Rare PTH Gene Mutations Causing Parathyroid Disorders: A Review.

Since parathyroid hormone (PTH) was first isolated and its gene (PTH) was sequenced, only eight PTH mutations have been discovered. The C18R mutation in PTH, discovered in 1990, was the first to be reported. This autosomal dominant mutation induces endoplasmic reticulum stress and subsequent apoptosis in parathyroid cells. The next mutation, which was reported in 1992, is associated with exon skipping. The substitution of G with C in the first nucleotide of the second intron results in the exclusion of the second exon; since this exon includes the initiation codon, translation initiation is prevented. An S23P mutation and an S23X mutation at the same residue were reported in 1999 and 2012, respectively. Both mutations resulted in hypoparathyroidism. In 2008, a somatic R83X mutation was detected in a parathyroid adenoma tissue sample collected from a patient with hyperparathyroidism. In 2013, a heterozygous p.Met1_Asp6del mutation was incidentally discovered in a case-control study. Two years later, the R56C mutation was reported; this is the only reported hypoparathyroidism-causing mutation in the mature bioactive part of PTH. In 2017, another heterozygous mutation, M14K, was detected. The discovery of these eight mutations in the PTH gene has provided insights into its function and broadened our understanding of the molecular mechanisms underlying mutation progression. Further attempts to detect other such mutations will help elucidate the functions of PTH in a more sophisticated manner.

Neurologic disorders of mineral metabolism and parathyroid disease.

Disorders of mineral metabolism may cause neurologic manifestations of the central and peripheral nervous systems. This is because plasma calcium stabilizes excitable membranes in the nerve and muscle tissue, magnesium is predominantly intracellular and is required for activation of many intracellular enzymes, and extracellular magnesium affects synaptic transmission. This chapter reviews abnormalities in electrolytes and minerals which can be associated with several neuromuscular symptoms including neuromuscular irritability, mental status changes, cardiac and smooth muscle changes, etc.

Parathyroid disorders.

Disorders of the parathyroid glands most commonly present with abnormalities of serum calcium. Patients with primary hyperparathyroidism, the most common cause of hypercalcemia in outpatients, are often asymptomatic or may have bone disease, nephrolithiasis, or neuromuscular symptoms. Patients with chronic kidney disease may develop secondary hyperparathyroidism with resultant chronic kidney disease-mineral and bone disorder. Hypoparathyroidism most often occurs after neck surgery; it can also be caused by autoimmune destruction of the glands and other less common problems. Evaluation of patients with abnormal serum calcium levels includes a history and physical examination; repeat measurement of serum calcium level; and measurement of creatinine, magnesium, vitamin D, and parathyroid hormone levels. The treatment for symptomatic primary hyperparathyroidism is parathyroidectomy. Management of asymptomatic primary hyperparathyroidism includes monitoring symptoms; serum calcium and creatinine levels; and bone mineral density. Patients with hypoparathyroidism require close monitoring and vitamin D (e.g., calcitriol) replacement.

Parathyroid and calcium metabolism disorders during pregnancy.

Parathyroid disorders are not common among pregnant women, but harbor a significant morbidity and mortality potential if they remain unrecognized and untreated. The symptoms caused by abnormally low or high blood free calcium level are mostly non-specific in the initial stages, thus when recognized might pose a real danger. Here we will survey the alterations in calcium metabolism induced by pregnancy, and describe the clinical manifestations, diagnosis and treatment of parathyroid and other calcium metabolism disorders during pregnancy. The current literature on the impact of calcium and vitamin D deficiency during pregnancy will also be reviewed.

Thyroid and parathyroid surgery in pregnancy.

The consideration of surgery during pregnancy requires weighing the benefit of urgent surgery against the risk to mother and fetus. Surgery during pregnancy involves an increase in both maternal and fetal risks. Thyroid and parathyroid surgery involves physiological risks to both mother and fetus specific to the disease and function of these endocrine glands. Evaluation of a thyroid mass is similar in pregnant patients with ultrasound and fine-needle aspiration biopsy providing the most important information, while the use of radiographic imaging is severely constrained except when specifically required. In general, thyroid surgery can be delayed until after delivery except in cases of airway compromise or aggressive cancer. In contrast, parathyroid surgery is recommended during pregnancy to avoid adverse effects to the neonate.

Endocrine and metabolic manifestations of invasive fungal infections and systemic antifungal treatment.

