Association between lithium treatment and renal, thyroid and parathyroid function: A cohort study of 6659 patients with bipolar disorder.

OBJECTIVES: Although potential adverse effects of lithium treatment on renal and endocrine systems have been extensively investigated, most prior studies are limited by selected populations and short follow-up. METHODS: Within the Psychiatric Services of the Central Denmark Region, we identified all patients with bipolar disorder and ≥1 serum-lithium (se-Li) measurements between January 1, 2013, and July 20, 2022, and reference patients with bipolar disorder matched on age, sex, and baseline creatinine. Outcomes were diagnoses of renal, thyroid and parathyroid disease, and blood tests measuring creatinine, estimated glomerular filtration rate (eGFR), thyroid-stimulating hormone (TSH), parathyroid hormone (PTH) and calcium. Analyses included unadjusted multilevel regression to describe changes in biochemical markers, and adjusted Cox regression to compare rates of disease/biochemical outcomes between lithium users and reference patients. RESULTS: Among 1646 lithium users (median age 36 years, 63% women) and 5013 reference patients, lithium users had decreasing TSH and eGFR, stable PTH, and increasing calcium levels over time. Lithium use was associated with increased rates of renal, thyroid and parathyroid disease, and levels of biochemical markers outside normal ranges (hazard rate ratios: 1.07-11.22), but the absolute number of severe outcomes was low (e.g., chronic kidney disease: N = 10, 0.6%). Notably, the rate of blood testing was substantially higher among lithium users than among reference patients (e.g., mean number of creatinine tests during the second year of follow-up: lithium users = 2.5, reference patients = 1.4). CONCLUSIONS: Severely adverse renal and endocrine outcomes are rare during lithium treatment. Observational studies of long-term lithium treatment are prone to detection bias.

Management of immune-related adverse events in endocrine organs induced by immune checkpoint inhibitors: clinical guidelines of the Japan Endocrine Society.

Immune checkpoint inhibitors (ICIs) have become a promising treatment for advanced malignancies. However, these drugs can induce immune-related adverse events (irAEs) in several organs, including skin, gastrointestinal tract, liver, muscle, nerve, and endocrine organs. Endocrine irAEs comprise hypopituitarism, primary adrenal insufficiency, thyroid dysfunction, hypoparathyroidism, and type 1 diabetes mellitus. These conditions have the potential to lead to life-threatening consequences, such as adrenal crisis, thyroid storm, severe hypocalcemia, and diabetic ketoacidosis. It is therefore important that both endocrinologists and oncologists understand the clinical features of each endocrine irAE to manage them appropriately. This opinion paper provides the guidelines of the Japan Endocrine Society and in part the Japan Diabetes Society for the management of endocrine irAEs induced by ICIs.

Long-term effects of lithium on renal, thyroid, and parathyroid function: a retrospective analysis of laboratory data.

BACKGROUND: Lithium is a widely used and highly effective treatment for mood disorders, but causes poorly characterised adverse effects in kidney and endocrine systems. We aimed to analyse laboratory information system data to determine the incidence of renal, thyroid, and parathyroid dysfunction associated with lithium use. METHODS: In a retrospective analysis of laboratory data from Oxford University Hospitals National Health Service Trust (Oxfordshire, UK), we investigated the incidence of renal, thyroid, and parathyroid dysfunction in patients (aged ≥18 years) who had at least two creatinine, thyrotropin, calcium, glycated haemoglobin, or lithium measurements between Oct 1, 1982, and March 31, 2014, compared with controls who had not had lithium measurements taken. We used survival analysis and Cox regression to estimate the hazard ratio (HR) for each event with lithium use, age, sex, and diabetes as covariates. FINDINGS: Adjusting for age, sex, and diabetes, presence of lithium in serum was associated with an increased risk of stage three chronic kidney disease (HR 1·93, 95% CI 1·76-2·12; p<0·0001), hypothyroidism (2·31, 2·05-2·60; p<0·0001), and raised total serum calcium concentration (1·43, 1·21-1·69; p<0·0001), but not with hyperthyroidism (1·22, 0·96-1·55; p=0·1010) or raised adjusted calcium concentration (1·08, 0·88-1·34; p=0·4602). Women were at greater risk of development of renal and thyroid disorders than were men, with younger women at higher risk than older women. The adverse effects occurred early in treatment (HR <1 for length of treatment with lithium). Higher than median lithium concentrations were associated with increased risk of all adverse outcomes. INTERPRETATION: Lithium treatment is associated with a decline in renal function, hypothyroidism, and hypercalcaemia. Women younger than 60 years and people with lithium concentrations higher than median are at greatest risk. Because lithium remains a treatment of choice for bipolar disorder, patients need baseline measures of renal, thyroid, and parathyroid function and regular long-term monitoring. FUNDING: None.

