Point-of-care ultrasound is a useful adjunct tool to a clinician's assessment in the evaluation of severe hyponatraemia.

INTRODUCTION: Hyponatraemia is the most common electrolyte disorder in inpatients resulting mainly from an imbalance in water homeostasis. Intravascular fluid status assessment is pivotal but is often challenging given multimorbidity, polypharmacy and diuretics use. We evaluated the utility of point-of-care ultrasound (POCUS) as an adjunct tool to standard practice for fluid assessment in severe hyponatraemia patients. METHODS: Patients presenting with severe hyponatremia (Serum Sodium [Na] < 120 mmol/L; Normal range: 135-145 mol/L), managed by standard care were included. Hyponatraemia biochemistry work-up and POCUS examination were undertaken. Both clinician and POCUS independently assigned one of the three fluid status groups of hypovolaemia, hypervolaemia or euvolaemia. The final diagnosis of three fluid status groups at admission was made at the time of discharge by retrospective case review. Clinician's (standard of care) and POCUS fluid assessments were compared to that of the final diagnosis at the time of discharge. RESULTS: n = 19 patients were included. Median Na on admission was 113 mmol/L (109-116), improved to 129 ± 3 mmol/L on discharge. POCUS showed the higher degree of agreement with the final diagnosis (84%; n = 16/19), followed by the clinician (63%; n = 12/19). A trend towards higher accuracy of POCUS compared to clinician assessment of fluid status was noted (84% vs. 63%, p = 0.1611). Biochemistry was unreliable in 58% (n = 11/19) likely due to renal failure, polypharmacy or diuretic use. Inappropriate emergency fluid management was undertaken in 37% (n = 7/19) of cases based on initial clinician assessment. Thirst symptom correlated to hypovolaemia in 80% (4/5) cases. CONCLUSION: As subjective clinical and biochemistry assessments of fluid status are often unreliable due to co-morbidities and concurrent use of medications, POCUS can be a rapid objective diagnostic tool to assess fluid status in patients with severe hyponatraemia, to guide accurate emergency fluid management.

Audit of long-term treatment outcomes of thyrotoxicosis in a single-centre virtual clinic: The utility of long-term antithyroid drugs.

OBJECTIVE: To investigate the long-term outcomes and prognosis of thyrotoxicosis in a large number of patients in a single UK county (Leicestershire). DESIGN: Retrospective cohort analysis of 56,741 thyroid function test (TFT) results, treatment modalities and outcomes in a well-established virtual thyrotoxicosis clinic database. PATIENTS: One thousand four hundred and eighty-nine patients were included with a median length of follow-up of 10.9 years. The aetiology of thyrotoxicosis was autoimmune (85.9%), nodular (9.1%) and mixed (5.0%). Treatment modalities included antithyroid drugs (ATDs), radioiodine (RAI; 555 MBq fixed dose) and thyroidectomy. METHODS: We analysed both individual TFTs and groups of sequential TFTs on or after the same thyroid treatment(s), which we describe as 'phase of thyroid care' (POTC). Patients studied entered the virtual clinic between 1 January 1995 and 1 January 2010; we exported data on every TFT sample up to April 2020. RESULTS: ATD had been used in 99.2% (median 2, maximum seven courses) with long-term ATD (>2 years) in 48%. RAI and thyroidectomy were used more commonly with nodular and mixed aetiology. Overall, T4 was more often controlled than thyroid-stimulating hormone (TSH), and at the latest follow-up, T4 was normal in >96%, TSH in >79% and both in >76% of different aetiologies. The mean percentage control of T4 was 85% and TSH 50%; in long-term ATD courses, this improved to 89% and 62%, respectively. In the latest POTC, control of T4 and TSH was best in cases off treatment (95%/87%) and on T4 without ablative therapy (94%/72%), but was broadly similar in patients on long-term ATD (90%/68%), after RAI (92%/60%) or after thyroidectomy (91%/58%). After the first course of ATD, remission or hypothyroidism was seen in 47.3% autoimmune, 20.9% nodular and 32.5% mixed, with 90% relapses seen within 4 years. Relapse was more common in patients with ophthalmopathy, but there was no difference between the sexes. CONCLUSIONS: Thyrotoxicosis can be well controlled with minimal specialist clinic attendance using a software-supported virtual shared-care scheme. Long-term ATD appears to be a valid patient choice achieving TFT control comparable to that seen after RAI or surgery. In patients with autoimmune disease, relapse is more common in patients with ophthalmopathy, and hypothyroidism is common after RAI. In nodular disease, we found that spontaneous remission may occur.

