ESPE Yearbook of Paediatric Endocrinology

Eur J Endocrinol. 2024; 191(3): 271-278. PMID: 39167533 doi: 10.1093/ejendo/lvae102. https://pubmed.ncbi.nlm.nih.gov/39167533/

Brief summary: This paper reports a crossover intervention study of 10 patients with primary hyperparathyroidism and 10 healthy volunteers, matched for sex and age.

Comment: It is infrequently noted that in hypoparathyroidism, deficiency in parathyroid hormone (PTH) is associated with lower concentrations of both aldosterone and corticosteroids (cortisol and cortisone) in tissues (1). There is evidence that PTH increases the secretion of aldosterone from the adrenals directly, as well as indirectly by activating the renin–angiotensin system (2). Upregulation of aldosterone synthesis might contribute to the higher risk of arterial hypertension and of cardiovascular damage in patients with primary hyperparathyroidism (3). A direct relation between PTH secretion and adrenocortical secretion is supported by the observation that PTH stimulates both cortisol and aldosterone from human adrenocortical cells and by the high expression of PTH1R in zona glomerulosa (4).

In this study, adrenocortical hormone concentrations were reduced in postsurgical hypoparathyroidism and partly restored by short-term continuous subcutaneous PTH (1-34) therapy. Tissue aldosterone and cortisone concentrations were lower in hypoparathyroid patients than in healthy controls, with no difference in tissue cortisol, but a higher cortisol to cortisone ratio. The ratio of cortisol to cortisone was higher in hypoparathyroid patients, indicating a potential shift in how these hormones are processed (1). Despite the reduced concentrations, both circadian (day-night) and ultradian (shorter than a day) rhythms of cortisol, cortisone, and aldosterone were still present in hypoparathyroid patients. In addition, hypoparathyroid patients displayed both ultradian and circadian rhythmicity for tissue cortisol, cortisone, and aldosterone. When treated with PTH (1-34), hypoparathyroid patients showed increased tissue concentrations of aldosterone, cortisol, and a decrease in the cortisol to cortisone ratio, suggesting a restoration of normal hormone balance.

Understanding these rhythm alterations and the impact of PTH therapy is of clinical significance as it can help clinicians optimize treatment strategies for hypoparathyroidism and potentially improve patient outcomes.

References: 1. Sinha SR, Prakash P, Keshari JR, KumariR, Prakash V. Assessment of Serum Cortisol Levels in Hypothyroidism Patients: A Cross-Sectional Study. Cureus, 2023; 15(12): e50199.2. Tomaschitz A, Ritz E, Pieske B, Fahrleitner-Pammer A, Kienreich K, Horina JH, Drechsler C, März W, Ofner M, Pieber TR, Pilz S. Aldosterone and parathyroid hormone: a precarious couple for cardiovascular disease, Cardiovascular Research, 2012; 94(1): 10–19.3. Hagström E, Hellman P, Larsson TE, et al. Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation. 2009;119(21):2765–2771.4. Mazzocchi G, Aragona F, Malendowicz LK, Nussdorfer GG, PTH and PTH-related peptide enhance steroid secretion from human adrenocortical cells. American Journal of Physiology-Endocrinology and Metabolism 2001; 280(2): E209-E213.