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Purpose: Prolactin (PRL)-secreting tumors are the most common functional pituitary adenomas. They usually respond to dopamine agonist (DA) treatment, with PRL normalization and adenoma shrinkage. Our aim was to characterize patients with prolactinoma resistant to DA treatment., Methods: This retrospective case series included patients diagnosed with DA-resistant prolactinomas between 1993-2017 in three medical centers. Resistance was defined as PRL levels above three times the upper limit of normal (ULN) despite a weekly dose of ≥2 mg cabergoline (CAB). Clinical and biochemical information, and response to treatment, were retrieved from medical records., Results: Twenty-six patients were identified; 20 males. Of 25 macroadenomas, three were giant tumors (>40 mm) and 15 (57.7%) were invasive. The mean age at diagnosis was 31.8 ± 14.9 years (range: 13-62). The median maximal CAB dose was 3.5 mg/week (IQR, 2.5-5). Half the patients received only CAB in escalating doses, nine received CAB and underwent transsphenoidal surgery, and four underwent surgery and radiotherapy in addition to CAB treatment. PRL levels at baseline between patients treated only with CAB and those operated were (91.6 [51.1-296.7] vs. 73.1 [22.6-170.9] XULN p = 0.355), and under maximal CAB dose PRL levels between patients treated only with CAB and those operated were similar (5.77 [1.27-11.27] vs 5.27 (2.9-26) XULN p = 0.317). At the last visit patients who received combined therapy achieved lower PRL levels than those treated with DA only (5.22 [1.7-21.6] vs 1.1 [0.44-3.99] XULN p = 0.017) PRL normalization was attained in seven patients and levels below 3 × ULN in fourteen patients; the overall response was 56%., Conclusions: Resistant prolactinomas usually require a multi-modal treatment strategy. We were able to control 14/25 (56%) of resistant tumors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To characterize a cohort of elderly men with prolactinomas and their response to treatment., Methods: We have identified 28 elderly men diagnosed after the age of 65 with prolactinomas at seven different endocrine clinics in Israel. A retrospective electronic chart review identified a control group of 76 younger men with macroprolactinomas treated in one of the centers., Results: Mean age at diagnosis was 71.3 ± 5.6 (range 65-86) years, and current age 76.6 ± 7.5 years. Initial complaints leading to diagnosis included sexual dysfunction in 17 males (61%), headaches in two patients (7%), and visual abnormalities in two (7%). Three men presented with osteoporosis. Ten patients (36%) were diagnosed incidentally following brain imaging for unrelated reasons. Seventeen patients (61%) had macroadenoma, while eleven (39%) presented with a microadenoma or no visible adenoma. Mean prolactin (PRL) at presentation was 1594 (median 382; range 50-18,329) ng/ml. Testosterone was low in 21 men. Patients were treated with cabergoline (max dose, 1.1 ± 0.5 mg/week), except for one given bromocriptine; none required pituitary surgery or radiotherapy. Treatment normalized PRL in 24 patients, and in three men PRL suppressed to <2 ULN. Fifteen men normalized testosterone, three improved without normalization, and in three the normal baseline level increased. After a mean follow-up of 5.3 years, 14/15 patients harboring a macroadenoma showed significant adenoma shrinkage. Most patients reported improvement of low libido/erectile dysfunction. In the control group 60 men (79%) achieved PRL normalization., Conclusions: Elderly men with prolactinomas are diagnosed incidentally in 36% of cases. Long-term medical therapy is successful, achieving biochemical remission, adenoma shrinkage, and clinical improvement in almost all patients.

Purpose: Recent work supports the use of T2-weighted MRI intensity as a tool for treatment stratification in acromegaly. Our study aimed to establish if the pattern of T2 intensity could be a predictor of hormonal and/or tumoral response to dopamine agonists (DAs) in prolactinomas., Methods: This was a retrospective study performed in two academic centers. We characterized the magnetic resonance T2-weighted aspect of prolactinomas (signal intensity and homogeneity in the whole tumors) before DA therapy and correlated this pattern to the prolactin (PRL) concentration at diagnosis and to hormonal and tumoral responses after 1 year of medical treatment. We separately analyzed a subgroup of prolactinomas visually very bright in more than 50% of the surface ("cystic" tumors)., Results: Out of 70 prolactinomas, 80% were T2 hyperintense and 40% were heterogeneous. At diagnosis, heterogeneous prolactinomas were more frequent in men (68% vs. 28.9%, p ≤ 0.011), larger (median area 304.5 mm 2 vs. 56.5 mm 2 , p ≤ 0.021), taller (mean height 18.6 mm vs. 9.9 mm, p < 0.001), more secreting (median PRL ULN&#95;area 23 µg/L/cm 2 vs. 12.6 µg/L/cm 2 , p ≤ 0.032) and had poorer hormonal response to DA as compared with homogeneous prolactinomas. "Cystic" tumors were diagnosed almost exclusively in women and secreted less prolactin, but showed similar hormonal and tumoral response as "non-cystic" tumors. In homogeneous prolactinomas, the T2-weighted intensity ratio was correlated to prolactin secretion, although not significantly, and did not predict hormonal and tumoral response to DA., Conclusions: Our study confirms that hypo/isointense prolactinoma is a rare finding and suggests for the first time that the heterogeneity of prolactinoma T2 signal at diagnosis might be correlated with a different clinical behavior and could be used as a negative predictor factor of hormonal response to DA.