Postradioiodine Graves' management: The PRAGMA study.

OBJECTIVE: Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post-RI and compare effectiveness of common management strategies. DESIGN: Retrospective, multicentre and observational study. PATIENTS: Adult patients with Graves' disease treated with RI with 12 months' follow-up. MEASUREMENTS: Euthyroidism was defined as both serum thyrotropin (thyroid-stimulating hormone [TSH]) and free thyroxine (FT4) within their reference ranges or, when only one was available, it was within its reference range; hypothyroidism as TSH ≥ 10 mU/L, or subnormal FT4 regardless of TSH; hyperthyroidism as TSH below and FT4 above their reference ranges; dysthyroidism as the sum of hypo- and hyperthyroidism; subclinical hypothyroidism as normal FT4 and TSH between the upper limit of normal and <10 mU/L; and subclinical hyperthyroidism as low TSH and normal FT4. RESULTS: Of 812 patients studied post-RI, hypothyroidism occurred in 80.7% and hyperthyroidism in 48.6% of patients. Three principal post-RI management strategies were employed: (a) antithyroid drugs alone, (b) levothyroxine alone, and (c) combination of the two. Differences among these were small. Adherence to national guidelines regarding monitoring thyroid function in the first 6 months was low (21.4%-28.7%). No negative outcomes (new-onset/exacerbation of Graves' orbitopathy, weight gain, and cardiovascular events) were associated with dysthyroidism. There were significant differences in demographics, clinical practice, and thyroid status postradioiodine between centres. CONCLUSIONS: Dysthyroidism in the 12 months post-RI was common. Differences between post-RI strategies were small, suggesting these interventions alone are unlikely to address the high frequency of dysthyroidism.

A review of the pathophysiology of functional hypothalamic amenorrhoea in women subject to psychological stress, disordered eating, excessive exercise or a combination of these factors.

INTRODUCTION: Functional hypothalamic amenorrhoea (FHA) is a common form of secondary amenorrhoea without an identifiable structural cause. Suppression of gonadotrophin-releasing hormone (GnRH) pulsatility results in reduced luteinizing hormone (LH) levels, with subsequent reduction in oestradiol, anovulation and cessation of menstruation. GnRH pulsatility suppression is a recognized complication of psychological stress, disordered eating, low body weight, excessive exercise or a combination of these factors. PATHOPHYSIOLOGY OF FHA: Individuals with FHA demonstrate low energy availability (EA), body fat percentage and energy expenditure. Documented adipocytokine changes notably, raised adiponectin, ghrelin, PYY, and decreased leptin, are associated with GnRH suppression. Other endocrine responses seen in this low EA state include low insulin levels, low total T3, increased basal cortisol levels and a reduced response to corticotrophin-releasing hormone (CRH) administration. FHA is associated with raised growth hormone (GH) and low insulin-like growth factor (IGF-1), suggesting relative GH resistance. Kisspeptins are a group of polypeptides, recently discovered to play a major role in the regulation of the reproductive axis through influencing GnRH release. KNDy (kisspeptin/neurokinin B/dynorphin) act on GnRH neurons and a multitude of factors result in their release. IMPLICATIONS FOR FUTURE TREATMENT: Management of FHA is imperative to prevent adverse outcomes in bone density, cardiovascular risk profile, psychological well-being and fertility. Outwith modification of nutritional intake and exercise, limited therapeutic strategies are currently available for women with FHA. Advancements in the understanding of the pathophysiological basis of this under-recognized and under-treated clinical entity will aid management and may result in the development of novel therapeutic approaches.

