[Apparent thyrotoxicosis in a patient with multiple sclerosis: biochemical assay interference due to high dose biotin use]. / Schijnbare thyreotoxicose door gebruik van biotine in hoge dosis.

BACKGROUND: Supraphysiological doses of biotin are being tested in patients with multiple sclerosis. Biotin can cause interference with laboratory assessment of thyroid function, and therefore give a false suggestion of thyrotoxicosis. CASE DESCRIPTION: A 64-year-old patient was referred for assessment of thyrotoxicosis, due to Graves' disease. Antithyroid medication was started, but there was no effect on laboratory results. In addition, he developed symptoms which subsequently could be attributed to iatrogenic hypothyroidism. Biotin interference, when assaying TSH and thyroxin, was suspected. Upon further investigation, the patient revealed to use high doses of biotin. After discontinuation of the biotin treatment, the thyroid function test normalized. CONCLUSION: It is expected that in the future, patients with multiple sclerosis will use biotin more often. Therefore, it is important for healthcare professionals to be aware that biotin can interfere with immunoassays for thyroid hormones, to avoid misdiagnosis and unnecessary treatment for hyperthyroidism.

[Guideline thyroid cancer including diagnostics of the nodule]. / Richtlijn schildkliercarcinoom inclusief diagnostiek van de nodus.

Thyroid cancer is comparatively rare. Thyroid nodules, on the other hand, are frequently diagnosed as a result of increasing use of diagnostic imaging. Cytological investigation of small nodules that have been found by chance often reveals micropapillary carcinoma that is probably not clinically relevant. The new guideline 'Thyroid cancer' advises that cytological investigation of these non-palpable, incidentally discovered thyroid nodules should only be performed on indication. The standard treatment for patients with papillary or follicular thyroid cancer consists of thyroidectomy followed by, if indicated, lymph-node dissection, ablation therapy with radioactive iodine and TSH-suppression. The extent of this treatment is determined on the basis of known prognostic factors and the results of initial treatment. Targeted systemic therapy is available for patients with metastatic progressive disease. There is more focus on the effects of short- and long-term treatment, in order to optimise quality of life.

A novel tool in the diagnosis and follow-up of (cyclic) Cushing's syndrome: measurement of long-term cortisol in scalp hair.

BACKGROUND: Measurement of cortisol in 24-h urine collections and midnight saliva are standard screening tests for Cushing's syndrome (CS). These tests reflect cortisol levels during a maximum of 24 h and do not provide historical information. Therefore, they can yield normal results in case of cyclic CS, which is a rare disorder that is characterized by alternating episodes of endogenous cortisol excess and normal cortisol secretion. The measurement of cortisol in scalp hair is a novel tool that might be helpful to establish the diagnosis of (cyclic) CS. Our aim was to study whether hair cortisol timelines correspond with clinical course in patients with CS and whether we could create retrospective timelines of cortisol exposure that correspond with symptomatic periods in patients suspected of cyclic CS. METHODS: Scalp hair was collected in 14 patients with confirmed CS and six patients suspected of cyclic CS. Cortisol was extracted from the hair samples with methanol, and an ELISA was used to measure cortisol levels in hair extracts. A group of 96 nonobese individuals were used as a control group. RESULTS: Hair cortisol levels were significantly elevated in CS patients (P<0.0001). Sensitivity and specificity of hair cortisol measurements for CS were 86 and 98%, respectively. Hair cortisol timelines of patients with CS and cyclic CS corresponded with clinical course. CONCLUSION: Hair samples can provide a historical timeline that corresponds with clinical course in patients with (cyclic) CS. This new diagnostic tool can contribute significantly to early recognition of patients suffering from cyclic CS.

[Four patients with incidentalomas of the thyroid discovered on 18-fluoro-deoxyglucose positron-emission tomography (FDG-PET)]. / Vier patiënten met een incidentaloom van de schildklier bij fluor-18-deoxyglucose-positronemissietomografie (FDG-PET).

