bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Checkpoint Inhibitor-Induced Hypophysitis in Renal Cell Carcinoma: Two Contrasting Case Presentations
Authors: Okigbo Chinelo , Kirk Deepa
Published: May 2021

Background: Increasing use of immune checkpoint inhibitor (ICI) therapy for malignancy has led to rising incidence of ICI-mediated endocrinopathies. We describe two varying cases of patients with renal cell carcinoma (RCC) who presented with ICI-mediated hypophysitis.

Cases: Patient A: A 72 year old female with RCC (T1bN0M0) diagnosed after an incidental renal mass was found on CT scan following a motor vehicle accident. After nephrectomy, she received 5 cycles of nivolumab (6/2019 to 10/2019). One month later, she presented in severe DKA and was diagnosed with ICI-mediated diabetes (low c-peptide, negative autoantibodies). ICI therapy was stopped. In 4/2020, she experienced a drastic reduction in her insulin requirement (~30 units/day of basal/bolus insulin to ~6 units/day of basal insulin only). She had a primary care visit for fatigue, nausea, and anorexia. Biochemical evaluation showed hyponatremia, normokalemia, normoglycemia, and no acid-base disorder. One week later, she presented to the emergency department (ED) with worsening symptoms. She was hypotensive (94/56 mmHg), hyponatremic (129 mmol/L), normokalemic, and azotemic. Cosyntropin stimulation test (CST) showed an inappropriate response [ACTH <5 pg/ml; cortisol response of 0.4 to 8.1 µg/dl]. Brain MRI showed a partially empty sella. She was diagnosed with secondary adrenal insufficiency (AI) due to hypophysitis and started on steroid replacement. A repeat CST after 3 months did not show HPA axis recovery. Her presentation is unique because she developed secondary AI six months after nivolumab therapy.

Patient B: A 43 year old female with RCC (T4N1M1) who received 4-cycles of ipilimumab and nivolumab (11/2019 to 1/2020). One month later, she presented to the ED with hypotension, anorexia, and fatigue. Biochemical evaluation showed severe DKA. She was diagnosed with ICI-mediated diabetes (low c-peptide, negative autoantibodies) and started on basal/bolus insulin. Her ICI-therapy was stopped. One month later, she was readmitted for hypotension and severe headaches and found to have hyponatremia (131 mmol/L), normokalemia, hyperprolactinemia (29 ng/ml), cortisol 4.5 µg/dl (previous random cortisol a month earlier was 33 µg/dl). Pituitary gland was normal on MRI. She was presumed to have secondary AI due to hypophysitis and started on steroid replacement. A CST performed after 3 months showed ACTH <5 pg/ml and cortisol response of 3.5 to 4.5 µg/dl. Her case was a usual presentation of ICI-mediated secondary AI as it occurred within 1-2 months of stopping ICI therapy.

Conclusion: As we continue to learn about ICI-mediated endocrinopathies, it is imperative to document the variation in timing of presentation. ICI-mediated hypophysitis can present at any time after the initiation of therapy. Given this variation, there is need for routine screening and early treatment of hypophysitis to reduce ED visits and readmission rates.
Interesting and Rare Case of Central Diabetes Insipidus in a Patient With Acute Myeloid Leukemia
Authors: Sherpa Chheki , Shrestha Bishow Chandra , Rijal Swarup S , Gabriely Ilan , Nallala Deepika , Singh Vinita
Published: May 2021

Introduction: Central Diabetes Insipidus (CDI) is the lack of antidiuretic hormone (ADH) leading to impaired urinary concentration and manifests with extreme thirst and excessive urination. Patients unable to drink fluids are at risk of severe dehydration and hypernatremia. CDI can be a rare complication of acute myeloid leukemia (AML). The occurrence of AML with CDI is extremely rare with only few case reports published. This combination of AML with CDI has been reported to be associated with monosomy 7 and inversion (3) (q21q26) and portends an overall a very poor treatment response resulting in poor outcomes.

Case Presentation: 66-year-old female with hypertension, polycythemia vera diagnosed in 2006 with transformation to AML in 2020. FISH studies revealed monosomy 7. Cytogenetic studies showed inv (3)(q21q26.2). Remission induction chemotherapy was initiated. Subsequently, neutropenic fever and sepsis secondary to Clostridium difficile colitis lead to hospitalization. Her sodium (Na) level gradually trended up and reached a peak of 157 mmol/l (range 136-145) and elevated serum osmolality at 311 mOsm/K with low urine osmolality 135 mOsm/K, low urine sodium at 13 and low urine specific gravity 1.006 concerning for CDI. She developed polyuria and received desmopressin (DDAVP) leading to improvements in urine osmolality to 267 mOsm/K, 30 minutes indicating CDI diagnosis. Her Na gradually normalized to 144 mmol/l, urine osmolality improved to 580 mOsm/K and urine specific gravity to 1.025. She is now on DDAVP 0.05 mg oral twice daily and her Na is in normal range. MRI pituitary did not show any evidence of metastatic lesion with intact pituitary bright spot. Her other pituitary hormonal workup was normal except for hypogonadotropic hypogonadism.

