The parathyroid gland is responsible for the synthesis and secretion of parathyroid hormone, which is synthesized and released at an inverse relationship to the level of ionized calcium in the blood. Primary hyperparathyroidism affects women more than men. There are various causes for hyperparathyroidism-induced hypercalcemia and the most common cause is parathyroid adenoma. A less common cause of vitamin D-mediated parathyroid hormone-independent hypercalcemia is the loss of function mutation of the CYP24A1 gene. The CYP24A1 gene encodes the vitamin D 24-hydroxylase enzyme, responsible for hydroxylating the active form of vitamin D into an inactive form, and mutations in the CY24A1 gene can lead to elevated active vitamin D metabolite levels. It can result in hypercalcemia and hypercalciuria-related complications. We present a case of a 72-year-old male patient referred to the endocrine clinic, who had repeated treatments for hypercalcemia and recurrent renal calculi. He underwent ultrasound, computerized tomography, and sestamibi scans, all reported as normal. Following this, the patient underwent a positron emission tomography (PET) scan, which was also normal. He then finally underwent genetic testing and tested positive for the CYP24A1 gene. He was started on fluconazole 50mg once a day and cinacalcet 30mg twice with normalization of calcium level. Three of his family members also tested positive for the condition.

Hypercalcemia is a common electrolyte abnormality with different causes. Hypercalcemia is most often associated with malignancy and primary hyperparathyroidism and malignancy together account for most cases. Primary hyperparathyroidism manifests as hypercalcemia owing to the overproduction of parathyroid hormone. In most cases, primary hyperparathyroidism manifests due to a solitary parathyroid adenoma. Based on calcium levels, hypercalcemia can be classified as mild, moderate, and severe. Hypercalcemia typically presents with non-specific clinical features. Here, we present the case of a 38-year-old male patient who presented to the emergency department (ED) with acute abdominal pain and a tender abdomen with absent bowel sounds. He had chest radiography and blood tests initially. Chest radiography showed left-sided pneumoperitoneum, and the patient was suspected to have a perforated peptic ulcer due to hypercalcemia secondary to a parathyroid adenoma during the second wave of the coronavirus disease 2019 (COVID-19) pandemic. The findings were confirmed by a computerized tomography scan of the abdomen, and the patient was treated with intravenous fluids for hypercalcemia and was managed conservatively for a sealed perforated peptic ulcer following discussion in the multi-disciplinary team meeting (MDT). The COVID-19 pandemic led to a long waiting list and delays in the timely management of patients requiring elective surgical intervention, such as parathyroidectomy. The patient made a complete recovery and had parathyroidectomy of the inferior right lobe two months later.

The most common cause of primary hyperparathyroidism (PHPT) is a solid parathyroid adenoma. Less than 2% of cases of PHPT are caused by cystic parathyroid adenomas formed from degeneration of pre-existing solid parathyroid adenomas. Cystic parathyroid adenomas are non-functional in over 90% of cases. In this case we describe management of a 56-year-old man with acute-onset polydipsia, polyuria, xerostomia, nausea, and constipation. Serum chemistry upon admission revealed hypercalcemia, hyperparathyroidism, and reduced serum phosphorus. Neck sonogram revealed a predominantly anechoic lesion later confirmed by pathology to be a cystic parathyroid adenoma in the right thyroid lobe. Sestamibi scan did not show uptake in parathyroid gland, and parathyroid hormone (PTH) was elevated in fine-needle aspiration sample. Otolaryngology removed the cystic lesion via surgical excision, which led to normalization of PTH level. This case demonstrates the importance of evaluation of cystic components for PTH levels and if confirmed should be treated as a parathyroid adenoma.

Hormonal coordination is tightly regulated within the human body and thus regulates human physiology. The parathyroid hormone (PTH), a member of the endocrine system, regulates the calcium and phosphate level within the human body. Under non-physiological conditions, PTH levels get upregulated (hyperparathyroidism) or downregulated (hypoparathyroidism) due to external or internal factors. In the case of hyperparathyroidism, elevated PTH stimulates cellular receptors present in the bones, kidneys, and intestines to increase the blood calcium level, leading to calcium deposition. This eventually causes various symptoms including kidney stones. Currently, there is no known medication that directly targets PTH in order to suppress its function. Therefore, it is of great interest to find novel small molecules or any other means that can modulate PTH function. The molecular signaling of PTH starts by binding of its N-terminus to the G-protein coupled PTH1/2 receptor. Therefore, any intervention that affects the N-terminus of PTH could be a lead candidate for treating hyperparathyroidism. As a proof-of-concept, there are various possibilities to inhibit molecular PTH function by (i) a small molecule, (ii) N-terminal PTH phosphorylation, (iii) fibril formation and (iv) residue-specific mutations. These modifications put PTH into an inactive state, which will be discussed in detail in this review article. We anticipate that exploring small molecules or other means that affect the N-terminus of PTH could be lead candidates in combating hyperparathyroidism.

Caffeine is the most used central nervous system stimulant drug to date. Many studies have shown the association of caffeine with bone remodeling, urinary calcium excretion, kidney stones, acid peptic disease, and the development of cancer. However, there has been very little research exploring the association between caffeine use and parathyroid gland disorders. We shed light on the possible connection between caffeine and parathyroid adenomas, as suggested in the literature.