Long-term follow-up of a large prospective cohort of patients with nonfunctioning pituitary adenomas: The outcome of a conservative management policy.

OBJECTIVE: To assess the clinical outcome of a strategy of conservative monitoring of patients with nonfunctioning pituitary adenomas (NFPA) after pituitary surgery and in patients without surgery. DESIGN: Retrospective study of outcomes, using a clinical information system. PATIENTS: An unselected, clinical series of patients seen in a single centre between 1989 and 2015. MEASUREMENTS: Review of clinical information system data to obtain details and dates of surgery, radiotherapy, pituitary imaging and outcomes. RESULTS: We identified 190 cases of NFPA. Trans-sphenoidal surgery (TSS) had been performed as primary therapy in 132 cases (all macro-adenomas). At a mean 7.6-years follow-up after TSS without immediate pituitary radiotherapy, recurrence occurred in 10.7% of cases with no visible postoperative residual adenoma, 38.8% with intrasellar and 66.7% with extrasellar residuum. Recurrence was defined as growth of residual tumour requiring intervention. On survival analysis, at 10 years, recurrence-free survival was 75% in patients with no residual tumour and 40% with intrasellar residuum. Recurrence occurred in 12.5% of 24 patients who had received postop radiotherapy. Patients were monitored conservatively without initial surgery in 65 patients. After a mean of 5-year monitoring, only 20% required intervention during follow-up (18.5% TSS) and 30.8% died of nonpituitary causes during follow-up. CONCLUSION: This study suggests that a conservative approach may be safe and appropriate in patients with NFPA if followed up with appropriate imaging surveillance, whether postoperative or without primary surgery.

Clinical characteristics of polycystic ovary syndrome: investigating differences in White and South Asian women.

OBJECTIVE: To understand the phenotypic presentation of women with polycystic ovary syndrome (PCOS) of different ethnicities and at different ages. DESIGN: Cross-sectional, retrospective data analysis (1988 - 2009). SETTING: Specialist clinic in a University Hospital, Leicestershire, UK. PARTICIPANTS: Women with PCOS, n = 1310 (mean age 26·2 years), 70·9% White and 29·1% South Asian (SA) attending a speciality clinic in Leicester UK. MAIN OUTCOMES MEASURES: Clinical and demographic characteristics of women with PCOS including age at first clinic appointment, signs and symptoms, body mass index (BMI) and blood pressure (BP). RESULTS: Compared to White women, the SA were younger (24·3 vs 27·1 years, P < 0·001), less likely to smoke (3·7% vs 17·9% P < 0·001) and had a higher prevalence of acanthosis nigricans (AN) (16·8% vs 3·1% P < 0·001), type 2 diabetes (T2DM) (8·1% vs 5·6%, P < 0·01) and hirsutism (88·5% vs 77·4%, P < 0·001), with lower systolic (126·5 vs 133·0 mmHg, P < 0·001), diastolic BP (71·8 vs 75·1 mmHg P = 0·008) and BMI (29·3 vs 31·5 kg/m(2) P = 0·002). Differences in body weight remained when participants were classified as obese, overweight and normal according to ethnicity-specific cut-off points (P = 0·048). In both ethnicities, those aged ≥30 years old had higher rates of obesity, T2DM, hypertension and infertility, and less acne, and oligomenorrhoea. Obesity was associated with increased T2DM, AN, systolic/diastolic BP, hirsutism and infertility. CONCLUSION: The phenotypic and metabolic presentations of women with PCOS appear to be significantly different depending on ethnicity, obesity and age. This has implications for management strategies in these groups.

AIP mutation in pituitary adenomas in the 18th century and today.

