Diagnostic utility of 11 C-methionine PET/CT in primary hyperparathyroidism in a UK cohort: A single-centre experience and literature review.

OBJECTIVE: Primary hyperparathyroidism is a common endocrine disorder, with 80% of all cases usually caused by one single hyperfunctioning parathyroid adenoma. Conventional imaging modalities for the diagnostic work-up of primary hyperparathyroidism (PHPT) include ultrasound of the neck, 99mTc-sestamibi scintigraphy, and four-dimensional computed tomography (4D-CT). However, the role of other imaging modalities, such as 11C-methionine PET/CT, in the care pathway for PHPT is currently unclear. Here, we report our experience of the diagnostic utility of 11C-methionine PET/CT in a single-center patient cohort (n = 45). DESIGN: Retrospective single-center cohort study. PATIENTS AND MEASUREMENTS: The data of eligible patients that underwent 11C-methionine PET/CT between 2014 and 2022 at Addenbrooke's Hospital (Cambridge, UK) were collected and analyzed. The clinical utility of imaging modalities was determined by comparing the imaging result with histopathological and biochemical outcomes following surgery. RESULTS: In patients with persistent primary hyperparathyroidism following previous surgery, 11C-methionine PET/CT identified a candidate lesion in 6 of 10 patients (60.0%), and histologically confirmed in 5 (50.0%). 11C-methionine PET/CT also correctly identified a parathyroid adenoma in 9 out of 12 patients (75.0%) that failed to be localized on other imaging modalities. 11C-methionine PET/CT had a sensitivity of 70.0% (95% CI 55.8 - 84.2%) for the detection of parathyroid adenomas. CONCLUSIONS: This study highlights a diagnostic role for 11C-methionine PET/CT in patients that have undergone unsuccessful prior surgery or have equivocal or negative prior imaging results, aiding localization and a targeted surgical approach.

The diagnosis and management of subclinical hypothyroidism is assay-dependent- Implications for clinical practice.

OBJECTIVE: We assessed the commutativity of Roche and Abbott thyroid assays in the diagnosis and management of subclinical hypothyroidism (SCH). The Roche and Abbott thyroid assays are used by approximately 75% of clinical laboratories in the UK. METHOD: Consecutive samples received from primary care on patients with SCH who had a raised thyroid-stimulating hormone (TSH) <10 mIU/L and a normal free thyroxine (fT4) from two laboratories using either Roche or Abbott thyroid assays were identified over 10 working days. Following identification, samples were analysed at the other site within 24 hours. Diagnostic and management discordance were studied using the relevant manufacturer-provided reference ranges. RESULTS: We identified 93 patients with SCH (53 using the Roche assay). Roche TSH and fT4 results were respectively 40% ± 15% and 16% ± 7% higher (P < .001) compared to Abbott results. Of the 93 patients, 41 (44%) were concordant for SCH on both methods. Of the 53 patients with SCH on the Roche assays, 40 (75.5%) had normal thyroid function and 13 (24.5%) had SCH when analysed using the Abbott assays. Of the 40 patients with SCH on the Abbott assays, 28 (70%) had SCH and 12 (30%) had results indicative for levothyroxine replacement when analysed on the Roche assays. Of these 12 patients, four had TSH > 10 mIU/L, five had low fT4 and three had both. CONCLUSION: The diagnosis and management of SCH is strikingly different when using TSH and fT4 assays provided by Abbott Laboratories and Roche Diagnostics. Clinicians and laboratorians should be aware that between-assay differences and variations in reference ranges will directly impact the diagnosis and management of subclinical hypothyroidism.

Endocrine Hypertension: A Practical Approach.

Elevated blood pressure resulting from few endocrine disorders (endocrine hypertension) accounts for a high proportion of cases of secondary hypertension. Although some features may be suggestive, many cases of endocrine hypertension remain silent until worked up for the disease. A majority of cases result from primary aldosteronism. Other conditions that can cause endocrine hypertension are: congenital adrenal hyperplasia, Liddle syndrome, pheochromocytomas, Cushing's syndrome, acromegaly, thyroid diseases, primary hyperparathyroidism and iatrogenic hormone manipulation. Early identification and treatment of the cause of endocrine hypertension may help to reduce morbidity and mortality related to these disorders. This article gives a comprehensive and practical approach to the diagnosis and management of endocrine hypertension.

