Endo Pills - 14

Informação cientifica de ação rápida - Ano 3 N° 14

Curso de Especialização em Endocrinologia - PUC
Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione
Prof.: Luiz César Povoa (A48)
Ricardo Martins Rocha Meirelles (A38)
Editores: Rosa Rita Santos Martins (A34), Isabela Bussade (A8) e Denise Momesso (R2)
Editores Associados: Walmir Coutinho (A22), Edna Pottes (A35) e Claudia Pieper (A22)
Composição Gráfica: Wallace Margoniner

Prezados colegas, nesta edição do Endo Pills trazemos alguns pôsteres apresentados no ICE- International Congress of Endocrinology pelo IEDE.

O ICE foi um grande orgulho, não só para o Brasil por ter sido sede de tão importante evento, mas principalmente para o Rio de Janeiro e nossa Instituição, que teve na presidência e vice presidência Dr Amélio Godoy e Dr Ricardo Meirelles, além de participação expressiva de grande numero de staffs e alunos do IEDE, tanto como congressistas, palestrantes como nas apresentações orais e pôsteres.
Nesta edição temos a possibilidade de ver, ou rever, o excelente nível do material científico que representou nossa instituição neste importante evento.
Boa leitura a todos
Isabela Bussade

HYPERPARATHYROIDISM AFTER RADIOACTIVE IODINE THERAPY

OBJECTIVE: To describe a case of parathyroid adenoma (pa) emerging 18 years after radioactive iodine therapy (rait).

MATERIAL AND METHODS: We report a case of a patient with graves` disease who developed primary hyperparathyroidism (hpt) 18 years after rait in the endocrinology service of the IEDE.

RESULTS: AASD, 63 years-old (yo), female with a previously known history of graves` disease, first diagnosed in 1973, with ocular disease associated, when she was 25 yo. Initial therapy was with methimazol for about 3 years. First remission occurred in 1976 when she stopped her medical treatment. On follow-up there was a recurrence in 1978 when she again restarted treatment, this time with propiltiouracil. In 1979 achieved remission again. For more two times on evolution remissions and fails occurred. After the last recurrence she underwent rait with 9 mci of 131i and thus hypothyroidism developed. levotiroxin (lt4) therapy was initiated and tittered until a dose of 62,5mcg per day. in 2005 she started bilateral legs and arms pain and fatigue that worsened in 2007 when laboratorial analysis was ordered as follows: total calcium (ca) 14,1mg/dl [normal range(nr): 8,5-10,2]; phosphorus (p) 1,8mg/dl (nr: 2,8-4,1); pth: 496pg/ml (nr: 16,6-65). Medical therapy for hypercalcemia was started with saline infusion, furosemide and pamidronete but was no effective. The new dosages of ca, p and pth were respectively 14; 2, 3 and 666. An ultrasound was obtained and a nodule in the posterior aspect of the left lobe was found. A fine needle aspiration (fna) with subsequent imunohistochemical analysis showed parathyroid cells. An inferior left parathyroid was performed and demonstrated a parathyroid adenoma.

CONCLUSION: according to some authors, the rait could be a risk factor for hpt, including pa. observations indicate that not only external radiation, but also radiation from 131i is a risk factor for development of hpt and it is emphasized that age at the time of radiation treatment may be of decisive importance in this context. In a recent review of cases the average latency time to the development of hpt after rait was 13,5 ± 9,1 years. Serum calcium surveillance has been suggested for patients who have undergone rait treatment.
Warszawski L; Canton APM; Puppin BA; Novaes FS; Frota RSC; Zagury RL; Campos SC

EXHAUSTED ACROMEGALY: CASE REPORT

INTRODUCTION: Pituitary apoplexy is a rare event, particularly in functioning pituitary adenomas. Tumor size reduction may follow, but endocrine remission has been rarely described.

