bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acromegaly in a Young Women With Pituitary Hyperplasia Secondary to a Neuroendocrine Tumor
Authors: Bano Gul 
Published: May 2021

Abstract
Acromegaly is rarely due to an excess of the GH-releasing hormone (GHRH) and pituitary hyperplasia on histology should alert to its presence. Clinical Case: A 35-year-old was referred to surgery with a confirmed diagnosis of symptomatic acromegaly. Her GH failed to suppress during an oral glucose tolerance test (OGTT), her IGF-1 and prolactin was high. Her serum calcium was normal and her chromogranin B was high. MRI scan suggested microadenoma. Her surgery was deferred because of Covid 19, and she was treated with somatostatin analog (SSA). She finally had surgery in July. The histology and immunocytochemistry suggested pituitary hyperplasia with diffuse positivity for chromogranin and synaptophysin. GH was positive in the majority of the cells with many cells positive for Prolactin and ACTH. FSH and LH were positive in scattered cells with patchy positivity of TSH. A solitary nodule was noted in her neck during an examination. We arranged to look for conditions associated with pituitary hyperplasia resulting in GHRH production, including the genetic tests for inherited conditions. Her calcitonin level was normal. She had an ultrasound scan guided fine needle aspiration of the thyroid nodule, this showed Thy3f oncocytic nodule with no features of medullary thyroid carcinoma. She had an NMGa68DOTATATE whole body PET CTand the scan showed a large DOTATAE avid mass from the right adrenal gland compatible with Pheochromocytoma. Her 24 hours total urinary metadrenaline and normetadrenalin was high. Her genetic test for MEN1, CDKN1B, and MEN2 are negative. We have requested the GHRH measurement. After a pituitary surgery, her GH suppressed adequately on OGTT. Her IGF-1 and prolactin is low and her hypogonadism is resolved. Conclusion: Excess production GHRH can result from neuroendocrine tumors of the lung, pancreas, thyroid (medullary thyroid cancer), or pheochromocytomas and hypothalamic gangliocytomas.
Several familial syndromes, multiple endocrine neoplasia type 1 (MEN1) and 4 (MEN4), familial isolated pituitary adenoma (FIPA), Carney complex, and sporadic germline mosaic disorder McCune-Albright disease predispose to pituitary hyperplasia. GHRH acromegaly should be suspected in a patient with biochemical/clinical features of acromegaly in the presence of co-existing neuroendocrine tumors when there is diffuse pituitary enlargement on imaging or resolution of acromegaly after the surgical resection of the primary neuroendocrine tumour or persistent acromegaly after surgery if there is histological evidence of somatotroph hyperplasia. References: Akirov A, ASA SL, AMER L Shimon I and Ezzat S. The clinicopathological spectrum of acromegaly. J. Clin. Med. 8(11), 1962 (2019) J. Clin. Med. 2019; 8: 11, 1962
Acute Ischaemic Stroke With Hyperprolactinemia:A Case Report
Authors: Wan Zain Wan Mohd Saifuhisam , Omar Julia , Ismail Tuan Salwani Tuan , Che Soh Noor Azlin Azraini 
Published: May 2021

Abstract
Background: Macroincidentalomas were reported in 0.2% of patient underwent imaging (CT scans) for central nervous symptoms (1). In acute ischaemic stroke with hyperprolactinemia, the diagnosis of a double pathology of ischemic stroke and sellar tumour especially prolactinoma need to be considered. Hyperprolactinemia itself may be considered as a risk factor for ischemic stroke due to its thrombogenic effect (3).
Clinical Case: A 47-year old man underlying hypertension and diabetes mellitus for 5 years presented with sudden onset of right sided body weakness associated with facial asymmetry and aphasia. No history of fever or trauma. Asymptomatic of hyperprolactinemia previously. On general examinations Glasgow Coma Scale 11/15 Eye 4 Verbal 1 Motor 6, blood pressure was unstable with readings of systolic 244mmHg and diastolic 142mmHg. Neurological examinations showed expressive aphasia, right hemianopia, right facial nerve palsy and absence of gag reflex. Cerebellar signs were negative. Motor function examinations of right upper and lower limbs showed hypertonia, reduce power of 2/5, normal reflexes and up going plantar response. Sensory functions of right upper and lower limbs were reduced. Clinically diagnosed as stroke with hypertensive emergency. CT brain showed multiple hypodensities due to recent infarct and incidental finding of an aggressive sellar mass. MRI brain showed left Middle Cerebral Artery territory infarct and an aggressive sphenoid sinus mass with suprasellar and bilateral cavernous sinus extension possibility of a macroadenoma. Serum prolactin level showed markedly hyperprolactinemia (21146 ng/ml, n 4.04 – 15.2 ng/ml) which level of 500ng/ml or greater is diagnostic of a macroprolactinoma (2). FSH level (0.929 IU/L, n 1.5-12.4 IU/L) and LH level (1.11 IU/L, n 1.7-8.6 IU/L) were low in this patient due to suppression of GnRH secretion from hypothalamus by prolactin. Testosterone level (0.15 nmol/L, n 8.64-29.0 nmol/L) was low secondary to low LH. Serum cortisol, growth hormone and TSH were normal. Platelet count and coagulation profiles were normal. The patient was treated conservatively in ward for acute ischaemic stroke and later was started on dopamine agonist cabergoline for hyperprolactinemia.
