Gulsah Elbuken

Investigation of insulin resistance in patients with normocalcemic primary hyperparathyroidism.

While derangements in glucose metabolism in patients with primary hyperparathyroidism are well-defined, this issue is not investigated in patients with normocalcemic primary hyperparathyroidism (NPHPT). The aim of this study was to investigate the presence of insulin resistance in patients with NPHPT. Eighteen patients with NPHPT (two males and 16 females) and 18 healthy volunteers were enrolled into the study. Secondary causes of parathyroid hormone elevations were excluded in all patients. Blood samples were obtained for the measurement of serum calcium, phosphate, alkaline phosphatase (ALP), albumin, creatinine, glucose, and serum lipid levels. Glucose and insulin responses to oral glucose tolerance test (OGTT) were obtained. Homeostasis model assessment (HOMA-IR) was also used as an indice of insulin resistance. Patients and control subjects had similar age, body mass index, and sex distribution. Although within normal limits, serum calcium and ALP levels were higher in patients than in the control subjects. None of the patients and the control subjects had diabetes mellitus, while eight patients and six control subjects had impaired glucose tolerance. Insulin responses to OGTT and HOMA-IR were not significantly different among the patient and control subjects. In addition, both groups have similar serum lipid levels. Patients with NPHPT do not exhibit insulin resistance and glucose intolerance. Since so little is known about this form of disease, subjects should be monitored regularly for the metabolic aspects of the disease as well as the progression of their disease.

Can basal cortisol measurement be an alternative to the insulin tolerance test in the assessment of the hypothalamic–pituitary–adrenal axis before and after pituitary surgery?

BACKGROUND The aims of this study were to evaluate the validity of preoperative basal serum cortisol levels measured in predicting preoperative adrenal insufficiency and also the validity of basal serum cortisol levels and early postoperative insulin tolerance test (ITT) in predicting postoperative adrenal insufficiency. METHODS The study was prospectively designed and included 64 patients who underwent pituitary surgery for conditions other than Cushings disease. An ITT was performed preoperatively, on the 6th postoperative day and at the 1st postoperative month. Basal serum cortisol levels were measured on the 2nd, 3rd, 4th, 5th, and 6th postoperative days. RESULTS Patients with a preoperative basal cortisol level of <165 nmol/l (6 microg/dl) showed insufficient cortisol response and those with levels higher than 500 nmol/l (18 microg/dl) had sufficient cortisol response to the preoperative ITT. The positive predictive value of the ITT performed on the 6th postoperative day was 69.7%, and the negative predictive value in predicting adrenal insufficiency at the 1st postoperative month was 58%. Patients were considered to have an insufficient cortisol response to ITT at the 1st postoperative month if their basal cortisol levels were <193 nmol/l (7 microg/dl) or 220 nmol/l (8 microg/dl) or 193 nmol/l (7 microg/dl) or 165 nmol/l (6 microg/dl) or 83 nmol/l (3 microg/dl) on the 2nd-6th postoperative days respectively. CONCLUSION Serum basal cortisol levels may be used as the first-line test in the assessment of the hypothalamic-pituitary-adrenal axis both preoperatively and postoperatively. Dynamic testing should be limited to the patients with indeterminate basal cortisol levels.

Micronucleus evaluation in mitogen-stimulated lymphocytes of patients with acromegaly

Acromegaly is a syndrome characterized by a sustained elevation of circulating growth hormone and insulin-like growth factor-1 (IGF-1). Insulin-like growth factor-1 is a potent mitogen and has a role in the transformation of normal cells to malignant cells. This study aims to evaluate the spontaneous micronucleus (MN) frequency by using the cytokinesis-block MN assay to determine genetic damage in the lymphocytes of patients with acromegaly. The study was carried out in 20 patients who had active acromegaly and in 20 age- and sex-matched healthy controls. The MN values were measured in binucleated cells obtained from mitogen-stimulated lymphocytes of patients and control subjects. The distribution of binucleated cells with 1, 2, 3, or more MNs was also measured. We found significantly higher MN frequency values in the lymphocytes of acromegalic patients than in those of the control subjects (2.23 ± 0.68 vs 1.03 ± 0.54, P = .001). The MN frequency increased with increasing IGF-1 levels of acromegalic patients (P = .036, R = 0.47). We observed that the number of binucleated cells with 2 MNs was higher for the majority of patients with acromegaly than for control subjects. Furthermore, the receiver operating characteristic curve (area under the curve = 0.914, P < .0001) was calculated to assess the discriminative power of the MN frequency. Our results indicate that increased MN frequency in the lymphocytes of patients with acromegaly may reflect genomic instability and this increased MN frequency may be associated with elevated levels of circulating growth hormone and IGF-1.

