Krzysztof Lewandowski - Academia.edu (original) (raw)

Papers by Krzysztof Lewandowski

Endocrine connections, 2018

Though insulin resistance (IR) is common in polycystic ovary syndrome (PCOS), there is no agreeme... more Though insulin resistance (IR) is common in polycystic ovary syndrome (PCOS), there is no agreement as to what surrogate method of assessment of IR is most reliable. In 478 women with PCOS, we compared methods based on fasting insulin and either fasting glucose (HOMA-IR and QUICKI) or triglycerides (McAuley Index) with IR indices derived from glucose and insulin during OGTT (Belfiore, Matsuda and Stumvoll indices). There was a strong correlation between IR indices derived from fasting values HOMA-IR/QUICKI, = -0.999, HOMA-IR/McAuley index, = -0.849 and between all OGTT-derived IR indices (e.g. = -0.876, for IRI/Matsuda, = -0.808, for IRI/Stumvoll, and = 0.947, for Matsuda/Stumvoll index, < 0.001 for all), contrasting with a significant ( < 0.001), but highly variable correlation between IR indices derived from fasting vs OGTT-derived variables, ranging from = -0.881 (HOMA-IR/Matsuda), through = 0.58, or = -0.58 (IRI/HOMA-IR, IRI/QUICKI, respectively) to = 0.41 (QUICKI/Stumvoll...

Endocrine, Jan 9, 2017

Copeptin (pre-proAVP) secreted in equimolar amounts with vasopressin closely reflects vasopressin... more Copeptin (pre-proAVP) secreted in equimolar amounts with vasopressin closely reflects vasopressin release. Copeptin has been shown to subtly mirror stress potentially mediated via corticotrophin-releasing hormone. To further test a potential direct interaction of corticotrophin-releasing hormone with copeptin release, which could augment vasopressin effects on pituitary function, we investigated copeptin response to corticotrophin-releasing hormone. Cortisol, adrenocorticotropin and copeptin were measured in 18 healthy controls and 29 subjects with a history of pituitary disease during standard corticotrophin-releasing hormone test. Patients with previous pituitary disease were subdivided in a group passing the test (P1, n = 20) and failing (P2, n = 9). The overall copeptin response was higher in controls than in subjects with pituitary disease (area under the curve, p = 0.04 for P1 + P2) with a maximum increase in controls from 3.84 ± 2.86 to 12.65 ± 24.87 pmol/L at 30 min, p < ...

Secretory products from adipocytes may contribute to deterioration in glycaemic control and incre... more Secretory products from adipocytes may contribute to deterioration in glycaemic control and increased insulin resistance (IR). Retinol-binding protein 4 (RBP-4) may increase IR in mice, with elevated levels in insulin-resistant mice and humans with obesity and type 2 diabetes. However, the mechanisms regulating RBP-4 synthesis remain not fully understood. It is not clear whether short-term glucose-induced hyperglycaemia and hyperinsulinaemia as well as glucocorticosteroid-induced increase in IR might be reflected in alterations in serum RBP-4 levels in humans. In order to investigate this, we measured serum RBP-4, glucose and insulin concentrations during 75.0 gram oral glucose tolerance test (OGTT) - Study 1, as well as before and after oral administration of dexamethasone - Study 2. Both studies included 35 subjects (8 males), age (mean +/- SD) 39.1 +/- 15.6 years, BMI 35.8 +/- 8.7 kg/m(2). Twenty-four of those subjects (5 males), age 38.7 +/- 15.1 years, BMI 34.4 +/- 8.3 kg/m(2), had 75 gram oral glucose tolerance test (OGTT) - Study 1. Blood samples were taken before (0 minutes), and at 60 and 120 minutes of OGTT. 17 subjects (3 males, 4 subjects with type 2 diabetes), age 43.1 +/- 18.1 years, BMI 36.7 +/- 9.0 kg/m(2) underwent screening for Cushing&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease/syndrome (Study 2). Dexamethasone was administered in a dose of 0.5 mg every 6 hours for 48 hours. Fasting serum concentrations of RBP-4, glucose and insulin were assessed before (D0) and after 48 hours of dexamethasone administration (D2). IR was assessed by HOMA in all non-diabetic subjects and in subjects participating in study 1 also by Insulin Resistance Index (IRI), which takes into account glucose and insulin levels during OGTT. Glucose administration resulted in significant increases in insulin and glucose (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). There was, however, no change in RBP-4 concentrations (124.1 +/- 32 mg/ml at 0 minutes, 123 +/- 35 mg/ml at 60 minutes and 126.5 +/- 37.5 mg/ml at 120 minutes of OGTT, p = ns). All subjects in Study 2 achieved suppression of cortisol below 50 nmo/l. Dexamethasone administration resulted in an increase in fasting insulin (from 11.6 +/- 6.8 to 17.1 +/- 7.2 muU/ml; p = 0.003), and an increase in HOMA (from 2.73 +/- 1.74 to 4.02 +/- 2.27; p = 0.015), although without a significant change in RBP-4 levels (119 +/- 26.8 vs. 117.5 +/- 24.8 mg/ml, p = ns). RBP-4 correlated with fasting insulin (r = 0.40, p = 0.025), fasting glucose (r = 0.41, p = 0.02) and HOMA (r = 0.43, p = 0.015), but not with IRI (r = 0.19, p = 0.31). There was, however, only a moderate correlation between HOMA and IRI (r = 0.49 [r(2) = 0.24]; p = 0.006, Spearman rank correlation), while the best correlation was obtained between the product of glucose and insulin levels at 60 min of OGTT and IRI in a non-linear model (r = 0.94 [r(2) = 0.88]; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.00001). In subjects who received dexamethasone, a positive correlation between RBP-4 and HOMA (p = 0.01) was lost after two days of dexamethasone administration (p = 0.61). RBP-4 levels do not change during oral glucose tolerance test or after a dexamethasone-induced increase in insulin resistance. This implies that it is highly unlikely that RBP-4 is involved in short-term regulation of glucose homeostasis in humans and that it responds to short-term changes in insulin resistance. A moderate correlation between RBP-4 and some insulin resistance indices (HOMA) does not exclude the fact that RBP-4 might be one of many factors that can influence insulin sensitivity in humans.

