Thyrotropinoma with silent somatotroph and lactotroph adenoma during pregnancy.

Summary: Thyrotropinomas are an uncommon cause of hyperthyroidism and are exceedingly rarely identified during pregnancy, with limited evidence to guide management. Most commonly they present as macroadenomas and may cause symptoms of mass effect including headache, visual field defects and hypopituitarism. We present a case of a 35-year-old woman investigated for headaches in whom a 13 mm thyrotropinoma was found. In the lead-up to planned trans-sphenoidal surgery (TSS), she spontaneously conceived and surgery was deferred, as was pharmacotherapy, at her request. The patient was closely monitored through her pregnancy by a multi-disciplinary team and delivered without complication. Pituitary surgery was performed 6 months post-partum. Isolated secondary hypothyroidism was diagnosed postoperatively and replacement thyroxine was commenced. Histopathology showed a double lesion with predominant pituitary transcription factor-1 positive, steroidogenic factor negative plurihormonal adenoma and co-existent mixed thyroid-stimulating hormone, growth hormone, lactotroph and follicle-stimulating hormone staining with a Ki-67 of 1%. This case demonstrates a conservative approach to thyrotropinoma in pregnancy with a successful outcome. This highlights the need to consider the timing of intervention with careful consideration of risks to mother and fetus. Learning points: Thyrotropinomas are a rare cause of secondary hyperthyroidism. Patients may present with hyperthyroidism or symptoms of mass effect, including headaches or visual disturbance. Thyrotropinoma in pregnancy presents a number of pituitary-related risks including pituitary apoplexy and compression of local structures. Hyperthyroidism in pregnancy raises the risk of complications including spontaneous abortion, preeclampsia, low birthweight and premature labour. Timing of medical and surgical therapies must be carefully considered. A conservative approach requires careful monitoring in case emergent intervention is required.

Physiotherapy-assisted prone or modified prone positioning in ward-based patients with COVID-19: a retrospective cohort study.

OBJECTIVES: To evaluate short-term change in oxygenation and feasibility of physiotherapy-assisted prone or modified prone positioning in awake, ward-based patients with COVID-19. DESIGN: Retrospective observational cohort study. SETTING: General wards, single-centre tertiary hospital in Australia. PARTICIPANTS: Patients were included if ≥18 years, had COVID-19, required FiO2 ≥ 0.28 or oxygen flow rate ≥4 l/minute and consented to positioning. MAIN OUTCOME MEASURES: Feasibility measures included barriers to therapy, assistance required, and comfort. Short-term change in oxygenation (SpO2) and oxygen requirements before and 15 minutes after positioning. RESULTS: Thirteen patients, mean age 75 (SD 14) years; median Clinical Frailty Scale score 6 (IQR 4 to 7) participated in 32 sessions of prone or modified prone positioning from a total of 125 ward-based patients admitted with COVID-19 who received physiotherapy intervention. Nine of thirteen patients (69%) required physiotherapy assistance and modified positions were utilised in 8/13 (62%). SpO2 increased in 27/32 sessions, with a mean increase from 90% (SD 5) pre-positioning to 94% (SD 4) (mean difference 4%; 95%CI 3 to 5%) after 15 minutes. Oxygen requirement decreased in 14/32 sessions, with a mean pre-positioning requirement of 8 l/minute (SD 4) to 7 l/minute (SD 4) (mean difference 2 l/minute; 95%CI 1 to 3 l/minute) after 15 minutes. In three sessions oxygen desaturation and discomfort occurred but resolved immediately by returning supine. CONCLUSION: Physiotherapy-assisted prone or modified prone positioning may be a feasible option leading to short-term improvements in oxygenation in awake, ward-based patients with hypoxemia due to COVID-19. Further research exploring longerterm health outcomes and safety is required.

Macrogonadotropinoma, a venous thromboembolic event and asymptomatic extensive periventricular white matter changes in a patient with Klinefelter syndrome.

Gonadotropinoma in Klinefelter syndrome (KS) is uncommon and may be a result of protracted stimulation of gonadotrophs from lack of androgen feedback. Associations of white matter changes and increased venous thromboembolic risk have been reported and need to be considered in patients with KS.

Ambulatory Blood Pressure Monitoring in Type 2 Diabetes Mellitus: A Cross-sectional Study.

