Secukinumab, Pituitary Enlargement and Panhypopituitarism: Are They Related?

Pituitary adenomas represent the most common etiology of hypopituitarism associated with a pituitary enlargement, but other causes have been emerging, namely immune checkpoint inhibitors-induced hypophysitis (ipilimumab, nivolumab and pembrolizumab). Secukinumab is a recently approved human monoclonal antibody used for the treatment of psoriasis, with no know reported cases of hypophysitis. We describe a challenging case of panhypopituitarism in a patient with a pituitary incidentaloma and a timing relationship between secukinumab initiation and the manifestation of clinical features suggestive of hypopituitarism. In such intricate work-up, differential diagnosis should be carefully equated, taking into account the therapeutic and prognostic implications.

Immune checkpoint inhibitor-induced hypophysitis: lessons learnt from a large cancer cohort

Immune checkpoint inhibitors (ICIs) can cause pituitary dysfunction due to hypophysitis. We aimed to characterize ICI-induced hypophysitis and examine its association with overall survival in this single-center retrospective cohort study of adult patients with cancer who received an ICI from January 1, 2012 through December 31, 2016. A total of 896 patients were identified who received ipilimumab alone (n=120); ipilimumab and nivolumab (n=50); ipilimumab before or after pembrolizumab (n=70); pembrolizumab alone (n=406); and nivolumab alone (n=250). Twenty-six patients (2.9%) developed hypophysitis after a median of 2.3 months. Median age at the start of ICI was 57.9 years and 54% were men. Hypophysitis occurred in 7.9% of patients receiving ipilimumab alone or in combination or sequence with a programmed cell death protein 1 inhibitor; 1.7% after pembrolizumab alone, never after nivolumab alone. Secondary adrenal insufficiency occurred in all hypophysitis cases. Use of ipilimumab alone or in combination was associated with pituitary enlargement on imaging and mass effects more frequently than pembrolizumab alone. Occurrence of hypophysitis was associated with improved overall survival by univariate analysis (median 50.7 vs 16.5 months; p=0.015) but this association was not observed in multivariable landmark survival analysis (HR for mortality 0.75; 95% CI 0.38 to 1.30; p=0.34) after adjusting for age, sex and malignancy type. To conclude, hypophysitis occurred most frequently after ipilimumab and manifested as anterior hypopituitarism affecting the corticotrophs more commonly than thyrotrophs and gonadotrophs. Mass effects and pituitary enlargement occurred more frequently in ipilimumab-induced hypophysitis. The association of hypophysitis with overall survival needs further investigation.

Atypical pituitary abscess lacking rim enhancement and diffusion restriction with an unusual organism, Moraxella catarrhalis: A case report and review of the literature

Background: Pituitary abscess (PA) can be fatal if diagnosed late. Rim enhancement is a typical radiological finding of PA on postgadolinium T1-weighted magnetic resonance imaging (MRI). Diffusion-weighted imaging is helpful in distinguishing PA from other sellar cystic lesions. Herein, we report the first atypical case of PA showing neither rim enhancement nor diffusion restriction with an unusual organism, Moraxella catarrhalis. Case Description: A 77-year-old woman presented with headache, polyuria, polydipsia, and fatigue for a month before presenting to a local hospital. MRI showed pituitary enlargement with contrast enhancement. She had neither fever nor visual deficits and was followed up with hormonal replacement. Six months later, she complained of visual impairment, and MRI showed further pituitary enlargement with a thickened stalk compressing the optic chiasma. Neither rim enhancement nor diffusion restriction was observed. Endoscopic endonasal transsphenoidal surgery was performed based on the radiological diagnosis of lymphocytic hypophysitis or pituitary tumors. A thick, creamy yellow pus was drained from the sellar lesion. Intraoperative rapid histopathological findings revealed polymorphonuclear leukocytes infiltrating the pituitary gland. PA was diagnosed, and irrigation and open drainage of the abscess was performed. Bacterial culture of the pus detected M. catarrhalis by mass spectrometer, confirming the diagnosis. She underwent appropriate antibiotic administration, and her visual deficits improved. Conclusion: We report the first atypical case of PA showing neither rim enhancement nor diffusion restriction with M. catarrhalis. Even if preoperative findings are not suggestive of PA, it should be considered as a differential diagnosis. Intraoperative rapid histopathological findings are useful for accurately diagnosing PA and initiating appropriate surgical treatment.

