leky-latky/cftr-protein/mutace/stitna-zlaza
CF and jodid draselný
Terapie kdysi s jódem
- Development of goiter and hypothyroidism reported in patients with cystic fibrosis (CF) since the 1970s
- Especially when treated with iodine-based expectorants
- Iodine-containing expectorants no longer in routine use
- Prevalence of thyroid dysfunction in CF patients is unknown
- CFTR found in human thyroid epithelium
Prevalence hypothyreózy u CF
- Dolan et al. and leater Azizi et al.
- 44% of CF patients given high-dose iodine developed goiter
- 83% of those developed hypothyroidism
- Iodine-related goiter or hypothyroidism may be due to failure to escape from the acute Wolff–Chaikoff effect
- Hypothesized to be related to potential underlying abnormalities in the thyroid gland
- Mechanism for the development of hypothyroidism in these patients with CF has not been clear
- Naehrlich et al. found a high prevalence (83.7%) of iodine deficiency in patients with CF in northern Germany
- May be a contributing factor for hypothyroidism in CF
- Study by Volta et al.
- no significant thyroid dysfunction observed in 17 CF patients compared to controls
- Concluded that this may be related to improved nutritional status and lack of iodine-containing medication use
Normal
- Intact intrathyroidal organification
- Normal serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH)
- (Segall-Blank et al.)
- Serum T3 levels between CF patients and age- and sex-matched controls
- Found no significant difference (Deluca et al. and Sack et al.)
Exaggerated TSH responses to TRH
- In CF patients (De Luca et al.)
Lower total triiodothyronine (T3) levels
- Seen in CF patients by Azizi et al. and Segall-Blank et al.
- Likely related to nonthyroidal illness with impaired thyroxine (T4) to T3 conversion
- CF patients frequently had height and weight below normal and suffered from intermittent illnesses
Selenium deficiency
- May also have played a role in the decreased total T3 levels
- CF patients evidence of undernutrition
Inadequate hepatic deiodinase activity
- Have been suggested in selenium deficiency
Isolated increase in reverse T3 (rT3) in CF patients compared to controls
- Hypothesized to be related to acute hypoxia
- Found no correlation to total T3 levels, weight percentile, or severity of the disease
Altered ion transport in thyroid epithelium seen in CFTR-deficient pigs
- Knockout animal model
- no changes in thyroid histology, growth pattern, or sodium–iodide symporter expression
- Diminished cAMP-activated chloride secretion
- May act as a counter-ion for iodine accumulation
- Leading to disruption of iodine accumulation in the thyroid
Výsledky nyní bez jódu v terapii
- 89 subjects (54% male, 91% white, Mage = 24.4 years, median FEV1 63%)
- 1 subject was on thyroid hormone replacement
- 93% were on pancreatic enzyme replacement
- 68% received antibiotics within six months
- 1 positive thyroid peroxidase (TPO) antibodies
- 87 subjects with measured TSH values
- 7 (8%) had abnormal levels (range 0.2–7.6 µIU/mL; one overt, four subclinical hypothyroidism, and two subclinical hyperthyroidism)
- 56 subjects with measured fT4 values
- 19 (34%) had slightly low levels (range 0.49–0.79 ng/dL; 17 isolated mild hypothyroxinemia)
- A positive correlation between age and body mass index (BMI; p < 0.001)
- Negative correlation between age and FEV1 (p = 0.041) were seen
- no meassured value was predictive of TSH, fT4, or thyroid dysfunction risk
- 24 (27%) of the patients had abnormal serum thyroid function tests
- Thyroid dysfunction was rare in this cohort of 89 patients with CF
- Degree of hypothyroxinemia was marginal, likely due to nonthyroidal illness
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939364/
