Skip to main content
SpringerLink
Log in

The effect of somatostatin analogs on vitamin D and calcium concentrations in patients with acromegaly

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Purpose

The goals of this study were to determine: (1) 25OH vitamin D (25OHD) and calcium levels in patients with acromegaly and their association with insulin-like growth factor (IGF-1) and (2) whether somatostatin analog (SSA) therapy effects calcium and 25OHD levels.

Methods

125 patients with acromegaly were studied. Serum calcium and 25OHD levels were compared prior to and after vitamin D supplementation between patients receiving versus not receiving SSA in whom medical therapy included pegvisomant and/or dopamine agonists. Calcium and 25OHD levels were also evaluated longitudinally prior to and during short-term (mean 3 months, range 1–5) and long-term (mean 49 months, range 7–180) SSA administration. Vitamin D2 50,000 units weekly were given to 3 patients in the cross sectional and 1 in the longitudinal group; 400–4,000 units/day of D3 were given to 11 and 5 in respective groups.

Results

In patients with a comparable mean IGF-1 index and season of testing, mean serum levels of 25OHD prior to vitamin D supplementation did not differ in patients receiving versus not receiving SSA (30 ± 3 vs. 30 ± 1 ng/ml, p = 0.99) and the prevalence of vitamin D sufficiency was similar between SSA and non SSA groups (42 vs. 57 %, p = 0.20), prior to vitamin D supplementation. In patients with a comparable mean IGF-1 index and season of testing, mean serum 25OHD levels in patients increased after vitamin D supplementation in both those who were (37 ± 2 ng/ml, N = 23, p = 0.007) and were not receiving SSA (35 ± 1 ng/ml, N = 69, p = 0.005) compared to pre-D supplementation levels but were not different between these groups, p = 0.95) after D supplementation. Calcium and albumin were normal throughout longitudinal follow up. Calcium correlated with IGF-1 index (ρ = 0.29, p = 0.001, N = 125). In the longitudinal subset, serum calcium decreased transiently, in patients receiving short-term SSA (pretreatment 9.9 ± 0.1 mg/dl vs. short-term SSA 9.5 ± 0.1, p = 0.004). After long-term SSA therapy, calcium increased compared to levels on short-term therapy (9.8 ± 0.1 mg/dl vs. 9.5 ± 0.1, p = 0.017) and were unchanged compared to baseline. Mean vitamin D levels were sufficient at baseline prior to SSA therapy (33 ± 5.0 ng/ml), and did not change during short term (29 ± 6 ng/ml, p = 0.85) and long term SSA therapy (35 ± 5 ng/ml, p = 0.43).

Conclusions

Prior to and after vitamin D supplementation, patients with acromegaly receiving long-term SSA had vitamin D levels similar to those receiving other therapies, suggesting that long-term SSA therapy does not affect serum vitamin D. However, given the limitations of this retrospective study, further prospective studies evaluating the impact of SSA on vitamin D levels are necessary to confirm these findings definitively. Calcium levels are positively associated with IGF-1 index in patients with acromegaly. There is a transient decrease in calcium levels with short-term SSA use. The acute effect of SSA on calcium does not appear to be mediated by albumin, 25OHD or PTH and resolves with long-term SSA treatment. The transient decrease in calcium with short-term SSA use resolved with long-term SSA therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Camanni F, Massara F, Losana O, Molinatti GM (1968) Increased renal tubular reabsorption of phosphorus in acromegaly. J Clin Endocrinol Metab 28(7):999–1005

    Article  CAS  PubMed  Google Scholar 

  2. Kamenicky P, Blanchard A, Gauci C, Salenave S, Letierce A, Lombes M, et al (2012) Pathophysiology of renal calcium handling in acromegaly: what lies behind hypercalciuria? J Clin Endocrinol Metab 97(6):2124–2133

    Google Scholar 

  3. Shah R, Licata A, Oyesiku NM, Ioachimescu AG (2012) Acromegaly as a cause of 1,25-dihydroxyvitamin D-dependent hypercalcemia: case reports and review of the literature. Pituitary 15(Suppl 1):17–22

    Article  Google Scholar 

  4. Bonadonna S, Mazziotti G, Nuzzo M, Bianchi A, Fusco A, De Marinis L et al (2005) Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women. J Bone Miner Res 20(10):1837–1844

    Article  PubMed  Google Scholar 

  5. Fiebrich HB, Van Den Berg G, Kema IP, Links TP, Kleibeuker JH, Van Beek AP et al (2010) Deficiencies in fat-soluble vitamins in long-term users of somatostatin analogue. Aliment Pharmacol Ther 32(11–12):1398–1404

    Article  CAS  PubMed  Google Scholar 

  6. Mosekilde L (2005) Vitamin D and the elderly. Clin Endocrinol (Oxf) 62(3):265–281

    Article  CAS  Google Scholar 

  7. de Boer IH, Levin G, Robinson-Cohen C, Biggs ML, Hoofnagle AN, Siscovick DS et al (2012) Serum 25-hydroxyvitamin D concentration and risk for major clinical disease events in a community-based population of older adults: a cohort study. Ann Intern Med 156(9):627–634