Discussion: The pathophysiology of AML and CDI is unclear. Leukemic cells infiltration of the neurohypophysis; thrombosis of small vessels in hypothalamic nuclei and the posterior pituitary; alterations of the neutrophil migration placed on the chromosome 7 leading to glycoprotein gp 130 production, a cell surface marker on granulocytes are some of hypothesis suggested. CDI has a variable onset in the course of myeloid malignancies. MRI pituitary can be normal in most of the cases.
Is It the COVID-19 and Untreated Panhypopituitarism a Deadly Combination: A Case Report?
Authors: Burekovic Azra , Divanovic Anida
Published: May 2021

Background: The possible long-term consequences of coronavirus disease (COVID-19) on the endocrine system are still not known. With the number of cases rising we have reported the first possible implications of COVID-19 on panhypopituitarism in Bosnia and Herzegovina. Clinical Case: A 59-year-old man was referred to the Endocrinology Counseling Center on 12/10/2020. For 15 years he did not take thyroid and adrenal replacement therapy. As a child, he was treated for short stature, as well as his two sisters. He had signs and symptoms of myxedema. He was urgently hospitalized to the Department of Endocrinology. His condition has worsened in the last month, more intensely in the last 10 days. He complained of general weakness, malaise, drowsiness, shortness of breath, fatigue, constipation, swelling of the lower legs. The patient was enormously adipose and moved harder with help of a walking stick. The thyroid gland appeared smaller on palpation. Laboratory investigations showed low and borderline levels of the following hormones TSH 0.590 (0.3-4.2 mU/L), FT4 1.44 (12.0-22.0 pmol/L), FT3 0.858 (3.1-6.8 pmol/L), ACTH at 8 am 2.59, ACTH at 16 pm 8.44 (7.20-63.3 pg/ml), GH 0.090 (0.0-14.0), FSH <0.7 (1.6-9.7 IU/L), LH <0.7 (0.7-7.8 IU/L), prolactin <30.8 (78-380 uIU/ml), testosterone 1.01 (above 50 years 2.5-21.6 nmol/l), cortisol at 8 am 557, cortisol at 16 pm 674, cortisol at 11 pm 674 (morning: 123-626 nmol/L, afternoon 46-389 nmol/L), DHS 1.87 (2.17-11.7 nmol/L). On 12/10/2020 he tested negative for SARS-CoV-2 infection. On 14/10/2020 his condition worsened. He was somnolent, and even though he was admitted to diuretic therapy, he had decreased urine output. His D-dimer was 3.93 (0-0.055 mcg/mL). CT findings of thoracic organs described cardiomegaly, atherosclerotic altered thoracic aorta, and changes in the pulmonary parenchyma on both sides. On 16/10/2020 the patient was transferred to the cardiology department. SARS-CoV-2 test was repeated, and it was positive. The patient exited due to pulmonary arrest on 17/10/2020. Conclusion: There are several possible mechanisms that may describe that COVID-19 infection exacerbates the symptoms of myxedema and panhypopituitarism, and consequently leads the patient to severe acute respiratory failure.
Isolated Central Adrenal Insufficiency Due to Nivolumab: A Case Report
Authors: Rjoob Hani , Khan Tayyab S
Published: May 2021

Background: Immune checkpoint inhibitors are immunomodulatory antibodies directed against programmed cell death 1 (PD-1), Nivolumab, or cytotoxic T-lymphocyte antigen-4 (CTLA-4) Ipilimumab. They have improved outcomes in patients with advanced cancers including renal cell carcinoma, non-small cell lung cancer and melanoma. Several immune related adverse events (irAEs) have been recognized with use of immune checkpoint inhibitors, including those involving the endocrine system. We present a case of a patient presenting with isolated central adrenal insufficiency in the context of Nivolumab use. Clinical Case: Our patient is a 54-year old man with pre-existing primary hypothyroidism and metastatic renal cell carcinoma treated with Nivolumab. After receiving a total of 14 cycles of Nivolumab, he presented to the Emergency room with his sister, who found him confused and lethargic. On presentation, he was found to be hypoglycemic (random glucose was 2.2 mmol/L). On physical examination, his vital signs were stable and he appeared euvolemic. He was disoriented without focal neurological deficits. Initial blood work revealed sodium 134 mmol/L, (Normal 135-145mmol/L), potassium 4.5 mmol/L (Normal 3.5-5 mmol/L), and TSH being 12.6 mIU/L (Normal 0.4-4 mIU/L). He was resuscitated with IV Dextrose 50% bolus then admitted to hospital and kept on an IV dextrose infusion. While his glucose improved, he was found to have hyponatremia, and confusion persisted. His nadir sodium was 116 mmol/L without seizures or loss of consciousness and required treatment with hypertonic saline. Giving hypoglycemia and hyponatremia, morning cortisol and ACTH were checked and came back 4 nmol/L (Normal 133-537 nmol/L) and undetectable (< 0.7 pmol/L, Normal 1.6-13.9 pmol/L) respectively. The diagnosis of central adrenal insufficiency was made likely secondary to Nivolumab. He was started on Dexamethasone 8 mg daily. Sodium level normalized and glucose level improved with steroids. He was discharged home on prednisone 50 mg and then switched to hydrocortisone. Further

work up confirmed preserved other anterior pituitary hormones. MRI of Sella did not show pituitary enlargement or inflammation. Conclusion: Our patient presented with hypoglycemia and hyponatremia; both could be the presenting manifestations of central adrenal insufficiency. Nivolumab has been commonly associated with thyroid dysfunction and thyroiditis. Given lack of expression of PD-1 in the pituitary, PD-1 inhibitors are less likely to be associated with hypopituitarism in general, or central adrenal insufficiency in particular. However, our report adds to the growing body of literature associating it with central adrenal insufficiency, which can be isolated. In so doing, it underscores the need for early recognition this association with Nivolumab, so as to avoid the potentially life threatening consequences of this condition.
Isolated Macroprolactinomas in Four Young Adult Males Harboring a Variant of the Aryl Hydrocarbon Interacting Protein (AIP) Gene: Isn’t It Too Much of a Coincidence?
Authors: Chaves Carolina Marques , Chaves Mariana M , Anselmo Joao
Published: May 2021

