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Lithium-associated hyperparathyroidism: Prevalence, Pathophysiology, Management
Örebro University, School of Medical Sciences.ORCID iD: 0000-0002-5162-0328
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lithium has been used in the treatment of bipolar disorder, formerly called manic depression, for nearly seven decades. Lithium-associated hyperparathyroidism (LHPT) is an ill-defined and less well known possible side-effect of chronic lithium therapy and was first described in 1973. The condition has been considered to be rare, though there exists conflicting evidence as to its prevalence, its pathophysiological background, and, if and when identified, what the appropriate medical or surgical treatment should be. The principal aim of this thesis was to understand and more comprehensively characterise this condition through studying a large patient cohort, with regards its prevalence, development, and additionally by providing an evaluation of surgical management up until now.

In Study I a population of 423 lithium-treated out-patients (251 women, 172 men) were recruited from Jönköping and Örebro County. We found that 18% met the criteria for hyperparathyroidism (HPT) and that a further 21% had intermittent episodes of hypercalcaemia. We then examined, in Study II, the effects of lithium only in patients with bipolar disorder and compared them, firstly, to patients with bipolar disorder without lithium and, secondly, to a control population. In total, 563 individuals participated in the study. Hypercalcaemia was found to be strongly associated to lithium therapy (adjusted OR 13.45; 95% CI 3.09, 58.55; p=0.001). Study III is a descriptive study of calcium homeostasis in 297 lithium-treated patients from Jönköping where three main groups could be discerned: 178 were normocalcaemic (60%), 102 hypercalcaemic (34%), and 17 hypocalcaemic (6%). Many patients demonstrate robust fluctuations in serum calcium intermittently. Of those with suspected LHPT, 31% had urinary calcium excretion values be-low 1.2 mmol/24hrs. Study IV analysed surgical results of 78 parathyroidectomies in 71 patients with concurrent lithium therapy. In strong contrast to surgical outcomes in those with primary HPT, the overall cure-rate was lower (58%) and the predominant histological diagnosis was hyperplasia (52%). Two patients had double adenomas.

Factors which should be particularly taken into consideration while monitoring lithium-treated patients are age, gender and lithium-duration.

Place, publisher, year, edition, pages
Örebro: Örebro University , 2018. , p. 70
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 174
National Category
Surgery
Identifiers
URN: urn:nbn:se:oru:diva-65002ISBN: 978-91-7529-234-2 (print)OAI: oai:DiVA.org:oru-65002DiVA, id: diva2:1182631
Public defence
2018-04-06, Örebro universitet, Campus USÖ, hörsal C3, Södra Grev Rosengatan 32, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2018-02-14 Created: 2018-02-14 Last updated: 2018-03-15Bibliographically approved
List of papers
1. The prevalence of lithium-associated hyperparathyroidism in a large Swedish population attending psychiatric outpatient units
Open this publication in new window or tab >>The prevalence of lithium-associated hyperparathyroidism in a large Swedish population attending psychiatric outpatient units
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2015 (English)In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 35, no 3, p. 279-285Article in journal (Refereed) Published
Abstract [en]

Objective: This retrospective study determined the prevalence of lithium-associated hyperparathyroidism (LHPT) in 2 geographically defined, equivalent populations in Sweden, with no other selection bias.

Methods: The medical journals of all patients receiving lithium treatment were examined specifically regarding their biochemistry: calcium, parathyroid hormone (PTH), creatinine, and vitamin D. The condition LHPT was defined biochemically. All patient data were noted, and the prevalence of the condition could thereby be calculated.

Results: A total of 423 patients were included (251 women and 172 men; 3: 2), treated over a mean of 13.5 years (range, 1-46 years), aged 19 to 92. 77 patients (18%) were identified with LHTP whose median serum calcium-was 2.55 mmol/L and PTH was 99 ng/L. A further 21% showed tendencies toward hypercalcemia. Forty-three percent had vitamin D insufficiency. Five patients (approximately 1%) had undergone parathyroidectomy.

Conclusion: The prevalence of LHPT is high and often goes undetected. Vitamin D insufficiency is common as is polypharmacy. Surgery, for unclear reasons, has not been performed extensively, possibly because of limited knowledge of the underlying pathophysiology or surgery's significance. We present standard recommendations on patient management and suggest continual, specific follow-up including the monitoring of calcium, PTH, and vitamin D at least annually. Surgery should be considered with intention to improve psychiatric well-being and provide multiorgan protection.

