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Calciumhomeostasis and Vitamin D in Obesity and Preeclampsia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Normal physiological functioning is highly dependent of calcium and the concentration range is very narrow. Normal calcium levels are so crucial to survival that the body will de-mineralize bone if the levels are insufficient. A prerequisite for normal calcium uptake is a normal Vitamin D level. Insufficient levels of Vitamin D are associated to several diseases.

The aims of this thesis were to study the relationship between pregnancies and hyperparathyroidism (pHPT) (I), between pHPT and pregnancy with preeclampsia (II) and also to determine if disturbances in calcium homeostasis with vitamin D deficiency are apparent in preeclamptic women (III).  The aim was also to study calciumhomeostasis in obese patients before and after bariatric surgery (IV and V) with emphasis on vitamin D status, parathyroid secretion and bone mineral density (BMD).

A correlation was found between a history of pHPT and pregnancy with preeclampsia, with an odds ratio of 6,89 ( 95% CI 2.30, 20.58).  Parathyroid hormone was significantly raised in preeclamptic pregnancies but vitamin D deficiency was present both in preeclamptic and healthy pregnancies. A certain polymorphism of the Vitamin D receptor (baT haplotype), overrepresented in pHPT, was not over expressed in preeclampsia. Hypovitaminosis D was present in more than 70% of bariatric patients preoperatively, which did not change after surgery, despite great weight loss and start of Vitamin D supplementation. BMD was significantly lower in bariatric patients with a negative correlation to the time elapsed since surgery. A small increase in BMD could be noted 10-13 years after bariatric surgery, possibly due to gradual weight gain. CiCa-clamping in obese patients demonstrated a disturbed calcium homeostasis with a left-shifted calcium-PTH relationship and a lower set-point of calcium. This disturbance persisted one year postoperatively.

In conclusion, derangements in calcium homeostasis with decreased levels of Vitamin D are present in preeclampsia and obesity. A history of pHPT should be viewed as a risk factor for preeclampsia. Life long follow-up is necessary after bariatric surgery, and an individually adjusted high dose Vitamin D substitute is probably needed to avoid a development of osteoporosis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2011. , 68 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 650
Keyword [en]
Calcium homeostasis, vitamin D, preeclampsia, obesity, parathyroid hormone
National Category
Surgery
Research subject
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-145209ISBN: 978-91-554-8017-2OAI: oai:DiVA.org:uu-145209DiVA: diva2:399586
Public defence
2011-04-08, Grönwallssalen, ing 70, Akademiska sjukhuset, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2011-03-18 Created: 2011-02-07 Last updated: 2011-05-04
List of papers
1. Childbearing and the risk of parathyroid adenoma - a dominant cause for primary hyperparathyroidism
Open this publication in new window or tab >>Childbearing and the risk of parathyroid adenoma - a dominant cause for primary hyperparathyroidism
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2001 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 250, 43-49 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-145193 (URN)
Available from: 2011-02-07 Created: 2011-02-07 Last updated: 2011-05-04
2. Association of parathyroid adenoma and pregnancy with preeclampsia
Open this publication in new window or tab >>Association of parathyroid adenoma and pregnancy with preeclampsia
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2009 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 94, no 9, 3394-3399 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Case reports have described associations between calcium metabolism disturbances and primary hyperparathyroidism with preeclampsia, suggesting parathyroid involvement in preeclampsia etiology. This study examines whether parathyroid adenoma, the main cause of hyperparathyroidism, diagnosed and treated before pregnancy is associated with preeclampsia. DESIGN: We conducted a register-based study to assess the association between parathyroid adenoma and subsequent preeclampsia. SETTING: Births among Sweden's general population were studied. POPULATION: The study population included 52 women with a diagnosis of parathyroid adenoma and 519 without, all of whom had a subsequent singleton pregnancy between 1973 and 1997. METHODS: We performed a conditional logistic regression investigating the association of parathyroid adenoma with subsequent preeclampsia in the first singleton pregnancy with adjustment for potential confounding factors. MAIN OUTCOME MEASURE: The main outcome was a diagnosis of preeclampsia that does not include women with prior chronic hypertension. To ensure that treatment of parathyroid adenoma was completed before pregnancy, those with a diagnosis of parathyroid adenoma made less than 2 yr before delivery (and the matched comparison women) were excluded. RESULTS: Statistically, parathyroid adenoma prior to delivery is significantly (P < 0.001) associated with preeclampsia, producing an adjusted odds ratio of 6.89 (95% confidence interval, 2.30, 20.58). CONCLUSION: A history of parathyroid adenoma should be viewed as a risk for preeclampsia.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-121064 (URN)10.1210/jc.2009-0012 (DOI)000269584600035 ()19531594 (PubMedID)
Available from: 2010-03-18 Created: 2010-03-18 Last updated: 2011-05-04Bibliographically approved
3. Calcium homeostasis derangements in women with preeclampsia 
Open this publication in new window or tab >>Calcium homeostasis derangements in women with preeclampsia 
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(English)Manuscript (preprint) (Other academic)
Keyword
preeclampsia, calciumhomeostasis, vitamin D
National Category
Surgery Obstetrics, Gynecology and Reproductive Medicine
Research subject
Surgery; Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-145207 (URN)
Available from: 2011-02-07 Created: 2011-02-07 Last updated: 2011-05-04
4. Left-Shifted Relation between Calcium and Parathyroid Hormone in Obesity
Open this publication in new window or tab >>Left-Shifted Relation between Calcium and Parathyroid Hormone in Obesity
2010 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, no 8, 3973-3981 p.Article in journal (Refereed) Published
Abstract [en]