CASE REPORT: A case of pituitary apoplexy resulting in acromegaly endocrine remission is reported. a 37-year-old male patient was referred to the diabetes and endocrinology state institute (IEDE), presenting acromegalic phenotype, with a 15- year evolution prior to diagnosis, along with recent complaints of headache, asteny and mucous-cutaneous paleness. A computed tomography (ct) scan was performed and revealed an intrasellar hipodense mass suggestive of pituitary adenoma. One year later, the patient had clinical and laboratorial findings of panhypopituitarism and was admitted for diagnostic procedures. A magnetic resonance imaging (mri) demonstrated disappearance of the mass and empty turcic sella.

DISCUSSION: acute pituitary apoplexy is the sudden neurological breakdown that follows a fulminant expansion of the gland, caused by isquemic or haemorrhagic events. The typical clinical presentation, with marked neurological signs and symptoms, is observed in only 6 to 10% of the cases, and can be the first pituitary adenoma manifestation. In the rest of the patients, the pytuitary function is rather preserved, with moderate symptoms, such as headache. In those cases, subclinical pituitary apoplexies frequently go underdiagnosed. Depending on the amount of destruction, permanent or transient, posterior or anterior pituitary disfunction might occur. gonadotrophins deficiency is more frequent, followed by acth and tsh deficiency, and less usually, abnomal prolactin secretion. Empty sella may appear as an outcome of massive pituitary tumor infarction. a few cases of growth hormone-secreting pituitary adenoma necrosis resulting in spontaneous remission and panhypopituitarism have been described in the literature. However, the term cure is not applicable, once the definitive evolution of those cases is still unknown.

CONCLUSION: this case report is ment to raise awareness of this rarely described syndrome, which is also known as exhausted acromegaly. Furthermore, the apoplexy is generally subclinical; wich imposes an even greater diagnostic challenge. Therefore, pituitary adenoma spontaneous resolution may be more prevalent than estimated.
Warzawsky L, Costa DFP, Bragança JB, Lemos H, Sterza L, Farage M

CASE HISTORY OF COEXISTENT THYROTOXICOSIS AND JAUNDICE

OBJECTIVE: to describe the association of the rare complication of jaundice with thyrotoxicosis.

MATERIALS AND METHODS: we report the clinical and laboratory findings of a case of severe jaundice (total bilirubin levels: 52, 30 mg/dl) associated with hiperthyroidism and heart failure. We made an overview of previously published cases of c oexistent thyrotoxicosis and jaundice, methimazole- and carbimazole-induced hepatotoxicity and approach to treatment found in a medline search.

RESULTS: in a 54 year-old white woman with hyperthyroidism, treatment with methimazole 40 mg /day was initiated. One month later, scleral icterus, dark urine, fatigue and abdominal discomfort prompted discontinuation of the therapy. Laboratory findings were: alanine and aspartate aminotransferase 46 u/i (n: <31) and 87 u/i (n: <31) respectively, alkaline phosphatase 226 u/i (n: 35-104), gamma-glutamyl transpeptidase 138 iu/i (n: 7-32) and bilirubin 44 mg/di (n: <1). Abdominal ultrasonography showed normal bile ducts; echocardiography showed heart failure. Lithium therapy was applied before radioiodine therapy. She was treated with 17 mci of 131i and, persisting in hyperthyroidism, five months later received a new treatment with 25 mci of 131i. The highest values of bilirubin were found in moments of heart failure exacerbation, reaching the upper value of 52, 30 mg/dl. Resolution of the jaundice occurred after 28 weeks without methimazole.