Conclusion: This is a case report of acute ischaemic stroke with markedly hyperprolactinemia secondary to incidentaloma macroprolactinoma.
Reference: (1)Freda PU, Beckers AM, Katznelson L, et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96 (4): 894-904.(2)Abha Majumdar and Nisha Sharma Mangal. Hyperprolactinemia. J Hum Reprod Sci. 2013 Jul-Sep; 6(3): 168–175.(3)Sankalp Kumar Tripathi, Pallavi Kamble, M.G. Muddeshwar. Serum Prolactin Level in Patients of Ischemic stroke. International Journal of Contemporary Medical Research 2016; 3(12): 3459-3460.
Can Long-Standing GnRH Therapy Cause a Pituitary Prolactinoma?
Authors: Nandu Nitish Singh , Dawahir Wafa , Paduri Swetha , Gilden Janice L , Citrin Dennis L 
Published: May 2021

Abstract
Background: Pituitary adenoma (PA) is the most common cause of sellar masses and accounts for about 10% of all intracranial tumors. Several physiological, pathological, drugs, and rare causes like hypothyroidism can cause PA. We describe a case of long-standing treatment with GnRH analogues possibly contributing to development of PA. Clinical Case: An 86-year-old man with a history of prostate cancer (PC) treated with medical therapy, presented to the hospital with progressively worsening loss of vision in his right eye associated with low-grade headaches over the past few years. Fifteen years prior to presentation, the patient was diagnosed with Gleason 6 (3 + 3) localized PC. He had refused surgical intervention and hence was treated with flutamide, then leuprolide. Labs were significant for an elevated prolactin 34.2 ng/mL [n= 2.5 -17.4], low LH 0.7 mIU/mL [n=1.2-10.6], with normal FSH, TSH, ACTH, IGF, Cortisol, and PTH. CT head and MRI brain identified a 2.7cm x 2.6.3 cm X 1.7 cm mass in the suprasellar region involving the left cavernous sinus and right optic chiasm. These findings were consistent with a diagnosis of Prolactinoma. Patient refused surgery and hence was started on bromocriptine. The findings were suspected to be secondary to long-standing GnRH agonist therapy, and leuprolide was discontinued. DEXA scan confirmed osteoporosis with a T score of --2.5, which was treated with denosumab. Subsequently his vision improved. The patient continues to follow with endocrinology for the management of osteoporosis and prolactinoma. Conclusion: Primary hypothyroidism predisposes to PA due to loss of thyroxine feedback inhibition to hypothalamus with overproduction of TRH with hyperplasia of lactotrophs. We speculate that constant stimulation of the pituitary by GnRH analogues can also lead to enlargement of the anterior pituitary in a similar fashion, and can lead to the development of prolactinoma. LHRH agonists such as Leuprolide, as palliative treatment for advanced prostate cancer, causes desensitization of the anterior pituitary and decreases the production of LH and FSH, which ultimately leads to decreased testosterone in males. Although not standard of care for treatment of locally advance tumors, medical therapy was chosen in this patient’s case due to refusal of surgical intervention. He then developed a clinically significant pituitary adenoma years after the therapy. We suggest that constant stimulation of the pituitary by GnRH analogues can lead to enlargement of the anterior pituitary in a similar fashion, resulting in the development of the prolactinoma.
