How do elevated prolactin (Prolactin) levels due to antipsychotic use affect Thyroid-Stimulating Hormone (TSH) levels?

Impact of Antipsychotic-Induced Hyperprolactinemia on TSH Levels

Antipsychotic-induced hyperprolactinemia can lead to subclinical hypothyroidism with elevated TSH levels, which occurs in approximately 4.9% of patients taking medications like quetiapine. 1

Mechanism of Interaction Between Prolactin and Thyroid Function

• Antipsychotics, particularly conventional antipsychotics and high-dose risperidone (>6 mg/day), block dopamine receptors in the tuberoinfundibular pathway, leading to hyperprolactinemia 2
• Hyperprolactinemia can disrupt the hypothalamo-pituitary-thyroid (HPT) axis, affecting TSH response to thyroid-releasing hormone (TRH) 3
• Primary hypothyroidism is reported in 43% of women and 40% of men with hyperprolactinemia, while subclinical hypothyroidism occurs in 36% of women and 32% of men 4
• Elevated prolactin may lead to compensatory mechanisms with slightly elevated basal TSH levels and TSH responses to TRH (typically within normal range) to maintain euthyroidism 5

Clinical Evidence from Medication Studies

• FDA data for quetiapine shows that antipsychotic use is associated with an increased incidence of TSH elevation (>5 mIU/L) in 4.9% of patients compared to 2.7% in placebo groups 1
• In short-term trials with quetiapine, the incidence of reciprocal shifts in T3 and TSH was 0.0%, while for T4 and TSH the shifts were 0.1% 1
• In children and adolescents taking quetiapine, elevated TSH was observed in 2.9% of patients versus 0.7% in placebo groups 1
• Phenothiazine antipsychotics primarily alter iodine capture and decrease TSH's response to TRH, while non-phenothiazine typical antipsychotics can elevate TSH levels 3

Clinical Implications

• Subclinical hypothyroidism and hyperprolactinemia have been found to be independently associated with sexual dysfunction in patients with schizophrenia 6
• The prevalence of hyperprolactinemia is significantly higher in patients with sexual dysfunction compared to those without (91.8% vs. 17.5%) 6
• Hyperprolactinemia inhibits gonadotropin secretion through inhibition of hypothalamic kisspeptin hormone, leading to hypogonadism 4
• Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male patients 1

Monitoring Recommendations

• Measure serum prolactin levels in patients on antipsychotics who develop symptoms of hyperprolactinemia 4
• Exclude other causes of hyperprolactinemia, such as hypothyroidism, renal or hepatic impairment 4, 7
• Monitor thyroid function in patients receiving antipsychotics, particularly those with elevated prolactin levels 3
• Use age-specific and sex-specific reference ranges for prolactin and thyroid hormone levels 8, 7

Differential Response by Antipsychotic Class

• Atypical antipsychotics like clozapine, olanzapine, quetiapine, sertindole, and ziprasidone are generally not associated with significant prolactin increases and thus have less impact on TSH levels 2
• Conventional antipsychotics and high-dose risperidone (>6 mg/day) are more likely to cause hyperprolactinemia and subsequent thyroid abnormalities 2
• Patients receiving lithium, phenothiazines, and tricyclic antidepressants should be closely monitored for thyroid function abnormalities 3

Pitfalls and Caveats

• Menstrual irregularities in hypothyroidism may not always correlate with hyperprolactinemia levels 9
• Psychotropic medications may confound the relationship between prolactin and TSH; antipsychotic drugs can cause persistent hyperprolactinemia even after TSH normalization 9
• Stress can elevate prolactin levels up to five times the upper limit of normal, potentially confounding diagnosis 4
• When evaluating thyroid function in patients with hyperprolactinemia, consider other factors that can affect prolactin levels, such as estrogens, opioids, and physical or psychic stress 2