The diagnostic value of late-night salivary cortisol for diagnosis of subclinical Cushing's syndrome.

INTRODUCTION: Late-night salivary cortisol is a frequently used and easily implemented diagnostically valuable test for the diagnosis of overt Cushing's syndrome. The use of late-night salivary cortisol in the diagnosis of subclinical Cushing's syndrome is somewhat controversial. In this study, we aimed to determine the diagnostic value of late-night salivary cortisol in diagnosing subclinical Cushing's syndrome and compare it with 24-hour urinary free cortisol levels (UFC). MATERIAL AND METHODS: The study consisted of 33 cases of subclinical Cushing's syndrome, 59 cases of non-functioning adrenal adenoma, and 41 control subjects. Late-night salivary cortisol and UFC were measured in all the cases. The diagnosis of subclinical Cushing's syndrome was based on combined results of 1 mg dexamethasone suppression test > 1.8 µg/dL and ACTH < 10 pg/mL. RESULTS: Mean late-night salivary cortisol levels in subjects with subclinical Cushing's syndrome were significantly higher than in subjects with non-functioning adrenal adenoma and the control group (p < 0.001). Using a cut-off value of 0.18 µg/dL, the sensitivity and specificity of late-night salivary cortisol for diagnosing subclinical Cushing's syndrome were determined as 82% and 60%, respectively. Using a cut-off value of 137 µg/day, the sensitivity and specificity of UFC was determined as 18% and 90%, respectively. CONCLUSIONS: Because the sensitivity of late-night salivary cortisol for the diagnosis of subclinical Cushing's syndrome is limited, using it as the sole screening test for subclinical Cushing's syndrome may lead to false negative results. However, using it as an adjunct test to other tests may be beneficial in the diagnosis of subclinical Cushing's syndrome. (Endokrynol Pol 2016; 67 (5): 487-492).

IS BIOCHEMICAL ASSESSMENT OF PHEOCHROMOCYTOMA NECESSARY IN ADRENAL INCIDENTALOMAS WITH MAGNETIC RESONANCE IMAGING FEATURES NOT SUGGESTIVE OF PHEOCHROMOCYTOMA?

OBJECTIVE: Currently, it is unclear whether pheochromocytomas can be ruled out based on low intensity on T2-weighted sequences and signal loss on out-of-phase magnetic resonance imaging (MRI) sequences. Hence, in this study, we investigated whether biochemical screening for pheochromocytoma in patients with adrenal incidentalomas (AIs) showing MRI features not suggesting pheochromocytoma would prove beneficial. METHODS: We performed MRI for 300 AIs in 278 consecutive patients. All patients were screened for pheochromocytoma with plasma metanephrine and normetanephrine. Patients with high plasma levels of metanephrine and/or normetanephrine were also assessed for pheochromocytoma by urinary metanephrines. RESULTS: Hyperintensity was detected on T2-weighted MRI sequences in 28 (9.3%) of the 300 AIs. Among these 28 incidentalomas, pheochromocytoma was diagnosed in 13 (46.4%) of the cases by histopathologic analysis. Hyperintensity on T2-weighted MRI was significantly higher in pheochromocytomas compared to the remaining AIs (P<.001). All 13 pheochromocytomas were characterized by hyperintensity on T2-weighted sequences and the absence of signal loss on out-of-phase MRI sequences. Pheochromocytoma was not detected in any of the 272 AIs that appeared hypointense or isointense on T2-weighted MRI sequences or in the 250 cases with signal loss on out-of-phase sequences. CONCLUSION: The results of this study suggest that AIs that appear hypointense or isointense on T2-weighted MRI sequences and those with signal loss on out-of-phase sequences may not require routine biochemical screening for pheochromocytoma. Further studies including a higher number of pheochromocytomas are required to confirm our results.

Expression of voltage gated potassium channel ether à go-go in pituitary adenomas of patients with acromegaly: A preliminary study.