Background: Germline mutations in the Aryl hydrocarbon receptor-Interacting Protein (AIP) gene are associated with pituitary adenomas in young patients usually in the setting of Familial Isolated Pituitary Adenomas (FIPA). The majority of these adenomas are somatotropinomas followed by prolactinomas, and rarely non-secreting adenomas. AIP-mutation-related prolactinomas predominantly affect men, as opposed to sporadic prolactinomas, that typically affect women. Clinical Case: We previously described an AIP gene mutation in two patients affected by prolactinomas. During the past years, we continued our study and have identified two more male patients with macroprolactinomas originally from the same small village and harboring the same AIP gene mutation. These male patients aged 19 to 44 years at the time of diagnosis. Two of them had neurological manifestations as the first clinical manifestation of the disease, one was studied because of hypogonadism and two patients had visual field defects. All of them had prolactin levels above 1000 ng/dl (mean 2946.5±948.7 ng/dl, reference range 10-21). In the imaging exams (CT/MRI) they presented pituitary adenomas larger than 20 mm (macroprolactinomas) and in two of the cases, the adenomas were even larger than 40 mm (giant prolactinomas). In order to exclude mutations most often associated with prolactinomas, DNA samples were obtained and analyzed by Next Generation Sequencing (NGS) using TruSightCancer Gene Set (Illumina) methodology. Investigation of significant deletions and/or duplications was performed using the MLPA (Multiplex ligation-dependent probe amplification) technique. None of the patients were positive for mutations of Multiple Endocrine Neoplasia type 1 (MEN1) gene. A variant of the AIP gene c.47G>A, expecting to lead to a substitution of arginine by histidine at position 16 (p.Arg16His) of the AIP was found in these four patients, including a father and his son. Seven asymptomatic carriers were identified among their first-degree relatives. In silico analysis and the information available in the literature, as well as in databases is not in agreement with the pathogenicity of this variant of the AIP gene. However, our findings point to a founder effect transmitted as a dominant trait with incomplete penetrance (4 out of 11 patients, 36%). Conclusion: The variant of the AIP gene identified in our patients behaved as a pathogenic mutation and was only associated with prolactinomas, including two giant prolactinomas.
Macroprolactinoma Presenting With Hyponatremia; A Rare Case Report
Authors: Ibrahim Safa , Wenkert David
Published: May 2021

Background: Hyponatremia is a common electrolyte abnormality, investigating the etiology can be challenging to the clinician, especially when the cause has rarely been associated with hyponatremia. Macroprolactinoma has rarely been reported as a cause of hyponatremia. We are reporting a case of macroprolactinoma presenting with hyponatremia.

Care Report: A 67 year old female previously healthy female, presented with a fall due to syncopal episode. Patient reported lightheadedness for a week prior to presentation. On physical examination, patient had bilateral periorbital ecchymoses, and swelling of the nose. Remaining of physical exam was unremarkable. Lab work showed hyponatremia with high urine osmolality and high urine sodium, consistent with syndrome of inappropriate antidiuretic hormone (SIADH). CT head showed Intrasellar soft tissue mass represents a pituitary macroadenoma. Pituitary hormonal workup showed high prolactin: 2,808 ng/mL, the rest of pituitary profile was normal, including pituitary-adrenal axis evaluation. Pituitary MRI confirmed a large pituitary macroadenoma measuring 1.7 x 2.9 x 2.5 cm, which displaces and compresses the optic chiasm and invades the right cavernous sinus. She was treated with fluid restriction and salt tablets with improvement of sodium level to normal. Cabergoline 0.25 mg twice a week was started with improvement of prolactin level to 156 ng/mL over 9 months period.

Discussion: Pituitary macroadenoma rarely associated with hyponatremia, and when reported it is usually secondary to hypopituitarism (low ACTH or low TSH). However, there are few cases reported of SIADH related hyponatremia in the presence of normal pituitary function. Although the exact mechanism of exaggerated production of arginine vasopressin (AVP) is not fully understood, the likely theory thought to be related to the mechanical pressure on the axonal terminal of AVP neurons by the large pituitary tumor.

Conclusion: Hyponatremia due to SIADH has been linked in few cases with nonfunctioning pituitary adenoma. Only two cases found in the literature reporting SIADH secondary to prolactin producing pituitary adenoma, with our case being the third reported case.
Panhypopituitarism Presenting as Progressive Visual Acuity Deterioration Secondary to Suprasellar Germinoma
Authors: Young Po Rainer Wandrew , Cating-Cabral Monica Therese B
Published: May 2021

Background: Overall the incidence of germ cell tumors worldwide is 0.1% with 60% comprising of germinomas. These may present in the suprasellar region a third of the time and thus impart variability in its presenting characteristics. Clinical Case: A 27-year male presented with progressive blurring of vision with incongruent visual acuity and refraction grade with optic disc pallor assessed with normal angiography. Patient also presented with increasing docility, sluggishness and more withdrawn behavior paired with polyuria, polydipsia and cold intolerance. Progressive worsening of vision led to cranial CT revealing an enhancing hyper density in the right caudate head later elucidated via MRI with several interspersed non-enhancing foci in the right caudate nucleus, both internal capsules with associated mild mass effect. The largest component located in the right capsular region with measurement of 21 x 21 x 16 mm with enhancing lesions in the hypothalamus and pituitary stalk. Endocrine evaluation revealed low serum cortisol at 91.03nmol/L (NV 138-685 nmol/L), responsive to ACTH stimulation test (65.94nmol/L to 387nmol/L), high prolactin at 856.9 mIU/L (42.4-296.8mIU/L) and low FT4 8.62pmol/l (9.01-19.05 pmol/L) despite normal TSH 1.528uIU/ml (0.35-4.94 uIU/mL). Optic nerve atrophy was now attributed to compressive intracranial mass. Secondary adrenal insufficiency was managed with hydrocortisone 50mgIV every 8 hours, and central hypothyroidism was managed with levothyroxine 75mcgtab 1tab once a day. Increased urinary output assessed as diabetes insipidus was given desmopressin 60mcg/tab ½ tab 2x a day at this time. Stereotactic biopsy of the brain revealed a germinoma of the right caudate lobe. Given the nature of the intracranial mass with high sensitivity to chemotherapeutic and radiotherapy, a multidisciplinary approach to treatment was taken with radiotherapy, hormonal and steroid replacement. Patient underwent external beam radiation therapy of the brain and spine for a total of 51 treatments allowing for improvement of visual acuity to counting, with polyuria less than 2-3 diaper changes per day. Conclusion: Optic disc pallor is a clinical sign that indicates optic nerve atrophy reflective of the optic tract. This may be an important clinical sign to increase clinical suspicion for intracranial mass lesion especially with correlation to manifestation of pituitary hormone deficiencies.
Pituitary Hyperplasia: To Operate or Not to Operate, That Is the Question
Authors: Rajwani Aakash , Ghalib Luma
Published: May 2021

