Diagnosis of hyperprolactinemia in women: A Position Statement from the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and the Brazilian Society of Endocrinology and Metabolism (SBEM).

Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correctcause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Societyof Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.

Macroprolactin over time: Is there any point in rechecking it in people with a persistently elevated serum prolactin?

OBJECTIVE AND DESIGN: Macroprolactinemia may influence the interpretation of serum prolactin levels-a recognised phenomenon since 1981. The degree of macroprolactinaemia over time is less well described. We determined how macroprolactin status (based on polyethylene glycol (PEG) precipitation) varied by analysing serial measurements in hyperprolactinaemic individuals over a period of 9 years. PATIENTS AND MEASUREMENTS: Results from 1810 individuals were included. All serum total prolactin results (measured using Roche Cobas 8000 analyser) were extracted from the laboratory information system for the period 1 January 2012 to 1 April 2021, along with relevant patient demographic/test data. Samples with a macroprolactin screening test performed (on samples with prolactin > 700 miu/L) were included in the main analysis. RESULTS: During the study period, 2782 macroprolactin checks were performed (12.5% of all prolactin tests) in 1810 individuals (599 males/2183 females, median-age: 35, interquartile range: 25-47, range: 16-93 years). Multiple macroprolactin checks were carried out on 465 patients (1437 measurements) with 94 patients (141 measurements) screening positive (<60% recovery). Only 19 patients (18 female) had at least one result above and one below the 60% screening cut-off, with 10 of these patients having results close to the 60% cut-off; in 9 patients, results were clearly different between repeat samples. In seven cases, the adjusted monomeric prolactin showed a potentially clinically significant difference. CONCLUSIONS: In this study, only 19/465 patients appeared to change macroprolactin status based on a 60% PEG recovery cut-off. The majority of these 19 patients were on antipsychotic/antidepressant medication(s) or had a prolactinoma; in only 7 did monomeric prolactin change significantly. This suggests that once macroprolactin status has been determined, clinical decision making is rarely affected by repeating it.

Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 2, specific diseases.

Pituitary adenomas are rare in children and young people under the age of 19 (hereafter referred to as CYP) but they pose some different diagnostic and management challenges in this age group than in adults. These rare neoplasms can disrupt maturational, visual, intellectual and developmental processes and, in CYP, they tend to have more occult presentation, aggressive behaviour and are more likely to have a genetic basis than in adults. Through standardized AGREE II methodology, literature review and Delphi consensus, a multidisciplinary expert group developed 74 pragmatic management recommendations aimed at optimizing care for CYP in the first-ever comprehensive consensus guideline to cover the care of CYP with pituitary adenoma. Part 2 of this consensus guideline details 57 recommendations for paediatric patients with prolactinomas, Cushing disease, growth hormone excess causing gigantism and acromegaly, clinically non-functioning adenomas, and the rare TSHomas. Compared with adult patients with pituitary adenomas, we highlight that, in the CYP group, there is a greater proportion of functioning tumours, including macroprolactinomas, greater likelihood of underlying genetic disease, more corticotrophinomas in boys aged under 10 years than in girls and difficulty of peri-pubertal diagnosis of growth hormone excess. Collaboration with pituitary specialists caring for adult patients, as part of commissioned and centralized multidisciplinary teams, is key for optimizing management, transition and lifelong care and facilitates the collection of health-related quality of survival outcomes of novel medical, surgical and radiotherapeutic treatments, which are currently largely missing.

[Overcoming therapy resistance in prolactinomas: from perspectives to real clinical practice].

The main treatment option of prolactin-secreting pituitary adenomas is dopamine agonist therapy, which demonstrates prolactin level normalizing and reducing the size of an adenoma in the majority of cases. However, significant amount of patients - about 20% - poorly responds even to high doses of dopamine agonists that is explained by the resistance to therapy. The occurrence of pharmacodynamic characteristics is one of the causes responsible for the development of resistance to typical therapy. Clinical manifestations of persistent hyperprolactinemia are due to following pathological factors: hormonal hypersecretion and the mass-effect of pituitary adenoma. Prevention of irreversible changes is possible only with timely detection of resistance and determination of the optimal personalized treatment algorithm.We report a clinical case of dopamine-agonist resistant microprolactinoma. Patient's health stabilisation, normal level of prolactin and reduction in size of adenoma were achieved due to administration of combined treatment with tamoxifen and dopamine agonists. Hyperprolactinaemia occurring because of prolactin-secreting pituitary adenoma and associated adverse effects are significant problem, decreasing quality of life and demographics in general. This underlines the importance of figuring out causes and identifying predictors of the therapy resistance.The results of the study, illustrated by a clinical example, are presented in the present paper.

