The primary empty Sella: An endocrine study on 36 cases

Introduction: The term primary empty sella (PES) makes reference to the herniation of the subarachnoid space within the sella turcica in patients with no history of pituitary tumor, surgery or radiotherapy. Materials and Methods: We studied 36 patients; 27 females and 9 males. The mean age at diagnosis was 50, 4 years [21-80 years]. Most diagnoses were made by magnetic resonance imaging (n = 32). The anterior pituitary function was evaluated by basal hormonal measurements. Then, we had compared two groups of patients: G1(n=17), who had a pituitary disorder, and G2 (n=10), patients without hormonal disease, in order to determine risk factors for endocrine dysregulation in PES. Results: The reasons for ordering pituitary scans were: headaches (65%), visual disturbances (32%) and neurological symptoms in 8% of cases. Sixty-six point five per cent of women were multiparous. Diabetes, obesity and hypertension were found in 19.45 %, 11 % and 19.45 % of the studied population respectively. Hyperprolactinemia was present in 17.24 % of patients. Fifty-five percent of our patients had some degree of hypopituitarism. We didn’t find any correlation in our study, between pituitary insufficiency and age, gender, weight, parity nor post-partum hemorrhage. Failure of lactation was significantly associated with a hormonal disorder. On the other hand, headache was negatively correlated with hormonal effects in PES. Conclusion: PES was most commonly found in middle-aged multiparous women. In most patients, PES is a heterogeneous condition that ranges from hypopituitarism to various degrees of isolated GH deficiency, and which needs careful endocrine assessment, treatment and follow-up.

Primary Endoscopic Endonasal Management of Giant Pituitary Adenomas: Outcome and Pitfalls from a Large Prospective Multicenter Experience

Purpose: To evaluate factors influencing clinical and radiological outcome of extended endoscopic endonasal transtuberculum/transplanum approach (EEA-TTP) for giant pituitary adenomas (GPAs). Methods: We recruited prospectively all consecutive GPAs patients undergoing EEA-TTP between 2015 and 2019 in 5 neurosurgical centers. Preoperative clinical and radiologic features, visual and hormonal outcomes, extent of resection (EoR), complications and recurrence rates were recorded and analyzed. Results: Of 1169 patients treated for pituitary adenoma, 96 (8.2%) had GPAs. Seventy-eight (81.2%) patients had visual impairment, 12 (12.5%) had headaches, 3 (3.1%) had drowsiness due to hydrocephalus, and 53 (55.2%) had anterior pituitary insufficiency. EoR was gross or near-total in 46 (47.9%) and subtotal in 50 (52.1%) patients. Incomplete resection was associated with lateral suprasellar, intraventricular and/or cavernous sinus extension and with firm/fibrous consistence. At the last follow-up, all but one patient (77, 98.7%) with visual deficits improved. Headache improved in 8 (88.9%) and anterior pituitary function recovered in 27 (50.9%) patients. Recurrence rate was 16.7%, with 32 months mean recurrence-free survival. Conclusions: EEA-TTP is a valid option for GPAs and seems to provide better outcomes, lower rate of complications and higher EoR compared to one- or multi-stage microscopic, non-extended endoscopic transsphenoidal, and transcranial resections.

Alternative cause for hypoglycaemia in insulin-treated diabetes mellitus

We present a case of a 73-year-old woman who developed recurrent hypoglycaemia during a prolonged hospital stay following a mechanical fall. She had a complex history of insulin-treated diabetes mellitus, hypothyroidism, diffuse systemic cutaneous sclerosis, Raynaud’s disease, previous breast cancer, Barrett’s oesophagus and previous partial gastrectomy for a benign mass. Hypoglycaemia persisted despite weaning of insulin. She had no clinical features of adrenal or pituitary insufficiency with an acceptable cortisol on stopping prednisolone and had an optimal thyroid replacement. A 72-hour fast elicited hypoglycaemia with corresponding low insulin level. Although the C-peptide was detectable, there were no clinical, biochemical or radiological features suggestive of insulinoma. Reactive hypoglycaemia post partial gastrectomy was ruled out based on limited relation of the hypoglycaemia to meals and the low insulin levels. Hydroxychloroquine (HCQ)-induced hypoglycaemia was considered based on previous case reports and the recent literature, with a successful resolution of hypoglycaemia on discontinuation of HCQ.