Background: A condition resembling secondary hyperparathyroidism (HPT), including raised levels of PTH and normal levels of serum calcium, has been reported in obesity. A plausible reason may be vitamin D deficiency, but conflicting data have been reported. Objective: Our objective was to investigate calcium homeostasis in obese individuals with emphasis on the function of the parathyroid glands. Design and Intervention: Morbidly obese patients (mean body mass index = 46.6 +/- 6) were examined for their status of calcium homeostasis. A subset was thoroughly investigated with calcium-citrate (CiCa) clamping. Patients: Of 108 morbidly obese patients, 11 underwent CiCa clamping as well as 21 healthy volunteers of normal weight and 15 with primary HPT (pHPT). Large patient cohorts of normal individuals and pHPT patients were also used as comparisons. Outcome Measures and Results: All obese individuals had normal serum calcium and creatinine levels. Mean levels of 25-OH-vitamin D-3 in serum were low, 53 nmol/liter (reference range 75-250 nmol/liter). Mean intact plasma PTH was 5.1 pmol/liter (reference range 1.1-6.9 pmol/liter). There was a significant positive correlation between PTH and duration of obesity. CiCa clamping in obese subjects revealed a remarkably high sensitivity for calcium and a left-shifted relation between plasma calcium and PTH (set point) compared with the normal population. CiCa clamping in pHPT patients demonstrated a right-shifted PTH-Ca curve. Conclusion: Although vitamin D levels in the obese individuals were low, few displayed overt signs of secondary HPT. The CiCa clamping implied a disturbance in the calcium homeostasis comparable to early renal insufficiency, with a left-shifted Ca-PTH curve and a lower set point compared with the normal population.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-135604 (URN)10.1210/jc.2009-2822 (DOI)000280652400057 ()20519351 (PubMedID)
Available from: 2010-12-07 Created: 2010-12-07 Last updated: 2013-08-15Bibliographically approved
5. Persisting disturbances in calcium homeostasis after gastric bypass surgery
Open this publication in new window or tab >>Persisting disturbances in calcium homeostasis after gastric bypass surgery
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(English)Manuscript (preprint) (Other academic)
Keyword
calciumhomeostasis, vitamin D, BMD, bariatric surgery
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-145208 (URN)
Available from: 2011-02-07 Created: 2011-02-07 Last updated: 2015-06-26

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