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- Thyroid autoimmunity in patients with hyperprolactinemia: an observational study. [Journal Article]
- Arq Bras Endocrinol Metabol 2014 Feb; 58(1):48-52.
Objective : To establish whether there is a relationship between hyperprolactinemia and primary thyroid disorders, focusing on patients with autoimmune features. Materials and methods : The medical records of 100 patients with hyperprolactinemia (HPRL) were retrospectively examined. Records of thyroid ultrasonography (USG), basal serum levels of thyroid stimulating hormone, circulating free thyroxine, free triiodothyronine, antithyroglobulin (anti-Tg), and antithyroperoxidase (anti-TPO) antibodies were analyzed. In 100 control subjects, matched by age and gender with HPRL patients, thyroid USG, thyroid function tests (TFTs), and autoantibody panel were obtained. Results : The median PRL in patients was 93 ng/mL (range: 37-470). Twenty-five patients (25%) and 22 controls (22%) had positive anti-Tg and/or anti-TPO titers (P = 0.739). The median serum PRL was 98 (37-470) ng/mL in patients with positive thyroid autoantibodies, and 92 (40-470) ng/mL in patients who were negative (P = 0.975). Among the individuals with autoantibody positivity TFTs abnormalities were more frequent in HPRL patients (60%, out of 25 patients, 14 with subclinical hypothyroidism and one with hyperthyroidism) than in controls (9.1%, out of 22 patients, 2 with subclinical hyperthyroidism) (P < 0.001). Twenty-seven patients with HPRL and 31 controls had goiter (27 vs. 31%, P = 0.437). Forty-six patients (46%) and 50 (50%) controls had one or more of the features of thyroid disorder, which were goiter, positive thyroid autoantibody, and thyroid function abnormality (P = 0.888). Conclusion : HPRL may be associated with more severe thyroid dysfunction in patients with thyroid autoimmunity.
- Challenges and pitfalls in the diagnosis of hyperprolactinemia. [Journal Article]
- Arq Bras Endocrinol Metabol 2014 Feb; 58(1):9-22.
The definition of the etiology of hyperprolactinemia often represents a great challenge and an accurate diagnosis is paramount before treatment. Although prolactin levels > 200-250 ng/mL are highly suggestive of prolactinomas, they can occasionally be found in other conditions. Moreover, as much as 25% of patients with microprolactinomas may present prolactin levels < 100 ng/mL, which are found in most patients with pseudoprolactinomas, drug-induced hyperprolactinemia, or systemic diseases. On the other hand, some conditions may lead to falsely low PRL levels, particularly the so-called hook effect, that is an assay artifact caused by an extremely high level of PRL, and can be confirmed by repeating assay after a 1:100 serum sample dilution. The hook effect must be considered in all patients with large pituitary adenomas and PRL levels within the normal range or only modestly elevated (e.g., < 200 ng/mL). An overlooked hook effect may lead to incorrect diagnosis and unnecessary surgical intervention in patients with prolactinomas. Another important challenge is macroprolactinemia, a common finding that needs to be identified, as it usually requires no treatment. Although most macroprolactinemic patients are asymptomatic, many of them may present galactorrhea or menstrual disorders, as well as neuroradiological abnormalities, due to the concomitance of other diseases. Finally, physicians should be aware that pituitary incidentalomas are found in at least 10% of adult population. Arq Bras Endocrinol Metab. 2014;58(1):9-22.
- Lesson of the month (1): cabergoline - 'i eat funny on that'. [Journal Article]
- Clin Med 2014 Apr; 14(2):205-7.
We present the case of a patient treated for hyperprolactinaemia with weekly doses of cabergoline for 12 years. Over this time she had suffered from binge eating and compulsive shopping which impacted on her weight and made her finances precarious. We discuss the features of impulse control disorders and suggest that seeking out these side effects in patients taking such agents is important. The behaviours may be embarrassing and patients may not volunteer them, likewise if the doctor dismisses them they may continue unabated, causing significant social harm.
- Women with prolactinomas presented at the postmenopausal period. [JOURNAL ARTICLE]
- Endocrine 2014 Apr 8.