Endocrine Toxicity and Outcomes in Patients with Metastatic Malignancies treated with Immune Checkpoint Inhibitors

Context Immune checkpoint inhibitors (ICIs) have gained a revolutionary role in management of many advanced malignancies. However, immune-related endocrine events (irEEs), have been associated with their use. irEEs have non-specific clinical presentations and variable timelines, making their early diagnosis challenging. Objective To identify risk factors, timelines, and prognosis associated with irEEs development. Design and setting Retrospective observational study within the Cleveland Clinic center. Patients Metastatic cancer adult patients who received ICIs were included. Methods 570 charts were reviewed to obtain information on demographics, ICIs used, endocrine toxicities, cancer response to treatment with ICI, and overall survival. Main Outcome Measures Incidence of irEEs, time to irEEs development, and overall survival of patients who develop irEEs. Results The final cohort included 551 patients. The median time for the diagnosis of irEEs was 11 weeks. Melanoma was associated with the highest risk for irEEs (31.3%). Ipilimumab appeared to have the highest percentage of irEEs (29.4%), including the highest risk of pituitary insufficiency (11.7%), the most severe (Grade 4 in 60%) and irreversible (100%) forms of irEEs. 45 % of patients with irEEs had adequate cancer response to ICI compared to 28.3 % of patients without irEEs (p= 0.002). Patients with irEEs had significantly better survival compared to patients without irEEs (P <0.001). Conclusions In the adult population with metastatic cancer receiving treatment with ICI, irEEs development may predict tumor response to immunotherapy and a favorable prognosis. Ipilimumab use, combination ICI therapy, and melanoma are associated with a higher incidence of irEEs.

Characterization of Gonadotroph Pituitary Adenomas Based on the Recent 2017 WHO Pituitary Tumor Classification

Introduction: More than 20% of pituitary adenomas are nonfunctional, the majority of which are of gonadotroph origin. Whereas previously, immunohistochemistry of pituitary hormones was used to classify adenoma subtypes, in 2017 the World Health Organization (WHO) reclassified pituitary adenomas using transcription factor expression in addition to immunohistochemistry. With this change, clinically nonfunctional gonadotroph adenomas can be distinguished among: (1) those staining for the transcription factor SF-1 and gonadotropins FSH and/or LH (FSH/LH+), (2) those that stain for SF-1 but not for FSH or LH (FSH/LH- SF1+), and (3) true null cell adenomas. It is unclear whether these three subgroups behave similarly clinically, or if they have distinct manifestations or outcomes. Our aim was to characterize these subgroups in regard to tumor size, recurrence and pituitary insufficiency. Methods: In a retrospective chart review, 71 patients from 2017-2020 who presented to the hospital for transsphenoidal resection of clinically nonfunctioning pituitary adenomas were reviewed. All patients with pituitary adenomas that stained positive for SF-1 and negative for T-PIT and PIT-1, and tumors that were negative for all three transcription factors were evaluated. Those lacking clinical data were excluded. Clinical characteristics examined include: demographics, tumor size, invasion of cavernous sinus, and hormone deficiencies. Results: Of the 71 pituitary tumors, 45% (n=32) stained positive for the beta subunit FSH and/or LH (FSH/LH+) and SF-1, 44% (n=31) stained for SF-1 with negative pituitary hormone stains (FSH/LH- SF1+), and 11% (n=8) were negative for all transcription factors and hormones (true null). All tumors were macroadenomas (>1 cm). While there were >50% males in the FSH/LH+ and FSH/LH- SF1+ groups, in the true null group only 25% of patients were male. Most patients were >50 years old in all 3 groups (81% FSH/LH+, 75% FSH/LH- SF1+, 88% true null). The prevalence of cavernous sinus involvement was 36% in both groups that stained for SF-1, but was 62% in the true null group. Both SF-1+ groups had similar tumor sizes and prevalence of panhypopituitarism (15-21%), but there were more episodes of recurrence since last known follow up in the FSH/LH- SF1+ group (20%), compared to FSH/LH+ tumors (7%). The true null group had ≥50% rates for both panhypopituitarism and recurrence. Conclusions: In this study, we highlighted the category of FSH/LH- SF1+ gonadotroph adenomas and compared these to FSH/LH+ and true null cell tumors. Based on clinical features, FSH/LH- SF1+ gonadotroph adenomas are similar to FSH/LH+ staining pituitary adenomas in regard to age, sex, size, and degree of cavernous sinus invasion, although there were more recurrences in the FSH/LH- SF1+ group. Though less common, our cohort suggests more aggressive tendencies in the true null group compared to SF-1 staining tumors.

Does Pituitary Dysfunction Always Occur Following Penetrating Head Trauma?

