Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease, though severe forms are rare. Management of GO is often suboptimal, largely because available treatments do not target pathogenic mechanisms of the disease. Treatment should rely on a thorough assessment of the activity and severity of GO and its impact on the patient's quality of life. Local measures (artificial tears, ointments and dark glasses) and control of risk factors for progression (smoking and thyroid dysfunction) are recommended for all patients. In mild GO, a watchful strategy is usually sufficient, but a 6-month course of selenium supplementation is effective in improving mild manifestations and preventing progression to more severe forms. High-dose glucocorticoids (GCs), preferably via the intravenous route, are the first line of treatment for moderate-to-severe and active GO. The optimal cumulative dose appears to be 4.5-5 g of methylprednisolone, but higher doses (up to 8 g) can be used for more severe forms. Shared decision-making is recommended for selecting second-line treatments, including a second course of intravenous GCs, oral GCs combined with orbital radiotherapy or cyclosporine, rituximab or watchful waiting. Rehabilitative treatment (orbital decompression surgery, squint surgery or eyelid surgery) is needed in the majority of patients when GO has been conservatively managed and inactivated by immunosuppressive treatment.

/pdf/the-2016-european-thyroid-association-european-group-on-jf6uco6055.pdf

The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy.

Summary of consensus a. All patients with GO should (Fig. 1):Be referred to specialist centers;Be encouraged to quit smoking;Receive prompt treatment in order to restore andmaintain euthyroidism.b. Patients with sight-threatening GO should be treatedwith i.v. GCs as the ﬁrst-line treatment; if the responseis poor after 1–2 weeks, they should be submitted tourgent surgical decompression.c. The treatment of choice for moderate-to-severe GO isi.v. GCs (with or without OR) if the orbitopathy isactive;surgery(orbitaldecompression,squintsurgery,and/or eyelid surgery in this order) should beconsidered if the orbitopathy is inactive.d. In patients with mild GO, local measures and anexpectant strategy are sufﬁcient in most cases, buttreatment may be justiﬁed if QoL is affectedsigniﬁcantly. In memoriam This document is dedicated to the memory of MarkPrummel (1956–2005), one of the founders ofEUGOGO, who greatly contributed to expanding ourunderstanding of clinical and therapeutic aspects of GO.

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Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO.

Graves’ ophthalmopathy is an debilitating disease impairing the quality of life of affected individuals. Despite recent progress in the understanding of its pathogenesis, treatment is often not satisfactory. In mild cases, local therapeutic measures (artificial tears and ointments, sunglasses, nocturnal taping of the eyes, prisms) can control symptoms and signs. In severe forms of the disease (3‐5%), aggressive measures are required. If the disease is active, high-dose glucocorticoids and/or orbital radiotherapy, or orbital decompression represent the mainstay of treatment. If the disease is severe but inactive, orbital decompression is preferred. Novel treatments such as somatostatin analogs or intravenous immunoglobulins are under evaluation. Rehabilitative (extraocular muscle or eyelid) surgery is often needed after treatment and inactivation of eye disease. Correction of both hyper- and hypothyroidism is crucial for the ophthalmopathy. Antithyroid drugs and thyroidectomy do not influence the course of the ophthalmopathy, whereas radioiodine treatment may cause the progression of preexisting ophthalmopathy, especially in smokers. The exacerbation, however, is prevented by glucocorticoids. In addition, thyroid ablation may prove beneficial for the ophthalmopathy in view of the pathogenetic model relating eye disease to autoimmune reactions directed against antigens shared by the thyroid and the orbit. (Endocrine Reviews 21: 168 ‐199, 2000)

/pdf/management-of-graves-ophthalmopathy-reality-and-perspectives-420985v7s4.pdf

Management of Graves' ophthalmopathy: reality and perspectives.

Patients with serious inflammatory Graves' ophthalmopathy should be treated with anti-inflammatory drugs or radiotherapy to prevent complications like fibrosis, while those with non-inflammatory ophthalmopathy may be treated by surgery immediately. It is often difficult, however, to distinguish inflammatory from non-inflammatory Graves' disease. We therefore present a simple clinical classification here to differentiate between these two conditions. This classification is based on the classical signs of inflammation--pain, redness, swelling, and impaired function. After two consecutive clinical examinations an 'activity score' can be determined, ranging from 0 to 10 points. In a retrospective study testing the efficacy of this classification we found that patients with an activity score of 3 or more at the beginning of therapy responded well to anti-inflammatory drugs, while those with a lower activity score mostly did not. Comparing the pretreatment activity score with the degree of enlargement of the extraocular muscles on the CT scan, we found a significant correlation between these two parameters: the higher the activity score, the more the enlargement of the muscles. We conclude that this classification facilitates the proper selection of patients for treatment.

https://bjo.bmj.com/content/bjophthalmol/73/8/639.full.pdf

Clinical criteria for the assessment of disease activity in Graves' ophthalmopathy: a novel approach.

