Cushing Syndrome Due to Primary Pigmented Nodular Adrenal Disease in Three Related Adolescent Girls With Carney Complex
Bibliographic record
Abstract
Primary pigmented nodular adrenal disease (PNNAD) is a rare cause of Cushing syndrome particularly during childhood and adolescence. Females are preferentially affected. The present work is aimed at assessing if there is a relationship between puberty and the development of Cushing syndrome due to PPNAD. We have followed an extended family with Carney complex (CNC) due to a dominantly inherited mutation of the gene encoding the regulatory subunit 1alpha (R1A) of the protein kinase A (PRKAR1A). The large majority of family members presenting with Cushing syndrome due to PPNAD were women (six out of seven). One of them died of an adrenocortical carcinoma at age 27 years. Genetic screening of entire family allowed follow-up of those family members harboring the mutation but without clinical manifestations of hypercortisolism. During the last 2 years, three related adolescent girls developed subclinical hypercortisolism starting shortly after menarche. None of their male relatives carrying the same mutation showed abnormal adrenal function. The first abnormality noticed in the patients was loss of the normal circadian variation of cortisol production. A low dose dexamethasone test (Liddle’s test) elicited a paradoxical increase in urinary excretion of free cortisol greater than 50% of basal values. Several months later, they complained of insidious manifestations of hypercortisolism including weight gain, hypertension and oligomenorrhea. They underwent laparoscopic bilateral adrenalectomy. Pathologically, the excised glands showed PPNAD. We conclude that female gender is a predisposing factor for expressing PPNAD. A paradoxical rise of urinary free cortisol (UFC) in response to dexamethasone is an early and specific laboratory marker of the disorder, allowing timely bilateral adrenalectomy which may not only prevent severe complications of hypercortisolism, but may also preclude the development of adrenocortical carcinoma. J Endocrinol Metab. 2015;5(4):261-266 doi: http://dx.doi.org/10.14740/jem299w
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".