Gigantism results when a growth hormone-secreting pituitary adenoma is present before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of an Irish patient who lived from 1761 to 1783, he noted an enlarged pituitary fossa. We extracted DNA from the patient's teeth and identified a germline mutation in the aryl hydrocarbon-interacting protein gene (AIP). Four contemporary Northern Irish families who presented with gigantism, acromegaly, or prolactinoma have the same mutation and haplotype associated with the mutated gene. Using coalescent theory, we infer that these persons share a common ancestor who lived about 57 to 66 generations earlier.

Diabetes and cardiovascular events in women with polycystic ovary syndrome: a 20-year retrospective cohort study.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) are potentially at increased risk of cardiovascular (CV) diseases due to well-established risk factors, including insulin resistance, obesity and type 2 diabetes mellitus (T2DM). However, data showing excess CV events in this population are still lacking. We investigated the incidence and prevalence of CV events in a cohort of women with PCOS. DESIGN: Retrospective cohort study (total follow-up >12,000 person-years). SETTING: Leicester, Leicestershire and Rutland (Total Female population of 434,859), UK. PARTICIPANTS: Two thousand three hundred and one women with PCOS (mean age = 29.6 years) attending a speciality clinic in Leicestershire, UK. MAIN OUTCOMES MEASURES: T2DM, myocardial infarction (MI), angina, heart failure (HF), stroke and CV-related death. RESULTS: Incidence of T2DM, MI, angina, HF, stroke and CV death was respectively 3.6, 0.8, 1.0, 0.3, 0.0 and 0.4 per 1000 person-years. At the end of follow-up, the prevalence of MI in the age groups 45-54, 55-64 and >65 years was 1.9%, 6.0% and 27.3% and of angina was 2.6%, 6.0% and 27.3%, respectively. Age-group-specific odds ratios for the prevalence of MI and angina compared to the local female population ranged between 2.6 (95% CI: 1.0-6.3) and 12.9 (CI: 3.4-48.6) with the highest ratio being for MI in the group >65 years old. Age, history of hypertension and smoking had significant correlations with CV outcomes in the PCOS patients. CONCLUSION: We have shown a high incidence and age-group-specific prevalence of T2DM, MI and angina in the women with PCOS, with over a quarter having had MI or angina in those >65 years. These findings should be considered in the treatment strategies and long-term planning for women with PCOS.

Nelson syndrome and perinatal challenges: A case report and systematic review of the literature.

Nelson syndrome is a rare and potentially life-threatening complication of treatment with total bilateral adrenalectomy for women with Cushing disease. A successful term pregnancy following fertility treatment in a patient with Nelson syndrome is presented. Our study provides guidance in the prenatal and intrapartum management of this condition. A case report and a systematic review of 14 papers describing 50 pregnancies are presented. An electronic database search included Medline (1946 to September 2022), Embase (1980 to September 2022), Cochrane Library, and UKOSS. A small number of pregnancies in women with Nelson syndrome are reported in literature, but there are no guidelines. Some authors detail the prenatal care provided to their patients. Four studies report prenatal monitoring with visual field checks and two report monitoring with X-rays. Five studies report the use of parenteral hydrocortisone at the time of delivery. Where described, women delivered appropriately grown newborns at term, with timing and mode of delivery dictated by obstetric indications. Preconception counseling and optimization of maternal health status improve pregnancy outcomes in women with Nelson syndrome. Multidisciplinary review in a combined obstetric-endocrine prenatal clinic is ideal. Awareness about potential complications during pregnancy and the postnatal period is crucial in providing optimal care to the mother and baby.

A study of acromegaly-associated headache with somatostatin analgesia.