Purpose: To assess biochemical and imaging therapeutic response rates, when these occur and their predictive factors in patients with macroprolactinomas treated with dopamine agonists (DA)., Methods: Retrospective, longitudinal study of patients with macroprolactinomas treated with DA for ≥12 months., Outcomes: prolactin normalization, reduction in maximum tumor diameter ≥50% and time until therapeutic responses., Results: We included 67 patients; 49.3% females, with median age at diagnosis of 43 years, 61.2% only treated with bromocriptine, 10.4% only with cabergoline, and 28.4% with both DA. Median follow-up time was 73 months. Prolactin levels normalized in 87%, mostly during the first 2 years. Prolactin levels after 6 months (HR 0.994, p = 0.012), 1 year (HR 0.970, p = 0.003), and 2 years (HR 0.970, p = 0.015) predicted its normalization time. Only 62% of the patients achieved a ≥50% reduction in maximum tumor diameter. Percent tumor diameter reduction after 1 year (OR 1.098, p = 0.022) and 2 years (OR 1.102, p = 0.008) predicted a ≥50% size reduction. Size reduction occurred later than prolactin normalization. Initial tumor diameter (HR 1.050, p = 0.032) and its percent reduction at 6 months (HR 1.110, p = 0.002), 1 (HR 1.060, p < 0.001), 2 (HR 1.045, p < 0.001), 3 (HR 1.048, p = 0.002), and 4 years (HR 1.074, p = 0.042) predicted the time until imaging response., Conclusion: A significant number of patients did not obtain an imaging response. Biochemical and imaging responses were asynchronous and occurred mainly in the first 4 years of treatment. This may allow an earlier identification of partially resistant and resistant macroprolactinomas, with consequent change in the therapeutic approach.

Purpose: To retrospectively evaluate the age of onset of MEN1-associated lesions in a group of affected children and adolescents and to compare the clinical features of our series with the evidence derived from the literature., Methods: The study population consisted of 22 Italian children and adolescents (age 6-31 years at the time of the inclusion in this study) all with a clinical and/or a genetic diagnosis of MEN1 performed before the age of 16 who have been followed-up regularly from 1998 to 2016 at the Regional Referral Center for Hereditary Endocrine Tumors. Clinical, biochemical, imaging and genetic data have been collected for each patient., Results: Ten subjects (45.5%) have not yet presented any clinical/biochemical/radiological manifestation of MEN1 disease, whereas 12 patients (54.5%) developed at least one MEN1-associated endocrine manifestation. The second group of patients was significantly older than the first one. The most frequent manifestation was primary hyperparathyroidism (50%), followed by pituitary tumors (prolactinomas) (31.8%) and nonfunctioning pancreatic neuroendocrine tumors (9%). The earliest cases of primary hyperparathyroidism and prolactinoma were a 12-year-old girl and a 13-year-old boy, respectively., Conclusions: MEN1 disease seems to present with different features in children and adolescents from those in adults. Our study confirms the fundamental importance of screening for tumors in young MEN1 patients beginning in early childhood, in order to avoid diagnostic and therapeutic delays.

Prolactinomas are the most common secretory pituitary adenoma. They typically occur in women in the 3rd-6th decade of life and rarely in the pediatric population or after menopause. Most women present with irregular menses and/or infertility. Dopamine (DA) agonists, used in their treatment, are safe during pregnancy, but in most cases are discontinued at conception with close monitoring for signs or symptoms of tumor growth. Breastfeeding is safe postpartum, provided there was no significant growth during pregnancy. Some women will experience normalization of prolactin levels postpartum. Menopause may also decrease prolactin levels and even those with macroprolactinomas may consider discontinuing their DA agonist with close follow-up. Prolactinomas may be associated with decreased quality of life scores in women, and play a role in bone health and cardiovascular risk factors. This review discusses the current literature and clinical understanding of prolactinomas throughout the entirety of the female life cycle.

