Parathyroid lithium

Many of the adverse effects of lithium can be ascribed to the action of lithium on adenylate cyclase, the key enz)nne that links many hormones and neurotransmitters with their intracellular actions. Thus antidiuretic hormone and thyroid-stimulating-hormone-sensitive adenylate cyclases are inhibited by therapeutic concentrations of the drug, which frequently leads to enhanced diuresis, h)rpoth)n oidism and even goitre. Aldosterone synthesis is increased following chronic lithium treatment and is probably a secondary consequence of the enhanced diuresis caused by the inhibition of antidiuretic-hormone-sensitive adenylate cyclase in the kidney. There is also evidence that chronic lithium treatment causes an increase in serum parathyroid hormone levels and, with this, a rise in calcium and magnesium concentrations. A decrease in plasma phosphate and in bone mineralization can also be attributed to the effects of the drug on parathyroid activity. Whether these changes are of any clinical consequence is unclear. 

Reports of hyperthyroidism associated with lithium include one in a woman who was also hypercalcemic with a normal parathyroid hormone (PTH) concentration (645) and two discovered while treating lithium toxicity (646). 

Ten patients who had taken lithium for less than 1 year and 13 who had taken it for more than 3 years were assessed for alterations in bone metabolism and parathyroid function (654). There were no differences in bone mineral density, serum calcium concentration, or PTH concentration, but both groups had increased bone turnover and the longterm group had nonsignificantly higher calcium and PTH concentrations (including one hyperparathyroid patient who had an adenoma excised). The authors conclusion that lithium therapy is not a risk factor for osteoporosis needs to be tempered by the small sample size, the case of adenoma, and the blood concentration trends. 

A 64-year-old woman who had taken lithium for over 10 years was admitted with altered consciousness, agitation, and disorientation. The serum calcium was 3.35 mmol/1 (reference range 2.1-2.6 mmol/1) and the PTH concentration was raised. With hydration and conversion from lithium to valproate, the serum calcium concentration normalized, but 2 years later disorientation and hypercalcemia recurred and a 150 mg parathyroid adenoma was removed surgically (665). 

A 53-year-old woman who had taken lithium for 9 years and carbamazepine for 3 years and had a 3-month history of lethargy was found to be hypercalcemic with a raised concentration of iPTH. She was saved from parathyroid surgery when withdrawal of lithium resolved the hypercalcemia (666). 

A 51-year-old man who had taken lithium for over 10 years presented with nausea, vomiting, anorexia, hypercalcemia (3.1 mmol/1), and increased PTH concentration (iPTH 110 ng/1). Abnormalities resolved after an oxyphilic parathyroid adenoma was excised (667). 

A woman who had taken lithium for 15 years who became hypercalcemic and stopped taking lithium, but 2 years later had two parathyroid adenomas removed surgically (670). 

A 42-year-old man who had taken lithium for 17 years and who had raised serum calcium and PTH concentrations which normalized after removal of a parathyroid adenoma (671). 

A lithium chloride solution caused changes in gravicur-vature, statocyte ultrastructure, and calcium balance in pea root, believed to be due to effects of lithium on the phosphoinositide second messenger system (678). The implications with regard to human parathyroid function are obscure. 

Of 12 patients who underwent parathyroid gland resection while maintaining their intake of lithium, only eight remained normocalcemic (679). Nevertheless, the authors recommended that surgery should be considered if there is hyperparathyroidism. 

Kusalic M, Engelsmann F. Effect of lithium maintenance therapy on thyroid and parathyroid function. J Psychiatry Neurosci 1999 24(3) 227-33. 

Mira SA, Gimeno EJ, Diaz-Guerra GM, Carranza YFH. Alteraciones tiroideas y paratiroideas asociadas al trata-miento cronico con litio. A proposito de un caso. [Thyroid and parathyroid alterations associated with chronic lithium treatment. A case report.] Rev Esp Enferm Metab Oseas 2001 10 153-6. 

Awad SS, Miskulin J, Thompson N. Parathyroid adenomas versus four-gland hyperplasia as the cause of primary hyperparathyroidism in patients with prolonged lithium therapy World J Surg 2003 27 486-8. 

Dwight T, Kytola S, Teh BT, Theodosopoulos G, Richardson AL, Philips J, Twigg S, Delbridge L, Marsh DJ, Nelson AE, Larsson C, Robinson BG. Genetic analysis of lithium-associated parathyroid tumors. Eur J Endocrinol 2002 146(5) 619-27. 

Morillas Arino C, Jordan Lluch M, Sola Izquierdo E, Serra Cerda M, Garzon Pastor S, Gomez Balaguer M, Hernandez Mijares YA. [Parathyroid adenoma and lithium therapy.JEndocrinol Nutr 2002 49 56-7. 

Rifai MA, Moles JK, Harrington DP. Lithium-induced hypercalcemia and parathyroid dysfunction. Psychosomatics 2001 42(4) 359-61. 

Valeur N, Andersen RS. Lithium induceret parathyreoi-deahormon dysfunktion. [Lithium induced dysfunction of the parathyroid hormone.] Ugeskr Laeger 2002 164(5) 639 10. 

Hundley JC, Woodrum DT, Saunders BD, Doherty GM, gauger PG. Revisiting lithium-associated hyperparathyroidism in the era of intraoperative parathyroid hormone monitoring. Surgery 2005 138 1027-31. 

In a review of the renal and metabolic complications of lithium, the example of a 78-year-old woman taking longterm lithium who had urinary incontinence, moderate renal insufficiency, a 5-7 litres 24-hour urine volume, and thyroid and parathyroid abnormalities was used to set the scene (306). 

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