Strikingly low prevalence of pituitary incidentalomas in a teaching hospital in Uruguay.

Background: Pituitary incidentalomas are an occurrence documented in 10.6% of post-mortem examinations, 4%-20% of computed tomography (CT) scans, and 10%-38% of magnetic resonance imaging (MRI) cases, primarily consisting of microincidentalomas (<1 cm in size). However, the prevalence of pituitary incidentalomas in Uruguay remains unexplored. This study aimed to ascertain the prevalence of pituitary incidentalomas at our hospital. Methods: In this investigation, we retrospectively identified patients who underwent brain CT and MRI at our hospital over a 1-year span due to conditions other than suspected or known pituitary disorders. The time frame covered was from 1 January to 31 December 2017. Our analysis encompassed all scans, and we conducted interviews with patients discovered to have pituitary incidentalomas. Furthermore, we conducted biochemical assessments in accordance with clinical and imaging traits. Results: During the study period, a total of 3,894 patients underwent imaging procedures. Of these, 1,146 patients underwent MRI scans, and 2,748 underwent CT scans. The mean age was 53.1 ± 19 years, with a relatively even distribution between genders (50.6% women). The majority of imaging requisitions originated from the emergency department (43%), followed by outpatient clinics (29%), and inpatient wards (28%). Common reasons for imaging requests included trauma (20.4%), headaches (11.3%), and stroke (10.9%). Among these cases, two pituitary incidentalomas were detected, resulting in a prevalence of 5 cases per 10,000 individuals annually (0.051%). Both of these cases were initially identified through CT scans, with subsequent MRI scans performed for further assessment. The final diagnoses were a vascular aneurysm and a sellar meningioma, with the latter patient also exhibiting secondary hypothyroidism. Notably, no instances of pituitary adenomas were encountered. Conclusions: The prevalence of pituitary incidentalomas within our hospital was notably low. Further research is necessary to more comprehensively investigate the occurrence of pituitary incidentalomas in our country.

Acute Sheehan's Syndrome Presenting with Hyponatremia Followed by a Spontaneous Pregnancy.

Background: Acute Sheehan's syndrome is rare, as well as hyponatremia as its initial manifestation. In addition, spontaneous pregnancy in patients after Sheehan's syndrome is unusual. To our knowledge, no cases of spontaneous pregnancy after acute Sheehan's syndrome have been reported. We describe a case of Sheehan's syndrome that presented with acute hyponatremia and a spontaneous pregnancy. Case: A 34-year-old female developed blood loss during delivery, which required a blood transfusion. On day seven postpartum, she presented with headaches, lethargy, and difficulty in breastfeeding. The workup showed hyponatremia (118 mEq/l), secondary hypothyroidism, and low prolactin levels. Magnetic resonance imaging showed pituitary necrosis. She was treated with NaCl, hydrocortisone (cortisol results were not available), and levothyroxine. Laboratory tests six weeks after discharge showed low IGF-1 and 8 AM cortisol and normal FT4, LH, FSH, and PRL levels. She was able to partially breastfeed until 4 months postpartum. Regular menstrual cycles started three months later. She became spontaneously pregnant one year later. Conclusion: Acute Sheehan's syndrome should be considered in the evaluation of postpartum patients with suggestive symptoms. Physicians should be aware that hyponatremia could be an initial manifestation of Sheehan's syndrome, which requires a high index of suspicion for diagnosis. Spontaneous pregnancy can occur after acute Sheehan's syndrome.

Pituitary Society Delphi Survey: An international perspective on endocrine management of patients undergoing transsphenoidal surgery for pituitary adenomas.

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.

18F-fallypride and 11C-methionine positron emission tomography/computed tomography for the study of prolactinomas and nonfunctioning pituitary adenomas: A case series.

Some studies have assessed the expression of dopaminergic dopamine 2 (D2)/3 receptors in prolactinomas and nonfunctioning pituitary adenomas (NFPA) by positron emission tomography/computed tomography (PET/CT) with 11C-raclopride, proving that this modality can be useful to predict the response to treatment with dopamine agonists. However, the use of 11C-labeled radiotracers is limited, as it requires a cyclotron in the PET center. 18F-fallypride is a radiotracer that has proven useful in assessing the expression of D2/3 receptors. As it is labeled with 18F, it can be produced and transported to distant PET centers. There are no studies on the usefulness of 18F-fallypride for the evaluation of patients with prolactinomas and NFPA. The aim of this study was to describe the first case series of patients with prolactinomas and NFPA studied with 18F-fallypride and 11C-methionine PET/CT to reveal D2/3 expression and amino acid (AA) metabolism. 18F-fallypride and 11C-methionine uptake were assessed in a case series of six patients, five with prolactinomas and one with a NFPA, and compared with clinical presentation and follow-up at 6-18 months. All patients presented with macroadenomas, with a wide range of AA metabolism, as revealed by 11C-methionine PET/CT. 18F-fallypride PET/CT identified low to moderate/high D2/3 expression in the tumors. The patient that presented low expression of D2/3 in the tumor and high AA metabolism showed a poor response to DA therapy. 18F-fallypride was able to reveal D2/3 receptor expression in prolactinomas and NFPA, with the advantage of been a more accessible radiotracer in comparison with previous 11C labeled analogs.