In women, prolactinomas (mainly microprolactinomas) are commonly diagnosed between 20-40-year old. In postmenopausal women, prolactinomas are rarely encountered and usually do not present with hyperprolactinemia-related symptoms as these are dependent on intact ovarian function. Therefore, the true incidence of prolactin (PRL)-secreting adenomas in postmenopausal woman is unknown. Our study objective was to characterize these rare and unique pituitary tumors. A retrospective study including a consecutive group of postmenopausal women followed and treated at 3 Endocrine academic clinics. Baseline clinical characteristics (PRL and gonadotropins levels, other pituitary hormones, adenoma size and invasiveness, visual fields) and response to treatment are reported. The cohort included 14 postmenopausal women with prolactinomas (mean age at diagnosis, 63.6 ± 7.1 years; range, 54-75 years). Mean adenoma size at presentation was 25.6 ± 12.4 mm (range, 8-50 mm). Six out of the 14 women had significant visual fields damage. Mean baseline PRL level was 1,783 ng/ml, and median PRL was 827 ng/ml (range, 85-6,732 ng/ml). Medical treatment with cabergoline was given to twelve of the patients. Cabergoline normalized/near-normalized PRL in eleven women; one woman was dopamine agonist-resistant. Five of the six subjects with visual disturbances normalized or improved their vision, and a pre-treatment diplopia in another patient disappeared. Two large pituitary tumors disappeared on MRI following long-term dopamine agonist therapy. All other treated prolactinomas, except the resistant adenoma, shrank following medical treatment. Prolactinomas are rarely diagnosed in postmenopausal women. These women usually harbor large and invasive macroadenomas, secreting high PRL levels, and usually respond to dopamine agonist treatment.
- Hypopituitarism patterns and prevalence among men with macroprolactinomas. [JOURNAL ARTICLE]
- Pituitary 2014 Apr 4.
Men with prolactin-secreting tumors usually harbor macroadenomas. The degree of pituitary dysfunction may vary among different adenoma size subgroups, as is recovery after treatment. Our study purpose was to characterize hypopituitarism and recovery after treatment in men with macroprolactinomas.A retrospective study, including a consecutive group of 81 men with pituitary macroadenomas (≥10 mm) and hyperprolactinemia (>7×ULN). Patients were divided into three categories according to adenoma size at presentation: 10-19 mm (group A), 20-39 mm (group B), and ≥40 mm (group C). We compared total testosterone, gonadotropins, cortisol, thyroid hormones and hemoglobin levels at presentation and after treatment.Eighty-one patients were included; 24, 31 and 26 patients in groups A, B and C, respectively. Pretreatment hypogonadism prevalence was 75.0, 93.5 and 90.9 % (p = 0.046; A vs B and C), central hypocortisolism - 0, 6.9 and 33.3 % (p = 0.005), and central hypothyroidism - 6.7, 17.9 and 26.1 % (NS) in groups A, B and C, respectively. Only 26.7 % of all patients presented with hypocortisolism and/or hypothyroidism (42.9 % in group C). Anemia (Hb < 13.5 g %) was detected in 31.3, 57.1 and 80.0 % in groups A, B and C, respectively (p = 0.04). Larger adenoma diameter correlated strongly with lower FT4 levels following treatment (r = -0.42, p = 0.043).Macroprolactinomas in men caused partial hypopituitarism, affecting testosterone in all adenoma size groups and cortisol more in patients with larger adenomas. However, most of the men did not have pituitary hormones affected, beside testosterone. Most patients recovered central hypocortisolism but not hypothyroidism following treatment.
- Second-generation and newly approved antipsychotics, serum prolactin levels and sexual dysfunctions: a critical literature review. [Journal Article]
- Expert Opin Drug Saf 2014 May; 13(5):605-24.
