Hyperparathyroidism in PCa.

[pjoshea13]

New Italian study below. Any ideas?

There are 4 parathyroid glands in the neck (near the thyroid) & they secrete parathyroidism hormone [PTH] in response to a drop in circulating calcium.

The kidneys respond to PTH by converting calcidiol (25-D) to calcitriol (1,25-D) - i.e. creating hormonal vitamin D. Calcitriol is involved in drawing dietary calcium from the gut, & ultimately, replacing calcium initially taken from bone to restore blood levels.

My understanding is that primary would not (by definition) be due to PCa. The effect would be to elevate blood levels of calcium.

"We found nine patients (of 69) with primary hyperparathyroidism in the group of prostate cancer vs. only one {of 53} in {non-PCa} cancer patients group".

The probability of hyperparathyroidism increased with Gleason score.

"... higher aggressiveness of prostate cancer, as determined by Gleason score, is a significant predictor of increased risk of developing primary hyperparathyroidism."

Which suggests that we are looking at secondary hyperparathyroidism - i.e. due to PCa. Secondary hyperparathyroidism is generally caused by calcium levels falling because of disease.

What's confusing here is that excess calcitriol production would normally be considered beneficial in PCa & be associated with lower Gleasons.

On the other hand, PCa might become more aggressive as the calcium:magnesium ratio increases. [2] [3] [4]

"Low blood Mg levels and a high Ca/Mg ratio were significantly associated with high-grade prostate cancer."

Seems important to know if hyperparathyroidism is the chicken or the egg. Primary hyperparathyroidism can perhaps be treated.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/286...

Endocrine. 2017 Jun 28. doi: 10.1007/s12020-017-1351-0. [Epub ahead of print]

Mineral metabolism abnormalities in patients with prostate cancer: a systematic case controlled study.

Minisola F1, Cipriani C2, Colangelo L2, Cilli M2, Sciarra A1, Von Heland M1, Nieddu L3, Anastasi E4, Pascone R5, Fassino V, Diacinti D6, Longo F6, Minisola S7, Pepe J2.

Author information

1

Department of Gynecology-Obstetrics & Urology, Sapienza University of Rome, Rome, Italy.

2

Department of Internal Medicine and Medical Disciplines, Sapienza University of Rome, Rome, Italy.

3

Faculty of Economics, UNINT University, Via delle Sette Chiese 139, 00147, Rome, Italy.

4

Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.

5

Department of Pediatrics and Infantile Neuropsychiatry, Sapienza University of Rome, Rome, Italy.

6

Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.

7

Department of Internal Medicine and Medical Disciplines, Sapienza University of Rome, Rome, Italy. [e-mail].

Abstract

PURPOSE:

Prostate cancer is the most common tumor in men. To the best of our knowledge a systematic assessment of bone and mineral abnormalities has not been performed in prostatic cancer patients consecutively enrolled.

METHODS:

This study was therefore carried out to investigate changes of skeletal and mineral metabolism in patients with prostate cancer (n  = 69). A population of patients with cancer of various origin was also investigated as a control group (n  = 53), since a comparison with non-prostate cancer patients has not been previously reported.

RESULTS:

In the prostatic cancer group, one patient had extremely high values of C-terminal Fibroblast Growth Factor 23, low values of tubular reabsorption of phosphate and very high values of bone alkaline phosphatase, suggesting the diagnosis of oncogenic osteomalacia. We found nine patients with primary hyperparathyroidism in the group of prostate cancer vs. only one in cancer patients group (p  <  0.026). We stratified the population on the basis of Gleason score, prostate specific antigen and hormonal therapy. Using a generalized linear model with a logit link to predict the probability of developing primary hyperparathyroidism, only Gleason score, C-terminal fibroblast growth factor 23 and hormonal therapy had a significant effect (p  < 0.05). Controlling for other covariates, a rise in fibroblast growth factor 23 increases the odds of developing primary hyperparathyroidism by 2% (p  = 0.017), while patients with higher values of Gleason score have a much greater probability of developing primary hyperparathyroidism (log-odds  =  3.6, p  <  0.01). The probability decreases with higher values of Gleason score while on hormonal therapy; a further decrease was observed in patients on hormonal treatment and lower values of GS. Finally, lower grade of Gleason score without hormonal therapy have a significant protective factor (p  <  0.01) decreasing the odds of developing primary hyperparathyroidism by 8%.

CONCLUSION:

We showed a remarkable prevalence of primary hyperparathyroidism in men with prostate cancer; the multivariate analysis demonstrates that higher aggressiveness of prostate cancer, as determined by Gleason score, is a significant predictor of increased risk of developing primary hyperparathyroidism.

KEYWORDS:

FGF23; Hypercalcemia; Hyperparathyroidism; Prostate cancer; Vitamin D

PMID: 28660378 DOI: 10.1007/s12020-017-1351-0

...

[2] ncbi.nlm.nih.gov/pubmed/231...

[3] ncbi.nlm.nih.gov/pubmed/215...

[4] ncbi.nlm.nih.gov/pubmed/108...

[AlanMeyer]

Curiously, I had a months long bout of hyperthyroidism the year before I was diagnosed with a Gleason 4+3 PCa. I never thought about whether there might be a link between them. The hyperthyroidism eventually went away without treatment - before treatment of the cancer began.

I had no PSA test the year I had the thyroid problem.

Alan

[pjoshea13 in reply to AlanMeyer]

Alan,

I don't know if there is any connection between hyperthyroidism & hyperparathyroidism, but I found [1] (first & last sentence) interesting:

"The American Food and Drug Administration approval of parathyroid hormone (PTH) administration for osteoporosis as well as the possibility for its future therapeutic applications requires an examination of the suggested association between PTH and cancer, particularly osteosarcomas."

"Since PTH may contribute to tumor invasiveness, screening for existing neoplasms, especially prostate and breast, before PTH treatment may be of importance."

For years, I have been warning that raising calcitriol (25-D) levels is only half the job with vitamin D supplementation. We should also not do anything that inhibits conversion to hormonal calcitriol (1,25-D). That conversion depends on PTH.

I cannot believe that PTH, at normal levels, is dangerous - & certainly, no more dangerous than suppressed calcitriol, but it appears that PTH has a darker side.

In study [2] (Secondary hyperparathyroidism & zoledronic acid):

"Secondary hyperparathyroidism is frequent in prostate cancer patients with bone metastases, and this condition is worsened by the administration of potent bisphosphonates. Serum parathyroid hormone (PTH) elevation can impair the efficacy of these drugs in terms of survival."

"... elevated baseline serum PTH level was negatively associated with overall survival (hazard ratio [HR], 1.448" (versus placebo)

"In patients with normal baseline PTH levels, there was a trend but insignificant association between zoledronic acid administration and a better survival outcome than with placebo (HR, 0.81 ..."

"Secondary hyperparathyroidism has a negative prognostic impact in metastatic prostate cancer patients undergoing zoledronic acid administration. Counteracting elevated PTH levels by adequate doses of vitamin D may improve the efficacy of this drug."

The last sentence should probably have been written differently. There is an avoidable form of hyperparathyroidism, due to inadeqate calcium intake &/or inadequate vitamin D - i.e. deficiency. "adequate doses" should not be taken to mean high doses IMO.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/165...

[2] ncbi.nlm.nih.gov/pubmed/225...

[AlanMeyer in reply to pjoshea13]

Thanks Patrick.

Not only did I not know about any relationship between thyroid hormones and PCa, I was also ignorant of "hyperparathyroidism" and just assumed, when reading your original posting, that it was the same thing as "hyperthyroidism".

Thanks for the follow-up.

Alan