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.

Rare but serious cause for hypokalaemia and hypertension.

Adrenocortical carcinoma is a rare tumour but hypertension conversely is very common. We present the case of a woman in her 30s, with poorly controlled hypertension on four antihypertensive agents. She was referred to the accident and emergency department with hypokalaemia. For a year, she had experienced oedema, weight gain, acne, hirsutism and oligomenorrhea. She had a classic Cushingoid appearance and marked striae. Cushing's syndrome was confirmed biochemically with an abnormal overnight dexamethasone suppression test. She was diagnosed with metastatic adrenocortical carcinoma following CT imaging. This was resected via a right adrenalectomy, nephrectomy and cholecystectomy. She also received mitotane. Unfortunately, she has a terminal prognosis having experienced a recurrence. This case demonstrates the value of a thorough clinical assessment. More importantly, it highlights the need to refer earlier patients under 40 with resistant hypertension to a specialist. Finally, it encourages clinicians to investigate hypokalaemia in the context of hypertension.

REMISSION OF LONGSTANDING INSULIN-TREATED DIABETES MELLITUS FOLLOWING SURGICAL RESECTION OF PHEOCHROMOCYTOMA.

OBJECTIVE: To describe the case of a woman with a longstanding misdiagnosis of type 1 diabetes mellitus (T1DM), in whom diabetes remission was achieved following surgical resection of adrenal pheochromocytoma. METHODS: We present a case report with accompanying biochemical, histologic, and genetic investigation results. RESULTS: We report the case of a 57-year-old woman with a 13-year history of apparent T1DM, and her presentation with intermittent exertional nausea. An abdominal ultrasound scan identified a rounded heterogeneous mass measuring 120 × 110 × 104 mm superior to her left kidney. Plasma metanephrine levels were markedly elevated with normetaneprhine at 17,856 pmol/L (reference range is 120 to 1,180 pmol/L), metanephrine >25,000 pmol/L (reference range is 80 to 510 pmol/L), 3-methoxytyramine at 1,393 pmol/L (reference range is 0 to 180 pmol/L). The mass demonstrated marked uptake on an iodine-123-meta-iodobenzylguanidine scan. The patient's hypertension was managed with phenoxybenzamine, and she underwent adrenalectomy. Following surgery, she was able to discontinue all diabetes medications and has maintained a hemoglobin A1c value <48 mmol/mol for over 12 months. CONCLUSION: The case illustrates that remission of T1DM is possible even after prolonged insulin treatment upon surgical resection of pheochromocytoma. It highlights the potential benefits of reevaluating the diagnostic classification of T1DM in the light of new clinical information.

Levothyroxine improves abnormal cardiac bioenergetics in subclinical hypothyroidism: a cardiac magnetic resonance spectroscopic study.

CONTEXT: It is well established that subclinical hypothyroidism (SCH) is associated with mild cardiac dysfunction, but it is unknown whether there is an underlying impairment of cardiac bioenergetic function. OBJECTIVE: The objective of the study was to quantify the cardiac phosphocreatine to adenosine triphosphate ratio (PCr to ATP) in SCH, compared with healthy controls, and to measure the effect of 6 months of levothyroxine treatment. DESIGN AND SETTING: This was a 6-month, prospective, case-controlled interventional study. PARTICIPANTS AND MAIN OUTCOME MEASURES: The PCr to ATP ratio was measured using phosphorus-31 magnetic resonance spectroscopy in subjects with SCH at baseline and after levothyroxine therapy (1.6 µg/kg · d) and compared with age- and gender-matched euthyroid controls. All subjects were free of overt heart disease. RESULTS: Twenty-one subjects with SCH (normal free T4 and serum TSH between 4.1 and 10 mIU/L) and 17 controls were matched for age (mean age 40.5 vs 43.3 y) and sex (females 81% vs 82%) but differed in mean TSH (6.5 vs 2.1 mIU/L, P < .001). At baseline the mean (± SD) PCr to ATP ratio in SCH was lower than in controls (1.80 ± 0.26 vs 2.07 ± 0.20, P = .001). In the 16 subjects studied after levothyroxine treatment, the PCr to ATP ratio improved (from 1.74 ± 0.24 to 1.91 ± 0.26, P = .004) and approached controls (borderline loss of significance, P = .051). On multivariate analysis, SCH was independently associated with a reduced PCr to ATP ratio, even after adjusting for confounding variables (body mass index and fasting glucose) (P = .001). CONCLUSION: Our results demonstrate early cardiac bioenergetic impairment in SCH, which is reversible with levothyroxine therapy. This mechanistic insight provides justification for longitudinal trials to determine whether improvement in bioenergetic function improves cardiovascular outcome.

Insulinoma presenting as postprandial hypoglycaemia.

Although insulinoma commonly presents as fasting hypoglycaemia it can rarely present as postprandial hypoglycaemia. We describe a case of insulinoma presenting as postprandial hypoglycaemia and type 2 diabetes mellitus (T2DM). A 60-year-old man presented with a 6 year history of postprandial hypoglycaemic symptoms. A diagnosis of T2DM was made using a standard oral glucose tolerance test to which patient's postprandial hypoglycaemia was attributed. He was given dietetic advice for postprandial hypoglycaemia and was followed up routinely. After 2 years, hypoglycaemic symptoms worsened by exercise and delayed meals. A number of supervised fasting glucose measurements failed to demonstrate biochemical hypoglycaemia. His insulin, c-peptide and pro-insulin levels were mildly elevated but plasma glucose levels were normal. A CT scan showed 20 mm lesion in the pancreas which was confirmed as insulinoma with pancreatic arterial calcium stimulation studies. Laparoscopic resection confirmed benign insulinoma and hypoglycaemia resolved. Our case illustrates the importance of considering insulinoma as a cause of postprandial hypoglycaemia.