Neuroendocrine Modulation of Cognitive Performance in the Patients with Fibromyalgia

<b><i>Background:</i></b> Fibromyalgia (FM) is a chronic widespread pain disorder associated with fatigue, tender points, sleep disturbances, and mood disorders. Symptoms associated with FM also include decreased cognitive function in which the neural basis is poorly understood. Neuroendocrine hormones may be correlated with cognitive performance under some ill conditions. However, we are unaware of current evidence on neuroendocrine hormones as factors influencing cognitive function in adults with FM. <b><i>Objectives:</i></b> The aim of the study was to assess whether neuroendocrine hormones could affect cognition in the patients with FM. <b><i>Study Design:</i></b> This study used a case-control trial design. <b><i>Setting:</i></b> Study patients were recruited from the neurological outpatient clinics in the Second Affiliated Hospital and Affiliated Chaohu Hospital of Anhui Medical University and met the American College of Rheumatology criteria for FM. <b><i>Methods:</i></b> Forty-six patients with FM were compared with twenty-nine healthy controls (HCs). Several measures of cognitive performance and serum levels of neuroendocrine hormones were used to make these comparisons, and the patients were also asked to complete questionnaires on depression and sleep quality. Partial correlation analysis was performed to control the confounders and linear regression analysis was used to examine the effects of neuroendocrine hormones on cognitive measures. <b><i>Results:</i></b> The FM patients had worse performance in attention, short-term memory, orientation, object working memory and spatial reference memory, higher depression scores, and worse sleep quality than HCs. The raised level of cortisol and gonadotropin-releasing hormone (GnRH) can protect general cognition, whereas the raised level of cortisol and thyroid-stimulating hormone (TSH) will damage spatial memory. <b><i>Limitations:</i></b> We did not study the sex hormones comprehensively. <b><i>Conclusions:</i></b> The FM patients showed significant cognitive impairment in several domains. The altered levels of cortisol, thyrotrophin-releasing hormone (TRH), and GnRH may mediate cognitive changes in FM.

Prolactinomas and hyperprolactinaemia (including macroprolactinaemia)

Prolactin promotes milk production in mammals. It was characterized as a hormone distinct from growth hormone, which also has lactogenic activity, as recently as 1971. In humans, the predominant prolactin species is a 23 kDa, 199 amino acid polypeptide synthesized and secreted by lactotroph cells in the anterior pituitary gland. Prolactin is produced also by other tissues including decidua, breast, T lymphocytes, and several regions of the brain, where its functions are largely unknown and its gene regulation different from that of the pituitary gene. Pituitary prolactin production is under tonic inhibitory control by hypothalamic dopamine, such that pituitary stalk interruption produces hyperprolactinaemia. The neuropeptides thyrotrophin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP) exert less important stimulatory effects on pituitary prolactin release (1). Following the discovery of prolactin as a separate hormone it became apparent that many apparently functionless ‘chromophobe’ pituitary adenomas were prolactinomas. Indeed, prolactinoma is the commonest type of functioning pituitary tumour diagnosed in humans. There is a marked female preponderance and prolactinoma is relatively rare in men. Several studies have revealed small prolactinomas in approximately 5% of autopsy pituitaries, most of which are undiagnosed during life. From a clinical standpoint, prolactinomas are divided arbitrarily into microprolactinomas (≤10 mm in diameter) and macroprolactinomas (>10 mm). This is a useful distinction which predicts tumour behaviour and indicates appropriate management strategies. Generally, microprolactinomas run a benign course. Some regress spontaneously, most stay unchanged over many years, and very few expand to cause local pressure effects. In contrast, macroprolactinomas may present with pressure symptoms, often increase in size if untreated and rarely disappear. Some clinicians find an intermediate category of meso-prolactinoma useful (10–20 mm in diameter), since this tumour group may have a more favourable treatment outcome than for larger macroprolactinomas. Prolactinomas are usually sporadic tumours. Molecular genetics has shown nearly all to be monoclonal, suggesting that an intrinsic pituitary defect is likely to be responsible for pituitary tumorigenesis (see Chapter 2.3.2). Occasionally, prolactinoma may be part of a multiple endocrine neoplasia syndrome type I, but this occurs too infrequently to justify screening in every patient with a prolactinoma. Mixed growth hormone and prolactin-secreting tumours are well recognized and give rise to acromegaly in association with hyperprolactinaemia. Most contain separate growth hormone and prolactin-secreting cells whereas a minority secrete growth hormone and prolactin from a single population of cells, the mammosomatotroph adenomas. Prolactin-secreting adenomas may produce other hormones such as thyroid-stimulating hormone (TSH) or adrenocorticotropic hormone (ACTH), but such tumours are uncommon. Malignant prolactinomas are also very rare. A few cases have been described which have proved resistant to aggressive treatment with surgery, radiotherapy, and dopamine agonists. In a small proportion, extracranial metastases in liver, lungs, bone, and lymph nodes have been documented. The alkylating agent temozolomide is effective against some aggressive prolactinomas (2).

Thyroid hormone resistance syndrome

Thyroid hormones (thyroxine T4 and triiodothyronine T3) regulate many cellular processes in virtually every type of tissue. The diverse effects of thyroid hormone include regulation of growth, control of basal metabolic rate, enhanced myocardial contractility, and functional differentiation of the central nervous system. The synthesis of thyroid hormones is controlled by hypothalamic thyrotrophin-releasing hormone (TRH) and pituitary thyroid-stimulating hormone (TSH), and in turn, T4 and T3 regulate TRH and TSH production as part of a negative feedback loop.

Safety and Efficacy of Galactogogues: Substances that Induce, Maintain and Increase Breast Milk Production

Poor production of breast milk is the most frequent cause of breast lactation failure. Often, physician prescribe medications or other substances to solve this problem. The use of galactogogues should be limited to those situations in which reduced milk production from treatable causes has been excluded. One of the most frequent indication for the use of galactogogues is the diminution of milk production in mothers using indirect lactation, particularly in the case of preterm birth. The objective of this review is to analyze to the literature relating to the principal drugs used as galactogogues (metoclopramide, domperidone, chlorpromazine, sulpiride, oxytocin, growth hormone, thyrotrophin releasing hormone, medroxyprogesterone). Have been also analyzed galactogogues based on herbs and other natural substances (fenugreek, galega and milk thistle). We have evaluated their mechanism of action, transfer to maternal milk, effectiveness and potential side effects for mother and infant, suggested doses for galactogogic effect, and recommendation for breastfeeding.