Erosion of the sella turcica and pituitary expansion secondary to polymicrobial brain abscesses: a case report

Introduction. Brain abscesses can lead to a diverse array of complications, especially when they are polymicrobial in nature. Multiple underlying pathogens may present with a unique set of clinical symptoms which require an early identification and treatment. Skull base osteomyelitis with sellar floor erosion and pituitary involvement with SIADH are such rare complications of brain abscesses which have never been reported previously in the literature. Case Presentation. We report the case of an immunocompetent 38-year-old male with altered mental sensorium and left hemiparesis due to polymicrobial brain abscess which required surgical evacuation. The post-operative recovery was complicated by severe hyponatremia secondary to SIADH which was treated uneventfully. Radiological imaging demonstrated pituitary enlargement with herniation through an eroded sella turcica without active CSF leak. Patient responded well to the antibiotic therapy based on microbiological susceptibility testing with a complete resolution of the pituitary enlargement on radiological follow-up. Conclusion. Conservative treatment with targeted antibiotics can lead to the resolution of pituitary enlargement secondary to a brain abscess. However, a close clinical follow-up is required to look for a CSF leak considering the sellar floor erosion due to osteomyelitis.

Pituitary Hyperplasia: To Operate or Not to Operate, That Is the Question

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.

Hypopituitarism as the Initial Presentation of Pituitary Metastasis From Lung Cancer

Introduction: The annual incidence of hypopituitarism 4.2 cases of 100,000. Causes include primary tumor, metastasis, and non-tumor causes such as radiation therapy, infiltrative lesions, infection, and traumatic brain injury. Metastatic pituitary tumors constitute about 7-9% of the cases, with lung and breast cancers are the most common primary tumors. Case Presentation: 48-year-old Caucasian female patient with 30 pack-year smoking history presented to the emergency department with abdominal pain, diarrhea, fatigue, and headache. Review of systems was significant for loss of appetite, left eye visual field defect, anorexia, cold intolerance, and shortness of breath. Physical examination was remarkable for decreased visual acuity. Vital signs notable for hypotension BP 92/63. Notable labs include glucose of 53 mg/dL, TSH 0.50 [0.49 - 4.67 uIU/mL], low free T4 0.52 ng/dL, low FSH 1.3 mIU/ml, low LH <0.2 mIU/ml, low ACTH 1.4 pg/mL, low morning cortisol 2.2 ug/dL, low DHEA-SO4 3ug/dL, low IGF-1 16 ng/ml. She was diagnosed with hypopituitarism and started on IV hydrocortisone 50 mg every 6 hours with 75 mcg levothyroxine daily. MRI brain showed interval growth of pituitary lesion into the suprasellar cistern with a mass-effect on the optic chiasm measuring 2.4 X1.6X 1.9 cm with a lesion in the right cerebellar hemisphere. Vertebral MRI showed multiple metastatic lesions in cervical/thoracic/lumbar vertebral bodies. On day two of hospital stay, she developed hypertonic hyponatremia (sodium 156 mmol/L, urine osmolarity 81 mOsm/kg, plasma osmolarity 328 mOsm/kg), and she was started on desmopressin 2 mg IV for diabetes insipidus. CT chest showed spiculated left upper lobe mass consistent with primary malignancy, and biopsy showed metastatic poorly differentiated epithelial malignancy likely from lung primary. Patient was discharged on desmopressin 100 mcg nightly, hydrocortisone 20 mg morning with 10 mg evening, levothyroxine 100 mcg daily with plans for further oncologic workup. Discussion: Patient’s 2011 MRI brain showed a mildly enlarged pituitary gland. MRI brain two months before admission showed a pituitary gland diameter of 1.6 cm, while an MRI at presentation showed a pituitary gland size of 2.4 cm with a new cerebellar lesion. She reported symptoms of nausea, vomiting, and weakness for more than one year ago but biochemical testing was not performed. The fact that the patient had pituitary enlargement eight years ago likely delayed the diagnosis of pituitary metastasis. Patient age precluded lung cancer screening despite smoking history and family history of lung cancer. Conclusion: Symptomatic patients with pituitary enlargement on brain imaging may benefit from a close follow-up and biochemical testing for early diagnosis and treatment, especially if they have risk factors for malignancy.