In 4 patients, an incidentaloma of the thyroid was found on 18-fluoro-deoxyglucose positron-emission tomography (FDG-PET). In the first patient, a 73-year-old man, a medullary thyroid carcinoma was discovered during the staging procedure ofa laryngeal carcinoma. In the second patient, an 81-year-old woman, a follicular thyroid carcinoma was found as a result of a FDG-PET evaluation of an adenocarcinoma of the lung. In the third patient, a 64-year-old woman, a papillary thyroid carcinoma was found during dissemination investigation after curative removal of an adrenocortical carcinoma. The last patient, a 78-year-old man, was found to have a thyroid incidentaloma on FDG-PET scan during staging ofa recurrence of a gastrointestinal stromal tumour. Thyroid incidentalomas are present on 1.2-2.3% of FDG-PET scans. Further diagnostic work-up of these lesions by fine needle aspiration is warranted since up to 50% are malignant. However, whether these malignant thyroid lesions are relevant is not always clear. Treatment depends on the primary disease for which the FDG-PET scan was initially made. This requires good evaluation and discussion with the patient.

[Guideline 'Differentiated thyroid carcinoma', including diagnosis of thyroid nodules]. / Richtlijn 'Gedifferentieerd schildkliercarcinoom', inclusief de diagnostiek van de schildkliernodus.

Differentiated thyroid carcinoma is a rare disease. Appropriate diagnosis, treatment and follow-up are complex but greatly influence treatment outcomes and patient quality of life. Patients with differentiated thyroid carcinoma present in many hospitals throughout the Netherlands, underscoring the need for uniformity in diagnosis and treatment. This prompted the Dutch Society of Nuclear Medicine and the Dutch Endocrine Society to develop an evidence-based guideline that emphasises not only new scientific developments but also the organisation of care. Thyroid-stimulating hormone (TSH) assessment and fine needle aspiration cytology play a central role in the diagnostic assessment of a patient with a thyroid nodule. Ablation of residual thyroid tissue with radioiodine (1-131) is recommended for all patients who have undergone total thyroidectomy. Follow-up protocols distinguish between patients with a low risk of thyroid-carcinoma recurrence and those with a non-low risk of recurrence.

Acromegaly caused by a growth hormone-releasing hormone secreting carcinoid tumour of the lung: the effect of octreotide treatment.

In acromegaly, the overproduction of growth hormone is usually caused by a pituitary adenoma. We report a 74-year-old woman with acromegaly caused by ectopic overproduction of growth hormone-releasing hormone (GHRH), a rare diagnosis. The GHRH appeared to be produced by a carcinoid tumour of the lung. Treatment with monthly long-acting octreotide resulted in a reduction in the symptoms and normalisation of the insulin-like growth factor-I, which has been maintained for more than two years now. A review of literature concerning causes and treatment of ectopic GHRH-producing tumours is presented.

[Pituitary apoplexy: an endocrinologic emergency]. / Apoplexie van de hypofyse: een endocrinologisch spoedgeval.

A 32-year-old woman, a 73-year-old man and a 26-year-old pregnant woman presented with headache, vomiting, and variable presence of visual disturbances, impaired consciousness, and circulatory shock. All three had pituitary apoplexy. In the first patient lymphocytic hypophysitis was diagnosed, the second had a nonfunctional adenoma and the last patient probably also. All three patients were treated conservatively with full recovery of signs and symptoms. However pituitary insufficiency remained in all three. Pituitary apoplexy is an acute event with significant morbidity and mortality. The cause is a rapid expansion of, usually, a pre-existing, often not yet known, adenoma by massive haemorrhage or infarction. Pressure, among other things, causes hypopituitarism, meningism, compression of the chiasma opticum and visual disturbances. Although many predisposing factors have been identified, pituitary apoplexy is often an unpredictable event. Diagnosis is made by the typical clinical presentation, eye examination, MRI and by measuring pituitary hormones. Treatment is with suppletion of the deficient hormones and in selected patients by transsphenoidal decompression surgery.