Case Report: Multiple prolactinomas in a young man with Kallmann syndrome and familial hypocalciuric hypercalcemia.

Introduction: The occurrence of prolactinomas in sex hormone treated patients with central hypogonadism is extremely rare. Case presentation: We present a Caucasian male patient who was diagnosed with Kallmann syndrome (KS) at age 15 years. Testosterone treatment was started. At age 26 the patient presented with mild headache. MRI revealed two separate pituitary adenomas along with the absence of the olfactory bulbs. Given the presence of marked hyperprolactinemia (17x upper limit of the reference range) the diagnosis prolactinoma was made and treatment with cabergoline was started which resulted in a complete biochemical response and in marked reduction of both adenomas in size. Hypogonadism persisted and testosterone replacement therapy was continued. Genetic testing of genes associated with pituitary tumors, Kallmann syndrome and idiopathic hypogonadotropic hypogonadism was negative. Mild concomitant hypercalcemia in accordance with familial hypocalciuric hypercalcemia (FHH) prompted mutation analysis of the calcium receptor (CASR) gene which yielded a pathogenic inactivating variant. Discussion/conclusion: The presence of two separate prolactinomas in a patient with KS has not yet been reported in the literature. The effect of sex hormone treatment of KS patients on the possible development of prolactinoma is unknown at present. The occurance of multiple prolactinomas in our patient suggests increased susceptibility. Although CaSR is expressed in GnRH neurons in mouse brain and CaSR deficient mice have a reduced hypothalamic GnRH neuronal population, the relevance of the CASR gene variant in our patient for the KS phenotype is unclear at present.

[Modern concepts of genetic and immunohistochemical features of prolactin-secreting pituitary adenomas].

Prolactinomas are the most common secreting adenomas of the pituitary. In 20% of cases resistance to dopamine-agonists treatment is observed. Medical therapy resistance causes progression of pathological symptoms of hyperprolactinemia and negative topographic and anatomical changes of prolactinoma. The causes of ineffectiveness of dopamine agonists therapy are not fully understood as well as approaches to managing patients require clarification. Current concepts of resistance are based on the data obtained as a result of surgery or after a period of long-term ineffective therapy. Thus, it is very important to find methods of assessing the sensitivity of prolactin-secreting adenomas to drug therapy before surgical treatment. Genetic and immunohistochemical studies find special place among these methods, making it possible to predict adenoma's response to drug therapy at early diagnostic stage. Obtained results will allow us to form personalized algorithm for managing patients.

GIANT PROLACTINOMA. A CASE REPORT.

AIM: Prolactinoma is a pituitary adenoma that secretes prolactin. Approximately 40% of all pituitary adenomas are prolactinomas. According to size, they are divided into micro, macro and giant prolactinomas. In women, prolactinomas cause irregularities of the menstrual cycle such as amenorrhea, galactorrhea, weight gain, in both sexes they cause sterility, hypogonadism, decreased libido and depression. In macroadenomas, symptoms due to the compression of the surrounding structures are also manifested, such as headache, vomiting, lower chiasmatic syndrome and ophthalmoplegia. Loss of the visual field due to compression of the optic chiasm is caused by a tumor larger than 10-15 mm with suprasellar spreading, which breaks through the diaphragma sellae. Giant prolactinomas are larger than 40 mm and make up 1-5% of all prolactinomas. CASE REPORT: In this article I present the case of a 38-year-old woman from Ukraine with advanced chiasmatic syndrome caused by a giant prolactinoma. The tumor is infiltrating the left cavernous sinus, causing left-sided amaurosis and right-sided temporal hemianopsia. CONCLUSION: Inferior chiasmatic syndrome is characterized by bitemporal hemianopsia, a deterioration of visual acuity, bilateral bow-tie descendent atrophy of the optic nerve disc, and hemianopic rigidity of the pupils. Macroprolactinomas occur more frequently in men than in women. The diagnosis is often delayed, probably because the symptoms of hyperprolactinemia are less obvious in men, while women tend to present earlier due to menstrual cycle irregularities. Prolactinomas usually have a good prognosis. Effective medical treatment with dopamine agonists is available. Knowledge of the prolactinoma symptoms could help the diagnosis of compressive lesions of the optic chiasm.

A giant invasive macroprolactinoma with recurrent nasal bleeding as the first clinical presentation: case report and review of literature.