The aim of this study is to characterise somatostatin analogue-responsive headache in acromegaly, hitherto not systematically documented in a significant cohort. Using the UK pituitary network, we have clinically characterised a cohort of 18 patients suffering from acromegaly-related headache with a clear response to somatostatin analogues. The majority of patients had chronic migraine (78%) as defined by the International Headache Society diagnostic criteria. Headache was present at the time of acromegaly presentation and clearly associated temporally with disease activity in all cases. Short-acting somatostatin analogues uniquely resolved pain within minutes and the mean duration of analgesia was 1-6 h. Patients on long-acting analogues required less short-acting injections (mean: 3.7 vs 10.4 injections per day, P = 0.005). 94% used somatostatin analogues to control ongoing headache pain. All patients presented with macroadenoma, most had incomplete resection (94%) and headache was ipsilateral to remnant tissue (94%). Although biochemical control was achieved in 78% of patients, headache remained in 71% of them. Patients selected for this study had ongoing headache post-treatment (mean duration: 16 years after diagnosis); only four patients reached headache remission 26 years (mean range: 14-33) after the diagnosis. Headache in acromegaly patients can be persistent, severe, unrelieved by surgery, long-lasting and uncoupled from biochemical control. We show here that long-acting analogues allow a decrease in the number of short-acting analogue injections for headache relief. Further studies are needed to understand the mechanisms, markers and tumour tissue characteristics of acromegaly-related headache. Until then, this publication serves to provide the clinical characteristics as a reference point for further study.

Natural history of non-functioning pituitary microadenomas: results from the UK non-functioning pituitary adenoma consortium.

OBJECTIVE: The optimal approach to the surveillance of non-functioning pituitary microadenomas (micro-NFPAs) is not clearly established. Our aim was to generate evidence on the natural history of micro-NFPAs to support patient care. DESIGN: Multi-centre, retrospective, cohort study involving 23 endocrine departments (UK NFPA consortium). METHODS: Clinical, imaging, and hormonal data of micro-NFPA cases between January, 1, 2008 and December, 21, 2021 were analysed. RESULTS: Data for 459 patients were retrieved [median age at detection 44 years (IQR 31-57)-152 males/307 females]. Four hundred and nineteen patients had more than two magnetic resonance imagings (MRIs) [median imaging monitoring 3.5 years (IQR 1.71-6.1)]. One case developed apoplexy. Cumulative probability of micro-NFPA growth was 7.8% (95% CI, 4.9%-8.1%) and 14.5% (95% CI, 10.2%-18.8%) at 3 and 5 years, respectively, and of reduction 14.1% (95% CI, 10.4%-17.8%) and 21.3% (95% CI, 16.4%-26.2%) at 3 and 5 years, respectively. Median tumour enlargement was 2 mm (IQR 1-3) and 49% of micro-NFPAs that grew became macroadenomas (nearly all >5 mm at detection). Eight (1.9%) patients received surgery (only one had visual compromise with surgery required >3 years after micro-NFPA detection). Sex, age, and size at baseline were not predictors of enlargement/reduction. At the time of detection, 7.2%, 1.7%, and 1.5% patients had secondary hypogonadism, hypothyroidism, and hypoadrenalism, respectively. Two (0.6%) developed hypopituitarism during follow-up (after progression to macroadenoma). CONCLUSIONS: Probability of micro-NFPA growth is low, and the development of new hypopituitarism is rare. Delaying the first follow-up MRI to 3 years and avoiding hormonal re-evaluation in the absence of tumour growth or clinical manifestations is a safe approach for micro-NFPA surveillance.

Central diabetes insipidus from a patient's perspective: management, psychological co-morbidities, and renaming of the condition: results from an international web-based survey.