[A Somali man with a painful thyroid mass: thyroid tuberculosis]. / Een Somalische man met een pijnlijke schildklierzwelling: thyreoiditis tuberculosa.

A 21-year-old man from Somalia presented with a painful mass in the thyroid, 6 months offatigue, weight loss and fever. Two separate courses of antibiotics did not improve his condition. Thyroid function tests were normal. The chest X-ray showed an enlarged hilus with some pulmonary infiltration around it. The diagnosis ofthyroid tuberculosis was established by cytological, microbiological and PCR testing of a fine needle aspirate of a thyroid lymph node. Treatment with antituberculosis agents resulted in a complete clinical response. The differential diagnosis of a painful thyroid mass encompasses subacute granulomatous thyroiditis, infectious thyroiditis, radiation- or trauma-induced thyroiditis and haemorrhage in the thyroid lymph nodes. Although thyroid tuberculosis is mainly a disease of developing countries, increasing immigration can lead to a higher incidence of this rare form of extrapulmonary tuberculosis and should therefore also be considered in patients with a painful thyroid mass.

Severe hypocalcaemia associated with extensive osteoblastic metastases in a patient with prostate cancer.

A patient with an untreated carcinoma of the prostate was admitted with dehydration, stupor and a surprisingly deep hypocalcaemia. The severe hypocalcaemia was largely attributed to extensive osteoblastic activity due to widespread skeletal metastases although contributing factors to the severity of the hypocalcaemia were a relative vitamin D deficiency, hypomagnesaemia and renal impairment, preventing the mounting of an adequate homeostatic response. There was significant clinical and biochemical improvement after antitumour treatment using androgen deprivation, and supplementation with calcium and vitamin D.

Pituitary apoplexy presenting during pregnancy.

Pituitary apoplexy during pregnancy is a rare but serious event with significant morbidity and even possible mortality if not recognised in time. A 26-year-old woman was admitted with sudden onset of severe headache, vomiting, disturbed consciousness and photophobia. MRI showed a pituitary apoplexy. Adrenal insufficiency with circulatory shock was present together with deficiency of the other hormones produced by the adenohypophysis. After treatment with glucocorticoids, diabetes insipidus developed for which treatment was given. She was treated conservatively and the clinical picture improved in a few days, followed by an uneventful pregnancy and delivery. A second MRI showed regression of mass effect with tumour expanding into the left cavernous sinus. No signs of tumour progression or abnormal hormone secretion have occurred up to one year after the event. Complete pituitary insufficiency has remained. The literature on the subject is reviewed with special emphasis on the circumstances in which pituitary apoplexy occurred and on the treatment of this endocrine emergency. In conclusion, pituitary apoplexy is a rare complication of pregnancy. The severe consequences of missing the diagnosis underline the importance of this potentially lethal endocrine emergency.

Cushing's syndrome caused by topical steroid therapy for psoriasis.

A 72-year-old woman developed manifestations of Cushing's syndrome after long-term topical steroid therapy for psoriasis. Shortly after tapering the dose of topical steroids she developed signs of adrenal insufficiency (provoked by a urinary tract infection) requiring intravenous administration of a stress dose of hydrocortisone. There have only been a few reports of systemic side effects of topically applied corticosteroids in adults. Considering their serious consequences physicians should be alert to signs of Cushing's syndrome in patients on long-term topical steroid therapy. Furthermore, clobetasol propionate ointment doses exceeding 50 g a week should not be prescribed and use of occlusive dressings should be avoided.

Doxazosin and hydrochlorothiazide equally affect arterial wall thickness in hypertensive males with hypercholesterolaemia (the DAPHNE study). Doxazosin Atherosclerosis Progression Study in Hypertensives in the Netherlands.