Excessive Maternal Weight and Diabetes Are Risk Factors for Macrosomia: A Cross-Sectional Study of 42,663 Pregnancies in Uruguay.

Objective: To evaluate the risk of macrosomia in newborns from women with gestational diabetes, pregestational diabetes, overweight, and obesity in Uruguay in 2012, as well as its association with prolonged pregnancy, maternal age, multiparity, and excessive gestational weight gain (EGWG). Methods: We performed a cross-sectional study of 42,663 pregnant women. The risk of macrosomia was studied using logistic regression. Results: Mean maternal age was 26.7 ± 6.8 years. Pregestational overweight and obesity was present in 20.9% and 10.7% of women, respectively. There were 28.1% and 19.8% of women overweight and obese at the end of the pregnancy, respectively. Furthermore, 0.5% had pregestational diabetes and 8.5% were multiparous. Twenty two percent developed gestational diabetes and 44.9% had EGWG. The prevalence of macrosomia was 7.9%, significantly more prevalent in males (10.0% vs. 5.5%, p<0.005). Univariate analysis showed that obesity and overweight pre-pregnancy, obesity and overweight at the end of pregnancy, EGWG, pregestational diabetes, gestational diabetes, multiparity, prolonged pregnancy, and male newborn were strongly associated with macrosomia (p<0.0001). Maternal age >35 years did not increase the risk of macrosomia. After multiple logistic regression macrosomia was more likely in pre-gestational obese women (OR 1.24; CI 1.07-1.44), overweight women at the end of pregnancy (OR 1.66; CI 1.46-1.87), obese women at the end of pregnancy (OR 2.21; CI 1.90-2.58), women with EGWG (OR 1.78; CI 1.59-1.98), pregestational diabetes (OR 1.75; CI 1.15-2.69), gestational diabetes (OR 1.39; CI 1.25-1.53), prolonged pregnancy (OR 2.67; CI 2.28-3.12), multiparity (OR 1.24; CI 1.04-1.48), and male newborn (OR 1.89; CI 1.72-2.08). Conclusion: Maternal overweight, obesity, EGWG, and gestational diabetes are prevalent in Uruguay, increasing the risk of macrosomia. Efforts to implement strategies to decrease the prevalence of overweight and obesity among women of reproductive age are essential to improve maternal and neonatal outcomes.

Pituitary society guidance: pituitary disease management and patient care recommendations during the COVID-19 pandemic-an international perspective.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral strain that has caused the coronavirus disease 2019 (COVID-19) pandemic, has presented healthcare systems around the world with an unprecedented challenge. In locations with significant rates of viral transmission, social distancing measures and enforced 'lockdowns' are the new 'norm' as governments try to prevent healthcare services from being overwhelmed. However, with these measures have come important challenges for the delivery of existing services for other diseases and conditions. The clinical care of patients with pituitary disorders typically involves a multidisciplinary team, working in concert to deliver timely, often complex, disease investigation and management, including pituitary surgery. COVID-19 has brought about major disruption to such services, limiting access to care and opportunities for testing (both laboratory and radiological), and dramatically reducing the ability to safely undertake transsphenoidal surgery. In the absence of clinical trials to guide management of patients with pituitary disease during the COVID-19 pandemic, herein the Professional Education Committee of the Pituitary Society proposes guidance for continued safe management and care of this population.

Factitious Cushing's Syndrome: A Diagnosis to Consider When Evaluating Hypercortisolism.