BACKGROUND: Central diabetes insipidus is a rare neuroendocrine condition. Data on treatment-associated side-effects, psychological comorbidities, and incorrect management are scarce. The aim of this study was to investigate patients' perspectives on their disease. METHODS: This study used a cross-sectional, web-based, anonymous survey, developed by endocrinologists and patient representatives, to collect the opinions of patients with central diabetes insipidus on management and complications of their disease, psychological comorbidities, degree of knowledge and awareness of the condition among health-care professionals, and renaming the disease to avoid confusion with diabetes mellitus (diabetes). FINDINGS: Between Aug 23, 2021, and Feb 7, 2022, 1034 patients with central diabetes insipidus participated in the survey. 91 (9%) participants were children and adolescents (37 [41%] girls and 54 [59%] boys; median age 10 years [IQR 6-15]) and 943 (91%) were adults (757 [80%] women and 186 [20%] men]; median age 44 years [34-54]). 488 (47%) participants had isolated posterior pituitary dysfunction and 546 (53%) had combined anterior and posterior pituitary dysfunction. Main aetiologies were idiopathic (315 [30%] of 1034 participants) and tumours and cysts (pre-surgical 217 [21%]; post-surgical 254 [25%]). 260 (26%; 95% CI [0·23-0·29]) of 994 patients on desmopressin therapy had hyponatraemia leading to hospitalisation. Patients who routinely omitted or delayed desmopressin to allow intermittent aquaresis had a significantly lower prevalence of hyponatraemia compared with those not aware of this approach (odds ratio 0·55 [95% CI 0·39-0·77]; p=0·0006). Of patients who had to be hospitalised for any medical reason, 71 (13%; 95% CI 0·10-0·16) of 535 patients did not receive desmopressin while in a fasting state (nil by mouth) without intravenous fluid replacement and reported symptoms of dehydration. 660 (64%; 0·61-0·67) participants reported lower quality of life, and 369 (36%; 0·33-0·39) had psychological changes subjectively associated with their central diabetes insipidus. 823 (80%; 0·77-0·82) participants encountered a situation where central diabetes insipidus was confused with diabetes mellitus (diabetes) by health-care professionals. 884 (85%; 0·83-0·88) participants supported renaming the disease; the most favoured alternative names were vasopressin deficiency and arginine vasopressin deficiency. INTERPRETATION: This is the largest survey of patients with central diabetes insipidus, reporting a high prevalence of treatment-associated side-effects, mismanagement during hospitalisation, psychological comorbidities, and a clear support for renaming the disease. Our data are the first to indicate the value of routinely omitting or delaying desmopressin. FUNDING: Swiss National Science Foundation, Swiss Academy of Medical Sciences, and G&J Bangerter-Rhyner-Foundation.

Risk of second brain tumour after radiotherapy for pituitary adenoma or craniopharyngioma: a retrospective, multicentre, cohort study of 3679 patients with long-term imaging surveillance.

BACKGROUND: Radiotherapy is a valuable treatment in the management algorithm of pituitary adenomas and craniopharyngiomas. However, the risk of second brain tumour following radiotherapy is a major concern. We assessed this risk using non-irradiated patients with the same primary pathology and imaging surveillance as controls. METHODS: In this multicentre, retrospective cohort study, 4292 patients with pituitary adenoma or craniopharyngioma were identified from departmental registries at six adult endocrine centres (Birmingham, Oxford, Leeds, Leicester, and Bristol, UK and Ferrara, Italy). Patients with insufficient clinical data, known genetic predisposition to or history of brain tumour before study entry (n=532), and recipients of proton beam or stereotactic radiotherapy (n=81) were excluded. Data were analysed for 996 patients exposed to 2-dimensional radiotherapy, 3-dimensional conformal radiotherapy, or intensity-modulated radiotherapy, and compared with 2683 controls. FINDINGS: Over 45 246 patient-years, second brain tumours were reported in 61 patients (seven malignant [five radiotherapy, two controls], 54 benign [25 radiotherapy, 29 controls]). Radiotherapy exposure and older age at pituitary tumour detection were associated with increased risk of second brain tumour. Rate ratio for irradiated patients was 2·18 (95% CI 1·31-3·62, p<0·0001). Cumulative probability of second brain tumour was 4% for the irradiated and 2·1% for the controls at 20 years. INTERPRETATION: Irradiated adults with pituitary adenoma or craniopharyngioma are at increased risk of second brain tumours, although this risk is considerably lower than previously reported in studies using general population controls with no imaging surveillance. Our data clarify an important clinical question and guide clinicians when counselling patients with pituitary adenoma or craniopharyngioma on the risks and benefits of radiotherapy. FUNDING: Pfizer.

Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of under-replacement with levothyroxine.