Systemic fungal infections are increasingly reported in immunocompromised patients with hematological malignancies, recipients of bone marrow and solid organ allografts, and patients with AIDS. Mycoses may infiltrate endocrine organs and adversely affect their function or produce metabolic complications, such as hypopituitarism, hyperthyroidism or hypothyroidism, pancreatitis, hypoadrenalism, hypogonadism, hypernatremia or hyponatremia, and hypercalcemia. Antifungal agents used for prophylaxis and/or treatment of mycoses also have adverse endocrine and metabolic effects, including hypoadrenalism, hypogonadism, hypoglycemia, dyslipidemia, hypernatremia, hypocalcemia, hyperphosphatemia, hyperkalemia or hypokalemia, and hypomagnesemia. Herein, we review how mycoses and conventional systemic antifungal treatment can affect the endocrine system and cause metabolic abnormalities. If clinicians are equipped with better knowledge of the endocrine and metabolic complications of fungal infections and antifungal therapy, they can more readily recognize them and favorably affect outcome.

[Parathyroid cyst associated with acute respiratory failure and jugular vein thrombosis].

Parathyroid cysts are much less common than other cystic lesions of the neck. The great majority of parathyroid cysts are endocrine non-functioning. Parathyroid cysts may become symptomatic because of hormonal activity or due to the size and pressure effects. This is a case history of a 43 year-old woman, who presented with dyspnea. A 9 + 8 + 6cm cervical-mediastinal parathyroid cyst causing dyspnea, dysphagia, respiratory failure and jugular vein thrombosis was found.

Endocrine sequelae of cancer and cancer treatments.

INTRODUCTION: Exposure to cancer and its treatments, including chemotherapy and radiotherapy, may result in late adverse effects including endocrine dysfunction. Endocrine disorders are the most commonly reported long-term complications of cancer treatment, especially by adult survivors of childhood cancers. This review will explore the endocrinologic adverse effects from non-endocrine cancer therapies. METHODS: Searches including various Internet-based medical search engines such as PubMed, Medline Plus, and Google Scholar were conducted for published articles. RESULTS: One hundred sixty-nine journal articles met the inclusion criteria. They included case reports, systematic analyses, and cohort reports. Endocrine disorders including hypothalamus dysfunction, hypopituitarism, syndrome of inappropriate anti-diuretic hormone secretion, diabetes insipidus, growth hormone disorders, hyperprolactinemia, gonadotropin deficiency, serum thyroid hormone-binding protein abnormalities, hypothyroidism, hyperthyroidism, hypomagnesium, hypocalcemia, hyperparathyroidism, hyperparathyroidism, adrenal dysfunction, gonadal dysfunction, hypertriglyceridemia, hypercholesterolemia, diabetes mellitus, and glycosuria were identified and their association with cancer therapies were outlined. DISCUSSION/CONCLUSIONS: The journal articles have highlighted the association of cancer therapies, including chemotherapy and radiotherapy, with endocrine dysfunction. Some of the dysfunctions were more often experienced than others. Especially in patients treated with radiotherapy, some endocrinologic disorders were progressive in nature. IMPLICATIONS FOR CANCER SURVIVORS: Recognition and awareness of endocrine sequelae of cancer treatments may permit for early detection and appropriate follow-up care for cancer survivors, thus improving their overall health and quality of life.

Ultrasonographic evaluation of parathyroid hyperplasia in dialysis patients.

Secondary hyperparathyroidism (SHPT) is one of the most common complications in patients with chronic kidney disease (CKD). Bone and mineral disorders, increased morbidity and mortality are the consequences of SHPT. Therefore, prevention and control of hyperparathyroidism is one of the main objectives in the management of patients with CKD, particularly in dialysis patients. It is well known that SHPT in CKD is not only a state of increased parathyroid hormone (PTH) synthesis and secretion, but more importantly, it is a state of parathyroid gland (PTG) hyperplasia. The serum concentration of intact PTH is the main method used to assess PTG overactivity. Unfortunately, estimating the size and shape of the PTG in SHPT diagnosis, i.e., parathyroid hyperplasia, is still neglected. Among the various procedures, ultrasonography could be the method of choice to detect PTG size and shape because of its simplicity and noninvasiveness. This method can be sufficiently sensitive to distinguish diffuse and nodular hyperplasia.