CONCLUSION: the data strongly suggest that in this patient, the hepatic dysfunction was primarily due to hyperthyroidism observing the long time to resolution of her jaundice. It is a rare complication and h ypotheses regarding the cause of cholestasis in hyperthyroidism per se suggest that the hypermetabolic state increases the hepatic oxygen consumption without simultaneous increasing in the hepatic blood flow thus lowering the oxygen tension and interfering with bile transport. Besides, increased liver metabolism in response to thyroid hormone increases the rate of bile flow to the point of saturation. Also, there is the possibility of direct toxic effect of t4, but studies have not confirmed this. Considering her cardiovascular disorder, therapy with lithium carbonate was a useful adjunct to rai therapy to prevent exacerbation of thyrotoxicosis. Coexistent heart failure is a predisponent factor to severe jaundice in association with hyperthyroidism.
Novaes, FS; Souza, MVL; Canton, APM; Puppin, BA

REVERSIBLE PULMONARY HYPERTENSION AND RIGHT HEART FAILURE ASSOCIATED WITH HYPERTHYROIDISM.

INTRODUCTION: Hyperthyrodism may present with a variety of cardiovascular symptoms. Recent reports suggest an association between hyperthyroidism with pulmonary hypertension (ph) and isolated right heart failure. We described a case report of a ph secondary to hyperthyroidism which improved after restoration of euthyroid state.

CASE REPORT: 72 years old women presented with exertion dyspnea, fatigue, palpitation, bilateral leg edema, ascites and weight lost. Physical examination showed irregular heart beat, signs of right heart failure and no evidence of pulmonary congestion or disease. atrial fibrillation was confirmed by electrocardiogram. Echocardiogram revealed isolated right heart failure, severe tricuspid regurgitation and ph, with pulmonary artery pressure (pap) of 65 mmhg. work up for the common secondary causes of ph was negative, including, congenital intra-cardiac shunts, left-side atrial or ventricular heart disease, disorders of the respiratory system including hypoxemia and pulmonary tromboembolism, collagen vascular disease, primary portal hypertension, hiv infection, schistossoma mansoni infection, as well as ph secondary to drugs or toxins. The only concurrent illness identified was graves disease, by laboratory findings of thyrotoxicosis and positive thyroid peroxidase (tpo) autoantibody. Treatment was initiated with propylthiouracil, oral anticoagulation (because of atrial fibrillation) and diuretics. One month later, euthyroid state was achieved and there was clinical resolution of right heart failure. After one year of outpatient follow-up, an echocardiogram was performed and revealed improvement of ph, with pap of 35 mmhg, mild tricuspid regurgitation and normal right heart function.

CONCLUSION: elevated pulmonary pressure may be a frequent finding in thyrotoxicosis, but often unrecognized. It may be asymptomatic or associated with right heart failure. The exact reasons for the development of ph in thyroid disease are not clear. Most importantly, hyperthyroidism is a potential reversible cause of ph and it should be included in the etiology of secondary pulmonary hypertension.
Momesso DP; Puppin BA; Tavares P; Mattos PE; Souza MVL.

MAURIAC SYNDROME: STILL A CONCERN?

INTRODUCTION:Mauriac’s Syndrome (MS) is a rare complication of diabetes mellitus type 1 (dm1), characterized by hepatomegaly, growth failure and poor glycemic control, described mainly in children and teenagers. We present an adult female with ms.

CASE REPORT: 22 years old female with dm1 since age of 6, presenting hepatomegaly, high hba1c and variability on smbg , great elevation of liver enzymes, triglicerides (>1000 mg/dl), total cholesterol (543 mg/dl), ldlc (245 mg/dl) and hba1c (13%), modest elevation of alkaline phosphatase and normal billirubin. weight 44 kg, height 1,51m, bmi of 18,8kg/m2. ultrasound detected hepatomegaly and fatty infiltration aspect. hepatitis panel showed only hepatitis b past immunization. ceruloplasmin, ferritin, transferring saturation were normal. autoimmune hepatitis was excluded. liver biopsy showed glycogen deposits in the hepatocytes and evidence of steatohepatitis. she was treated with pioglitazone, ursodiol, genfibrozil, atorvastatin , glargine and lispro insulins. liver enzymes trended downwards as her glucose management improved, but it took 4 years to normalize.