Thyroid autoantibodies.

Thyroid-stimulating hormone (TSH) receptor antibody (TSH-R-Ab or TRAb) testing plays a pivotal role in arriving at the aetiological diagnosis in patients with thyrotoxicosis. A positive test establishes the diagnosis of Graves' disease (GD) while a negative result in conjunction with imaging studies supports other possible aetiologies. In patients with GD, TRAb levels at diagnosis and at the time of withdrawal of antithyroid drugs can identify patients who are unlikely to achieve remission and guide clinical management decisions. We provide an algorithm that incorporates TRAb in the decision-making process for the management of thyrotoxicosis. The utility of TRAb in predicting the risk of fetal and neonatal thyroid dysfunction is established and widely accepted in guidelines. TRAb may also help in the diagnosis of Graves' orbitopathy, especially in euthyroid or hypothyroid patients and its role in guiding its management is evolving as a useful adjunct to the clinical parameters used in making therapeutic decisions.Anti-thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibodies (TgAb) indicate thyroid autoimmunity. The most common use of TPOAb is to identify patients at a higher risk of progression to treatment-requiring hypothyroidism. They also aid the diagnosis of immune thyroiditis and Hashimoto's encephalopathy. Thyroglobulin measurement is used to help guide differentiated thyroid cancer treatment. TgAb is used as an accompanying test with thyroglobulin measurement as its presence can interfere with the thyroglobulin assay. A negative TgAb result reduces the likelihood of, but does not exclude, interference with thyroglobulin assay.

Impact of hyperthyroidism and its treatment on the outcome of mental health, occupational functioning, and quality of life: A naturalistic, prospective study.

Context Background: Hyperthyroidism has a major impact on mental health. Aims: We intended to determine the magnitude of the unmet need for mental health support in patients with hyperthyroidism attending an endocrinology clinic. Settings and Design: General Hospital Endocrine Department, Prospective Study. Methods and Material: In a naturalistic, prospective study, consecutive (n = 176) hyperthyroid patients were assessed for anxiety (generalized anxiety disorder, GAD-7), depression (Patient Health Questionnaire PHQ-9), functional impairment (work and social adjustment scale, WSAS), and quality of life (EuroQol ED5D) using standardized instruments. Statistical Analysis Used: Percentages, mean and standard deviation (SD), Chi-square, Student's t-test, ANOVA, Spearman's correlation. Results: A considerable proportion (40.5%) of patients had moderate and severe anxiety, around half (50.6%) had moderate or severe depression, and 20.8% had severe functional impairment at presentation. Mean EQ5D score was 59.6 ± 23.5. The scores of anxiety, depression, and functional impairment were significantly correlated with each other and negatively correlated with QOL. Following treatment of hyperthyroidism, improvement in psychiatric symptoms was noted which could be correlated with the lowering of T4. However, a significant proportion of patients continued to have psychiatric symptoms and functional impairment despite achieving euthyroidism. There was no correlation between the severity of hyperthyroidism to persistence of mental health parameters. Conclusions: Our findings of high prevalence and persistence of impairment of mental health and functional status of patients with hyperthyroidism have highlighted the unmet needs for these patients.

Biochemical assessment of adequate levothyroxine replacement in primary hypothyroidism differs with different TSH assays: potential clinical implications.

AIM: Thyroid stimulating hormone (TSH) assays provided by Abbott Laboratories and Roche Diagnostics are used by approximately 75% of laboratories in the UK. We assessed the potential impact of Abbott and Roche TSH assay differences on the biochemical assessment of levothyroxine replacement in primary hypothyroidism. METHOD: Samples from 100 consecutive primary care patients (83 women, median age 64 years, IQR 51-73 years) with primary hypothyroidism on adequate levothyroxine based on an Abbott Architect TSH in the reference range were analysed for TSH on Roche cobas within 24 hours. The Abbott and Roche TSH results were compared. Over 1 year, TSH results from patients in primary care from the laboratories with Abbott and Roche methods were compared. RESULTS: The median (IQR) Roche TSH (2.5 (1.3-3.6) mIU/L) was 30%±10% higher (p<0.001) than Abbott TSH (1.9 (1.1-2.6) mIU/L). Although all Abbott TSH results were in the Abbott specific reference range, 14 patients (14%) had Roche TSH results above the Roche specific reference range. In the 1 year gather, Roche TSH (1.9 (1.3-2.9) mIU/L, n=103 932) results were higher (p<0.001) than Abbott TSH (1.5 (1.0-2.2) mIU/L, n=1 10 544) results. The TSH results were above their assay-specific upper reference limit in 10.7% of Roche results and 4.2% of Abbott results. CONCLUSION: Biochemical assessment of levothyroxine replacement may be dependent on the type of TSH assay. Laboratorians and clinicians should be aware that the lack of harmonisation between TSH methods and their assay-specific reference ranges may potentially lead to different patient management decisions. We suggest lot verification in laboratories should include processes to identify cumulative drift in assay performance.