Reference(1) Du J, Ji H, Jin J, Gao S, Yan X, Hu S. Pituitary adenoma secondary to primary hypothyroidism: Two case reports. Medicine (Baltimore). 2020;99(8). https://journals.lww.com/md-journal/Fulltext/2020/02210/Pituitary_adenoma_secondary_to_primary.47.aspx
Case of a Giant Prolactinoma Measuring Greater Than 10 CM in a Post-Menopausal Woman
Authors: Imamudeen Nasvin , Zafar Aiman , Bettadahalli Shankar 
Published: May 2021

Abstract
Prolactinomas are the most common type of pituitary adenomas. Macroprolactinoma is the name used for tumors when their size exceeds 1 cm and giant prolactinomas are those that exceeds 4 cm. Females are more commonly reported to have microprolactinomas with female-to-male ratio of 20:1, on the contrary macroprolactinomas are usually diagnosed in men aged 20-50 years with a reported male-to-female ratio of 9:1. We are presenting the case of a 63-year-old female with history of cataracts and hypertension who presented with complaints of progressive decrease in vision in both of her eyes (right greater than left) for several months and declining night vision without headache. Her only other symptoms were tiredness and cold intolerance. A detailed visual exam led to the findings of bitemporal hemianopsia and possible right optic neuropathy. Her neurological exam otherwise was intact. Subsequently contrast magnetic resonance imaging (MRI) of the brain showed a large sellar and suprasellar mass measuring greater than 10 cm x 6 cm in size invading right cavernous sinus, surrounding vessels and compressing optic chiasm with extension into the right temporal lobe, left frontal lobe and subfalcine shift to the right. Laboratory studies indicated elevated prolactin level of 4932 ng/mL (2.8 - 29.2 ng/mL) consistent with prolactinoma. Pituitary hormone function testing revealed suppressed gonadotropins, subnormal ACTH stimulation test and central hypothyroidism. She was started on medical therapy with cabergoline. At one month follow-up, serum prolactin level significantly decreased to 136.2 ng/mL but the size of the mass did not significantly decrease on follow up brain MRI. Patient currently wants to try medical management alone.
Conclusion: Macroprolactinomas measuring &gt;4 cm are rare, accounting for only 1–5% of all prolactinomas and are more commonly seen in men, however they can be seen in postmenopausal women as well. Headaches and visual field disturbances are common presenting symptoms due to compressive effect and warrant further investigation with MRI of the brain. Medical therapy alone can sometimes suffice and surgery is a second line option as it confers morbidity risks.
COVID-19 and Cushing Disease: A Protective or a Deadly Combination?
Authors: Mehfooz Ayesha , Araki Takako , Burmeister Lynn Ann 
Published: May 2021

Abstract
Background: Manifestations of Cushing disease, including diabetes mellitus, hypertension, and obesity are risk factors for severe novel coronavirus disease 2019 (COVID-19) disease. A potential for severe COVID-19 disease might be hypothesized in Cushing disease patients. We present a finding of asymptomatic COVID-19 positive nasopharyngeal PCR test in an untreated Cushing disease patient. Case: A 19 year old female presented in January 2020 reporting amenorrhea and cushingoid facies. Her last menstrual period was two years ago. Low energy, fatigue, easy bruising and dark stretch marks on her legs, axillae and flanks were reported. Physical exam showed blood pressure 123/83 mmHg, pulse 89 bpm, BMI 20.80 kg/m². She had a cushingoid appearance with fullness in the face, neck and supraclavicular area, mild proptosis, pink cheeks and a few faint lavender striae on the inner thighs and flanks. Test results relevant to or supporting a diagnosis of Cushing disease included the following: 1 mg overnight dexamethasone suppression test: AM cortisol 23.9 ug/dl (6.7-22.6 ug/dl). Random 1019 hrs AM ACTH was 32 pg/ml (&lt;47 pg/ml), cortisol 6.5 ug/dl (4-22ug/dl). Repeat 1 mg overnight dexamethasone suppression test: AM cortisol was 36.5 ug/dl (4-22 ug/dl), Dexamethasone 249.2 ng/dl (140-295 expected post 1 mg DXA the night before). 24 hr urine free cortisol was 391.4 (&lt;=45.0 ug/d). Other endocrine labs were within normal limits. Left sided hypoenhancing lesion (2mmx2mmx2mm) consistent with pituitary microadenoma was seen on pituitary MRI. Inferior petrosal sinus sampling supported the presence of central disease and left pituitary location, concordant with the MRI. The time course from first clinical presentation to surgery was impacted by the COVID 19 pandemic temporarily halting elective surgical treatments and her access to care. At August, 2020 pre-op evaluation, the COVID-19 nasopharyngeal PCR was positive. Surgery was rescheduled. She denied symptoms of COVID-19 but recalled community exposure, including known COVID-19 positive contacts, while working as a waitress. Discussion: Increased susceptibility to and increased severity of COVID-19 manifestations might be feared in Cushing disease patients due to Cushing disease-associated immunosuppression, hyperglycemia, hypertension, obesity and venous thromboembolism. In contrast, randomized control trials have shown glucocorticoids, at doses sufficient to produce iatrogenic Cushing syndrome, may improve mortality in COVID-19 patients. Although asymptomatic COVID-19 infection is known to occur in young adults, the finding of asymptomatic COVID-19 positive test in a young woman with untreated Cushing disease also raises the possibility that endogenous hypercortisolism confers a similar benefit against severe manifestations of COVID-19 infection.