BACKGROUND: Giant prolactinoma (> 4 cm in dimension) is a rare disorder. Invasive macroprolactinoma has the potential to cause base of skull erosion and extend into the nasal cavity or even the sphenoid sinus. Nasal bleeding caused by intranasal tumor extension is a rare complication associated with invasive giant prolactinoma. We report a case of giant invasive macroprolactinoma with repeated nasal bleeding as the initial symptom. CASE PRESENTATION: A 24-year-old man with an invasive giant prolactinoma in the nasal cavity and sellar region who presented with nasal bleeding as the initial symptom, misdiagnosed as olfactory neuroblastoma. However, markedly elevated serum prolactin levels (4700 ng/mL), and a 7.8-cm invasive sellar mass confirmed the diagnosis of invasive giant prolactinoma. He was treated with oral bromocriptine. Serum prolactin was reduced to near normal after 6 months of treatment. Follow-up magnetic resonance imaging showed that the sellar lesion had disappeared completely and the skull base lesions were reduced. CONCLUSION: This case is notable in demonstrating the aggressive nature of untreated invasive giant prolactinomas which can cause a diagnostic difficulty with potential serious consequences. Early detection of hormonal levels can avoid unnecessary nasal biopsy. Early identification of pituitary adenoma with nasal bleeding as the first symptom is particularly important.

Diagnosis and Management of Pituitary Adenomas: A Review.

Importance: Pituitary adenomas are neoplasms of the pituitary adenohypophyseal cell lineage and include functioning tumors, characterized by the secretion of pituitary hormones, and nonfunctioning tumors. Clinically evident pituitary adenomas occur in approximately 1 in 1100 persons. Observations: Pituitary adenomas are classified as either macroadenomas (≥10 mm) (48% of tumors) or microadenomas (<10 mm). Macroadenomas may cause mass effect, such as visual field defects, headache, and/or hypopituitarism, which occur in about 18% to 78%, 17% to 75%, and 34% to 89% of patients, respectively. Thirty percent of pituitary adenomas are nonfunctioning adenomas, which do not produce hormones. Functioning tumors are those that produce an excess of normally produced hormones and include prolactinomas, somatotropinomas, corticotropinomas, and thyrotropinomas, which produce prolactin, growth hormone, corticotropin, and thyrotropin, respectively. Approximately 53% of pituitary adenomas are prolactinomas, which can cause hypogonadism, infertility, and/or galactorrhea. Twelve percent are somatotropinomas, which cause acromegaly in adults and gigantism in children, and 4% are corticotropinomas, which secrete corticotropin autonomously, resulting in hypercortisolemia and Cushing disease. All patients with pituitary tumors require endocrine evaluation for hormone hypersecretion. Patients with macroadenomas additionally require evaluation for hypopituitarism, and patients with tumors compressing the optic chiasm should be referred to an ophthalmologist for formal visual field testing. For those requiring treatment, first-line therapy is usually transsphenoidal pituitary surgery, except for prolactinomas, for which medical therapy, either bromocriptine or cabergoline, is usually first line. Conclusions and Relevance: Clinically manifest pituitary adenomas affect approximately 1 in 1100 people and can be complicated by syndromes of hormone excess as well as visual field defects and hypopituitarism from mass effect in larger tumors. First-line therapy for prolactinomas consists of bromocriptine or cabergoline, and transsphenoidal pituitary surgery is first-line therapy for other pituitary adenomas requiring treatment.

Approach to the Patient With Prolactinoma.

Prolactinomas are the most common pituitary tumor histotype, with microprolactinomas being prevalent in women and macroprolactinomas in men. Hyperprolactinemia is among the most common causes of hypogonadotropic hypogonadism in both sexes, prompting medical advice for hypogonadism (infertility, oligo-amenorrhea, impotence, osteoporosis/osteopenia) in both sexes, and for signs and symptoms of mass effects (hypopituitarism, visual loss, optic chiasm compression, cranial nerve deficits, headaches) predominantly in men. Diagnostic workup involves a single prolactin measurement and pituitary imaging, but some laboratory artifacts (ie, the "hook effect" and macroprolactin) can complicate or delay the diagnosis. The treatment of choice for prolactinomas is represented by dopamine agonists, mainly cabergoline, which are able to induce disease control, restore fertility in both sexes, and definitively cure one-third of patients, thus permitting treatment discontinuation. Pregnancy and menopause may promote spontaneous prolactin decline and anticipate cabergoline discontinuation in women. Surgery and/or radiotherapy are indicated in case of resistance to cabergoline not overcome by the increase in drug dose up to the maximally tolerated or the patient's personal choice of surgery. The evidence of resistance to cabergoline in invasive and proliferative tumors may indicate biological aggressiveness, thus requiring alternative therapeutic approaches mainly based on temozolomide use as monotherapy or combined with radiotherapy. In uncontrolled patients, new medical approaches (alternative hormonal treatments, cytotoxic drugs, peptide receptor radionuclide therapy, mTOR/Akt inhibitors, tyrosine kinase inhibitors, or immunotherapy) may be offered but the experience collected to date is still very scant. This article reviews different facets of prolactinomas and discusses approaches to the condition in more common clinical situations.