Pituitary hyperplasia is defined as an absolute increase in the number of one or more adenohypophyseal cell subtypes, manifesting radiologically as pituitary enlargement beyond what is considered normal. It has been noted in certain physiological conditions like pregnancy however can also be seen in pathological conditions with end organ insufficiency like severe hypothyroidism.

21- year old female with a past medical history of Primary Hypothyroidism secondary to Hashimoto’s thyroiditis presented initially for evaluation of worsening headache and blurry vision. She was diagnosed with hypothyroidism at 10 years of age and had an extensive family history of hypothyroidism. At the time of presentation, she was 11 months post- partum and had been on and off her levothyroxine supplementation, having stopped it completely for a few months after delivery. MRI brain showed an 18 mm homogeneously enhancing intrasellar mass with suprasellar extension. She was referred to Neurosurgery for further evaluation. Workup revealed a TSH >100 (0.27 - 4.2 mIU/L) and FT4 <0.4 (0.8 - 2 ng/dL). In the context of severe untreated hypothyroidism and MRI findings consistent with pituitary hyperplasia with abutment but no mass effect on the optic apparatus, initial plan was to treat the hypothyroidism medically and observe closely. Patient was started on levothyroxine supplementation. Her TSH improved to 3.367 (0.550 - 4.780 uIU/mL) and FT4 to 2.00 (0.89 - 1.76 ng/dL), ηοωεϖερ she continued to have worsening of visual symptoms. Surgery was considered to decompress the optic nerve, but pre-operative MRI showed a significant decrease in size of the pituitary gland with decreased suprasellar bulging and no mass effect on the optic chiasm. Surgery was subsequently cancelled.

Prolonged primary hypothyroidism leads to pituitary hyperplasia due to loss of negative feedback from lack of circulating T4 and T3, leading to excessive TRH secretion from the hypothalamus. The high TRH can lead to thyrotroph as well as lactotroph hyperplasia. Subsequently patients can present with headache, vision changes along with signs and symptoms of hypothyroidism and increased prolactin secretion. It is important to differentiate hyperplasia from other sellar lesions like pituitary macroadenoma or hypophysitis. Patients with hypothyroidism, who have pituitary enlargement diagnosed on brain imaging, should be promptly diagnosed and treated with thyroid hormone replacement. With a higher frequency and improved quality of imaging techniques, we are increasingly coming across scenarios of abnormal findings on imaging. Correlation of radiographic imaging results with a thorough history and biochemical testing is essential prior to proceeding with surgical intervention.
Pituitary Hyperplasia Secondary to Primary Hypothyroidism Mimicking a Macroadenoma With Optical Chiasm Compression
Authors: Fujiwara Mariana Tazima , Daniel Karla Borges , Trentin Marília Bortolotto Felippe , Cerci Murilo Oliveira , Garmes Heraldo Mendes
Published: May 2021

Background: A long term untreated primary hypothyroidism can stimulate thyrotropes proliferation, leading to pituitary hyperplasia. This condition is known as pituitary hyperplasia secondary to primary hypothyroidism (PHPH). It is a rare condition that mimics pituitary adenoma and can achieve large proportions with optic chiasm compression. A misdiagnosis may be catastrophic, and a pituitary resection wrongly performed. Clinical Case: A 25-year-old woman with a medical history of delayed neuro psychomotor development and epilepsy due to congenital CNS malformation had a Brain MRI performed for epilepsy follow-up three years earlier. At that time, neuroimaging had shown a pituitary enlargement, and laboratory data were diagnostic of severe primary hypothyroidism with TSH of 290.6 uUI/mL (normal range 0.4 to 4.5 uUI/mL) and T4L <0.23 ng/dL (normal range: 0.9 to 1.8 ng/dL). She then had received a 75 mcg levothyroxine prescription. However, the patient missed medical follow-up and returned three years later, when sella turcica MRI showed a 0.9x1.0x1,4 cm pituitary lesion, consistent with a macroadenoma with suprasellar extent near the optic chiasm. Because of the cognitive impairment, the patient was not able to complete the visual field test. Neurology service referred the patient to endocrinology evaluation for surgical treatment. Hypothyroidism was still uncontrolled with TSH 157.1 uUI/mL and T4L 0.28 ng/dL. We had adjusted the levothyroxine dose to 125 mcg and advised adherence. Subsequent thyroid function tests had shown TSH 6.91 uUI/mL and T4L 1.15 ng/dL. After thyroid function stabilization, the patient performed a new sella turcica MRI, which had not evidenced pituitary lesion. Pituitary hyperplasia secondary to primary hypothyroidism was her final diagnosis. Conclusion: This case report illustrates the importance of the correct diagnosis and treatment of PHPH. Levothyroxine replacement, with TSH normalization, reverses the gland hyperplasia within 2 to 4 months.