Retinal vein occlusion as the presenting feature of Cushing's syndrome.

A 53-year-old man presented to his optician with blurring of vision in the right eye and was diagnosed to have branch retinal vein occlusion. Over the following 3 months, he had further progressive visual impairment due to right central retinal vein occlusion (CRVO) and then left CRVO. Soon thereafter, during a hospital admission for infected submandibular gland, he was noted to have secondary hypothyroidism and persistent hypokalaemia which led to the diagnosis of Cushing's syndrome. This case was unusual as the patient did not manifest any classical features of Cushing's syndrome at the time of presentation with bilateral CRVO, and only 3 months later had dramatic weight loss, muscle weakness and acute psychosis. He received intravenous etomidate and underwent emergency transsphenoidal hypophysectomy with dramatic clinical and biochemical improvement and complete visual recovery in the left eye but unfortunately vision in the right eye remained limited to hand movements.

Recurrent primary hyperparathyroidism: a diagnostic and management dilemma.

SUMMARY: Primary hyperparathyroidism requires a surgical approach to achieve a long-term cure. However, post-surgical recurrence significantly complicates the management of this condition. A number of causes for recurrent disease are well understood and several diagnostic modalities exist to localise the culprit parathyroid adenoma although none of them is efficacious in localisation of the recurrent lesion. In this case report, we highlight a novel causative mechanism and describe a unique diagnostic sequence that enabled curative treatment to be delivered. LEARNING POINTS: In the case described herein, we describe a novel location for a parathyroid adenoma causing recurrent PHPT. The case elucidates well the difficulties presented by such cases in terms of surgical planning and show the utility of PVS in such cases. Based on this case, we make the following recommendations: Meticulous care must be taken to prevent seeding of adenomatous tissue during primary excision. To consider the use of PVS in patients with discordant imaging in the setting of recurrent/persistent PHPT as a method to localise the causative adenoma. Same day PVS and surgery is a viable option for patients who either represent an anaesthetic risk or who are extremely anxious about the prospect of two separate procedures. Disordered calcium homeostasis is an important but forgotten cause of dysphagia which can be extremely debilitating for affected patients.

Hypothalamic-pituitary-adrenal axis suppression - The value of salivary cortisol and cortisone in assessing hypothalamic-pituitary-adrenal recovery.

BACKGROUND: The 0.25 mg short synacthen test is used to assess recovery from hypothalamic-pituitary-adrenal suppression due to chronic glucocorticoid administration. We assessed the potential role of salivary cortisol and cortisone in predicting hypothalamic-pituitary-adrenal function using the short synacthen test as the gold standard test. METHOD: Between 09:00 and 10:30, salivary and blood samples were collected just prior to a short synacthen test to assess hypothalamic-pituitary-adrenal axis recovery in patients previously treated with oral glucocorticoids. The cut-off for a normal short synacthen test was a 30-min cortisol ≥450 nmol/L. RESULTS: Fifty-six short synacthen tests were performed on 47 patients. Of these, 15 were normal. The area under receiver operating characteristic curves for serum cortisol, salivary cortisone and salivary cortisol were 0.772, 0.785 and 0.770, respectively. From the receiver operating characteristic analysis, the cut-offs for baseline serum cortisol (≥365 nmol/L) and salivary cortisone (≥37.2 nmol) predicted hypothalamic-pituitary-adrenal axis recovery with 100% specificity in 26.7% of pass short synacthen tests, whereas salivary cortisol predicted none. Baseline serum cortisol (≤170 nmol/L), salivary cortisone (≤9.42 nmol/L) and salivary cortisol (≤1.92 nmol/L) predicted hypothalamic-pituitary-adrenal suppression with 100% sensitivity in 58.5%, 53.7% and 51.2% of failed short synacthen tests, respectively. Using these cut-offs, baseline serum cortisol, salivary cortisone and salivary cortisol could reduce the need for short synacthen tests by 50%, 46% and 37%, respectively. CONCLUSION: Although marginally inferior to early morning serum cortisol, early morning salivary cortisone may be used as a first-line test for assessing hypothalamic-pituitary-adrenal function. We plan to incorporate salivary cortisone into a home-based patient pathway to identify patients with hypothalamic-pituitary-adrenal recovery, continuing hypothalamic-pituitary-adrenal suppression and those who require a short synacthen test.