Factitious Cushing's syndrome is exceptionally rare. The diagnosis is challenging due to the interference of exogenous corticosteroids with cortisol immunoassays. We present a case of a 26 year old female that presented with clinical and biochemical features of Cushing's syndrome. She denied any exogenous corticosteroid use. She had a suppressed ACTH level with normal adrenal glands on CT scans. There was a paradoxical increase of cortisol with a 100% rise in 24 h urinary free cortisol (UFC) during the Liddle's test suggestive of primary pigmented nodular adrenocortical disease (PPNAD). However, basal UFC levels were within normal values, interpreted as an intermittent variation of cortisol secretion maybe due to cyclic Cushing's. At this point a synthetic glucocorticoid serum screening was ordered, which was denied by the administrators because the test was not available in our hospital. A positron emission tomography (PET)-CT using 18 F-Flurodeoxyglucose did not show any uptake in the adrenal glands. With the diagnosis of probable primary pigmented nodular adrenocortical disease a unilateral right adrenelectomy was performed. Histopathological examination revealed normal adrenal gland. A synthetic glucocorticoid serum screen by liquid chromatography-tandem mass spectrometry (LC-MS/MS) sent to Mayo Clinic lab revealed high levels of serum prednisone and prednisolone. In conclusion, factitious Cushing's syndrome is an important diagnosis to consider in patients being evaluated for hypercortisolism. Discordant hormonal test results as well as normal findings on adrenal glands on CT scan should raise suspicion of this entity, and prompt measurement of synthetic corticosteroids using LC-MS/MS.

Chronic cluster-like headache in a patient with a macroprolactinoma presenting with falsely low prolactin levels: bromocriptine versus cabergoline?

Cluster-like headache may be associated with pituitary tumors, mostly prolactinomas. Pituitary imaging and prolactin measurement should be assessed in patients presenting with cluster-like headaches with atypical features or unsatisfactory response to treatment. Furthermore, large pituitary adenomas with moderate increase in prolactin levels should prompt prolactin dilutions to avoid "hook effect".

Brain and Optic Chiasm Herniation into Sella after Pituitary Tumor Apoplexy.

Brain and optic chiasm herniation has been rarely reported following dopamine agonist treatment for large prolactinomas. We report a case of brain and optical chiasm herniation, secondary to an empty sella due to apoplexy of a prolactinoma, and we focus on the specific presentation of this case. A 32-year-old female presented to a neurologist complaining of headaches. Her past medical history was significant for acute vision loss in both eyes accompanied by right third nerve palsy when she was 16 years old. She does not recall any endocrine or imaging evaluation at that time and she had spontaneous partial recovery of left eye vision within 3 months, with permanent blindness of right eye. She did not return to any follow-up until her neurologist consultation. Brain magnetic resonance imaging (MRI) revealed herniation of frontal lobe and optic chiasm into the pituitary sella, as well as a pituitary hypointense lesion measuring 5 mm × 5 mm after gadolinium injection. Prolactin levels were 206 ng/ml (4.79-23.3 ng/ml). Repeated prolactin was 258 ng/ml (4.79-23.3 ng/ml). She was started on bromocriptine 2.5 mg/day. Prolactin levels and menstrual cycles normalized. A repeat brain MRI performed 5 months later showed disappearance of pituitary mass, with no changes in brain and chiasmal herniation. To our knowledge, this is the first reported case of brain associated with chiasm herniation secondary to pituitary apoplexy of a prolactinoma. In conclusion, this case highlights that frontal lobe herniation in combination with optic chiasm herniation can be a complication of pituitary tumor apoplexy. Long-term surveillance of patients with pituitary apoplexy is warranted to detect delayed complications.

Papillary Thyroid Microcarcinoma Arising Within a Mature Ovarian Teratoma: Case Report and Review of the Literature.

Mature cystic teratoma is the most common kind of ovarian germ cell tumor. Malignant transformation is uncommon, with thyroid cancer rarely found. Papillary thyroid microcarcinoma has rarely been described as associated with ovarian teratomas. We report a case of a 34-year-old woman who presented with abdominal pain and an ovarian mass. After surgery, the patient was diagnosed with a follicular variant papillary thyroid microcarcinoma that arose within a mature cystic ovarian teratoma. Based on the small size of the primary lesion and patient preferences, no further treatment was performed. To our knowledge, this is the third reported case of papillary thyroid microcarcinoma arising within a mature ovarian teratoma without struma ovarii. There is no consensus on the surgical approach and postoperative management of this condition. Whether further therapy with total thyroidectomy and radioiodine ablation may be beneficial is unknown. In conclusion, papillary thyroid microcarcinoma can also arise within mature ovarian teratomas. Although a favorable prognosis is anticipated, there is limited information about its history or prognosis.

Reduction of false-negative results in inferior petrosal sinus sampling with simultaneous prolactin and corticotropin measurement.