References: 1. Cao J, Lei T, Chen F, Zhang C, Ma C, Huang H. Primary hypothyroidism in a child leads to pituitary hyperplasia: A case report and literature review. Medicine (Baltimore). 2018 Oct;97(42):e12703.2. Shivaprasad KS, Siddardha K. Pituitary Hyperplasia from Primary Hypothyroidism. N Engl J Med. 2019 Feb 21;380(8):e9.
Presyncope in a Woman With Incidental Bladder Mass: A Case of De Novo SDHB Mutation Bladder Paraganglioma
Authors: Grover Ashna , Rodriguez Ana Del Carmen Rivadeneira , Pandit Zuha , McLaughlin Christine D
Published: May 2021

Background: Paragangliomas (PGLs) are catecholamine secreting neuroendocrine tumors originating from extra-adrenal neural crest cells. Urinary bladder paragangliomas (UBPGLs) are extremely rare, accounting for only 0.06% of all bladder tumors. Sporadic UBPGLs associated with Succinate Dehydrogenase B (SDHB) mutation have a higher malignant potential versus patients with a positive family history due to a lack of screening. We present a case of sporadic UBPGL detected early due to follow-up of an incidental bladder mass.

Clinical Case: A 31 year-old female presented to the ER with presyncope and lower abdominal pain while running. On arrival she was mildly hypertensive with BP 140/88 mmHg, HR was 98 beats/min, other vital signs were stable. Denied headaches, diaphoresis, or weight loss. No known personal or family history of any endocrine disorders or cancer. CT abdomen pelvis performed for the evaluation of her abdominal pain revealed a large fibroid along with an unexpected finding of a 3 cm enhancing lesion in the right bladder wall, suggestive of a PGL. 24 hr urine total catecholamines and plasma total metanephrines were elevated at 284 mcg (normal range 26-121 mcg/24h), and 386 pg/mL (normal <205 pg/ml) respectively, confirming the diagnosis of UBPGL. Chromogranin A was within the normal range. Metastasis was ruled out with metaiodobenzylguanidine (MIBG) whole-body scan and octreotide scan which showed isolated uptake in the bladder. Pan CT scan was negative for other SBHB mutation associated tumors such as RCC (14% incidence), GIST, and thyroid carcinoma. Genetic testing with PGLNest revealed a heterozygous SDHB mutation (5’-3’ UTR_5’-3’ UTR deletion). Her parents were found to be negative for the mutation. During follow up she developed episodic palpitations. She was treated with alpha followed by beta blocker and underwent successful resection of the tumor with partial cystectomy, and of the fibroid with myomectomy on the same day (TAH was avoided to minimize manipulation of the uterus hence decreasing the risk of intra-abdominal HTN crisis). She has been tumor-free in the three years of follow up post-surgery with imaging and biochemical surveillance.

Conclusion: This case illustrates the importance of following up on incidental radiographic findings and adds to the limited literature on sporadic UBPGLs, an uncommon, yet potentially life-threatening tumor. The diagnosis of these tumors is especially challenging when patients present with non-specific symptoms. Fortunately, in our case, the imaging study clued us into the possibility of a PGL. SDHB mutation associated PGLs, in particular, are notorious for their late presentation with metastasis and associated tumors. Hence, timely detection with close follow-up of these patients will likely have an impact on their mortality.
Secondary Adrenal Insufficiency and Primary Hypothyroidism: A Complication of Cancer Immunotherapy
Authors: Manrique Helard Andres
Published: May 2021

Background: Immunotherapy has a fundamental role in cancer treatment. However, there have been found secondary effects in different organs due to its use, such as thyroid gland, pituitary gland, and adrenal glands,. This case report describes a case in relation with nivolumab, an antibody that blocks PD1 protein activity, promoting apoptosis Clinical Case: 67 years-old woman, with history of vulvar melanoma since 2016, complicated by pulmonary metastases. She was started with Nivolumab on 2018, every three weeks. After the her last immunotherapy session, she had less appetite, confusion, and incoherent speaking, and was admitted to the hospital In the Emergency, her blood pressure was 70/40mmHg, heart reate was 120 beats per minute. She was treated with fluid replacement. Her initial lab tests showed sodium 115.0 mmol/l(135.0 - 145.0), Chloride 85.9 mmol/l(98.0 - 109.0), Potassium 4.61 mmol/l (3.5 - 5.1), Hemoglobin 12.0, Leucocytes 6500, Platelets 282000, Total Proteins 7.0 (Albumin 4.0 Globulin 3.1), Alanine aminotransferase 10.0U/L (7-56), Aspartate aminotransferase 33.0 U/L (4-50) Creatinine 0.53. Hormonal Profile: T3 (triiodothyronine) 1.33 ng/ml(0.8 - 2.0), T4 (tetraiodothyronine) 7.27 ug/dl (5.1 - 14.1), TSH (thyroid stimulating hormone) ultrasensitive 12.87 uU/mL(0.27 - 4.2), FSH (Follicle stimulating hormone) 26.6mUI/ml, LH (Hormone)10.86 mIU/ml, Prolactin 60.96 ng/ml (6.0 - 29.9), Cortisol (am)0.22 ug/dl (4.2 - 38.4), ACTH (Corticotrophin-releasing hormone) <1.00, Anti TPO (Anti-Thyroid Peroxidase) negative, Glucose: 145 mg /dl, C Peptide: 0.4 ng/ml (0.9 - 7.1). Her brain MRI did not showcerebral edema or metastases. Conclusion: This case concerns metabolic encephalopathy due to severe hyponatremia caused by a secondary adrenal insufficiency (partial hypopituitarism), subclinical hypothyroidism and hyperprolactinemia, related to Nivolumab immunotherapy. Endocrinologists should be aware PD-1 inhibitor’s side effects, of its immunologic modulation mechanisms as they can cause hypophysitis, pituitary pituitary and thyroid dysfunction
Severe Hyperprolactinemia in a Patient With Concurrent ESRD and Medication Use
Authors: Johns Allison , Gorris Matthew
Published: May 2021