Cyclosporin is a lipophilic cyclic polypeptide which produces calcium-dependent, specific, reversible inhibition of transcription of interleukin-2 and several other cytokines, most notably in T helper lymphocytes. This reduces the production of a range of cytokines, inhibiting the activation and/or maturation of various cell types, including those involved in cell-mediated immunity. Thus, cyclosporin has immunosuppressive properties, and has a proven place as first line therapy in the prophylaxis and treatment of transplant rejection. Cyclosporin has also been evaluated in a large range of disorders where immunoregulatory dysfunction is a suspected or proven aetiological factor, and this is the focus of the present review. In patients with severe disease refractory to standard treatment, oral cyclosporin is an effective therapy in acute ocular Behcet's syndrome, endogenous uveitis, psoriasis, atopic dermatitis, rheumatoid arthritis, active Crohn's disease and nephrotic syndrome. Concomitant low dose corticosteroid therapy may improve response rates in some disorders. The drug can be considered as a first line therapy in patients with moderate or severe aplastic anaemia who are ineligible for bone marrow transplantation, with the additional benefit of reducing platelet alloantibody titres. It may also be of considerable therapeutic benefit in patients with primary biliary cirrhosis, particularly those with less advanced disease. Limited evidence suggests cyclosporin is effective in patients with intractable pyoderma gangrenosum, polymyositis/dermatomyositis or severe, corticosteroid-dependent asthma. Indeed, the steroid-sparing effect of cyclosporin is a significant advantage in a number of indications. Furthermore, the drug has shown some efficacy in a wide range of other, generally uncommon disorders in which controlled clinical trials are lacking and/or are unlikely to be performed. Cyclosporin does not appear to be effective in patients with allergic contact dermatitis, multiple sclerosis or amyotrophic lateral sclerosis. It is only temporarily effective in patients with type I (insulin-dependent) diabetes mellitus and should not be used in this indication. To avoid relapse after control of active disease, patients should receive cyclosporin maintenance therapy at the lowest effective dosage. However, maintenance therapy appears to be of no benefit in patients with Crohn's disease and cyclosporin should be discontinued in these patients once active disease is controlled. Hypertrichosis, gingival hyperplasia, and neurological and gastrointestinal effects are the most common adverse events in cyclosporin recipients, but are usually mild to moderate and resolve on dosage reduction. Changes in laboratory variables indicating renal dysfunction are relatively common, although serious irreversible damage is rare.(ABSTRACT TRUNCATED AT 400 WORDS)

/pdf/cyclosporin-a-review-of-its-pharmacodynamic-and-2wjzyh5l5a.pdf

Cyclosporin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders.

Forty patients with Graves' ophthalmopathy stages III-V were divided into two groups in a random manner according to their year of birth. Group I received prednisone in decreasing dosage. Group II received prednisone at a comparable dosage and ciclosporin. Steroids were discontinued after 10 weeks in the two groups. In the patients of group II, ciclosporin was continued over 12 months. The therapeutic effect was assessed by an activity score based on subjective and objective symptoms (computerized tomography and sonography of the orbit, Hertel values, clinical findings). All signs of endocrine ophthalmopathy improved significantly in both groups (P less than 0.01 in group I; P less than 0.001 in group II). The improvement was significantly greater in group II (P less than 0.05) according to the predefined score. After corticosteroids were discontinued, inflammatory signs recurred in nine patients in group I and in one of group II. During the observation period of 12 months, relapses occurred in eight out of twenty patients in group I and in only one out of twenty in group II. Muscle thickness decreased in nine patients in group II, 6 months after beginning therapy. At this time, the results were not influenced in any of the twenty patients in group I. Microsomal antibodies decreased significantly (P less than 0.001) in the ciclosporin group, whereas no change was seen in the other group. Renal values rose within the normal range in group II. In this group, an infection with Klebsiella pneumoniae occurred in one patient after 4 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Ciclosporin and prednisone v. prednisone in treatment of Graves' ophthalmopathy: a controlled, randomized and prospective study

Treatment of APUDomas with the Long-Acting Somatostatin Analogue SMS 201-995: Investigations of Therapeutic Use and Digestive Side Effects

Simultaneous bilateral venous sampling of blood from the inferior petrosal sinuses helps in the differentiation between peripheral and central ACTH hypersecretion. One can also locate the site of a hormonally active hypophyseal micro-adenoma that cannot be demonstrated by other methods. The authors have experience with fifteen patients and discuss the indications, technique and problems as well as the advantages of using digital subtraction angiography.

Selektive Blutentnahme aus dem Sinus petrosus inferior mit digitaler Subtraktionsangiographie

High-resolution real-time sonography was performed in 15 cases of clinically and chemically suspected primary hyperparathyroidism and in 20 patients with different thyroid nodules. The suspected enlarged parathyroid glands and the thyroid nodules were percutaneously punctured under sonographic control. Concentrations of parathyroid hormone, human thyroglobulin, and human calcitonin were measured in the aspirate, and immunocytology was performed. The mean concentration of the aspirated parathyroid hormone in the parathyroid glands was 4,013.6 pmol/l +/- 4,519 (SD) as compared with 14.9 pmol/l +/- 8.7 in the thyroid nodules. Thyroglobulin was present in the aspirated fluid of parathyroid adenomas located behind the thyroid (mean +/- SD, 398.1 ng/ml +/- 317). In comparison, the aspirated thyroglobulin from the thyroid nodules averaged 9,689.7 ng/ml +/- 3,732. Immunocytology for parathyroid hormone was positive in 14 of the 15 biopsied specimens. Of 15 patients who were scanned for suspected hyperparathyroidism, six had concomitant thyroid nodules. It is concluded that the measurement of high concentrations of parathyroid hormone in the aspirate from a cervical mass, with sonographic control of needle position and/or positive immunocytology provides absolute localization of parathyroid tissue.

Fine-needle biopsy of parathyroid adenomas.

Homme de 61 ans ayant des antecedents de coliques nephretiques depuis 1952. Le diagnostic d'adenome a ete confirme par la chirurgie

G. Kahaly

Papers

Ciclosporin and prednisone v. prednisone in treatment of Graves' ophthalmopathy: a controlled, randomized and prospective study

Treatment of APUDomas with the Long-Acting Somatostatin Analogue SMS 201-995: Investigations of Therapeutic Use and Digestive Side Effects

Selektive Blutentnahme aus dem Sinus petrosus inferior mit digitaler Subtraktionsangiographie

Fine-needle biopsy of parathyroid adenomas.

Darstellung eines Parathyreoideaadenoms mit der Magnetresonanztomographie