Retinol binding protein-4 (RBP4) is an adipokine reportedly linked to physiological states of ins... more Retinol binding protein-4 (RBP4) is an adipokine reportedly linked to physiological states of insulin resistance and impaired glycaemia. Pregnancy is a physiological state characterised by changes in carbohydrate metabolism and increased insulin resistance. Our aim was to ...

Ginekologia Polska, Jul 1, 2010

A 32-year-old Caucasian was admitted at 14 weeks of gestation with hypotension and weight loss. F... more A 32-year-old Caucasian was admitted at 14 weeks of gestation with hypotension and weight loss. Family members noted that she appeared "tired" prior to pregnancy Past medical history included primary hypothyroidism treated with thyroxine (100 microg/day). She had a healthy daughter aged 2.5 years who had been born small for gestational age. At about 8 weeks of gestation she started to vomit several times a day. She was treated with antiemetics and intravenous fluids. Following discharge she remained nauseated, weak and lightheaded and lost about 8 kg of weight. After readmission she appeared ill and dehydrated, BMI 16.6 kg/m2, BP 90/60 mmHg supine, 70/50 mmHg upright (with faint-like sensation), normal heart sounds, chest clinically clear, abdomen soft and not tender Investigations revealed severe hyponatraemia (sodium 112 mmol/L), normal potassium level 4.3 mmol/L, normal renal function, TSH 1.31 microIU/mL (reference range (RR): 0.27-4.2), freeT4 1.99 ng/dL (RR: 0.93-1.7), freeT3 3.29 pg/mL (RR: 2.57-4.43), anti-TPO antibodies 467 IU/mL (RR: <34)). She was hyperpigmented, hypotensive and hyponatraemic despite rehydration. Cortisol & ACTH, followed by a 250 microg short Synacthen test were requested and revealed peak cortisol response of 17 nmol/L (RR: above 550 nmol/l) as well as high baseline ACTH (969 pg/mL, RR: 0-46 pg/mL). She was started on hydrocortisone and felt tremendously better A diagnosis of Addisons disease was made (in view of hypothyroidism as a part of Autoimmune Polyglandular Syndrome type II). She was discharged on hydrocortisone and fludrocortisone replacement. Further during her pregnancy there was about two-week foetal growth delay. She, however delivered a healthy female infant at 36 weeks of gestation. Conclusions: New onset Addison's disease is rare in pregnancy but may present with prolonged vomiting and weight loss. Therefore adrenal failure should be included in the differential diagnosis of hyperemesis gravidarum.