Background: A mild increase in prolactin has been previously reported in patients with pathological conditions, such as ESRD, as well as with several medications. Typically this is a mild elevation (<100 ng/mL), though certain medications have been shown to increase prolactin up to 200 ng/mL. However, we report a case of severe hyperprolactinemia in a patient with ESRD and on medications known to cause mild prolactin elevations. Clinical Case: Our patient is a 35-year-old female presenting for hyperprolactinemia. She has a history of uncontrolled diabetes with complications of ESRD on iHD, gastroparesis, and neuropathy. Further history revealed galactorrhea for 15 years following the birth of her second child as well as amenorrhea for the last 1.5 years. At the time of evaluation, she was not breastfeeding and did not have any reported life stressors. Medications were unchanged and included metoclopramide 10 mg daily and promethazine 25 mg PRN. Initial prolactin level one year prior to visit was 618 ng/mL. TSH 1.33. Brain MRI at that time did not reveal a pituitary mass, though pituitary protocol was not performed. Prolactin repeated on our initial visit had increased to 1352 ng/mL. Pituitary MRI was without evidence of pituitary mass. Despite discussing the importance of estrogen replacement, the patient was not interested in OCP therapy due to prior intolerance. Clinical Lesson(s): Hyperprolactinemia can be seen in patients on hemodialysis as a result of increased secretion in the uremic state and decreased clearance. Dialysis does not significantly improve the prolactin level. A recent study revealed a median prolactin of 65.2 ng/mL in dialysis patients. Our case emphasizes that the degree of hyperprolactinemia as a result of ESRD and medications can vary widely. It remains important to continue to consider the diagnosis of pituitary pathology in patients with a prolactin level that is higher than expected. However, if imaging is unrevealing, as in our patient, hyperprolactinemia may be attributed to medications and pathological disease states. Elevated serum prolactin has been shown to increase cardiovascular and all-cause mortality in a level-dependent effect. Hyperprolactinemia has also been associated with insulin resistance and worsened diabetes control. As we continue to learn more regarding the negative side effects of prolactin, it may become increasingly important to monitor and reduce prolactin levels in our patients, especially those on dialysis already with an elevated risk of cardiovascular disease.
Silent Pituitary Adenoma in Nasal Cavity
Authors: Bashir Bilal , Adam Safwaan , Cains Fiona , Higham Claire Emily , Pathmanaban Omar , Dhage Shaishav
Published: May 2021

Introduction: Silent corticotroph adenomas (SCA) represent 3-6% of all pituitary adenomas. SCA are confirmed on post-surgical histological tumour staining and can either have no prior clinical or biochemical evidence of excess ACTH or alternatively only biochemical (not clinical) evidence of Cushing’s disease. SCA are potentially large and aggressive tumours with a greater tendency to post-surgical recurrence. We present a case of a giant SCA which pre-operatively didn’t exhibit any clinical signs of cortisol excess but showed signs of early recurrence on follow up imaging. Case: A 40-year-old man presented with frontal and maxillary sinus pain and nasal stuffiness. Nasal endoscopy revealed a mass in the nasal cavity and sphenoid sinus. Subsequent CT scan of his sinuses and MRI Pituitary reported a 4 x 3.5 x 2.5 cm sellar mass extending through the floor of sella into the sphenoid sinus and nasal cavity. Despite no clinical features of any pituitary hormone excess (including Cushing’s) or deficiency, his biochemical parameters were consistent with hypercortisolaemia. Post-low dose dexamethasone (2 mg over 48 hours) suppression cortisol was inadequate: 106 nmol/L (<50nmol/L). His corresponding serum dexamethasone level was 8.6 nmol/L (>3nmol/L), ACTH 46 ng/L (0-46 ng/L) and 24-hour urinary free cortisol levels were 502 and 260 nmol/24 hours (<165 nmol/24 hours)) on 2 separate occasions. The remainder of his pituitary profile was normal. He therefore underwent expanded endonasal endoscopic resection of tumour without significant complication. His post-operative cortisol was <50nmol/L (other pituitary hormone measurements normal) so hydrocortisone replacement therapy was commenced. A 3-month post-operative MRI pituitary scan revealed near total resection of the tumour with peripheral enhancement within the tumour resection site representing post-surgical changes. Histopathology showed sparsely granulated, diffuse cytokeratin immunostaining and immunopositivity for ACTH and T-pit consistent with a corticotroph PitNet of the sparsely granulated variety with low Ki 67 index. His six month post-operative scan showed recurrent sellar mass of 2.2 x 0.9 x 1.4 cm. Again there was an absence of clinical features of Cushing’s syndrome. After multidisciplinary discussion clinical, biochemical and radiological surveillance was continued with a view to further transsphenoidal surgery and/or radiotherapy depending on the progress of the tumour.

