uu.seUppsala universitets publikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Left-shifted relation between calcium and parathyroid hormone in Graves' Disease
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
2014 (Engelska)Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, nr 2, s. 545-551Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background:

Patients with Graves' disease (GD) have disturbances in calcium regulation with manifestations such as postoperative hypocalcemia. We have investigated the thyroid as well as the parathyroid function in detail.

Material and Method:

A series of patients undergoing total thyroidectomy for GD (n=56) or Multi Nodular Goitre (MNG, n=50) were scrutinized for postoperative hypocalcemia, need for calcium and/or vitamin D substitution. CiCa-clamp was used in 14 patients and 21 controls to quantify the secretion of PTH in relation to the ionized plasma calcium level. The setpoint, equal to the plasma ionized calcium concentration at which 50% of the maximal secretion of PTH is inhibited, as well as other CiCa-related parameters were calculated.

Results:

Hypocalcemia was present in 48% of GD and 41.2% of patients with MNG postoperatively. Patients with GD had lower calcium levels, 18% had S-Ca< 2.00 mmol/L compared to 4.0% in the MNG group, p=0.02. A higher degree of GD patients were given parenteral calcium-substitution during the hospital stay (3.6% vs 0 %) and oral calcium substitution at discharge (48% vs 10%), although they had normal vitamin D3 levels. The GD group showed a significantly left-shifted setpoint compared to the normal group on CiCa clamp, 1.16 mmol/l vs. 1.20 mmol/L (p<0.001), as well as an increased PTH release to hypocalcemic stimulus. GD patients also show an association between degree of subclinical toxicosis at time of surgery and risk for developing postoperative hypocalcemia.

Conclusion:

Patients with GD demonstrate dysregulation of the calcium homeostasis by several parameters. GD patients have lower postoperative S-calcium compared to patients with MNG, lower calcium/PTH setpoint and a significantly increased release of PTH to hypocalcemic stimulus compared to controls. The CiCa clamp response in GD patients with normal 25-OH-vitamin D3 levels mimics that of obese patients in which vitamin D insufficiency has been proposed as an underlying cause.

Ort, förlag, år, upplaga, sidor
2014. Vol. 99, nr 2, s. 545-551
Nationell ämneskategori
Kirurgi
Identifikatorer
URN: urn:nbn:se:uu:diva-212144DOI: 10.1210/jc.2013-2500ISI: 000333460300053PubMedID: 24248181OAI: oai:DiVA.org:uu-212144DiVA, id: diva2:676602
Tillgänglig från: 2013-12-06 Skapad: 2013-12-06 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
Ingår i avhandling
1. Calcium Homeostasis in Patients with Graves' Disease
Öppna denna publikation i ny flik eller fönster >>Calcium Homeostasis in Patients with Graves' Disease
2016 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Patients with Graves´ Disease (GD) have a higher risk of developing more severe and prolonged hypocalcaemia after total thyroidectomy (TT) than patients who undergo surgery for benign atoxic goitre. Since TT is the most effective treatment for GD, it is crucial to identify mechanisms for postoperative hypocalcaemia. The aim of this thesis was to study the mechanisms of calcium metabolism in patients with GD.

It is safe to operate on GD patients with TT. Results in Paper I showed fewer recurrences and equal complication rates compared to patients who underwent subtotal thyroidectomy (ST). The transient lowering of PTH seen in the hypocalcaemic patients was fully restored one month after surgery (Papers II and V).

The calcium-sensing receptor (CaSR) is crucial for maintaining plasma calcium, and single nucleotide polymorphisms (SNPs) in the gene may alter the sensing function. Thus, we analysed SNPs in CaSR in GD patients (Paper II) and showed that they had a more left-shifted calcium-PTH set-point compared to controls, implicating higher sensitivity. This is also supported by the results in the group of postoperatively hypocalcaemic patients. They already had lower plasma calcium preoperatively (Papers II, IV and V) and lacked the T/G G/A G/C, a haplotype shown in Paper III to have a close relationship to higher p-calcium levels. Moreover, a lack of the T allele in rs1801725 was seen in the group of patients needing permanent treatment with calcium and vitamin D, i.e. > 12 months, (paper V).

Patients who became hypocalcaemic (p-calcium < 2.00 mmol/L) on day one postoperatively, had lower preoperative levels of thyroid stimulating hormone (TSH) and higher levels of  T3, this was also applied to the patient groups requiring temporary or permanent postoperative treatment (Papers II and V). In addition, hypocalcaemic patients treated for less than six months with anti-thyroid drugs had higher levels of bone metabolism markers CTX and P1NP than normocalcaemic patients (Paper V).

In conclusion, the postoperative period of hypocalcaemia seen in patients with GD is a complex medical condition, caused by a combination of surgical trauma, different SNPs in CaSR, and high bone metabolism related to preoperative thyroid metabolism.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2016. s. 51
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1212
Nyckelord
Graves' Disease, Calcium homeostasis, Total thyroidectomy, Bone metabolism, Calcium sensing receptor
Nationell ämneskategori
Klinisk medicin
Forskningsämne
Kirurgi
Identifikatorer
urn:nbn:se:uu:diva-283075 (URN)978-91-554-9552-7 (ISBN)
Disputation
2016-06-02, Föreläsningssalen Falu Lasarett, Söderbaums väg 8, entré I, Falun, 10:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2016-05-12 Skapad: 2016-04-10 Senast uppdaterad: 2016-06-01

Open Access i DiVA

Fulltext saknas i DiVA

Övriga länkar

Förlagets fulltextPubMed

Personposter BETA

Annerbo, MariaHultin, HellaStålberg, PeterHellman, Per

Sök vidare i DiVA

Av författaren/redaktören
Annerbo, MariaHultin, HellaStålberg, PeterHellman, Per
Av organisationen
Endokrinkirurgi
I samma tidskrift
Journal of Clinical Endocrinology and Metabolism
Kirurgi

Sök vidare utanför DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 849 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf