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Clinical consequences of prolactinoma include endocrine sequalae of hyperprolactinemia, local mass effects of the underlying adenoma, and insufficiency of other pituitary axes
Source publication
Prolactinomas are the most frequently seen pituitary adenomas in clinical practice. A correct biochemical diagnosis of hyperprolactinemia is a prerequisite for further investigation but may be hampered by analytical difficulties as well as a large number of potentially overlapping conditions associated with increased prolactin levels. Suspicion sho...
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Objective
Control of prolactin excess is associated with the improvement in gluco-insulinemic and lipid profile. The current study aimed at investigating the effects of pituitary surgery and medical therapy with high dose cabergoline (≥2mg/week) on metabolic profile in patients with prolactinoma resistant to cabergoline conventional doses (<2mg/wee...
Purpose
Dopamine agonists (DAs) have long been the recommended first-line treatment for prolactinoma. Given the remarkable developments in surgical techniques, however, surgery is on the rise. We compared the treatment outcomes of patients with noninvasive prolactinomas receiving two different initial treatments (DAs and transsphenoidal surgery)....
Citations
... Repeated or cannulated prolactin venipuncture sampling for testing is recommended with serum levels of prolactin less than five times ULN or if an influence of stress is suspected 44,45 . Physiological prolactin increases can occur after exercise, high-protein meals and alcohol consumption 46,47 . Patients with polycystic ovary syndrome (PCOS) require further evaluation of elevated serum levels of prolactin, as PCOS per se is rarely associated with hyperprolactinaemia 48 . ...
... A correct biochemical diagnosis of hyperprolactinaemia is a prerequisite for further investigation, but can be hampered by potentially overlapping conditions associated with increased measurement values for prolactin 47,55 . Suspicion of an assay artefact should arise in patients whose symptoms and biochemical results are not consistent. ...
... Repeated or cannulated prolactin venipuncture sampling for testing is recommended with serum levels of prolactin less than five times ULN or if an influence of stress is suspected 44,45 . Physiological prolactin increases can occur after exercise, high-protein meals and alcohol consumption 46,47 . Patients with polycystic ovary syndrome (PCOS) require further evaluation of elevated serum levels of prolactin, as PCOS per se is rarely associated with hyperprolactinaemia 48 . ...
... A correct biochemical diagnosis of hyperprolactinaemia is a prerequisite for further investigation, but can be hampered by potentially overlapping conditions associated with increased measurement values for prolactin 47,55 . Suspicion of an assay artefact should arise in patients whose symptoms and biochemical results are not consistent. ...
This Consensus Statement from an international, multidisciplinary workshop sponsored by the Pituitary Society offers evidence-based graded consensus recommendations and key summary points for clinical practice on the diagnosis and management of prolactinomas. Epidemiology and pathogenesis, clinical presentation of disordered pituitary hormone secretion, assessment of hyperprolactinaemia and biochemical evaluation, optimal use of imaging strategies and disease-related complications are addressed. In-depth discussions present the latest evidence on treatment of prolactinoma, including efficacy, adverse effects and options for withdrawal of dopamine agonist therapy, as well as indications for surgery, preoperative medical therapy and radiation therapy. Management of prolactinoma in special situations is discussed, including cystic lesions, mixed growth hormone-secreting and prolactin-secreting adenomas and giant and aggressive prolactinomas. Furthermore, considerations for pregnancy and fertility are outlined, as well as management of prolactinomas in children and adolescents, patients with an underlying psychiatric disorder, postmenopausal women, transgender individuals and patients with chronic kidney disease. The workshop concluded that, although treatment resistance is rare, there is a need for additional therapeutic options to address clinical challenges in treating these patients and a need to facilitate international registries to enable risk stratification and optimization of therapeutic strategies.
... La PRL es una hormona peptídica producida por los lactotropos de la hipófisis y su función principal radica en la estimulación de la lactancia, de ahí la naturaleza de su nombre, mientras que el control de la secreción de la PRL está dado por estímulos inhibitorios de la dopamina (7). Por su parte, la hiperprolactinemia puede deberse a diversas situaciones fisiológicas y patológicas, así como a múltiples fármacos que alteran la producción, el transporte o la acción de la dopamina (15). De igual forma, se han postulado otros factores promotores de la hormona como la oxitocina, el péptido intestinal vasoactivo (VIP), la angiotensina II, el neuropéptido Y (NPY), la galanina, la sustancia P, péptidos similares a la bombesina y la neurotensina (16). ...
Introducción: los prolactinomas son el tipo más común de tumor hipofisario, donde los pacientes con prolactinomas presentan signos y síntomas de hipogonadismo y galactorrea. Por su parte, el aldosteronismo primario (AP) es una causa infradiagnosticada de hipertensión, caracterizada por una secreción autónoma de aldosterona. La concomitancia de estos dos síndromes ha sido reportada con poca frecuencia en la literatura. Objetivo: presentar un caso de coexistencia de prolactinoma-AP con el fin de destacar la ocurrencia conjunta de ambas entidades y exponer el potencial vínculo fisiopatológico entre la hiperprolactinemia/prolactinoma y el AP. Presentación del caso: mujer de 38 años con historia de varios años de oligomenorrea sin galactorrea. Bioquímica inicial con hiperprolactinemia y resonancia magnética de silla turca que reveló un prolactinoma. Durante el seguimiento, la paciente cursa con hipertensión arterial de difícil control, por lo que se exploró una causa secundaria que reveló un ratio aldosterona/actividad de renina plasmática de 232 ng/dl/ng/ml/h en presencia de un adenoma suprarrenal izquierdo de 10 mm, lo que confirmó el diagnóstico de hiperaldosteronismo primario. Discusión y conclusión: la coexistencia de estos dos hallazgos es una condición raramente descrita en la literatura y se plantea la hipótesis de que las concentraciones elevadas de PRL podrían desempeñar un papel en la patogénesis del AP en pacientes que no forman parte del síndrome genético de neoplasia endocrina múltiple tipo 1 (MEN1 por sus siglas en inglés).
... While newer automated immunoassay platforms are likely to detect the "hook effect", this may not be the case in older assays, which are still in use in many countries. Therefore, there is potential for misdiagnosis [21,22], especially when surgery is performed at an institution where automated Box 1 Consensus on the evaluation and management of patients undergoing transsphenoidal surgery ...
Purpose:
In adults and children, transsphenoidal surgery (TSS) represents the cornerstone of management for most large or functioning sellar lesions with the exception of prolactinomas. Endocrine evaluation and management are an essential part of perioperative care. However, the details of endocrine assessment and care are not universally agreed upon.
Methods:
To build consensus on the endocrine evaluation and management of adults undergoing TSS, a Delphi process was used. Thirty-five statements were developed by the Pituitary Society's Education Committee. Fifty-five pituitary endocrinologists, all members of the Pituitary Society, were invited to participate in two Delphi rounds and rate their extent of agreement with statements pertaining to perioperative endocrine evaluation and management, using a Likert-type scale. Anonymized data on the proportion of panelists' agreeing with each item were summarized. A list of items that achieved consensus, based on predefined criteria, was tabulated.
Results:
Strong consensus (≥ 80% of panelists rating their agreement as 6-7 on a scale from 1 to 7) was achieved for 68.6% (24/35) items. If less strict agreement criteria were applied (ratings 5-7 on the Likert-type scale), consensus was achieved for 88% (31/35) items.
Conclusions:
We achieved consensus on a large majority of items pertaining to perioperative endocrine evaluation and management using a Delphi process. This provides an international real-world clinical perspective from an expert group and facilitates a framework for future guideline development. Some of the items for which consensus was not reached, including the assessment of immediate postoperative remission in acromegaly or Cushing's disease, represent areas where further research is needed.
... The patient had gone through menopause around 1 year ago at 50 years old, and she had no galactorrhea or headache. Since she was taking only lansoprazole and sucralfate, drug-induced hyperprolactinemia was unlikely (9). She had no other causes of hyperprolactinemia, including hypothyroidism and renal failure (Table 1) (9). ...
... Since she was taking only lansoprazole and sucralfate, drug-induced hyperprolactinemia was unlikely (9). She had no other causes of hyperprolactinemia, including hypothyroidism and renal failure (Table 1) (9). The inadequate response of PRL to TRH stimulation supported the conclusion that the patient's pituitary tumor had caused hyperprolactinemia, although we were unable to eliminate the possibility of macroprolactinemia. ...
A 51-year-old woman was admitted because of hypercalcemia. Neck ultrasonography and computed tomography revealed the presence of parathyroid cysts on both sides. After primary hyperparathyroidism was diagnosed by technetium-99 m-methoxyisobutylisonitrile scintigraphy, the patient was successfully treated with total parathyroidectomy and autotransplantation. She also had a non-functioning pancreatic neuroendocrine tumor, prolactinoma, and adrenal tumors with subclinical Cushing's syndrome. Given these clinical features and her family history, multiple endocrine neoplasia type 1 (MEN1) was suspected, and germline DNA sequencing revealed a missense mutation (c.1013T > G, p.Leu338Pro) in exon 7 of MEN1. This case demonstrates the phenotypic and genetic diversity of MEN1.
