Corticosteroids low in post-surgical hypoparathyroidism patients
Calcium, Vitamin D failed to restore adrenal gland hormones, per study
People with hypoparathyroidism due to surgery have reduced levels of corticosteroids, or hormones produced by the adrenal gland, despite adequate treatment with calcium and vitamin D supplementation, a small study reported.
Data showed that short-term replacement parathyroid hormone (PTH) therapy partly restored these hormones to normal levels.
Low hormone levels may contribute to reduced health-related quality of life in treated hypoparathyroidism patients, the researchers noted. “The findings indicate that hypoparathyroid patients with very low PTH are in a constant low corticosteroid state,” they wrote, suggesting that “patients need treatment with PTH not only to restore calcium metabolism but also corticosteroid secretion.”
The study, “Corticosteroid rhythms in hypoparathyroid patients,” was published in the European Journal of Endocrinology.
In hypoparathyroidism, the parathyroid glands, four small glands in the neck, produce low levels of PTH. This results in low calcium and high phosphorus levels in the bloodstream, which can lead to symptoms including muscle weakness, cramps, pain, and twitching.
Hypoparathyroidism treatment
The most common type of hypoparathyroidism is acquired, usually caused by damage to the parathyroid glands during head or neck surgery. The disease can also be congenital, genetically inherited, or triggered by a mistaken immune response against the parathyroid glands.
Hypoparathyroidism treatment aims to ease symptoms by restoring calcium levels, mainly via supplementation with calcium and activated vitamin D (calcitriol), which promotes calcium absorption in the gut. Replacement therapy with a lab-made source of PTH is also available and is used in combination with calcium and vitamin D supplements.
Even when treatment restores calcium levels in the bloodstream, many people with hypoparathyroidism can experience a low quality of life.
Studies in animal and human cells have suggested a link between PTH and the secretion of hormones produced by the adrenal glands, which sit atop the kidneys. Such adrenocortical hormones include cortisol, cortisone, and aldosterone, all of which play essential roles in various bodily functions.
However, “the physiological role of PTH on adrenocortical secretion and its clinical implications, if any, are unclear,” the researchers wrote.
The scientists in Norway conducted a Phase 1 trial (NCT02986607) to determine whether low PTH can interfere with the secretion of adrenocortical hormones in adults with postsurgical hypoparathyroidism. The team also assessed whether PTH replacement therapy alters secretion patterns.
The study enrolled 10 adults, ages 30-60, who had post-surgical hypoparathyroidism and very low PTH levels while on stable treatment with active vitamin D and calcium. A group of 10 age- and sex-matched healthy volunteers served as controls.
Cortisol, cortisone, and aldosterone levels were measured over 24 hours from subcutaneous (under-the-skin) tissue. Cortisol was also measured in blood, saliva, and urine, and aldosterone in blood samples.
Tests found that both patient and control groups showed circadian and ultradian rhythms for tissue cortisol, cortisone, and aldosterone. Circadian rhythms refer to fluctuations of hormone levels over a one-day cycle, while ultradian rhythms are recurrent cycles repeated throughout the day.
“This is the first study to show that patients with [hypoparathyroidism] exhibit a similar circadian rhythm of adrenocortical hormone secretion with ultradian fluctuations, akin to that observed in healthy individuals,” the team wrote.
PTH has ‘stimulatory effect’
Even with these matching fluctuations, tissue cortisone and aldosterone levels were significantly lower in hypoparathyroidism patients on standard calcium/active vitamin D treatment than in healthy controls.
Although there were no differences in tissue cortisol between the two groups, the cortisol-to-cortisone ratio and the fraction of cortisol (the percentage of the total cortisol and cortisone) were significantly higher in hypoparathyroidism patients than in healthy controls.
When patients received continuous PTH treatment, cortisol, aldosterone, and cortisone tissue levels significantly increased, and the cortisol-to-cortisone ratio and fraction of cortisol significantly decreased. In particular, tissue cortisol and aldosterone were above the mean control levels after PTH treatment. In contrast, mean cortisone levels were still lower than in controls, and cortisol-to-cortisone ratio and fraction of cortisol were still higher.
Regardless, there were no marked differences in adrenocortical hormones between the groups when measured in blood, urine, or saliva because “the subtle changes in hormones shown in tissue are probably too small to be detected in blood, saliva, and urine,” the researchers noted. “Our data support that PTH has a stimulatory effect on tissue levels of cortisol, cortisone, and aldosterone, and reduce the cortisol to cortisone ratio in tissue toward the levels seen in healthy subjects,” they concluded.
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