Hemoglobin decline as a signal for hyperprolactinemia onset prior to prolactinoma diagnosis in hypogonadal men.

BACKGROUND: Men harboring prolactinomas frequently suffer from central hypogonadism with secondary anemia. They present insidious and nonspecific symptoms of hypogonadism, making it difficult to diagnose the disease and determine its duration. The result is a delay in diagnosis, which may have harmful hormonal and metabolic consequences. We hypothesized that a decrease in hemoglobin (HB) levels prior to prolactinoma diagnosis, may signal hyperprolactinemia onset and estimate disease duration. METHODS: We retrospectively evaluated the prediagnosis temporal trends in HB levels of 70 males with prolactinoma, diagnosed from January 2010 to July 2022. Men without hypogonadism, patients that received testosterone, and those with unrelated anemia were excluded. RESULTS: Sixty-one of seventy men (87%) with prolactinoma presented with hypogonadism, and forty men (57%) had HB levels ≤13.5 g/dL at diagnosis. We identified 25 patients with "informative" HB curves (mean age, 46.1±14.9 years; median prolactin, 952 ng/mL; median follow-up, 14.0 years), demonstrating an obvious prediagnosis HB decrease (greater than 1.0 g/dL), from a prediagnosis baseline HB of 14.4 ± 0.3 to 12.9 ± 0.5 g/dL at diagnosis. The median "low-HB duration" (from the first low HB measurement to hyperprolactinemia diagnosis) was 6.1 years (IQR, 3.3-8.8 years). In symptomatic patients, we identified a correlation between "low-HB duration" and patient-reported sexual dysfunction duration (n = 17, R = 0.502, p = 0.04). The "low-HB duration" was significantly longer than the reported sexual dysfunction duration (7.0 ± 4.5 vs. 2.9 ± 2.5 years, p = 0.01). CONCLUSIONS: In our cohort of men with prolactinomas and hypogonadism, we found a marked decrease in HB levels that preceded prolactinoma diagnosis by a median of 6.1 years, with a mean delay of 4.1 years between HB decrease and hypogonadal symptoms appearance. These results suggest that HB decline prior to prolactinoma diagnosis may serve as a marker for hyperprolactinemia onset in a subset of hypogonadal men and allow a more accurate assessment of disease duration.

Ectopic Cavernous Sinus Microprolactinoma Treated Medically.

Ectopic prolactin-secreting microadenomas are rare and management is often surgical in contrast to intrasellar pituitary prolactin-secreting microadenomas. We present a case of ectopic dopamine-resistant microprolactinoma treated with cabergoline which led to symptom resolution, hormonal remission, and cystic degeneration of the tumor. A 30-year-old active duty male presented with a chief complaint of inability to maintain an erection for 6 months. Initial workup revealed suppressed serum testosterone of 128.60 ng/ml with an elevated prolactin level at 275.10 ng/ml. Pituitary magnetic resonance imaging showed a small mass measuring 9 mm in the left cavernous sinus. Medical management was initiated with cabergoline, which was titrated over the course of a year from 0.5 mg a week to 3.5 mg a week at its peak before being weaned off completely at 54 months. After treatment, the patient's symptoms resolved, his prolactin decreased to 29.5 ng/ml, near-normal, and his tumor had decreased size with cystic degeneration. Management for any prolactinoma has three primary goals: remittance of symptoms, decrease in prolactin levels, and decrease in tumor size. These are achieved through primarily medical management or surgery. Even though ectopic microprolactinomas are still frequently addressed surgically, this case shows that medical therapy can successfully treat ectopic prolactin-secreting pituitary microadenomas even in cases of dopamine resistance.

The Effect of Prolactinoma on Tear Film Function.

