Endocrine Abstracts

Case history: A 50-year-old lady, on Lithium for 30 years, presented with a history of progressively increasing thirst since 12 months; associated with polyuria and nocturia. She had been having some joint aches and was finding it more difficult to get up and down stairs. She was found to be hypothyroid few months back and prior to that had been falling asleep easily. There had been an improvement in her energy levels after starting Levothyroxine. She gave no history of renal calculi. Her father had been on Lithium and her mother had renal calculi.

Investigations: 6 months back, her adjusted calcium was 2.61 mmol/l, phosphate was 0.79 mmol/l with PTH elevated at 9.0 pmol/l. A repeat test done the following month showed an adjusted calcium of 2.71 mmol/l, with PTH 10.0 of pmol/l and a normal 25-hydroxy vitamin-D of 62 nmol/l. Her most recent TSH was 0.84 mU/l and plasma sodium was 144 mmol/l. Ultrasound of the neck showed a mild diffuse goitre with changes consistent with lithium-induced thyroiditis, with normal parathyroids.

Results and treatment: Suspecting Lithium-induced nephrogenic DI, urine and plasma osmolalities were done after overnight water deprivation, which were 153 mOsm/kg and 303 mOsm/kg respectively. Hence, she was started on Amiloride to manage the nephrogenic DI. Elevated PTH was likely secondary to Lithium effect.

Conclusions and point for discussion: Lithium inhibits AVP-stimulated translocation of cytoplasmic urinary aquaporin-2 (AQP2) to the apical membrane. Failure of AQP2 insertion leads to delivery of a hypo-osmotic fluid to the medullary collecting duct, whose capacity to reabsorb water is blunted, resulting in the excretion of large volumes of dilute urine. Long-term exposure to Lithium may also down-regulate AQP2 gene expression. Amiloride inhibits the uptake of lithium in the collecting duct, leading to reduced mean urine volume, increased urine osmolality, and better renal response to ADH. Lithium alters the set point of CaSR in parathyroid cells, thus promoting excess parathyroid release. Lithium affects normal thyroid functioning through multiple mechanisms. At the cellular level, it decreases thyroid hormone synthesis and release. It also decreases peripheral deiodination of thyroxine by decreasing the activity of type-I 5’ de-iodinase enzyme. Hypothyroidism and goitre (clinically and/ultrasonographically) are the most prevalent thyroid abnormalities among patients on long-term lithium therapy. Our case was unique since she exhibited 3 different endocrinopathies simultaneously-Lithium-induced nephrogenic DI, hypothyroidism (secondary to thyroiditis) and hyperparathyroidism.