title: High prevalence of nodular thyroid disease in patients with Cushing's disease.
abstract: OBJECTIVE
  In the recent past, we have noted a frequent occurrence of thyroid nodules in our patients with Cushing's disease. We therefore elected to evaluate thyroid structure and function in these patients and also in patients with Cushing's syndrome of primary adrenal origin.
  
  
  METHODS
  In 33 of the 37 patients (30 women and 3 men aged 19-66 years) with endogenous hypercortisolism referred to our Institution during the last five years, measurement of T4, T3, FT4, FT3, TSH serum levels and thyroid ultrasonography were performed, at first admission in 15 cases and subsequently in the course of follow-up in 18 cases. At the time of the study, 16 of the 33 patients had active Cushing's disease while 9 were in remission after successful surgery, 6 patients had an adrenal tumour and 2 patients had previously undergone unilateral adrenalectomy for an adrenal adenoma. Thyroid function and ultrasonography were also evaluated in 55 normal subjects, 40 women and 15 men aged 20-73 years.
  
  
  RESULTS
  In 25 patients with Cushing's disease, we found a significantly higher prevalence of thyroid nodular disease than that recorded in 55 control subjects (60.0 vs 20.0%, chi 2 = 10.779, P < 0.005) and comparable to that in patients with active disease (56.2%) and those in remission (66.6%). Multiple nodules were present in 8 Cushing's patients and in 4 normal subjects while a single nodule was detected in 7 patients and in 7 controls. A markedly lower occurrence of thyroid abnormality was found in the 8 patients with adrenal tumours (25.0%, NS vs controls). In 9/17 (52.9%) patients with ultrasonographic evidence of thyroid nodules, these were palpable. As expected, serum thyroid hormone and TSH levels were reduced in patients with active Cushing's syndrome compared to normal controls.
  
  
  CONCLUSIONS
  We found a significantly higher prevalence of nodular thyroid disease in patients with Cushing's disease with respect to a group of controls in whom the prevalence of thyroid nodules was comparable to that reported for the general population in Europe. The possibility that glucocorticoid excess is responsible for the development of thyroid changes does not seem likely since in our small series of patients with adrenal tumours the prevalence was only slightly higher than that observed in control subjects. Other factors related to hyperactivity of the corticotrophic cell, or a growth factor stimulating both corticotroph and thyrocyte proliferation might be involved. Evaluation of a larger series of patients with adrenal tumours may help to distinguish between these possibilities.
authors.affiliation: 2nd Chair of Endocrinology, University of Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Invitti
authors.forename: R
authors.initials: R
authors.lastname: Manfrini
authors.forename: B M
authors.initials: BM
authors.lastname: Romanini
authors.forename: F
authors.initials: F
authors.lastname: Cavagnini
mesh_terms: D000328:Adult; D000368:Aged; D003480:Cushing Syndrome / Q000097:blood / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D013963:Thyroid Hormones / Q000097:blood; D016606:Thyroid Nodule / Q000150:complications* / Q000453:epidemiology; D013972:Thyrotropin / Q000097:blood
chemical_list: D013963:Thyroid Hormones; D013972:Thyrotropin