Diabetes mellitus remission in three cats with hypersomatotropism after cabergoline treatment

Case summary Three diabetic cats presented with polyuria, polydipsia, polyphagia and poor glycemic control. Cat 1 displayed prognathia inferior and had a body condition score (BCS) of 4/5; cat 2 had a BCS of 5/5; and cat 3 had broad facial features. Serum insulin-like growth factor 1 concentrations were compatible with hypersomatotropism in cat 1 and cat 2 (>1500 ng/ml and 1200 ng/ml, respectively) and just below the cut-off of 1000 ng/ml (947 ng/ml) in cat 3; in this last cat diagnosis was further supported by the presence of pituitary enlargement on MRI. Oral cabergoline (10 μg/kg q48h) was initiated. Insulin requirements progressively reduced, as evidenced by daily blood glucose monitoring and weekly blood glucose curves. Diabetic remission occurred in all three cats between the second and third months of cabergoline treatment. At the time of writing, remission has persisted thus far (cat 1: 23 months; cat 2: 14 months; cat 3: 38 months). Relevance and novel information To our knowledge, these are the first reported cases of diabetic remission in cats with hypersomatotropism after cabergoline treatment, despite previous reports of this being an ineffective treatment. Further work is indicated to determine why some cats do, and others do not, respond to this treatment.

Dome-Shaped Pituitary Enlargement in Primary Hypothyroidism: Avoiding Neurosurgical Interventions

We describe three cases of primary hypothyroidism which presented initially to neurosurgery department with pituitary hyperplasia. We have found a novel pattern of ‘dome shaped’ enlargement of pituitary in MRI of these patients. Out of these 3 patients, in two of them, the planned surgery was deferred when endocrinologists were consulted and the pituitary hyperplasia completely resolved with levothyroxine treatment. In the third case, pituitary surgery was already performed before endocrinology consultation and histopathology revealed thyrotroph hyperplasia. The hyperplastic lesions described typically have a homogenous symmetrical ‘dome’ shaped architecture unlike the non-functioning pituitary adenoma (NFPA), which usually might often be of varying shapes and homogeneity. Analysis of pituitary images from similar case reports published in literature, also showed this typical ‘dome’ shaped pituitary enlargement. This imaging characteristic can be a clue to look for underlying hormone deficiency, especially in primary hypothyroidism. Therefore, a thorough endocrine evaluation especially looking for primary hypothyroidism in such dome shaped pituitary lesions are mandatory to prevent unwarranted neuro-surgical intervention as treatment of primary hypothyroidism may result in resolution of the abnormal enlargement.

A Chinese case of X-linked acrogigantism and systemic review

Introduction: To describe a Chinese case of X-linked acrogigantism (X-LAG) and summarize the characteristics and treatment of all reported cases. Methods: Clinical materials and biological samples from a 5-year and 2-month-old female due to “growth acceleration for 4 years” were collected. Array comparative genomic hybrid (aCGH) and further verification were performed. All X-LAG cases from the PubMed and Web of Science databases were collected and summarized using available data. Results: The patient presented accelerating growth since 1 year of age, and her height reached 134.6 cm (+5.24 standard deviation score, SDS) when she was 5 years and 2 months old. She also had coarsening facial features, snoring, and acral enlargement. Growth hormone (GH) was not suppressed by the glucose-GH inhibition test, and insulin-like growth factor 1 (IGF-1) and prolactin levels were elevated. Pituitary magnetic resonance imaging (MRI) revealed a pituitary enlargement with a maximum diameter of 22.3 mm. Octreotide imaging indicated the presence of a pituitary adenoma. The tumor shrank slightly after three courses of somatostatin analog but without clinical or biochemical remissions, of which the GH nadir value was 9.4 ng/ml, and IGF-1 was elevated to 749 ng/ml. Therefore, she underwent transsphenoidal surgery. Immunohistochemistry showed GH-positive and PRL-positive cells in the pituitary adenoma. Xq26.3 microduplication of the patient’s germline DNA was identified by aCGH. Of all 35 reported cases, females accounted for 71.43%. There were 93.10% and 53.83% patients with hyperprolactinemia and hyperinsulinemia, respectively. Pathology showed that 75.00% of cases were adenomas. Ninety percent of cases had germline variants. The clinical and biochemical remission rates were 78.26% and 82.61%, respectively. However, the rate of complication occurrence during therapy reached 80%. Conclusion: It is important to recognize the possibility of X-LAG when a child under 2 years old presents overgrowth. Early diagnosis and treatment are of great importance for better treatment efficacy and clinical outcome.