title: Severe hyperthyroidism: aetiology, clinical features and treatment outcome.
abstract: BACKGROUND
  Severe hyperthyroidism (SH) is a serious medical disorder that can compromise life. There have not been systematic studies in which SH has been evaluated in detail. Here, our aims were: (1) to analyse both clinical and analytical features and outcome in patients with SH and (2) to compare these data with those found in more usual forms of hyperthyroidism. Patients and methods All patients diagnosed of SH (free thyroxine, FT4 > 100 pmol/l, NR: 11-23) seen in our endocrinology clinic in the last 15 years were studied and compared with a sample of patients with mild (mH; FT4, 23-50 pmol/l) and moderate (MH; FT4, 51-100 pmol/l) hyperthyroidism. Aetiology, clinical analytical and imaging data at diagnosis, therapeutic response and outcome were registered. Results A total of 107 patients with overt hyperthyroidism (81 females, mean age +/- SD 46.9 +/- 16.1 years) were evaluated. We studied a historic group with SH (n = 21; 14 females, 40.9 +/- 17.2 years) and, as a comparator group, we analyszed the data of 86 hyperthyroid patients (67 females, 48.4 +/- 15.5.6 years, NS) comparable in age and gender. The comparator group was classified in MH (n = 37, 26 females, 47.2 +/- 16.6 years) and mH (n = 49, 41 females, 49.4 +/- 14.8 years). In comparison with mH group, SH patients were significantly (P < 0.05) younger and showed a greater proportion of first episode of thyroid hyperfunction (P < 0.05). Graves' disease was the main aetiology in the three groups, but patients with SH showed the highest titre of TSH-receptor antibodies (TRAb) (P < 0.001). Heart rate and size of goitre were higher in SH group than in mH and MH groups (P < 0.01). Atrial fibrillation was more frequently reported in SH group than in MH and mH groups (15.8%vs. 5.4% and 0%, respectively, P < 0.05).
  
  
  RESULTS
  from logistic regression analysis showed that younger age [OR 0.958 (95% CI, 0.923-0.995), P = 0.026], presence of asthenia [OR 4.35 (1.48-12.78), P = 0.008] and higher heart rate [OR 1.03 (1.01-1.06), P = 0.013] were independent clinical variables associated to SH. SH patients showed similar biochemical parameters in comparison with mH group, except for increased serum aspartate aminotransferase (AST) (P < 0.01) and calcium (P < 0.05) levels, and decreased serum cholesterol (P < 0.05) and albumin (P < 0.05) concentrations. Logistic regression analysis showed that only AST [OR 1.07 (1.02-1.11), P = 0.005] was an independent biochemical variable associated to SH. No differences in the type of therapy, cure rate and time in achieving cure were found in SH subjects in relation to patients with milder forms of hyperthyroidism. FT4 was the only independent predictor of cure [OR 0.98 (CI 95%, 0.97-0.99), P < 0.05].
  
  
  CONCLUSIONS
  Graves' disease is the most common aetiology in patients with SH. This type of hyperthyroidism is usually de novo and is accompanied by more clinical signs, symptoms, and analytical derangements, as well as higher titres of TRAb at diagnosis than milder forms of hyperthyroidism. The present data are not able to show differences in treatment modality, time to achieve cure, and remission rate among patients with mild, moderate and severe hyperthyroidism.
authors.affiliation: Department of Endocrinology, Hospital Ramón y Cajal., 28034 Madrid, Spain. piglo65@gmail.com
authors.forename: P
authors.initials: P
authors.lastname: Iglesias
authors.forename: O
authors.initials: O
authors.lastname: Dévora
authors.forename: J
authors.initials: J
authors.lastname: García
authors.forename: P
authors.initials: P
authors.lastname: Tajada
authors.forename: C
authors.initials: C
authors.lastname: García-Arévalo
authors.forename: J J
authors.initials: JJ
authors.lastname: Díez
mesh_terms: D000208:Acute Disease; D000328:Adult; D005260:Female; D006042:Goiter / Q000150:complications; D006111:Graves Disease / Q000150:complications; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D018828:Immunoglobulins, Thyroid-Stimulating / Q000032:analysis; D008297:Male; D008875:Middle Aged; D013974:Thyroxine / Q000097:blood; D016896:Treatment Outcome
chemical_list: D018828:Immunoglobulins, Thyroid-Stimulating; C094372:thyrotropin-binding inhibitory immunoglobulin; D013974:Thyroxine