Background: Pituitary dysfunction and panhypopituitarism remain underdiagnosed in penetrating and blunt head trauma and can occur in both acute and chronic settings. Case: A 56 years old male with no significant PMH was admitted with a gunshot wound to the left T9 rib paraspinally with bullet deflection cranially along the left lung, left sternocleidomastoid, and resting anterior to the suprasellar cistern just above the midline of the sphenoid sinus close to the pituitary gland. Moderate volume pneumocephalus, chest hemopneumothorax, and sudden loss of right-sided vision required neurosurgical and pulmonary intervention. Endocrinology was consulted to evaluate pituitary function in the context of the bullet within the cranium. Physical examination showed intact mental status, non-focal exam, right-sided blindness, and foley catheter with normal urine output. Laboratory hormonal assessment for hypothalamic-pituitary axis (HPA) was performed consistent with normal sodium, potassium, FSH of 14.2 mIU/ml (1.0-13.0 mIU/ml), LH of 4.5 mIU/ml (1.0-9.0 mIU/ml), AM cortisol of 13.6 ug/dl (5-25 ug/dl), free cortisol of 2.06, ACTH of 10 pg/ml (10-60 pg/ml), IGF-1 of 80 ng/ml (78-220 ng/ml), TSH 1.93 mIU/L (0.5-5.0 mIU/L), FT4 1.05 ng/dl (0.8-1.8 ng/dl), Prolactin of 14.2 ng/ml (4-23 ng/ml) and HbA1c 5.1%. He reported no symptoms of adrenal insufficiency and remained hemodynamically stable. He was monitored for symptoms of pituitary insufficiency and suppression of the HPA axis along with urine output which remained normal and reassuring for the absence of central DI. The patient will continue outpatient endocrine surveillance. Discussion: The development of hormone deficiencies is directly related to the severity of head trauma. Mild traumatic brain injury (TBI) patients discharged from the ED, without loss of consciousness or post-traumatic amnesia less than 30 minutes do not require endocrine surveillance. Pituitary dysfunction occurs in 20-40% of patients with moderate to severe TBI. Pituitary ischemia leads to pituitary injury, due to changes in cerebral blood flow, cerebral hypoxia, and increased intracranial pressure. Compressive effects on the stalk from increased intracranial pressure is another indirect mechanism for pituitary dysfunction. Hospitalizations longer than 48 hours following TBI, require pituitary screening at 3-6 months. Chronic hypopituitarism develops in 15-20% of patients within 2-3 years with ACTH and GH deficiencies. Other changes in LH, FSH, TSH, and development of central diabetes insipidus can occur. However, despite severe TBI, acute pituitary hormonal involvement may not always occur, as in our patient. References: Tan CL, Alavi SA, Baldeweg SE, et al. The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance. J Neurol Neurosurg Psychiatry. 2017 Nov;88(11):971-981.

Complications and Comorbidities of Acromegaly—Retrospective Study in Polish Center

IntroductionIn acromegaly, chronic exposure to impaired GH and IGF-I levels leads to the development of typical acromegaly symptoms, and multiple systemic complications as cardiovascular, metabolic, respiratory, endocrine, and bone disorders. Acromegaly comorbidities contribute to decreased life quality and premature mortality. The aim of our study was to assess the frequency of acromegaly complications and to evaluate diagnostic methods performed toward recognition of them.Materials and MethodsIt was a retrospective study and we analyzed data of 179 patients hospitalized in the Department of Endocrinology, Diabetes and Isotope Therapy in Wroclaw Medical University (Poland) in 1976 to 2018 to create a database for statistical analysis.ResultsThe study group comprised of 119 women (66%) and 60 men (34%). The median age of acromegaly diagnosis was 50.5 years old for women (age range 20–78) and 46 for men (range 24–76). Metabolic disorders (hyperlipidemia, diabetes, and prediabetes) were the most frequently diagnosed complications in our study, followed by cardiovascular diseases and endocrine disorders (goiter, pituitary insufficiency, osteoporosis). BP measurement, ECG, lipid profile, fasting glucose or OGTT were performed the most often, while colonoscopy and echocardiogram were the least frequent.ConclusionsIn our population we observed female predominance. We revealed a decrease in the number of patients with active acromegaly and an increase in the number of well-controlled patients. More than 50% of patients demonstrated a coexistence of cardiac, metabolic and endocrine disturbances and only 5% of patients did not suffer from any disease from those main groups.

Pituitary insufficiency as a complication of COVID-19

We here report a case of multiple endocrine disorders—hypopituitarism with multiple hormone insufficiency and primary hypogonadism—that developed after recovery from respiratory failure in an individual with COVID-19.