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Secondary hyperparathyroidism of nonrenal origin — Clinical Guidelines

Overview

Secondary hyperparathyroidism of nonrenal origin arises from factors other than renal disease, leading to elevated parathyroid hormone levels due to hypocalcemia and often associated with vitamin D deficiency 6.

Diagnosis

Elevated serum parathyroid hormone (PTH) levels 6.

Low serum calcium levels 6.

Often accompanied by low 25-hydroxyvitamin D levels 6.

Clinical manifestations may include bone pain, fractures, and muscle weakness 6.

Genetic testing may be necessary for suspected hereditary forms 5 13.

Management

Vitamin D supplementation: Typically cholecalciferol or ergocalciferol, dose adjusted based on deficiency severity and response 6 17 18.

Calcium supplementation: To address hypocalcemia and support bone health 6 17.

Monitoring: Regular assessment of serum calcium, PTH, and 25-hydroxyvitamin D levels to guide treatment adjustments 6 17.

Special Populations

Elderly: Higher prevalence of hypovitaminosis D; supplementation with 2,000 IU/day of vitamin D3 can be effective 17 18.

Pediatrics: Pseudo-vitamin-D deficiency rickets should be considered in cases with normal vitamin D levels but persistent symptoms 8.

Comorbidities: In patients with malabsorption syndromes, higher doses or parenteral vitamin D may be required 19.

Key Recommendations

Initiate vitamin D supplementation targeting serum 25-hydroxyvitamin D levels of at least 25 ng/ml in men and 30 ng/ml in women to manage secondary hyperparathyroidism 6 (Evidence: Moderate).

Monitor serum calcium and PTH levels regularly to assess response to vitamin D and calcium supplementation 6 17 (Evidence: Moderate).

Consider genetic testing in cases of suspected hereditary forms of rickets or resistant secondary hyperparathyroidism 5 13 (Evidence: Weak).

References

1 Liang S, Zhang H, Jiao L, Shao R, Lan Y, Liao X et al.. Vitamin D promotes the folate transport and metabolism in zebrafish (. American journal of physiology. Endocrinology and metabolism 2024. link 2 Liu J, Tian C, Tang Y, Geng B. Associations of the serum vitamin D with mortality in postmenopausal women. Clinical nutrition (Edinburgh, Scotland) 2024. link 3 Ponti L, Gabutti L, Faré PB, Janett S, Bianchetti MG, Schulz PJ et al.. Vitamin D Supply of Multivitamins Commercialized Online by Amazon in Western and Southern Europe: A Labeling Analysis. Nutrients 2023. link 4 Annweiler C, Grant WB, Holick MF. Why fear the coming of Winter in Game Of Thrones? The hypovitaminosis D hypothesis. Geriatrie et psychologie neuropsychiatrie du vieillissement 2022. link 5 Al Homyani DK, Alhemaiani SK. Novel Homozygous CYP27B1 Gene Mutation in Vitamin D-Dependent Rickets Type 1A (VDDR1A) Disorder: A Case Report. Frontiers in endocrinology 2022. link 6 Bennouar S, Bachir Cherif A, Makrelouf M, Ait Abdelkader B, Taleb A, Abdi S. Reconsidering vitamin D optimal values based on parathyroid hormone levels in a North Algerian cohort: stratification by gender and season. Archives of osteoporosis 2022. link 7 Alizadeh K, Ahmadi S, Sarchahi AA, Mohri M. The effects of age, sex, breed, diet, reproductive status and housing condition on the amounts of 25(OH) vitamin D in the serum of healthy dogs: Reference values. Veterinary medicine and science 2022. link 8 Rahul M, Gowthaman K, Tewari N, Mathur V. Dental manifestations of pseudo-vitamin-D deficiency rickets in a paediatric patient. BMJ case reports 2021. link 9 Le Moigno JM, Annweiler G, Karras SN, Llewellyn DJ, Riou J, Annweiler C. Clinical identification of older adults with hypovitaminosis D: Feasibility, acceptability and accuracy of the 'Vitamin D Status Diagnosticator' in primary care. The Journal of steroid biochemistry and molecular biology 2020. link 10 Callaby R, Hurst E, Handel I, Toye P, Bronsvoort BMC, Mellanby RJ. Determinants of vitamin D status in Kenyan calves. Scientific reports 2020. link 11 Moon RJ, Davies JH, Cooper C, Harvey NC. Vitamin D, and Maternal and Child Health. Calcified tissue international 2020. link 12 Teshima T, Kurita S, Sasaki T, Matsumoto H, Niina A, Abe D et al.. A genetic variant of CYP2R1 identified in a cat with type 1B vitamin D-dependent rickets: a case report. BMC veterinary research 2019. link 13 Özcabı B, Tahmiscioğlu Bucak F, Jaferova S, Oruç Ç, Adrovic A, Ceylaner S et al.. A Case of Vitamin D-Dependent Rickets Type 1A with a Novel Mutation in the Uzbek Population. Journal of clinical research in pediatric endocrinology 2016. link 14 Cuervo C, Abitbol CL, Zilleruelo GE, Freundlich M. Fibroblast growth factor-23 and renin-angiotensin system levels in vitamin-D-dependent rickets type I. Pediatric nephrology (Berlin, Germany) 2016. link 15 Moore D, Wahl R, Levy P. Hypovitaminosis D presenting as diffuse myalgia in a 22-year-old woman: a case report. The Journal of emergency medicine 2014. link 16 Neyestani TR, Hajifaraji M, Omidvar N, Nikooyeh B, Eshraghian MR, Shariatzadeh N et al.. Calcium-vitamin D-fortified milk is as effective on circulating bone biomarkers as fortified juice and supplement but has less acceptance: a randomised controlled school-based trial. Journal of human nutrition and dietetics : the official journal of the British Dietetic Association 2014. link 17 Sakalli H, Arslan D, Yucel AE. The effect of oral and parenteral vitamin D supplementation in the elderly: a prospective, double-blinded, randomized, placebo-controlled study. Rheumatology international 2012. link 18 Cherniack EP, Florez HJ, Hollis BW, Roos BA, Troen BR, Levis S. The response of elderly veterans to daily vitamin D3 supplementation of 2,000 IU: a pilot efficacy study. Journal of the American Geriatrics Society 2011. link 19 Einarsdóttir K, Preen DB, Clay TD, Kiely L, Holman CD, Cohen LD. Effect of a single 'megadose' intramuscular vitamin D (600,000 IU) injection on vitamin D concentrations and bone mineral density following biliopancreatic diversion surgery. Obesity surgery 2010. link

Secondary hyperparathyroidism of nonrenal origin