Introduction: Using antipsychotic (AP) medication can increase prolactin (PRL) levels and place the patient at risk of sexual dysfunction (SD). Areas covered: The aim of this review is to describe the PRL propensity of the different second-generation and newly approved APs. It then considers the prevalence rates of SDs associated with these compounds in patients with schizophrenia and treatment strategies for the management of SDs and/or hyperprolactinemia (HPRL). Furthermore, we address the lingering question regarding the association between SDs and PRL. Expert opinion: SD (particularly long-term) data remain scarce for several APs. A wide variety of assessment techniques used in SD research make reliable comparisons between APs impossible. The majority of these reports do not equally allow us to distinguish between treatment (AP and co-medication)-emergent SDs and illness-related SDs. This makes it difficult to assess the degree to which these side effects are associated with 'PRL-raising' APs, and what part of this fraction is directly reducible to serum PRL levels. Also, few evidence-based treatment strategies for HPRL and associated side effects are available. Therefore, longer-term randomized controlled trials, using reliable and valid structured interviews or questionnaires, are necessary to establish the precise relationship between APs, PRL levels and SDs rates and develop valuable treatment options.
- The prevalence of endocrinopathies among Lebanese women presenting with hirsutism to an endocrine clinic. [Journal Article]
- J Med Liban 2014 Jan-Mar; 62(1):27-32.
Hirsutism is a common condition in women characterized by excessive growth of terminal hair in a male pattern distribution. It may be a manifestation of underlying pathologies. Since there is no data published about the prevalence of endocrinopathies among hirsute women in Lebanon, this study's aim was to reveal the most common etiologies of hirsutism in this population.The study is a descriptive review of cases of 160 females with hirsutism presenting to a single endocrinologist clinic. Data about history, physical exam, blood tests and imaging results were collected after review of medical charts.Out of the 160 cases reviewed, 14 females (8.8%) were left undiagnosed. Out of 146 subjects diagnosed, 72.6% were found to have polycystic ovary syndrome (PCOS), 18.5% idiopathic hirsutism (IH), 4.6% non-classic congenital adrenal hyperplasia, 2.6% hyperprolactinemia, 0.6% Cushing's syndrome and 0.6% hypothyroidism. A higher percentage of irregular menses and a trend for overweight were found among the PCOS group.PCOS remains the most common cause of hirsutism in an endocrine referral clinic, similar to other populations. A low threshold for diagnostic workup is in order, especially when there is associated menstrual irregularity or overweight.
- Identification of IgG-κ type macroprolactin found in the serum of an 8-year-old girl. [JOURNAL ARTICLE]
- Clin Chim Acta 2014 Mar 26.:206-208.
We report a case of macroprolactin (macroPRL) in an 8-year-old girl complaining of an enlarged and painful breast who showed elevated PRL levels by enzyme immunoassay.Size-exclusion high-performance liquid chromatography (HPLC) was carried out on a Superose 12 column to estimate the PRL molecular profile. To identify the type of immunoglobulin bound to PRL, immunoprecipitation reactions were performed using three types of anti-heavy chain antibody and two types of anti-light chain.PRL in the patient's serum was eluted at a size slightly larger than the IgG peak by size-exclusion HPLC on a Superose 12 column. In the immunoprecipitation reaction, the PRL concentration of the supernatant mixed with anti-gamma heavy chain and anti-κ light chain was dramatically decreased compared to other types of antiserum. These results indicated that macromolecular PRL was composed of PRL and IgG-κ.A rare case of PRL-IgG-κ-type complex was identified in the serum of the girl and the type of immunoglobulin light chain was determined for the first time. When encountering a child with hyperprolactinemia, pediatricians should take into account the possibility of macroPRL to avoid unnecessary investigation and/or treatment.
- The Effects of Novel and Newly Approved Antipsychotics on Serum Prolactin Levels: A Comprehensive Review. [JOURNAL ARTICLE]
- CNS Drugs 2014 Mar 28.