OBJECTIVE: To determine immunohistochemical expression of Eag1 in pituitary adenomas of patients with acromegaly and to assess the correlation between Eag1 expression with cavernous sinus invasion, tumoral Ki-67 labeling index (LI), age and gender of the patients. METHODS: The paraffin embedded pituitary adenoma tissue sections of 28 patients with acromegaly who were diagnosed as monohormonal growth hormone (GH) secreting adenomas were immunostained for Eag1 using the avidin-biotin-peroxidase complex method. Eag1 immunoreactivity was scored according to the extensity of the cytoplasm and cell membrane immunoreactivity for Eag1 (score 1 = <10%, score 2 = 10-25%, score 3 = 25-50% and score 4 = >50% of the adenoma cells showed immunoreactivity for Eag1, respectively). RESULTS: Overall, GH secreting pituitary adenomas displayed diverse levels of Eag1 immunoreactivity, however, 64% of the adenomas displayed a strong Eag1 immunoreactivity (score 3 and 4). Five of the tumors displayed Eag1 immunoreactivity score 1, 5 displayed score 2, 10 displayed score 3 and 8 displayed score 4, respectively. No correlation was found between Eag1 immunoreactivity with cavernous sinus invasion, Ki-67 LI, age and gender of the patients. CONCLUSIONS: Our results suggest Eag1 is strongly expressed in the majority of GH secreting pituitary adenomas. However, we could not find any correlation between immunoreactivity of Eag1 with cavernous sinus invasion, Ki-67 LI, age and gender of the patients. Further studies with larger sample sizes are required to demonstrate the role of Eag1 on tumorigenesis, angiogenesis, invasion and response to the treatment in GH secreting pituitary adenomas.

Anterior pituitary hormone deficiency in subjects with total and partial primary empty sella: do all cases need endocrinological evaluation?

AIM: To compare anterior pituitary functions between subjects with total and partial primary empty sella (PES) and to assess whether all cases with PES need endocrinological evaluation. MATERIAL AND METHODS: Eighty-one subjects with PES (34 total and 47 partial) were included in the study. Basal anterior pituitary and its target hormones were assessed and those with low insulin like growth factor-1 and/or low basal cortisol levels underwent insulin tolerance test (ITT). RESULTS: 67.4% of the subjects with total and 14.9% of those with partial PES had different degrees of hypopituitarism. However, the frequency of hypopituitarism was significantly higher in cases with total PES. The odds ratio (OR) and 95% confidence interval (CI) of secondary hypothyroidism, secondary adrenal, growth hormone and gonadotropin deficiency in subjects with total compared to those with partial PES were as follows: OR = 20.0, 95% CI 4.16 - 95.9, OR = 2.4, 95% CI 1.34 - 5.7, OR = 15.3, 95% CI 4.48 - 52.6 and OR = 10.6, 95% CI 3.37 - 33.5, respectively. CONCLUSION: A substantial number of subjects with PES, particularly those with total PES, have pituitary hormone deficiency, so regardless of the type of PES, all subjects must be promptly and carefully evaluated for anterior pituitary hormone deficiency.

The relationship between low maternal serum 25-hydroxyvitamin D levels and gestational diabetes mellitus according to the severity of 25-hydroxyvitamin D deficiency

OBJECTIVE: To assess the relationship between low maternal serum 25-hydroxyvitamin D levels and gestational diabetes mellitus in Turkish pregnant women according to the severity of 25-hydroxyvitamin D deficiency and assess intact parathyroid hormone levels in women with gestational diabetes mellitus and controls with low and sufficient 25-hydroxyvitamin D levels. METHODS: We analyzed serum 25-hydroxyvitamin D and intact parathyroid hormone levels in 234 women with gestational diabetes mellitus and 168 controls. To define the deficiency status, 25-hydroxyvitamin D levels were further classified into severely deficient, deficient, insufficient and sufficient groups. RESULTS: Women with gestational diabetes mellitus had significantly lower 25-hydroxyvitamin D levels compared to controls (30.8±16.3 vs. 36.0±16.2 nmol/L). However, when subgroups of 25-hydroxyvitamin D were analyzed, gestational diabetes mellitus was significantly more common only in women with severely deficient 25-hydroxyvitamin D levels. After adjusting for covariates, only severely deficient 25-hydroxyvitamin D levels were independently associated with an increased relative risk of gestational diabetes mellitus. The relative risk of gestational diabetes mellitus in women with insufficient and deficient 25-hydroxyvitamin D levels was not statistically significant. Intact parathyroid hormone concentrations were also significantly higher in women with gestational diabetes mellitus compared to the controls (45.3±26.2 vs. 38.7±27.6 pg/ml). CONCLUSIONS: The results obtained from this study provide novel data indicating that only severely deficient maternal serum 25-hydroxyvitamin D levels are significantly associated with an elevated relative risk of gestational diabetes mellitus, even after adjusting for established risk factors of gestational diabetes mellitus. .