Cushing’s Disease (CD) Due to ACTH-Secreting Pituitary Microadenoma Incidentally Discovered on a Sestamibi Scan for Primary Hyperparathyroidism
Authors: Mehmood Hassan , Gordon Murray B 
Published: May 2021

Abstract
Introduction: MIBI scintigraphy is commonly being used for the preoperative localization of parathyroid adenomas. Multiple studies showed MIBI uptake in pituitary adenomas are likely due to higher metabolic activity. When hyperfunctioning pituitary adenomas were reported, both had CD [1,2]. We present the third case of increased pituitary uptake on a MIBI scan later confirmed as CD. CaseA 64-year-old Caucasian female s/p renal transplantation for RPGN who presented for evaluation of hypercalcemia. Evaluation confirmed primary hyperparathyroidism with persistently elevated PTH levels 74-108 pg/ml (11-68), serum calcium levels 10.0-10.4 mg/dl (8.4-10.3), albumin 4.1-4.3 g/dl (3.6-5.1), phosphorus 3.0-3.2 mg/dl (2.5-4.5), creatinine 0.94-1.07 mg/dl. 24-hour urine calcium 60 mg/day (35-250). Vitamin D-25 OH level was 37 ng/dL (30-100). A sestamibi scan showed uptake in the right lower parathyroid, the midsternal chest region and the pituitary gland. MRI of the pituitary revealed a 7mm cystic pituitary microadenoma in the right posterior pituitary. CD was confirmed by the findings of persistently elevated 8 AM serum cortisol levels of 28.4 and 24.2 mcg/dl (4-22), ACTH levels of 59 and 39 pg/ml (10-48), and an elevated plasma free cortisol of 1.43 mcg/dl (0.07-0.93). CT of the abdomen showed L adrenal thickening suggesting adrenal hyperplasia from CD. Plasma cortisol suppressed to 1.2 mg/dl following 1 mg of dexamethasone. 24 urine for free cortisol 26.7 mcg/day (4-50). The patient had no proximal muscle weakness, striae or Cushingoid facial features. She had no hyperglycemia or hypertension. Patient was diagnosed with an ACTH secreting pituitary microadenoma with mild CD and adrenal hyperplasia. Her DXA scan showed osteoporosis. Genetic testing for MEN1 mutation was negative. Patient did not wish surgery for either her hyperparathyroidism or her CD and is being evaluated for medical treatment of hypercortisolism. Conclusion: There are two prior case reports of an incidentally discovered pituitary adenoma on sestamibi scan later diagnosed as CD [1,2]. Corticotrophs may have a strong affinity for sestamibi. Our case is the first, to our knowledge, of pituitary MRI confirmation of the ACTH secreting pituitary incidentaloma initially suspected by pituitary uptake on a sestamibi scan in a patient with hyperparathyroidism. Reference1. Kuhadiya ND et al. Incidentally Discovered ACTH-Secreting Pituitary Adenoma on a Sestamibi Scan in a Patient With Hyperparathyroidism. AACE Clinical Case Reports. 2015;1(3):e152-5. 2. Gierach M et al. The case of Cushing’s disease imaging by SPECT examination without manifestation of pituitary adenoma in MRI examination. Nuclear Medicine Review. 2005;8(2):137-9.