Keywords
hypercalcemia; hyperparathyroidism; Lithium; prevalence
National Category
Pharmacology and Toxicology Psychiatry
Research subject
Psychiatry
Identifiers
urn:nbn:se:oru:diva-44863 (URN)10.1097/JCP.0000000000000303 (DOI)000353817400011 ()25853371 (PubMedID)2-s2.0-84929161233 (Scopus ID)
Available from: 2015-06-09 Created: 2015-06-09 Last updated: 2018-06-30Bibliographically approved
2. Lithium-Associated Hypercalcemia: Pathophysiology, Prevalence, Management
Open this publication in new window or tab >>Lithium-Associated Hypercalcemia: Pathophysiology, Prevalence, Management
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2018 (English)In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 2, p. 415-424Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Lithium-associated hypercalcemia (LAH) is an ill-defined endocrinopathy. The aim of the present study was to determine the prevalence of hypercalcemia in a cohort of bipolar patients (BP) with and without concomitant lithium treatment and to study surgical outcomes for lithium-associated hyperparathyroidism.

METHODS: Retrospective data, including laboratory results, surgical outcomes and medications, were collected from 313 BP treated with lithium from two psychiatric outpatient units in central Sweden. In addition, data were collected from 148 BP without lithium and a randomly selected control population of 102 individuals. Logistic regression was used to compare odds of hypercalcemia in these respective populations.

RESULTS: The prevalence of lithium-associated hypercalcemia was 26%. Mild hypercalcemia was detected in 87 out of 563 study participants. The odds of hypercalcemia were significantly higher in BP with lithium treatment compared with BP unexposed to lithium (adjusted OR 13.45; 95% CI 3.09, 58.55; p = 0.001). No significant difference was detected between BP without lithium and control population (adjusted OR 2.40; 95% CI 0.38, 15.41; p = 0.355). Seven BP with lithium underwent surgery where an average of two parathyroid glands was removed. Parathyroid hyperplasia was present in four patients (57%) at the initial operation. One patient had persistent disease after the initial operation, and six patients had recurrent disease at follow-up time which was on average 10 years.

CONCLUSION: The high prevalence of LAH justifies the regular monitoring of calcium homeostasis, particularly in high-risk groups. If surgery is necessary, bilateral neck exploration should be considered in patients on chronic lithium treatment. Prospective studies are needed.

Place, publisher, year, edition, pages
Springer, 2018
National Category
Psychiatry Surgery
Identifiers
urn:nbn:se:oru:diva-63997 (URN)10.1007/s00268-017-4328-5 (DOI)000419886700015 ()29260296 (PubMedID)2-s2.0-85038405849 (Scopus ID)
Available from: 2018-01-09 Created: 2018-01-09 Last updated: 2018-08-16Bibliographically approved
3. Characterization of Calcium homeostasis in Lithium-treated Patients: Disturbances reveal both hypercalcemia and hypocalcemia
Open this publication in new window or tab >>Characterization of Calcium homeostasis in Lithium-treated Patients: Disturbances reveal both hypercalcemia and hypocalcemia
(English)Manuscript (preprint) (Other academic)
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:oru:diva-65826 (URN)
Available from: 2018-03-15 Created: 2018-03-15 Last updated: 2018-03-15Bibliographically approved
4. Long-term results of surgery for lithium-associated hyperparathyroidism
Open this publication in new window or tab >>Long-term results of surgery for lithium-associated hyperparathyroidism
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2010 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 97, no 11, p. 1680-1685Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Lithium therapy for affective bipolar disease is frequently associated with hyperparathyroidism (HPT), but the results of surgical treatment are virtually unknown. The aim of this retrospective review was to analyse the long-term outcome after surgery for lithium-induced HPT in a large series of patients.

METHODS: Seventy-one patients on chronic lithium therapy who underwent surgery in three university and three district hospitals in Sweden were followed for a median of 6.3 years. Histopathology, complications of surgery and normocalcaemia at 6 months after surgery and last follow-up were analysed.

RESULTS: The primary histopathological diagnoses were adenoma (45 per cent), double adenomas (3 per cent) and hyperplasia (52 per cent). No permanent paresis of the recurrent laryngeal nerve was recorded but 13 per cent of the patients suffered from permanent hypoparathyroidism. At follow-up, the rate of persistent and recurrent HPT was 42 per cent regardless of the histopathological diagnosis.

CONCLUSION: The results of conventional surgery for lithium-associated HPT are poor. The surgical approach should be adjusted for the multiglandular disease that is usually the cause of HPT in patients on chronic lithium therapy.

National Category
Surgery
Identifiers
urn:nbn:se:oru:diva-65825 (URN)10.1002/bjs.7199 (DOI)000282651100015 ()20665482 (PubMedID)2-s2.0-78049394343 (Scopus ID)
Available from: 2018-03-15 Created: 2018-03-15 Last updated: 2018-03-15Bibliographically approved

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