| 1. |
- Astradsson, Arnar, et al.
(författare)
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Cerebral infarction after fractionated stereotactic radiation therapy of benign anterior skull base tumors
- 2019
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Ingår i: Clinical and Translational Radiation Oncology. - : Elsevier BV. - 2405-6308. ; 15, s. 93-98
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose of this study was to examine the occurrence of cerebral infarction (ischemic stroke), in a large combined cohort of patients with anterior skull base meningiomas, pituitary adenomas and craniopharyngiomas, after fractionated stereotactic radiation therapy (FSRT). Material and Methods: All patients, 18 years and older, with anterior skull base meningiomas, pituitary adenomas and craniopharyngiomas, treated with fractionated stereotactic radiation, in our center, from January 1999 to December 2015 were identified. In total 169 patients were included. The prescription dose to the tumor was 54 Gy for 164 patients (97%) and 46.0–52.2 Gy for 5 patients (3%). Cases of cerebral infarctions subsequent to FSRT were identified from the Danish National Patient Registry and verified with review of case notes. The rate of cerebral infarction after FSRT was compared to the rate in the general population with a one sample t-test after standardization for age and year. We explored if age, sex, disease type, radiation dose and dose per fraction was associated with increased risk of cerebral infarction using univariate Cox models. Results: At a median follow-up of 9.3 years (range 0.1–16.5), 7 of the 169 patients (4.1%) developed a cerebral infarction, at a median 5.7 years (range 1.2–11.5) after FSRT. The mean cerebral infarction rate for the general population was 0.0035 and 0.0048 for the FSRT cohort (p = 0.423). Univariate cox models analysis showed that increasing age correlated significantly with the cerebral infarction risk, with a hazard ratio of 1.090 (p = 0.013). Conclusion: Increased risk of cerebral infarction after FSRT of anterior skull base tumors was associated with age, similar to the general population. Our study revealed that FSRT did not introduce an excess risk of cerebral infarction.
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| 2. |
- Granfors, Michaela, 1972-
(författare)
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Hypothyroidism and Pregnancy
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hypothyroidism is a common endocrine disorder affecting women of reproductive age. On a global level, iodine deficiency is still the most common cause of hypothyroidism. Also genetic variations, in particular SNP rs4704397 in the PDE8B gene, are responsible for a significant proportion of TSH variations. Untreated hypothyroidism has significant adverse effects on pregnancy and fetal outcome. Most international guidelines suggest targeted thyroid testing in pregnant women with risk factors for thyroid disturbances.In a case-control study, an association between homozygous A/A as well as homozygous G/G carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage was found. The explanation for this association is unknown.In a nationwide survey, all guidelines for thyroid testing and management of hypothyroidism during pregnancy in Sweden were collected and compared with international guidelines. The local guidelines were variable and poorly compliant with the international guidelines.In a follow-up in one district, 5,254 pregnant women were included for subsequent review of their medical reports. We found a targeted thyroid testing rate of 20.1% in clinical practice, with an overall frequency of women with trimester-specific elevated TSH of 18.5%. More disturbingly, half of the women who were on levothyroxine treatment at the time of conception had an elevated TSH level at thyroid testing.In a subsequent cohort study of the 5,254 women, we found the prevalence of trimester-specific elevated TSH and overt hypothyroidism to be equal in targeted thyroid tested and untested women.In a cross-sectional study, a median urinary iodine concentration (UIC) of 98 μg/l was found in the study population. According to WHO/UNICEF/IGN criteria, the population-based median UIC during pregnancy should be 150-249 μg/l.In conclusion, genetic variations may contribute to adverse pregnancy outcomes. In clinical practice, thyroid testing and the management of hypothyroidism during pregnancy is unsatisfactory, regarding the whole chain from development of local guidelines to their implementation and to targeted thyroid testing. Moreover, our results indicate insufficient iodine status in the pregnant population of Sweden.
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| 3. |
- Höybye, Charlotte, et al.
(författare)
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Change in baseline characteristics over 20 years of adults with growth hormone (GH) deficiency on GH replacement therapy
- 2019
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 181:6, s. 629-638
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Clinical observations over time of adults with growth hormone (GH) deficiency (GHD) have indicated a shift in patient characteristics at diagnosis. The objective of this study was to compare baseline characteristics of patients diagnosed with adult-onset GHD naive to GH replacement during t hree study periods (1994-1999 (P1), 2000-2004 (P2), and 2005-2012 (P3)) using the KIMS (Pfizer's International Metab olic) database. Methods: Data were retrieved for a total of 6069 patients with adult-on set GHD from six countries (Belgium, Germany, Netherlands, Spain, Sweden, and UK): P1 (n = 1705), P2 (n = 2397), and P3 (n = 1967). Results: The proportions of patients with pituitary/hypothalamic tumors and patients with multiple pituitary hormone deficiencies decreased per entry year period, while the proporti ons with hypertension and diabetes increased. The lag time from diagnosis of pituitary disease to start of GH treatme nt decreased by 2.9 years over the entry year periods. IGF-1 increased by 0.1 standard deviation score per entry year period. Maximum GH following various stimulation tests, BMI, and waist circumference increased. The use of radio therapy, glucocorticoid replacement doses, and the proportion of women >50 years on estrogen replacement therapy decreased. The effects of 1 year of GH replacement were similar over the entry year periods despite changes in the patients' baseline characteristics. An expected increase in fasting blood glucose was seen after 1 year of GH treatment. Conclusions: The degree of confirmed GHD became less pronounced and more pat ients with co-morbidities and diabetes were considered for GH replacement therapy, possibly r eflecting increased knowledge and confidence in GH therapy gained with time.
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| 4. |
- Marina, Djordje, et al.
(författare)
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Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues - Observations in two patients with acromegaly and severe headache
- 2015
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 25:5, s. 262-267
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Tidskriftsartikel (refereegranskat)abstract
- Background: Somatotropinomas have unique "fingerprints" of somatostatin receptor (sst) expression, which are targets in treatment of acromegaly with somatostatin analogues (SSAs). However, a significant expression of sst is not always related to the biochemical response to SSAs. Headache is a common complaint in acromegaly and considered a clinical marker of disease activity. SSAs are reported to have an own analgesic effect, but the sst involved are unknown. Patients and methods: We investigated sst expression in two acromegalic patients with severe headache and no biochemical effects of octreotide, but a good response to pasireotide. We searched the literature for determinants of biochemical and analgesic effects of SSAs in somatotropinomas. Results: Case 1 had no biochemical or analgesic effects of octreotide, a semi-selective SSA, but a rapid and significant effect of pasireotide, a pan-SSA Case 2 demonstrated discordance between analgesic and biochemical effects of octreotide, in that headache disappeared, but without biochemical improvement. In contrast, pasireotide normalized insulin-like growth factor 1. Both adenomas were sparsely granulated and had strong membranous expressions of sst2a in 50-75% and sst5 in 75-100% of tumor cells. The truncated sst5 variant TMD4 (sst5TMD4) showed expression in 20-57% of tumor cells. Conclusions: A poor biochemical response to octreotide may be associated with tumor expression of a truncated sst5 variant, despite abundant sst2a expression, suggesting an influence from variant sst5 on common sst signaling pathways. Furthermore, unrelated analgesic and biochemical effects of SSAs supported a complex pathogenesis of acromegaly-associated headache. Finally, assessment of truncated sst5 in addition to full length sst could be important for a choice of postoperative SSA treatment in somatotropinomas.
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