BACKGROUND: Observational studies suggest a synergistic effect of hypertension and hyperlipidaemia on the progression of atherosclerosis. The alpha-blocker doxazosin has favourable effects on plasma lipids, insulin resistance and blood pressure, while the diuretic hydrochlorothiazide (HCTZ) principally affects blood pressure and increases insulin resistance. METHODS: A randomised double-blind study over 36 months was performed to compare the effects of doxazosin and HCTZ on fasting lipids and on progression of peripheral atherosclerosis. Eighty males (45 to 70 years) with peripheral atherosclerotic disease and increased cholesterol levels (5.2-8.0 mmol/l) were treated for essential hypertension with either doxazosin (n = 41) or HCTZ (n = 39). Main outcome measures were arterial intima-media thickness (IMT) of the carotid and femoral arteries and fasting lipid parameters. RESULTS: In the doxazosin-treated group, significant changes were observed in the concentration of triglycerides (-13.7%, p < 0.01), HDLc (+25.7%, p < 0.05) and IDLc (-30.1%, P < 0.05). In the HCTZ-treated group no significant changes in plasma lipid levels were observed. On follow-up visits systolic blood pressure in the doxazosin-treated group was 6 mm higher than in the HCTZ group. Nevertheless, the groups treated with doxazosin or HCTZ showed no differential effect on IMT after three years of treatment (p = 0.8). A significant reduction of the IMT of combined carotid and femoral arterial walls was shown in both treatment groups (p < 0.005). CONCLUSIONS: Hypertension treatment with doxazosin or HCTZ resulted in a comparable change in arterial IMT after three years, in spite of differences in effect on plasma lipids. The study emphasises the importance of blood pressure control in patients with peripheral vascular disease and hypercholesterolaemia.

Graves' disease induced by Na(131)I therapy for toxic multinodular goitre.

A 59-year-old woman developed manifestations of Graves' disease several months after treatment with radioiodine (Na(131)) for toxic multinodular goitre. During subsequent treatment with additional radioiodine therapy Graves' ophthalmopathy developed which was severe and required treatment with prednisone and orbital radiotherapy. The literature on development of Graves' disease following Na(131) therapy is reviewed and possible pathophysiological mechanisms are discussed. In this case, possibly the first radioiodine therapy has illicited Graves' thyrotoxicosis and the subsequently added radioiodine treatments for the persistent Graves' thyrotoxicosis led to serious ophthalmopathy. Physicians should recognise Graves-like disease as a complication of Na(131)I therapy for toxic multinodular goitre and carefully consider the timing of consecutive radioiodine therapy.

Giant-cell arteritis presenting as an orbital pseudotumor.

In this report a woman with giant-cell arteritis presenting as an orbital pseudotumor is described. Other causes of orbital pseudotumor were excluded in this patient. The pathogenesis of orbital pseudotumor caused by giant-cell arteritis is discussed. The concurrent arteritis of the superficial temporal artery and the rapid resolution of signs and symptoms after prednisone therapy supports the causal relationship between orbital pseudotumor and giant-cell arteritis in this patient.

The additional effects of acipimox to simvastatin in the treatment of combined hyperlipidaemia.

OBJECTIVES: Nicotinic acid, an effective drug for treatment of combined hyperlipidaemia, is often not tolerated because of side-effects. Acipimox is a nicotinic acid like lipid lowering drug with less side-effects. We studied whether the addition of acipimox to simvastatin improves the lipid profile in patients with a combined hyperlipidaemia. DESIGN: Randomized double-blind placebo controlled crossover trial. SETTING: Outpatient lipid clinic of a tertiary referral centre. SUBJECTS: Eighteen patients with combined hyperlipidaemia treated with diet and 20-40 mg simvastatin for at least 3 months. INTERVENTION: Acipimox in a daily dose of 3 X 250 mg for 12 weeks. MAIN OUTCOME MEASURES: Effects on the concentration of LDLc, TG, HDLc, Lp(a) and Apolipoprotein B, as well as on LDL-size and LDL-resistance to oxidative modification. RESULTS: Acipimox reduced Lp(a) levels by 8% (P < 0.05). A substantial but not statistically significant change in TG (-32%) and HDLc (+6%) levels was seen. All patients were found to have small dense LDL, with a size of 229 +/- 4 A. LDL size and the resistance to oxidation, reflected in the lag phase during in vitro oxidation, were not affected by the addition of acipimox. In a subgroup of 8 patients with the most severe hypertriglyceridaemia (baseline TG > 4 mmol L- [1]), acipimox induced a significant increase in HDLc (+ 15%, P < 0.01). The effects on TG (-41%), LDLc (-10%) and lag phase (+17%) were also more pronounced than in the group with a lower baseline TG, but none of these changes reached the level of significance. CONCLUSIONS: Adding acipimox to simvastatin reduced Lp(a) and substantially but not significantly lowered TG. However, in patients with the highest TG levels. HDLc was also significantly improved.