BACKGROUND: Ambulatory blood pressure (ABP) monitoring in type 2 diabetes (T2DM) is not yet routine in clinical practice. OBJECTIVES: To quantify abnormal ABP patterns and their associations with diabetic complications, and to assess the reliability of office blood pressure (OBP) for assessing BP in T2DM. METHODS: In a cross-sectional study, eligible patients with T2DM underwent OBP and 24- hour ABP measurements under standardized conditions and screening for diabetic complications. RESULTS: 56 patients (mean age 67 ± 10 years, males 50%) completed assessment. 43(73%) had a known history of hypertension. Non-dipping and nocturnal systolic hypertension (SHT) were prevalent in 31(55%) and 32(57%) patients, respectively. 16(29%) demonstrated masked phenomenon, but only three (7%) demonstrated white coat effect. Nocturnal SHT had a significant association with composite microvascular complications independent of daytime systolic BP control (adjusted odds ratio (OR) 1.72(CI 1.41-4.25). There was no association between other abnormal ABP patterns and diabetic complications. The sensitivity and specificity of OBP for diagnosing HT or assessing BP control was 59% and 68% respectively. The positive and negative predictive values were 74% and 52% respectively. CONCLUSION: Non-dipping, reverse dipping, nocturnal SHT and masked phenomenon are highly prevalent in patients with T2DM with or without a known history of hypertension. Compared with non-dipping, nocturnal SHT may be a stronger predictor of end organ damage. The reliability of OBP for assessing BP in T2DM is only modest. Patients with T2DM are likely to benefit from routine ABP monitoring.

Clinical challenges of a co-secreting TSH/GH pituitary adenoma.

SUMMARY: Co-secreting thyrotropin/growth hormone (GH) pituitary adenomas are rare; their clinical presentation and long-term management are challenging. There is also a paucity of long-term data. Due to the cell of origin, these can behave as aggressive tumours. We report a case of a pituitary plurihormonal pit-1-derived macroadenoma, with overt clinical hyperthyroidism and minimal GH excess symptoms. The diagnosis was confirmed by pathology showing elevated thyroid and GH axes with failure of physiological GH suppression, elevated pituitary glycoprotein hormone alpha subunit (αGSU) and macroadenoma on imaging. Pre-operatively the patient was rendered euthyroid with carbimazole and underwent successful transphenoidal adenomectomy (TSA) with surgical cure. Histopathology displayed an elevated Ki-67 of 5.2%, necessitating long-term follow-up. LEARNING POINTS: Thyrotropinomas are rare and likely under-diagnosed due to under-recognition of secondary hyperthyroidism. Thyrotropinomas and other plurihormonal pit-1-derived adenomas are more aggressive adenomas according to WHO guidelines. Co-secretion occurs in 30% of thyrotropinomas, requiring diligent investigation and long-term follow-up of complications.

Chronic idiopathic normocytic anaemia in older people: the risk factors and the role of age-associated renal impairment.

OBJECTIVES: To characterise the risk factors for chronic idiopathic normocytic anaemia (CINA) in older people, particularly the role of age-associated renal impairment. METHODS: Patients aged ≥65 years admitted to a medical unit over 12 months were assessed. Those with secondary causes of anaemia including chronic kidney disease (CKD) were excluded. CINA was defined as a haemoglobin <130 g/l for men and <120 g/l for women for at least 6 months without any apparent cause. Renal function was determined by estimating creatinine clearance (CrCl) using Cockcroft-Gault formula, and glomerular filtration rate (GFR) using modification of diet in renal disease (MDRD) and chronic kidney disease epidemiology collaboration (CKD-EPI) formulas. RESULTS: 116 had CINA. Controls were 572. The mean estimates of renal function were significantly lower in cases as compared with controls (P < 0.001). The risk of CINA increased by 12.6, 10.4 and 12 %, respectively, for each unit decrease in CrCl, MDRD-eGFR and CKD-EPI-eGFR, independent of age and other covariates. The adjusted odds ratios for CINA in those with CrCl, MDRD or CKD-EPI eGFR <60 ml/min/1.73 m2 were 2.68 (CI 1.53-4.70); 2.70 (CI 1.57-4.62) and 2.12 (CI 1.46-3.74), respectively. Other covariates in the model that were independently associated with CINA included advanced age, diabetes mellitus (DM), use of angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), history of dementia and living in a residential care facility. CONCLUSIONS: Age-associated renal impairment independently contributes to CINA. Other potential risk factors for CINA include advanced age, DM and ACEI or ARB use.