Conclusion: Our patient solely had biochemical (not clinical) evidence of Cushing’s disease despite a large pituitary tumour in keeping with an SCA, which are aggressive, have high recurrence rate and shorter time to recurrence after surgery. Close and frequent post-operative clinical, biochemical and radiological surveillance is critical to detect and manage early recurrence that may require multimodal therapy.
Stuck at the Checkpoint: Pembrolizumab Induced Hypophysitis With ‘Normal’ Cosyntropin Response
Authors: Kasiri Elnaz , Pinsker Richard W , Ravich Marina , Patel Bijal
Published: May 2021

Introduction: Pembrolizumab is an immune checkpoint inhibitor (ICI) that blocks programmed cell death receptor 1 (PD-1) and is indicated in treatment of malignancies including lung adenocarcinoma and melanoma. Anti-PD-1 therapies are responsible for immune related adverse events including endocrine dysfunction. Here we present a case of Pembrolizumab induced hypophysitis causing central adrenal insufficiency apparently missed by a 250 mcg cosyntropin test.

Clinical Case: A 68 year old female with history of COPD and stage 4 lung adenocarcinoma with bone metastases presented to the ED with hypotension during her 14th cycle of treatment with Pembrolizumab. Other symptoms included fatigue and anorexia for about 4 weeks. She denied vomiting, diarrhea, bleeding episodes or chronic steroid use. On exam, patient was obese and pale appearing, with decreased bilateral breath sounds without edema. Random cortisol on admission at 4:44 pm was 6.9 ug/dl, ACTH - was in process, Na was 135 (137 - 145 mEq/L) and K was 3.7 (3.5 - 5.1 mEq/L). A 250 mcg cosyntropin stimulation test resulted in 30 min cortisol level of 22.5 µg/dL and 60 min cortisol level of 34 µg/dL. Patient was treated with fluids, salt tabs and eventually midodrine, however BP remained borderline low. On day 5, the patient was started on IV methylprednisolone 40 mg Q8 hrs for COPD exacerbation. A few days later pre-steroid ACTH was reported as <5 pg/ml (6-50 pg/ml) which prompted further workup for hypopituitarism. LH and FSH levels were inappropriately low for a postmenopausal female at 0.2 and 2.6 mIU/ml respectively, Free T3 was 2.02 pg/ ml (2.77-5.27 pg/ml), free T4 was 1.07 ng/dl (0.80-2.20 ng/dl), and TSH was 0.67 uIU/ml (0.47-4.70 uIU/ml). MRI brain showed partially empty sella. Patient was diagnosed clinically with Pembrolizumab induced hypophysitis causing central adrenal insufficiency. Eventually, steroids were tapered to prednisone 5 mg daily maintenance dose and patient was discharged with stress dosing instructions.

Conclusion: Diagnosis of adrenal insufficiency is challenging as advanced malignancy and adrenal insufficiency can cause similar symptoms. The finding of an empty sella here is a confounding factor. Checkpoint inhibitors are known to cause hypophysitis, thyroiditis and primary adrenal insufficiency, however incidence is <1%. We report a case of missed adrenal insufficiency by a falsely assuring cosyntropin test. Based on our experience, we conclude that when suspecting a diagnosis of checkpoint inhibitor induced adrenal insufficiency, we should start by checking random cortisol and ACTH value. A standard 250 mcg cosyntropin test should not be used solely to completely rule out this diagnosis.
Successful Multimodal Treatment of a TSH-Secreting Pituitary Adenoma (TSH-oma)
Authors: Lee Donna , Mahali Lakshmi , Tabatabaie Vafa
Published: May 2021

Background: TSH-omas are rare tumors accounting for 0.5-2% of all pituitary adenomas. Due to their indolent nature, most TSH-omas are diagnosed at the stage of invasive macroadenomas. Over the past several decades, the management of TSH-omas has evolved substantially. While surgery remains first-line therapy, somatostatin analogs have emerged as important therapeutic agents as a result of their effectiveness in normalizing thyroid hormone levels in ~95% of patients with severe hyperthyroidism and reducing TSH-oma size in ~50% of patients.

Clinical Case: A 52-year-old woman with a history of multinodular goiter was incidentally found to have a 2.2 x 1.8 x 2.1 cm pituitary macroadenoma with suprasellar extension, mass effect on the optic chiasm, and left cavernous sinus involvement when she presented with chest pain, palpitations, headache, and left-sided numbness and weakness. Laboratory results showed high FT4/T4/T3 with inappropriately high TSH, elevated α-subunit, and low cortisol with low-normal ACTH highly suggestive of TSH-oma with concurrent secondary adrenal insufficiency. An ophthalmology exam revealed a left superior temporal defect. The patient was treated with atenolol, prednisone, and octreotide two weeks before surgery with symptomatic improvement and near-normalization of FT4. Following an uncomplicated transsphenoidal resection, FT4 normalized within one week. At her one-month follow-up, both TSH and FT4 were normal, and her secondary adrenal insufficiency had resolved. Her visual field defect also recovered.

Laboratory Results: TSH 5.35 (normal range 0.40-4.60 μU/mL), FT4 3.0 (0.8-1.7 ng/dL), T4 18.1 (5.0-12.0 μg/dL), T3 235 (80-200 ng/dL), ACTH 10 (6-50 pg/mL), cortisol 4.5 (5.0-25.0 μg/dL), α-subunit 8.0 (0.1-1.5 ng/mL); after 2 weeks on SQ octreotide 50mg q12h: TSH 1.93 (0.30-4.20 μU/mL), FT4 1.7 (0.6-1.5 ng/dL); 1 month post-op: TSH 1.53 (0.30-4.20 μU/mL), FT4 0.8 (0.6-1.5 ng/dL), ACTH 12 (7.2-63 pg/mL), cortisol 6.9 (4.0-20.0 μg/dL)