Acute adrenal failure: a potentially fatal consequence of an adulterated herbal remedy.

Herbal remedies adulterated with glucocorticoids can cause Cushing's syndrome. We report a severe presentation of a 'herbal remedy' adulterated with glucocorticoids; causing a potentially fatal adrenal crisis precipitated by acute illness. Investigations were consistent with adrenal suppression and confirmed, after tablet analysis, to be due to a 'herbal remedy' containing synthetic betamethasone/dexamethasone. This case highlights the need for clinical vigilance and patient education about the potential risks associated with the use of unlicensed treatments and the role of tablet analysis in routine biochemistry.

Ectopic adrenocorticotrophic hormone syndrome (EAS) with phaeochromocytoma: a challenging endocrine case with a happy ending.

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is rarely caused by a phaeochromocytoma. We report a case of a 51-year-old woman with an 8-year history of severe constipation who underwent extensive investigations including gastroscopy, colonoscopy, ultrasonography, colonic transit studies and isotope defeacography, which did not reveal any pathology other than slow colonic transit time. The unifying diagnosis of ectopic ACTH and phaeochromocytoma was made after the case was initially investigated for an adrenal incidentaloma. Multiple challenges had to be overcome prior to surgery for the functioning adrenal adenoma including management of refractory hypokalaemia, poor nutritional status, persistent hyperglycaemia, labile blood pressure and florid hypercortisolaemia driving the metabolic derangements. She underwent an uneventful left-sided adrenalectomy and required no medication thereafter with normal blood pressure, blood glucose and serum potassium and resolution of constipation and abdominal symptoms. In conclusion, patients with EAS related to phaeochromocytoma are rare and present with distinctive diagnostic and management challenges but if diagnosed successfully and managed intensively, they are curable.

Normocalcaemic primary hyperparathyroidism: a pragmatic approach.

It is well recognised that over the past three to four decades the incidence of asymptomatic primary hyperparathyroidism has increased significantly. However, more recently this pattern has further evolved into a presentation with normocalcaemia and raised parathyroid hormone (PTH) level without the presence of a recognised stimulus for its rise, in the form of vitamin D deficiency or renal impairment. A diagnostic label of normocalcaemic hyperparathyroidism (NPHPT) has been given to this phenotype and in most such individuals, the initial PTH measurement is driven by the presence of metabolic bone disease. The reported prevalence, degree of end-organ involvement and the rate of progression vary considerably and are related to patients studied and the biochemical cut-offs used in its definition. A majority of patients are diagnosed during assessment of metabolic bone disease of varying degrees. Once the diagnosis is confirmed by excluding confounding factors, the patient should undergo full assessment of end-organ involvement, which is the main determinant of further therapeutic decisions. Surgery, with prior localisation, is considered in patients with significant end-organ involvement in keeping with the guidance for hypercalcaemic patients. If a patient does not meet these criteria, annual clinical and biochemical surveillance is recommended to identify progression to hypercalcaemia or worsening end-organ involvement. It is less clear if patients identified during 'routine' requests for evaluation of unrelated symptoms require similar close monitoring. In conclusion, in this review on NPHPT we focus on its definition, planning of further investigations, selection of patients for intervention and devising an appropriate follow-up strategy.

Screening for Addison's disease in patients with type 1 diabetes mellitus and recurrent hypoglycaemia.

