Lowest Glucagon/Highest C-Peptide in Oral Glucose Tolerance Test: Clinical Utility in Monitoring Glucose Control in Type 2 Diabetes Mellitus.

Purpose: Understanding factors that influence blood glucose levels in patients with type 2 diabetes mellitus (T2DM) is crucial for managing hyperglycemia. Currently, there is no standardized interpretation method for glucagon levels in oral glucose tolerance test (OGTT). This study aims to assess the relationship between the lowest glucagon/highest C-peptide ratio (Lglc/Hcp) in OGTT and glucose control levels in T2DM. Patients and Methods: Clinical data from 120 patients with T2DM were examined to compare the correlations of Lglc/Hcp and other pancreatic islet function-associated indices with fasting blood glucose (G0), glucose at 120 minutes in OGTT (G120), hemoglobin A1c (HbA1c), and the area under the glucose curve in OGTT (AUCglu). Additionally, the study investigated difference in Lglc/Hcp between patient groups based on the highest blood glucose levels (Hglu) in OGTT (Hglu ≥ 16.7 mmol/L vs Hglu < 16.7 mmol/L). Results: The generalized linear model suggested that Lglc/Hcp significantly correlated with G0 (B = 0.85, P < 0.001), G120(B = 1.46, P < 0.001), HbA1c (B = 0.67, P < 0.001), and AUCglu (B = 3.46, P < 0.001). This correlation surpassed C-peptide and glucagon-related parameters, even after adjusting for confounding factors. Furthermore, Lglc/Hcp was notably higher in patients with Hglu ≥ 16.7 mmol/L compared to those with Hglu < 16.7 mmol/L (Z = -3.71, p < 0.001). Conclusion: Lglc/Hcp in OGTT closely relates to blood glucose control in patients with T2DM, potentially reflecting the overall pancreatic islet function in regulating glucose levels. Moreover, inhibiting glucagon secretion may be a crucial consideration for patients requiring insulin treatment.

Distinct serum steroid profiles between adrenal Cushing syndrome and Cushing disease.

Background: Differentiating between adrenal Cushing syndrome (adrenal CS) and Cushing disease (CD) can be challenging if there are equivocal or falsely elevated adrenocorticotropic hormone (ACTH) values. We aim to investigate the diagnostic value of serum steroid profiles in differentiating adrenal CS from CD. Method: A total of 11 serum steroids in adrenal CS (n = 13) and CD (n = 15) were analyzed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Age- and gender-specific steroid ratios were generated by dividing the actual steroid concentration by the upper limit of the relevant reference range. A principal component analysis (PCA) and an orthogonal partial least squares discriminant analysis (OPLS-DA) were performed. Results: The PCA and OPLS-DA analyses showed distinct serum steroid profiles between adrenal CS and CD. Dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), and androstenedione ratios were identified as biomarkers for discrimination by variable importance in projection (VIP) in combination with t-tests. The sensitivity and specificity of DHEA-S ratios <0.40 were 92.31% (95% CI 64.0%-99.8%) and 93.33% (95% CI 68.1%-99.8%), respectively, in identifying adrenal CS. The sensitivity and specificity of DHEA ratios <0.18 were 100% (95% CI 75.3%-100.0%) and 100% (95% CI 78.2%-100.0%), respectively, in identifying adrenal CS. Conclusion: Our data support the clinical use of the DHEA-S and DHEA ratios in the differential diagnosis of adrenal CS and CD, especially when falsely elevated ACTH is suspected.

Effect of hypercortisolism on bone mineral density and bone metabolism: A potential protective effect of adrenocorticotropic hormone in patients with Cushing's disease.

Objective To investigate the effects of Cushing's disease (CD) and adrenal-dependent Cushing's syndrome (ACS) on bone mineral density (BMD) and bone metabolism. Methods Data were retrospectively collected for 55 patients with hypercortisolism (CD, n = 34; ACS n = 21) from January 1997 to June 2014. BMD was examined in all patients, and bone turnover markers were tested in some patients. Healthy controls (n = 18) were also recruited. Results The lumbar spine and femoral neck BMD were significantly lower in the ACS and CD groups than in the control group. Lumbar BMD was significantly lower in the ACS than CD group. The collagen breakdown product (CTX) concentrations were significantly higher while the osteocalcin and procollagen type I N-terminal propeptide (PINP) concentrations were significantly lower in the ACS and CD groups than in the control group. The PINP concentration was significantly lower while the CTX concentration was significantly higher in the ACS than CD group. In the CD group only, lumbar BMD and serum adrenocorticotropic hormone had a significant positive correlation. Conclusions Bone turnover markers indicated suppressed osteoblast and enhanced osteoclast activities. PINP and CTX changes might indicate bone mass deterioration. Adrenocorticotropic hormone might be protective for lumbar BMD in patients with CD.

Symptomatic Cushing syndrome and hyperandrogenemia revealing steroid cell ovarian neoplasm with late intra-abdominal metastasis.

BACKGROUND: Steroid cell tumors of ovary account for less than 0.1% of all ovarian tumors and these tumours may present at any age in association with interesting presentations related to hormonal activities. The subtype, not otherwise specified (NOS), is associated with androgenic changes in 56-77% and Cushing syndrome in 6-10%. Due to the rarity of available data regarding these tumors, little is known about their malignant potential and metastatic behaviour. We hereby report an unusual metastasis of steroid cell ovarian neoplasm presented with both Cushing syndrome and hyperandrogenemia. CASE PRESENTATION: A 31-year-old woman, who had a past medical history of ovarian tumor resection (left ovarian thecoma was initially diagnosed at that time), presented with hirsutism, hypertension and menstrual disorder. Also, laboratory work-up revealed hypercortisolism and androgen excess. Computerized tomography (CT) of the abdomen showed abdominal paraaortic masses, multiple intrahepatic nodules and retroperitoneal lymph nodes enlargement. Positron emission tomography/computed tomography (PET/CT) scan demonstrated metastatic lesions. Her ovarian tumor sections were re-examined and pathology result was corrected to steroid cell tumor (NOS) associated with active cell growth and necrosis. Subsequent excision of metastatic lesions yielded clinical improvement promptly and metastasis of steroid cell tumor was confirmed by postoperative pathological studies. However, one year after the surgical management of metastasis, recurrence happened while radiotherapy was ineffective. The patient finally died of tumor metastatic recurrence. CONCLUSION: This case reports a rare coexistence of Cushing syndrome and hyperandrogenemia which occurs based on metastasis of steroid cell ovarian neoplasm. It presents a real diagnostic challenge to both clinicians and pathologists. Therefore, it is very important to establish a final diagnosis by pathological studies along with clinical manifestations and imaging findings. Besides, it is necessary to improve follow-up of patients with this kind of tumors.