Acromegaly is associated with decreased skin transepidermal water loss and temperature, and increased skin pH and sebum secretion partially reversible after treatment.

BACKGROUND Acromegaly is characterized by an acquired progressive somatic disfigurement, mainly involving the face and extremities, besides many other organ involvement. Wet and oily skin was described in acromegaly patients and it was attributed to hyperhidrosis and increased sebum production but this suggestion has not been evaluated with reliable methods. OBJECTIVE The aim of this study was to examine the skin parameters of patients with acromegaly using measurements of skin hydration, sebum content, transepidermal water loss, pH and temperature and particularly the effects of 12 months of treatment on these parameters. METHODS 52 patients with acromegaly and 24 healthy control subjects were included in this two blinded prospective study. Skin properties were measured on forehead and forearm by Corneometer CM825, Sebumeter SM810, Tewameter TM210 and Phmeter PH900 as non-invasive reliable measuring methods. Serum GH, IGF-1 and all measurements of skin properties on forehead and forearm were repeated at the end of the 3, and 6 months of therapy in 20 cases. Patients were treated with appropriate replacement therapy for deficient pituitary hormones. RESULTS The sebum content and pH of the skin of acromegalic patients were significantly higher and transepidermal water loss and skin temperature were found to be significantly lower in acromegalic patients when compared to the control group both on forehead and forearm. GH and IGF-1 levels were positively correlated with sebum levels and negatively correlated with skin temperature on both forehead and forearm. The sebum levels of the patients were significantly decreased both on forehead and forearm at 3rd and 6th months of treatment. CONCLUSION The present study demonstrated increased sebum secretion, decreased transepidermal water loss, alkali and hypothermic skin surface in patients with acromegaly by reliable methods for the first time. These data suggest that GH and/or IGF-I may have a modulatory role on several skin characteristics which can be at least partially reversible with treatment.

The Effects of Gonadotropin Replacement Therapy on Metabolic Parameters and Body Composition in Men with Idiopathic Hypogonadotropic Hypogonadism

Testosterone replacement therapy (TRT) in idiopathic hypogonadotrophic hypogonadism (IHH) slows the process of metabolic syndrome (MetS), diabetes mellitus, and cardiovascular diseases by its inversing effects on insulin resistance, dyslipidemia, and blood pressure. Since there are not enough data regarding the effects of gonadotropin replacement therapy (GRT), we aimed to investigate the impact of GRT on MetS parameters in IHH patients. Sixteen patients with IHH and 20 age and body mass index (BDI)-matched healthy controls were enrolled into the study. Patients were evaluated at baseline and 6 months after the GRT. Sex hormones, insulin like growth factor-1, prolactin, insulin, C-reactive protein (CRP), homocysteine, and lipid levels were measured at baseline and after the treatment. Anthropometric measurements, including BMI, body fat ratio (BFR), fat free mass (FFM), waist circumference, and waist-to-hip ratio (WHR), were also performed. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. Body fat ratio, triglyceride, HOMA-IR, and CRP levels were higher, whereas bone age, fat free mass, and creatinine levels were lower in the patients with hypogonadism. HOMA-IR indices and basal insulin levels decreased significantly after 6 months of GRT compared with baseline levels. Triglyceride levels, and BFRs diminished significantly by an accompanying decline in WHR. FFM of the patients increased following the GRT. No significant changes were detected in CRP, homocysteine, total and LDL-cholesterol levels. Similar to TRT, hCG treatment decreases HOMA-IR, triglyceride levels, BFR and WHRs, and increases FFM in patients with IHH.

Erratum to: Comparison of salivary and calculated free cortisol levels during low and standard dose of ACTH stimulation tests in healthy volunteers

Salivary cortisol (SC) has been increasingly used as a surrogate biomarker of free cortisol (FC) for the assessment of hypothalamo-pituitary-adrenal (HPA) axis, but there are not enough data regarding its use during ACTH stimulation tests. Therefore, we aimed to determine the responses of SC, calculated free cortisol (cFC) and free cortisol index (FCI) to ACTH stimulation tests in healthy adults. Forty-four healthy volunteers (24 men and 20 women) were included in the study. Low-dose (1 µg) and standard-dose (250 µg) ACTH stimulation tests were performed on two consecutive days. Basal and stimulated total cortisol (TC) and cortisol-binding globulin (CBG) levels and SC levels were measured during both doses of ACTH stimulation tests. cFC (by Coolens’ equation) and FCI levels were calculated from simultaneously measured TC and CBG levels. The minimum SC, cFC, FCI levels after low-dose ACTH stimulation test were 0.21, 0.33, 16.06 µg/dL, and after standard-dose ACTH were 0.85, 0.46, 26.11 µg/dL, respectively, in healthy individuals who all had TC responses higher than 20 µg/dL. Peak CBG levels after both doses of ACTH stimulation tests were found to be higher in women than in men. So, by its effect, peak cFC and FCI levels were found to be lower in female than in male group. Neither TC nor SC levels were affected by gender. cFC and FCI levels depend on CBG levels and they are affected by gender. Cut-off levels for SC, cFC, FCI levels after both low- and standard-dose ACTH stimulation are presented. Studies including patients with adrenal insufficiency would be helpful to see the diagnostic value of these suggested cut-off levels.