Parathyroid hemorrhage occurring after administration of cinacalcet in a patient with secondary hyperparathyroidism.

We herein report an unusual case of spontaneous parathyroid gland rupture. A man was admitted with respiratory distress in September 2010. He had been receiving hemodialysis since 1995. He was diagnosed secondary hyperparathyroidism in 2006 and began receiving cinacalcet therapy in 2009. His intact parathyroid hormone (iPTH) level decreased, and massive traumatic bleeding occurred, following which rupture of the parathyroid gland was detected during surgery. The ruptured gland showed nodular hyperplasia. Previous reports have indicated that parathyroid bleeding is associated with glandular hypertrophy. This is the first report of parathyroid apoplexy occurring after suppression of elevated parathyroid function caused by cinacalcet therapy.

Cisplatin and carboplatin induced changes in the neurohypophysis and parathyroid, and their role in nephrotoxicity.

Cytochemical and ultrastructural studies in Wistar rats [Crl: (WI)BR] show that cisplatin treatment (5-9 mg/kg) induces a release of neurosecretory granules from the neurohypophysis with a corresponding decrease in the urine output in a time and dose dependent fashion. Cisplatin induces low blood calcium and phosphate levels with a corresponding increase in the dark cells of the parathyroid gland. Injections of calcium before and during the treatment of cisplatin are effective in combating hypocalcemia, nephrotoxicity and gastrointestinal toxicity due to cisplatin. Carboplatin, a less nephrotoxic agent, does not demonstrate any of these changes.

Parathyroid glands in chronic aluminum intoxication.

In chronic renal failure, aluminum overload may influence parathyroid function. In a study of possible aluminum-induced parathyroid abnormalities, parathyroid glands from nine parathyroidectomized patients on hemodialysis were examined by light and electron microscopy and by X-ray microanalysis. Aluminum overload was assessed by the presence of stainable aluminum (aluminum surface, 23.3% +/- 11% of total surface) in bone biopsy specimens. The mean plasma aluminum concentration was 7.7 +/- 1.9 mumol/L. All patients but one had elevated plasma concentrations of immunoreactive parathyroid hormone as well as osteitis fibrosa. The aluminum concentrations in bone and parathyroid gland from these patients were significantly higher than those in tissue from patients on hemodialysis without stainable bone aluminum. Abundant aluminum deposits were present in parathyroid chief cell cytoplasm in lipoid bodies, lipofuscin granules, and mitochondria. These cells exhibited features of active hormonal synthesis and contained numerous secretory granules. The data show that in the parathyroid glands of these aluminum-intoxicated patients the presence of aluminum deposits neither induced cellular damage or chief cell necrosis nor interfered with the production of parathyroid hormone.

Pathologic effects of chronic administration of hydrochlorothiazide, with and without sodium nitrite, to F344 rats.

The diuretic drug hydrochlorothiazide was administered to 24 male and 24 female F344 rats as a mixture of 0.1% in powdered food. A parallel group of the same size was given 0.1% hydrochlorothiazide plus 0.2% sodium nitrite in the food. A third group received 0.2% sodium nitrite in the food and there was a similar group of untreated controls. The treatments were well tolerated and there was no significant life shortening. A majority of the rats given hydrochlorothiazide, with or without nitrite, developed chronic progressive nephropathy, which was more severe in males than in females. Associated with this were diffuse parathyroid hyperplasia in both groups receiving the drug, also more severe in males than in females, and parallel increases in lesions of the blood vessels (mural thrombosis of the heart and polyarteritis). The few adenomas of the parathyroid and tubular cell adenomas of the kidney in rats ingesting hydrochlorothiazide were not statistically significant.

Thirty years of fluoridation: a review.