DISCUSSION: The differential diagnosis of her liver disease included autoimmune hepatitis, acute hepatitis, wilson`s disease and hemochromatosis, which were excluded. Her signs and symptoms could be explained by ms: hepatomegaly, glycogen infiltration of the liver and short stature in people with poorly controlled diabetes. hypertriglyceridemia is due to poor glycemic control and ms. steatosis and glycogenosis should be distinguished by histology. Whereas steatosis may progress to fibrosis and cirrhosis, glycogenosis does not. Liver biopsy, on this case, showed both glycogenosis and steatohepatitis. The better glycemic control reverted liver enzymes alterations and hepatomegaly, suggesting that the major component of hepatic disease was glycogenosis. Other medications, such as pioglitazone, might have collaborated to improvement.

CONCLUSION: even though ms has become rare, it should be considered not only in children, but also in adults with dm1, acute hepatomegaly and abnormal liver function. The diagnosis is important because prolonged improvement of hba1c can normalize liver function, hypertriglyceridemia and also prevent dm1 acute and chronic complications.

Kupfer R, Farage M, Costa DFP, Bragança JB, Sterza L, Lemos H - IEDE

ATIPICAL PROGRESSION OF GRAVES´ ORBITOPATHY AFTER THYROID RESSECTION.

INTRODUCTION: Thyroid eye disease (ted), the most frequent extrathyroidal manifestation of graves` disease, is an auto-immune disorder. It can occur before, concomitantly or after hyperthyroidism. Different forms of treatments for thyrotoxicosis can influence the ted course. thyroidectomy should be theoretically more beneficial to graves` orbitopathy outcome because of the removal of the source of both thyroid- orbit cross reaction auto antigens and auto reactive t lymphocytes.

CASE REPORT: A 58 years old women presented with graves disease and was initially treated with thionamides for two years. At the diagnosis she had only mild left exophthalmos and no eye complaint. Subsequently, thyroid resection was indicated as a result of goiter enlargement, development of nodules and compressive symptoms. euthyroid state was achieved. Four months after surgery, progression of orbitopathy was observed. She developed ocular manifestations like pain on eye movement, eyelid edema, conjunctival injection, double vision and bilateral exophthalmos. Orbital radiotherapy and intravenous glucocorticoids used in combination improved her eye disease.

DISCUSSION: According to literature, thionamides are associated with improve or does no affect the course of ted. The relationship between radioiodine therapy and ted is a matter of controversy. The few randomized and controlled studies available, suggest a small but definitive risk of causing ted progression, but can be prevented by concomitant glucocorticoids. The effect of thyroid surgery on ted has been extensively reported in the literature, and the reports usually advocate thyroid resection as an important treatment to improve eye disease. We described a case in which ted occurred after surgery, despite the removal of the source of autoantigens and the control of thyroid function. This observation suggests that the choice of treatment for thyrotoxicosis may not influence ted outcome.

CONCLUSION: Graves´ orbitopathy pathogenesis and natural history may involve several different mechanisms which have still to be more deeply studied. Most importantly, ted might have a clinical course independent of thyroid disease and type of treatment.
Puppin, BA; Momesso, DP; Satake, F; Canton, AP; Souza, MVL.

TYPE 1 DIABETES MELLITUS AND MYASTHENIA GRAVIS: ASSOCIATION OR COINCIDENCE?

INTRODUCTION: Autoimmune diseases often coexist in clinical practice and may be associated with autoimmune polyendocrine syndrome (aps). the diagnosis of aps should be suspected in the natural history of any autoimmune disease.

