The Case of the Missing Hormone
Lauren is a delightful 51-year-old female who I had been seeing for several years for osteoporosis when her calcium levels began to rise slowly but surely. Blood tests revealed overactive parathyroid gland(s), not to be confused with the thyroid gland. In contrast to the thyroid, which controls metabolism, the parathyroid gland simply keeps calcium levels stable in the bloodstream. When the parathyroid gland goes haywire and spews out its namesake hormone, calcium levels increase. Imaging revealed that all four of her parathyroid glands were overfiring. This condition is called parathyroid hyperplasia and is problematic for many reasons. While it is non-cancerous, the excess parathyroid hormone breaks down bone, and the elevated calcium levels increase the risk of kidney stones and kidney dysfunction. In addition, according to many studies, the condition also causes a non-specific malaise or “brain fog”.
I recommended that Lauren consult with a surgeon at Columbia. In early 2025, Lauren had 3.5 out of her 4 parathyroid glands removed as per normal surgical protocol. Her remaining ½ parathyroid gland was then implanted in her forearm muscle. The hope for this type of surgery is that the parathyroid tissue in the forearm “magically” produces the optimal amount of hormone to normalize calcium levels. Unfortunately for Lauren, shortly after surgery, she developed tingling around her mouth and in her fingers and toes. These were telltale signs of low calcium due to the absence of adequate parathyroid hormone. Since parathyroid hormone is necessary to activate vitamin D in the bloodstream, without parathyroid hormone, vitamin D remains inactive and virtually useless.
Traditionally, the treatment for surgery-induced hypoparathyroidism (low parathyroid hormone) is a medication called calcitriol. Calcitriol is just an activated form of vitamin D used to circumvent the issue of the missing parathyroid hormone. More recently, a synthetic form of parathyroid hormone, called Yorvipath, hit the market. The question is, why would it be advantageous to take parathyroid hormone rather than simply taking activated vitamin D?
Until Yorvipath’s release, EVERY OTHER missing hormone in the body had a synthetic replacement form (there was another brand of synthetic parathyroid hormone which was on the market from 2015 until 2022). Although calcitriol effectively deals with the issue of low calcium with hypoparathyroidism, there are long term concerns about kidney function and calcium deposits throughout the body. Without parathyroid hormone, normal calcium balance can’t be restored at the level of the skeletal system, nervous system and brain. Many studies have demonstrated improvement mentally and physically in patients who switched from calcitriol to parathyroid replacement therapy[1], [2]. In addition, studies have shown a higher long-term risk of schizophrenia, depression, anxiety in hypoparathyroid patients treated exclusively with calcitriol.
Last week, I was finally able to start Lauren on the holy grail of endocrinology, her missing parathyroid hormone. Although it is too soon to know if this will improve her long-term outcomes, her calcium levels are now perfect without calcitriol or high dose calcium supplements. Her brain fog has already lifted, and stay tuned for updates regarding her bone density…
[1] Santonati A, Palermo A, Maddaloni E, et al. ; Hypoparathyroidism AME Group PTH(1-34) for surgical hypoparathyroidism: a prospective, open-label investigation of efficacy and quality of life. J Clin Endocrinol Metab. 2015;100(9):3590–3597.
[2] Palermo A, Santonati A, Tabacco G, et al. PTH(1-34) for surgical hypoparathyroidism: a 2-year prospective, open-label investigation of efficacy and quality of life. J Clin Endocrinol Metab. 2018;103(1):271–280.