Evaluation of peripheral blood CD34+ cell count in the acute phase of traumatic brain injury and chest trauma

Abstract Aim: To determine the impact of traumatic brain injury (TBI) and chest trauma (CT) on the number of peripheral blood (PB) stem cells in affected patients in comparison to normal controls. Additionally, the aim was to determine the relationship between CD34+ cell counts and TBI-induced hypothalamus-pituitary-adrenal axis dysfunction in the acute phase of trauma. Patients and method: Thirty patients with TBI, 12 patients with CT and 53 healthy subjects were included in the study. Results: CD34+ cell counts within the first 24–48 hours of TBI were found to be lower than those obtained on the 7th day of TBI and those in the healthy controls. CD34+ cell counts obtained on the 2nd day of CT were lower than those in the healthy group, but did not differ from those measured on the 7th day of CT. There was no correlation between CD34+ cell counts and serum total cortisol (STC) levels on the 2nd and 7th days in the TBI or CT groups. Conclusion: An increase in CD34+ cell counts as observed on the 7th day in both TBI and CT groups suggested that CD34 changes were not specific to TBI. Moreover, this study showed for the first time that CD34 response was not affected by changes in cortisol levels induced by TBI and severity of TBI.

Primary hyperparathyroidism detected in a patient undergoing two prior thyroidectomies for follicular thyroid carcinoma: a case report

Conclusion: PHPT in the presence of thyroid follicular carcinoma is a rare occurrence. Non-visualization of parathyroid tissue by imaging studies in a patient with two prior thyroidectomy operations and RAI therapy makes our case quite an interesting one. Cinacalcet therapy is a good therapeutic option to control calcium levels in cases where excessive secretion of PTH cannot be achieved by surgical intervention. A 57-year-old female patient underwent left total and right subtotal thyroidectomy operations on 18.05.2009 for multinodular goiter. Pathological examination revealed a 5.5 cm follicular carcinoma in the left lobe. Lymphovascular invasion of the tumor was present. On 30.06.2009, she underwent completion thyroidectomy, and central compartment and ipsilateral lateral cervical lymph nodes dissection. Subsequently received ablative therapy with radioactive iodine (RAI) at a dose of 150 mCi. Elevated calcium and reduced phosphorus levels were found during her follow-up visits (Table). While the findings of several tests were consistent with primary hyperparathyroidism, only a slightly echoic, wellcircumscribed lesion (5x5x11 mm) located close to the former place of the inferior pole of the right thyroid gland was detected by neck ultrasound images and its vascularization was shown by Doppler ultrasound (Figure-1). However, no increase in activity or uptake was observed during parathyroid scintigraphy (Figure-2) and neck CT did not show a tumor mass formation. Her serum calcitonin level was normal (Table). The possibility of a thyroid medullary carcinoma was excluded by reexamining of her paraffin-embedded thyroid blocks. The patient who already had undergone two major surgeries and one course of RAI treatment refused another neck operation. Thus, treatment with Cinacalcet was initiated. Calcium values returned to normal after the treatment (Table).

Assessment of the hypothalamic–pituitary–adrenal axis in critical illness

Cortisol is the main corticosteroid secreted from the human adrenal cortex, and it has a crucial role for survival in stressful conditions. An adequate increase in levels of cortisol helps patients to cope with the severity of the disease in the acute phase of critical illness. Either higher or lower than expected cortisol levels were found to be related to increased mortality. Prolonged activation of the hypothalamic–pituitary–adrenal (HPA) axis can result in hypercortisolemia or hypocortisolemia; both can be detrimental to recovery from critical illness. Primary and secondary adrenal insufficiency, relative adrenal insufficiency, tissue resistance to glucocorticoids, adrenocorticotrophic hormone deficiency and immune-mediated inhibition of the HPA axis can be the cause of the impairment of the secretion or action of cortisol in critically ill patients. Recently, some authors offered the term ‘critical illness-related corticosteroid insufficiency’ to better point out the relative adrenal insufficiency that is seen during critical illness. Patients with critical illness-related corticosteroid insufficiency not only have insufficient circulating cortisol but also have impaired cellular utilization of cortisol. In this article, how adrenal dysfunction presents in critical illness and how appropriate diagnosis and management can be achieved in the critical care setting will be discussed.