Cushing’s Disease: Not Always Black and White
Authors: Shah Kajal , Chang Alan , Jarahzadeh Natalie 
Published: May 2021

Abstract
Cushing’s Disease is a well known entity but the difficulty of diagnosis is often underappreciated. Given the wide spectrum of clinical presentation and pitfalls with each diagnostic evaluation, diagnosis of Cushing’s Disease (CD) is often difficult in clinical practice, even with pathological analysis. A 37 year old female with a history of Cushing’s Disease presented for her third transphenoidal resection to our institution. She was diagnosed with a pituitary microadenoma 16 years ago based on MRI, as she had persistent headaches and vision abnormalities. The patient also reported unexplained weight gain, “buffalo hump”, and moon facies at the time. She was diagnosed with CD due to an abnormal 1 mg overnight dexamethasone suppression test (DST) with AM cortisol of 3.03 ug/dl (normal &lt;1.8 microgram/dl). She was on an oral contraceptive pill (OCP) at the time. The patient underwent her first pituitary transsphenoidal resection and was symptom free for about 10 years, after which she had a recurrence of her initial symptoms. She had another abnormal DST while on an OCP and pituitary MRI revealed growth of the pituitary adenoma. Patient underwent a second pituitary surgery with benign postoperative course with a recurrence about 5 years later. The workup prior to her third surgery revealed an abnormal DST while on OC pills with the 8am cortisol being 3.36 ug/dl (&lt;1.8ug/dl), urinary free cortisol 35.4 mcg/24 hour (4-50 mcg/24 hour). 8am ACTH done on a separate day was 48 pg/ml (6-50 pg/ml) with a cortisol of 14.5 ug/dl. Midnight salivary cortisol was not performed. Interval history was still positive for weight gain and headaches, hence she was referred for her third pituitary surgery. Post surgery, the patient was on a short taper of hydrocortisone and 8am cortisol was 32 ug/dl the next day. After a discussion with the pathologist, it was determined that the pathology was suggestive of a corticotroph adenoma with moderate ACTH staining and patchy nuclear staining for TPIT, although the pathologist stated that it was difficult to be certain due to the small tissue size. From the current literature, this patient had an incomplete and equivocal biochemical work up while on OCPs but still had tissue diagnosis supporting CD. Whether this was a recurrence of Cushing’s disease, silent corticotroph adenoma, or non-functioning pituitary adenoma is unclear. This case illustrates the multiple challenges in the diagnosis of Cushing’s disease that may be encountered. 1.Braun LT et al. Recurrence after pituitary surgery in adult Cushing’s disease: a systematic review on diagnosis and treatment. Endocrine. 2020;70(2):218-231.
Diverse Manifestation of Acromegaly With Suspicion of Ectopic GHRH Secretion. Report of Two Cases
Authors: Godlewska Magdalena , Nowak Andrzej Jerzy , Boguslawska Anna , Kluczynski Lukasz , Grochowska Anna , Hubalewska-Dydejczyk Alicja , Gilis-Januszewska Aleksandra 
Published: May 2021

Abstract
Introduction: Acromegaly can rarely be caused by an ectopic production of GH or GHRH by various neoplasms, most commonly neuroendocrine tumors of pancreatic or pulmonary origin. Squamous cell carcinoma of the lung has not been associated with ectopic GHRH secretion yet. The authors present two cases of acromegaly with suspicion of GHRH ectopy. Presentation of the Cases: Case 1. A male born in 1945 presenting with typical morphologic features of acromegaly. Pituitary MRI revealed a cuneatic-shaped, hypointense focal lesion (8x7x6 mm) in the right posterior part of the anterior pituitary lobe, radiologically interpreted as either hyperplasia of the intermediate lobe or atypical adenoma in a normal-sized pituitary. IGF-1 and no suppression of GH secretion after oral glucose load were observed. Furthermore, a polycyclic tumor in the 2nd segment of the right lung with pathological metabolic activity in 18FDG- PET/CT was discovered. Ga68- DOTA TATE PET/CT revealed no pathological accumulation of the tracer. After upper right lobectomy, squamous cell carcinoma, non-keratinizing, G3, with a negative immunohistochemical reaction for GH was confirmed. IHC for GHRH and serum GHRH have been scheduled. After surgery and chemotherapy, no biochemical remission of acromegaly was observed and the pituitary MRI showed stable radiological image of the pituitary tumor, suggesting rather a possible metastasis to the pituitary. Due to unfavorable prognosis, the patient was disqualified from neurosurgical resection of the pituitary tumor. Case 2. a male born in 1948 with typical symptoms of acromegaly, elevation of IGF-1 and no suppression of GH in OGTT. Due to MRI contraindications, only CT of the head was performed- it revealed partially empty sella, compressed pituitary with maximal diameter 3 mm and no focal lesions. Treatment with somatostatin analogue was introduced, however, only partial biochemical control was achieved. Ga68- DOTA TATE PET/CT performed after 8 years showed pathological expression of somatostatin receptors in the pancreatic tail. Abdominal CT confirmed a focal lesion in this location, 14x9 mm, with a strong enhancement after contrast administration, suggesting a neuroendocrine tumor. The patient refused to undergo any invasive procedures and remains treated with SRL. Serum GHRH has been scheduled. Conclusion: The authors report two cases of ectopic acromegaly suspicion, with an ambiguous clinical and radiological presentation. In unclear cases of acromegaly, ectopic production of GHRH should be taken into consideration.