Neuro Endocrinology Letters, 2011

Objective: As increased frequency of gonadotrophin-releasing hormone (GnRH) pulses is characteris... more Objective: As increased frequency of gonadotrophin-releasing hormone (GnRH) pulses is characteristic for polycystic ovary syndrome (PCOS), we assessed gonadotrophin response to GnRH in women with PCOS with normal and raised androgens and in regularly menstruating controls. Design, patients and methods: The study involved 155 subjects: PCOS, n=121, age (mean±SD) 24.8±5.4 yrs, BMI 24.5±6.0 kg/m2, all with oligo-/amenorrhoea and PCO morphology, and 34 controls. Gonadotrophins were measured in early follicular phase after GnRH stimulation (0, 30 and 60 minutes). Results: Fifty four (41.9%) women with PCOS had androgens (testosterone, androstendione, dihydroepiandrosterone sulphate) within the reference range, and would fulfil the "Rotterdam", but not the Androgen Excess Society PCOS criteria. Baseline and stimulated LH concentrations were higher in PCOS (9.09±5.56 vs 4.83±1.71 IU/l, 35.48±31.4 vs 16.30±6.68 IU/l, 33.86±31.8 vs 13.45±5.2 IU/l, at 0, 30 and 60 min post GnRH, respectively, p<0.0001). An LH/FSH ratio in PCOS increased further after GnRH stimulation. ROC analysis revealed that LH30min/FSH30min >2.11 or LH60min/FSH60min >1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81.3% specificity for diagnosis of PCOS. Both baseline and GnRH-stimulated LH and FSH concentrations were similar in women with PCOS and raised androgens and with androgens within the reference range (p=0.71 and p=0.20 for LH and FSH, respectively). Conclusions: Regardless of their androgen status, women with PCO morphology and oligo-/amenorrhoea have higher baseline and GnRH-stimulated LH concentrations and higher GnRH-stimulated LH/FSH ratio than controls, suggestive of similar underlying mechanism accounting for menstrual irregularities. These observations support validity of PCOS diagnostic criteria based on the Rotterdam consensus.

Clin Endocrinol, 2001

... Selke, G., Melson, AK, Newcomer, JW (1997) Robust leptin secretory responses to dexamethasone... more ... Selke, G., Melson, AK, Newcomer, JW (1997) Robust leptin secretory responses to dexamethasone in obese subjects. Journal of Clinical Endocrinology and Metabolism, 82 32303233. ... G. &amp;amp;amp; Salvador, J. (2000) Relation between leptin and the regulation of glucose ...

Endokrynologia Polska, 2011

Introduction: Polycystic ovary syndrome (PCOS) is characterised by increased frequency of hypotha... more Introduction: Polycystic ovary syndrome (PCOS) is characterised by increased frequency of hypothalamic GnRH pulses leading to a relative increase in LH synthesis by the pituitary. As GnRH stimulation can reveal a relative LH excess, we have endeavoured to assess whether GnRH test might be useful in the diagnosis of PCOS. Material and methods: The study involved 185 subjects: a PCOS group, n = 151, all with oligoor amenorrhoea, aged (mean ± SD) 24.8 ± ± 5.4 years, BMI 24.5 ± 6.0 kg/m 2 ; and regularly menstruating controls, n = 34, aged 26.6 ± 5.0 years, BMI 24.6 ± 5.5 kg/m 2. In 121 subjects with PCOS and in 32 controls, serum LH and FSH were measured before (0 minutes) and 30 and 60 minutes after GnRH stimulation (100 µg i.v.). Insulin resistance was assessed by HOMA and Insulin Resistance Index derived from glucose and insulin concentrations during 75 gram oral glucose tolerance test. Results: Women with PCOS had higher testosterone (p = 0.0002), androstendione (p = 0.0021), 17OH-progesterone (p < 0.0001) and were more insulin resistant. Raised concentrations of at least one androgen were, however, found only in 58.1% of women with PCOS. Baseline and stimulated LH concentrations were higher in

Thyroid Research, 2016

Background: A change in a thyrometabolic state from severe hypothyroidism to thyrotoxicosis is ve... more Background: A change in a thyrometabolic state from severe hypothyroidism to thyrotoxicosis is very uncommon, but possible in some circumstances. Case presentation: A 27-year old female presented with clinical and biochemical thyrotoxicosis with a previous history chemo-and radiotherapy (including the neck region) for a Hodgkin's lymphoma (at the age of 18). At the age of 20 this was followed by severe hypothyrodism [TSH > 100 μIU/mL (reference range: 0.27-4.2)]. She was stated on L-thyroxine, but the dose was later reduced and subsequently discontinued. She had significantly elevated titres of both anti-thyroid peroxidase antibodies and anti-TSH-receptor antibodies throughout the course of disease. Thyroid scintigraphy revealed a normal and homogenous iodine uptake. Conclusions: We suspect that a gradual switch from thyroid-blocking to thyroid-stimulating antibodies resulted in development of an overt thyrotoxicosis, possibly with a contributory effect of neck irradiation on her autoimmune status.

