The Underlying Mechanisms: How Hypothyroidism Affects the Formation of Common Bile Duct Stones—A Review
For decades, one well-known risk factor for the development of gallbladder stones has been hypothyroidism. Recent studies have interestingly reported that the risk in particular for common bile duct (CBD) stones increases in clinical and subclinical hypothyroidism. There are multiple factors that may contribute to the formation and/or accumulation of CBD stones in hypothyroid patients, including decreased liver cholesterol metabolism, diminished bile secretion, and reduced sphincter of Oddi relaxation. This paper focuses on the mechanisms possibly underlying the association between hypothyroidism and CBD stones. The authors conclude that when treating patients with CBD stones or microlithiasis, clinicians should be aware of the possible hypothyroid background.
3. Prevalence of Clinical and Subclinical Hypothyroidism in CBD Stone Patients
4. How Hypothyroidism May Affect the Formation of CBD Stones?
4.1. Hypothyroidism Decreases Liver Cholesterol Metabolism
4.2. Hypothyroidism May Reduce Hepatic Bile Secretion
4.3. Hypothyroidism Reduces Bile Flow into the Duodenum
4.4. Hypothyroidism Leads to Impaired SO Relaxation
5. Mechanisms by Which Thyroxine Mediates SO Relaxation
6. Conclusions and Clinical Implications
In summary, several recent studies report an association between hypothyroidism, or subclinical hypothyroidism, and CBD stones. The higher prevalence of hypothyroidism in CBD stone patients compared to gallbladder stone patients suggests that not only changes in the cholesterol metabolism, or bile excretion rate, but particularly changes in the function of the SO that may underline the association between CBD stones and hypothyroidism. It remains to be investigated whether hypothyroid individuals who have had their gallbladder removed are at an increased risk to develop CBD stones when compared to euthyroid individuals in the same situation.
It seems likely that the lack of thyroxine in hypothyroidism gives rise to a reduction in bile flow in many ways. In addition to the increased cholesterol load in bile and the reduced bile secretion rate, the deficiency of the prorelaxant effect of thyroxine on the SO appears to be a crucial factor leading to the reduced bile flow in hypothyroidism.
The initial formation of bile cholesterol crystals may begin during the untreated period of hypothyroidism, and the stones may continue to develop or mature even after the thyroxine replacement therapy has begun. It is possible that thyroxine replacement therapy is not sufficient in all patients to maintain normal SO function, causing increased risk of CBD stone formation. Studies with subclinical hypothyroid patients have demonstrated that a positive effect on the changes in the serum cholesterol level, on cardiovascular effects, or on neuromuscular symptoms may be achieved with early replacement treatment with thyroxine [10, 11], and it can be assumed that patients at risk of forming CBD stones due to subclinical hypothyroidism may also benefit from such early treatment. Most importantly, when treating patients with CBD stones or microlithiasis, clinicians should be aware of the possible hypothyroid background and consider examining the thyroid function, at least in female patients over 60 years of age, in which group the prevalence of clinical and subclinical hypothyroidism is the highest.