OBJECTIVE: Achieving optimal thyroid hormone replacement is more difficult in TSH deficiency compared to primary hypothyroidism because of the inability to be guided by serum TSH levels. A combination of clinical symptoms and free thyroxine levels (fT4) are typically used to make a diagnosis and monitor replacement. We investigated the diagnosis of TSH deficiency in patients with pituitary disease and the adequacy of levothyroxine replacement compared with primary thyroid disease. DESIGN: Using our department's clinical information system, we identified all patients with a diagnosis of any type of pituitary tumour who had been seen in clinic over a 2-year period. We divided the patients into those at high risk and low risk of TSH deficiency based on the presence of macroadenoma and/or intervention by surgery or radiotherapy. We compared fT4 values in these patients with values in patients with primary thyroid disease in our thyrotoxicosis shared-care scheme (TSC) and hypothyroid register within the same timescale, assessing only those samples considered euthyroid in which TSH was in the normal range. RESULTS: A database query identified 525 patients with a pituitary tumour of whom 344 were considered at high risk of TSH deficiency. A free T4 (fT4) value was found for 514 patients (97·9%). TSC and thyroid register databases revealed fT4 values for comparison with simultaneous normal TSH in patients on no treatment (n = 3777 samples) or on levothyroxine alone (n = 11,805). fT4 levels overall were lower in pituitary patients than in equivalent controls. Of the high risk group not taking levothyroxine 17% had a free T4 ≤ 11 pmol/l compared to only 8·4% of untreated controls. Furthermore, 38·9% of patients on levothyroxine had a free T4 ≤ 13 pmol/l compared to 9·5% of controls on levothyroxine with previous thyrotoxicosis and 13·4% of controls with primary hypothyroidism. Median fT4 in controls on levothyroxine was 16 pmol/l and 20-80th centile range was 14-19 pmol/l. CONCLUSION: Levothyroxine doses were generally under-replaced in pituitary patients compared to primary thyroid disease and the data imply that some untreated patients were actually TSH deficient. The distribution of fT4 in patients with primary thyroid disease on levothyroxine may guide optimum replacement levels in pituitary disease.

The association of pituitary tumors and headache.

Pituitary tumors may give rise to headache via numerous mechanisms. The traditional explanation for headache is dural stretch and cavernous sinus invasion, although this is not borne out by clinical studies. Certain functional pituitary tumors are associated with headache, notably growth hormone and prolactin-secreting tumors. The observation that somatostatin analogues can have a dramatic analgesic effect in acromegaly suggests that biochemical properties of the tumor may be important. The genetic predisposition of the patient to primary headache also determines whether headache occurs with pituitary tumors. This article attempts to outline the clinical features, management strategies, and key academic questions regarding the subject of pituitary tumors and headache.

How reliably can autoimmune hypophysitis be diagnosed without pituitary biopsy.

Autoimmune hypophysitis is a rare chronic inflammatory condition of the pituitary gland which typically presents with hypopituitarism and a pituitary mass. Cases involving anterior pituitary alone (65%) are six times more common in women, typically presenting during pregnancy or postpartum (57%). Anterior and posterior pituitary involvement (25%) are twice as common in women, and neurohypophysis alone (10%) occurs equally in both sexes. It has a prevalence of around 5 per million, an annual incidence of 1 in 7 to 9 million and in our experience represents the known or suspected cause of 0.5% of cases of hypopituitarism, <1% of pituitary masses and 2% of nonfunctioning macro lesions presenting to an endocrine clinic. However, 'missed' cases of autoimmune hypophysitis may be the aetiology of some other unexplained cases of hypopituitarism. Clinically, headache and visual disturbance are common. Anterior hypopituitarism shows a characteristic but atypical pattern of deficiency of ACTH followed by TSH, gonadotrophins and prolactin deficiency or hyperprolactinaemia. Eighteen percent of cases have evidence of another autoimmune condition. On magnetic resonance imaging (MRI), autoimmune hypophysitis is typically symmetrical and homogeneous with thickened but undisplaced stalk in contrast to typical findings with pituitary tumours. Ultimately, the histological diagnosis of autoimmune hypophysitis can only be confirmed by surgery but a presumptive diagnosis can often be made on the basis of a combination of context and clinical features, and pituitary biopsy is not always clinically necessary for effective clinical management of the patient.