Considerable evidence attests to the role of the hypothalamic-pituitary endocrine axis (HPA) in the maintenance of normal immunocompetence. The immune and neuroendocrine systems are integrally linked and coordinated with bidirectional communication maintaining immune balance. Any disturbance of the normal function of the HPA may significantly alter native immunocompetence and therefore be associated with the development of disorders which have a clearly established autoimmune basis. Molecular and functional evidence shows prolactin, produced by the anterior pituitary, to be a cytokine, exerting its effect via both paracrine and endocrine mechanisms [1]. Its involvement in the activation of multiple immune responses may adversely upregulate certain autoimmune diseases. Myasthenia gravis (MG) has long been recognized as an autoimmune disorder. In this mini review, we present the coterminous presentation of MG and prolactin-secreting macroadenoma. We review published cases in the world literature, discuss pathological mechanism, and consider future targeted therapies.

Intracranial tumors of different histologic types infrequently affect patients with pituitary adenomas and no history of head irradiation. The association with craniopharyngioma is extremely rare. Aims of this paper are: (1) to provide a critical literature review of typical features of pituitary adenoma presenting in association with craniopharyngioma; (2) to describe the first documented (clinically, biochemically, histologically, and radiologically) case of aggressive, suprasellar papillary craniopharyngioma presenting with amenorrhea, progressive reduction of visual field, and severe headache in a 38-year-old woman, a decade after surgical cure for microprolactinoma associated with empty sella, during which she had carried two pregnancies; and (3) to discuss common etiopathogenetic mechanisms, in relation to the management of these lesions. Systematic literature search for English literature focusing on the association of craniopharyngioma and pituitary adenoma was performed using PubMed database. Additional relevant articles from references lists were also included. Clinical, laboratory, and radiological examinations performed in our patient for the two brain lesions at diagnosis and follow up were collected. Literature search retrieved nine articles. Typically, craniopharyngioma were of adamantinomatous type, occurred simultaneously to pituitary adenoma, presented with headache and visual loss, and affected men. No case of clearly documented metachronous lesion affecting a woman after pregnancy had been described before. Although very rare and with uncertain etiopathogenesis, second tumors (i.e., craniopharyngioma) should be considered in patients with a history of pituitary adenoma, presenting with suggestive signs and symptoms, even after a long disease-free period, in order to provide proper and prompt treatment.

The objective of this study was to evaluate characteristics that discriminate prolactinoma from non-functioning pituitary macroadenoma with hyperprolactinemia. We included 117 patients with hyperprolactinemic pituitary macroadenomas. Patients were divided into three groups according to treatment outcomes and pathologic results: (A) prolactinoma that responded to dopamine agonist (DA) treatment (PRDA); (B) prolactinoma requiring surgical treatment (PRS); and (C) non-functioning pituitary adenoma with hyperprolactinemia (NFPAH). Old age, low serum prolactin levels, and extrasellar extension were associated with NFPAH. Most patients with NFPAH had serum prolactin levels less than 100 ng/ml. Visual defects and GH deficiency were more common in patients with NFPAH compared with patients with PRS and PRDA, without difference of tumor size. Galactorrhea and amenorrhea were less frequent in patients with NFPAH than in patients with PRS and PRDA. Post-operative remission of hyperprolactinemia was achieved in 100% of patients with NFPAH and in 72.5% of patients with PRS. DA administration was required in 25.5% of patients with PRS; however, no patients with NFPAH required DA administration. In conclusion, old age, extrasellar tumor extension with relatively low prolactin levels, visual defect, and GH deficiency were considered suggestive of non-functioning pituitary adenoma rather than prolactinoma in hyperprolactinemic pituitary macroadenoma.

We report an interesting case of a 47-yr-old who had a large goiter and multiple rib tumors. The patient was initially suspected of having thyroid cancer, which had metastasized on the ribs, based on imaging studies. However, laboratory tests revealed a high level of ionized calcium and parathyroid hormone (PTH). The large goiter was diagnosed as having parathyroid tumors owing to the high level of PTH in the tissue fluid. The biopsy specimen from a rib tumor was diagnosed as containing brown tumors associated with primary hyperparathyroidism (PHP). The patient also had prolactinoma and pancreatic gastrinoma. Her daughter had both prolactinoma and PHP, and her brother and her father had PHP. Thus, the patient was diagnosed as having multiple endocrine neoplasia type 1.