Fluoride contributes to stability of both teeth and bones and to reduction of caries, especially if ingested before eruption of teeth. Reduction of caries continues at about 60% in persons drinking fluoridated water only as long as fluoride washes over teeth. One-half the population of the US does not have access to water with an optimal fluoride concentration of about 1 mg/L. Misinformation about fluoridation contributes to reluctance of communities to supplement the natural but inadequate fluoride of those water supplies. Fluoridation of water has no positive or negative effect on incidence or mortality rates due to cancer, heart disease, intracranial lesions, nephritis, cirrhosis, mongoloid births, or from all causes together. The collective decision to increase the natural fluoride content of water supplies is not an infringement of civil rights, nor does it establish a precedent in the binding sense of the law. Supplemental fluoride in water makes it available to all members of the community in a safe, practical, economical and reliable manner. Fluoridation saves money in dental costs and time lost from work. Fluoridation is an appropriate action of government in promoting the health and welfare of society.

Atypical cilia in ciliated cysts of the parathyroid glands of dogs exposed to ozone.

This report deals with the occurrence of atypical cilia in ciliated cysts of parathyroid glands in dogs after exposure to ozone inhalation at 0.75 ppm close level for 48 h. Electron microscopic examination revealed cytoplasmic blebs with none, one, two ore more axial microtubule complexes (compound) surrounded by a single membrane and containing little or excessive matrix. Also seen where helicoidal cilia. The present anomalous behaviour of the cilia in the prevalent ciliated cysts in ozone treated dogs is consistent with the previously described effects of ozone inhalation on the parathyroid glands.

Occurrence of APUD-type cells in the ciliated cyst of the parathyroid gland of ozone-exposed dogs.

Presence of APUD-type cells in the ciliated cysts of the parathyroid glands of ozonized dog is described in this report. These cells were present on the abluminal side of the cyst wall and contained secretory granules with dense core, homogeneous matrix and coated vesicles throughout the cytoplasm. Intermixed with the granules were sheaves of microfilaments which were mostly seen in the perinuclear area. The APUD cells formed hemidesmosomes with the basal lamina.

The role of toxicity in the carcinogenicity of endosulfan.

Two studies have been undertaken on the toxicity and carcinogenicity of endosulfan, a chlorinated cyclodiene - the NCI Endosulfan Rat Study and the NCI Endosulfan Mouse Study. Histological sections have been examined and the results of this review are based on my diagnoses. Endosulfan is highly toxic for male and female osborne-Mendel rats, particularly for male rats. The chemical causes interstitial fibrosis or acute tubular necrosis of the kidney and death. These lesions, as well as atrophy of the testes, polyarteritis, parathyroid hyperplasia, osteitis fibrosis of bone, and abscesses of the lung, interfere with the health of the animals and with the development of neoplasms. Endosulfan, even though it is extremely toxic, is carcinogenic for male and female Osborne-Mendel rats. The chemical induced malignant neoplasms at all sites in male and female rats and the endocrine organs in male rats. Rats of both sexes developed lymphosarcomas, and female rats had neoplasms of the reproductive system. Endosulfan is also carcinogenic for the liver of female mice.

Morphology of microvascular changes and endothelial regeneration in experimental ozone-induced parathyroiditis. III. Some pathologic considerations.

Proliferation of the vascular endothelium of the parathyroid glands of dogs exposed to ozone inhalation was studied. Direct observation of mitoses in the endothelial cells were made. Focal hemorrhages in the form of the presence of erythrocytes, clotting, and fibrin deposition in the extravascular spaces were seen. Ultrastructural analysis of transverse section of blood vessels showed intravascular platelet aggregation. Lymphoid cells were observed in the lumen of the blood vessels as well as in the perivascular areas as infiltrates. The possibility is discussed that present vascular reactions signify the morphologic equivalent of an immunologic response.

Magnesium toxicity: bone lesions.

Broiler chicks fed corn-soy rations supplemented with toxic levels of magnesium from one day of age grew poorly, developed diarrhea, and exhibited characteristic skeletal abnormalities. Tibiae from magnesium intoxicated chicks were shortened, thickened, and bowed. Percent tibial ash was greatly reduced. Upon microscopic examination, the bone lesion appeared rachitic as evidenced by widened and lengthened growth plates, excessive osteoid seams on endochandral bone, and osteoid or bone capped metaphyseal blood vessels with very few associated osteoblasts. Tibial calcium to phosphorus mass ratios decreased while tibial magnesium to phosphorus mass ratios increased concomitantly with increased dietary magnesium. Calcium and phosphorus homeostasis was possibly affected as evidenced by a general decrease in size and cellularity of parathyroid glands and a general increase in size and cellularity of ultimobranchial glands.