Twelve-hour insulin infusions, in low doses adjusted over the 1st 2 h to produce plasma glucose concentrations of 3.6 mmol/l (65 mg/dl) and then fixed at that dose, resulted in significantly (P less than 0.0001) lower late plasma glucose concentrations in the patients, without and with replacement. The 12-h plasma glucose concentrations were 2.9 +/- 0.1 mmol/l (53 +/- 1 mg/dl) in the control subjects, 2.4 +/- 0.1 mmol/l (43 +/- 2 mg/dl; P less than 0.001 vs. control) in the deficient patients, and 2.5 +/- 0.1 mmol/l (45 +/- 2 mg/dl; P less than 0.01 vs. control) in the replaced patients. Rates of glucose recovery from hypoglycemia after discontinuation of insulin were identical in all three studies. Thus growth hormone, cortisol, or probably both play a demonstrable role in defense against prolonged, in contrast to short-term, hypoglycemia in humans. This does not appear to be the result of permissive actions of the hormones and is therefore best attributed to their increments during hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Circadian Rhythm; Epinephrine; Fatty Acids, Nonesterified; Glucagon; Growth Hormone; Homeostasis; Humans; Hydrocortisone; Hypopituitarism; Insulin; Norepinephrine; Recombinant Proteins; Reference Values

Nineteen normal male volunteers underwent a 10-h glucose clamp study to examine the duration and mechanism of insulin resistance after hypoglycaemia. Dextrose delivery by the Biostator to maintain the target blood glucose level fell below baseline 2 h after induction of hypoglycaemia and remained suppressed for at least 7 h after insulin hypoglycaemia. Insulin secretion as manifested by C-peptide levels remained suppressed for 3-4 h after insulin hypoglycaemia despite return of blood glucose to baseline by 90 min. Glucose kinetic data (3-3H-glucose) performed in six of the subjects indicated that the prolonged insulin resistance was due to significantly increased hepatic glucose production and to suppressed glucose utilisation, persisting for at least 4 h after counterregulatory hormone levels had returned to normal. Post-hypoglycaemic insulin resistance as determined by dextrose delivery was markedly attenuated and the rise in hepatic glucose output totally eliminated in five hypopituitary subjects without growth hormone or cortisol responses to hypoglycaemia. We conclude that post-hypoglycaemic insulin resistance occurs in non-diabetic subjects and persists for at least 7 h following hypoglycaemia. This prolonged insulin resistance is largely related to release of growth hormone and cortisol.

Topics: Adult; C-Peptide; Glucose; Humans; Hypoglycemia; Hypopituitarism; Insulin; Insulin Resistance; Male; Time Factors

Three women with insulin-dependent diabetes mellitus (IDDM) from childhood and early development of diabetic retinopathy are described. Insulin requirement was reduced to 5-12 IU daily in all three after relatively uncomplicated births and all had very brittle diabetes on this dosage. At re-examination 16-22 years after these births and after 34-42 years of IDDM, regression of retinopathy was observed in two patients, while the third had a light retinopathy at the same level as initially. Other diabetic complications were few and none of the patients had nephropathy. Pituitary examination revealed incomplete hypopituitarism in all cases, human growth hormone (HGH) being the sole common factor lacking. These findings and a review of four similar cases reported previously lend some support to the hypothesis of HGH as a possible pathogenetic co-determinant in the development of diabetic retinopathy.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Female; Humans; Hypopituitarism; Middle Aged; Pituitary Function Tests; Pituitary Hormones, Anterior; Remission, Spontaneous; Thyroid Hormones; Time Factors