OBJECTIVE: To investigate the value of prolactin as an independent marker of catheter placement to improve the diagnostic accuracy of inferior petrosal sinus sampling (IPSS) in patients with corticotropin-dependent Cushing syndrome. METHODS: In this retrospective cohort study, we reviewed hospital records of patients who underwent IPSS procedures at the Cleveland Clinic between 1997 and 2009. Serum prolactin and plasma corticotropin levels were measured prospectively in peripheral and inferior petrosal sinus (IPS) samples. RESULTS: Forty-one patients underwent 42 IPSS procedures at our institution during the study period. Among 35 patients with Cushing disease, 1 patient had erroneous IPSS results: all pre-corticotropin-releasing hormone (CRH) and post-CRH IPS to peripheral (IPS:P) ACTH ratios were less than 2 and less than 3, respectively. Despite radiologic evidence of appropriate IPS catheter placement, concurrent IPS:P prolactin ratios indicated that successful IPS venous sampling was not achieved. A second case with equivocal IPSS results could also be explained by corresponding IPS:P prolactin ratios. During IPSS, all patients with an identifiable ACTH-staining adenoma localizing to 1 side of the pituitary gland (n = 22) who demonstrated absent IPS:P ACTH gradients (<2 before or <3 after CRH administration) on the ipsilateral side of the corticotroph adenoma had corresponding IPS:P prolactin ratios less than 1.3. CONCLUSIONS: Measurement of prolactin during IPSS testing may reduce false-negative results in patients with Cushing disease who do not demonstrate an appropriate central-to-peripheral ACTH gradient. In our series, all false-negative IPS:P ACTH ratios had a corresponding IPS:P prolactin ratio less than 1.3.

Poor correlation of serum alpha-subunit concentration and magnetic resonance imaging following pituitary surgery in patients with nonfunctional pituitary macroadenomas.

OBJECTIVE: To review the clinical utility of measuring serum alpha-subunit as a marker for residual tumor in a group of patients with surgically resected nonfunctional pituitary adenomas. METHODS: In this retrospective cross-sectional chart review using the pituitary database at the Cleveland Clinic, we identified patients with nonfunctional pituitary macroadenomas over a 4-year period (2000-2004) and selected those patients who had an elevated alpha-subunit concentration measured before pituitary surgery. Presurgery and post-surgery measurements of alpha-subunit, luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone were documented. Findings from preoperative and postoperative pituitary magnetic resonance imaging (MRI) were reviewed. RESULTS: We identified 54 patients who were evaluated for nonfunctional pituitary macroadenomas during the study period. Of the 39 who underwent pituitary surgery, 34 had a serum alpha-subunit concentration measured before surgery. Eight of 34 patients had elevated preoperative alpha-subunit levels with a median value of 1.8 ng/mL (range, 1.0-3.4 ng/mL). Of the 8 patients, 7 had follow-up MRI a median of 12 months (range, 6-52 months) after surgery. One patient was lost to follow-up. Three of 7 patients had persistently elevated alpha-subunit levels postoperatively; in 2 of these 3, MRI did not identify residual tumor. Among the 4 patients with postoperative normalization of alpha-subunit, 2 patients had residual tumor on MRI. CONCLUSION: The discrepancy between alpha-subunit levels and postoperative MRI calls into question the value of routine alpha-subunit measurement as a tumor marker in patients with nonfunctional pituitary macroadenomas.

Giant invasive pituitary prolactinoma with falsely low serum prolactin: the significance of 'hook effect'.

The authors report a case of a patient with giant, invasive skull base tumor extending to the parasellar area discovered incidentally during the work-up for decreased memory. The patient's neurological exam was otherwise unremarkable. Endocrine evaluation performed at a local hospital showed a moderate hyperprolactinemia 103 ng/ml (normal up to 20 ng/ml). Given the large size of the tumor, the elevated prolactin (PRL) was interpreted to be secondary to stalk effect and patient underwent debulking surgery through a transcranial approach. Immunostaining of the excised tumor tissue was strongly positive for prolactin. His prolactin was found to be 13,144 ng/ml in our lab after surgery confirming the diagnosis of invasive giant prolactinoma. The patient developed a complete right third, fourth and sixth nerve palsy postoperatively. He was started on Cabergoline with normalization of his prolactin level and more than 50% decrease in residual tumor size over 9 months periods. There has been no clinically significant improvement in his right eye ophthalmoplegia since surgery. This case highlights the importance of 'Hook Effect' resulting in falsely low prolactin level, which may have significant therapeutic implication.