... Serum prolactin concentrations are usually between 100 and 250 ng/mL for microprolactinomas and greater than 200 ng/mL for macroprolactinomas. 87 Medications such as anticonvulsants, antipsychotics, and selective serotonin uptake inhibitors may be associated with elevated prolactin concentrations typically less than 100 ng/mL. Individuals with anatomic anomalies affecting mullerian duct derivatives (Fallopian tubes, uterus, and upper vagina) often present with primary amenorrhea. ...
Puberty is the process through which reproductive competence is achieved and comprises gonadarche and adrenarche. Breast development is the initial physical finding of pubertal onset in girls and typically occurs between 8 and 13 years. Menarche normally occurs 2 to 3 years after the onset of breast development. Pubertal onset is controlled by the gonadotropin-releasing hormone pulse generator in the hypothalamus; however, environmental factors such as alterations in energy balance and exposure to endocrine-disrupting chemicals can alter the timing of pubertal onset. Improvement in nutritional and socioeconomic conditions over the past two centuries has been associated with a secular trend in earlier pubertal onset. Precocious puberty is defined as onset of breast development prior to 8 years and can be central or peripheral. Delayed puberty can be hypogonadotropic or hypergonadotropic and is defined as lack of breast development by 13 years or lack of menarche by 16 years. Both precocious and delayed puberty may have negative effects on self-esteem, potentially leading to psychosocial stress. Patients who present with pubertal differences require a comprehensive assessment to determine the underlying etiology and to devise an effective treatment plan.
... Clinical manifestations vary according to age and sex of the patient and to the magnitude of PRL secretion increase. Clinical presentation in women with oligomenorrhea, amenorrhea, galactorrhea, decreased libido, infertility, and decreased bone mass is generally more clear and occurs earlier than in men [1][2][3][4][5][6][7][8][9]. The most common symptoms in men are erectile dysfunction, decreased libido, infertility, gynecomastia, decreased bone mass, while galactorrhea is rare [1][2][3][4][5][6][7][8][9]. ...
... Clinical presentation in women with oligomenorrhea, amenorrhea, galactorrhea, decreased libido, infertility, and decreased bone mass is generally more clear and occurs earlier than in men [1][2][3][4][5][6][7][8][9]. The most common symptoms in men are erectile dysfunction, decreased libido, infertility, gynecomastia, decreased bone mass, while galactorrhea is rare [1][2][3][4][5][6][7][8][9]. ...
... Prolactinomas, that account for 25-30% of functioning pituitary tumors, are the most frequent cause of high PRL [1][2][3][4][5][6][7][8][9]. Prolactinomas can be microadenomas, more common in premenopausal women, and macroadenomas, more common in men and postmenopausal women [1][2][3][4][5][6][7][8][9]. ...
Hyperprolactinemia can have different causes: physiological, pharmacological, and pathological. When investigating the etiology of hyperprolactinemia, clinicians need to be aware of several conditions leading to misdiagnosis. The most popular pitfalls are: acute physical and psychological stress, macroprolactin, hook effect, even though antibodies interferences and biotine use have to be considered. A 52-year-old woman was referred to Endocrinology clinic for oligomenorrhoea and headache. She worked as a butcher. Hormonal evaluation showed very high PRL (305 ng/ml, reference interval: <24 ng/ml) measured with the ECLIA immunoassay analyzer Elecsys 170. The patient's pituitary MRI was normal and macroprolactin was normal. Hormonal workup showed LH: 71.5 mU/ml (2-10.9 mU/ml), FSH: 111.4 mU/ml (3.9-8.8 mU/ml), Estradiol: 110.7 pg/mL (27-122 pg/ml). Since an interference was suspected, the sample was sent to another laboratory using a different assay. After antibody blocking tubes treatment (Heterophilic Blocking Tube, Scantibodies) PRL was 28.8 ng/ml (reference interval < 29.2 ng/ml). Analytical interference should be suspected when assay results are not consistent with the clinical picture. Endogenous antibodies (EA) include heterophile, human anti-animal, autoimmune and other nonspecific antibodies, and rheumatoid factors, that have structural similarities and can cross-react with the antibodies employed by the immunoassay, causing hyperprolactinemia misdiagnosis. The patient's job (butcher), led us to suspect the presence of anti-animal antibodies. Clinicians should also carefully investigate the use of supplements. Biotin can falsely increase hormone concentration in competitive assays. Many clinicians are still not informed about these pitfalls that are not mentioned in some recent reviews on PRL measurement.