Objectives: To compare dry eye parameters in prolactinoma patients and healthy controls and evaluate their correlation with prolactin (PRL) levels and the duration of hyperprolactinemia. Materials and Methods: Consecutive patients with prolactinoma and healthy controls were included in the study. Schirmer, tear break-up time (TBUT), tear osmolarity values, and ocular surface disease index (OSDI) scores were evaluated for each patient. Follow-up time and total duration of hyperprolactinemia were recorded for prolactinoma patients. Results: The study included 39 eyes of 39 patients with prolactinoma and 39 eyes of 39 age- and gender-matched healthy controls. Prolactinoma patients showed lower Schirmer (14.1±8.4 vs. 24.8±8.9 mm; p<0.001) and TBUT values (7.0±3.2 vs. 11.6±2.6 s; p<0.001) and higher OSDI scores (20.6±16.6 vs. 5.8±2.4; p<0.001) compared to the healthy controls. While the mean osmolarity of the prolactinoma patients was 301.6±8.3 mOsm/L, it was 297.7±12.5 mOsm/L for the healthy controls (p=0.07). The duration of hyperprolactinemia in prolactinoma patients showed a negative correlation with Schirmer (r=-0.395; p=0.013) and TBUT values (r=-0.377; p=0.018) and a positive correlation with OSDI scores (r=0.337; p=0.036). Conclusion: Prolactinoma patients had significantly lower Schirmer and TBUT levels and higher OSDI scores compared to the healthy controls, but no significant difference in tear osmolarity. The effect of high PRL levels on tear film function was duration-dependent.

Diagnostic criteria of small sellar lesions with hyperprolactinemia: Prolactinoma or else.

Objective: To evaluate the combined predictive value of MRI criteria with the prolactin-volume-ratio (PVR) to differentiate prolactinoma from non-prolactinoma, in small sellar lesions with hyperprolactinemia. Methods: Retrospective analysis of 55 patients with sellar lesions of ≤15 mm diameter on MRI and hyperprolactinemia of ≤150 ng/mL, surgically treated between 2003 and 2020 at the Medical University of Vienna, with a conclusive histopathological report. Serum prolactin levels, extent of pituitary stalk deviation, size and volume of the lesion were assessed. The PVR was calculated by dividing the preoperative prolactin level by tumor volume. Results: Our study population consisted of 39 patients (71%) with a prolactin-producing pituitary adenoma (group A), while 16 patients (29%) had another type of sellar lesion (group B). Patients in group A were significantly younger (p=0.012), had significantly higher prolactin levels at diagnosis (p<0.001) as well as smaller tumor volume (p=0.036) and lower degree of pituitary stalk deviation (p=0.009). The median PVR was significantly higher in group A (243 ng/mL per cm3) than in group B (83 ng/mL per cm3; p=0.002). Furthermore, the regression operating characteristics analysis revealed a PVR >100 ng/mL per cm3 to be predictive for distinguishing prolactin-producing lesions from other small sellar lesions. Conclusion: In patients with small sellar lesions, Prolactin-Volume-Ratios >100 represents a possible predictive marker for the diagnosis of prolactin-producing pituitary adenomas.

The factors associated with the persistence of hypogonadism in male patients with prolactinoma.

PURPOSE: It was aimed to compare the testosterone level during the treatment and the factors associated with the persistence of hypogonadism in prolactinoma. MATERIAL AND METHODS: Thirty-five patients with hypogonadism who were diagnosed with prolactinoma were recruited to this retrospective study. Age, hemoglobin, hematocrit, glucose, lipid parameters, prolactin, follicle-stimulating hormone, luteinizing hormone, total testosterone, and the adenoma size were compared at the baseline and 6th month of the treatment. The parameters were also compared between the patients with hypogonadism (n=8) and the patients without hypogonadism at the 6th month of the treatment (n=27). Correlation analysis was also performed in terms of parameters that may be associated with the testosterone levels at the 6th month of the treatment. RESULTS: The mean current age of the whole study group was 45.6±13.0 years, and the mean adenoma size was 23.9±11.4 mm. Thirty patients had macroadenoma, and five patients had microadenoma. Eight patients (23%) had low testosterone levels and hypogonadism symptoms at the 6th month of the prolactinoma treatment. The adenoma size was larger in patients with persistent hypogonadism than the patients without hypogonadism at the 6th month of the treatment, while the prolactin levels were similar between the groups, and macroadenoma was detected in all patients with persistent hypogonadism. A negative correlation was found between the testosterone levels at the 6th month of the prolactinoma treatment with the adenoma size. CONCLUSION: Adenoma size is the prominent factor than prolactin levels for predicting persistent hypogonadism in patients with male prolactinoma.

