Interferon-induced Raynaud's syndrome

OBJECTIVE: To review the clinical features, diagnosis, treatment, and outcome of interferon-induced Raynaud's phenomenon. METHODS: The medical literature was reviewed from 1967 to November 2001 with the assistance of a MEDLINE search using the key words: Raynaud, Interferon, ischemia, thrombosis and necrosis. A qualitative review was performed after the articles were abstracted and the relevant information was summarized. RESULTS: Twenty-four cases of interferon-induced Raynaud's phenomenon (including our patient) are described. Interpheron-alpha was the most common causative agent (14 cases). The symptoms appeared weeks to years after beginning treatment and varied from mild vasospasm to occlusion of digital arteries and tissue necrosis (14 cases), sometimes necessitating finger amputation (6 patients). Digital plethysmography, arteriography and capillaroscopy were valuable diagnostic tools. In 4 cases, cardiac, ophthalmic, or central nervous system drug-induced ischemia accompanied the peripheral Raynaud's phenomenon. Of the 15 cases with a documented outcome, withdrawal of the drug alone resulted in complete (6 patients) or partial (1 patient) recovery. In the others, supportive therapy was needed. The recovery period lasted from 2 weeks to 3 months. In 2 patients, continuation of treatment was possible. CONCLUSIONS: Raynaud's phenomenon and related complications must be recognized as possible side effects of interferon therapy. Early diagnosis and withdrawal of the drug may prevent unnecessary morbidity and disability.     

Interferon-induced granulomatous lung disease

PURPOSE OF REVIEW: Interferon therapy can induce or exacerbate sarcoidosis. With the increasing use of interferons it is highly likely that more cases of sarcoidosis will be encountered by clinicians. We describe three unusual cases of interferon-induced sarcoidosis and review the most recent relevant literature on this subject. RECENT FINDINGS: Interferons, on account of their antiviral antigrowth and immunomodulatory effects, are used to treat various internal and dermatological diseases. Exogenously administered interferons stimulate the Th-1 response, which plays a major role in granuloma formation. In most of the patients with interferon-induced sarcoidosis, the disease subsides when interferon is discontinued. Occasionally, treatment with corticosteroids may become necessary. SUMMARY: Interferon therapy can induce or exacerbate sarcoidosis, the disease disappears when interferon is discontinued, sometimes treatment with corticosteroids is required.     

Gigantism with hypopituitarism

A forty-one year old man described in 1963 as having hypo-pituitarism with gigantism due to normal or excessive growth hormone secretion associated with a deficiency of other pituitary hormones was reevaluated with specific tests of growth hormone reserve. Deficiency of thyrotropin, corticotropin and gonadotropins was confirmed. Immunoreactive growth hormone was virtually absent in the fasting state and failed to be released during insulin-induced hypoglycemia or with the administration of arginine, glucagon or Pitressin®. These new methods for the direct measurement of pituitary hormones suggest that this patient has insufficiency of all pituitary hormones, including growth hormone, and that his tall stature was due to eunuchoid growth rather than to pituitary gigantism.     

Interferon-induced depression: prevalence and management

BACKGROUND: Interferon-induced depression ranges from 0 to 50%. Interferon schedule and a history of psychiatric illnesses are not enough to predict who will develop symptoms and who will not. AIMS: To assess the prevalence of depression during interferon therapy; to test whether Minnesota Multiphasic Personality Inventory is useful in clinical practice for the early identification of patients at risk of depression; whether and how the depression can be cured. PATIENTS: One hundred and eighty-five patients treated with interferon and ribavirin for chronic hepatitis C. METHODS: Before therapy, all patients underwent a Minnesota Multiphasic Personality Inventory and a clinical examination, specifically for the identification of depressive symptoms. RESULTS: Thirty-one patients developed a psychiatric disorder, 11 of them requiring treatment with anti-depressant drugs. Among the 18 patients with Minnesota Multiphasic Personality Inventory positive tests, 16 developed a psychiatric disorder, 8 of them a severe disorder (sensitivity of 0.58; 0.73 for severe disorders). Among the 154 who did not develop psychiatric side effects, 152 had a negative Minnesota Multiphasic Personality Inventory (specificity: 0.99). Severe psychiatric disorders were successfully treated with anti-depressant drugs. CONCLUSIONS: Psychiatric side effects are easy to see during interferon therapy. A psychiatric evaluation should be considered on all patients before treatment. If depression develops, it should be treated aggressively, and selective serotonin re-uptake inhibitors are the anti-depressants of choice.     

Hypophysial tuberculoma with hypopituitarism

In this patient with a caseating pituitary tuberculoma the diagnosis of hypopituitarism was established antemortem by modern tests of pituitary function. Pituitary tuberculoma is rare and may resemble pituitary adenoma. Tuberculoma should be considered in patients with hypopituitarism or enlargement of the sella turcica, or both, who have or have had tuberculosis of any site. Antituberculous therapy should be instituted in such patients, especially when surgery is contemplated.     

Interferon-induced thyroid dysfunction in chronic hepatitis C

Background:  Treatment of chronic hepatitis C with interferon is known to be associated with thyroid dysfunction (TD) in 5–14% of patients. We studied the incidence, types, outcome and risk factors predictive of thyroid dysfunction.
Methods:  A retrospective analysis was performed on all patients treated with interferon alpha (IFN) or pegylated interferon alpha (PEG-IFN) ± ribavirin (RBV), who developed abnormal thyroid function tests (TFTs). These cases were compared with treatment-matched controls to identify factors predictive of thyroid dysfunction. Statistical methods consisted of: χ² test, Fischer's exact test, Welch's t -test, and multivariate analysis.
Results:  From a total of 511 patients, 45 cases with TD were identified (8.8%). Pegylated interferon alpha was associated with higher rates of TD than IFN (14.1% vs 6.0%, P  = 0.0029). Female sex (OR 5.6, 95% CI 1.1–7) and Asian ethnicity (OR 2.7, 95% CI 1.4–22) were independent predictors of developing TD. Cytology was obtained in 13 patients: benign follicular pattern (8); thyroiditis (3); and normal (2). Thyroid peroxidase (TPO) antibodies ( P  = 0.004) and earlier onset of dysfunction ( P  = 0.03) were associated with need for treatment. Sixteen patients had persistent TD by the end of the follow-up period, predicted by female sex, non-Asian ethnicity, prior history of TD and TPO antibodies.
Conclusions:  Pegylated interferon alpha, female sex and Asian ethnicity are independent risk factors for TD. Thyroid peroxidase antibodies and earlier TD within the course of IFN are associated with the requirement for treatment. Thyroid function tests should be monitored during and after IFN-based therapy. The most common cytological finding is a benign follicular pattern.     

Hypothalamic origin of idiopathic hypopituitarism

Two adult male patients with anterior pituitary insufficiency of unknown etiology were studied during acute challenge with thyrotropin releasing hormone (TRH) and aqueous vasopressin (AVP). Each patient had previously documented thyrotropin (TSH) adrenocorticotropin (ACTH) and gonadotropin deficiencies dating back to childhood. Plasma growth hormone (GH) was undetectable in each following insulin and arginine stimuli. Intravenous administration of synthetic TRH produced in both patients a prompt rise in serum TSH similar to the response observed in normal subjects. AVP injection was followed by a significant elevation of plasma 17-hydroxycorticosteroids in each patient and a rise in plasma GH in one of them. These results demonstrate that the adenohypophysis of these two patients could respond to stimuli of hypothalamic origin. It is concluded that the anterior pituitary failure was due to a deficiency of hypothalamic “releasing factors” caused by a disorder of hypothalamic function of unknown etiology.