Response to Letter to the Editor: “IGSF1 Deficiency Results in Human and Murine Somatotrope Neurosecretory Hyperfunction”
Bibliographic record
Abstract
We thank Dr Faucz and colleagues for sharing their hypothesis that hypothyroidism, rather than growth hormone (GH) excess, may be the main driver for the acromegaloid facies observed in our patients with immunoglobulin superfamily member 1 (IGSF1) deficiency. This is a valid idea and one we gave careful consideration in the course of our study. Significantly, the majority (two-thirds) of affected participants received thyroxine replacement from shortly after birth. However, the presence or absence of acromegalic facies did not differ between untreated individuals and those on long-term levothyroxine at the time of facial photography. Although it is true that hypothyroidism may cause coarse facies, patients with IGSF1 deficiency typically have mild to moderate hypothyroidism, especially when compared with the more severe thyroid hormone deficits that occur in primary hypothyroidism. In our clinical experience, the facies we observe in some of our patients with IGSF1 deficiency are not found in the context of biochemically comparable congenital hypothyroidism due to other etiologies. Additionally, some individuals with IGSF1 deficiency are not diagnosed with central hypothyroidism until late into adulthood, possibly due to preservation of circulating triiodothyronine levels, which mitigate clinical and metabolic manifestations of hypothyroidism (1). Adult height is also maintained in IGSF1 deficiency, arguing against significant skeletal hypothyroidism (2). Clinical evaluation of our patients with IGSF1 deficiency revealed subtle facial coarsening without facial puffiness. Given the challenges in quantifying this impression objectively, we used facial image analysis to compare our patients’ facial characteristics with those of participants with confirmed acromegaly and with control participants. In the context of elevated median insulin-like growth factor 1 levels, increased GH secretion, and with other supportive clinical features (increased finger soft tissue thickness), we contend that an effect of excess GH remains a plausible explanation of our findings. The increased skeletal growth and organomegaly in Igsf1-deficient mice further support this contention. Nevertheless, we agree that further studies are required to investigate the molecular basis for our observations. The complex endocrinopathy seen in patients who are IGSF1 deficient mandates that the interpretation of their clinical phenotypes must derive from a consideration of the potential effects of multiple hormone abnormalities. growth hormone immunoglobulin superfamily member 1 Disclosure Summary: The authors have nothing to disclose.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.021 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.032 | 0.027 |
| Insufficient payload (model declined to judge) | 0.005 | 0.005 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".