Conclusion: Since the first reported case of TSH-oma in 1960, the diagnostic and therapeutic management of these rare pituitary adenomas have evolved due to the emergence of ultrasensitive TSH assays, advanced imaging and surgical techniques, and somatostatin analogs. However, to this day, most TSH-omas are still diagnosed at the stage of invasive macroadenomas, when successful surgical resection becomes more difficult. Hence, up to two-thirds of patients may require adjuvant therapy with medication or radiation. As evidenced in our patient, who achieved a near-euthyroid state within just two weeks of starting low dose octreotide, somatostatin analogs are highly effective in controlling hyperthyroidism and have solidified their place in the therapeutic management of TSH-omas. This case highlights the success of a multimodal approach to the treatment of TSH-omas.
The Sodium See-Saw: Prolonged Second Phase of Diabetes Insipidus and Complete Resolution Following Surgical Resection of a Supra-Sellar Meningioma
Authors: Pradeep Pallavi , Gandhi Shriya , Amin-Hanjani Sepideh , Kukreja Subhash C
Published: May 2021

Background: Diabetes insipidus (DI) is a common occurrence after sellar/suprasellar surgery. However, signs of recovery after a few days should be treated with caution as this may precede a “triple response”, seen in 3.4% of the patients. In this response, initial postoperative DI gives way to a period of remission or clinically inappropriate antidiuresis before eventual recurrence of DI.

Clinical Case: A 38-year-old Hispanic female was admitted to the hospital for elective transcranial resection of a suprasellar meningioma extending along the planus sphenoidale, measuring 23x19x17mm. Preoperatively, all pituitary hormones were in the normal range. On POD1, she was noted to have polyuria with urine output of >400ml/h, uptrending sodium levels (148, RR: 135-145mmol/L), low urine specific gravity (<1.005, RR:1.005-1.030) and low urine osmolality (82, RR:300-900mOsm/kg). She was diagnosed with DI and was treated with DDAVP over the following three days. Follow-up MRI was done. In addition to post-surgical changes, it showed acute ischemia in the region of the anterior commissure.

After short-term improvement in her clinical status, she was noted to have decreased thirst and decreased urine output on POD6. Sodium was low at 132mmol/L. Urine specific gravity was 1.017. Serum osmolality was 258 mOsm/kg (RR:279-300 mOsm/kg). There was concern for developing SIADH vs concurrent adrenal insufficiency. Patient had received methylprednisolone perioperatively, hence AM cortisol testing would have been inaccurate. Fluid restriction, along with empiric glucocorticoid replacement, was initiated. Sodium continued to worsen with nadir of 122mmol/L and patient reported new onset headache. She was started on 3% (hypertonic) saline continuous infusion and salt tablets. Hyponatremia gradually resolved by POD13, 7 days after onset of SIADH. Salt tablets and fluid restriction were discontinued. Patient was seen in clinic on POD17 and reported normal thirst and urine output. Sodium was noted to be 143mmol/L.

Conclusion: This case highlights the rare presentation of a partial triphasic sodium imbalance after resection of a suprasellar mass, with a prolonged second phase lasting for 7 days. A few studies have reported that it may last longer when pituitary gland is not damaged preoperatively, as was the case in our patient. Similarly, complete recovery may also occur if the hypothalamus and pituitary are normal preoperatively. Postoperatively, patient was noted to have an anterior commissural ischemia. This could have contributed to the fluctuations in ADH secretion, due to the rostral proximity of the hypothalamus to the anterior commissure.

Despite adequate measures, sodium may continue to drop dramatically in the second phase. Patients should be monitored for changes in thirst and normalization of urine output, as these may indicate early symptoms of impending SIADH before hyponatremia develops.
Thyrotropin-Producing Pituitary Adenomas
Authors: Arguello Mingxue , Levy Shiri
Published: May 2021

Thyrotropin-producing pituitary adenomas are rare cause of hyperthyroidism and it compose about 0.5-3% of all functioning pituitary tumors. Diagnosis of thyrotropin-producing pituitary adenomas can be challenging because TSH concentrations can be normal with only elevated T4. As a result, patient would be simply treated as primary hyperthyroidism. The latency between onset of hyperthyroidism and diagnosis of pituitary adenoma was reported to be 4-6 years. Many patients had radioactive iodine treatment or thyroidectomy treatment for primary hyperthyroidism at the time of diagnosis.

A 35-year-old male with history of intermittent FT4 elevation for the past 3 years presented at endocrine clinic for evaluation. Patient also had recent headache and dizziness. TSH was only marginally elevated once in the past 3 years. Alpha-subunit was found to be 2.6 ng/mL with negative heterophile antibody. MRI showed a 13.7 mm x 20.4mm x16.1mm sellar and suprasellar mass without cavernous sinus invasion but with chiasmal compression. Other pituitary hormone co-secretion was not found in this patient. Patient was treated with octreotide 20mg monthly for 3 month with normalization of T4 and size of the tumor also decreased on the medication. Patients was prepared for transsphenoidal surgery.

Treatment for thyrotropin-producing pituitary adenomas is mainly surgery. However, medical therapy with somatostatin analogs does play an important part in terms of inducing euthyroid prior to surgery. There are also articles describing shrinkage of the tumor prior to surgery while on somatostatin analogs. There were also rare case reports of thyroid storm from thyrotropin-producing pituitary adenomas when patients were not treated with somatostatin analogs prior to surgery. The surgical outcome was determined by the size of the tumor. Transient hypothyroidism or hypopituitarism can happen after the surgery. However, it is more common in external beam radiotherapy or radiosurgery treatment. For thyrotropin-producing pituitary microadenomas, transsphenoidal surgery is the treatment of choice with high remission rate. In some difficult cases where octreotide was not controlling the hyperthyroidism, methimazole use in combination with octreotide after surgery was also documented in the literature. The idea of using somatostatin analogs as primary treatment of thyrotropin-producing pituitary adenomas due to the risk of hypopituitarism with transsphenoidal surgery was explored in some literature. But, no strong evidence of better outcome with medication treatment alone was found.