    Article  PubMed Central  PubMed  Google Scholar 

  8. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357(3):266–281

    Article  CAS  PubMed  Google Scholar 

  9. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP et al (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(7):1911–1930

    Article  CAS  PubMed  Google Scholar 

  10. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B (2006) Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84(1):18–28

    CAS  PubMed  Google Scholar 

  11. Singh RJ, Taylor RL, Reddy GS, Grebe SK (2006) C-3 epimers can account for a significant proportion of total circulating 25-hydroxyvitamin D in infants, complicating accurate measurement and interpretation of vitamin D status. J Clin Endocrinol Metab 91(8):3055–3061

    Article  CAS  PubMed  Google Scholar 

  12. Farrell CJ, Martin S, McWhinney B, Straub I, Williams P, Herrmann M (2012) State-of-the-art vitamin D assays: a comparison of automated immunoassays with liquid chromatography-tandem mass spectrometry methods. Clin Chem 58(3):531–542

    Article  CAS  PubMed  Google Scholar 

  13. Mazziotti G, Bianchi A, Cimino V, Bonadonna S, Martini P, Fusco A et al (2008) Effect of gonadal status on bone mineral density and radiological spinal deformities in adult patients with growth hormone deficiency. Pituitary 11(1):55–61

    Article  CAS  PubMed  Google Scholar 

  14. Wassenaar MJ, Biermasz NR, Hamdy NA, Zillikens MC, van Meurs JB, Rivadeneira F et al (2011) High prevalence of vertebral fractures despite normal bone mineral density in patients with long-term controlled acromegaly. Eur J Endocrinol 164(4):475–483

    Article  CAS  PubMed  Google Scholar 

  15. McKeage K, Cheer S, Wagstaff AJ (2003) Octreotide long-acting release (LAR): a review of its use in the management of acromegaly. Drugs 63(22):2473–2499

    Article  CAS  PubMed  Google Scholar 

  16. Cappelli C, Gandossi E, Agosti B, Cerudelli B, Cumetti D, Castellano M et al (2004) Long-term treatment of acromegaly with lanreotide: evidence of increased serum parathormone concentration. Endocr J 51(6):517–520

    Article  CAS  PubMed  Google Scholar 

  17. Legovini P, De Menis E, Breda F, Billeci D, Carteri A, Pavan P et al (1997) Long-term effects of octreotide on markers of bone metabolism in acromegaly: evidence of increased serum parathormone concentrations. J Endocrinol Invest 20(8):434–438

    Article  CAS  PubMed  Google Scholar 

  18. Fredstorp L, Pernow Y, Werner S (1993) The short and long-term effects of octreotide on calcium homeostasis in patients with acromegaly. Clin Endocrinol (Oxf) 39(3):331–336

    Article  CAS  Google Scholar 

  19. Bergeim O, Stewart FT, Hawk PB (1914) A study of the metabolism of calcium, magnesium, sulphur, phosphorus, and nitrogen in acromegaly. J Exp Med 20(3):218–224

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. White HD, Ahmad AM, Durham BH, Chandran S, Patwala A, Fraser WD et al (2006) Effect of active acromegaly and its treatment on parathyroid circadian rhythmicity and parathyroid target-organ sensitivity. J Clin Endocrinol Metab 91(3):913–919

    Article  CAS  PubMed  Google Scholar 

  21. Lai JK, Lucas RM, Clements MS, Harrison SL, Banks E (2010) Assessing vitamin D status: pitfalls for the unwary. Mol Nutr Food Res 54(8):1062–1071

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by an investigator-initiated grant from Ipsen.

Conflict of interest

The authors declare they have no conflict of interest to report.

Author information

Authors and Affiliations

  1. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St, Bulfinch 457, Boston, MA, 02114, USA

    Adnan Ajmal, Arezoo Haghshenas, Shirin Attarian, Maya Barake, Nicholas A. Tritos, Anne Klibanski, Karen K. Miller & Lisa B. Nachtigall

  2. Neuroendocrine Clinical Center, 0 Emerson Place Suite 112, Massachusetts General Hospital, Boston, MA, 02114, USA

    Lisa B. Nachtigall

Authors
  1. Adnan Ajmal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arezoo Haghshenas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shirin Attarian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maya Barake
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nicholas A. Tritos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anne Klibanski
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Karen K. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lisa B. Nachtigall
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lisa B. Nachtigall.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PPT 102 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ajmal, A., Haghshenas, A., Attarian, S. et al. The effect of somatostatin analogs on vitamin D and calcium concentrations in patients with acromegaly. Pituitary 17, 366–373 (2014). https://doi.org/10.1007/s11102-013-0514-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-013-0514-0

Keywords

Search

Navigation