Thyroid Research, 2015

Background: Though compliance (or adherence) problems, as well as inappropriate levothyroxine (L-... more Background: Though compliance (or adherence) problems, as well as inappropriate levothyroxine (L-T 4) intake (e.g. with meal, other drugs or certain foods that can significantly affect absorption) are very common, the issue is often either not mentioned or even frankly denied by patients. Case Presentation: We describe three cases of patients who presented with high TSH (ranging from about 30 to 200 mIU/l), with concomitantly either high, normal or low free thyroxine (FT 4), despite treatment with high doses of L-T 4. The above mentioned problems with adjustment of L-T 4 dose persisted for several months or even years. Coeliac disease screen was negative in all cases. In all these patients administration of a single bolus of L-T 4 (1000 μg) or two doses of 1000 μg of L-T 4 within 48 h resulted in a quick increase in FT 4 (thus confirming proper absorption) and in normalization of TSH within a week. No adverse effects of administration of these high doses of L-T 4 were observed. Conclusions: Our data support the efficacy, as well as safety of administration of single bolus of high dose L-T 4 as a test for possible compliance/adherence problems.

Endocrine, 2015

Stimulation of growth hormone (GH) and adrenocorticotropic hormone (ACTH) secretion by glucagon i... more Stimulation of growth hormone (GH) and adrenocorticotropic hormone (ACTH) secretion by glucagon is a standard procedure to assess pituitary dysfunction but the pathomechanism of glucagon action remains unclear. As arginine vasopressin (AVP) may act on the release of both, GH and ACTH, we tested here the role of AVP in GST by measuring a stable precursor fragment, copeptin, which is stoichiometrically secreted with AVP in a 1:1 ratio. ACTH, cortisol, GH, and copeptin were measured at 0, 60, 90, 120, 150, and 180 min during GST in 79 subjects: healthy controls (Group 1, n = 32), subjects with pituitary disease, but with adequate cortisol and GH responses during GST (Group 2, n = 29), and those with overt hypopituitarism (Group 3, n = 18). Copeptin concentrations significantly increased over baseline 150 and 180 min following glucagon stimulation in controls and patients with intact pituitary function but not in hypopituitarism. Copeptin concentrations were stimulated over time and the maximal increment correlated with ACTH, while correlations between copeptin and GH were weaker. Interestingly, copeptin as well as GH secretion was significantly attenuated when comparing subjects within the highest to those in the lowest BMI quartile (p \ 0.05). Copeptin is significantly released following glucagon stimulation. As this release is BMI-dependent, the timedependent relation between copeptin and GH may be obscured, whereas the close relation to ACTH suggests that AVP/copeptin release might be linked to the activation of the adrenal axis.

Endocrine Abstracts, 2015

Neuro endocrinology letters, 2011

As increased frequency of gonadotrophin-releasing hormone (GnRH) pulses is characteristic for pol... more As increased frequency of gonadotrophin-releasing hormone (GnRH) pulses is characteristic for polycystic ovary syndrome (PCOS), we assessed gonadotrophin response to GnRH in women with PCOS with normal and raised androgens and in regularly menstruating controls. The study involved 155 subjects: PCOS, n=121, age (mean±SD) 24.8±5.4 yrs, BMI 24.5±6.0 kg/m2, all with oligo-/amenorrhoea and PCO morphology, and 34 controls. Gonadotrophins were measured in early follicular phase after GnRH stimulation (0, 30 and 60 minutes). Fifty four (41.9%) women with PCOS had androgens (testosterone, androstendione, dihydroepiandrosterone sulphate) within the reference range, and would fulfil the "Rotterdam", but not the Androgen Excess Society PCOS criteria. Baseline and stimulated LH concentrations were higher in PCOS (9.09±5.56 vs 4.83±1.71 IU/l, 35.48±31.4 vs 16.30±6.68 IU/l, 33.86±31.8 vs 13.45±5.2 IU/l, at 0, 30 and 60 min post GnRH, respectively, p<0.0001). An LH/FSH ratio in PCOS i...

Annals of agricultural and environmental medicine : AAEM, 2014

Deficiency of vitamin D in pregnancy leads to higher incidences of preeclampsia, gestational diab... more Deficiency of vitamin D in pregnancy leads to higher incidences of preeclampsia, gestational diabetes, preterm birth, bacterial vaginosis, and also affects the health of the infants. According to Polish recommendations published in 2009, vitamin D supplementation in pregnant women should be provided from the 2nd trimester of pregnancy in daily dose of 800-1000 IU. The aim of the presented study is: 1) to estimate how many pregnant women comply with those recommendations and 2) to determine the 25(OH)D levels in pregnant women. The study included 88 pregnant women, aged 20-40 years, between 12-35 week of gestation. Vitamin D concentrations [25(OH)D] were measured by a direct electrochemiluminescence immunoassay (Elecsys, Roche). 31 of 88 pregnant women (35.2%) did not use any supplementation. Mean level of 25(OH)D was 28.8 ± 14.8 ng/mL (range from 4.0 - 77.5 ng/mL). Vitamin D deficiency, defined as 25(OH)D concentration below 20 ng/mL, was found in 31.8% of the women (28/88). Insuffi...

Endocrine Abstracts, 2014