Since the 1970s, clinicians have increasingly become more familiar with hyperprolactinemia (HPRL) as a common adverse effect of antipsychotic medication, which remains the cornerstone of pharmacological treatment for patients with schizophrenia. Although treatment with second-generation antipsychotics (SGAs) as a group is, compared with use of the first-generation antipsychotics, associated with lower prolactin (PRL) plasma levels, the detailed effects on plasma PRL levels for each of these compounds in reports often remain incomplete or inaccurate. Moreover, at this moment, no review has been published about the effect of the newly approved antipsychotics asenapine, iloperidone and lurasidone on PRL levels. The objective of this review is to describe PRL physiology; PRL measurement; diagnosis, causes, consequences and mechanisms of HPRL; incidence figures of (new-onset) HPRL with SGAs and newly approved antipsychotics in adolescent and adult patients; and revisit lingering questions regarding this hormone. A literature search, using the MEDLINE database (1966-December 2013), was conducted to identify relevant publications to report on the state of the art of HPRL and to summarize the available evidence with respect to the propensity of the SGAs and the newly approved antipsychotics to elevate PRL levels. Our review shows that although HPRL usually is defined as a sustained level of PRL above the laboratory upper limit of normal, limit values show some degree of variability in clinical reports, making the interpretation and comparison of data across studies difficult. Moreover, many reports do not provide much or any data detailing the measurement of PRL. Although the highest rates of HPRL are consistently reported in association with amisulpride, risperidone and paliperidone, while aripiprazole and quetiapine have the most favorable profile with respect to this outcome, all SGAs can induce PRL elevations, especially at the beginning of treatment, and have the potential to cause new-onset HPRL. Considering the PRL-elevating propensity of the newly approved antipsychotics, evidence seems to indicate these agents have a PRL profile comparable to that of clozapine (asenapine and iloperidone), ziprasidone and olanzapine (lurasidone). PRL elevations with antipsychotic medication generally are dose dependant. However, antipsychotics having a high potential for PRL elevation (amisulpride, risperidone and paliperidone) can have a profound impact on PRL levels even at relatively low doses, while PRL levels with antipsychotics having a minimal effect on PRL, in most cases, can remain unchanged (quetiapine) or reduce (aripiprazole) over all dosages. Although tolerance and decreases in PRL values after long-term administration of PRL-elevating antipsychotics can occur, the elevations, in most cases, remain above the upper limit of normal. PRL profiles of antipsychotics in children and adolescents seem to be the same as in adults. The hyperprolactinemic effects of antipsychotic medication are mostly correlated with their affinity for dopamine D2 receptors at the level of the anterior pituitary lactotrophs (and probably other neurotransmitter mechanisms) and their blood-brain barrier penetrating capability. Even though antipsychotics are the most common cause of pharmacologically induced HPRL, recent research has shown that HPRL can be pre-existing in a substantial portion of antipsychotic-naïve patients with first-episode psychosis or at-risk mental state.
- Effects of high affinity leptin antagonist on prolactin receptor deficient male mouse. [Journal Article]
- PLoS One 2014; 9(3):e91422.
Hyperprolactinemia occurs during gestation and lactation with marked hyperphagia associated with leptin resistance. Prolactin (PRL) induces the expression of orexigenic neuropeptide Y (NPY) in hypothalamic dorsomedial nucleus (DMH) leading to hyperphagia. Along this line prolactin receptor deficient (PRLR-/-) mice are resistant to obesity under high fat diet due to increased energy expenditure. As these mice have an altered food intake, our objective was to test whether leptin is responsible for these characteristics. PRLR-/- male mice and control littermates were injected subcutaneously every other day with 12 mg/kg pegylated superactive mouse leptin antagonist (PEG-SMLA) for 3 weeks. We tested the effect of PEG-SMLA on body weight, food intake and metabolic parameters. The antagonist led to a rapid increase in body weight (20%) but increased adipose mass in PEG-SMLA treated mice was less pronounced in PRLR-/- than in WT mice. Food intake of PEG-SMLA-injected animals increased during the first week period of the experiment but then declined to a similar level of the control animals during the second week. Interestingly, PRLR-/- mice were found to have the same bone volume than those of control mice although PEG-SMLA increased bone mass by 7% in both strains. In addition, PEG-SMLA led to insulin resistance and glucose intolerance as well as an altered lipid profile in treated mice. Altogether, these results suggest that PRLR-/- mice respond to leptin antagonist similarly to the control mice, indicating no interaction between the actions of the two hormones.