At the endocrine glandular level, we found that patients with BD-mania had overall lower TT3 and TT4 and higher FT4 levels. After comparing the subgroups, we found that sex may be responsible for the differences. Male patients had higher FT4 levels, while female patients had lower TT3 and TT4. The increase in peripheral secreted THs leads to high risk of hyperthymia, irritability, and distractibility, thus, the increase of FT4 in the male BD-mania group was consistent with symptoms of a mania-like state. The hypothyroidism theory in BD is usually explained by the compensatory mechanism of the thyroid. It is important to note that the results of the female BD-mania group were inconsistent with the biological peripheral roles of T3 and T4. Although there were no differences between men and women shown in the BSDS and YMRS for the clinical diagnosis of BD, our data of the female BD-mania group supported the compensatory hyposecretion of TT4 in BD-mania. In addition, the decreased TT3 level may result from the simultaneous decrease in TT4 as high-functioning T3 mainly originates from the deiodination of T4. Thus both may reduce the release of TT3. As a result, this negative feedback increases long term TSH secretion in the anterior pituitary. This trend was seen in the female patient subgroup (1.95 mIU/L VS. 1.77 mIU/L), however it was not significant in the acute first-episode after Bonferroni correction. In the disease condition, BD-mania neuroendocrine regulation may differ among genders. A previous study found that the compensatory feedback of the HPTA may decline with chronic deferment of the disease. Thus, increased FT4 and TSH becomes a comparatively steady state under chronic psychiatric stress, and the sex differences may disappear.
At the anterior pituitary level, there is no evident difference of TSH level in BD-mania, on the other hand, the negative feedback regulation of the anterior pituitary gland might not be established so soon in the onset of BD-mania. Özerdem et al found that TSH increased more frequently in female patients and that self-regulation triggers the compensation mechanism of the thyroid gland in the disease. As previously mentioned, the classic negative feedback regulation is in contrast to the traditional biomedical model that states hyperthyroidism can lead to clinical manifestations of manic symptoms. A higher prevalence of thyroid dysfunction was found in BD, with 11.4–24.5% being above or below the RR of TSH considered for BD-mania. Therefore, the current explanation hardly fits both theories. If these theories are not accepted simultaneously, then according to the monism analysis of the disease, abnormal thyroid function and BD-mania are not due to comorbidity.
In order to discuss the relationship between the differences of sex in thyroid disease and hyperprolactinemia, we needed to know whether they both significantly correlated to sex . We thus recruited patients aged 16 to 40 with sexual characteristics set as a confounding factor. Due to the physiological effects of PRL, sex differences were evident. Post-pubertally, the expression of growth hormone and PRL is sexually dimorphic with males exhibiting higher growth hormone levels and females higher PRL levels. The aberrant increase of PRL causes side effects on the pathological lactation and menstruation of women. Additionally, thyroid-stimulating hormone level might be sensitive to changes in circulating estrogen in women and increases after an induced acute increase of estradiol with PRL, which is a classic estradiol-upregulated pituitary hormone. Previous studies have indicated that women with BD are at a higher risk for mood episodes during periods of intense hormonal fluctuation (e.g., postpartum, premenstrual, perimenopause). Profound interactions between the immune system and the HPTA exist and both immune and endocrine factors mediate neuroplastic effects.
Furthermore, several neuropeptides, vasoactive intestinal peptides, and TSH have been reported to stimulate the release of PRL under psychological stress. The TSH acts on the pituitary PRL cells to stimulate the expression of PRL mRNA, thus promoting it’s synthesis and secretion, which may explain the correlation between TSH and PRL in females with BD-mania. The increase of PRL may lead to galactorrhea, sexual dysfunction, osteoporosis and other pathological changes that should be paid serious attention, particularly in women. Bromocriptine, a dopamine agonist widely used in the treatment of hyperprolactinemia may further explain elevated PRL as it blocks the dopamine channel in the tubero-infundibular system and the dopamine antagonist effects of antipsychotic drugs. Studies have shown that BD does not change the sensitivity of dopamine neurons in the hypothalamus-pituitary system anomalies. In our study, there might be a correlation between the increased PRL in BD-mania and the onset of manic symptoms. Therefore, a correlation study of the hormones secreted by PRL and the pituitary is expected to be a potential biomarker for clinicians to use in medical treatment.
In order to discuss the interactions of pituitary hormones, we needed to know whether anterior pituitary dysfunction effected only certain kinds of anterior pituitary cells or several kinds. Theoretically, in the condition that hyposecretion of peripheral glands occurs, feedback information is transmitted to the hypothalamus, then positive or negative feedback of the hypothalamus secretes hormone releasing factors that stimulate both peripheral glands and the hypersecretion of PRL. Neuroimmunology research has found that TSH interacts with PRL through tumor necrosis factor-α and interleukin-1β to affect the neural immune system. Although female neural diseases of the immune system are more common, the relationship is not clear yet. A recently published systematic literature search indicated that most of the previous studies ignored the complexity and timeliness of the effects of medicine on the neuroendocrine of BD-mania. Benvenga S et al  found that women with an estradiol-dependent increase in TSH do however exist, as do PRL-dependent increases. Based on the above theory, we attempted to make a related analysis of TSH and PRL in first-episode BD-mania. We found that PRL in female patients with BD-mania might have a weak negative and a moderate inverse relationship with TSH even when TSH secretion did not increase. Thus, we assume that the increase in both is not easily synchronized, with the loss of synchrony previously found during prolonged critical illness. Aromatase expression in TSH and PRL may have a regulatory role on the synthesis and secretion of these hormones. Capozzi A et al  indicated that BD-mania, as an acute stress reaction, together with hypothyroidism, renal failure, or interruption of hypothalamic-pituitary dopaminergic pathways are other frequent conditions of hyperprolactinemia.