Giant prolactinoma in children and adolescents: a single-center experience and systematic review.

PURPOSE: Giant prolactinoma (GP) in childhood and adolescence is a rare entity with scarce literature. We aimed to describe clinical features, biochemistry, radiology, genetics, management, and outcome in pediatric (≤ 20 years) GP. METHODS: Retrospective record review of 18 pediatric GP patients from our center and systematic review including these and 77 from the literature (total cohort: 95). RESULTS: GP constituted 20% of our pediatric prolactinoma cohort. In the total cohort (age: 15.4 ± 3.5 years), the majority (77, 82.8%) were males. Mass effect symptoms (88.6%), and pubertal delay/arrest in males (82.1%) were frequent. Median basal prolactin was 8649 (3246-17,532) ng/ml and the maximum tumor dimension was 5.5 ± 1.5 cm. MEN1 and AIP mutations were noted in 7 (21.9%) and 6 (18.8%) patients, respectively. Males with central hypogonadism had baseline bi-testicular volume of 20.2 ± 8.4 cc, lower LH than FSH (-2.04 ± 0.9 vs. -0.7 ± 1.6 SDS, p = 0.0075), and mostly, normal inhibin B. Majority (49/76, 64.5%) received dopamine agonist (DA) as first-line treatment with additional therapy in 35% (17/49). DA monotherapy arm had less frequent central hypothyroidism (42.9% vs 87.1%, p = 0.002) and central adrenal insufficiency (7.1% vs 66.7%, p = 0.0003) than multimodal therapy. A smaller tumor dimension (4.7 vs. 5.7 cm, p = 0.04) was associated with normoprolactinemia on DA monotherapy and AIP mutations (33.3% vs. nil, p = 0.02) with multimodal therapy. CONCLUSION: GP is characterized by male predominance with frequent delay/arrest of puberty (82%), but relative sparing of the FSH-inhibin B axis in boys. DA monotherapy may be preferred as the first-line therapy in pediatric GP.

Paraneoplastic cast nephropathy associated with malignant prolactinoma: A case report and literature review.

Malignant prolactinomas are very rare and are diagnosed when a prolactin-producing pituitary adenoma has metastasized. We report on a 54-year-old man with a history of macroprolactinoma transforming into a pituitary carcinoma secreting both prolactin and growth hormone with metastases to the stomach, bone, lungs, retroperitoneum, and kidney. Reviewing the literature, this case is the first reporting of a pituitary carcinoma with biopsy-proven paraneoplastic cast nephropathy. Symptoms and renal function improved following a course of palliative chemotherapy and radiotherapy. After 2 years, his disease progressed requiring further palliative treatment that was complicated by severe chest sepsis. He was not fit for further chemotherapy, receiving symptomatic relief in a hospice, and died soon after. The case highlights the importance of considering a patient's past medical history in the context of persistent unexplained renal impairment and systemic metastases when unexplained systemic symptoms and multi-organ involvement is present. The importance of renal biopsy for definitive diagnosis and before using potentially nephrotoxic chemotherapy is also highlighted. Renal diagnosis helped inform the decision to give chemotherapy, with the importance of this evidenced by an improvement in renal function following chemotherapy.

Macroprolactinoma-Induced Syndrome of Inappropriate Antidiuresis and Its Reversal with Dopamine Agonist Therapy.

Hyponatremia is an uncommon manifestation of pituitary adenomas. Herein, I report a case of syndrome of inappropriate antidiuresis (SIAD) caused by a macroprolactinoma that rapidly resolved with dopamine agonist therapy. A 29-year-old White woman presented with euvolemic, hypotonic hyponatremia, normal thyroid and glucocorticoid axes, and inappropriately concentrated urine. She was found to have a 1.2-cm sellar mass. Investigation of additional pituitary axes revealed an elevated prolactin level of 193.7 ng/mL. The SIAD experienced by the patient corrected rapidly with initiation of cabergoline. The patient could not tolerate dopamine agonist therapy, and after 1 year, she underwent transsphenoidal resection of the mass after the prolactin began to increase. Pathological examination confirmed the diagnosis of macroprolactinoma. There was no recurrence of the tumor, and the patient continued to have normonatremia and normoprolactinemia 7 years after her operation. To my knowledge, this is the first report in the literature of pathology-confirmed macroprolactinoma marked by SIAD that showed rapid normalization of water metabolism with dopamine agonist therapy.