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.

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.

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.

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.

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.

Salivary cortisol and cortisone responses to tetracosactrin (synacthen).

BACKGROUND: To establish cutoff values for salivary liquid chromatography tandem mass spectroscopy cortisol and cortisone in defining adequate adrenocortical function during a standard synacthen test. METHODS: We compared salivary liquid chromatography tandem mass spectroscopy cortisol and cortisone responses to those of serum cortisol measured on the Roche E170 immunoassay analyser and the Abbott Architect i2000 before and 30 min and 60 min following 0.25 mg of intravenous synacthen. RESULTS: Correlations of salivary cortisol and cortisone were bimodal and linear, respectively. Based on these correlations, adequate salivary cortisol and cortisone responses to synacthen were extrapolated from a serum cortisol (Roche) cut-off of 550 nmol/L and defined as 15 nmol/L and 45 nmol/L, respectively. The Abbott method correlated well with the Roche but gave results that were about 20% lower than the Roche method. CONCLUSIONS: Measurement of salivary cortisol and cortisone responses offers an alternative to those of serum cortisol during a synacthen test in the investigation of adrenal hypofunction.