CASE REPORT: 25 year-old woman, presented with muscle weakness and dysarthria that increased during periods of activity. Myasthenia gravis was diagnosed and treatment with pyridostigmine and prednisone was started. After 2 weeks, she developed blurred vision, polydipsia, polyuria, vaginal pruritus and was admitted in our hospital with non-ketotic hyperglycemia. Laboratory evaluation: glycemia=1374mg/dl, c peptide=5.1ng/ml (1.1–5.0), anti-insulin antibody (ab) =3.0u/ml (<1.0), anti-gad ab=1.0u/ml (<1.0), anti-islets ab=1.1u/ml (<1.0), anti-acetylcholine receptor ab=9.02nmol/l (<0.15), anti-peroxidase<20 ui/ml (<40). Subcutaneous rapid insulin, then nph, was started. She was discharged in use of nph 28 + 12 ui, rapid insulin before meals according to scale and pyridostigmine. At the outpatient clinic, adequate metabolic control was achieved (hba1c=5%) with low doses of insulin (0.2u/kg/day) and the posterior laboratory evaluation showed positive anti-gad ab=9.6u/ml and normal c peptide level=1.7ng/ml. After 2 years, she developed polydipsia, polyuria, nausea, vomiting and hyperglycemia, hba1c was 10.7% and it was necessary to increase insulin doses. A morning plasma cortisol of 22mcg/dl excluded adrenal insufficiency.

DISCUSSION: Screening of serological organ-specific autoantibodies identifies patients who may develop autoimmune polyendocrinopathies. aps type ii involves the coexistance of addison´s disease with type 1 diabetes mellitus (dm) and/or autoimmune thyroid disease. Some patients also present with, or later develop other organ-specific autoimmune disorders, including myasthenia gravis. This patient presented with myasthenia gravis and type 1 dm. at the moment, there is no evidence of adrenal insufficiency in order to diagnose aps ii, but in up to 30% of patients dm1 is diagnosed before adrenal insufficiency.

CONCLUSION: Patients with endocrine autoimmune diseases should be screened for the presence of APS.
Lima GAB, Mattos PE, Tavares P, Momesso DP, Henriques RP, Kupfer R.

GLYBURIDE INDUCED CUTANEOUS VASCULITIS

OBJECTIVE: To describe a case of cutaneous vasculitis glyburide induced and to discuss its frequency, clinical, pathophisiological and histological issues.

materials and methods- 51 year’s old male with long standing type 2 diabetes mellitus admitted as an inpatient to our hospital with an itching cutaneous rash, fever, polyartalgia, malaise and edema of the upper and lower limbs. He related a recent onset of glyburide use two weeks before presentation. He denied use of other medications. On physical examination there was a generalized cutaneous discamation with exulcerations and fissure associated. Superior and inferior limbs edema, bilateral cervical, mandibular and inguinal adenopathy was also seen.he had right superior quadrant tenderness and hepatomegaly on abdominal palpation. glyburide was then discontinued and intensive insulin therapy was started. Laboratory analysis was ordered to check wbc, rbc, platelet count, erythrocyte sedimentation rate (esr), alt, ast, sodium, potassium, urea, creatinin, glucose and a skin biopsy.

RESULTS: The exams revealed an normocitic and normochromic anemia, esr elevation with normal liver tests. The skin biopsy showed a difuse mononuclear inflammatory infiltration with eosinophils within it. thickness of capilar walls and extravasation of hematias suggestive of drug induced vasculitis. eight days after drug withdrawal, anti-hystaminic oral therapy and topical corticosteroids the patient underwent a complete resolution of the lesions and was discharged to our outpatient clinic.

CONCLUSION: After extensive medical literature research on the major journals of the area we have found only a few case reports similar to this one. Over a clinical point of view we can classificate this picture as a pharmacodermia probably glyburide induced. The physiopathology is centered on the immune complex deposition due to chronic exposition to the drug itself or its radicals so eventually cross reaction is seen with sulfonamides antibiotics. The hystopathologic analysis confirms the clinical hypothesis as drug induced cutaneous vasculitis. The clinical manifestations can be restricted to the skin but in some cases as it was in the case described above systemic involvement is seen denoting a more severe form. cutaneous parefects of glyburide are rarely seen although once its wast use its real incidence maybe higher than described on literature.

Rosane Kupfer, Maria Teresa Menegat, Rosana Leal Santos, Roberto Zagury, Roberta Frota, Ronei Gustavo Paim de Vargas.