Outcomes of Patients with Nelson's Syndrome after Primary Treatment: A Multicenter Study from 13 UK Pituitary Centers.

CONTEXT: Long-term outcomes of patients with Nelson's syndrome (NS) have been poorly explored, especially in the modern era. OBJECTIVE: To elucidate tumor control rates, effectiveness of various treatments, and markers of prognostic relevance in patients with NS. PATIENTS, DESIGN, AND SETTING: Retrospective cohort study of 68 patients from 13 UK pituitary centers with median imaging follow-up of 13 years (range 1-45) since NS diagnosis. RESULTS: Management of Cushing's disease (CD) prior to NS diagnosis included surgery+adrenalectomy (n = 30; eight patients had 2 and one had 3 pituitary operations), surgery+radiotherapy+adrenalectomy (n = 17; two received >1 courses of irradiation, two had ≥2 pituitary surgeries), radiotherapy+adrenalectomy (n = 2), and adrenalectomy (n = 19). Primary management of NS mainly included surgery, radiotherapy, surgery+radiotherapy, and observation; 10-year tumor progression-free survival was 62% (surgery 80%, radiotherapy 52%, surgery+radiotherapy 81%, observation 51%). Sex, age at CD or NS diagnosis, size of adenoma (micro-/macroadenoma) at CD diagnosis, presence of pituitary tumor on imaging prior adrenalectomy, and mode of NS primary management were not predictors of tumor progression. Mode of management of CD before NS diagnosis was a significant factor predicting progression, with the group treated by surgery+radiotherapy+adrenalectomy for their CD showing the highest risk (hazard ratio 4.6; 95% confidence interval, 1.6-13.5). During follow-up, 3% of patients had malignant transformation with spinal metastases and 4% died of aggressively enlarging tumor. CONCLUSIONS: At 10 years follow-up, 38% of the patients diagnosed with NS showed progression of their corticotroph tumor. Complexity of treatments for the CD prior to NS diagnosis, possibly reflecting corticotroph adenoma aggressiveness, predicts long-term tumor prognosis.

Long-term outcome of hyperthyroidism diagnosed in childhood and adolescence: a single-centre experience.

Background The objective of the study was to evaluate the long-term outcome of paediatric-onset hyperthyroidism with follow-up into adulthood and to identify any early predictors of a need for definitive therapy (DT). Methods In a retrospective analysis of patients diagnosed with hyperthyroidism under the age of 18 years and at follow-up, a comparison was made by categorising them into those who underwent definitive therapy (DT group), i.e. thyroidectomy/radioactive iodine (RAI), those who remained on antithyroid drugs (ATD) (CBZ group) and those who had complete remission (RE group). Results Sixty-one (49 females, 12 males) patients with a median age of 15.1 years (range: 3.6-18) at diagnosis were studied. The duration of the first course of ATD varied from <1 year (7%), 1-2 years (26%), >2 years (46%) and ATD never discontinued (21%). Disease relapsed in 69% of patients with <1 year of ATD vs. 79% with >2 years of ATD. At follow-up, the median duration since diagnosis was 8.75 years (range 2.0-20.7 years) and the median age at follow-up was 23.2 years (8-36 years). Thirty-three percent (20/61) had undergone DT (DT group) - with 16.5% (n=10) on RAI and 16.5% (n=10) on surgery, 36% (22/61) were on ATD (CBZ group), whilst 32% (19/61) had undergone full remission (RE group). The comparison did not identify any statistically significant difference for predictor factors at diagnosis including age, T4 and free T4 levels, thyroid peroxidise antibody levels (TPO) and the duration of the first course of carbimazole (CBZ) treatment. Conclusion Long-term complete remission of paediatric-onset hyperthyroidism in our study was 31%. There were no predictors identified that could help predict the long-term outcome, especially into adulthood.