... Specifically, with oral antipsychotics, PRL levels tend to normalize within 48 to 96 hours after the last dose 8,15 . However, elevated levels can persist as long as about 3 weeks depending on drug half-life and storage in fatty tissue 39 . ...
... With the PEG test, the higher molecular weight forms of PRL are removed by precipitation leading to the residual monomeric form in the sample supernatant. If the recovery of monomeric PRL after precipitation with PEG is less than 40% of the initial total value, then macroprolactin is the predominant variant present of immunoreactive PRL 5,39 . ...
... It is important to be aware of the presence of nonfunctioning adenomas or other clinically silent pituitary lesions reported in about 10% of MRI images that may not correspond to a prolactinoma, even in the presence of altered serum PRL levels 39 . Figure 2 proposes an algorithm for the evaluation of patients with hyperprolactinemia ...
Hyperprolactinemia may be associated with psychiatric disorders in the context of two scenarios: antipsychotic-induced hyperprolactinemia and psychiatric disorders arising from the medical treatment of hyperprolactinemia. Both situations are particularly common in psychiatric and endocrine clinical practice, albeit generally underestimated or unrecognized. The aim of this article is to provide tools for the diagnosis and treatment of hyperprolactinemia associated with psychiatric disorders to raise awareness, especially among psychiatrists and endocrinologists, so that these professionals can jointly focus on the appropriate management of this clinical entity.
... Accordingly, prolactin measurement should be made in dilution when values are not as high as expected in a patient with a large pituitary macroadenoma, in which the case the serum prolactin levels should be re-measured after a 1:100 serum sample dilution to exclude the possibility of falsely low value due to the high dose hook effect (before providing a label of NFPA). 51 Furthermore, laboratory findings can indicate high prolactin levels in the absence of typical symptoms of hyperprolactinaemia. Therefore, it is important to assess for the presence of macroprolactin to avoid clinical confusion and inappropriate management. ...
Non-functioning pituitary adenomas (NFPAs) are benign pituitary tumours that constitute about one-third of all pituitary adenomas. They typically present with symptoms of mass effects resulting in hypopituitarism, visual symptoms, or headache. Most NFPAs are macroadenomas (>1 cm in diameter) at diagnosis that can occasionally grow quite large and invade the cavernous sinus causing acute nerve compression and some patients may develop acute haemorrhage due to pituitary apoplexy. The progression from benign to malignant pituitary tumours is not fully understood; however, genetic and epigenetic abnormalities may be involved. Non-functioning pituitary carcinoma is extremely rare accounting for only 0.1% to 0.5 % of all pituitary tumours and presents with cerebrospinal, meningeal, or distant metastasis along with the absence of features of hormonal hypersecretion. Pituitary surgery through trans-sphenoidal approach has been the treatment of choice for symptomatic NFPAs; however, total resection of large macroadenomas is not always possible. Recurrence of tumours is frequent and occurs in 51.5% during 10 years of follow-up and negatively affects the overall prognosis. Adjuvant radiotherapy can decrease and prevent tumour growth but at the cost of significant side effects. The presence of somatostatin receptor types 2 and 3 (SSTR3 and SSTR2) and D2-specific dopaminergic receptors (D2R) within NFPAs has opened a new perspective of medical treatment for such tumours. The effect of dopamine agonist from pooled results on patients with NFPAs has emerged as a very promising treatment modality as it has resulted in reduction of tumour size in 30% of patients and stabilization of the disease in about 58%. Despite the lack of long-term studies on the mortality, the available limited evidence indicates that patients with NFPA have higher standardized mortality ratios (SMR) than the general population, with women particularly having higher SMR than men. Older age at diagnosis and higher doses of glucocorticoid replacement therapy are the only known predictors for increased mortality.
... In her report on 'Pathology of prolactinomas-any predictive value?' Lopes discusses potential prognostic markers which support development of a clinical classification [4]. Furthermore, to aid early detection and correct diagnosis of unrecognized prolactinomas, Petersenn in his article 'Biochemical diagnosis of prolactinomassome caveats' reviews potential pitfalls when measuring prolactin [5]. If sufficient clinical and biochemical evidence supports the diagnosis of a prolactinoma, MRI scan will be necessary to confirm the presence of an underlying pituitary adenoma. ...