BACKGROUND: Addison's disease may present with recurrent hypoglycaemia in subjects with type 1 diabetes mellitus. There are no data, however, on the prevalence of Addison's disease presenting with recurrent hypoglycaemia in patients with diabetes mellitus. METHODS: Three year retrospective study of diabetic patients with "unexplained" recurrent hypoglycaemia investigated with a short Synacthen test to exclude adrenocortical insufficiency. RESULTS: 95 patients with type 1 diabetes mellitus were studied. Addison's disease was identified as the cause of recurrent hypoglycaemia in one patient with type 1 diabetes mellitus. CONCLUSION: Addison's disease is a relatively rare but remedial cause of recurrent hypoglycaemia in patients with type 1 diabetes mellitus. A low threshold for investigating patients with type 1 diabetes mellitus and recurrent hypoglycaemia to detect Addison's disease is therefore suggested.

The price of a 15-year delay in diagnosis of Sheehan's syndrome.

We describe a case of a 48-year-old woman who presented with a 15-year history of recurrent episodes of hypoglycemia and hyponatremia leading to altered behavior and generalized seizures. She underwent full clinical assessment, endocrine tests, and a pituitary magnetic resonance scan that showed pananterior hypopituitarism secondary to postpartum pituitary necrosis (Sheehan's syndrome). She was commenced on appropriate hormone replacement therapy, which led to significant improvement in lethargy, anorexia, muscle weakness, and episodes of hypoglycemia. In addition to the alleviation of her physical symptoms, she experienced a significant improvement in her psychological well-being and reduction in hospital visits. This case illustrates the impact of delay in diagnosis of an easily treatable medical condition and its socioeconomic implications, especially for the population of a developing country like India.

Interaction of interferon alpha therapy with thyroid function tests in the management of hepatitis C: a case report.

BACKGROUND: Interferon alpha is a widely used therapeutic agent in the treatment of hepatitis C virus infection. Clinical thyroid disease is seen in nearly 15 % of patients receiving interferon alpha for hepatitis C virus infection. The mechanism of thyroid dysfunction with interferon alpha is either autoimmune or inflammatory. We report a case of young woman who developed biphasic thyroid dysfunction posing a diagnostic challenge, while receiving interferon alpha treatment for hepatitis C virus infection. CASE PRESENTATION: A 29-year-old, Caucasian woman with type 1 diabetes and hepatitis C virus infection was referred with hyperthyroidism, while she was at 17 weeks of a planned 24-week course of interferon alpha therapy. A laboratory investigation revealed a thyroid stimulation hormone level of 0.005 mU/L (0.350-4.94), free thyroxine of 45.6 pmol/L (9.0-19.0) and free tri-iodothyronine of 12.6 pmol/L (2.6-5.7). She had a mild neutropenia and alanine aminotransferase at double the reference value. Her thyroid peroxidase antibody level was 497 ku/L (<5.6) and thyroid inhibitory factor 7 IU/L (>1.8 iu/l is positive). Thyroid scintigraphy with technetium99 scan confirmed a normal-sized thyroid gland with diffuse but normal overall uptake. A diagnosis of interferon alpha-triggered autoimmune hyperthyroidism as opposed to an inflammatory thyroiditis was made. She was offered radioactive iodine therapy, as thionamides were considered inappropriate in view of her liver disease and mild neutropenia. Due to our patient's personal circumstances, radioactive iodine therapy was delayed by 8 weeks and her thyrotoxic symptoms were controlled with beta-blockers alone. A repeat thyroid function test, 4 weeks post treatment with interferon alpha, indicated spontaneous conversion to hypothyroidism with a thyroid stimulation hormone level of 100 mU/L, free thyroxine of 5.2 pmol/L and free tri-iodothyronine of 1.7 pmol/L. She subsequently received levothyroxine for 4 months only and had remained euthyroid for the last 3 months without any treatment. CONCLUSIONS: Initial investigations favored the autoimmune nature of hyperthyroidism but follow-up of the case, interestingly, was more consistent with inflammatory thyroiditis. We propose that this can be explained either on the basis of autoimmune subacute thyroiditis or a change in the nature of thyroid stimulation hormone receptor antibody production from stimulating-type to blocking-type antibodies, with disappearance of the latter on discontinuation of interferon alpha.