The additional effects of acipimox to simvastatin in the treatment of combined hyperlipidaemia.

OBJECTIVES: Nicotinic acid, an effective drug for treatment of combined hyperlipidaemia, is often not tolerated because of side-effects. Acipimox is a nicotinic acid like lipid lowering drug with less side-effects. We studied whether the addition of acipimox to simvastatin improves the lipid profile in patients with a combined hyperlipidaemia. DESIGN: Randomized double-blind placebo controlled crossover trial. SETTING: Outpatient lipid clinic of a tertiary referral centre. SUBJECTS: Eighteen patients with combined hyperlipidaemia treated with diet and 20-40 mg simvastatin for at least 3 months. INTERVENTION: Acipimox in a daily dose of 3 x 250 mg for 12 weeks. MAIN OUTCOME MEASURES: Effects on the concentration of LDLc, TG, HDLc, Lp(a) and Apolipoprotein B, as well as on LDL-size and LDL-resistance to oxidative modification. RESULTS: Acipimox reduced Lp(a) levels by 8% (P < 0.05). A substantial but not statistically significant change in TG (-32%) and HDLc (+6%) levels was seen. All patients were found to have small dense LDL, with a size of 229 +/- 4 A. LDL size and the resistance to oxidation, reflected in the lag phase during in vitro oxidation, were not affected by the addition of acipimox. In a subgroup of 8 patients with the most severe hypertriglyceridaemia (baseline TG < 4 mmol L- [1]), acipimox induced a significant increase in HDLc (+15%, P < 0.01). The effects on TG (-41%), LDLc (-10%) and lag phase (+17%) were also more pronounced than in the group with a lower baseline TG, but non of these changes reached the level of significance. CONCLUSIONS: Adding acipimox to simvastatin reduced Lp(a) and substantially but not significantly lowered TG. However, in patients with the highest TG levels, HDLc was also significantly improved.

Oral physiological magnesium supplementation for 6 weeks with 1 g/d magnesium oxide does not affect increased Lp(a) levels in hypercholesterolaemic subjects.

Twenty hyperlipidaemic patients on a cholesterol-poor diet were selected on the basis of a raised lipoprotein (a) (Lp(a); apo (a) > 300 U/litre) and treated with 1000 mg MgO per day during 6 weeks. Serum magnesium slightly increased compared to pretreatment levels (P < 0.001). Serum apo(a) concentrations (mean +/- S.D.) were not affected: pretreatment level 963 +/- 552 U/litre; during treatment 999 +/- 536 U/litre; and after washout 995 +/- 524 U/litre. Serum cholesterol increased slightly during MgO treatment because of an increase in LDL-cholesterol (10 per cent) and returned to pretreatment levels after a washout period.

Vertebral bone destruction in sickle cell disease: infection, infarction or both.

Infectious and vaso-occlusive vertebral bone and joint destruction in two patients with sickle cell disease (SCD) are featured by H-shaped vertebrae, kyphotic angulation, osteolysis of endplates and collapse of intervertebral discs as shown by X-ray films and magnetic resonance imaging. Staphylococcal serology supported the diagnosis of staphylococcal osteomyelitis/spondylo-discitis in both SCD patients. The difficulties of establishing the causes and treatment of the osteoarthropathy in these particular cases are discussed in the light of the literature.